The EnRiCH Community Resilience Framework for High-Risk Populations.
Resilience has been described in many ways and is inherently complex. In essence, it refers to the capacity to face and do well when adversity is encountered. There is a need for empirical research on community level initiatives designed to enhance resilience for high-risk groups as part of an upstream approach to disaster management. In this study, we address this issue, presenting the EnRiCH Community Resilience Framework for High-Risk Populations. The framework presented in this paper is empirically-based, using qualitative data from focus groups conducted as part of an asset-mapping intervention in five communities in Canada, and builds on extant literature in the fields of disaster and emergency management, health promotion, and community development. Adaptive capacity is placed at the centre of the framework as a focal point, surrounded by four strategic areas for intervention (awareness/communication, asset/resource management, upstream-oriented leadership, and connectedness/engagement). Three drivers of adaptive capacity (empowerment, innovation, and collaboration) cross-cut the strategic areas and represent levers for action which can influence systems, people and institutions through expansion of asset literacy. Each component of the framework is embedded within the complexity and culture of a community. We present recommendations for how this framework can be used to guide the design of future resilience-oriented initiatives with particular emphasis on inclusive engagement across a range of functional capabilities.


Induction of mRNA for tumor necrosis factor-alpha and interleukin-1 beta in mice brain, spleen and liver in an animal model of Shigella-related seizures.
The pathogenesis of neurological symptoms, the most common extraintestinal complication of childhood shigellosis, is unclear. To elucidate the mechanisms involved, we developed an animal model and demonstrated that TNF alpha and IL-1 beta play a role. To determine whether TNF alpha and IL-1 beta genes are expressed in the brain following peripheral administration of Shigella dysenteriae 60R. Expression of mRNA for TNF alpha and IL-1 beta was examined in the brain structures (hypothalamus and hippocampus) and peripheral organs by reverse transcriptase polymerase chain reaction, at different time points after intraperitoneal injection of S. dysenteriae sonicate. In our animal model of Shigella-related seizures, TNF alpha and IL-1 beta mRNA were induced in the brain, spleen and liver already 1 hour after injection of S. dysenteriae sonicate. The expression of TNF alpha and IL-1 beta mRNA in spleen, hippocampus and hypothalamus decreased after 6 h and increased again at 18 h post-injection. Local production of TNF alpha and IL-1 beta in the brain may be involved in the enhanced seizure response of mice after administration of S. dysenteriae. It is possible that intracerebral production of TNF alpha and IL-1 beta plays a role in neurological disturbances of human shigellosis.


Dietary quality is associated with diabetes and cardio-metabolic risk factors.
In this study, our aim was to investigate the associations between diet quality and newly diagnosed diabetes, prediabetes, and cardio-metabolic risk factors. The analysis was based on 7441 participants of the Australian Diabetes, Obesity and Lifestyle study, a cross-sectional study of adults aged > or =25 y involving a 75-g oral glucose tolerance test. Diet quality was assessed via a dietary guideline index and FFQ data. Associations between diet quality and diabetes, prediabetes (impaired fasting glycemia, impaired glucose tolerance), and cardiovascular risk factors were investigated using linear and logistic regression adjusted for age, education, smoking, physical activity, sedentary behavior, and BMI. Higher diet quality was significantly associated with lower systolic and diastolic blood pressure among men, lower fasting plasma glucose among men and women, and lower systolic blood pressure, fasting plasma insulin, and 2-h plasma glucose and greater insulin sensitivity among women. Diet quality was inversely associated with abdominal obesity [odds ratio (OR) for top quartile: 0.68, 0.48-0.96], hypertension (OR: 0.50, 0.31-0.81), and type 2 diabetes (OR: 0.38, 0.18-0.80) among men. Lack of compliance with established dietary guidelines was associated with type 2 diabetes and cardio-metabolic risk factors. Further work is required to determine whether this dietary index has predictive validity for health in longitudinal studies.


