Moral and prudential considerations in adopting electronic medical records.
One might argue that beneficence entails a moral obligation for health care providers and systems to adopt electronic medical records (EMR). But this argument is thwarted because EMR systems are currently not required to meet existing standards of care for health care services. Yet using EMR systems may still be prudent if benefits of adoption significantly outweigh burdens. Future moral questions regarding EMR systems will shift from obligations of adoption to that of proper use.


Protein expression of brain endothelial cell E-cadherin after hypoxia/aglycemia: influence of astrocyte contact.
The blood-brain barrier (BBB) plays a crucial role in protecting the central nervous system (CNS) from any changes in homeostasis brought about by pathological conditions. Cerebrovascular permeability is an important factor in the development of cerebral edema following stroke [M. Plateel, E. Teissier, R. Cecchelli, Hypoxia, dramatically increases the nonspecific transport of blood-borne proteins to the brain. J. Neurochem. 68 (1997) 874-877] and any changes in its function can have detrimental neurological consequences. Recently, research has shown that an in vitro model of the BBB is sensitive to short exposures of hypoxia/aglycemia and that changes in endothelial cell calcium flux may be responsible for structural and functional variations in the BBB during ischemic stress [T.J. Abbruscato, T.P. Davis, Combination of hypoxia/aglycemia compromises in vitro BBB. J. Pharmacol. Exp. Ther. 289 (1999) 668-675]. Present experiments investigated bovine brain microvessel endothelial cell (BBMEC) expression of a Ca(2+)-dependent cell-cell adhesion molecule, E-cadherin, which has been shown to be important for blood-brain barrier function [D. Pal, K.L. Audus, T.J. Siahaan, Modulation of cellular adhesion in bovine brain microvessel endothelial cells by a decapeptide. Brain Research 747 (1997) 103-113]. Since it is believed that astrocyte-endothelial cell interaction is crucial for maintenance of in vivo BBB characteristics, we have attempted to optimize our isolation and culturing techniques to produce a reliable, in vitro model of the BBB that is suitable to study pathological conditions. Immunofluoresence experiments showed positive staining for E-cadherin, yet failed to show any change in cellular distribution of E-cadherin upon hypoxic/aglycemic exposure. In addition, culturing BBMECs with C6 conditioned medium (CM) had no effect on the localization of E-cadherin. Western blotting experiments showed that BBMECs express E-cadherin and this protein is decreased in a time dependent manner after various hypoxic/aglycemic exposures when endothelial cells are cultured alone or with C6 astrogliomas grown on a separate culture surface. When C6 astrocytes are grown directly opposed to endothelial cells, with a porous membrane between, we observed a slight attenuation in the decreased BBMEC expression of E-Cadherin after hypoxia/aglycemia exposure. This work has shown that the mammalian brain endothelial/astrocyte co-culture system is a useful model for studies of pathological conditions where BBB characteristics are maintained.


Exact unconditional tests for a 2 x 2 matched-pairs design.
The problem of comparing two proportions in a 2 x 2 matched-pairs design with binary responses is considered. We consider one-sided null and alternative hypotheses. The problem has two nuisance parameters. Using the monotonicity of the multinomial distribution, four exact unconditional tests based on p-values are proposed by reducing the dimension of the nuisance parameter space from two to one in computation. The size and power of the four exact tests and two other tests, the exact conditional binomial test and the asymptotic McNemar's test, are considered. It is shown that the tests based on the confidence interval p-value are more powerful than the tests based on the standard p-value. In addition, it is found that the exact conditional binomial test is conservative and not powerful for testing the hypothesis. Moreover, the asymptotic McNemar's test is shown to have incorrect size; that is, its size is larger than the nominal level of the test. Overall, the test based on McNemar's statistic and the confidence interval p-value is found to be the most powerful test with the correct size among the tests in this comparison.


Characterization of a partial wheat-Thinopyrum intermedium amphiploid and its reaction to fungal diseases of wheat.
Partial amphiploids between wheat (Triticum aestivum L.) and Thinopyrum species play an important role in the transfer and use of traits from alien species. A wheat-Thinopyrum intermedium partial amphiploid, TAI8335, and its alien parent were characterized by a combination of genomic in situ hybridization (GISH) and cytological observations. Evidence from GISH indicated that the donor parent Th. intermedium possessed seven pairs of S, seven J(s) and 21 J chromosomes. Mitotic observation showed that the majority of TAI8335 plants had 56 chromosomes, but a few had 54 to 55, in some cases with two to three additional telochromosomes. The chromosomes in most pollen mother cells of plants with 2n = 56 formed 28 bivalents, averaging 27.12 in 223 cells, suggesting a basic cytological stability. Sequential GISH patterns using genomic Pseudoroegneria spicata and genomic Th. intermedium DNA as probes revealed that TAI8335 had fourteen chromosomes derived from Th. intermedium and its alien genome consisted of one pair of S-, three pairs of J(s) - and one pair of J-genome chromosomes as well as two translocated chromosome pairs, one being a Robertsonian translocation and another an intercalary translocation, both of which involved J and S genome. Two of the telochromosomes in the aneuploid plants originated from the J genome and one from wheat. Disease screening demonstrated this line was highly resistant to leaf rust, stem rust, stripe rust and powdery mildew. This study showed that the partial amphiploid TAI8335 appears to serve as a novel source for the transfer of resistance genes for multiple fungal pathogens to wheat.


Impact of Exercise on Cardiometabolic Component Risks in Spinal Cord-injured Humans.
Spinal cord injury (SCI) creates a complex pathology, characterized by low levels of habitual physical activity and an increased risk of cardiometabolic disease. This study aimed to assess the effect of a moderate-intensity upper-body exercise training intervention on biomarkers of cardiometabolic component risks, adipose tissue metabolism, and cardiorespiratory fitness in persons with SCI. Twenty-one inactive men and women with chronic (>1 yr) SCI (all paraplegic injuries) 47 ± 8 yr of age (mean ± SD) were randomly allocated to either a 6-wk prescribed home-based exercise intervention (INT; n = 13) or control group (CON; n = 8). Participants assigned to the exercise group completed 4 × 45-min moderate-intensity (60%-65% peak oxygen uptake (V˙O2peak)) arm-crank exercise sessions per week. At baseline and follow-up, fasted and postload blood samples (collected during oral glucose tolerance tests) were obtained to measure metabolic regulation and biomarkers of cardiovascular disease. Abdominal subcutaneous adipose tissue biopsies were also obtained, and cardiorespiratory fitness was assessed. Compared with CON, INT significantly decreased (P = 0.04) serum fasting insulin (Δ, 3.1 ± 10.7 pmol·L for CON and -12.7 ± 18.7 pmol·L for INT) and homeostasis model assessment of insulin resistance (HOMA2-IR; Δ, 0.06 ± 0.20 for CON and -0.23 ± 0.36 for INT). The exercise group also increased V˙O2peak (Δ, 3.4 mL·kg·min; P ≤ 0.001). Adipose tissue metabolism, composite insulin sensitivity index (C-ISIMatsuda), and other cardiovascular disease risk biomarkers were not different between groups. Moderate-intensity upper-body exercise improved aspects of metabolic regulation and cardiorespiratory fitness. Changes in fasting insulin and HOMA2-IR, but not C-ISIMatsuda, suggest improved hepatic but not peripheral insulin sensitivity after 6 wk of exercise training in persons with chronic paraplegia.


Use of an open-access gastroscopy service by a general practice: findings and subsequent specialist referral rate.
An analysis of 102 open-access gastroscopy requests from one general practice over 38 months showed that the detection rate of abnormalities was 58%. Even though no predetermined investigation criteria were used these results compare favourably with gastroscopy findings generally and are superior to the detection rate of lesions using barium meals. Only 12% of the patients who underwent gastroscopy required subsequent referral to a consultant. This represents a major benefit, hitherto undocumented, of an open-access gastroscopy service. Considerations of accuracy, safety and cost effectiveness coupled with the availability of efficacious drugs appear to favour the case for open-access gastroscopy for general practitioners.


Evaluation of Efficacy of Surgical Periodontal Therapy with the Use of Bone Graft in the Treatment of Periodontal Intrabony Defects.
One of the most important goals of periodontitis therapy is the elimination of deep periodontal pockets. In regenerative periodontal therapy, different types of bone grafts, membranes, growth factors, etc. are used to improve regeneration of lost periodontal tissue. The aim of this study was to evaluate the effect of surgical therapy supported by the use of bone replacement material in the treatment of deep intrabony pockets, compared to surgical treatment (flap surgery) without the use of bone replacement in advanced periodontitis. The study included 50 patients of both sexes with advanced periodontitis, divided into two groups. After initial periodontal therapy was performed, plaque index (PI), papillary bleeding index (PBI) were verified, and depth of periodontal pockets was measured in both groups. One group (group 1) of the patients underwent surgical therapy, open flap surgery, while the other group (group 2) underwent the same surgical treatment method (open flap surgery), during which bone defects were filled with bone replacement material. The results showed that both group 1 and group 2 experienced improvements after periodontal surgical therapy. In group 1, there are no statistically significant changes in all three plaque index measurements (PI), while there has been a significant reduction in PI in group 2 following the surgery. For the PBI index, it was determined that there were statistically significant changes in values in group 1, both after surgical procedures and six months later, as well as in group 2. Statistical analysis of the results of the probing depth of pockets has shown that there are significant changes in the measurement of the depth of periodontal pocket one month after the surgery, as well as six months later, meaning that there has been a significant reduction in the depth of the periodontal pocket one month following the surgery as well as six months later, for both groups. However, we did not determine a statistically significant difference in the probing depth of pockets between these two groups. Six months after a surgical therapy, clinical parameters showed a reduction of the probing depth of the periodontal pocket in both examined groups. The use of bone replacement did not yield significantly better results in reducing the depth of probing compared to the standard flap surgery. We believe that future research should focus on testing the effectiveness of new regenerative methods and materials (bone replacements with various properties, membranes, and surgical methods) that will result in better treatment results with predictable outcomes.


