Effectiveness of an Electronic Partogram: A Mixed-Method, Quasi-Experimental Study Among Skilled Birth Attendants in Kenya.
Timely identification and management of intrapartum complications could significantly reduce maternal deaths, intrapartum stillbirths, and newborn deaths due to hypoxia. The World Health Organization (WHO) identifies monitoring of labor using the paper partograph as a high-priority intervention for identifying abnormities in labor and fetal well-being. This article describes a mixed-method, quasi-experimental study to assess the effectiveness of an Android tablet-based electronic, labor clinical decision-support application (ePartogram) in limited-resource settings. The study, conducted in Kenya from October 2016 to May 2017, allocated 12 hospitals and health centers to an intervention (ePartogram) or comparison (paper partograph) group. Skilled birth attendants (SBAs) in both groups received a 2-day refresher training in labor management and partograph use. The intervention group received an additional 1-day orientation on use and care of the Android-based ePartogram app. All outcomes except one compare post-ePartogram intervention versus paper partograph controls. The exception is outcome of early perinatal mortality pre- and post-ePartogram introduction in intervention sites compared to control sites. We used log binomial regression to analyze the primary outcome of the study, suboptimal fetal outcomes. We also analyzed for secondary outcomes (SBAs performing recommended actions), and conducted in-depth interviews with facility in-charges and SBAs to ascertain acceptability and adoptability of the ePartogram. We compared data from 842 clients in active labor using ePartograms with data from 1,042 clients monitored using a paper partograph. SBAs using ePartograms were more likely than those using paper partographs to take action to maintain normal labor, such as ambulation, feeding, and fluid intake, and to address abnormal measurements of fetal well-being (14.7% versus 5.3%, adjusted relative risk=4.00, 95% confidence interval [CI]=1.95-8.19). Use of the ePartogram was associated with a 56% (95% CI=27%-73%) lower likelihood of suboptimal fetal outcomes than the paper partograph. Users of the ePartogram were more likely to be compliant with routine labor observations. SBAs stated that the technology was easy to use but raised concerns about its use at high-volume sites. Further research is needed to evaluate costs and benefit and to incorporate recent WHO guidance on labor management. ePartogram use was associated with improvements in adherence to recommendations for routine labor care and a reduction in adverse fetal outcomes, with providers reporting adoptability without undue effort. Continued development of the ePartogram, including incorporating new clinical rules from the 2018 WHO recommendations on intrapartum care, will improve labor monitoring and quality care at all health system levels.


Recommendations for evaluation of computational methods.
The field of computational chemistry, particularly as applied to drug design, has become increasingly important in terms of the practical application of predictive modeling to pharmaceutical research and development. Tools for exploiting protein structures or sets of ligands known to bind particular targets can be used for binding-mode prediction, virtual screening, and prediction of activity. A serious weakness within the field is a lack of standards with respect to quantitative evaluation of methods, data set preparation, and data set sharing. Our goal should be to report new methods or comparative evaluations of methods in a manner that supports decision making for practical applications. Here we propose a modest beginning, with recommendations for requirements on statistical reporting, requirements for data sharing, and best practices for benchmark preparation and usage.


Dynamics of gamma bursts in local field potentials.
In this letter, we provide a stochastic analysis of, and supporting simulation data for, a stochastic model of the generation of gamma bursts in local field potential (LFP) recordings by interacting populations of excitatory and inhibitory neurons. Our interest is in behavior near a fixed point of the stochastic dynamics of the model. We apply a recent limit theorem of stochastic dynamics to probe into details of this local behavior, obtaining several new results. We show that the stochastic model can be written in terms of a rotation multiplied by a two-dimensional standard Ornstein-Uhlenbeck (OU) process. Viewing the rewritten process in terms of phase and amplitude processes, we are able to proceed further in analysis. We demonstrate that gamma bursts arise in the model as excursions of the modulus of the OU process. The associated pair of stochastic phase and amplitude processes satisfies their own pair of stochastic differential equations, which indicates that large phase slips occur between gamma bursts. This behavior is mirrored in LFP data simulated from the original model. These results suggest that the rewritten model is a valid representation of the behavior near the fixed point for a wide class of models of oscillatory neural processes.


Acute Supplementation with Nitrate-Rich Beetroot Juice Causes a Greater Increase in Plasma Nitrite and Reduction in Blood Pressure of Older Compared to Younger Adults.
Nitrate-rich beetroot juice supplementation has been shown to improve cardiovascular and cognitive function in younger and older adults via increased nitric oxide production. However, it is unclear whether the level of effects differs between the two groups. We hypothesized that acute supplementation with nitrate-rich beetroot juice would improve cardiovascular and cognitive function in older and younger adults, with the potential for greater improvements in older adults. Thirteen younger (18-30 years) and 11 older (50-70 years) adults consumed either 150 mL of nitrate-rich beetroot juice (BR; 10.5 mmol nitrate) or placebo (PL; 1 mmol nitrate) in a double-blind, crossover design, 2.25 h prior to a 30-min treadmill walk. Plasma nitrate and nitrite concentrations, blood pressure (BP), heart rate (HR), cognitive function, mood and perceptual tests were performed throughout the trial. BR consumption significantly increased plasma nitrate (p < 0.001) and nitrite (p = 0.003) concentrations and reduced systolic BP (p < 0.001) in both age groups and reduced diastolic BP (p = 0.013) in older adults. Older adults showed a greater elevation in plasma nitrite (p = 0.038) and a greater reduction in diastolic BP (p = 0.005) following BR consumption than younger adults. Reaction time was improved in the Stroop test following BR supplementation for both groups (p = 0.045). Acute BR supplementation increased plasma nitrite concentrations and reduced diastolic BP to a greater degree in older adults; whilst systolic BP was reduced in both older and younger adults, suggesting nitrate-rich BR may improve cardiovascular health, particularly in older adults due to the greater benefits from reductions in diastolic BP.


Advances in arterial spin labelling MRI methods for measuring perfusion and collateral flow.
With the publication in 2015 of the consensus statement by the perfusion study group of the International Society for Magnetic Resonance in Medicine (ISMRM) and the EU-COST action 'ASL in dementia' on the implementation of arterial spin labelling MRI (ASL) in a clinical setting, the development of ASL can be considered to have become mature and ready for clinical prime-time. In this review article new developments and remaining issues will be discussed, especially focusing on quantification of ASL as well as on new technological developments of ASL for perfusion imaging and flow territory mapping. Uncertainty of the achieved labelling efficiency in pseudo-continuous ASL (pCASL) as well as the presence of arterial transit time artefacts, can be considered the main remaining challenges for the use of quantitative cerebral blood flow (CBF) values. New developments in ASL centre around time-efficient acquisition of dynamic ASL-images by means of time-encoded pCASL and diversification of information content, for example by combined 4D-angiography with perfusion imaging. Current vessel-encoded and super-selective pCASL-methodology have developed into easily applied flow-territory mapping methods providing relevant clinical information with highly similar information content as digital subtraction angiography (DSA), the current clinical standard. Both approaches seem therefore to be ready for clinical use.


Recent Advances in Placenta-Heart Interactions.
Congenital heart defects (CHD) occur in ∼1 in every 100 live births. In addition, an estimated 10% of fetal loss is due to severe forms of CHD. This makes heart defects the most frequently occurring birth defect and single cause of in utero fatality in humans. There is considerable evidence that CHD is heritable, indicating a strong contribution from genetic risk factors. There are also known external environmental exposures that are significantly associated with risk for CHD. Hence, the majority of CHD cases have long been considered to be multifactorial, or generally caused by the confluence of several risk factors potentially from genetic, epigenetic, and environmental sources. Consequently, a specific cause can be very difficult to ascertain, although patterns of associations are very important to prevention. While highly protective of the fetus, the in utero environment is not immune to insult. As the conduit between the mother and fetus, the placenta plays an essential role in maintaining fetal health. Since it is not a fully-formed organ at the onset of pregnancy, the development of the placenta must keep pace with the growth of the fetus in order to fulfill its critical role during pregnancy. In fact, the placenta and the fetal heart actually develop in parallel, a phenomenon known as the placenta-heart axis. This leaves the developing heart particularly vulnerable to early placental insufficiency. Both organs share several developmental pathways, so they also share a common vulnerability to genetic defects. In this article we explore the coordinated development of the placenta and fetal heart and the implications for placental involvement in the etiology and pathogenesis of CHD.


Maintenance ECT in schizophrenia: A systematic review.
Relapse after discontinuation of ECT is significant in patients with schizophrenia. The purpose of this systematic review was to examine use of M-ECT in schizophrenia to guide clinical decision making for relapse prevention in schizophrenia. We reviewed studies examining the role of continuation (C-ECT) and maintenance electroconvulsive therapy (M-ECT) in schizophrenia. Following PRISMA guidelines, we included randomized controlled trials, open label trials, retrospective chart reviews, case reports, and case series in this review. We evaluated adjunctive pharmacological regimens; ECT treatment parameters, including frequency, duration of continued treatment, electrode placement; clinical outcomes including cognitive side effects and relapse rates from included studies. Our findings suggest M-ECT could provide an effective form of relapse prevention in these patients and persistent cognitive side effects are minimal.


Isolation of specific clones from nonarrayed BAC libraries through homologous recombination.
We have developed a new approach to screen bacterial artificial chromosome (BAC) libraries by recombination selection. To test this method, we constructed an orangutan BAC library using an E. coli strain (DY380) with temperature inducible homologous recombination (HR) capability. We amplified one library segment, induced HR at 42°C to make it recombination proficient, and prepared electrocompetent cells for transformation with a kanamycin cassette to target sequences in the orangutan genome through terminal recombineering homologies. Kanamycin-resistant colonies were tested for the presence of BACs containing the targeted genes by the use of a PCR-assay to confirm the presence of the kanamycin insertion. The results indicate that this is an effective approach for screening clones. The advantage of recombination screening is that it avoids the high costs associated with the preparation, screening, and archival storage of arrayed BAC libraries. In addition, the screening can be conceivably combined with genetic engineering to create knockout and reporter constructs for functional studies.


