Effect of vegetarian dietary patterns on cardiometabolic risk factors in diabetes: A systematic review and meta-analysis of randomized controlled trials.
To update the European Association for the Study of Diabetes (EASD) clinical practice guidelines for nutrition therapy, we conducted a systematic review and meta-analysis of randomized controlled trials to summarize the evidence for the effect of vegetarian dietary patterns on glycemic control and other established cardiometabolic risk factors in individuals with diabetes. We searched MEDLINE, EMBASE, and Cochrane databases through February 26, 2018 for randomized controlled trials ≥3 weeks assessing the effect of vegetarian dietary patterns in individuals with diabetes. The primary outcome was HbA1c. Secondary outcomes included other markers of glycemic control, blood lipids, body weight/adiposity, and blood pressure. Two independent reviewers extracted data and assessed risk of bias. Data were pooled by the generic inverse variance method and expressed as mean differences (MD) with 95% CIs. Heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic). The overall certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Nine trials (n = 664 participants) met the eligibility criteria. Vegetarian dietary patterns significantly lowered HbA1c (MD = -0.29% [95% CI: -0.45, -0.12%]), fasting glucose (MD = -0.56 mmol/L [95% CI: -0.99, -0.13 mmol/L]), LDL-C (MD = -0.12 mmol/L [95% CI: -0.20, -0.04 mmol/L]), non-HDL-C (MD = -0.13 mmol/L [95% CI: -0.26, -0.01 mmol/L]), body weight (MD = -2.15 kg [95% CI: -2.95, -1.34 kg]), BMI (MD = -0.74 kg/m2 [95% CI: -1.09, -0.39 kg/m2]) and waist circumference (MD = -2.86 cm [95% CI: -3.76, -1.96 cm]). There was no significant effect on fasting insulin, HDL-C, triglycerides or blood pressure. The overall certainty of evidence was moderate but was low for fasting insulin, triglycerides and waist circumference. Vegetarian dietary patterns improve glycemic control, LDL-C, non-HDL-C, and body weight/adiposity in individuals with diabetes, supporting their inclusion for diabetes management. More research is needed to improve our confidence in the estimates. CLINICALTRIALS. NCT02600377.


Carbon isotope fractionation of amino acids in fish muscle reflects biosynthesis and isotopic routing from dietary protein.
1. Analysis of stable carbon isotopes is a valuable tool for studies of diet, habitat use and migration. However, significant variability in the degree of trophic fractionation (Delta(13)C(C-D)) between consumer (C) and diet (D) has highlighted our lack of understanding of the biochemical and physiological underpinnings of stable isotope ratios in tissues. 2. An opportunity now exists to increase the specificity of dietary studies by analyzing the delta(13)C values of amino acids (AAs). Common mummichogs (Fundulus heteroclitus, Linnaeus 1766) were reared on four isotopically distinct diets to examine individual AA Delta(13)C(C-D) variability in fish muscle. 3. Modest bulk tissue Delta(13)C(C-D) values reflected relatively large trophic fractionation for many non-essential AAs and little to no fractionation for all essential AAs. 4. Essential AA delta(13)C values were not significantly different between diet and consumer (Delta(13)C(C-D) = 0.0 +/- 0.4 per thousand), making them ideal tracers of carbon sources at the base of the food web. Stable isotope analysis of muscle essential AAs provides a promising tool for dietary reconstruction and identifying baseline delta(13)C values to track animal movement through isotopically distinct food webs. 5. Non-essential AA Delta(13)C(C-D) values showed evidence of both de novo biosynthesis and direct isotopic routing from dietary protein. We attributed patterns in Delta(13)C(C-D) to variability in protein content and AA composition of the diet as well as differential utilization of dietary constituents contributing to the bulk carbon pool. This variability illustrates the complicated nature of metabolism and suggests caution must be taken with the assumptions used to interpret bulk stable isotope data in dietary studies. 6. Our study is the first to investigate the expression of AA Delta(13)C(C-D) values for a marine vertebrate and should provide for significant refinements in studies of diet, habitat use and migration using stable isotopes.


Effects of music therapy on autonomic nervous system activity, incidence of heart failure events, and plasma cytokine and catecholamine levels in elderly patients with cerebrovascular disease and dementia.
Music therapy (MT) has been used in geriatric nursing hospitals, but there has been no extensive research into whether it actually has beneficial effects on elderly patients with cerebrovascular disease (CVD) and dementia. We investigated the effects of MT on the autonomic nervous system and plasma cytokine and catecholamine levels in elderly patients with CVD and dementia, since these are related to aging and chronic geriatric disease. We also investigated the effects of MT on congestive heart failure (CHF) events.Eighty-seven patients with pre-existing CVD were enrolled in the study. We assigned patients into an MT group (n = 55) and non-MT group (n = 32). The MT group received MT at least once per week for 45 minutes over 10 times. Cardiac autonomic activity was assessed by heart rate variability (HRV). We measured plasma cytokine and catecholamine levels in both the MT group and non-MT group. We compared the incidence of CHF events between these two groups. In the MT group, rMSSD, pNN50, and HF were significantly increased by MT, whereas LF/HF was slightly decreased. In the non-MT group, there were no significant changes in any HRV parameters. Among cytokines, plasma interleukin-6 (IL-6) in the MT group was significantly lower than those in the non-MT group. Plasma adrenaline and noradrenaline levels were significantly lower in the MT group than in the non-MT group. CHF events were less frequent in the MT group than in the non-MT group (P < 0.05). These findings suggest that MT enhanced parasympathetic activities and decreased CHF by reducing plasma cytokine and catecholamine levels.


Vitamin C-enriched gelatin supplementation before intermittent activity augments collagen synthesis.
Musculoskeletal injuries are the most common complaint in active populations. More than 50% of all injuries in sports can be classified as sprains, strains, ruptures, or breaks of musculoskeletal tissues. Nutritional and/or exercise interventions that increase collagen synthesis and strengthen these tissues could have an important effect on injury rates. This study was designed to determine whether gelatin supplementation could increase collagen synthesis. Eight healthy male subjects completed a randomized, double-blinded, crossover-design study in which they consumed either 5 or 15 g of vitamin C-enriched gelatin or a placebo control. After the initial drink, blood was taken every 30 min to determine amino acid content in the blood. A larger blood sample was taken before and 1 h after consumption of gelatin for treatment of engineered ligaments. One hour after the initial supplement, the subjects completed 6 min of rope-skipping to stimulate collagen synthesis. This pattern of supplementation was repeated 3 times/d with ≥6 h between exercise bouts for 3 d. Blood was drawn before and 4, 24, 48, and 72 h after the first exercise bout for determination of amino-terminal propeptide of collagen I content. Supplementation with increasing amounts of gelatin increased circulating glycine, proline, hydroxyproline, and hydroxylysine, peaking 1 h after the supplement was given. Engineered ligaments treated for 6 d with serum from samples collected before or 1 h after subjects consumed a placebo or 5 or 15 g gelatin showed increased collagen content and improved mechanics. Subjects who took 15 g gelatin 1 h before exercise showed double the amino-terminal propeptide of collagen I in their blood, indicating increased collagen synthesis. These data suggest that adding gelatin to an intermittent exercise program improves collagen synthesis and could play a beneficial role in injury prevention and tissue repair. This trial was registered at the Australian New Zealand Clinical Trials Registry as ACTRN12616001092482.


The role of nitric oxide in experimental cerulein induced pancreatitis.
An enhanced formation of nitric oxide (NO), due to the induction of inducible nitric oxide synthase (iNOS), has been implicated in the pathogenesis of shock and inflammation, but its role in acute pancreatitis still remains controversial. To clarify the role of NO in acute pancreatitis, the present experiment investigated the expression of iNOS and the effect of NOS inhibition on cerulein-induced pancreatitis in rats. Group I received intraperitoneal (ip) injection of normal saline. Group II received two ip injections of cerulein (20 microgram/kg). Group III received injections of N(G)-nitro-L-arginine methyl ester (L-NAME) (30 mg/kg) with cerulein. Group IV received L-arginine (250 mg/kg) with cerulein and L-NAME. The expression of iNOS in the pancreas was examined by western blot analysis. The plasma concentration of NO metabolites was measured. The severity of pancreatitis was assessed by measuring serum amylase, pancreas water content and histopathological examination. Compared with controls, the cerulein group displayed significantly increased expression of iNOS and raised plasma NO metabolites. Treatment with L-NAME significantly decreased hyperamylasemia, plasma NO level, and the extent of pancreatic injury. Treatment with L-arginine reversed the effects of L-NAME. These findings suggest that an enhanced formation of NO by iNOS plays an important role in the development of acute pancreatitis, and inhibition of NO production has the beneficial effects in reducing pancreas injury.


Regulation of retinoic acid distribution is required for proximodistal patterning and outgrowth of the developing mouse limb.
Exogenous retinoic acid (RA) induces marked effects on limb patterning, but the precise role of endogenous RA in this process has remained unknown. We have studied the role of RA in mouse limb development by focusing on CYP26B1, a cytochrome P450 enzyme that inactivates RA. Cyp26b1 was shown to be expressed in the distal region of the developing limb bud, and mice that lack CYP26B1 exhibited severe limb malformation (meromelia). The lack of CYP26B1 resulted in spreading of the RA signal toward the distal end of the developing limb and induced proximodistal patterning defects characterized by expansion of proximal identity and restriction of distal identity. CYP26B1 deficiency also induced pronounced apoptosis in the developing limb and delayed chondrocyte maturation. Wild-type embryos exposed to excess RA phenocopied the limb defects of Cyp26b1(-/-) mice. These observations suggest that RA acts as a morphogen to determine proximodistal identity, and that CYP26B1 prevents apoptosis and promotes chondrocyte maturation, in the developing limb.