Interfacial Organization and Forces Arising from Epithelial-Cancerous Monolayer Interactions.
The interfacial interactions between epithelia and cancer cells have profound relevance for tumor development and metastasis. Through monolayer confrontation of MCF10A (nontumorigenic human breast epithelial cells) and MDA-MB-231 (human epithelial breast cancer cells) cells, we investigate the epithelial-cancerous interfacial interactions at the tissue level. We show that the monolayer interaction leads to competitive interfacial morphodynamics and drives an intricate spatial organization of MCF10A cells into multicellular finger-like structures, which further branch into multiple subfinger-like structures. These hierarchical interfacial structures penetrate the cancer monolayer and can spontaneously segregate or even envelop cancer cell clusters, consistent with our theoretical prediction. By tracking the substrate displacements via embedded fluorescent nanobeads and implementing nanomechanical modeling that combines atomic force microscopy and finite element simulations, we computed mechanical force patterns, including traction forces and monolayer stresses, caused by the monolayer interaction. It is found that the heterogeneous mechanical forces accumulated in the monolayers are able to squeeze cancer cells, leading to three-dimensional interfacial bulges or cell extrusion, initiating the p53 apoptosis signaling pathways of cancer cells. We reveal that intercellular E-cadherin and P-cadherin of epithelial cells differentially regulate the interfacial organization including migration speed, directionality, spatial correlation, F-actin alignment, and subcellular protrusions of MCF10A cells; whereas E-cadherin governs interfacial geometry that is relevant to force localization and cancer cell extrusion, P-cadherin maintains interfacial integrity that enables long-range force transmission. Our findings suggest that the collaborative molecular and mechanical behaviors are crucial for preventing epithelial tissues from undergoing tumor invasion.


High caregiver adverse childhood experiences are associated with pediatric influenza and COVID-19 vaccination uptake.
Factors surrounding vaccine uptake are complex. Although anxiety, which could influence vaccination decisions, has been associated with adverse childhood experiences (ACEs), little is known about links between caregiver ACEs and pediatric vaccine uptake. We evaluated associations between caregivers' ACEs and decisions to vaccinate their children with influenza and COVID-19 vaccines. A cross-sectional study of caregivers of patients ≥6 months at one pediatric primary care center was performed. Caregivers completed a 19-question survey examining caregiver ACEs, influenza vaccine acceptance and beliefs, and intention to vaccinate their child with the COVID-19 vaccine. Demographic characteristics, social risks (e.g., housing and food insecurity), and vaccination data for children present with each caregiver were extracted from the electronic health record. Statistical analyses included chi-square tests for categorical and t-tests for continuous variables. A total of 240 caregivers participated, representing 283 children (mean age of 5.9 years, 47% male). Twenty-four percent (n=58) had high ACEs (≥4). Of those with high ACEs, 55% accepted pediatric influenza vaccination compared to 38% with low ACEs (p=0.02). Those with high ACEs had more positive attitudes toward influenza vaccine safety and efficacy (p≤0.02). Those with high, compared to low, ACEs were also more likely to accept COVID-19 vaccination (38% vs. 24%; p=0.04). Pediatric influenza vaccination rates and intention to vaccinate children against COVID-19 differed between caregivers with high and low ACEs: those with more ACEs were more likely to vaccinate. Further studies assessing the role of caregiver ACEs on vaccine decision-making are warranted.


Assisting cultivation of photosynthetic microorganisms by microbial fuel cells to enhance nutrients recovery from wastewater.
Spirulina was cultivated in cathodic compartments of photo-microbial fuel cells (P-MFC). Anodic compartments were fed with swine-farming wastewater, enriched with sodium acetate (2.34gCODL-1). Photosynthetic oxygen generation rates were sufficient to sustain cathodic oxygen reduction, significantly improving P-MFC electrochemical performances, as compared to water-cathode control experiments. Power densities (0.8-1Wm-2) approached those of air-cathode MFCs, run as control. COD was efficiently removed and only negligible fractions leaked to the cathodic chamber. Spirulina growth rates were comparable to those of control (MFC-free) cultures, while pH was significantly (0.5-1unit) higher in P-MFCs, due to cathodic reactions. Alkaliphilic photosynthetic microorganisms like Spirulina might take advantage of these selective conditions. Electro-migration along with diffusion to the cathodic compartment concurred for the recovery of most nutrients. Only P and Mg were retained in the anodic chamber. A deeper look into electro-osmotic mechanisms should be addressed in future studies.


A pilot study: bovine colostrum supplementation and hormonal and autonomic responses to competitive cycling.
The aim of this pilot investigation was to examine the influence of bovine colostrum protein concentrate (CPC) supplementation on salivary hormones, salivary IgA and heart rate variability over consecutive days of competitive cycling. Ten highly-trained male road cyclists (mean±SEM; age=22.2±4.7 yr; mass=70.5±4.5 kg; VO2max=72.9±3.8 mL.kg-1.min-1) were randomly assigned to a control (N.=6, 10g whey protein concentrate/day) or bovine CPC group (N.=4, 10 g bovine CPC/day). Cyclists provided a baseline saliva sample before commencing eight weeks of supplementation, and competing in a five day cycle race. Cyclists provided saliva samples and measured heart rate variability (HRV) each day of the race. Saliva samples were analysed for cortisol, testosterone and IgA concentrations. Bovine CPC supplementation was associated with increased morning cortisol concentration on the first day of racing when compared to the control group (P=0.004) and significantly prevented a decrease in testosterone concentration over the race period (P≤0.05). Across the race period parasympathetic indices of HRV were elevated in the bovine CPC group and reduced in the control group (P≤0.05), while there were no significant differences in salivary IgA between groups. Bovine CPC supplementation maintained salivary testosterone concentration and modulated autonomic activity over consecutive days of competitive cycling. This pilot study provides justification to explore the effects of bovine CPC on recovery in endurance athletes further.


Regulation of Osteoblast Metabolism by Wnt Signaling.
Wnt/β-catenin signaling plays a critical role in the achievement of peak bone mass, affecting the commitment of mesenchymal progenitors to the osteoblast lineage and the anabolic capacity of osteoblasts depositing bone matrix. Recent studies suggest that this evolutionarily-conserved, developmental pathway exerts its anabolic effects in part by coordinating osteoblast activity with intermediary metabolism. These findings are compatible with the cloning of the gene encoding the low-density lipoprotein related receptor-5 (LRP5) Wnt co-receptor from a diabetes-susceptibility locus and the now well-established linkage between Wnt signaling and metabolism. In this article, we provide an overview of the role of Wnt signaling in whole-body metabolism and review the literature regarding the impact of Wnt signaling on the osteoblast's utilization of three different energy sources: fatty acids, glucose, and glutamine. Special attention is devoted to the net effect of nutrient utilization and the mode of regulation by Wnt signaling. Mechanistic studies indicate that the utilization of each substrate is governed by a unique mechanism of control with β-catenin-dependent signaling regulating fatty acid β-oxidation, while glucose and glutamine utilization are β-catenin-independent and downstream of mammalian target of rapamycin complex 2 (mTORC2) and mammalian target of rapamycin complex 1 (mTORC1) activation, respectively. The emergence of these data has provided a new context for the mechanisms by which Wnt signaling influences bone development.


MVsCarta: A protein database of matrix vesicles to aid understanding of biomineralization.
Matrix vesicles (MVs) are membranous nanovesicles released by chondrocytes, osteoblasts, and odontoblasts. They play a critical role in modulating mineralization. Here, we present a manually curated database of MV proteins, namely MVsCara to provide comprehensive information on MVs of protein components. In the current version, the database contains 2,713 proteins of six organisms identified in bone, cartilage, tooth tissues, and cells capable of producing a mineralized bone matrix. The MVsCarta database is now freely assessed at http://bioinf.xmu.edu.cn/MVsCarta. The search and browse methods were developed for better retrieval of data. In addition, bioinformatic tools like Gene Ontology (GO) analysis, network visualization and protein-protein interaction analysis were implemented for a functional understanding of MVs components. Similar database hasn't been reported yet. We believe that this free web-based database might serve as a useful repository to elucidate the novel function and regulation of MVs during mineralization, and to stimulate the advancement of MV studies.


The complexes of mammalian target of rapamycin.
The mammalian target of rapamycin (mTOR) has attracted substantial attention because of its involvement in a variety of diseases, such as cancer, cardiac hypertrophy, diabetes and obesity. Current knowledge indicates that mTOR functions as two distinct multiprotein complexes, mTORC1 and mTORC2. mTORC1 phosphorylates p70 S6 kinase (S6K1) and eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1), and regulates cell growth, proliferation, and survival by integrating hormones, growth factors, nutrients, stressors and energy signals. In contrast, mTORC2 is insensitive to nutrients or energy conditions. However, in response to hormones or growth factors, mTORC2 phosphorylates Akt, and regulates actin cytoskeleton and cell survival. These findings not only reveal the crucial role of mTOR in physiology and pathology, but also reflect the complexity of the mTOR signaling network. In this review, we discuss the advances in studies of the mTOR complexes, including the interacting proteins, the upstream regulators and the downstream effectors of mTOR complexes, as well as their implication in certain human diseases.


Dehydrins in cold-acclimated apices of birch (Betula pubescens ehrh. ): production, localization and potential role in rescuing enzyme function during dehydration
Dehydrins accumulate in various plant tissues during dehydration. Their physiological role is not well understood, but it is commonly assumed that they assist cells in tolerating dehydration. Since in perennials the ability of the shoot apex to withstand dehydration is pivotal for survival through winter, we investigated if and how dehydrins may be involved. A first step in assessing such a role is the identification of their subcellular location. We therefore mapped the location of dehydrin homologues, abscisic acid-responsive (RAB 16-like) polypeptides, in the apex of birch (Betula pubescens Ehrh.). In non-cold-acclimated plants a single low-abundant RAB 16-member (a 33-kDa polypeptide) was produced, and localized in the cytoplasm only. During cold acclimation two additional members were produced (24 and 30 kDa) and accumulated in nuclei, storage protein bodies and starch-rich amyloplasts. Western blots of proteins isolated from purified starch granules and from protein bodies revealed the presence of the 24-kDa dehydrin. Since starch and protein reserves are gradually consumed during winter, serving cell maintenance, starch- and protein-degrading enzymes must remain locally active. We therefore investigated the hypothesis that dehydrins might create local pools of water in otherwise dehydrated cells, thereby maintaining enzyme function. In agreement with our hypothesis, enzyme assays showed that under conditions of low water activity a partially purified dehydrin fraction was able to improve the activity of alpha-amylase (EC 184.108.40.206.) relative to fractions from which dehydrin was removed by immunoprecipitation. The results confirm the general belief that dehydrins serve desiccation tolerance, and suggest that a major function is to rescue the metabolic processes that are required for survival and re-growth.