Breakfast staple types affect brain gray matter volume and cognitive function in healthy children.
Childhood diet is important for brain development. Furthermore, the quality of breakfast is thought to affect the cognitive functioning of well-nourished children. To analyze the relationship among breakfast staple type, gray matter volume, and intelligence quotient (IQ) in 290 healthy children, we used magnetic resonance images and applied voxel-based morphometry. We divided subjects into rice, bread, and both groups according to their breakfast staple. We showed that the rice group had a significantly larger gray matter ratio (gray matter volume percentage divided by intracranial volume) and significantly larger regional gray matter volumes of several regions, including the left superior temporal gyrus. The bread group had significantly larger regional gray and white matter volumes of several regions, including the right frontoparietal region. The perceptual organization index (POI; IQ subcomponent) of the rice group was significantly higher than that of the bread group. All analyses were adjusted for age, gender, intracranial volume, socioeconomic status, average weekly frequency of having breakfast, and number of side dishes eaten for breakfast. Although several factors may have affected the results, one possible mechanism underlying the difference between the bread and the rice groups may be the difference in the glycemic index (GI) of these two substances; foods with a low GI are associated with less blood-glucose fluctuation than are those with a high GI. Our study suggests that breakfast staple type affects brain gray and white matter volumes and cognitive function in healthy children; therefore, a diet of optimal nutrition is important for brain maturation during childhood and adolescence.


Bench to bedside: A role for erythropoietin in sepsis.
Sepsis is the systemic inflammatory response to infection and can result in multiple organ dysfunction syndrome with associated high mortality, morbidity and health costs. Erythropoietin is a well-established treatment for the anaemia of renal failure due to its anti-apoptotic effects on red blood cells and their precursors. The extra-haemopoietic actions of erythropoietin include vasopressor, anti-apoptotic, cytoprotective and immunomodulating actions, all of which could prove beneficial in sepsis. Attenuation of organ dysfunction has been shown in several animal models and its vasopressor effects have been well characterised in laboratory and clinical settings. Clinical trials of erythropoietin in single organ disorders have suggested promising cytoprotective effects, and while no randomised trials have been performed in patients with sepsis, good quality data exist from studies on anaemia in critically ill patients, giving useful information of its pharmacokinetics and potential for harm. An observational cohort study examining the microvascular effects of erythropoietin is underway and the evidence would support further phase II and III clinical trials examining this molecule as an adjunctive treatment in sepsis.


Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome.
Infection-triggered disease onset, chronic immune activation and autonomic dysregulation in CFS point to an autoimmune disease directed against neurotransmitter receptors. Autoantibodies against G-protein coupled receptors were shown to play a pathogenic role in several autoimmune diseases. Here, serum samples from a patient cohort from Berlin (n=268) and from Bergen with pre- and post-treatment samples from 25 patients treated within the KTS-2 rituximab trial were analysed for IgG against human α and β adrenergic, muscarinic (M) 1-5 acetylcholine, dopamine, serotonin, angiotensin, and endothelin receptors by ELISA and compared to a healthy control cohort (n=108). Antibodies against β2, M3 and M4 receptors were significantly elevated in CFS patients compared to controls. In contrast, levels of antibodies against α adrenergic, dopamine, serotonin, angiotensin, and endothelin receptors were not different between patients and controls. A high correlation was found between levels of autoantibodies and elevated IgG1-3 subclasses, but not with IgG4. Further patients with high β2 antibodies had significantly more frequently activated HLA-DR+ T cells and more frequently thyreoperoxidase and anti-nuclear antibodies. In patients receiving rituximab maintenance treatment achieving prolonged B-cell depletion, elevated β2 and M4 receptor autoantibodies significantly declined in clinical responder, but not in non-responder. We provide evidence that 29.5% of patients with CFS had elevated antibodies against one or more M acetylcholine and β adrenergic receptors which are potential biomarkers for response to B-cell depleting therapy. The association of autoantibodies with immune markers suggests that they activate B and T cells expressing β adrenergic and M acetylcholine receptors. Dysregulation of acetylcholine and adrenergic signalling could also explain various clinical symptoms of CFS.


Efficacy and safety of mirodenafil in men taking antihypertensive medications.
Mirodenafil is a recently developed oral phosphodiesterase type 5 inhibitor, which was observed to significantly improve erectile function and was well tolerated in men with broad-spectrum erectile dysfunction (ED). To investigate the efficacy and safety of mirodenafil treatment compared with placebo in men taking at least one antihypertensive medication. A multicenter, double-blind, placebo-controlled, parallel group, fixed-dose study was conducted with 109 subjects who were randomized to placebo or mirodenafil 100 mg for 12 weeks on an "as needed" basis. The primary efficacy measures were the changes from baseline in sum of scores on International Index of Erectile Function-erectile function domain (IIEF-EF) questions 1 to 5 and 15 with treatment. The secondary efficacy measures included scores on IIEF question 3 and 4 (Q3 and Q4), all domain scores of IIEF, and Sexual Encounter Profile Question 2 and 3 (SEP2 and SEP3) along with responses to Global Assessment Question (GAQ) and Life Satisfaction Checklist (LSC). The safety assessments included laboratory tests, vital signs, 12-lead electrocardiogram recordings, and patients' reporting of adverse events. The mirodenafil group showed significantly greater increase in IIEF-EF scores at 12 weeks compared with the placebo group (9.35 ± 6.86 vs. 2.66 ± 6.44, P<0.001). The mirodenafil group also demonstrated significantly greater improvement in scores of IIEF Q3 and Q4, other four domains of IIEF, SEP2, SEP3, and LSC along with percentages of patients responding positively to GAQ compared with the placebo group. During the study, no clinically significant changes were observed regarding blood pressure, heart rate, electrocardiographic findings, or laboratory values. Facial flushing and headache were the most common treatment-associated adverse events, which were mild or moderate in severity, resolving spontaneously. Mirodenafil was effective and safe in men with ED concomitantly taking antihypertensive medications.


Subthreshold depression and regional brain volumes in young community adolescents.
Neuroimaging findings have been reported in regions of the brain associated with emotion in both adults and adolescents with depression, but few studies have investigated whether such brain alterations can be detected in adolescents with subthreshold depression, a condition at risk for major depressive disorder. In this study, we searched for differences in brain structure at age 14 years in adolescents with subthreshold depression and their relation to depression at age 16 years. High-resolution structural magnetic resonance imaging was used to assess adolescents with self-reported subthreshold depression (n = 119) and healthy control adolescents (n = 461), all recruited from a community-based sample. Regional gray and white matter volumes were compared across groups using whole-brain voxel-based morphometry. The relationship between subthreshold depression at baseline and depression outcome was explored using causal mediation analyses to search for mediating effects of regional brain volumes. Adolescents with subthreshold depression had smaller gray matter volume in the ventromedial prefrontal and rostral anterior cingulate cortices and caudates, and smaller white matter volumes in the anterior limb of internal capsules, left forceps minor, and right cingulum. In girls, but not in boys, the relation between subthreshold depression at baseline and high depression score at follow-up was mediated by medial-prefrontal gray matter volume. Subthreshold depression in early adolescence might be associated with smaller gray and white matter volumes in regions of the frontal-striatal-limbic affective circuit, and the occurrence of depression in girls with subthreshold depression might be influenced by medial-prefrontal gray matter volume. However, these findings should be interpreted with caution because of the limitations of the clinical assessment methods.


High-resolution analysis of parent-of-origin allelic expression in the mouse brain.
Genomic imprinting results in preferential expression of the paternal or maternal allele of certain genes. We have performed a genome-wide characterization of imprinting in the mouse embryonic and adult brain. This approach uncovered parent-of-origin allelic effects of more than 1300 loci. We identified parental bias in the expression of individual genes and of specific transcript isoforms, with differences between brain regions. Many imprinted genes are expressed in neural systems associated with feeding and motivated behaviors, and parental biases preferentially target genetic pathways governing metabolism and cell adhesion. We observed a preferential maternal contribution to gene expression in the developing brain and a major paternal contribution in the adult brain. Thus, parental expression bias emerges as a major mode of epigenetic regulation in the brain.


Progressive motor weakness in transgenic mice expressing human TDP-43.
Familial ALS patients with TDP-43 gene mutations and sporadic ALS patients share common TDP-43 neuronal pathology. To delineate mechanisms underlying TDP-43 proteinopathies, transgenic mice expressing A315T, M337V or wild type human TDP-43 were generated. Multiple TDP-43 founders developed a severe early motor phenotype that correlated with TDP-43 levels in spinal cord. Three A315T TDP-43 lines developed later onset paralysis with cytoplasmic ubiquitin inclusions, gliosis and TDP-43 redistribution and fragmentation. The WT TDP-43 mouse line with highest spinal cord expression levels remains asymptomatic, although these mice show spinal cord pathology. One WT TDP-43 line with high skeletal muscle levels of TDP-43 developed a severe progressive myopathy. Over-expression of TDP-43 in vivo is sufficient to produce progressive motor phenotypes by a toxic gain of function paradigm. Transgenic mouse lines expressing untagged mutant and wild type TDP-43 under the same promoter represent a powerful new model system for studying TDP-43 proteinopathies in vivo.


Inhibition of hedgehog signalling prevents experimental fibrosis and induces regression of established fibrosis.
Tissue fibrosis is a leading cause of death in patients with systemic sclerosis (SSc). Effective antifibrotic treatments are not available. Here, the authors investigated inhibition of hedgehog signalling by targeting Smoothened (Smo) as a novel antifibrotic approach. The activation status of the hedgehog pathway was assessed by immunohistochemistry for Gli transcription factors and by quantification of hedgehog target genes. Hedgehog signalling was inhibited by the selective inhibitor LDE223 and by small interfering RNA against Smo in the models of bleomycin-induced dermal fibrosis and in tight-skin-1 mice. Hedgehog signalling is activated in SSc and in murine models of SSc. Inhibition of Smo either by LDE223 or by small interfering RNA prevented dermal thickening, myofibroblast differentiation and accumulation of collagen upon challenge with bleomycin. Targeting Smo also exerted potent antifibrotic effects in tight-skin-1 mice and did prevent progression of fibrosis and induced regression of pre-established fibrosis. Inhibition of hedgehog signalling exerted potent antifibrotic effects in preclinical models of SSc in both preventive and therapeutic settings. These findings might have direct translational implications because inhibitors of Smo are already available and yielded promising results in initial clinical trials.