Discriminating the molecular basis of hepatotoxicity using the large-scale characteristic molecular signatures of toxicants by expression profiling analysis.
Predicting the potential human health risk posed by chemical stressors has long been a major challenge for toxicologists, and the use of microarrays to measure responses to toxicologically relevant genes, and to identify selective, sensitive biomarkers of toxicity is a major application of predictive and discovery toxicology. To investigate this possibility, we investigated whether carcinogens (at doses known to induce liver tumors in chronic exposure bioassays) deregulate characteristic sets of genes in mice. Male C3H/He mice were dosed with two hepatocarcinogens (vinyl chloride (VC, 50-25 mg/kg), aldrin (AD, 0.8-0.4 mg/kg)), or two non-hepatocarcinogens (copper sulfate (CS, 150-60 mg/kg), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T, 150-60 mg/kg)). Large-scale molecular changes elicited by these four hepatotoxicants in liver tissues were analyzed using DNA microarray. Three days after administration, no significant phenotypic changes were induced by these four different hepatotoxicants in terms of histological examination or blood biochemical assay. However, unsupervised hierarchical analysis of gene expressional changes induced by hepatotoxicants resulted in two major gene subclusters on dendrogram, i.e., a carcinogen (VN, AD) and non-carcinogen group (CS, 2,4,5-T), and also revealed that distinct molecular signatures exist. These signatures were founded on well-defined functional gene categories and may differentiate genotoxic and non-genotoxic carcinogens. Furthermore, Venn diagram analysis allowed us to identify carcinogen and non-carcinogen-associated molecular signatures. Using statistical methods, we analyzed outlier genes for four different classes (genotoxic-, non-genotoxic-carcinogen, genotoxic-, non-genotoxic non-carcinogen) in terms of their potential to predict different modes-of-action. In conclusion, the identification of large-scale molecular changes in different hepatocarcinogen exposure models revealed that different types of hepatotoxicants are associated with different epigenetic changes and molecular pathways and that these large-scale characteristic molecular changes could be used as predictable toxicity markers.


Incidence and severity of primary graft dysfunction after lung transplantation using rejected grafts reconditioned with ex vivo lung perfusion.
Ex vivo lung perfusion (EVLP) is a novel technique used to evaluate and recondition marginal or rejected grafts. Primary graft dysfunction (PGD) is a major early complication after lung transplantation (LTx). The use of marginal or initially rejected grafts may increase its incidence and severity. The aim of this study is to evaluate the incidence of PGD after LTx using rejected grafts reconditioned with EVLP. PGD has been evaluated immediately after LTx (t0) and after 72 h (t72) in patients receiving standard (Group A) or reconditioned (Group B) grafts. EVLP was performed using a controlled acellular perfusion according to the Toronto technique. From July 2011 to February 2013, 36 LTxs have been performed: 28 patients (21 M/7 F, mean age 51.7 ± 14.7 years) in Group A and 8 (6 M/2 F, mean age 46.6 ± 9.8 years) in Group B (successful recondition rate of 73%, 8 of 11 cases). Incidence rate of PGD 3 at t0 and at t72 (Group A versus Group B) was 50 vs 37% (P = NS) and 25 vs 0% (P = NS), respectively. Post-transplant extracorporeal membrane oxygenation was required in 5 and 2 patients in Groups A and B, respectively (P = NS). The use of initially rejected grafts treated with EVLP does not increase the incidence and severity of PGD after LTx. Although comparison of PGD 3 incidence in the two groups did not reach a statistical difference, all EVLP patients suffering from severe PGD early after transplant recovered normal lung function at 72 h, suggesting a protective role of EVLP against PGD occurrence and severity.


Clinical prediction of Parkinson's disease: planning for the age of neuroprotection.
As a chronic progressive disease, Parkinson's disease (PD) has a presymptomatic interval; that is, a period during which the pathological process has begun, but motor signs required for the clinical diagnosis are absent. The ability to identify this preclinical stage may be critical in the development and eventual use of neuroprotective therapy. Recently proposed staging systems of PD have suggested that degeneration may occur initially in areas outside the substantia nigra, suggesting that non-motor manifestations may be markers of presymptomatic PD. Decreased olfaction has recently been demonstrated to predict PD in prospective pathological studies, although the lead time may be relatively short, and the positive predictive value is low. Idiopathic RBD has a very high predictive value, with approximately 50% of affected individuals developing PD or dementia within 10 years. This implies that idiopathic RBD patients are ideal candidates to test potential preclinical markers. However, the specificity of symptom screens for RBD is not established, not all persons with PD develop RBD, and there are only limited ways to predict which RBD patients will develop PD. Other simple screens based upon autonomic symptoms, depression and personality changes, quantitative motor testing and other sleep disorders may also be useful markers, but have not been extensively tested. Other more expensive measures such as detailed autonomic testing, cardiac MIBG-scintigraphy, dopaminergic imaging and transcranial ultrasound may be especially useful in defining disease risk in those identified through primary screening.