Emergence of resistant Candida glabrata in Germany.
Candida glabrata is the second leading fungal pathogen causing candidaemia and invasive candidiasis in Europe. This yeast is recognized for its rapid ability to acquire antifungal drug resistance. We systematically evaluated 176 C. glabrata isolates submitted to the German National Reference Center for Invasive Fungal Infections (NRZMyk) between 2015 and 2019 with regard to echinocandin and fluconazole susceptibility. Susceptibility testing was performed using a reference protocol (EUCAST) and a range of commercial assays. Hot spot regions of the echinocandin target FKS genes were sequenced using Sanger sequencing. In total, 84 of 176 isolates were initially classified as anidulafungin-resistant based on EUCAST testing. Of those, 71 harboured mutations in the glucan synthase encoding FKS genes (13% in FKS1, 87% in FKS2). Significant differences in anidulafungin MICs were found between distinct mutation sites. 11 FKS wild-type (WT) isolates initially classified as resistant exhibited anidulafungin MICs fluctuating around the interpretation breakpoint upon re-testing with multiple assays. Two FKS WT isolates consistently showed high anidulafungin MICs and thus must be considered resistant despite the absence of target gene mutations. Over one-third of echinocandin-resistant strains displayed concomitant fluconazole resistance. Of those, isolates linked to bloodstream infection carrying a change at Ser-663 were associated with adverse clinical outcome. Resistant C. glabrata strains are emerging in Germany. Phenotypic echinocandin testing can result in misclassification of susceptible strains. FKS genotyping aids in detecting these strains, however, echinocandin resistance may occur despite a wild-type FKS genotype.


Sudden hearing loss: a ten-year outpatient experience.
The aim of this study was to determine the effects of various treatment modalities employed for patients with sudden sensorineural hearing loss (SHL). We retrospectively evaluated the records of patients treated in the sudden hearing loss section of the Otolaryngology Department at Clinic Hospital, School of Medicine, University of São Paulo, Brazil, between 1996 and 2006. Our study included patients with SHL of sudden onset (occurring over a 72-hour period) at equal to or greater than 30 dB at three consecutive frequencies. We divided patients into five groups by profile and treated them with dextran, dexamethasone, acyclovir, nicotinic acid, and papaverine hydrochloride (with or without vitamin A). We performed audiometry at baseline and on days 30, 90, 120, and 180 of treatment. We determined outcome as the difference between day-0 and day-180 pure-tone averages (PTAs). Among the 139 patients evaluated, baseline PTA was similar in all groups. We observed significant improvements in PTAs after 180 days of treatment and noted a significant linear correlation between time from SHL onset to initial visit and recovery. However, no significant difference was evident among the treatment groups. In the treatment of SHL, dextran provided no more benefit than did dexamethasone or acyclovir. Earlier initiation of treatment improves the prognosis for patients with SHL.


The use of linear instrumental variables methods in health services research and health economics: a cautionary note.
To investigate potential bias in the use of the conventional linear instrumental variables (IV) method for the estimation of causal effects in inherently nonlinear regression settings. Smoking Supplement to the 1979 National Health Interview Survey, National Longitudinal Alcohol Epidemiologic Survey, and simulated data. Potential bias from the use of the linear IV method in nonlinear models is assessed via simulation studies and real world data analyses in two commonly encountered regression setting: (1) models with a nonnegative outcome (e.g., a count) and a continuous endogenous regressor; and (2) models with a binary outcome and a binary endogenous regressor. The simulation analyses show that substantial bias in the estimation of causal effects can result from applying the conventional IV method in inherently nonlinear regression settings. Moreover, the bias is not attenuated as the sample size increases. This point is further illustrated in the survey data analyses in which IV-based estimates of the relevant causal effects diverge substantially from those obtained with appropriate nonlinear estimation methods. We offer this research as a cautionary note to those who would opt for the use of linear specifications in inherently nonlinear settings involving endogeneity.


A synthesis of clinical recommendations and primary research for survivors of prostate or breast cancer.
Studies have documented the efficacy of cancer treatments available, specifically for patients with prostate or breast cancer, but few articles have compared prostate or breast cancer recommendations from the patient's perspective. In this article, the authors compare and contrast published clinical recommendations for advanced practice RNs who treat patients with prostate or breast cancer to qualitative studies that explore the experiences of cancer survivors. Treatment options, along with recommendations and resources, are included. The nurse clinician's role in caring for patients with prostate or breast cancer is diverse and complex, and evidence supports the role of the nurse clinician in improving patient care. Implementing findings from qualitative studies that focus on patients' perspectives in conjunction with clinical recommendations is essential when developing care plans for patients with cancer.


Intrinsic rippling enhances static non-reciprocity in a graphene metamaterial.
In mechanical systems, Maxwell-Betti reciprocity means that the displacement at point B in response to a force at point A is the same as the displacement at point A in response to the same force applied at point B. Because the notion of reciprocity is general, fundamental, and is operant for other physical systems like electromagnetics, acoustics, and optics, there is significant interest in understanding systems that are not reciprocal, or exhibit non-reciprocity. However, most studies on non-reciprocity have occurred in bulk-scale structures for dynamic problems involving time reversal symmetry. As a result, little is known about the mechanisms governing static non-reciprocal responses, particularly in atomically-thin two-dimensional materials like graphene. Here, we use classical atomistic simulations to demonstrate that out-of-plane ripples, which are intrinsic to graphene, enable significant, multiple orders of magnitude enhancements in the statically non-reciprocal response of graphene metamaterials. Specifically, we find that a striking interplay between the ripples and the stress fields that are induced in the metamaterials due to their geometry impacts the displacements that are transmitted by the metamaterial, thus leading to a significantly enhanced static non-reciprocal response. This study thus demonstrates the potential of two-dimensional mechanical metamaterials for symmetry-breaking applications.


Effect of a new treatment protocol called Functional Chewing Training on chewing function in children with cerebral palsy: a double-blind randomised controlled trial.
Cerebral palsy (CP) is a group of permanent sensorimotor impairments. Children with CP have various feeding difficulties including chewing disorder, which may affect their nutritional status. Functional Chewing Training (FuCT) was designed as a holistic approach to improve chewing function by providing postural alignment, sensory and motor training, and food and environmental adjustments. This study aimed to investigate the effect of FuCT on chewing function in children with CP. This study was designed as a double-blind, randomised controlled trial. Eighty CP children with chewing disorder were randomised and split between the FuCT group (31 males, 19 females; mean age 3·5 ± 1·9 years) and the control group (16 males, 14 females; 3·4 ± 2·3 years) receiving traditional oral motor exercises. Each group received the training programme for 12 weeks with weekly follow-up and with two evaluations at baseline and end of 12 weeks. Chewing function was evaluated by analysing video recordings and scored with the Karaduman Chewing Performance Scale (KCPS). The Behavioral Pediatrics Feeding Assessment Scale (BPFAS) was used to evaluate feeding behaviours of children. A significant improvement was observed in KCPS scores at 12 weeks after training in the FuCT group (P < 0·001), but no change was found in the control group (P = 0·07). A significant improvement was detected in all parameters of BPFAS at 12 weeks after training in the FuCT group (P < 0·001) and in four parameters of BPFAS in the control group (P = 0·02, P = 0·02). FuCT is an effective method to improve chewing function compared with traditional oral motor exercises.


Phylogeny of Steinernema travassos, 1927 (Cephalobina: Steinernematidae) inferred from ribosomal DNA sequences and morphological characters.
Entomopathogenic nematodes in Steinernema, together with their symbiont bacteria Xenorhabdus, are obligate and lethal parasites of insects that can provide effective biological control of some important lepidopteran, dipteran, and coleopteran pests of commercial crops. Phylogenetic relationships among 21 Steinernema species were estimated using 28S ribosomal DNA (rDNA) sequences and morphological characters. Sequences of the rDNA internal transcribed spacers were obtained to provide additional molecular characters to resolve relationships among Steinernema carpocapsae, Steinernema scapterisci, Steinernema siamkavai, and Steinernema monticolum. Four equally parsimonious trees resulted from combined analysis of 28S sequences and 22 morphological characters. Clades inferred from analyses of molecular sequences and combined datasets were primarily reliably supported as assessed by bootstrap resampling, whereas those inferred from morphological data alone were not. Although partially consistent with some traditional expectations and previous phylogenetic studies, the hypotheses inferred from molecular evidence, and those from combined analysis of morphological and molecular data, provide a new and comprehensive framework for evaluating character evolution of steinernematids. Interpretation of morphological character evolution on 6 trees inferred from sequence data and combined evidence suggests that many structural features of these nematodes are highly homoplastic, and that some structures previously used to hypothesize relationships represent ancestral character states.


Evaluation of 3'-phosphate as a transient protecting group for controlled enzymatic synthesis of DNA and XNA oligonucleotides.
Chemically modified oligonucleotides have advanced as important therapeutic tools as reflected by the recent advent of mRNA vaccines and the FDA-approval of various siRNA and antisense oligonucleotides. These sequences are typically accessed by solid-phase synthesis which despite numerous advantages is restricted to short sequences and displays a limited tolerance to functional groups. Controlled enzymatic synthesis is an emerging alternative synthetic methodology that circumvents the limitations of traditional solid-phase synthesis. So far, most approaches strived to improve controlled enzymatic synthesis of canonical DNA and no potential routes to access xenonucleic acids (XNAs) have been reported. In this context, we have investigated the possibility of using phosphate as a transient protecting group for controlled enzymatic synthesis of DNA and locked nucleic acid (LNA) oligonucleotides. Phosphate is ubiquitously employed in natural systems and we demonstrate that this group displays most characteristics required for controlled enzymatic synthesis. We have devised robust synthetic pathways leading to these challenging compounds and we have discovered a hitherto unknown phosphatase activity of various DNA polymerases. These findings open up directions for the design of protected DNA and XNA nucleoside triphosphates for controlled enzymatic synthesis of chemically modified nucleic acids.


α-Actinin/titin interaction: A dynamic and mechanically stable cluster of bonds in the muscle Z-disk.
Stable anchoring of titin within the muscle Z-disk is essential for preserving muscle integrity during passive stretching. One of the main candidates for anchoring titin in the Z-disk is the actin cross-linker α-actinin. The calmodulin-like domain of α-actinin binds to the Z-repeats of titin. However, the mechanical and kinetic properties of this important interaction are still unknown. Here, we use a dual-beam optical tweezers assay to study the mechanics of this interaction at the single-molecule level. A single interaction of α-actinin and titin turns out to be surprisingly weak if force is applied. Depending on the direction of force application, the unbinding forces can more than triple. Our results suggest a model where multiple α-actinin/Z-repeat interactions cooperate to ensure long-term stable titin anchoring while allowing the individual components to exchange dynamically.