Pregnancy outcomes following systemic prenatal acyclovir exposure: Conclusions from the international acyclovir pregnancy registry, 1984-1999.
Oral acyclovir is commonly used for genital herpes and other herpesvirus infections. Data on potential fetal risk are extremely limited. From 1984 to 1998, the Acyclovir in Pregnancy Registry monitored birth outcomes of women exposed to oral or intravenous acyclovir during pregnancy. This report describes the final results. The registry was publicized to health care providers most likely to diagnose pregnancy; providers called the registry telephone number, then mailed in a brief questionnaire. Pregnancy outcomes were categorized either as outcomes with birth defects or outcomes without birth defects, subcategorized as live births, spontaneous pregnancy losses (including stillbirths), and induced abortions. Birth defects were defined using a modification of the CDC definition for birth defects surveillance systems. Observed rates were compared to the rate (3.2%) of birth defects expected in the general population. Between June 1, 1984 and June 30, 1998, 1695 pregnancies exposed to oral or IV acyclovir were registered; 461 (27%) were lost to follow-up. A total of 1234 pregnancies in 24 countries were followed, with a total of 1246 outcomes. Among 1246 pregnancy outcomes, 756 involved acyclovir exposure in the first trimester, 197 in the second trimester, and 291 in the third trimester. Among live births with first trimester acyclovir exposure, risk of birth defects was 19 of 596 (3.2%; 95% CI, 2.0-5.0%). No unusual defects or pattern of defects were apparent. The observed rates and types of birth defects for pregnancies exposed to acyclovir did not differ significantly from those in the general population. Birth Defects Research (Part A), 2004. Published 2004 Wiley-Liss, Inc.


A majority rule approach for region-of-interest-guided streamline fiber tractography.
Hand-drawn gray matter regions of interest (ROI) are often used to guide the estimation of white matter tractography, obtained from diffusion-weighted magnetic resonance imaging (DWI), in healthy and in patient populations. However, such ROIs are vulnerable to rater bias of the individual segmenting the ROIs, scan variability, and individual differences in neuroanatomy. In this report, a "majority rule" approach is introduced for ROI segmentation used to guide streamline tractography in white matter structures. DWI of one healthy participant was acquired in ten separate sessions using a 3 T scanner over the course of a month. Four raters identified ROIs within the left hemisphere [Cerebral Peduncle (CPED); Internal Capsule (IC); Hand Portion of the Motor Cortex, or Hand Bump, (HB)] using a group-established standard operating procedure for ROI definition to guide the estimation of streamline tracts within the corticospinal tract (CST). Each rater traced the ROIs twice for each scan session. The overlap of each rater's two ROIs was used to define a representative ROI for each rater. These ROIs were combined to create a "majority rules" ROI, in which the rule requires that each voxel is selected by at least three of four raters. Reproducibility for ROIs and CST segmentations were analyzed with the Dice Similarity Coefficient (DSC). Intra-rater reliability for each ROI was high (DSCs ≥ 0.83). Inter-rater reliability was moderate to adequate (DSC range 0.54-0.75; lowest for IC). Using intersected majority rules ROIs, the resulting CST showed improved overlap (DSC = 0.82) in the estimated streamline tracks for the ten sessions. Despite high intra-rater reliability, there was lower inter-rater reliability consistent with the expectation of rater bias. Employing the majority rules method improved reliability in the overlap of the CST.


Gender, sexuality and the discursive representation of access and equity in health services literature: implications for LGBT communities.
This article considers how health services access and equity documents represent the problem of access to health services and what the effects of that representation might be for lesbian, gay, bisexual and transgender (LGBT) communities. We conducted a critical discourse analysis on selected access and equity documents using a gender-based diversity framework as determined by two objectives: 1) to identify dominant and counter discourses in health services access and equity literature; and 2) to develop understanding of how particular discourses impact the inclusion, or not, of LGBT communities in health services access and equity frameworks.The analysis was conducted in response to public health and clinical research that has documented barriers to health services access for LGBT communities including institutionalized heterosexism, biphobia, and transphobia, invisibility and lack of health provider knowledge and comfort. The analysis was also conducted as the first step of exploring LGBT access issues in home care services for LGBT populations in Ontario, Canada. A critical discourse analysis of selected health services access and equity documents, using a gender-based diversity framework, was conducted to offer insight into dominant and counter discourses underlying health services access and equity initiatives. A continuum of five discourses that characterize the health services access and equity literature were identified including two dominant discourses: 1) multicultural discourse, and 2) diversity discourse; and three counter discourses: 3) social determinants of health (SDOH) discourse; 4) anti-oppression (AOP) discourse; and 5) citizen/social rights discourse. The analysis offers a continuum of dominant and counter discourses on health services access and equity as determined from a gender-based diversity perspective. The continuum of discourses offers a framework to identify and redress organizational assumptions about, and ideological commitments to, sexual and gender diversity and health services access and equity. Thus, the continuum of discourses may serve as an important element of a health care organization's access and equity framework for the evaluation of access to good quality care for diverse LGBT populations. More specfically, the analysis offers four important points of consideration in relation to the development of a health services access and equity framework.


Development of a health status measure for older African-American women with type 2 diabetes.
To develop a health status measure in older African-American women with type 2 diabetes. African-American women, age > or =40 years with type 2 diabetes, were recruited from central North Carolina to participate in three sequential phases: 1) Seven focus groups were convened and transcripts evaluated to generate questions and identify plausible domains; 2) Ten one-on-one cognitive response interviews were performed to ensure clarity and cultural appropriateness of the questions; and 3) 217 women participated in psychometric evaluation to establish the internal consistency and validity of the instrument. Three broad categories--mental, physical, and social well-being--captured important issues generated during the focus groups. "My diabetes" was added during the cognitive response interviews as a way of separating the impact of diabetes from coexisting issues that affect health status. The response option was changed from a six- to a four-point Likert scale to accommodate subject preference. Using principal components and subsequent promax rotation, we identified two hierarchical domains (mental and social well-being) and a physical symptom index. The internal consistency (Cronbach's alpha) of the mental and social well-being subscales are 0.83 and 0.93, respectively. A priori hypothesized correlations between subscales along with each subscale and glycated hemoglobin, diabetes duration, physical activity, and a perceived health competence scale helped establish the construct validity of the instrument. A culturally appropriate disease-specific health status measure for older African-American women with type 2 diabetes has been developed. We have established the internal consistency, construct validity, and factor analytic properties of the measure. This measure should prove useful for investigators who seek a health status instrument that addresses issues germane to African-American women with type 2 diabetes.


The in chemico-in silico interface: challenges for integrating experimental and computational chemistry to identify toxicity.
A number of toxic effects are brought about by the covalent interaction between the toxicant and biological macromolecules. In chemico assays are available that attempt to identify reactive compounds. These approaches have been developed independently for pharmaceuticals and for other nonpharmaceutical compounds. The assays vary widely in terms of the macromolecule (typically a peptide) and the analytical technique utilised. For both sets of methods, there are great opportunities to capture in chemico information by using in silico methods to provide computational tools for screening purposes. In order to use these in chemico and in silico methods, integrated testing strategies are required for individual toxicity endpoints. The potential for the use of these approaches is described, and a number of recommendations to improve this extremely useful technique, in terms of implementing the Three Rs in toxicity testing, are presented.


Decidua and implantation of the embryo from a historical perspective.
Implantation of the embryo is critical for the initiation of intrauterine development of early embryos. It depends on the proper soil formed by the decidualized pregnant uterus. In the present article I have reviewed the evolution of the modern concepts of decidualization and embryonic implantation, emphasizing how closely interrelated these two processes are. Special emphasis and recognition is given to the Boston pathologist Arthur T. Hertig, who studied for 15 years with another Bostonian, John Rock, a gynecologist, human implantation and early embryogenesis, thus providing the basis for future studies of human reproductive biology, infertility and contraception.


The Effect of Air Tourniquet on Interleukin-6 Levels in Total Knee Arthroplasty.
Air tourniquet-induced skeletal muscle injury increases the concentrations of some cytokines such as interleukin-6 (IL-6) in plasma. However, the effect of an air tourniquet on the IL-6 concentrations after total knee arthroplasty (TKA) is unclear. We therefore investigated the impact of tourniquet-induced ischemia and reperfusion injury in TKA using the IL-6 level as an index. Ten patients with primary knee osteoarthrosis who underwent unilateral TKA without an air tourniquet were recruited (Non-tourniquet group). We also selected 10 age- and sex-matched control patients who underwent unilateral TKA with an air tourniquet (Tourniquet group). Venous blood samples were obtained at 3 points; before surgery, 24 h after surgery, and 7 days after surgery. The following factors were compared between the two groups; IL-6, C-reactive protein (CRP), creatine phosphokinase (CPK), the mean white blood cell (WBC) counts, and the maximum daily body temperatures. The IL-6 level at 24 h after surgery was significantly higher than that at any other point (p<0.01). No significant differences were observed in the WBC count, the body temperature, or the CRP, CPK, or IL-6 levels of the two groups at any of the time points. The effect of ischemia and reperfusion due to the use of an air tourniquet on increasing the IL-6 level was much smaller than that induced by surgical stress in TKA.