Multiphase chemical kinetics of OH radical uptake by molecular organic markers of biomass burning aerosols: humidity and temperature dependence, surface reaction, and bulk diffusion.
Multiphase reactions of OH radicals are among the most important pathways of chemical aging of organic aerosols in the atmosphere. Reactive uptake of OH by organic compounds has been observed in a number of studies, but the kinetics of mass transport and chemical reaction are still not fully understood. Here we apply the kinetic multilayer model of gas-particle interactions (KM-GAP) to experimental data from OH exposure studies of levoglucosan and abietic acid, which serve as surrogates and molecular markers of biomass burning aerosol (BBA). The model accounts for gas-phase diffusion within a cylindrical coated-wall flow tube, reversible adsorption of OH, surface-bulk exchange, bulk diffusion, and chemical reactions at the surface and in the bulk of the condensed phase. The nonlinear dependence of OH uptake coefficients on reactant concentrations and time can be reproduced by KM-GAP. We find that the bulk diffusion coefficient of the organic molecules is approximately 10(-16) cm(2) s(-1), reflecting an amorphous semisolid state of the organic substrates. The OH uptake is governed by reaction at or near the surface and can be kinetically limited by surface-bulk exchange or bulk diffusion of the organic reactants. Estimates of the chemical half-life of levoglucosan in 200 nm particles in a biomass burning plume increase from 1 day at high relative humidity to 1 week under dry conditions. In BBA particles transported to the free troposphere, the chemical half-life of levoglucosan can exceed 1 month due to slow bulk diffusion in a glassy matrix at low temperature.


Rabbit eye exposure to broad-spectrum fluorescent light.
Two F40CW fluorescent lamps mounted in an EYS-2404 fixture and 300 nm, 5 nm waveband UV radiation were used to expose pigmented rabbit eyes. The results of the exposures to the eye were evaluated with the biomicroscope, ophthalmoscope, light microscope and electron microscope. The following conclusions were reached: The adverse ocular responses to fluorescent radiation exposure were due to long-duration, broadband radiation. These reactions were more generalized for fluorescent exposures when the cornea and lens are compared to UV exposures. The differences between the levels of threshold exposure needed to cause damage for the fluorescent source and UV radiation were attributed to exposure duration and the rate of delivery of the radiation. Corneal and lenticular damage was mild when compared with UV 300 nm exposures, and the threshold occurred after 8 h to 12 h of exposure. The effect of the radiation was to interfere with the normal functions of the cell while changes to the inert materials in the tissues was secondary to injury to the cell. The damage was mild in the corneal epithelium, somewhat more severe in the corneal endothelium, but minimal in the corneal stroma. Early retinal changes were found after 8 h of exposure to the fluorescent source. These induced changes were evident in the neural retina as spaces and were assumed to represent oedema. The retinal oedema was initially found only in the receptor cell, outer nuclear and nerve fibre layers. Many vacuoles or spaces were located in the junctional area between the ganglion cell and nerve fibre layers while smaller spacing occurred also within the nerve fibre layer. Twelve h of exposure to the fluorescent source produced a further increase in the oedema in the retina. The outer segments of the receptor cells appear to disintegrate and significant open spaces are evident among the inner and outer segments of the receptors. The inner plexiform layer shows an increased number of spaces within and among the neural elements, and the mitochondria appeared to be undergoing changes. The 20-h and longer exposure induced severe changes affecting all layers of the retina. These changes include massive retinal oedema with degenerative signs in all retinal neurons. A sympathetic reaction of the unexposed, contralateral eye occurred as the result of the damage to the exposed eye. Minimal sympathetic responses to the cornea and the lens began at exposure durations at or above 12 h, while the retina showed the sympathetic reaction beginning at 8 h.(ABSTRACT TRUNCATED AT 400 WORDS)


Soft tissue digestion of Paradiplozoon vaalense for SEM of sclerites and simultaneous molecular analysis.
Classification of most monogeneans is primarily based on size, shape, and arrangement of haptoral sclerites. These structures are often obscured or misinterpreted when studied using light microscopy, leading to confusion regarding defining characters. Scanning electron microscopy (SEM) has predominantly been used to study haptoral sclerites in smaller monogeneans, focusing on hooks and anchors. In the Diplozoidae, SEM has not been used to study haptoral sclerites. Using new and modified techniques, the sclerites of diplozoids collected in South Africa were successfully studied using SEM. The digestion buffer from a DNA extraction kit was used to digest the surrounding tissue, and Poly-L-lysine-coated and concavity slides were employed to limit the movement and loss of sclerites, with the latter being more user-friendly. In addition to the success of visualizing the sclerites using SEM, the digested tissue from as little as half of the haptor provided viable genetic material for molecular characterization. From the results presented here, the study of the sclerites of larger monogeneans using SEM, including those bearing clamps, is a viable possibility for future research. Also, this method may be beneficial for the study of other, non-haptoral sclerites, such as cirri in other families of monogeneans. During this study, Labeo capensis was noted as a valid host of Paradiplozoon vaalense in a region of the Vaal River where the type host, Labeo umbratus, appears to be absent.