Effect of gallic acid on chronic restraint stress-induced anxiety and memory loss in male BALB/c mice.
Long-term exposure to stress leads to memory deficits and certain mood disorders such as depression and anxiety. We aimed to study the effect of gallic acid (GA) on chronic restraint stress (CRS) induced anxiety and memory deficits in male BALB/c mice. Ninety male BALB/c mice were assigned to nine groups including caged control (CC): food-water deprived (FWD), under chronic restraint stress (CRS), CRS+ gallic acid (5, 10, and 20 mg/kg), and gallic acid (5, 10, and 20 mg/kg). Behavioral assays were performed after 21 days of daily treatment with CRS and GA. Serum and brain levels of malondialdehyde (MDA) and total antioxidant capacity (TCA) and serum corticosterone level were also measured. Treatment of CRS mice with GA significantly improved passive avoidance memory in the shuttle box and ameliorated anxiety-like behaviors in the elevated plus maze (EPM) and open filed test (OFT). GA treatment significantly reduced elevated levels of serum and brain MDA and increased brain TCA. CRS and GA did not affect serum corticosterone levels. Treatment of healthy mice with GA had some adverse effects and induced some anxiety and oxidative stress. GA exerted protective effects against stress-induced mood and memory deficit disorders.


HLA tissue typing has no effect on the outcome of patients undergoing a living-donor liver transplant: a single-center experience in Egypt.
To analyze the effect of human leukocyte antigen tissue typing on outcome of live-donor liver transplant. Fifty recipients underwent live-donor liver transplant in the Dar Al-Fouad Hospital in Egypt and were retrospectively evaluated. Patients were classified into 2 groups: those with human leukocyte antigen +ve, and those with human leukocyte antigen -ve and donors. Hepatitis C virus-related end-stage liver disease was the main indication for transplant. Demographic data, preoperative laboratory data, results of human leukocyte antigen tissue typing, Child score, model for end-stage liver disease score, graft/recipient weight-ratio, ischemia times, surgical complications, postoperative laboratory data, liver biopsy, immunosuppression, and pulse steroids were collected. Graft and patient survivals were studied using Kaplan-Meier curves. The mean model end-stage liver disease score was 18 ± 3.61 in group 1 and 17.73 ± 3.72 in group 2, with no significant difference. Graft/recipient weight ratio, ischemia times, and postoperative complications showed P = NS. Cyclosporine and tacrolimus were used in 5/9, 8/41, and 4/9 in group 1, and 32/41 in group 2 (P = NS). Rejection and pulse steroids were reported in 3/9 and 12/41 of group 1, and 3/12 and 11/41 of group 2 (P = NS). Hepatitis C virus-recurrence was diagnosed in 5/9 of patients (55%) and 8/41 of patients (29.5%) in groups 1 and 2 (P < .05). No statistical difference was found regarding mortality; 5-year patient and graft survival was 35/50 (70% in group 1 [human leukocyte antigen +ve]), 7/9 (77.8%), and 28/41 in group 2 (68.3%) (human leukocyte antigen -ve). Positive human leukocyte antigen typing before live-donor liver transplant has no effect on the incidence of postoperative complications, rejection episodes, and patient or graft survival. Recipients with positive human leukocyte antigen typing may have increased risk of hepatitis C virus-recurrence after live-donor liver transplant.


Bithiophene imide and benzodithiophene copolymers for efficient inverted polymer solar cells.
Bithiophene imide (BTI) and benzodithiophene (BDT) copolymers are synthesized for application in organic photovoltaic (OPV) cells. The electron deficiency of the BTI units leads to polymers with a low-lying HOMOs (∼-5.6 eV). Inverted solar cells are fabricated to investigate the OPV performance of the BTI-based polymers and achieve power conversion efficiencies up to 5.5%, with substantial V(oc)s above 0.9 V which are among the highest V(oc)s reported to date for polymer/PCBM solar cells. The results indicate that the BTI is a promising building block for constructing polymer donors for OPV applications.


The architecture of active zone material at the frog's neuromuscular junction.
Active zone material at the nervous system's synapses is situated next to synaptic vesicles that are docked at the presynaptic plasma membrane, and calcium channels that are anchored in the membrane. Here we use electron microscope tomography to show the arrangement and associations of structural components of this compact organelle at a model synapse, the frog's neuromuscular junction. Our findings indicate that the active zone material helps to dock the vesicles and anchor the channels, and that its architecture provides both a particular spatial relationship and a structural linkage between them. The structural linkage may include proteins that mediate the calcium-triggered exocytosis of neurotransmitter by the synaptic vesicles during synaptic transmission.


Serum potassium and risk of cardiovascular disease: the Framingham heart study.
Published studies of the association between serum potassium concentration and risk for cardiovascular disease in community-based populations have reported conflicting results. We sought to determine the association between serum potassium concentration and cardiovascular disease risk in the Framingham Heart Study. A total of 3151 participants (mean age, 43 years; 48% men) in the Framingham Heart Study who were free of cardiovascular disease and not taking medications affecting potassium homeostasis had serum potassium levels measured (1979-1983). Proportional hazards models were used to determine the association of serum potassium concentration at baseline with the incidence of cardiovascular disease at follow-up. During mean follow-up of 16 years, 313 cardiovascular disease events occurred, including 46 cardiovascular disease-related deaths. After adjustment for age, serum potassium level was marginally associated with risk of cardiovascular disease (hazard ratio [HR] per 1 mg/dL increment, 1.03; 95% confidence interval [CI], 1.00-1.05; P =.02). However, after further adjustment for multiple confounders, serum potassium level was not significantly associated with cardiovascular disease risk (HR, 1.00; 95% CI, 0.98-1.03). There were no significant associations between serum potassium level and cardiovascular disease-related death in either age- and sex-adjusted models (HR, 1.06; 95% CI, 0.99-1.12) or multivariable-adjusted models (HR, 1.04; 95% CI, 0.97-1.11). In our community-based sample of individuals free of cardiovascular disease and not taking medications that affect potassium homeostasis, serum potassium level was not associated with risk of cardiovascular disease.


Faculty Respond to COVID-19: Reflections-on-Action in Field Education.
The field placement process has become increasingly challenging for schools of social work, particularly for large graduate programs situated in urban centers with competing schools. The unprecedented circumstances created by the COVID-19 public health crisis further strained the placement process, revealing a delicate balance of interdependent systems that schools must address when confronted with an unforeseen disruption of field education. This paper reflectively examines the steps taken by the field faculty and department of one large school of social work to address the impact of the pandemic on field education and its placement process. Utilizing crisis and shared trauma perspectives, the field disruptions, continuity of learning, contingency plans, and the attendant anxiety caused by COVID-19 are discussed, as are the lessons learned. Though COVID-19 has significantly altered the placement process, this reflective frame allows faculty to take the lessons emerging from the crisis and use them to improve services and learning opportunities for students in the future.


Ectopic expression of the maize kn1 gene phenocopies the Hooded mutant of barley.
The homeobox gene, knotted1, (kn1) is expressed in shoot meristems and is required for maintaining indeterminacy and preventing cellular differentiation. Awns, extensions of the bract-like lemma found in all grass inflorescences, are normally determinate structures. We show that ectopic expression of kn1 in the barley awn is sufficient to direct the development of ectopic meristems, forming inflorescence-like structures. This homeotic transformation is similar to the phenotype produced by misexpression of the barley hvknox3 gene, associated with the dominant Hooded mutant (Müller, K. J., Romano, N., Gerstner, O., Garcia-Maroto, F., Pozzi, C., Salamini, F. and Rohde, W. (1995) Nature 374, 727-730). We suggest that the inverse polarity of the ectopic flowers seen in Hooded and transgenic kn1 plants results from the transformation of the awn into reiterative inflorescence axes. We observed that the protein and mRNA localization of the transgene, driven by a constitutive promoter, is similar to the expression pattern of hvknox3 in awns of Hooded mutants, suggesting posttranscriptional regulation.


An association of prune belly anomaly with trisomy 21.
We report on two patients with prune belly anomaly (PBA) and trisomy 21 documented by clinical examination and cytogenetic investigation. The first infant was diagnosed at birth. A distended bladder was detected prenatally by ultrasound in the second patient, and chromosome studies were performed on cells obtained from fetal "bladdercentesis." We discuss the importance of cytogenetic studies in cases where fatal surgery is a consideration.


Psychological distress in pregnancy and preterm delivery.
To investigate if psychological distress during pregnancy is associated with increased risk of preterm delivery. Prospective, population based, follow up study with repeated measures of psychological distress (general health questionnaire), based on the use of questionnaires. Antenatal care clinic and delivery ward, Aarhus University Hospital, Denmark. 8719 women with singleton pregnancies attending antenatal care for the initial visit between 1 August 1989 and 30 September 1991; 5872 women (67%) completed all questionnaires. Preterm delivery. Estimation of gestational age at delivery was mainly based on early ultrasound measurements. In 197 cases (3.6%) the woman delivered prematurely (less than 259 days). A dose-response relation between psychological distress in the 30th week of pregnancy and risk of preterm delivery was found, but distress measured in the 16th week was not related to preterm delivery. Control of confounding was secured by the use of multivariate logistic regression models. Relative risk for preterm delivery was 1.22 (95% confidence interval 0.84 to 1.79) for moderate distress and 1.75 (1.20 to 2.54) for high distress in comparison to low distress. Psychological distress later in pregnancy is associated with an increased risk of preterm delivery. Future interventional studies should focus on ways of lowering psychological distress in late pregnancy.