Risk of self-harm and suicide in people with specific psychiatric and physical disorders: comparisons between disorders using English national record linkage.
Background Psychiatric illnesses are known risk factors for self-harm but associations between self-harm and physical illnesses are less well established. We aimed to stratify selected chronic physical and psychiatric illnesses according to their relative risk of self-harm. Design Retrospective cohort studies using a linked dataset of Hospital Episode Statistics (HES) for 1999-2011. Participants Individuals with selected psychiatric or physical conditions were compared with a reference cohort constructed from patients admitted for a variety of other conditions and procedures. Setting All admissions and day cases in National Health Service (NHS) hospitals in England. Main outcome measures Hospital episodes of self-harm. Rate ratios (RRs) were derived by comparing admission for self-harm between cohorts. Results The psychiatric illnesses studied (depression, bipolar disorder, alcohol abuse, anxiety disorders, eating disorders, schizophrenia and substance abuse) all had very high RRs (> 5) for self-harm. Of the physical illnesses studied, an increased risk of self-harm was associated with epilepsy (RR = 2.9, 95% confidence interval [CI] 2.8-2.9), asthma (1.8, 1.8-1.9), migraine (1.8, 1.7-1.8), psoriasis (1.6, 1.5-1.7), diabetes mellitus (1.6, 1.5-1.6), eczema (1.4, 1.3-1.5) and inflammatory polyarthropathies (1.4, 1.3-1.4). RRs were significantly low for cancers (0.95, 0.93-0.97), congenital heart disease (0.9, 0.8-0.9), ulcerative colitis (0.8, 0.7-0.8), sickle cell anaemia (0.7, 0.6-0.8) and Down's syndrome (0.1, 0.1-0.2). Conclusions Psychiatric illnesses carry a greatly increased risk of self-harm as well as of suicide. Many chronic physical illnesses are also associated with an increased risk of both self-harm and suicide. Identifying those at risk will allow provision of appropriate monitoring and support.


Adsorption in zeolites using mechanically embedded ONIOM clusters.
We have explored mechanically embedded three-layer QM/QM/MM ONIOM models for computational studies of binding in Al-substituted zeolites. In all the models considered, the high-level-theory layer consists of the adsorbate molecule and of the framework atoms within the first two coordination spheres of the Al atom and is treated at the M06-2X/6-311G(2df,p) level. For simplicity, flexibility and routine applicability, the outer, low-level-theory layer is treated with the UFF. We have modelled the intermediate-level layer quantum mechanically and investigated the performance of HF theory and of three DFT functionals, B3LYP, M06-2X and ωB97x-D, for different layer sizes and various basis sets, with and without BSSE corrections. We have studied the binding of sixteen probe molecules in H-MFI and compared the computed adsorption enthalpies with published experimental data. We have demonstrated that HF and B3LYP are inadequate for the description of the interactions between the probe molecules and the framework surrounding the metal site of the zeolite on account of their inability to capture dispersion forces. Both M06-2X and ωB97x-D on average converge within ca. 10% of the experimental values. We have further demonstrated transferability of the approach by computing the binding enthalpies of n-alkanes (C1-C8) in H-MFI, H-BEA and H-FAU, with very satisfactory agreement with experiment. The computed entropies of adsorption of n-alkanes in H-MFI are also found to be in good agreement with experimental data. Finally, we compare with published adsorption energies calculated by periodic-DFT for n-C3 to n-C6 alkanes, water and methanol in H-ZSM-5 and find very good agreement.


Protective Effect of Pure Sour Cherry Anthocyanin Extract on Cytokine-Induced Inflammatory Caco-2 Monolayers.
Anthocyanins have several beneficial effects, especially on inflammatory and oxidative conditions. The pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), induce damage in the intestinal barrier and participate in the pathogenesis of chronic bowel diseases. A number of fruits have high anthocyanin contents with strong biological activity which can support protective actions. Sour cherry (Prunus cerassus) is one of the richest fruits in anthocyanins; especially it has high content of cyanidins. The aim of this study was to test the biological effects of a pure sour cherry anthocyanin extract under inflammatory conditions on the intestinal barrier. Caco-2 monolayers were stimulated with 50 ng/mL TNF-α and 25 ng/mL IL-1β, and the protective effects of the anthocyanin extract were examined. We demonstrated the safety of 500, 50, 5 and 0.5 µM anthocyanin extracts through cell impedance measurements. The 50 µM anthocyanin extract inhibited the cytokine-induced Caco-2 permeability and the nuclear translocation of NF-κB p65 subunits. The extract significantly reduced the release of IL-6 and IL-8 production in intestinal cells and glutathione peroxidase activity stimulated by cytokines. We demonstrated, for the first time, the beneficial effects of pure sour cherry anthocyanin extract on inflammatory Caco-2 monolayers, indicating that this substance could be protective in inflammatory bowel diseases and is an excellent raw material for further applications and formulations.


Strategic control in word reading: evidence from speeded responding in the tempo-naming task.
To investigate strategic control over response initiation in word reading, the authors introduce the tempo-naming task. Relative to baseline performance in the standard-naming task, participants were induced to respond with faster latencies, shorter durations, and lower levels of accuracy by instructing them to time response initiation with an experimentally controlled tempo. The tempo response cue attenuated stimulus effects, and as faster tempos reduced latencies, the number of spelling-sound errors remained constant, whereas the number of word, nonword, and articulatory errors increased. To explain these results, the authors propose input gain as a mechanism of control over processing speed. The experimenters sketch how input gain could account for the current results as well as for the results from stimulus-blocking experiments testing the route emphasis and time criterion hypotheses of strategic control.


Flagella and motility alterations in Pseudomonas aeruginosa strains from patients with cystic fibrosis: relationship to patient clinical condition.
Selected physiological parameters of 31 classic and rough Pseudomonas aeruginosa strains from respiratory tract cultures of patients with cystic fibrosis were examined. An association of a patient's clinical condition (good or poor) with strain physiology was made. Rough strains from patients in poor clinical condition demonstrated severe alterations in motility when compared with M-2, a highly motile and chemotactic burn strain. Of the 10 rough strains from patients in poor clinical condition, 70% lacked flagella, as determined by electron microscopy. The remaining few flagellated strains from this group exhibited weak motility both in soft agar and by the capillary assay. Their chemotactic response to three amino acids, when compared with that of strain M-2, was reduced approximately 30 to 90%. Classic strains from patients in poor clinical condition were less chemotactic than those from patients in good clinical condition. A majority of classic and rough strains from patients in good clinical condition were comparable to M-2 in both chemotaxis and motility. Changes in other physiological characteristics indicated by reduced growth rates, or auxotrophy, were seldom observed in the cystic fibrosis strains studied. The data suggest that host-selective pressures, associated primarily with patients with cystic fibrosis that are in poor clinical condition, result in the loss of factors related to invasiveness such as motility and chemotaxis. We propose that these results may reflect that there is a more general alteration in the cell envelope of cystic fibrosis strains.


Interaction between the patatin-like phospholipase domain-containing protein 3 genotype and coffee drinking and the risk for acute alcoholic hepatitis.
Only a subset of subjects with excessive alcohol consumption develops alcoholic liver disease (ALD). One of the major risk factors for ALD is the genetic variant of the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene. Coffee is one of the most commonly consumed beverages, and coffee consumption has been associated with lower levels of serum alanine aminotransferase. The aim of this study was to investigate the role of coffee drinking and PNPLA3 rs738409 and their association with alcoholic hepatitis (AH) in a well-characterized cohort of subjects from the Translational Research and Evolving Alcoholic Hepatitis Treatment consortium. AH subjects and heavy drinking controls without a history of liver disease who were enrolled between May 2013 and May 2016 were included (n = 339), and the details of alcohol and coffee consumption were assessed. The PNPLA3 variant was determined among participants of European ancestry (n = 183). Relationships between baseline data and AH status were determined, and multivariable logistic regression modeling was performed. During the study period, 189 cases with AH and 150 heavy drinking controls were prospectively enrolled. The prevalence of regular coffee consumption was significantly lower in patients with AH compared to controls (20% versus 43%; P < 0.0001). The overall minor allele frequency of the PNPLA3 variant was higher in AH cases. Multivariable logistic regression revealed that coffee consumption and PNPLA3 were significantly associated with AH status at baseline after adjusting for relevant patient characteristics. Conclusion: We found a higher prevalence of AH among heavy drinkers with PNPLA3 G/G and G/C genotypes regardless of coffee consumption status and a higher prevalence of AH among heavy drinkers who were not regular coffee drinkers. These findings remained after considering relevant baseline patient characteristics. Further studies are needed to confirm our observation. (Hepatology Communications 2018;2:29-34).


The evolution of fecundity is associated with female body size but not female-biased sexual size dimorphism among frogs.
Sexual size dimorphism (SSD) is one of the most common ways in which males and females differ. Male-biased SSD (when males are larger) is often attributed to sexual selection favouring large males. When females are larger (female-biased SSD), it is often argued that natural selection favouring increased fecundity (i.e. larger clutches or eggs) has coevolved with larger female body size. Using comparative phylogenetic and multispecies regression model selection approaches, we test the hypothesis that among-species variation in female fecundity is associated with the evolution of female-biased SSD. We also ask whether the hypothesized relationship between SSD and fecundity is relaxed upon the evolution of parental care. Our results suggest a strong relationship between the evolution of fecundity and body size, but we find no significant relationship between fecundity and SSD. Similarly, there does not appear to be a relationship between fecundity and the presence or absence of parental care among species. Thus, although female body size and fecundity coevolve, selection for increased fecundity as an explanation for female-biased SSD is inconsistent with our analyses. We caution that a relationship between female body size and fecundity is insufficient evidence for fecundity selection driving the evolution of female-biased SSD.