Version 6 of the consensus yeast metabolic network refines biochemical coverage and improves model performance.
Updates to maintain a state-of-the art reconstruction of the yeast metabolic network are essential to reflect our understanding of yeast metabolism and functional organization, to eliminate any inaccuracies identified in earlier iterations, to improve predictive accuracy and to continue to expand into novel subsystems to extend the comprehensiveness of the model. Here, we present version 6 of the consensus yeast metabolic network (Yeast 6) as an update to the community effort to computationally reconstruct the genome-scale metabolic network of Saccharomyces cerevisiae S288c. Yeast 6 comprises 1458 metabolites participating in 1888 reactions, which are annotated with 900 yeast genes encoding the catalyzing enzymes. Compared with Yeast 5, Yeast 6 demonstrates improved sensitivity, specificity and positive and negative predictive values for predicting gene essentiality in glucose-limited aerobic conditions when analyzed with flux balance analysis. Additionally, Yeast 6 improves the accuracy of predicting the likelihood that a mutation will cause auxotrophy. The network reconstruction is available as a Systems Biology Markup Language (SBML) file enriched with Minimium Information Requested in the Annotation of Biochemical Models (MIRIAM)-compliant annotations. Small- and macromolecules in the network are referenced to authoritative databases such as Uniprot or ChEBI. Molecules and reactions are also annotated with appropriate publications that contain supporting evidence. Yeast 6 is freely available at http://yeast.sf.net/ as three separate SBML files: a model using the SBML level 3 Flux Balance Constraint package, a model compatible with the MATLAB® COBRA Toolbox for backward compatibility and a reconstruction containing only reactions for which there is experimental evidence (without the non-biological reactions necessary for simulating growth). Database URL: http://yeast.sf.net/


Quantification of co-transcriptional splicing from RNA-Seq data.
During gene expression, protein-coding transcripts are shaped by multiple processing events: 5' end capping, pre-mRNA splicing, RNA editing, and 3' end cleavage and polyadenylation. These events are required to produce mature mRNA, which can be subsequently translated. Nearly all of these RNA processing steps occur during transcription, while the nascent RNA is still attached to the DNA template by RNA polymerase II (i.e. co-transcriptionally). Polyadenylation occurs after 3' end cleavage or post-transcriptionally. Pre-mRNA splicing - the removal of introns and ligation of exons - can be initiated and concluded co-transcriptionally, although this is not strictly required. Recently, a number of studies using global methods have shown that the majority of splicing is co-transcriptional, yet not all published studies agree in their conclusions. Short read sequencing of RNA (RNA-Seq) is the prevailing approach to measuring splicing levels in nascent RNA, mRNA or total RNA. Here, we compare four different strategies for analyzing and quantifying co-transcriptional splicing. To do so, we reanalyze two nascent RNA-Seq datasets of the same species, but different cell type and RNA isolation procedure. Average co-transcriptional splicing values calculated on a per intron basis are similar, independent of the strategy used. We emphasize the technical requirements for identifying co-transcriptional splicing events with high confidence, e.g. how to calculate co-transcriptional splicing from nascent RNA- versus mRNA-Seq data, the number of biological replicates needed, depletion of polyA+RNA, and appropriate normalization. Finally, we present guidelines for planning a nascent RNA-Seq experiment.


Origami-Based Reconfigurable Metamaterials for Tunable Chirality.
Origami is the art of folding two-dimensional (2D) materials, such as a flat sheet of paper, into complex and elaborate three-dimensional (3D) objects. This study reports origami-based metamaterials whose electromagnetic responses are dynamically controllable via switching the folding state of Miura-ori split-ring resonators. The deformation of the Miura-ori unit along the third dimension induces net electric and magnetic dipoles of split-ring resonators parallel or anti-parallel to each other, leading to the strong chiral responses. Circular dichroism as high as 0.6 is experimentally observed while the chirality switching is realized by controlling the deformation direction and kinematics. In addition, the relative density of the origami metamaterials can be dramatically reduced to only 2% of that of the unfolded structure. These results open a new avenue toward lightweight, reconfigurable, and deployable metadevices with simultaneously customized electromagnetic and mechanical properties.


[Telepsychiatry provides new opportunities for the prevention and treatment of mental health disorders].
Digital technologies in mental healthcare are envisioned to offer easier, faster and more cost-effective access to mental healthcare. The scope for integrating digital technology into mental healthcare is vast: video conferencing, developing novel treatments using interactive software, mobile applications, and sensor technologies. We outline technology-based interventions, which are relevant to clinical practice, and present the evidence base for using digital technology as well as emerging challenges for their implementation in clinical practice.


Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Febrile Neonates.
Most severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in pediatric patients are mild or asymptomatic. However, infants have emerged at higher risk of hospitalization and severe outcomes in pediatric coronavirus disease 2019 (COVID-19). We report a case series of 4 full-term neonates hospitalized with fever and found to have SARS-CoV-2 infection with a spectrum of illness severities. Two neonates required admission to the intensive care unit for respiratory insufficiency and end organ involvement. Half of the patients were found to have a coinfection. One neonate received antiviral therapy with remdesivir and is, to our knowledge, the youngest patient to receive this drug for COVID-19. All neonates had favorable outcomes.


Effects of dopants on the adhesion and electronic structure of a SnO2/Cu interface: a first-principles study.
Doping has been adopted as a versatile approach for tuning the adhesion of metal oxide/metal interfaces. Understanding the mechanism of doping at the interface adhesion on the atomic and electronic scale is crucial for the rational design and optimization of metal oxide/metal composites. In this work, we have investigated the effects of dopants on the adhesion of SnO2/Cu interfaces through first-principles calculations. Firstly, O-terminated a SnO2(110)/Cu(111) interface (denoted as I) was considered and the work of separation values of the interfaces with various dopants (Mo, Sb, Ti, Zn and Cu) were calculated to evaluate the interface adhesion strength. It was demonstrated that low-valence dopants (Zn2+ and Cu2+) enhance the adhesion strength of interface I, while high-valence dopants (Mo6+ and Sb5+) play the opposite role. Secondly, the strengthening effects of low-valence dopants were further verified in four candidate interfacial models with different atomic structures (denoted as II-V). The work of separation values indicated that the adhesion of all of the interfaces involved could be enhanced by low-valence doping. The electronic structure of the interface was demonstrated through density of states, charge density and charge density difference analyses. The results revealed that upon low-valence doping, the holes facilitate charge transfer between Cu and SnO2, which generates strong covalent bonds across the interface and thus significantly enhances the interface adhesion. This work not only provides insight into rational doping to enhance the adhesion of SnO2/Cu composites but can also be expanded upon for the design of other metal oxide/metal composites with strong interface adhesion.


Service utilization differences for Axis I psychiatric and substance use disorders between white and black adults.
Although studies have shown disparities between black and white populations in service utilization for mental disorders, little information exists on whether such disparities apply equally across disorders. The objective of this study was to examine racial differences in lifetime prevalence of service utilization for mood and anxiety disorders and for alcohol and drug use disorders, with controls for predisposing, enabling, and need-for-service variables unequally distributed between racial-ethnic groups. Data were from a face-to-face epidemiologic survey of 32,752 non-Hispanic white or black adults ages 18 and older residing in households and group quarters in the United States. Main outcome measures were treatment for mood, anxiety, and alcohol and drug use disorders. White adults were consistently more likely than black adults to have had treatment for mood disorders (odds ratio [OR]=2.16, 95% confidence interval [CI]=1.80-2.59) and anxiety disorders (OR=1.77, 95% CI=1.43-2.19) after adjustment for predisposing and enabling factors and need for service (severity of disorder). In contrast no evidence of lower service utilization for treatment of alcohol use disorders emerged among black respondents (OR=.87, 95% CI=.69-1.10). Moreover, white respondents with drug use disorders were significantly less likely than black respondents to receive treatment for a drug problem (OR=.64, 95% CI=.47-.88). Differences in treatment between black and white adults depended on the specific disorder and type of treatment considered. Prevention and intervention strategies should address disorder-specific disparities in services received.


Intravascular imaging with a storage phosphor detector.
The aim of this study is to develop and test an intravascular positron imaging system based on a storage phosphor detector for imaging and detecting vulnerable plaques of human coronary arteries. The radiotracer F18-FDG accumulates in vulnerable plaques with inflammation of the overlying cap. The vulnerable plaques can, therefore, be imaged by recording positrons emitted from F18-FDG with a detector inserted into the artery. A prototype intravascular detector was constructed based on storage phosphor. The detector uses a flexible storage phosphor tube with 55 mm length, 2 mm diameter and 0.28 mm wall thickness. The intravascular detector is guided into the vessel using x-ray fluoroscopy and the accumulated x-ray signal must be erased prior to positron imaging. For this purpose, a light diffuser, 0.9 mm in diameter and 55 mm in length, was inserted into the detector tube. The light diffuser was connected to a laser source through a 2 m long optical fiber. The diffuser redirected the 0.38 W laser light to the inner surface of the phosphor detector to erase it. A heart phantom with 300 cm(3) volume and three coronary arteries with 3.2 mm diameter and with several plaques was constructed. FDG solution with 0.5 microCi cm(-3) activity concentration was filled in the heart and coronary arteries. The detector was inserted in a coronary artery and the signal from the plaques and surrounding background activity was recorded for 2 min. Then the phosphor detector was extracted and read out using a storage phosphor reader. The light diffuser erased the signal resulting from fluoroscopic exposure to level below that encountered during positron imaging. Vulnerable plaques with area activities higher than 1.2 nCi mm(-2) were visualized by the detector. This activity is a factor of 10-20 lower than that expected in human vulnerable plaques. The detector was able to image the internal surface of the coronary vessels with 50 mm length and 360 degrees circumference. Spatial resolution was 0.6-1.2 mm FWHM with a readout pixel resolution of 80 microm. The detector is flexible, reusable and easy to handle; it provides virtually real-time imaging. An intravascular imaging detector based on storage phosphor has shown a potential for imaging human coronary artery plaques. The detector provides the sensitivity, spatial resolution, flexibility and short imaging times necessary for clinical applications. Future research will decrease the detector diameter from 2 mm to 1 mm, and will apply the design to in vivo animal experiments.