Provider delay among patients with breast cancer in Germany: a population-based study.
Delaying the diagnosis and initiation of treatment of cancer is likely to result in tumor progression and a worse prognosis. We examined sources and consequences of provider delay among female breast cancer patients in a population-based study in Germany. Three hundred eighty women, who were ages 18 to 80 years and who had invasive breast cancer, were interviewed with respect to the diagnostic process. Provider delay was defined as time from first presentation to a health care provider until initiation of cancer treatment. Median provider delay was 15 days and did not substantially differ by the specialty of first consulted physician. Delays in the diagnostic work-up were mainly because of erroneous initial suspicion of a benign breast disease or because of time constraints by patients or physicians. Provider delay over 3 months was found in 11% of all breast cancer cases and was associated with patient characteristics such as higher education (odds ratio [OR] = 2.6; 95% confidence interval [CI], 1.3 to 5.4), full-time employment (OR = 2.5; 95% CI, 1.1 to 5.5), family history of breast cancer (OR = 2.8; 95% CI, 1.2 to 6.2), and presenting with a non-breast symptom (OR = 4.3; 95% CI, 1.7 to 10.9). The association between duration of diagnostic work-up and stage at diagnosis was U shaped, with the highest proportions of metastasized breast cancer tumors among women with very short (< 7 days) or very long (> 3 months) duration. Diagnostic work-up is within reasonably short time limits among most patients with breast cancer in Germany. Although the association between delay and tumor stage seems to be complex, any delay in diagnostic work-up should be kept to a minimum.


Hispanic chronic disease self-management: a randomized community-based outcome trial.
In light of health disparities and the growing prevalence of chronic disease, there is a need for community-based interventions that improve health behaviors and health status. These interventions should be based on existing theory. This study aimed to evaluate the health and utilization outcomes of a 6-week community-based program for Spanish speakers with heart disease, lung disease, or type 2 diabetes. The treatment participants in this study (n = 327) took a 6-week peer-led program. At 4 months, they were compared with randomized wait-list control subjects (n = 224) using analyses of covariance. The outcomes for all the treatment participants were assessed at 1 year, as compared with baseline scores (n = 271) using t-tests. At 4 months, the participants, as compared with usual-care control subjects, demonstrated improved health status, health behavior, and self-efficacy, as well as fewer emergency room visits (p <.05). At 1 year, the improvements were maintained and remained significantly different from baseline condition. This community-based program has the potential to improve the lives of Hispanics with chronic illness while reducing emergency room use.


[Neonatal Caffey-Silverman disease with thrombocytosis, increase in C-reactive protein and immunoglobulins].
An unusual case of Caffey-Silverman's disease with thrombocythemia and increased type M immunoglobulins and C-reactive protein levels is reported. These particularities were rarely reported in the literature. These conditions suggest that control should be exercised before steroid treatment in view of the known thrombocythemic effect of the drug. These hematologic abnormalities suggest that this syndrome is infectious in origin and emphasize the risk of steroid treatment.


Eating out and getting fat? A comparative study between urban and rural China.
In parallel with the increased prevalence of overweight and obesity, the rate of food away from home (FAFH) consumption in China has increased notably in recent years. Under the long-term urban-rural dual structure in China, the purpose of this study was to investigate the impact of FAFH consumption on body mass index (BMI) by a comparative study between rural and urban areas, using 26,244 subjects from the 2004-2011 China Health and Nutrition Survey. The results indicated that urban residents have a higher rate of FAFH consumption than rural residents with the difference narrowing over time. The empirical results illustrated that the frequency of meals consumed away from home had a significantly positive effect on BMI in urban China, whereas no significant association was observed in rural China. The urban-rural difference resulted from different levels of surplus energy, which was mainly due to the different labor intensity among rural and urban residents.


Dropped Head Syndrome Caused by Thoracolumbar Deformity: A Report of 3 Cases.
We present 3 patients with dropped head syndrome (DHS) caused by thoracolumbar kyphotic deformity who were successfully treated with thoracolumbar corrective surgery only. After the surgery, their symptoms, neck pain, and horizontal gaze difficulty disappeared, and cervical kyphotic alignment was improved indirectly. At the final follow-up, the whole spinal alignment was maintained, and there was no recurrence of symptoms. Surgeons should consider thoracolumbar spine deformity as the possible primary cause of typical DHS symptoms and recognize that thoracolumbar corrective surgery is an effective method for treating DHS patients with thoracolumbar deformity.


Potential treatment of herpes simplex virus encephalitis by brain-specific delivery of trifluorothymidine using a dihydropyridine in equilibrium pyridinium salt type redox delivery system.
A newly described, drug-carrier delivery system in which a lipophilic derivative is enzymatically converted to a hydrophilic compound was used to treat experimental herpes simplex virus (HSV) encephalitis. Because trifluorothymidine (TFT) does not cross the blood brain barrier, the lipophilic dihydropyridine derivative 3'-(N-methyl-1, 4-dihydronicotinoyl)-5-'pivaloyltrifluorothymidine (DHTFT) was synthesized and characterized by HPLC. After intravenous administration of 20 mg/kg of DHTFT to rats, the quaternary, intermediate compound 3'-N-methyl-1,4-nicotinoyltrifluorothymidine was measured at levels of 7-8 micrograms/g brain at 1 hour and 13.5 +/- 0.8 micrograms/g brain at 4 hours. This compound had antiviral activity equivalent to that of TFT against HSV-1 in a plaque reduction assay (ID 50 = 0.5-1.0 microgram/ml), either directly or by conversion to TFT. Although survival was not prolonged in a rat model of HSV encephalitis, a statistically significant reduction in titer of HSV/g brain was achieved with daily intravenous treatment with DHTFT. TFT was not detected in brains of rats at 1 and 4 hours after intravenous DHTFT, but a low level was observed at 18 hours, 0.3 +/- 0.05 microgram/g brain. These data suggest that the lipophilic compound DHTFT or a lipophilic metabolite crossed the blood brain barrier and was converted to a quaternary compound, which accumulated in the brain and which was either active directly or was converted to TFT. The drug-carrier delivery system described here can potentially be used in the treatment of HSV or other viral encephalitides.


Purifying selection in deeply conserved human enhancers is more consistent than in coding sequences.
Comparison of polymorphism at synonymous and non-synonymous sites in protein-coding DNA can provide evidence for selective constraint. Non-coding DNA that forms part of the regulatory landscape presents more of a challenge since there is not such a clear-cut distinction between sites under stronger and weaker selective constraint. Here, we consider putative regulatory elements termed Conserved Non-coding Elements (CNEs) defined by their high level of sequence identity across all vertebrates. Some mutations in these regions have been implicated in developmental disorders; we analyse CNE polymorphism data to investigate whether such deleterious effects are widespread in humans. Single nucleotide variants from the HapMap and 1000 Genomes Projects were mapped across nearly 2000 CNEs. In the 1000 Genomes data we find a significant excess of rare derived alleles in CNEs relative to coding sequences; this pattern is absent in HapMap data, apparently obscured by ascertainment bias. The distribution of polymorphism within CNEs is not uniform; we could identify two categories of sites by exploiting deep vertebrate alignments: stretches that are non-variant, and those that have at least one substitution. The conserved category has fewer polymorphic sites and a greater excess of rare derived alleles, which can be explained by a large proportion of sites under strong purifying selection within humans--higher than that for non-synonymous sites in most protein coding regions, and comparable to that at the strongly conserved trans-dev genes. Conversely, the more evolutionarily labile CNE sites have an allele frequency distribution not significantly different from non-synonymous sites. Future studies should exploit genome-wide re-sequencing to obtain better coverage in selected non-coding regions, given the likelihood that mutations in evolutionarily conserved enhancer sequences are deleterious. Discovery pipelines should validate non-coding variants to aid in identifying causal and risk-enhancing variants in complex disorders, in contrast to the current focus on exome sequencing.


Deleterious and adaptive mutations in plant germplasm conserved ex situ.
Conserving more than 7 million plant germplasm accessions in 1,750 genebanks worldwide raises the hope of securing the food supply for humanity for future generations. However, there is a genetic cost for such long-term germplasm conservation, which has been largely unaccounted for before. We investigated the extent and variation of deleterious and adaptive mutations in 490 individual plants representing barley, wheat, oat, soybean, maize, rapa, and sunflower collections in a seed genebank using RNA-Seq technology. These collections were found to have a range of deleterious mutations detected from 125 (maize) to 83,695 (oat) with a mean of 13,537 and of the averaged sample-wise mutation burden per deleterious locus from 0.069 to 0.357 with a mean of 0.200. Soybean and sunflower collections showed that accessions acquired earlier had increased mutation burdens. The germplasm with more years of storage in several collections carried more deleterious and fewer adaptive mutations. The samples with more cycles of germplasm regeneration revealed fewer deleterious and more adaptive mutations. These findings are significant for understanding mutational dynamics and genetic cost in conserved germplasm and have implications for long-term germplasm management and conservation.


A ten-year experience with blunt trauma to the abdomen in children.
Twenty-two children with significant blunt abdominal trauma who were admitted to the Surgical Service of an active city-county hospital over the past ten years are presented with discussion of their injuries and treatment. The two mortalities (9%) are presented as case reports. On patient with severe multiple trauma had residual brain damage, and one other patient required a secondary procedure for complications subsequent to the original injury. The results represent an improvement in both complications and mortality when compared to previous reports from similar institutions.


Multimodality durable salvage of recurrent brain metastases refractory to LITT, SRS and immunotherapy with resection and cesium-131 brachytherapy: case report and literature review.
Brain metastases (BrM) are treated with multimodality therapy, however the optimal combination and timing of modalities in the setting of recurrent tumours that have failed prior treatments remain poorly defined. We present a case of a patient with biopsy-confirmed renal cell carcinoma BrM with good performance status initially treated with laser interstitial thermal ablation therapy (LITT) followed by stereotactic radiosurgery and dual checkpoint inhibitor immunotherapy. He subsequently developed rapid in-field recurrence which was treated with salvage surgical resection and implantation of intracavitary cesium-131 brachytherapy. The patient's disease remained stable through 18 months postoperatively. This case illustrates the range of options available and provides a combination salvage therapy strategy in a select group of locally recurrent patients who have exhausted conventional treatment options.


Heterologous expression of the Rhodobacter capsulatus BchI, -D, and -H genes that encode magnesium chelatase subunits and characterization of the reconstituted enzyme.
Magnesium chelatase inserts Mg2+ into protoporphyrin IX in the chlorophyll and bacteriochlorophyll biosynthetic pathways. In photosynthetic bacteria, the products of three genes, bchI, bchD, and bchH, are required for magnesium chelatase activity. These genes from Rhodobacter capsulatus were cloned separately into expression plasmids pET3a and pET15b. The pET15b constructs produced NH2-terminally His6-tagged proteins. All proteins were highly expressed and were purified to near homogeneity. The BchI and BchH proteins were soluble. BchD proteins were insoluble, inactive inclusion bodies that were renatured by rapid dilution from 6 M urea. The presence of BchI in the solution into which the urea solution of BchD was diluted increased the yield of active BchD. A molar ratio of 1 BchI:1 BchD was sufficient for maximum renaturation of BchD. All of the proteins were active in the magnesium chelatase assay except His-tagged BchI, which was inactive and inhibited in incubations containing non-His-tagged BchI. Expressed BchH proteins contained tightly bound protoporphyrin IX, and they were susceptible to inactivation by light. Maximum magnesium chelatase activity per mol of BchD occurred at a stoichiometry of 4 BchI:1 BchD. The optimum reaction pH was 8.0. The reaction exhibited Michaelis-Menten kinetics with respect to protoporphyrin IX and BchH.