Blood bank safety practices: mislabeled samples and wrong blood in tube--a Q-Probes analysis of 122 clinical laboratories.
Although a rare occurrence, ABO incompatible transfusions can cause patient morbidity and mortality. Up to 20% of all mistransfusions are traced to patient misidentification and/or sample mislabeling errors that occur before a sample arrives in the laboratory. Laboratories play a significant role in preventing mistransfusion by identifying wrong blood in tube and rejecting mislabeled samples. To determine the rates of mislabeled samples and wrong blood in tube for samples submitted for ABO typing and to survey patient identification and sample labeling practices and sample acceptance policies for ABO typing samples across a variety of US institutions. One hundred twenty-two institutions prospectively reviewed inpatient and outpatient samples submitted for ABO typing for 30 days. Labeling error rates were calculated for each participant and tested for associations with institutional demographic and practice variable information. Wrong-blood-in-tube rates were calculated for the 30-day period and for a retrospective 12-month period. A concurrent survey collected institution-specific sample labeling requirements and institutional policies regarding the fate of mislabeled samples. For all institutions combined, the aggregate mislabeled sample rate was 1.12%. The annual and 30-day wrong-blood-in-tube aggregate rates were both 0.04%. Patient first name, last name, and unique identification number were required on the sample by more than 90% of participating institutions; however, other requirements varied more widely. The rates of mislabeled samples and wrong blood in tube for US participants in this study were comparable to those reported for most European countries. The survey of patient identification and sample labeling practices and sample acceptance policies for ABO typing samples revealed both practice uniformity and variability as well as significant opportunity for improvement.


Antibiotics and specialized metabolites from the human microbiota.
Covering: 2000 to 2017Decades of research on human microbiota have revealed much of their taxonomic diversity and established their direct link to health and disease. However, the breadth of bioactive natural products secreted by our microbial partners remains unknown. Of particular interest are antibiotics produced by our microbiota to ward off invasive pathogens. Members of the human microbiota exclusively produce evolved small molecules with selective antimicrobial activity against human pathogens. Herein, we expand upon the current knowledge concerning antibiotics derived from human microbiota and their distribution across body sites. We analyze, using our in-house chem-bioinformatic tools and natural products database, the encoded antibiotic potential of the human microbiome. This compilation of information may create a foundation for the continued exploration of this intriguing resource of chemical diversity and expose challenges and future perspectives to accelerate the discovery rate of small molecules from the human microbiota.


Amygdala reactivity as a marker of differential susceptibility to socioeconomic resources during early adulthood.
Models of differential susceptibility hypothesize that neural function may be a marker of differential susceptibility to context, but no studies have tested this hypothesis. Using a sample of 310 young men from low-income urban neighborhoods, this study investigated amygdala reactivity to facial expressions as a moderator of the relations between socioeconomic resources and later antisocial behavior (AB) and income. For individuals with high amygdala reactivity, greater socioeconomic resources at age 20 predicted less AB and greater income at age 22. For young men with low amygdala reactivity, however, socioeconomic resources at age 20 did not predict later outcomes. Amygdala reactivity to fearful facial expressions, key to the etiology of AB, moderated links between resources and AB. In contrast, amygdala reactivity more generally to multiple facial expressions moderated the effects of resources on later income attainment. Both interactions met rigorous quantitative criteria for patterns of differential susceptibility rather than diathesis stress or vantage sensitivity. Moreover, these associations remained significant after inclusion of socioeconomic resources during earlier developmental periods. These results suggest that greater amygdala reactivity to facial expressions is a marker of greater susceptibility to context, for better or for worse, during the transition to adulthood. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Rapid urine-based screening for tuberculosis to reduce AIDS-related mortality in hospitalized patients in Africa (the STAMP trial): study protocol for a randomised controlled trial.
HIV-associated tuberculosis (TB) co-infection remains an enormous burden to international public health. Post-mortem studies have highlighted the high proportion of HIV-positive adults admitted to hospital with TB. Determine TB-LAM and Xpert MTB/RIF assays can substantially increase diagnostic yield of TB within one day of hospital admission. However, it remains unclear if this approach can impact clinical outcomes. The STAMP trial aims to test the hypothesis that the implementation a urine-based screening strategy for TB can reduce all cause-mortality among HIV-positive patients admitted to hospital when compared to current, sputum-based screening. The trial is a pragmatic, individually randomised, multi-country (Malawi and South Africa) clinical trial with two study arms (1:1 recruitment). Unselected HIV-positive patients admitted to medical wards, irrespective of presentation, meeting the inclusion criteria and giving consent will be randomized to screening for TB using either: (i) 'standard of care'- testing of sputum using the Xpert MTB/RIF assay (Xpert) or (ii) 'intervention'- testing of sputum using Xpert and testing of urine using (a) Determine TB-LAM lateral-flow assay and (b) Xpert following concentration of urine by centrifugation. Patients will be excluded if they have received TB treatment in the previous 12 months, if they have received isoniazid preventive therapy in the last 6 months, if they are aged <18 years or they live outside the pre-specified geographical area. Results will be provided to the responsible medical team as soon as available to inform decisions regarding TB treatment. Both the study and routine medical team will be masked to study arm allocation. 1300 patients will be enrolled per arm (equal numbers at the two trial sites). The primary endpoint is all-cause mortality at 56 days. An economic analysis will be conducted to project long-term outcomes for shorter-term trial data, including cost-effectiveness. This pragmatic trial assesses an intervention to reduce the high mortality caused by HIV-associated TB, which could feasibly be scaled up in high-burden settings if shown to be efficacious and cost-effective. We discuss the challenges of designing a trial to assess the impact on mortality of laboratory-based TB screening interventions given frequent initiation of empirical treatment and a failure of several previous clinical trials to demonstrate an impact on clinical outcomes. We also elaborate on the practical and ethical issues of 'testing a test' in general. ISRCTN Registry ( ISRCTN71603869 ) prospectively registered 08 May 2015; the South African National Controlled Trials Registry (DOH-27-1015-5185) prospectively registered October 2015.


Thymoquinone protects DRG neurons from axotomy-induced cell death.
Peripheral nerve injury (PNI) is a significant health problem that is linked to sensory, motor, and autonomic deficits. This pathological condition leads to a reduced quality of life in most affected individuals. Schwann cells (SCs) play a crucial role in the repair of PNI. Effective agents that promote SC activation may facilitate and accelerate peripheral nerve repair. Thymoquinone (TQ), a bioactive component of Nigella sativa seeds, has an antioxidant, anti-inflammatory, immunomodulatory, and neuroprotective properties. In the present study, the neuroprotective efficacy of TQ was investigated by using a laser microdissection technique in a mouse PNI model. Single cells were isolated from dorsal root ganglions (DRGs) of 6-8-week-old mice, maintained in defined culture conditions and treated with or without TQ at different concentrations. Axons were cut (axotomy) using a controllable laser microbeam to model axonal injury in vitro. Under fluorescence microscopy, cell viability was evaluated using the fluorescent dyes. The behavior of the cells was continuously monitored with time-lapse video microscopy. TQ significantly increased neuronal survival by promoting the survival and proliferation of SCs and fibroblasts, as well as the migration of SCs. Furthermore, TQ improved the ability to extend neurites of axotomized neurons. The regenerative effect of TQ was dose-dependent suggesting a target specificity. Our studies warrant further preclinical and clinical investigations of TQ as a potential regenerative agent to treat peripheral nerve injuries. TQ exhibits a regenerative potential for the treatment of damaged peripheral nerves.


Worldwide Differences in Regulations of Clozapine Use.
Clozapine remains the drug of choice for treatment-resistant schizophrenia. As a consequence of its long history and complex pharmacology, we suspected wide variation in the regulations of clozapine use across different countries. The summaries of product characteristics (SPCs) from clozapine manufacturers, as well as local and national guidelines in the following selected countries, were reviewed: China, Denmark, Ireland, Japan, The Netherlands, New Zealand, Romania, the UK and the US. Clozapine is available as tablets in all countries, as an oral suspension in all included countries, with the exception of Japan and Romania, as orally disintegrating tablets in the US and China, and as an injectable in The Netherlands. General practitioner prescribing is only available in The Netherlands, New Zealand, the UK and the US, although with some restrictions in some of the countries. In Ireland and China, clozapine is only dispensed through hospital pharmacies. Hematological monitoring is mandatory in all countries but varies substantially in frequency, e.g. in Denmark hematologic monitoring is mandatory weekly for 18 weeks, followed by monthly monitoring, compared with Japan where blood work is required weekly for 26 weeks, followed by biweekly hematologic monitoring thereafter. In most included countries, with the exception of Denmark, Romania and The Netherlands, the manufacturer provides a mandatory hematological monitoring database, and dispensing of clozapine is not permissible without acceptable white blood count and absolute neutrophil count results. Local guidelines in New Zealand recommend echocardiography and routine troponin during the initial phases of treatment with clozapine. Regulations of clozapine vary widely with regard to rules of prescribing and monitoring. A worldwide update and harmonization of these regulations is recommended.


Equal Footing of Thermal Expansion and Electron-Phonon Interaction in the Temperature Dependence of Lead Halide Perovskite Band Gaps.
Lead halide perovskites, which are causing a paradigm shift in photovoltaics, exhibit an atypical temperature dependence of the fundamental gap: it decreases in energy with decreasing temperature. Reports ascribe such a behavior to a strong electron-phonon renormalization of the gap, neglecting contributions from thermal expansion. However, high-pressure experiments performed on the archetypal perovskite MAPbI3 (MA stands for methylammonium) yield a negative pressure coefficient for the gap of the tetragonal room-temperature phase, which speaks against the assumption of negligible thermal expansion effects. Here we show that for MAPbI3 the temperature-induced gap renormalization due to electron-phonon interaction can only account for about 40% of the total energy shift, thus implying thermal expansion to be more if not as important as electron-phonon coupling. Furthermore, this result possesses general validity, holding also for the tetragonal or cubic phase, stable at ambient conditions, of most halide perovskite counterparts.