The artificial zinc finger coding gene 'Jazz' binds the utrophin promoter and activates transcription.
Up-regulation of utrophin gene expression is recognized as a plausible therapeutic approach in the treatment of Duchenne muscular dystrophy (DMD). We have designed and engineered new zinc finger-based transcription factors capable of binding and activating transcription from the promoter of the dystrophin-related gene, utrophin. Using the recognition 'code' that proposes specific rules between zinc finger primary structure and potential DNA binding sites, we engineered a new gene named 'Jazz' that encodes for a three-zinc finger peptide. Jazz belongs to the Cys2-His2 zinc finger type and was engineered to target the nine base pair DNA sequence: 5'-GCT-GCT-GCG-3', present in the promoter region of both the human and mouse utrophin gene. The entire zinc finger alpha-helix region, containing the amino acid positions that are crucial for DNA binding, was specifically chosen on the basis of the contacts more frequently represented in the available list of the 'code'. Here we demonstrate that Jazz protein binds specifically to the double-stranded DNA target, with a dissociation constant of about 32 nM. Band shift and super-shift experiments confirmed the high affinity and specificity of Jazz protein for its DNA target. Moreover, we show that chimeric proteins, named Gal4-Jazz and Sp1-Jazz, are able to drive the transcription of a test gene from the human utrophin promoter.


Evolution in the recognition of infantile hypertrophic pyloric stenosis.
To analyze changes in the clinical condition at presentation and methods of establishing the diagnosis of infantile hypertrophic pyloric stenosis (IHPS). Retrospective review of patients who underwent pyloromyotomy (PM) for suspected IHPS at two institutions from 1969 through 1994 was performed. For the purposes of comparison, the population was divided into five equal time periods. Over the 25-year period, 901 infants underwent PM. Patients presented at a younger age, weighed more, and had a shorter length of illness in the most recent time period. Hypochloremic alkalosis was found half as frequently in the most recent time period compared to the earliest group. A palpable pyloric tumor was present in 79% of patients in the earliest time period compared with 23% in the most recent time period. Sixty-one percent of patients in the earliest group and 96% in the latest group underwent an imaging study, reflecting the referring physician's evaluation before referral to the surgeon. Currently, patients with IHPS less frequently present with the clinical hallmarks of the disease. The use of imaging studies to establish the diagnosis has become common practice. The result has been the diagnosis of IHPS before alkalosis has developed, a shorter clinical course, less morbidity, and a shorter postoperative hospital stay.


Survival after in-hospital cardiopulmonary resuscitation.
The use of postarrest variables to predict survival after discharge following in-hospital cardiopulmonary resuscitation has not been definitive. This study evaluates whether the duration of cardiopulmonary resuscitation (CPR) and other variables affect discharge rates and survival rates after discharge. Prospective cohort survival data and arrest variables were collected, including initial observed rhythm, duration of CPR, time of arrest, and number of arrests. Arrests on unmonitored general medical units, monitored telemetry units, and critical care units were included. Outcome measures were: survival after CPR, 24 hours post-CPR, survival to discharge, and to six months postdischarge. At both discharge and six months after discharge, ventricular fibrillation and ventricular tachycardia were associated with better survival rates than other initial rhythms (P < 0.001). There were significantly higher survival rates (P < 0.001) for those receiving CPR for < or =10 minutes as compared with those receiving CPR >10 minutes. Multiple versus single arrests and monitored versus unmonitored arrests approached significance. The time of day of the arrest was not a significant factor. Duration of CPR >10 minutes was predictive of significantly decreased survival to discharge and six months postdischarge. Low six-month survival rates may reflect the relatively high proportion of initial rhythms other than ventricular in the study group.


Cystic fibrosis transmembrane conductance regulator gene mutation and lung cancer risk.
The cystic fibrosis transmembrane conductance regulator (CFTR) holds an important role in retaining lung function, but its association with lung cancer is unclear. A case-control study was conducted to determine the possible associations of the genetic variants in the CFTR gene with lung cancer risk. Genotypes of the most common deletion DeltaF508, one functional SNP, and eight tag SNPs in the CFTR gene were determined in 574 lung cancer patients and 679 controls. A logistic regression model, adjusting for known risk factors, was used to evaluate the association of each variant with lung cancer risk, as confirmation haplotype and sub-haplotype analyses were performed. DeltaF508 deletion and genotypes with minor alleles in one tag SNP, rs10487372, and one functional SNP, rs213950, were inversely associated with lung cancer risk. The results of haplotype and sub-haplotype analyses were consistent with single variant analysis, all pointing to deletion DeltaF508 being the key variant for significant haplotypes and sub-haplotypes. Individuals with 'deletion-T' (DeltaF508/rs10487372) haplotype had a 68% reduced risk for lung cancer compared to common haplotype 'no-deletion-C' (OR=0.32; 95% CI=0.15-0.68; p=0.01). Genetic variations in the CFTR gene might modulate the risk of lung cancer. This study, for the first time, provides evidence of a protective role of the CFTR deletion carrier in the etiology of lung cancer.


Organic chelate-free and azido-rich metal clusters and coordination polymers from the use of Me3SiN3: a new synthetic route to complexes with beautiful structures and diverse magnetic properties.
In this Feature Article, we highlight the feasibility of a new, recently developed approach towards the synthesis of high-spin molecules and single-molecule magnets (SMMs). The key to the preparation of such molecular compounds is the organic azide precursor Me3SiN3, which fosters the formation of 3d-metal azido clusters and coordination polymers without requiring the assistance of any organic chelating/bridging group. All the isolated compounds contain metallic cores which are surrounded by end-on bridging N3- groups. Consequently, the reported molecular materials exhibit ferromagnetic exchange interactions between the spin carriers, resulting in the stabilization of the maximum possible spin ground states. The additional presence of magnetic anisotropy, depending on the 3d-metal ion used, gives rise to SMM properties with interesting and rare features. This article intends to introduce the readers to an unexplored, but in coordination chemistry very useful azido-based reagent and emphasize the pronounced differences in the structures and magnetic properties of the compounds that result from the reactions between 3d-metals and NaN3 or Me3SiN3 in the presence of organic bridging groups, and 3d-metals with Me3SiN3 alone.


A review of primary and secondary burn services in the Western Cape, South Africa.
In 2011, the Department of Health of the Western Cape Province, South Africa, requested a review of current burn services in the province, with a view to formulating a more efficient and cost-effective service. This article considers the findings of the review and presents strategies to improve delivery of appropriate burn care at primary and secondary levels. Surveys were conducted at eight rural and urban hospitals, two outreach workshops on burn care, four regional hospitals and at least 60 clinics in Cape Town and in the Western Cape as far as Ladismith. A survey on community management of paediatric burns was also included in the study. The incidence of burns was highest in the winter months, more than half of those affected were children, and the majority of burns were scalds from hot liquids. Most burn injuries managed at primary level were minor, with 75% of patients treated by nurse practitioners and discharged. The four regional secondary hospitals managed the majority of moderate to severe burns. There is room for improvement in terms of treatment facilities and consumables at all levels, regional hospitals being particularly restricted in terms of outdated equipment, a shortage of intensive care unit beds, and difficulties in transferring patients with major burns to a burns unit when indicated. The community management of paediatric burns was satisfactory, although considerable delays in transfer and insufficient pain control hampered appropriate care. A great need for ongoing education at all levels was identified. Ten strategies are presented that could, if implemented, lead to tangible improvements in the management of burn patients at primary and secondary levels in the Western Cape.


Biomaterial and biomechanical considerations to prevent risks in implant therapy.
This paper is aimed to present a biomaterials perspective in implant therapy that fosters improved bone response and long-term biomechanical competence from surgical instrumentation to final prosthetic rehabilitation. Strategies to develop implant surface texturing will be presented and their role as an ad hoc treatment discussed in light of the interplay between surgical instrumentation and implant macrogeometric configuration. Evidence from human retrieved implants in service for several years and from in vivo studies will be used to show how the interplay between surgical instrumentation and implant macrogeometry design affect osseointegration healing pathways, and bone morphologic and long-term mechanical properties. Also, the planning of implant-supported prosthetic rehabilitations targeted at long-term performance will be appraised from a standpoint where personal preferences (eg, cementing or screwing a prosthesis) can very often fail to deliver the best patient care. Lastly, the acknowledgement that every rehabilitation will have its strength degraded over time once in function will be highlighted, since the potential occurrence of even minor failures is rarely presented to patients prior to treatment.


Physiological adaptation of Desulfitobacterium hafniense strain TCE1 to tetrachloroethene respiration.
Desulfitobacterium spp. are ubiquitous organisms with a broad metabolic versatility, and some isolates have the ability to use tetrachloroethene (PCE) as terminal electron acceptor. In order to identify proteins involved in this organohalide respiration process, a comparative proteomic analysis was performed. Soluble and membrane-associated proteins obtained from cells of Desulfitobacterium hafniense strain TCE1 that were growing on different combinations of the electron donors lactate and hydrogen and the electron acceptors PCE and fumarate were analyzed. Among proteins increasingly expressed in the presence of PCE compared to fumarate as electron acceptor, a total of 57 proteins were identified by mass spectrometry analysis, revealing proteins involved in stress response and associated regulation pathways, such as PspA, GroEL, and CodY, and also proteins potentially participating in carbon and energy metabolism, such as proteins of the Wood-Ljungdahl pathway and electron transfer flavoproteins. These proteomic results suggest that D. hafniense strain TCE1 adapts its physiology to face the relative unfavorable growth conditions during an apparent opportunistic organohalide respiration.


Terror-inflicted thermal injury: A retrospective analysis of burns in the Israeli-Palestinian conflict between the years 1997 and 2003.
Terror attacks have changed in the past decade, with a growing tendency toward explosives and suicide bombings, which led to a rise in the incidence of thermal injuries among victims. The Israeli-Palestinian conflict of October 2000 marked a turning point when an organized terror campaign commenced. This article presents data of terror-associated burns from the Israeli National Trauma Registry (ITR) during the years 1997 to September 2000 and October 2000 to 2003. We analyzed demographic and clinical characteristics of 219 terror-related burn patients and 6,546 other burn patients admitted to hospitals in Israel between 1997 and 2003. Data were obtained from the ITR. Burns contributed about 9% of all terror related trauma and about 5% of all other trauma (p < 0.0001). These percentages have not changed significantly before and after October 2000. Terror-related burns afflict Jewish males more than predicted by their percentage in the population, whereas other burns afflict non-Jewish males more than predicted. Adults and young adults (15-59 years) are the predominant group in terror-related burns (80%), whereas children younger than 15 years are the predominant group in other burns (50%). Large burns (20% to 89% total body surface area) are more common in terror casualties, with greater mortality (6.4% in terror-related versus 3.4% in others; p = 0.0258). Although the incidence of burns has risen because of an organized campaign, this change was noticeable in other trauma forms as well in similar proportions. Terror-related burns afflict a targeted population, and generally take on a more severe course with greater mortality rates, thus requiring appropriate medical treatment.