The protective effect of Hypericum connatum on stress-induced escape deficit in rat is related to its flavonoid content.
Context Hypericum perforatum L. (Hypericaceae), used in moderate depression treatment, is active in experimental tests for antidepressant activity. For H. connatum Lam., a South American species lacking hyperforin, antidepressant effects have not been demonstrated. Objective This study evaluates the antidepressant-like effect of H. connatum in rats and identifies the components involved in this activity. Materials and methods First, the effects of acute and 14-d oral administrations of an extract derived from H. connatum aerial parts were studied using the Escape Deficit (ED) test. Next, methanol-extracted flavonoid-enriched fractions B and C and fraction-purified flavonoids (quercetin, rutin and isoquercitrin) were evaluated in the ED test after acute administration. To rule out possible confounding effects of the flavonoids, we examined nociceptive threshold using the tail-flick test and anxious behaviour using the elevated plus maze (EPM) test. Results Hypericum connatum increased reactivity of unavoidable stress-exposed rats after acute (0.5 and 1 g/kg: ED = 18.6/30 and 19.8/30, respectively) and repeated administration (0.5 g/kg twice daily: ED = 17.8/30). Protective effects were observed for fractions B and C (250 mg/kg: ED = 18.1/30 and 18.8/30, respectively), quercetin (2.5, 5 and 10 mg/kg: ED = 15.3/30, 18.3/30 and 21.6/30, respectively), rutin (5 and 10 mg/kg: ED = 15.4/30 and 13.0/30, respectively) and isoquercitrin (2.5 mg/kg: ED = 19.2/30). The flavonoids did not modify nociceptive threshold or performance in the EPM test. Discussion and conclusion Hypericum connatum showed protective activity in the ED test, a correlate of potential antidepressant-like effects that appeared to be related to the flavonoid components of this species.


Value of serial sonography in the in utero detection of duodenal atresia.
Duodenal atresia can be fatal unless promptly diagnosed and treated surgically. Death occurs in the newborn secondary to emesis, aspiration, and electrolyte imbalance. Serial ultrasound scans were obtained for 2 patients, but duodenal atresia was not detected until 29 and 32 weeks' gestation, respectively. With prior knowledge of an infant with Down syndrome and duodenal atresia, management of fetal distress with subsequent operative delivery can be altered. Early prenatal diagnosis by ultrasonography and subsequent amniocentesis plays an important role in the antenatal and postpartum counseling and management of these patients and neonates.


The human proteinase-activated receptor-3 (PAR-3) gene. Identification within a Par gene cluster and characterization in vascular endothelial cells and platelets.
Proteolytically activated receptors (PARs) represent an emerging subset of seven transmembrane G protein-coupled receptors that mediate cell activation events by receptor cleavage at distinct scissile bonds located within receptor amino termini. Differential genomic blotting using a yeast artificial chromosome known to contain the PAR-1 and PAR-2 genes identified the PAR-3 gene within a PAR gene cluster spanning approximately 100 kilobases at 5q13. The PAR-3 gene is relatively small (approximately 12 kilobases); and, like the PAR-1 and PAR-2 genes, it displays a two-exon structure, with the majority of the coding sequence and the proteolytic cleavage site contained within the larger second exon. Sequence analysis of the 5'-flanking region demonstrates that the promoter is TATA-less, similar to that seen with PAR-1, with the identification of nucleic acid motifs potentially involved in transcriptional gene regulation, including AP-1, GATA, and octameric sequences. PAR-3 transcripts were apparent in human vascular endothelial cells, although at considerably lower levels than those of PAR-1 and not significantly modulated by the endothelial cell stimulus tumor necrosis factor-alpha. Likewise, although PAR-3 mRNA was evident in human platelets, receptor cell surface expression was modest (approximately 10%) compared with that of PAR-1. Thus, although PAR-3 is postulated to represent a second thrombin receptor, its modest endothelial cell and platelet expression suggest that PAR-3 activation by alpha-thrombin is less relevant for physiological responses in these mature cells. Rather, given its disparately greater expression in megakaryocytes (and megakaryocyte-like human erythroleukemia cells), a regulatory role in cellular development (by protease activation) could be postulated.


Immunoaffinity carrier prepared by immobilization of antibody via Co3+-chelate.
A method for the immobilization of antibodies to inert matrix represents an important factor that affects results of immunoaffinity chromatography. Binding antibodies to immobilized metal ions is an example of oriented immobilization that avoids a random coupling of a protein. Preparation of a stable immunoaffinity sorbent using immobilized metal ions was described. Antibodies were bound to chelated Co3+ ions that were prepared by oxidation of Co2+-iminodiacetic acid agarose using hydrogen peroxide. The formation of a stable complex of the antibody with immobilized Co3+ ions was proved. Antibodies bound by this way were not released with solutions of 50 mM EDTA, 6 M urea, 3 M NaCl, 20% v/v dioxane, 0.1 M imidazole and buffers of pH 2.5 and pH 11.0. If needed, antibody could be released from the carrier by the reduction of Co3+ ions with a reducing agent (e.g. dithiotreitol or 2-mercaptoethanol). Antibody released from the carrier could be then replaced by another antibody. The method described in this paper was used for the immobilization of polyclonal rabbit anti-ovalbumin antibody or egg yolk antibody (IgY) produced in chicken. In a model experiment, immobilized polyclonal rabbit antibodies were used for the separation of ovalbumin from egg white and conditions of chromatography were described.


Standardizing inpatient colonoscopy preparations improves quality and provider satisfaction.
Inpatient colonoscopy bowel preparation quality is frequently suboptimal. This quality improvement (QI) intervention is focused on regimenting this process to impact important outcomes. Define, Measure, Analyze, Improve and Control (DMAIC) methodology was employed, including generating a root-cause analysis to identify factors associated with inpatient bowel quality. These findings motivated the creation of a standardized electronic health record (EHR)-based order set with consistent instructions and anticipatory guidance for administering providers. There were 264 inpatient colonoscopies evaluated, including 198 procedures pre-intervention and 66 post-intervention. The intervention significantly improved the adequacy of right colon bowel preparations (75.0 percent vs 86.9 percent, p = 0.04) but not overall preparation quality (73.7 percent vs 80.3 percent, p = 0.22). The intervention led to numerical improvement in the proportion of procedures in which the preparation quality interfered with making a diagnosis (10 percent-6 percent, p = 0.29) or resulted in an aborted procedure (3.5 percent-1.5 percent, p = 0.39). After the intervention, provider satisfaction with the ordering process significantly increased (23.3 percent vs 61.1 percent, p < 0.001). The QI intervention significantly reduced the number of inpatient colonoscopies with inadequate preparation in the right colon, while also modestly improving the diagnostic yield and proportion of aborted procedures. Importantly, the standardized EHR order set substantially improved provider satisfaction, which should justify broader use of such tools. Novel clinical outcomes such as ability to answer diagnostic questions were improved using this intervention. The results align with strategic goals to enhance provider experience and continuously improve quality of patient care.


Pancreatic protein secretion and gastrointestinal hormone release in response to parenteral amino acids and lipid in dogs.
Parenteral nutrition has been advocated for and used in clinical situations in which provision of calories without stimulation of pancreatic secretion is desired. A recent report, however, provided evidence for substantial stimulation of pancreatic secretion after parenteral administration of amino acids and fat. We have studied the effect of intravenous administration of crystalline amino acids and lipid on pancreatic protein secretion and release of gastrointestinal hormones in five dogs with chronic pancreatic fistulas. The amino acids were given as a 4.25% solution in 5% glucose at 2 gm/hr. Parenteral fat was administered as Intralipid 10% at 3.5 ml/kg/hr. Plasma concentrations of cholecystokinin (CCK) and pancreatic polypeptide (PP) and serum concentrations of gastrin, measured by radioimmunoassay, were determined before, and at intervals during, infusion of amino acids and fat. Pancreatic juice was collected simultaneously with blood sampling, and volume and protein output were measured. Basal concentrations of CCK, PP, and gastrin were not affected by intravenous infusion of amino acids. Pancreatic protein secretion and volume were also unaffected by parenteral amino acids. Parenteral infusion of fat resulted in a significant inhibition of integrated gastrin release but had no effect on plasma concentrations or integrated release of CCK or PP. Neither the volume nor protein output of pancreatic secretion was affected by intravenous fat administration. In summary, no stimulation of pancreatic secretion or release of CCK, PP, or gastrin occurred as a result of parenteral amino acid or fat administration. There is, therefore, no contraindication to the use of parenteral nutrition in situations in which it is desirable to keep the pancreas at rest.


If brain scans really detected deception, who would volunteer to be scanned?
Recent neuroimaging studies investigating the neural correlates of deception among healthy people, have raised the possibility that such methods may eventually be applied during legal proceedings. Were this so, who would volunteer to be scanned? We report a "natural experiment" casting some light upon this question. Following broadcast of a television series describing our team's investigative neuroimaging of deception in 2007, we received unsolicited (public) correspondence for 12 months. Using a customized template to examine this material, three independent assessors unanimously rated 30 of an initial 56 communications as unequivocally constituting requests for a "scan" (to demonstrate their author's "innocence"). Compared with the rest, these index communications were more likely to originate from incarcerated males, who were also more likely to engage in further correspondence. Hence, in conclusion, if neuroimaging were to become an acceptable means of demonstrating innocence then incarcerated males may well constitute those volunteering for such investigation.