Scrapie in Swine: a Diagnostic Challenge.
A naturally occurring prion disease has not been recognized in swine, but the agent of bovine spongiform encephalopathy does transmit to swine by experimental routes. Swine are thought to have a robust species barrier when exposed to the naturally occurring prion diseases of other species, but the susceptibility of swine to the agent of sheep scrapie has not been thoroughly tested. We conducted this experiment to test the susceptibility of swine to U.S. scrapie isolates by intracranial and oral inoculation. Scrapie inoculum was a pooled 10% (w/v) homogenate derived from the brains of clinically ill sheep from the 4th passage of a serial passage study of the U.S scrapie agent (No. 13-7) through susceptible sheep (homozygous ARQ at prion protein residues 136, 154, and 171, respectively). Pigs were inoculated intracranially (n=19) with a single 0.75 mL dose or orally (n=24) with 15 mL repeated on 4 consecutive days. Necropsies were done on a subset of animals at approximately six months post inoculation (PI): the time the pigs were expected to reach market weight. Remaining pigs were maintained and monitored for clinical signs of transmissible spongiform encephalopathies (TSE) until study termination at 80 months PI or when removed due to intercurrent disease (primarily lameness). Brain samples were examined by immunohistochemistry (IHC), western blot (WB), enzyme immunoassay (EIA), and for a subset of pigs in each inoculation group, bioassay in mice expressing porcine prion protein. At six-months PI, no evidence of scrapie infection was noted by any diagnostic method. However, at 51 months of incubation or greater, 5 animals were positive by one or more methods: IHC (n=4), WB (n=3), or EIA (n=4). Furthermore, positive bioassay results were obtained from all inoculated groups (oral and intracranial; market weight and end of study) suggesting that swine are potential hosts for the agent of scrapie.


Rapid dynamics of cell-shape recovery in response to local deformations.
It is vital that cells respond rapidly to mechanical cues within their microenvironment through changes in cell shape and volume, which rely upon the mechanical properties of cells' highly interconnected cytoskeletal networks and intracellular fluid redistributions. While previous research has largely investigated deformation mechanics, we now focus on the immediate cell-shape recovery response following mechanical perturbation by inducing large, local, and reproducible cellular deformations using AFM. By continuous imaging within the plane of deformation, we characterize the membrane and cortical response of HeLa cells to unloading, and model the recovery via overdamped viscoelastic dynamics. Importantly, the majority (90%) of HeLa cells recover their cell shape in <1 s. Despite actin remodelling on this time scale, we show that cell-shape recovery time is not affected by load duration, nor magnitude for untreated cells. To further explore this rapid recovery response, we expose cells to cytoskeletal destabilizers and osmotic shock conditions, which uncovers the interplay between actin and osmotic pressure. We show that the rapid dynamics of recovery depend crucially on intracellular pressure, and provide strong evidence that cortical actin is the key regulator in the cell-shape recovery processes, in both cancerous and non-cancerous epithelial cells.


Systematics and evolution of tribe Sinningieae (Gesneriaceae): evidence from phylogenetic analyses of six plastid DNA regions and nuclear ncpGS.
For nearly all species in the three genera of tribe Sinningieae (Gesneriaceae), Sinningia, Paliavana, and Vanhouttea (mostly in southeastern Brazil) plus 10 outgroups, we have sequenced six non-coding DNA regions (i.e., plastid intergenic spacers trnT-trnL, trnL-trnF, trnS-trnG, atpB-rbcL, and introns in the trnL and rpl16 genes) and four introns in nuclear plastid-expressed glutamine synthetase gene (ncpGS). Separate and combined analyses of these data sets using maximum parsimony supported the monophyly of Sinningieae, but the genera Paliavana and Vanhouttea were found embedded within Sinningia; therefore a new infrageneric classification is here proposed. Mapping of pollination syndromes on the DNA-based trees supported multiple origins of hummingbird and bee syndromes and derivation of moth and bat syndromes from hummingbird flowers. Perennial tubers were derived from perennial stems in non-tuberous plants.


Determination of catechins in matcha green tea by micellar electrokinetic chromatography.
Catechins in green tea are known to have many beneficial health properties. Recently, it has been suggested that matcha has greater potential health benefits than other green teas. Matcha is a special powdered green tea used in the Japanese tea ceremony. However, there has been no investigation to quantitate the catechin intake from matcha compared to common green teas. We have developed a rapid method of analysis of five catechins and caffeine in matcha using micellar electrokinetic chromatography. Results are presented for water and methanol extractions of matcha compared with water extraction of a popular green tea. Using a mg catechin/g of dry leaf comparison, results indicate that the concentration of epigallocatechin gallate (EGCG) available from drinking matcha is 137 times greater than the amount of EGCG available from China Green Tips green tea, and at least three times higher than the largest literature value for other green teas.


The anatomic findings during operative exploration for non-palpable testes: A prospective evaluation.
We conducted a randomized trial comparing 1 and 2-stage laparoscopic orchiopexy for intra-abdominal testes. During recruitment, it became apparent that most patients with non-palpable testes do not require vascular division. In this report, we outline the location and quality of testes found during operative exploration in patients who consented for the study but were not randomized. Analysis was performed on 80 patients undergoing operative exploration for non-palpable testes between 2007 and 2014. The location and pathology of undescended testes were analyzed. There were 87 preoperative non-palpable testes in 80 patients that were consented but not randomized to 1 or 2 stage orchiopexy with vascular division. Forty (46%) of nonrandomized testes were atrophic or absent, and 47 (54%) were normal in appearance. Sixty eight testes were evaluated via laparoscopy. The most common location for normal (81%) and absent/atrophic (70%) testes was the inguinal canal. Atrophic testes were more often left sided (72.5%) with normal testes equally divided. Patients with atrophic or absent testicles were more likely to have a closed internal ring (p<0.01). This study demonstrates the majority of patients undergoing operative exploration for non-palpable testes will not require vascular division, and instead would be either atrophic or able to undergo traditional orchiopexy. III.


Anesthetic experience of methemoglobinemia detected during general anesthesia for gastrectomy of advanced gastric cancer -A case report-.
Methemoglobinemia is an uncommon but potentially fatal disorder. Most cases have no adverse clinical consequence and require no treatment, but methemoglobinemia is often overlooked as a cause of low oxygen saturation, and often mistaken for the more common causes of hypoxia by anesthesiologists despite simple bedside tests that indicate the presence of this treatable abnormality. We present a 68-year-old female patient who underwent gastrectomy for advanced gastric cancer with bleeding. In the preoperative period, the patient showed cyanosis and oxygen saturation was 85% by pulse oximeter, but oxygen saturation by arterial blood gas analysis was 100%. After tracheal intubation, the methemoglobin level was 18.3%. Ascorbic acid and methylene blue were administered. During preanesthetic evaluation, the patient had not informed the anesthesiologist that she had been taking dapsone.


Effects of sludge retention time on oxic-settling-anoxic process performance: Biosolids reduction and dewatering properties.
In this study, the effect of sludge retention time (SRT) on oxic-settling-anoxic (OSA) process was determined using a sequencing batch reactor (SBR) attached to external aerobic/anoxic reactors. The SRT of the external reactors was varied from 10 to 40d. Increasing SRT from 10 to 20d enhanced volatile solids destruction in the external anoxic reactor as evidenced by the release of nutrients, however, increasing the SRT to 40d did not enhance volatile solids destruction further. Relatively short SRT (10-20d) favoured the conversion of destroyed solids into inert products. The application of an intermediate SRT (20d) of the external reactor showed the highest sludge reduction performance (>35%). Moreover, at the optimum SRT, OSA improved sludge dewaterability as demonstrated by lower capillary suction time and higher dewatered cake solids content.


Rap1p requires Gcr1p and Gcr2p homodimers to activate ribosomal protein and glycolytic genes, respectively.
Efficient transcription of ribosomal protein (RP) and glycolytic genes requires the Rap1p/Gcr1p regulatory complex. A third factor, Gcr2p, is required for only the glycolytic (specialized) mode of transcriptional activation. It is recruited to the complex by Gcr1p and likely mediates a change in the phosphorylation state and/or conformation of the latter. We show here that leucine zipper motifs in Gcr1p and Gcr2p (1LZ and 2LZ) are each specific to one of the two activation mechanisms-mutations in 1LZ and 2LZ impair transcription of RP and glycolytic genes, respectively. Although neither class of mutations causes more than a mild growth defect, simultaneous impairment of 1LZ and 2LZ results in a severe synthetic defect and a reduction in the expression of both sets of genes. Intracistronic complementation by point mutations in the charged e and g positions confirmed that Gcr1p/Gcr1p and Gcr2p/Gcr2p homodimers are the forms required for the different roles of the activator complex. Direct heterodimerization between 1LZ and 2LZ apparently does not occur. Dichotomous Rap1p activation and its striking requirement for distinct homodimeric subunits give cells the capacity to switch between coordinated and uncoupled RP and glycolytic gene regulation.


Temperature differentially facilitates spontaneous but not evoked glutamate release from cranial visceral primary afferents.
Temperature is fundamentally important to all biological functions including synaptic glutamate release. Vagal afferents from the solitary tract (ST) synapse on second order neurons in the nucleus of the solitary tract, and glutamate release at this first central synapse controls autonomic reflex function. Expression of the temperature-sensitive Transient Receptor Potential Vanilloid Type 1 receptor separates ST afferents into C-fibers (TRPV1+) and A-fibers (TRPV1-). Action potential-evoked glutamate release is similar between C- and A-fiber afferents, but TRPV1 expression facilitates a second form of synaptic glutamate release in C-fibers by promoting substantially more spontaneous glutamate release. The influence of temperature on different forms of glutamate release is not well understood. Here we tested how temperature impacts the generation of evoked and spontaneous release of glutamate and its relation to TRPV1 expression. In horizontal brainstem slices of rats, activation of ST primary afferents generated synchronous evoked glutamate release (ST-eEPSCs) at constant latency whose amplitude reflects the probability of evoked glutamate release. The frequency of spontaneous EPSCs in these same neurons measured the probability of spontaneous glutamate release. We measured both forms of glutamate from each neuron during ramp changes in bath temperature of 4-5 °C. Spontaneous glutamate release from TRPV1+ closely tracked with these thermal changes indicating changes in the probability of spontaneous glutamate release. In the same neurons, temperature changed axon conduction registered as latency shifts but ST-eEPSC amplitudes were constant and independent of TRPV1 expression. These data indicate that TRPV1-operated glutamate release is independent of action potential-evoked glutamate release in the same neurons. Together, these support the hypothesis that evoked and spontaneous glutamate release originate from two pools of vesicles that are independently modulated and are distinct processes.