Quick detection of herpes viruses from skin vesicles and exudates without nucleic acid extraction using multiplex PCR.
Distinguishing herpes virus infection from other skin diseases is sometimes difficult. This study aims to detect herpes virus DNA by multiplex real-time PCR without nucleic acid extraction in a short period of time. Specimens of cutaneous vesicles and swabs were obtained from 23 patients suspected of having herpes virus infection. These specimens were stored at -80 degrees C after dissolving them in sterilized water. DNA extraction was not performed. Specific real-time PCR primers for herpes simplex virus (HSV) 1 and 2 and varicella-zoster virus (VZV) were designed. These primers were used to perform realtime PCR with the frozen solution as template. Results clearly revealed a type-specific dissociation curve. Agarose gel electrophoresis was also performed and produced a single band of the expected size. In addition to using multiplex PCR, other steps were used to reduce the time even further. Each experiment took only 2 h to complete; the type of Herpes virus was successfully detected by multiplex real-time PCR without nucleic acid extraction in a short period of time. In conclusion, omission of the nucleic acid extraction step prior to real-time PCR does not negatively affect downstream reactions. Using multiplex PCR may allow more rapid qualitative analysis of HSV1, 2 and VZV.


Complementarity of PALM and SOFI for super-resolution live-cell imaging of focal adhesions.
Live-cell imaging of focal adhesions requires a sufficiently high temporal resolution, which remains a challenge for super-resolution microscopy. Here we address this important issue by combining photoactivated localization microscopy (PALM) with super-resolution optical fluctuation imaging (SOFI). Using simulations and fixed-cell focal adhesion images, we investigate the complementarity between PALM and SOFI in terms of spatial and temporal resolution. This PALM-SOFI framework is used to image focal adhesions in living cells, while obtaining a temporal resolution below 10 s. We visualize the dynamics of focal adhesions, and reveal local mean velocities around 190 nm min-1. The complementarity of PALM and SOFI is assessed in detail with a methodology that integrates a resolution and signal-to-noise metric. This PALM and SOFI concept provides an enlarged quantitative imaging framework, allowing unprecedented functional exploration of focal adhesions through the estimation of molecular parameters such as fluorophore densities and photoactivation or photoswitching kinetics.


An open-label study to investigate the cardiac safety profile of cabazitaxel in patients with advanced solid tumors.
This study assessed the cardiovascular safety of cabazitaxel, based on thorough evaluation of QT and non-QT variables, and the relationship between pharmacokinetic and pharmacodynamic electrocardiographic (ECG) profiles and the occurrence of Grade ≥3 cardiovascular adverse events. Patients with advanced solid tumors were treated with cabazitaxel 25 mg/m(2) every 3 weeks. Digital ECG recordings were obtained during Cycle 1 over 24 h after dosing. The primary end point was effect of cabazitaxel on QT interval corrected by the Fridericia formula (QTcF). Secondary end points were additional ECG parameters (QT, PR and QRS intervals, and heart rate), plasma pharmacokinetics of cabazitaxel and overall clinical safety. The pharmacodynamic (ECG) population included 94 patients. In 63 patients with a full 24-h ECG evaluation, the maximum upper bound of 90 % confidence interval (CI) for mean QTcF change from baseline was 7.46 ms (mean 4.8 ms), occurring at 1 h 30 min post-infusion. The slope of QTcF change from baseline versus cabazitaxel concentration was slightly negative (-0.012 [95 % CI -0.017; -0.008], equivalent to a 1.2 ms decrease per 100 ng/mL increase in cabazitaxel concentration). For non-QT variables, no effect was noted. No Grade ≥3 cardiac adverse events were observed; Grade ≥3 hypotension and lymphocele occurred in two patients and one patient, respectively. These results suggest that cabazitaxel has no clinically significant cardiovascular adverse effects in patients with advanced solid tumors.


Diet learning through post-ingestive consequences in sheep: the case of starch and casein variously combined in the same foods.
Ruminants generally succeed in selecting an appropriate diet relative to their nutrient requirements, and macronutrients such as energy and protein are considered as playing a primary role in their food preferences. Diet learning through post-ingestive consequences, evidenced by many studies that involved situations with simple discrimination tasks, may explain this ability to select a suitable diet. However, in more complex feeding environments where animals are faced with many plants varying both in their energy and protein contents, the extent to which such a mechanism operates is still uncertain. Our objective was to investigate a more complex feeding situation than previously tested and to determine whether lambs were able to associate three forages with both energy-based and protein-based post-ingestive consequences of various intensities. The doses of starch and casein used to elicit these post-ingestive consequences were chosen so that the apparent metabolisable energy and crude protein values of hays were within the range found in plants normally encountered under field conditions. We applied five treatments: EmPm, EhPm, EmPh, EhPh, where medium (m) or high (h) levels of nutrients (E = energy and P = protein) were associated with different hays, and E0N0 where no stimuli were associated. Each animal experienced only three treatments: E0N0-EmPm-EhPm or E0N0-EmPh-EhPh, each one being associated with one hay during conditioning, on the basis of one treatment per day over three consecutive days. Animals then had a choice between the hay associated with E0N0 and one of the two others, successively on the two following days. This procedure was repeated through five 1-week-long periods, and applied to two groups of lambs (n = 12) maintained at feeding levels sufficient for maintenance or for a 150 g/day growth rate. This experiment was complemented by a methodological trial that aimed to estimate the doses of starch and casein eliciting preferences and a post-trial that aimed to evaluate the effect of our treatments on sheep ruminal environment. The methodological trial showed that lambs perceived the stimuli and the doses, and the post-trial showed that treatments affected the ruminal environment. In the main experiment, the lambs preferred the rewarded hays but did not discriminate in their choices the variation of post-ingestive consequences due to energy and protein. This suggests that in situations closer to reality where animals experience many foods varying in nutrient contents, the learning process may be impaired. The lambs do not seem to have strictly relied on it for shaping their diet choices.


High financial hardship and mental health burden among gay, bisexual and other men who have sex with men.
Prior research has documented the ways in which financial hardships negatively impact health, particularly mental health. However, this association between financial hardships and mental health outcomes has rarely been examined in sexual minorities. The purpose of this study was to examine associations between financial hardships and mental health burdens among a sample of gay, bisexual and other men who have sex with men (MSM) in Paris, France. Participants (n = 580) completed a cross-sectional survey advertised on a geosocial networking application. Participants responded to measures of mental health, financial hardship, and socio-demographics. Modified Poisson models were used to estimate risk ratios (RRs) and 95% confidence intervals (CI) for the associations between financial hardship and the following outcomes: 1) depressive symptoms, 2) anxiety symptoms, and 3) psychological distress. After adjusting for socio-demographics, high financial hardships were associated with depressive symptoms (aRR: 1.48, 95% CI: 1.04, 2.11) and psychological distress (aRR: 1.56, 95% CI: 1.09, 2.23). Analyses also demonstrated that stress acts as a mediating variable. These preliminary results suggest that future interventions to reduce financial hardships may have positive effects on the mental health of such a population.


Early hyperglycemia predicts multiple organ failure and mortality but not infection.
Previous studies attempting to characterize the association between early hyperglycemia (EH) and subsequent outcome have been performed without utilization of a strict glycemic control protocol. We sought to characterize the clinical outcomes associated with EH in a cohort of severely injured trauma patients, when a strict glycemic control protocol was used. Data were obtained from a multicenter prospective cohort study evaluating clinical outcomes in blunt injured adults with hemorrhagic shock. Known diabetics and patients with isolated traumatic brain injury were excluded from the analysis. A strict glycemic protocol (target glucose, 80-110 mg/dL) was employed. Cox proportional hazard regression was used to evaluate the effects of EH on multiple organ failure (MOF), nosocomial infection (NI), and mortality, after adjusting for the effects of early death on subsequent infection rates. Overall mortality, MOF, and NI rates for the entire cohort were 19.6%, 37.5%, and 42.2%, respectively, with a mean Injury Severity Score of 31.6 +/- 14. Cox proportional hazard regression confirmed that EH was independently associated with almost a twofold higher mortality rate and a 30% higher incidence of MOF, but was not an independent risk factor for NI, after controlling for all important confounders. There continued to be no independent association between EH and NI, even when stratified by infection type (pneumonia, catheter-related blood stream infection, or urinary tract infection). These results suggest that EH is a marker of severe physiologic insult after injury, and that strict glycemic control may reduce or prevent the infectious complications previously shown to be associated with hyperglycemia early after injury.


Addressing the 'forgotten art of fundoscopy': evaluation of a novel teaching ophthalmoscope.
Direct ophthalmoscopy is an essential skill that students struggle to learn. A novel 'teaching ophthalmoscope' has been developed that allows a third person to observe the user's view of the fundus. To evaluate the potential use of this device as an aid to learning, and as a tool for objective assessment of competence. Participants were randomised to be taught fundoscopy either with a conventional direct ophthalmoscope (control) or with the teaching device (intervention). Following this teaching session, participant competence was assessed within two separate objective structured clinical examination (OSCE) stations: the first with the conventional ophthalmoscope and the second with the teaching device. Each station was marked by two independent masked examiners. Students were also asked to rate their own confidence in fundoscopy on a scale of 1-10. Scores of competence and confidence were compared between groups. The agreement between examiners was used as a marker for inter-rater reliability and compared between the two OSCE stations. Fifty-five medical students participated. The intervention group scored significantly better than controls on station 2 (19.8 vs 17.6; P=0.01). They reported significantly greater levels of confidence in fundoscopy (7.3 vs 4.9; P<0.001). Independent examiner scores showed significantly improved agreement when using the teaching device during assessment of competence, compared to the conventional ophthalmoscope (r=0.90 vs 0.67; P<0.001). The teaching ophthalmoscope is associated with improved confidence and objective measures of competence, when compared with a conventional direct ophthalmoscope. Used to assess competence, the device offers greater reliability than the current standard.