Impact of the Great East Japan Earthquake on Child's IQ.
To assess the neurodevelopmental effects of the Great East Japan Earthquake in resident children. The disaster on March 11, 2011, caused severe damage to the Sanriku coastal area, where we had been conducting a birth cohort study since 2003. It occurred in the middle of our 7-year-old examination. Approximately 500 mother-child pairs were compulsorily divided into 2 groups: 123 children finished the examination in the predisaster period, and 289 did in the postdisaster period. The remainder died or moved from that area. At the time of 7-year-old examination, we administered the Wechsler Intelligence Scale for Children-Third Edition and electrocardiography to assess autonomic function. According to the Child Behavior Checklist for ages 2-3 years and the Kaufman Assessment Battery for Children that had been administered at 30 months and 42 months of age, respectively, there were no significant differences in them between the 2 groups. Verbal IQ, including information, arithmetic, and vocabulary subscores of the Wechsler Intelligence Scale for Children-Third Edition, at 7 years of age was significantly lower in the postdisaster group than in the predisaster group. However, there were no significant differences in performance IQ, full-scale IQ, or autonomic nervous indicators between the 2 groups. Since many schools were utilized as primary refuges after the disaster, the deficits in verbal IQ of 7-year-old children may have been due to the interrupted schooling. Further follow-up and more specific posttraumatic stress disorder testing will be required to determine the cause and long-term implications.


N-Acetyl-L-cysteine potentiates interleukin-1beta induction of nitric oxide synthase : role of p44/42 mitogen-activated protein kinases.
We have reported previously that N-acetyl-L-cysteine facilitated interleukin-1beta-induced nitric oxide synthase (iNOS) expression in rat vascular smooth muscle cells. The present study compares the effect of N-acetyl-L-cysteine with other antioxidants and tested the possibility that N-acetyl-L-cysteine potentiates iNOS induction by a mechanism involving activation of p44/42 mitogen-activated protein kinases (MAPKs). The effect of N-acetyl-L-cysteine on potentiating interleukin-1beta-induced nitrite production and iNOS expression was mimicked either by the enantiomers, L-cysteine and D-cysteine, or by a non-thiol-containing antioxidant, L-ascorbic acid. Interleukin-1beta activated p44/42 MAPK, and this activation was enhanced in the presence of N-acetyl-L-cysteine. Inhibition of p44/42 MAPK phosphorylation by the selective inhibitor PD98059 clearly inhibited iNOS expression induced by interleukin-1beta either in the absence or in the presence of N-acetyl-L-cysteine. These observations, combined with previous results, indicate that p44/42 MAPK activation is required for interleukin-1beta induction of iNOS and that N-acetyl-L-cysteine may act as a reducing agent and facilitate interleukin-1beta-induced iNOS expression through a reduction/oxidation-related mechanism involving potentiation of cytokine activation of the p44/42 MAPK signaling pathway.


L3T4 and Lyt-2 T cells are both involved in the generation of low-dose streptozotocin-induced diabetes in mice.
In order to determine the role of different T lymphocyte subsets in the pathogenesis of low-dose streptozotocin (LD-Sz) induced diabetes, we treated mice with Sz together with repeated injections of rat monoclonal antibodies (MoAb) with specificity towards the mouse T cell differentiation markers L3T4 ('helper/inducer' T cells and some macrophages), Lyt-2 ('cytotoxic/suppressor' T cells and NK cells) and Thy-1 (pan T lymphocytes). Treatment depleted target cells in peripheral blood and spleen; decreased the ability of spleen cells to respond to mitogens; and, in the case of depletion of the L3T4 T cell subset, prevented a humoral immune response to SRBC. Treatment with MoAb against either of the two T cell subtypes could protect from hyperglycaemia and loss of body weight, suggesting that both T cell subsets were implicated in the development of LD-Sz induced diabetes. Immunocytochemical analysis of pancreatic sections showed that both L3T4+ and Lyt-2+ cells participated in islet infiltration together with macrophages. Treatment with MoAb markedly reduced islet infiltration by both L3T4+ and Lyt-2+ cells but not by macrophages. The suppressive effect of MoAb against either L3T4 or Lyt-2 on diabetes development suggests that the pathomechanism involved is different from that in experimental autoimmune neuritis and adjuvant arthritis where Lyt-2 cells are not involved.


Fear Mediates Trophic Cascades: Nonconsumptive Effects of Predators Drive Aquatic Ecosystem Function.
Predators control prey populations and influence communities and the functioning of ecosystems through a combination of consumptive and nonconsumptive effects. These effects can be locally confined to one ecosystem but can also be extended to neighboring ecosystems. In this study, we investigated the nonconsumptive effects of terrestrial avian predators on the communities of aquatic invertebrates inhabiting bromeliads and on the functioning of these natural ecosystems. Bromeliads with stuffed birds placed nearby showed a decrease in aquatic damselfly larvae abundance and biomass, and we can infer that these changes were caused by antipredator responses. These larvae, which are top predators in bromeliad ecosystems, changed the composition of the entire aquatic invertebrate community. While total species richness, mesopredator richness, and shredder abundance increased in the presence of birds, scraper biomass decreased, possibly as a consequence of the increase in mesopredator richness. High scraper biomass in the absence of birds may have accelerated detrital decomposition, making more nutrients available for bromeliads, which grew more. These results show that nonconsumptive effects triggered by terrestrial predators can cascade down to lower trophic levels and dramatically affect the functioning of aquatic ecosystems, which can in turn alter nutrient provision to terrestrial ecosystems.


Paeonocanthus antarcticensis (Hewitt, 1965): a rare copepod parasite of bathypelagic fish, Bathylagus antarcticus Günther, from the Antarctic Ocean.
Paeonocanthus antarcticensis (Hewitt, 1965) is redescribed based on four specimens recovered from a deep-sea smelt, Bathylagus antarcticus Günther, collected in the Antarctic Ocean (65 degrees S, 139 degrees 59.6'E). Studies on the morphological variations of these four specimens plus comparison with the three documented specimens yielded that the sphyriid reported as P. antarcticensis from the goiter blacksmelt, Bathylagus euryops Goode & Bean, taken in the Northwest Atlantic Ocean is a different species. It is renamed Paeonocanthus hogansi n. sp.


Modified release itraconazole amorphous solid dispersion to treat Aspergillus fumigatus: importance of the animal model selection.
Previously, modified release itraconazole in the form of a melt-extruded amorphous solid dispersion based on a pH dependent enteric polymer combined with hydrophilic additives (HME-ITZ), exhibited improved in vitro dissolution properties. These properties agreed with pharmacokinetic results in rats showing high and sustained itraconazole (ITZ) systemic levels. The objective of the present study was to better understand the best choice of rodent model for evaluating the pharmacokinetic and efficacy of this orally administered modified release ITZ dosage form against invasive Aspergillus fumigatus. A mouse model and a guinea pig model were investigated and compared to results previously published. In the mouse model, despite similar levels as previously reported values, plasma and lung levels were variable and fungal burden was not statistically different for placebo controls, HME-ITZ and Sporanox® (ITZ oral solution). This study demonstrated that the mouse model is a poor choice for studying modified release ITZ dosage forms based on pH dependent enteric polymers due to low fluid volume available for dissolution and low intestinal pH. To the contrary, guinea pig was a suitable model to evaluate modified release ITZ dosage forms. Indeed, a significant decrease in lung fungal burden as a result of high and sustained ITZ tissue levels was measured. Sufficiently high intestinal pH and fluids available for dissolution likely facilitated the dissolution process. Despite high ITZ tissue level, the primary therapeutic agent voriconazole exhibited an even more pronounced decrease in fungal burden due to its reported higher clinical efficacy specifically against Aspergillus fumigatus.


Visible and near-infrared imaging of the nerve fiber layer of the isolated rat retina.
To develop an isolated rat retina preparation suitable for the study of the reflectance of the mammalian retinal nerve fiber layer (RNFL). A rat retina with a short piece of optic nerve attached was dissected free from the eye and stretched over a slit in a black membrane. The retina was placed in a black chamber perfused with warmed and oxygenated physiologic solution. Imaging microreflectometry was used to acquire images of the RNFL at wavelengths from 400 to 830 nm and over time. At all wavelengths the isolated retina provided high-contrast images of nerve fiber bundles against a uniform, dark background. The nerve fiber bundles had a speckled texture, especially at long wavelengths. Time-lapse movies showed that over a period of several minutes the speckle pattern slowly changed. Although the general appearance of the bundles was similar at two closely spaced wavelengths (660 and 680 nm), the detailed patterns were completely different. The isolated retina preparation is well suited to the study of the optical properties of the RNFL. The speckled texture of nerve fiber bundles probably results from optical interference in the scattered light. The slow change in pattern implies that the size and/or shape of the scattering structures must change with time.


Failure of reversion of neuromuscular block with sugammadex in patient with myasthenia gravis: case report and brief review of literature.
Myasthenia gravis (MG) is a challenge for anesthesia management. This report shows that the use of rocuronium-sugammadex is not free from flaws and highlights the importance of cholinesterase inhibitors management and neuromuscular block monitoring in the perioperative period of myasthenic patients. Myasthenic female patient submitted to general balanced anesthesia using 25 mg of rocuronium. Under train-of-four (TOF) monitoring, repeated doses of sugammadex was used in a total of 800 mg without recovery of neuromuscular blockade, but TOF ratio (TOFR) was stabilized at 60%. Neostigmine administration led to the improvement of TOFR. Although the use of rocuronium-sugammadex seems safe, we should consider their unpredictability in myasthenic patients. This report supports the monitoring of neuromuscular blockade as mandatory in every patient, especially the myasthenic ones.


Epitope discovery and their use in peptide based vaccines.
With recent advances in the design and delivery of peptide-based therapeutics there has been a growing interest on the use of peptides in vaccine design. Moreover, functional dissection and proteomic analysis of the immunogenic epitopes of proteins from pathogenic micro-organisms, cancers and self-tissues targeted by autoimmune responses, have broadened the range of target epitopes and given clues to enhancing peptide immunogenicity. Consistent with these observations; peptides can be synthesised with defined chemical modifications to mimic natural epitopes and/or deliberately introduce protease resistant peptide bonds to regulate their processing independent of tissue specific proteolysis and to stabilize these compounds in vivo. We discuss the potential of peptide-based vaccines for the treatment of chronic viral diseases and cancer and review recent developments in the field of epitope discovery and peptide-based vaccines.