Intake of dairy foods and risk of Parkinson disease.
To prospectively examine the association between commonly consumed dairy products and the risk of Parkinson disease (PD) in women and men. Analyses were based on data from 2 large prospective cohort studies, the Nurses' Health Study (n = 80,736) and the Health Professionals Follow-up Study (n = 48,610), with a total of 26 and 24 years of follow-up, respectively. Both US-based studies were conducted via mailed biennial questionnaires. Dietary intake was assessed with food frequency questionnaires administered repeatedly over the follow-up period. Incident cases of PD (n = 1,036) were identified via questionnaires and subsequently confirmed by reviewing medical records. We also conducted a meta-analysis to combine our study with 3 previously published prospective studies on total milk intake and PD risk and 1 study on total dairy intake and PD risk. While total dairy intake was not significantly associated with PD risk in our cohorts, intake of low-fat dairy foods was associated with PD risk. The pooled, multivariable-adjusted hazard ratio (HR) comparing people who consumed at least 3 servings of low-fat dairy per day to those who consumed none was 1.34 (95% confidence interval [CI] 1.01-1.79, p trend = 0.04). This association appeared to be driven by an increased risk of PD associated with skim and low-fat milk (HR 1.39, 95% CI 1.12-1.73, p trend <0.01). Results were similar in women and men (p for heterogeneity >0.05). In the meta-analysis, the pooled relative risk comparing extreme categories of total milk intake was 1.56 (95% CI 1.30-1.88), and the association between total dairy and PD became significant (HR 1.27, 95% CI 1.04-1.55). Frequent consumption of dairy products appears to be associated with a modest increased risk of PD in women and men.


Colonization of Anopheles cracens: a malaria vector of emerging importance.
Anopheles cracens has been incriminated as a vector for the simian malaria parasite, Plasmodium knowlesi, that is the fifth Plasmodium species infecting humans. Little experimental data exists on this mosquito species due to the lack of its availability in laboratories. The population of An. cracens, collected from Kuala Lipis, Pahang was maintained at the insectary of the Department of Parasitology, Faculty of Medicine, University Malaya at 24-26°C and 60-80% relative humidity. The mosquitoes were maintained with artificial mating and blood-fed on humans and hamsters. The colony has been established since November 2011 and to date has reached its sixth generation. This is the first description of maintaining the Malaysian strain An. cracens colony by artificial mating. Colonization of An. cracens will provide fundamental information for genetic studies and will be useful in assessing comparative susceptibility to Plasmodium parasites.


Alcohol consumption in movies and adolescent binge drinking in 6 European countries.
The goal of this study was to investigate whether the association between exposure to images of alcohol use in movies and binge drinking among adolescents is independent of cultural context. A cross-sectional survey study in 6 European countries (Germany, Iceland, Italy, Netherlands, Poland, and Scotland) was conducted. A total of 16 551 pupils from 114 public schools with a mean (± SD) age of 13.4 (± 1.18) years participated. By using previously validated methods, exposure to alcohol use in movies was estimated from the 250 top-grossing movies of each country (years 2004-2009). Lifetime binge drinking was the main outcome measure. Overall, 27% of the sample had consumed >5 drinks on at least 1 occasion in their life. After controlling for age, gender, family affluence, school performance, television screen time, sensation seeking and rebelliousness, and frequency of drinking of peers, parents, and siblings, the adjusted β-coefficient for lifetime binge drinking in the entire sample was 0.12 (95% confidence interval: 0.10-0.14; P < .001). The crude relationship between movie alcohol use exposure and lifetime binge drinking was significant in all countries; after covariate adjustment, the relationship was still significant in 5 of 6 countries. A sensitivity analysis revealed that the association is content specific, as there was no significant association between lifetime binge drinking and exposure to smoking in movies. The link between alcohol use in movies and adolescent binge drinking was robust and seems relatively unaffected by cultural contexts.


SET7/9-dependent methylation of ARTD1 at K508 stimulates poly-ADP-ribose formation after oxidative stress.
ADP-ribosyltransferase diphtheria toxin-like 1 (ARTD1, formerly PARP1) is localized in the nucleus, where it ADP-ribosylates specific target proteins. The post-translational modification (PTM) with a single ADP-ribose unit or with polymeric ADP-ribose (PAR) chains regulates protein function as well as protein-protein interactions and is implicated in many biological processes and diseases. SET7/9 (Setd7, KMT7) is a protein methyltransferase that catalyses lysine monomethylation of histones, but also methylates many non-histone target proteins such as p53 or DNMT1. Here, we identify ARTD1 as a new SET7/9 target protein that is methylated at K508 in vitro and in vivo. ARTD1 auto-modification inhibits its methylation by SET7/9, while auto-poly-ADP-ribosylation is not impaired by prior methylation of ARTD1. Moreover, ARTD1 methylation by SET7/9 enhances the synthesis of PAR upon oxidative stress in vivo. Furthermore, laser irradiation-induced PAR formation and ARTD1 recruitment to sites of DNA damage in a SET7/9-dependent manner. Together, these results reveal a novel mechanism for the regulation of cellular ARTD1 activity by SET7/9 to assure efficient PAR formation upon cellular stress.


Enhancing IgG distribution to lung mucosal tissue improves protective effect of anti-Pseudomonas aeruginosa antibodies.
IgG antibodies are abundantly present in the vasculature but to a much lesser extent in mucosal tissues. This contrasts with antibodies of the IgA and IgM isotype that are present at high concentration in mucosal secretions due to active delivery by the polymeric Ig receptor (pIgR). IgG is the preferred isotype for therapeutic mAb development due to its long serum half-life and robust Fc-mediated effector function, and it is utilized to treat a diverse array of diseases with antigen targets located in the vasculature, serosa, and mucosa. As therapeutic IgG antibodies targeting the luminal side of mucosal tissue lack an active transport delivery mechanism, we sought to generate IgG antibodies that could be transported via pIgR, similarly to dimeric IgA and pentameric IgM. We show that an anti-Pseudomonas aeruginosa IgG fused with pIgR-binding peptides gained the ability to transcytose and be secreted via pIgR. Consistent with these results, pIgR-binding IgG antibodies exhibit enhanced localization to the bronchoalveolar space when compared with the parental IgG antibody. Furthermore, pIgR-binding mAbs maintained Fc-mediated functional activity and promoted enhanced survival compared with the parental mAb in a P. aeruginosa acute pneumonia model. Our results suggest that increasing IgG accumulation at mucosal surfaces by pIgR-mediated active transport can improve the efficacy of therapeutic mAbs that act at these sites.


Clocks, Viruses, and Immunity: Lessons for the COVID-19 Pandemic.
Circadian rhythms are evolutionarily conserved anticipatory systems that allow the host to prepare and respond to threats in its environment. This article summarizes a European Biological Rhythms Society (EBRS) workshop held in July 2020 to review current knowledge of the interplay between the circadian clock and viral infections to inform therapeutic strategies against SARS-CoV-2 and COVID-19. A large body of work supports the role of the circadian clock in regulating various aspects of viral replication, host responses, and associated pathogenesis. We review the evidence describing the multifaceted role of the circadian clock, spanning host susceptibility, antiviral mechanisms, and host resilience. Finally, we define the most pressing research questions and how our knowledge of chronobiology can inform key translational research priorities.


Solitary blood cultures: a College of American Pathologists Q-probes study of 132,778 blood culture sets in 333 small hospitals.
To determine the frequency with which solitary blood culture samples were submitted to laboratories serving small hospitals and to ascertain whether certain hospital practices relating to the performance of blood cultures were associated with lower solitary blood culture rates (SBCRs). Participants in the College of American Pathologists Q-Probes laboratory quality improvement program collected data prospectively on the numbers of solitary blood culture sets from adult patients submitted to their laboratories and answered questions about their institutions' practice characteristics relating to the collection of blood culture specimens. Three hundred thirty-three public and private institutions with a median occupied bed size of 57. Participants were located in the United States (n = 329), Canada (n = 3), and Australia (n = 1). The solitary blood culture rate was defined as the number of instances in which only 1 blood culture venipuncture was performed on an individual patient during a 24-hour period divided by the total number of blood culture venipunctures that were performed during the study period. Participants submitted data on 132 778 adult patient blood culture sets. The SBCRs were 3.4% or less in the top-performing 10% of participating institutions (90th percentile and above), 12.7% in the midrange of participating institutions (50th percentile), and 42.5% or more in the bottom-performing 10% of participating institutions (10th percentile and below). In half the participating institutions, the SBCRs for inpatients were 8.3% or less and for outpatients, 22% or less. Solitary blood culture rates were lower for institutions in which phlebotomists rather than nonphlebotomists routinely collected blood culture specimens, in which internal policies required drawing at least 2 blood culture sets, in which hospital personnel contacted clinicians when their laboratories received requests for solitary blood culture sets, and in which quality control programs monitored SBCRs routinely. Hospitals can achieve SBCRs under 5%. Those hospitals with particularly high SBCRs may lower their rates by altering certain institutional practices.


Rapid detection of varicella-zoster virus infection by a loop-mediated isothermal amplification method.
The reliability of varicella-zoster virus (VZV) loop-mediated isothermal amplification (LAMP) was evaluated for rapid diagnosis of viral infection. VZV-specific primers only amplified VZV DNA; no LAMP products were observed in reactions performed with other viral DNA templates. The specificity of this method was confirmed by two independent determinations, agarose gel electrophoresis and a turbidity assay. The sensitivity of VZV LAMP, determined by agarose gel electrophoresis, were 500 copies/tube. Detection using the turbidity assay, however, gave a sensitivity of 1,000 copies/tube. After these initial validation studies, reliability of VZV LAMP was evaluated for the detection of viral DNA in clinical specimens. Thirty-two swab samples collected from patients with vesicular skin eruptions were tested for VZV DNA. VZV was confirmed in sample numbers 10-32 by VZV real-time PCR, a previously established technique. VZV LAMP products were detected using turbidity from samples 13 to 32 (sensitivity; 87.0%, specificity; 100%, positive predictive value; 100%, negative predictive value; 75%). Although low levels of VZV DNA could be detected in the three samples exhibiting divergent results (samples numbers 10-12), no VZV LAMP product was detected in these samples, indicating a higher detection limit for this assay. Requirement of a DNA extraction step in the VZV LAMP method was examined in next experiment. The turbidity assay detected a VZV LAMP product in all of the 20 positive swab samples (samples numbers 13-32), regardless of DNA extraction.