PrP(106-126) activates neuronal intracellular kinases and Egr1 synthesis through activation of NADPH-oxidase independently of PrPc.
Prion diseases are characterised by severe neural lesions linked to the presence of an abnormal protease-resistant isoform of cellular prion protein (PrPc). The peptide PrP(106-126) is widely used as a model of neurotoxicity in prion diseases. Here, we examine in detail the intracellular signalling cascades induced by PrP(106-126) in cortical neurons and the participation of PrPc. We show that PrP(106-126) induces the activation of subsets of intracellular kinases (e.g., ERK1/2), early growth response 1 synthesis and induces caspase-3 activity, all of which are mediated by nicotinamide adenine dinucleotide phosphate hydrogen-oxidase activity and oxidative stress. However, cells lacking PrPc are similarly affected after peptide exposure, and this questions the involvement of PrPc in these effects.


Isometric back extension endurance tests: a review of the literature.
To review the literature that describes and evaluates the use of isometric back extension endurance tests. Relevant articles in English were retrieved through a search of MEDLINE and the Index to Chiropractic Literature. Key search terms were back muscle endurance, isometric back endurance, trunk extensors, back muscle performance, and Sorensen test. The principal criterion for inclusion was as follows: any study that discussed or tested an isometric type of back endurance extension test. Studies that were excluded did not use an isometric testing protocol. Thirty-seven of the initial studies are included in this review. Six different types of isometric back extension endurance testing methods were found. Three of these procedures require special testing devices. Much of the research on this topic has centered on a procedure known as the Sorensen test. Normative databases have been established for the Sorensen test and 2 other test types. Validity and reliability have been assessed for some of the procedures. The influence of motivation and effort exerted by the subject are limiting factors in all of the tests reviewed. These psychologic factors warrant further research. On the basis of the literature reviewed, we determined that the Sorensen is probably the most clinically useful of these tests; it is easy to perform, requires no special equipment, and enjoys the most support from the literature.


The Use of Pistacia Lentiscus Chia Resin Versus Omeprazole in Protecting Male Rats Peptic Mucosa Against Cold Restraint Stress.
Peptic mucosal damage induced by acute stress is a serious cause of morbidity and mortality in critically ill patients. The study aimed to investigate the protective, antioxidant and anti-inflammatory effects of pretreatment with Chios mastic gum (CMG), a traditionally consumed herbal resin naturally deriving from the trunk of Pistacia Lentiscus var. Chia compared to Omeprazole, a standard medication used in the prevention and treatment of gastritis, against the effects of cold restraint stress (CRS) in rat gastric and colonic mucosa. Twenty-one male Wistar rats were randomly assigned to three groups: Control (C), Omeprazole (O), and CMG (M), according to the pre-treatment regime, and were subjected to CRS at 40C for 3 hours. The gastric and colonic mucosal lesions were histologically assessed. ELISA measured blood concentrations of TNF-α, IL-1β, peroxidase, superoxide dismutase (SOD) and total antioxidant capacity (TEAC). In both groups, O and M, gastric mucosal hyperemia, haemorrhagic infiltration and mucosal oedema, as well as colonic mucosal hyperaemia and haemorrhagic infiltration were significantly reduced compared to the controls (p<0.05). No significant differences were observed between Groups O and M. TNF-α levels were significantly lower in group M compared to Group O (p=0.013). IL-1β levels were significantly depressed in groups M and O compared to control (p≤ 0.001). The activity of both peroxidase and SOD enzymes decreased in group M compared to group O (p= 0.043 and p=0.047 respectively) and the control (p=0.018 and p< 0.001 respectively). The natural Chios mastic gum is a promising nutritional supplement with protective properties to the peptic mucosa against CRS, exerting anti-inflammatory and antioxidant effects.


Pharmacogenomics: candidate gene identification, functional validation and mechanisms.
Pharmacogenetics is the study of the role of inheritance in variation in drug response phenotypes. Those phenotypes can range from life-threatening adverse drugs reactions at one end of the spectrum to equally serious lack of therapeutic efficacy at the other. Over the past half century, pharmacogenetics has--like all of medical genetics--evolved from a discipline with a focus on monogenetic traits to become pharmacogenomics, with a genome-wide perspective. This article will briefly review recent examples of the application of genome-wide techniques to clinical pharmacogenomic studies and to pharmacogenomic model systems that vary from cell line-based model systems to yeast gene deletion libraries. Functional validation of candidate genes and the use of genome-wide techniques to gain mechanistic insights will be emphasized for the establishment of biological plausibility and as essential follow-up steps after the identification of candidate genes.


Immunochemical study on the pathway of electron flow in reduced nicotinamide adenine dinucleotide-dependent microsomal lipid peroxidation.
NADH could support the lipid peroxidation of rat liver microsomes in the presence of ferric ions chelated by ADP(ADP-Fe). The reaction had a broad pH optimum (pH 5.8--7.4) and was more active in the acidic pH range. Antibodies to NADH-cytochrome b5 reductase [EC 18.104.22.168] and cytochrome b5 inhibited NADH-dependent lipid peroxidation in the presence of ADP-Fe, whereas the antibody against NADPH-cytochrome c reductase [EC 126.96.36.199] showed no inhibition. These oberservations suggest that the electron from NADH was supplied to the lipid peroxidation reaction via NADH-cytochrome b5 reductase and cytochrome b5. On the other hand, NADPH-supported lipid peroxidation was strongly inhibited by the antibody against NADPH-cytochrome c reductase, confirming the participation of this this flavoprotein in the NADPH-dependent reaction. In the presence of both ADP-Fe and ferric ions chelated by EDTA(EDTA-Fe), NADH-dependent lipid peroxidation was highly stimulated up to the level of the NADPH-dependent reaction. In this case, the antibody against cytochrome b5 could not inhibit the reaction, while the antibody against NADH-cytochrome b5 reductase did inhibit it, suggesting the direct transfer of electrons from NADH-cytochrome b5 reductase to EDTA-Fe complex.


In situ K-edge X-ray absorption spectroscopy of the ligand environment of single-site Au/C catalysts during acetylene hydrochlorination.
The replacement of HgCl2/C with Au/C as a catalyst for acetylene hydrochlorination represents a significant reduction in the environmental impact of this industrial process. Under reaction conditions atomically dispersed cationic Au species are the catalytic active site, representing a large-scale application of heterogeneous single-site catalysts. While the metal nuclearity and oxidation state under operating conditions has been investigated in catalysts prepared from aqua regia and thiosulphate, limited studies have focused on the ligand environment surrounding the metal centre. We now report K-edge soft X-ray absorption spectroscopy of the Cl and S ligand species used to stabilise these isolated cationic Au centres in the harsh reaction conditions. We demonstrate the presence of three distinct Cl species in the materials; inorganic Cl-, Au-Cl, and C-Cl and how these species evolve during reaction. Direct evidence of Au-S interactions is confirmed in catalysts prepared using thiosulfate precursors which show high stability towards reduction to inactive metal nanoparticles. This stability was clear during gas switching experiments, where exposure to C2H2 alone did not dramatically alter the Au electronic structure and consequently did not deactivate the thiosulfate catalyst.


High-resolution MRI with cardiac and respiratory gating allows for accurate in vivo atherosclerotic plaque visualization in the murine aortic arch.
Genetically engineered mouse models provide enormous potential for investigation of the underlying mechanisms of atherosclerotic disease, but noninvasive imaging methods for analysis of atherosclerosis in mice are currently limited. This study aimed to demonstrate the feasibility of MRI to noninvasively visualize atherosclerotic plaques in the thoracic aorta in mice deficient in apolipoprotein-E, who develop atherosclerotic lesions similar to those observed in humans. To freeze motion, MR data acquisition was both ECG- and respiratory-gated. T(1)-weighted MR images were acquired with TR/TE approximately 1000/10 ms. Spatial image resolution was 49 x 98 x 300 micro m(3). MRI revealed a detailed view of the lumen and the vessel wall of the entire thoracic aorta. Comparison of MRI with corresponding cross-sectional histopathology showed excellent agreement of aortic vessel wall area (r = 0.97). Hence, noninvasive MRI should allow new insights into the mechanisms involved in progression and regression of atherosclerotic disease.


Life table analysis for immatures and female adults of the predatory beetle, Delphastus catalinae, feeding on whiteflies under three constant temperatures.
Immature development and reproductive life history of Delphastus catalinae (Horn) (Coleoptera: Coccinellidae) feeding on Bemisia tabaci biotype B (Gennadius) (Homoptera: Aleyrodidae) (= B. argentifolii Bellows and Perring) immatures was studied at three constant temperatures: 22, 26 and 30 degrees C. Lower developmental threshold temperatures (T0) were estimated at 9 and 9.9 degrees C, for males and females, respectively. Female adults weighed slightly more than males (0.587 and 0.505 mg, respectively). As temperature increased from 22 to 30 degrees C, developmental time from eggs to eclosion of the adult declined from 24 to 15 days. Thermal units required for immature development was approximately 300 degree-days. Percentage egg hatch declined at increasing temperatures, but no significant effect of time was found. The intrinsic rate of increase, r, increased from 0.048 to 0.082 and doubling time decreased from 14.44 to 8.45 days as temperature increased from 22 to 26 degrees C. Mean daily fecundity was modeled as a function of time and temperature to create a 3-dimensional surface. Overall, Delphastus catalinae was found to perform better at 22 and 26 degrees C while 30 degrees C was detrimental to immature development and adult reproduction.


Altered toxicity of the prion protein peptide PrP106-126 carrying the Ala(117)-->Val mutation.
The inherited prion diseases such as Gerstmann-Sträussler-Scheinker syndrome (GSS) are linked to point mutations in the gene coding for the cellular isoform of the prion protein (PrP(C)). One particular point mutation A117V (Ala(117)-->Val) is linked to a variable pathology that usually includes deposition of neurofibrillary tangles. A prion protein peptide carrying this point mutation [PrP106-126(117V)] was generated and compared with a peptide based on the normal human sequence [PrP106-126(117A)]. The inclusion of this point mutation increased the toxicity of PrP106-126 which could be linked to an increased beta-sheet content. An assay of microtubule formation in the presence of tau indicated that PrP106-126 decreased the rate of microtubule formation that could be related to the displacement of tau. PrP106-126 carrying the 117 mutation was more efficient at inhibiting microtubule formation. These results suggest a possible mechanism of toxicity for protein carrying this mutation via destabilization of the cytoskeleton and deposition of tau in filaments, as observed in GSS.