Platelets alter gene expression profile in human brain endothelial cells in an in vitro model of cerebral malaria.
Platelet adhesion to the brain microvasculature has been associated with cerebral malaria (CM) in humans, suggesting that platelets play a role in the pathogenesis of this syndrome. In vitro co-cultures have shown that platelets can act as a bridge between Plasmodium falciparum-infected red blood cells (pRBC) and human brain microvascular endothelial cells (HBEC) and potentiate HBEC apoptosis. Using cDNA microarray technology, we analyzed transcriptional changes of HBEC in response to platelets in the presence or the absence of tumor necrosis factor (TNF) and pRBC, which have been reported to alter gene expression in endothelial cells. Using a rigorous statistical approach with multiple test corrections, we showed a significant effect of platelets on gene expression in HBEC. We also detected a strong effect of TNF, whereas there was no transcriptional change induced specifically by pRBC. Nevertheless, a global ANOVA and a two-way ANOVA suggested that pRBC acted in interaction with platelets and TNF to alter gene expression in HBEC. The expression of selected genes was validated by RT-qPCR. The analysis of gene functional annotation indicated that platelets induce the expression of genes involved in inflammation and apoptosis, such as genes involved in chemokine-, TREM1-, cytokine-, IL10-, TGFβ-, death-receptor-, and apoptosis-signaling. Overall, our results support the hypothesis that platelets play a pathogenic role in CM.


Feature, Function, and Information of Drug Transporter-Related Databases.
With the rapid progress in pharmaceutical experiments and clinical investigations, extensive knowledge of drug transporters (DTs) has accumulated, which is valuable data for the understanding of drug metabolism and disposition. However, such data are largely dispersed in the literature, which hampers its utility and significantly limits its possibility for comprehensive analysis. A variety of databases have, therefore, been constructed to provide DT-related data, and they were reviewed in this study. First, several knowledge bases providing data regarding clinically important drugs and their corresponding transporters were discussed, which constituted the most important resources of DT-centered data. Second, some databases describing the general transporters and their functional families were reviewed. Third, various databases offering transporter information as part of their entire data collection were described. Finally, customized database functions that are available to facilitate DT-related research were discussed. This review provided an overview of the whole collection of DT-related databases, which might facilitate research on precision medicine and rational drug use. SIGNIFICANCE STATEMENT: A collection of well established databases related to drug transporters were comprehensively reviewed, which were organized according to their importance in drug absorption, distribution, metabolism, and excretion research. These databases could collectively contribute to the research on rational drug use.


High-resolution melting analysis for the detection of two erythromycin-resistant Bordetella pertussis strains carried by healthy schoolchildren in China.
Two erythromycin-resistant strains of Bordetella pertussis were isolated from nasopharyngeal specimens of two asymptomatic schoolchildren in China. High-resolution melting and sequencing analyses confirmed the homogeneous A2047G mutation in 23S rRNA genes of the two isolates. High-resolution melting (HRM) analysis is a useful assay for the rapid detection of erythromycin-resistant B. pertussis. The appearance of erythromycin-resistant B. pertussis strains in China is alarming.


Grooming reflexes and Brown-Séquard epilepsy in cats with pontile lesions.
The literature on the relation between the scratch reflex and Brown-Séquard epilepsy in the guinea pig indicates that the scratch reflex is a stimulus-induced myoclonus that is the first component of a complete seizure. Cats with pontile lesions and cats with frontal neocortical lesions exhibit the scratch reflex and other grooming reflexes. The grooming reflexes in cats with pontile lesions develop over a period of a year or more into complete seizures that are similar to Brown-Séquard epilepsy as described for the guinea pig by Brown-Séquard and others. Cinematographic analyses revealed that the scratch reflex in cats with pontile lesions and in cats with frontal neocortical lesions has the same frequency and the same complex spatial and temporal pattern as normal scratching behavior. In addition, the myoclonus of the complete seizures is identified as the scratch reflex, representing a very vigorous and long-lasting afterdischarge. Reconstruction of the pontile lesions indicate that the lateral and rostral portions of the paralemniscal tegmental fields were destroyed along with portions of the pontile gray and pyramidal tract.


Short-term fluctuations in identity: introducing a micro-level approach to identity formation.
The present study was aimed at examining one relatively neglected part of the identity formation process: the short-term dynamics of identity formation. The short-term dynamics were assessed by examining (a) the day-to-day course of 2 key dimensions of identity formation (i.e., commitment and reconsideration) and (b) the impact of fluctuations in commitment and reconsideration on subsequent levels of these 2 dimensions. Longitudinal data on 580 early adolescents (54.8% boys, 45.2% girls) were used to test these assertions. The authors found evidence for a commitment-reconsideration dynamic that operated on a day-to-day basis. Furthermore, the findings confirmed E. H. Erikson's (1950) assertion that identity reflects a sense of sameness and continuity as a more stable identity (reflected by little day-to-day fluctuations) was predictive of higher levels of commitment and lower levels of reconsideration. Taken together, the present study underscores the importance of the short-term dynamics of identity formation.


Ultrasensitive NIR-II Ratiometric Nanothermometers for 3D In Vivo Thermal Imaging.
Luminescent nanothermometry, particularly the one based ratiometric, has sparked intense research for non-invasive in vivo or intracellular temperature mapping, empowering their uses as diagnosis tools in biomedicine. However, ratiometric detection still suffers from biased sensing induced by wavelength-dependent tissue absorption and scattering, low thermal sensitivity (Sr ), and lack of imaging depth information. Herein, we construct an ultrasensitive NIR-II ratiometric nanothermometer with self-calibrating ability for 3D in vivo thermographic imaging, in which temperature-insensitive lanthanide nanocrystals and strongly temperature-quenched Ag2 S quantum dots are co-assembled to form a hybrid nanocomposite material. Precise control over the amount ratio between two sub-materials enables the manipulation of heat-activated back energy transfer from Ag2 S to Yb3+ in lanthanide nanoparticles, thereby rendering Sr up to 7.8% °C-1 at 43.5 °C, and higher than 6.5% °C-1 over the entire physiological temperature range. Moreover, the luminescence intensity ratio between two separated spectral regions within the narrow Yb3+ emission peak is used to determine the depth information of nanothermometers in living mice and correct the effect of tissue depth on 2D thermographic imaging, and therefore allows a proof-of-concept demonstration of accurate 3D in vivo thermographic imaging, constituting a solid step towards the development of advanced ratiometric nanothermometry for biological applications. This article is protected by copyright. All rights reserved.


Safety in medical signal analysis.
A number of issues are raised about the possibility of erroneous results obtained from signal analysis techniques that could lead to an incorrect diagnosis or an inadequate decision. An example is the use of a filter to attenuate interference when the (unidimensional) signal of interest contains wavelets. The output wavelets may be distorted by the filter in such a way that their interpretation leads to an incorrect diagnosis. In medical imaging, peripheral hot spots and sunburst streaking in computed tomography, blurring of tomographic reconstruction of cardiac images (as in single-photon-emission computed tomography, or SPECT) due to organ movement, and artifact due to image enhancement are among the difficulties introduced by signal analysis methodology. Some general recommendations are put forward as to how to deal with these kinds of problems.


Shear Bond Strength and Microleakage of a New Self-etching/Self-adhesive Pit and Fissure Sealant.
To evaluate shear bond strength and microleakage of a new self-etching/self-adhesive fissure sealant on prismless enamel compared with conventional fissure sealing. A total of 90 extracted third molars were assigned to 3 main groups: group 1: self-etching/self-adhesive sealant, without acid etching; group 2: self-etching/self-adhesive sealant, with prior acid etching; group 3: conventional fissure sealing (control group). After specimen preparation, each group was divided into 3 subgroups according to storage time (1-day water storage, 3-month water storage, and 1-day water storage followed by 5000x thermocycling). The shear bond strength was determined with a universal testing machine, according to ISO standard 29022. Afterwards, the failure mode was analyzed. An additional 24 third molars were used for microleakage assessment. The fissure pattern was sealed in strict accordance with the manufacturers' instructions. After thermocycling, the dye penetration was examined. Data were analyzed using the Mann-Whitney U-Test at a significance level of 0.05. The shear bond strength of the self-etching/self-adhesive fissure sealant without prior acid etching was significantly lower (4.3 MPa) than that of the self-etching/self-adhesive fissure sealant with prior acid etching (17.1 MPa) and the conventional fissure sealing (19.1 MPa). Microleakage was significantly lower in the control group (1.1%) and in the group with the self-etching/self-adhesive sealant with prior acid etching (0.8%) compared to the group that used the self-etching/self-adhesive material alone (49.4%). The self-etching/self-adhesive fissure sealant can be recommended for clinical use when enamel is etched with phosphoric acid. The self-etching/self-adhesive sealant without prior acid etching showed significantly inferior results.


Prestimulus oscillations in the alpha band of the EEG are modulated by the difficulty of feature discrimination and predict activation of a sensory discrimination process.
Recent work has demonstrated that the occipital-temporal N1 component of the ERP is sensitive to the difficulty of visual discrimination, in a manner that cannot be explained by simple differences in low-level visual features, arousal, or time on task. These observations provide evidence that the occipital-temporal N1 component is modulated by the application of top-down control. However, the timing of this control process remains unclear. Previous work has demonstrated proactive, top-down modulation of cortical excitability for cued spatial attention or feature selection tasks. Here, the possibility that a similar top-down process facilitates performance of a difficult stimulus discrimination task is explored. Participants performed an oddball task at two levels of discrimination difficulty, with difficulty manipulated by modulating the similarity between target and nontarget stimuli. Discrimination processes and cortical excitability were assessed via the amplitude of the occipital-temporal N1 component and prestimulus alpha oscillation of the EEG, respectively. For correct discriminations, prestimulus alpha power was reduced, and the occipital-temporal N1 was enhanced in the hard relative to the easy condition. Furthermore, within the hard condition, prestimulus alpha power was reduced, and the occipital-temporal N1 was enhanced for correct relative to incorrect discriminations. The generation of ERPs contingent on relative prestimulus alpha power additionally suggests that diminished alpha power preceding stimulus onset is related to enhancement of the occipital-temporal N1. As in spatial attention, proactive control appears to enhance cortical excitability and facilitate discrimination performance in tasks requiring nonspatial, feature-based attention, even in the absence of competing stimulus features.