Does the authenticity of preclinical teaching format affect subsequent clinical clerkship outcomes? A prospective randomized crossover trial.
Educational theories predict conflicting results for the effect of increasing the authenticity of the teaching format of complex information on educational outcomes. We sought to determine the effect of increasingly authentic small-group, preclerkship teaching format on clerkship outcomes to further enlighten this debate. Students enrolled in a prospective randomized crossover trial that involved three content areas. For each content area, three teaching formats were tested. Participants were randomized to teaching format by content area. Clerkship outcomes were performance on an objective structured clinical exam, a DVD exam, internal medicine clerkship grades, and performance on the subject examination. The data were analyzed using a multivariate analysis of covariance. One hundred and thirty-three (78%) students participated. Teaching format did not have a statistically significant effect on any of the specified clerkship outcomes. However, number of patients seen was significantly associated with higher scores in respective outcomes by topic. Second-year teaching format did not directly influence subsequent clerkship performance. Our study adds to the literature by demonstrating that the authenticity of preclinical teaching format does not appear to matter for clerkship performance; however, the number of actual patients seen does appear to influence related clerkship outcomes.


Anti-inflammatory activity of Tetragronula species from Indonesia.
Anti-inflammatory drugs inhibit inflammation, particularly those classified as nonsteroidal anti-inflammatory drugs (NSAIDs). Several studies have reported that propolis has both anti-ulcerogenic and anti-inflammatory effects. In this study, we investigated the bioactive compound and in vivo anti-inflammatory properties of both smooth and rough propolis from Tetragronula sp. To further identify anti-inflammatory markers in propolis, LC-MS/MS was used, and results were analyzed by Mass Lynx 4.1. Rough and smooth propolis of Tetragonula sp. were microcapsulated with maltodextrin and arabic gum. Propolis microcapsules at dose 25-200 mg/kg were applied for carrageenan-induced rat's paw-inflammation model. Data were analyzed by one-way ANOVA and Kruskal-Wallis statistical tests. LC-MS/MS experiments identified seven anti-inflammatory compounds, including [6]-dehydrogingerdione, alpha-tocopherol succinate, adhyperforin, 6-epiangustifolin, deoxypodophyllotoxin, kurarinone, and xanthoxyletin. Our results indicated that smooth propolis at 50 mg/kg inhibited inflammation to the greatest extent, followed by rough propolis at a dose of 25 mg/kg. SPM and RPM with the dose of 25 mg/kg had inflammatory inhibition value of 62.24% and 58.12%, respectively, which is comparable with the value 70.26% of sodium diclofenac with the dose of 135 mg/kg. This study suggests that propolis has the potential candidate to develop as a non-steroid anti-inflammatory drug.


Assessment of interactive effects of elevated salinity and three pesticides on life history and behavior of southern toad (Anaxyrus terrestris) tadpoles.
Because habitats are increasingly exposed to multiple stressors simultaneously, assessing the interactive effects of stressors is crucial for understanding how populations respond to human-altered habitats. Salinization of freshwater habitats is increasing and has the potential to interact with other stressors. Chemical pollutants also contribute to habitat degradation in freshwater environments, and both salinity and various pesticides can harm amphibians. The present study used a factorial experiment to investigate the effect of elevated salinity alone and in combination with each of 3 pesticides-atrazine, carbaryl, and glyphosate-on life history and behavior of southern toad larvae (Anaxyrus terrestris). Tadpoles were negatively affected by elevated salinity and by exposure to the insecticide carbaryl, with the most deleterious outcomes associated with both stressors combined. Carbaryl exposure led to reduced survival as well as sublethal effects on growth, activity and feeding behavior, escape response swimming, and time to metamorphosis. Tadpoles reared at elevated salinity were also smaller and less active, and ultimately metamorphosed later and at smaller size. Together, carbaryl and elevated salinity had a synergistic effect, resulting in particularly poor growth, depressed activity and feeding, and sluggish escape swimming among tadpoles exposed to both stressors simultaneously. These results suggest that both elevated salinity and carbaryl represent threats for amphibian populations and that pesticide exposure in salinized habitats may pose a particularly high risk.


Measuring the Environmental Burden of Disease in South Korea: A Population-Based Study.
This study attempted to measure the environmental burden of disease by examining mortality and disability rates in South Korea, permitting international comparisons. Disability-adjusted life years (DALY) was used to analyze data from public records. Years of life lost (YLL) and years lost to disability (YLD) were measured in terms of incidence rate and number of deaths. Attributable risks were based on those for WHO Western Pacific Regions. For air pollution, attributable risk was calculated using local PM10 levels and relative risk. The total Korean environmental burden of disease was 17.98 per 1000 persons and the most serious risk factor was air pollution, at 6.89 per 1000 persons. Occupation was the second highest contributing factor, at 3.29 per 1000 persons, followed by indoor air pollution at 2.91 per 1000 persons. The DALY of air-pollution (indoor and outdoor) was 9.80 per 1000 persons, accounting for more than half of the total environmental burden of disease. The burden of chronic obstructive pulmonary disease, lung cancer, and asthma were 4.07, 3.16, and 1.96 per 1000 persons, respectively. Respiratory illnesses comprised most of the disease burden, the majority of which was linked to air pollution. The present results are important as they could be used to make evidence-based decisions regarding the management of diseases and environmental-risk factors.


Laparoscopic Adjustable Gastric Band Erosion Into the Stomach and Colon.
Morbid obesity has reached epidemic proportions in the United States and constitutes a significant cause of morbidity and mortality. Bariatric surgery represents a viable and effective means of weight loss. Laparoscopic adjustable gastric band placement is the most commonly used and least invasive bariatric surgical technique. Although the complication rate is low, various complications have been described, including erosion of the gastric band into the stomach. The authors present a case of laparoscopic adjustable gastric band erosion, where both the band and the tubing eroded into the stomach and colon, and the tubing further eroded out of and back into the colon several times.


A guide to the contained use of plant virus infectious clones.
Plant virus infectious clones are important tools with wide-ranging applications in different areas of biology and medicine. Their uses in plant pathology include the study of plant-virus interactions, and screening of germplasm as part of prebreeding programmes for virus resistance. They can also be modified to induce transient plant gene silencing (Virus Induced Gene Silencing - VIGS) and as expression vectors for plant or exogenous proteins, with applications in both plant pathology and more generally for the study of plant gene function. Plant viruses are also increasingly being investigated as expression vectors for in planta production of pharmaceutical products, known as molecular farming. However, plant virus infectious clones may pose a risk to the environment due to their ability to reconstitute fully functional, transmissible viruses. These risks arise from both their inherent pathogenicity and the effect of any introduced genetic modifications. Effective containment measures are therefore required. There has been no single comprehensive review of the biosafety considerations for the contained use of genetically modified plant viruses, despite their increasing importance across many biological fields. This review therefore explores the biosafety considerations for working with genetically modified plant viruses in contained environments, with focus on plant growth facilities. It includes regulatory frameworks, risk assessment, assignment of biosafety levels, facility features and working practices. The review is based on international guidance together with information provided by plant virus researchers.


[Documentation of good distribution practice of medicines and its implementation in Lithuanian drug distribution companies].
Good Distribution Practice of medicinal products for human use is a quality warranty system, which includes requirements for purchase, receiving, storage and export of drugs, intended human consumption. A drug is a specific product and its mishandling is dangerous to human health and life. Therefore it is necessary to strictly control the movement of the drug from the producer to the consumer so that poor quality drugs do not have access to the market. Good Distribution Practice rules set the general requirements for good wholesale distribution practice of drugs, intended for human consumption. In order for company to meet the specified requirements, the drug distribution company must have all suitable and necessary premises, machinery, equipment, the required number of employees and specified documentation. The preparation of the Good Distribution Practice documentation is one of the most important and complex aspects when implementing the Good Distribution Practice in the companies. The article deals with the analysis of results obtained during the research of drug distribution companies in Lithuania. The research revealed that drug distribution companies put emphasis on the equipment of storage premises. Less attention is being paid to the preparation of the documents of Good Distribution Practice. The article thus presents the analysis of Good Distribution Practice documents prepared by the drug distribution companies.


Impact of vitamin B6 status on psychological distress in a longitudinal study of HIV-1 infection.
Inadequate vitamin B6 status has been associated with altered neuropsychiatric function, possibly through its effect on the metabolism of neurotransmitters, including serotonin (5-HT). The present eighteen month longitudinal study evaluated the relationship between vitamin B6 status and psychological distress in HIV-1 infected individuals, controlling for the influence of negative life events, social support and coping style. Biochemical measurements of nutritional status, and dietary intake evaluations were obtained in HIV-1 seropositive homosexual men, (at baseline: CDC Stages II and III, n = 70; Stage IVA, IVC2 n = 18) at six month intervals. Alterations in nutrient status (e.g., vitamin B6 adequate to inadequate; inadequate to adequate), were compared with changes in psychological distress, measured by the Profile of Mood States, using a multiple regression analysis. A significant decline in psychological distress was demonstrated with normalization of vitamin B6 status from inadequate to adequate status (p < 0.02). A decrease in psychological distress was also observed with increased tryptophan intake in subjects who were vitamin B6 adequate (p < 0.02). Significant effects for the nutritional variables remained even when negative life event stressors, social support, and coping style were controlled, suggesting that vitamin B6 status may be an important co-factor in determining level of psychological distress over time in HIV-1 infected individuals.