Korean Adolescents' Health Behavior and Psychological Status according to Their Mother's Nationality.
This study was conducted to compare adolescents' health behaviors and psychological status according to whether or not their mother was born in Korea. This secondary analysis used nationally representative data from the 2015 Korean Youth Risk Behavior Web-based Survey. The self-administered questionnaire included computer measured socio-demographic variables, 15 health behaviors, and psychological status. Data from 65,426 middle school and high school students were analyzed. Multiple logistic regression, adjusting for socio-demographic variables, was used to analyze differences in health behaviors and psychological status between adolescents with a foreign-born mother and those with a Korean mother. Adolescents who have foreign-born mothers had a lower level of current drinking and subjective happiness, but a higher stress level. The stress levels of the adolescents with foreign-born mothers could be affected by their multicultural background. It is necessary to analyze stress-influencing factors of multicultural adolescents by comparing them to adolescents from Korean parents. Additionally, our society should pay more attention to the mental health of multicultural adolescents. Schools should also make various efforts to protect multicultural adolescents by adopting mental health management programs led by school nurses and counselors.


Classification of painful or painless diabetic peripheral neuropathy and identification of the most powerful predictors using machine learning models in large cross-sectional cohorts.
To improve the treatment of painful Diabetic Peripheral Neuropathy (DPN) and associated co-morbidities, a better understanding of the pathophysiology and risk factors for painful DPN is required. Using harmonised cohorts (N = 1230) we have built models that classify painful versus painless DPN using quality of life (EQ5D), lifestyle (smoking, alcohol consumption), demographics (age, gender), personality and psychology traits (anxiety, depression, personality traits), biochemical (HbA1c) and clinical variables (BMI, hospital stay and trauma at young age) as predictors. The Random Forest, Adaptive Regression Splines and Naive Bayes machine learning models were trained for classifying painful/painless DPN. Their performance was estimated using cross-validation in large cross-sectional cohorts (N = 935) and externally validated in a large population-based cohort (N = 295). Variables were ranked for importance using model specific metrics and marginal effects of predictors were aggregated and assessed at the global level. Model selection was carried out using the Mathews Correlation Coefficient (MCC) and model performance was quantified in the validation set using MCC, the area under the precision/recall curve (AUPRC) and accuracy. Random Forest (MCC = 0.28, AUPRC = 0.76) and Adaptive Regression Splines (MCC = 0.29, AUPRC = 0.77) were the best performing models and showed the smallest reduction in performance between the training and validation dataset. EQ5D index, the 10-item personality dimensions, HbA1c, Depression and Anxiety t-scores, age and Body Mass Index were consistently amongst the most powerful predictors in classifying painful vs painless DPN. Machine learning models trained on large cross-sectional cohorts were able to accurately classify painful or painless DPN on an independent population-based dataset. Painful DPN is associated with more depression, anxiety and certain personality traits. It is also associated with poorer self-reported quality of life, younger age, poor glucose control and high Body Mass Index (BMI). The models showed good performance in realistic conditions in the presence of missing values and noisy datasets. These models can be used either in the clinical context to assist patient stratification based on the risk of painful DPN or return broad risk categories based on user input. Model's performance and calibration suggest that in both cases they could potentially improve diagnosis and outcomes by changing modifiable factors like BMI and HbA1c control and institute earlier preventive or supportive measures like psychological interventions.


Effects of stroke resistance on rowing economy in club rowers post-season.
In the sport of rowing, increasing the impulse applied to the oar handle during the stroke can result in greater boat velocities; this may be facilitated by increasing the surface area of the oar blade and/or increasing the length of the oars. The purpose of this study was to compare the effects of different rowing resistances on the physiological response to rowing. 5 male and 7 female club rowers completed progressive, incremental exercise tests on an air-braked rowing ergometer, using either low (LO; 100) or high (HI; 150) resistance (values are according to the adjustable "drag factor" setting on the ergometer). Expired air, blood lactate concentration, heart rate, rowing cadence, and ergometer power output were monitored during the tests. LO rowing elicited significantly greater cadences (P<0.01) and heart rates (P<0.05), whereas rowing economy (J · L O(2) equivalents(-1)) was significantly greater during HI rowing (P<0.05). These results suggest that economically, rowing with a greater resistance may be advantageous for performance. Moreover, biomechanical analysis of ergometer rowing support the notion that the impulse generated during the stroke increases positively as a function of rowing resistance. We conclude that an aerobic advantage associated with greater resistance parallels the empirical trend toward larger oar blades in competitive rowing. This may be explained by a greater stroke impulse at the higher resistance.


Cesarean scar pregnancy: a systematic review of treatment studies.
To study treatment modalities for cesarean scar pregnancies (CSPs), focusing on efficacy and complications in relation to study quality. Systematic review. Not applicable. A total of 2,037 women with CSP. Review of MEDLINE, EMBASE, and Cochrane Library to find studies including five or more women. Data were extracted on primary treatment modality/efficacy, complications, and future fertility. The level of evidence was categorized according to Oxford Centre for Evidence-based Medicine guidelines. Quality was assessed using The Cochrane Collaboration's Risk of Bias Tools for Randomized Controlled Trials and the modified Delphi techniques for case series. Meta-analysis was impossible owing to multifarious treatments. Successful first-line treatment. Complications were hysterectomy, laparotomy, bleeding >1,000 mL, or blood transfusion. Fifty-two studies were included: four randomized, controlled trials and 48 case series. Fifteen of the 52 analyzed studies were scored as high quality. Treatment modalities were condensed to 14 different approaches. Combining study quality, level of evidence, efficacy, and safety, five approaches for treating CSP are recommended, depending on availability, severity of patient symptoms, and surgical skills: [1] resection through a transvaginal approach, [2] laparoscopy, [3] uterine artery embolization in combination with dilatation and curettage and hysteroscopy, [4] uterine artery embolization in combination with dilatation and curettage, and [5] hysteroscopy. This review recommends treatment options for CSP in clinical practice, based on efficacy and safety. The literature supports an interventional rather than medical approach. Present recommendations are primarily based on case series. Multicenter, well-designed studies are needed to draw definite conclusions on how to treat CSP.


[Effectiveness of endoscopic sclerotherapy in the treatment of bleeding esophageal varices].
92 patients to whom urgent endoscopy and sclerotherapy of esophageal varices was performed are studied retrospectively. After the bleeding episode, elective sclerosis sessions were performed to eradicate varices, to prevent hemorrhagic complications and post-sclerotic stenosis somatostatin, H2 antagonists and sucralfate were administered. The Total number of sessions was 331, with a mean of 3.6 per patient (range 1-10). Immediate hemostasis was achieved in 93% of patients, with an early relapse in 10.4% of them. Hemorrhagic relapse two years following therapy was 35.8%. Mortality was 41%; 8% of the decreased patients belonged to Child's A functional grade, 24% belonged to B; and 68% to C. There was a 44% of complications, but only one death was due to the technique. No patient developed symptomatic stenosis neither hemorrhage secondary to esophageal ulceration. We conclude that endoscopic sclerotherapy is one of the principal therapeutic options in the hemorrhage due to esophageal varices, although new studies are necessary to define the role of somatostatin and H2 antagonists in the prophylaxis of complications.


Climate change and the potential effects on maternal and pregnancy outcomes: an assessment of the most vulnerable--the mother, fetus, and newborn child.
In 2007, the Intergovernmental Panel on Climate Change (IPCC) presented a large amount of evidence about global warming and the impact of human activities on global climate change. The Lancet Commission have identified a number of ways in which climate change can influence human health: lack of food and safe drinking water, poor sanitation, population migration, changing disease patterns and morbidity, more frequent extreme weather events, and lack of shelter. Pregnant women, the developing fetus, and young children are considered the most vulnerable members of our species and are already marginalized in many countries. Therefore, they may have increased sensitivity to the effects of climate change. Published literature in the fields of climate change, human health, tropical diseases, and direct heat exposure were assessed through the regular search engines. This article demonstrates that climate change will increase the risk of infant and maternal mortality, birth complications, and poorer reproductive health, especially in tropical, developing countries. Thus, climate change will have a substantial impact on the health and survival of the next generation among already challenged populations. There is limited knowledge regarding which regions will be most heavily affected. Research efforts are therefore required to identify the most vulnerable populations, fill knowledge gaps, and coordinate efforts to reduce negative health consequences. The effects of malnutrition, infectious diseases, environmental problems, and direct heat exposure on maternal health outcomes will lead to severe health risks for mothers and children. Increased focus on antenatal care is recommended to prevent worsening maternal health and perinatal mortality and morbidity. Interventions to reduce the negative health impacts caused by climate change are also crucial. Every effort should be made to develop and maintain good antenatal care during extreme life conditions as a result of climate change.


The Impact of Credit on Village Economies.
This paper evaluates the short-term impact of Thailand's 'Million Baht Village Fund'program, among the largest scale government microfinance iniative in the world, using pre- and post-program panel data and quasi-experimental cross-village variation in credit-per-household. We find that the village funds have increased total short-term credit, consumption, agricultural investment, income growth (from business and labor), but decreased overall asset growth. We also find a positive impact on wages, an important general equilibrium effect. The findings are broadly consistent qualitatively with models of credit-constrained household behavior and models of intermediation and growth.


Identification and characterization of glima 38, a glycosylated islet cell membrane antigen, which together with GAD65 and IA2 marks the early phases of autoimmune response in type 1 diabetes.
Immunoprecipitating IgG autoantibodies to glutamic acid decarboxylase, GAD65, and/or a tyrosine phosphatase, IA2, are present in the majority of individuals experiencing pancreatic beta cell destruction and development of type 1 diabetes. Here we identify a third islet cell autoantigen, a novel 38-kD protein, which is specifically immunoprecipitated with sera from a subset of prediabetic individuals and newly diagnosed type 1 diabetic patients. The 38-kD autoantigen, named glima 38, is an amphiphilic membrane glycoprotein, specifically expressed in islet and neuronal cell lines, and thus shares the neuroendocrine expression patterns of GAD65 and IA2. Removal of N-linked carbohydrates results in a protein of 22,000 Mr. Glima 38 autoantibodies were detected in 16/86 (19%) of newly diagnosed patients, including three very young children, who had a rapid onset of disease, and in 6/44 (14%) of prediabetic individuals up to several years before clinical onset. The cumulative incidence of GAD65 and glima 38 antibodies in these two groups was 83 and 80%, respectively, and the cumulative incidence of GAD65, glima 38, and IA2 antibodies in the same groups was 91 and 84%, respectively. GAD65, IA2, and glima 38 represent three distinct targets of immunoprecipitating IgG autoantibodies associated with beta cell destruction and type 1 diabetes.