Safety of Adding Salmeterol to Fluticasone Propionate in Children with Asthma.
Long-acting beta-agonists (LABAs) have been shown to increase the risk of asthma-related death among adults and the risk of asthma-related hospitalization among children. It is unknown whether the concomitant use of inhaled glucocorticoids with LABAs mitigates those risks. This trial prospectively evaluated the safety of the LABA salmeterol, added to fluticasone propionate, in a fixed-dose combination in children. We randomly assigned, in a 1:1 ratio, children 4 to 11 years of age who required daily asthma medications and had a history of asthma exacerbations in the previous year to receive fluticasone propionate plus salmeterol or fluticasone alone for 26 weeks. The primary safety end point was the first serious asthma-related event (death, endotracheal intubation, or hospitalization), as assessed in a time-to-event analysis. The statistical design specified that noninferiority would be shown if the upper boundary of the 95% confidence interval of the hazard ratio for the primary safety end point was less than 2.675. The main efficacy end point was the first severe asthma exacerbation that led to treatment with systemic glucocorticoids, as assessed in a time-to-event analysis. Among the 6208 patients, 27 patients in the fluticasone-salmeterol group and 21 in the fluticasone-alone group had a serious asthma-related event (all were hospitalizations); the hazard ratio with fluticasone-salmeterol versus fluticasone alone was 1.28 (95% confidence interval [CI], 0.73 to 2.27), which showed the noninferiority of fluticasone-salmeterol (P=0.006). A total of 265 patients (8.5%) in the fluticasone-salmeterol group and 309 (10.0%) in the fluticasone-alone group had a severe asthma exacerbation (hazard ratio, 0.86; 95% CI, 0.73 to 1.01). In this trial involving children with asthma, salmeterol in a fixed-dose combination with fluticasone was associated with the risk of a serious asthma-related event that was similar to the risk with fluticasone alone. (Funded by GlaxoSmithKline; VESTRI ClinicalTrials.gov number, NCT01462344 .).


Parallel and divergent interpreting in an elementary school classroom.
The study examined the extent to which a highly qualified interpreter remained parallel with or diverged from the original classroom discourse in her interpreting for a 3rd-grade deaf student in science, social studies, and resource room. The interpreter's signed and verbalized expressions were compared to the class participants' expressions for meaning equivalence. Parallel interpreting, occurring 33.2% of the time, closely matched the content of the speaker's message. Divergent interpreting, whereby the interpreter added or dropped elements of meaning, occurred 66.8% of the time. Qualitative analyses of classroom footage as well as interviews with the interpreter and the teachers revealed how, when, and why the interpreter diverged from the message. While the interpreter often made intentional reductions and additions to the discourse to achieve greater student understanding of language and course content, there was little awareness of these changes among individualized educational program team members.


Isolation and characterization of the major capsid protein of bovine papilloma virus type 1.
The major capsid protein of bovine papilloma virus type 1 (BPV-1) was isolated by gel filtration following disruption of purified virus particles with guanidine hydrochloride. The capsid protein, VP1, has a mol. wt. of about 53 500. Amino acid composition studies of VP1 showed that it is a highly acidic protein containing almost twice the average number of acidic residues than basic residues. Relatedness was observed between VP1 and the major capsid proteins of simian virus 40 (SV40) and polyoma virus.


Amiodarone keratopathy. Correlation to dosage and duration.
Amiodarone hydrochloride, a benzofurane derivative used for the treatment of cardiac arrhythmias, is known to cause a verticillate epithelial keratopathy, which has been classified into three stages. Patients receiving low dosages of 100 to 200 mg of amiodarone daily retain clear corneas or show stage 1 changes only, regardless of duration of treatment or total amount of substance ingested. Patients receiving higher dosages of 400 to 1,400 mg/day show stage 2 and 3 changes, depending on duration of treatment. This keratopathy progresses, even with reduced dosage; however, complete regression occurs once administration of medication is discontinued.


Evidence of common and specific genetic effects: association of the muscarinic acetylcholine receptor M2 (CHRM2) gene with alcohol dependence and major depressive syndrome.
Several correlated phenotypes, alcohol dependence, major depressive syndrome, and an endophenotype of electrophysiological measurements, event-related oscillations (EROs), have demonstrated linkage on the long arm of chromosome 7. Recently, we reported both linkage and association between polymorphisms in the gene encoding the muscarinic acetylcholine receptor M2 (CHRM2) and EROs. In this study, we evaluated whether genetic variation in the CHRM2 gene is also a risk factor for the correlated clinical characteristics of alcoholism and depression. The CHRM2 gene contains a single coding exon and a large 5' untranslated region encoded by multiple exons that can be alternatively spliced. Families were recruited through an alcohol dependent proband, and multiplex pedigrees were selected for genetic analyses. We examined 11 single nucleotide polymorphisms (SNPs) spanning the CHRM2 gene in these families. Using the UNPHASED pedigree disequilibrium test (PDTPHASE), three SNPs (one in intron 4 and two in intron 5) showed highly significant association with alcoholism (P=0.004-0.007). Two SNPs (both in intron 4) were significantly associated with major depressive syndrome (P=0.004 and 0.017). Haplotype analyses revealed that the most common haplotype (>40% frequency), T-T-T (rs1824024-rs2061174-rs324650), was under-transmitted to affected individuals with alcohol dependence and major depressive syndrome. Different complementary haplotypes were over-transmitted in alcohol dependent and depressed individuals. These findings provide strong evidence that variants within or close to the CHRM2 locus influence risk for two common psychiatric disorders.


Sleep quantity, sleep difficulties and their perceived consequences in a representative sample of some 2000 British adults.
Sleep problems and sleep restriction are popular topics of discussion, but few representative data are available. We document Britain's sleep based on a nationally representative sample of 1997, 16-93 year olds, who participated in face-to-face interviews. Fifty-eight per cent of respondents reported sleep problems on one or more nights the previous week and 18% reported that the sleep they obtained was insufficient on the majority of nights. Sleep durations were longest in the youngest participants (16-24 years), who slept on average 1 h longer than the 7.04 (SD 1.55) sample average. Sleep duration showed no appreciable change beyond middle age. Men and women reported sleeping similar amounts but women reported more sleep problems. Men reported sleeping less when there were more children in their household. Workers (i.e. employees) reported sleeping less on workdays than on non-workdays, but those based at home and those not employed did not. Inability to switch off from work was related to sleep duration on non-workdays. Across all participants average sleep duration exhibited a non-monotonic association with quality of life (i.e. contribution of sleep to energy, satisfaction and success in work, home and leisure activities). Quality of life was positively associated with sleep duration, for durations up to 9 h, but negatively associated with quality of life beyond this. Comparison of our data with the US national sleep poll revealed that Britain sleeps as little or less, whereas a comparison with data reported 40 years ago revealed no statistically reliable reductions. Although we may not sleep less than four decades ago, when we report sleeping less we also tend to associate that lack of sleep with poor performance and quality of life.


Depression Moderates the Relationship between Trait Anxiety, Worry and Attentional Control in Melanoma Survivors.
Cancer survivors commonly contend with concurrent cognitive difficulties such as problems with attention and concentration, and psychological distress, including anxiety and depression. However, the associations between attentional and emotional difficulties within the specific context of melanoma survivors remain relatively unexplored. Premised on attentional control theory, the current study employed a cross-sectional design to explore the interplay among trait anxiety (dispositional) and situational anxiety (cancer-related worry), depression and attentional control (ability to inhibit distractors and flexibly shift within and between tasks) in a sample of 187 melanoma survivors aged 18 to 58 years (Mage = 36.83 years, SDage = 5.44 years; 93% female). Data were analyzed using a moderated multiple regression, with anxiety, cancer worry and depression as predictors, and attentional control as the criterion variable. After statistically controlling for the variance of chemotherapy, we found that individuals with higher trait anxiety and higher cancer-related worry reported greater attentional control at low levels of depression, yet poorer attentional control at high depression, relative to individuals with low anxiety. Our findings suggest that anxiety and depression are differentially related to attentional control in melanoma survivors. The results provide a marker for clinicians addressing anxiety and depression in this population. Implications for primary healthcare are discussed.


The English Seasonal Flu Immunization Programme for Poultry Workers 2007: a challenging task.
English Primary Care Trusts (PCTs) immunized the poultry worker population with the seasonal influenza vaccine in the 2007 winter season. In Warwickshire, the provision of vaccinations progressed in two phases: four weekday evening clinics were offered initially, then one weekend clinic was offered, plus on-site vaccination at three farms and vaccination in general practice. There were 253 registered premises in Warwickshire. Eighty-eight persons were vaccinated in five clinics; 131 persons were immunized on-site. Nobody attended their general practice for vaccination; the overall uptake rate was 32%, far exceeding the expected 20%. On-site vaccination during working hours was by far the most effective method of vaccinating this population; community clinics were not cost-effective, nor were general practices apparently accessed. The number of workers recorded in the contact list of registered poultry premises provided by DEFRA/DH has been shown to be unreliable; this has implications for the future implementation and evaluation of this programme. Immigrant workers within the poultry worker population make communication about the benefits of vaccination and access to primary care an issue, both factors which impact on uptake. Strategies for engaging smaller farms, immigrant and non-registered workers need to be developed.


Predicting tobacco smoking among male adolescents in Hamadan City, west of Iran in 2014: an application of the prototype willingness model.
As adolescent tobacco smoking has become a widespread problem in developing countries, it is time to understand the cognitive determinants of adolescents' decisions to engage in tobacco smoking. This study aimed to investigate the predicting factors associated with tobacco smoking among male adolescents based on Prototype Willingness Model (PWM) as a theoretical framework. This descriptive-analytical study was carried out on 810 male adolescents of Hamadan City western Iran, recruited with a multistage sampling method. The data-gathering tool consisted of a questionnaire based on the PWM constructs. Data analysis was performed using SPSS-19 software, by bivariate correlations, liner and logistic regression tests. The prevalence of current tobacco smoking was 17.2%. Behavioral willingness and subjective norms were the most important predictors of behavioral intentions, whereas subjective norms, attitude and prototype were the most important predictors for behavioral willingness. The result obtained from logistic regression analysis revealed that both pathways of PWM constructs [behavioral intention (OR=1.207; 95% CI: 1.13, 1.28) and behavioral willingness (OR=1.334; 95% CI: 1.25, 1.41) were significant predicting factors for tobacco smoking among male adolescents. The framework of the PWM is applicable and useful in understanding tobacco smoking among male adolescents. In addition, the results revealed the importance of social reaction path when examining adolescents' smoking status.