Prenatal malnutrition and adult cognitive impairment: a natural experiment from the 1959-1961 Chinese famine.
The current measures of cognitive functioning in adulthood do not indicate a long-term association with prenatal exposure to the Dutch famine. However, whether such association emerges in China is poorly understood. We aimed to investigate the potential effect of prenatal exposure to the 1959-1961 Chinese famine on adult cognitive impairment. We obtained data from the Second National Sample Survey on Disability implemented in thirty-one provinces in 2006, and restricted our analysis to 387 093 individuals born in 1956-1965. Cognitive impairment was defined as intelligence quotient (IQ) score under 70 and IQ of adults was evaluated by the Wechsler Adult Intelligence Scale - China Revision. Famine severity was defined as excess death rate. The famine impact on adult cognitive impairment was estimated by difference-in-difference models, established by examining the variations of famine exposure across birth cohorts. Results show that compared with adults born in 1956-1958, those who were exposed to Chinese famine during gestation (born in 1959-1961) were at greater risk of cognitive impairment in the total sample. Stratified analyses showed that this effect was evident in males and females, but only in rural, not in urban areas. In conclusion, prenatal exposure to famine had an enduring deleterious effect on risk of cognitive impairment in rural adults.


Intensive insulin therapy in the neurocritical care setting is associated with poor clinical outcomes.
Studies devoted to intensive glucose control suggested that the intensive insulin therapy (IIT) approach could effectively reduce complications associated with critical illness. A program of IIT with the goal of achieving a blood glucose of 80-120 mg/dL was, therefore, adopted in this study. To explore the impact of this approach in patients admitted to a neurocritical care unit, we compared the short-term outcomes of patients treated before and after our policy change. Retrospectively extracted data from the electronic medical records of 1913 patients admitted between Feb 1, 2005 and Aug 30, 2006 were included in the standard insulin therapy group (SIT targeted to maintain blood glucose levels less than 150 mg/dL) and 1796 patients admitted between Sept 1, 2006 and March 30, 2008 were included in the IIT group (IIT-targeted to maintain blood glucose levels between 80 and 120 mg/dL). Mean glucose levels were lower in the IIT compared to SIT (136.9 mg/dL, SD 47.6 vs. 143.8 mg/dL, SD 46.4); however, this strategy was also associated with an increased incidence of hypoglycemia (OR: 1.8, and 95% CI: 1.5-2.3). The likelihood of mortality increased proportionally as the severity of hypoglycemia worsened (any blood glucose value <70 mg/dL, OR: 3.26, and 95% CI: 2.52-4.22, any blood glucose <40, OR: 3.65, and 95% CI: 2.21-6.02, any blood glucose <20, OR: 6.25, and 95% CI: 2.41-16.23). IIT was not only able to reduce overall mean glucose levels, but also resulted in significantly more episodes of hypoglycemia, increased mortality, and increased length of stay. The relationship between hypoglycemia and mortality indicates that efforts to control glucose levels should also aggressively avoid induction of hypoglycemia.


Organization of the SH3-SH2 unit in active and inactive forms of the c-Abl tyrosine kinase.
The tyrosine kinase c-Abl is inactivated by interactions made by its SH3 and SH2 domains with the distal surface of the kinase domain. We present a crystal structure of a fragment of c-Abl which reveals that a critical N-terminal cap segment, not visualized in previous structures, buttresses the SH3-SH2 substructure in the autoinhibited state and locks it onto the distal surface of the kinase domain. Surprisingly, the N-terminal cap is phosphorylated on a serine residue that interacts with the connector between the SH3 and SH2 domains. Small-angle X-ray scattering (SAXS) analysis shows that a mutated form of c-Abl, in which the N-terminal cap and two other key contacts in the autoinhibited state are deleted, exists in an extended array of the SH3, SH2, and kinase domains. This alternative conformation of Abl is likely to prolong the active state of the kinase by preventing it from returning to the autoinhibited state.


A scenario for the evolution of selective egg coloration: the roles of enemy-free space, camouflage, thermoregulation and pigment limitation.
Behavioural plasticity can drive the evolution of new traits in animals. In oviparous species, plasticity in oviposition behaviour could promote the evolution of new egg traits by exposing them to different selective pressures in novel oviposition sites. Individual females of the predatory stink bug Podisus maculiventris are able to selectively colour their eggs depending on leaf side, laying lightly pigmented eggs on leaf undersides and more pigmented eggs, which are more resistant to ultraviolet (UV) radiation damage, on leaf tops. Here, we propose an evolutionary scenario for P. maculiventris egg pigmentation and its selective application. We experimentally tested the influence of several ecological factors that: (i) could have favoured a behavioural shift towards laying eggs on leaf tops and thus the evolution of a UV-protective egg pigment (i.e. exploitation of enemy-reduced space or a thermoregulatory benefit) and (ii) could have subsequently led to the evolution of selective pigment application (i.e. camouflage or costly pigment production). We found evidence that a higher predation pressure on leaf undersides could have caused a shift in oviposition effort towards leaf tops. We also found the first evidence of an insect egg pigment providing a thermoregulatory advantage. Our study contributes to an understanding of how plasticity in oviposition behaviour could shape the responses of organisms to ecological factors affecting their reproductive success, spurring the evolution of new morphological traits.


Tobacco-Product Use by Adults and Youths in the United States in 2013 and 2014.
Noncigarette tobacco products are evolving rapidly, with increasing popularity in the United States. We present prevalence estimates for 12 types of tobacco products, using data from 45,971 adult and youth participants (≥12 years of age) from Wave 1 (September 2013 through December 2014) of the Population Assessment of Tobacco and Health (PATH) Study, a large, nationally representative, longitudinal study of tobacco use and health in the United States. Participants were asked about their use of cigarettes, e-cigarettes, traditional cigars, cigarillos, filtered cigars, pipe tobacco, hookah, snus pouches, other smokeless tobacco, dissolvable tobacco, bidis, and kreteks. Estimates of the prevalence of use for each product were determined according to use category (e.g., current use or use in the previous 30 days) and demographic subgroup, and the prevalence of multiple-product use was explored. More than a quarter (27.6%) of adults were current users of at least one type of tobacco product in 2013 and 2014, although the prevalence varied depending on use category. A total of 8.9% of youths had used a tobacco product in the previous 30 days; 1.6% of youths were daily users. Approximately 40% of tobacco users, adults and youths alike, used multiple tobacco products; cigarettes plus e-cigarettes was the most common combination. Young adults (18 to 24 years of age), male adults and youths, members of racial minorities, and members of sexual minorities generally had higher use of tobacco than their counterparts. During this study, 28% of U.S. adults were current users of tobacco, and 9% of youths had used tobacco in the previous 30 days. Use of multiple products was common among tobacco users. These findings will serve as baseline data to examine between-person differences and within-person changes over time in the use of tobacco products. (Funded by the National Institute on Drug Abuse and the Food and Drug Administration.).


Health Seeking Behaviour and Treatment Intentions of Dengue and Fever: A Household Survey of Children and Adults in Venezuela.
Dengue in Venezuela is a major public health problem with an increasing incidence of severe cases. Early diagnosis and timely treatment influences the outcome of dengue illness, as delay in care-seeking is significantly associated with complications leading to severe dengue. We aimed to understand patterns of health seeking behaviour (HSB) in individuals exposed to high dengue incidence in order to improve early attendance to health centres. Between September 2013 and February 2014 a cross-sectional household survey was performed in Maracay, Venezuela. Intended HSB of adults and children's parents/guardians was assessed with respect to fever or suspected dengue. Data was collected through structured questionnaires from 105 individuals. Most individuals felt at risk of dengue and believed it could be a deadly disease. In the case of suspected dengue, the majority (60%) would choose to first seek medical help versus first treating at home, in contrast to 11% in the case of fever. Amongst those who decided to visit a doctor, a suspected dengue infection would prompt them to search medical help earlier than if having only fever (p<0.001). Multivariate analysis modelling showed that the independent factors associated with the intention to firstly visit a doctor versus treating at home in the case of dengue were feeling at risk (OR = 3.29; p = 0.042) and being an adult (as opposed to caring for a child as a parent/guardian; OR = 3.33, p = 0.021), while having had a previous dengue infection (OR = 0.29; p = 0.031) and living in the neighbourhood Caña de Azúcar (OR = 0.28, p = 0.038) were negatively associated with seeking medical care as their first action. Knowledge of HSB related to dengue is scarce in the Americas, our study attempts to contribute to a better understanding of HSB in this region. Improving early dengue disease recognition and awareness may enhance prompt attendance to medical care in affected populations and thereby reduce mortality and severity of dengue. Especially for those with a previous dengue infection, efforts have to be made to promote prompt health centre attendance.


An ultra-low-input native ChIP-seq protocol for genome-wide profiling of rare cell populations.
Combined chromatin immunoprecipitation and next-generation sequencing (ChIP-seq) has enabled genome-wide epigenetic profiling of numerous cell lines and tissue types. A major limitation of ChIP-seq, however, is the large number of cells required to generate high-quality data sets, precluding the study of rare cell populations. Here, we present an ultra-low-input micrococcal nuclease-based native ChIP (ULI-NChIP) and sequencing method to generate genome-wide histone mark profiles with high resolution from as few as 10(3) cells. We demonstrate that ULI-NChIP-seq generates high-quality maps of covalent histone marks from 10(3) to 10(6) embryonic stem cells. Subsequently, we show that ULI-NChIP-seq H3K27me3 profiles generated from E13.5 primordial germ cells isolated from single male and female embryos show high similarity to recent data sets generated using 50-180 × more material. Finally, we identify sexually dimorphic H3K27me3 enrichment at specific genic promoters, thereby illustrating the utility of this method for generating high-quality and -complexity libraries from rare cell populations.