Dynamic Prevalence of Sleep Disorders Following Stroke or Transient Ischemic Attack: Systematic Review and Meta-Analysis.
The exact prevalence of sleep disorders following stroke or transient ischemic attack (TIA) remains unclear. We aimed to determine the prevalence of sleep-disordered breathing, insomnia, periodic leg movement during sleep, and restless leg syndrome following stroke or TIA in acute, subacute, and chronic phases and examine the moderating effects of patient characteristics (eg, age) and methodological features (eg, study quality) on the prevalence. We performed a systematic review and meta-analysis. Embase and PubMed were searched from inception to December 18, 2019. We included 64 047 adults in 169 studies (prospective, retrospective, case-control, and cross-sectional study designs) reporting the prevalence of sleep disorders following stroke or TIA. In the acute phase, the overall prevalence of mild, moderate, and severe sleep-disordered breathing was 66.8%, 50.3%, and 31.6% (95% CIs, 63.8-69.7, 41.9-58.7, and 24.9-39.1). In the subacute phase, the prevalence of mild, moderate, and severe sleep-disordered breathing was 65.5%, 44.3%, and 36.1% (95% CIs, 58.9-71.5, 36.1-52.8, and 22.2-52.8). In the chronic phase, the summary prevalence of mild, moderate, and severe sleep-disordered breathing was 66.2%, 33.1%, and 25.1% (95% CIs, 58.6-73.1, 24.8-42.6, and 10.9-47.6). The prevalence rates of insomnia in the acute, subacute, and chronic phases were 40.7%, 42.6%, and 35.9% (95% CIs, 31.8-50.3, 31.7-54.1, and 28.6-44.0). The pooled prevalence of periodic leg movement during sleep in the acute, subacute, and chronic phases was 32.0%, 27.3%, and 48.2% (95% CIs, 7.4-73.5, 11.6-51.7, and 33.1-63.5). The summary prevalence of restless leg syndrome in the acute and chronic phases was 10.4% and 13.7% (95 CIs, 6.4-16.4 and 2.3-51.8). Age, sex, comorbidities, smoking history, and study region had significant moderating effects on the prevalence of sleep disorders. Sleep disorders following stroke or TIA are highly prevalent over time. Our findings indicate the importance of early screening and treating sleep disorders following stroke or TIA.


Risk factors for complete molar pregnancy: a study in Iran.
To evaluate some of the risk factors of complete molar pregnancy. A case-control study was performed on 91 cases of complete molar pregnancy (case group) and 295 cases of normal, term pregnancy with a live neonate (control group). Then the maternal age, parity and gravidity, blood group and Rh, history of molar pregnancy, consanguinity, history of spontaneous abortion, contraception method and nationality (Afghan or Iranian) were compared in the 2 groups. History of molar pregnancy (OR [odds ratio], 95% CI 5.7 [1.2-25.61), spontaneous abortion (OR, 95% CI 2.1 [1.7-2.61), maternal age > 35 years old (OR, 95% CI 2.3 [1.3-3.9]) and < 20 years old (OR, 95% CI 1.6 [1.4-1.9]), consanguinity (OR, 95% CI 1.3 [1.1-1.51) and Iranian nationality (OR, 95% CI 1.9 [(1.5-2.4]) were found to be risk factors for molar pregnancy. History of molar pregnancy and spontaneous abortion, maternal age > 35 and < 20, consanguinity and nationality may be risk factors for molar pregnancy.


Justifying a presumption of restraint in animal biotechnology research.
Articulating the public's widespread unease about animal biotechnology has not been easy, and the first attempts have not been able to provide an effective tool for navigating the moral permissibility of this research. Because these moral intuitions have been difficult to cash out, they have been belittled as representing nothing more than fear or confusion. But there are sound philosophical reasons supporting the public's opposition to animal biotechnology and these arguments justify a default position of resistance I call the Presumption of Restraint. The Presumption of Restraint constitutes a justificatory process that sets out the criteria for permitting or rejecting individual biotechnology projects. This Presumption of Restraint can be overridden by compelling arguments that speak to a project's moral and scientific merit. This strategy creates a middle-of-the-road stance that can embrace particular projects, while rejecting others. The Presumption of Restraint can also serve as a model for assessing moral permissibility in other areas of technological innovation.


Relationship between Fibroblast Growth Factor 23 and Biochemical and Bone Histomorphometric Alterations in a Chronic Kidney Disease Rat Model Undergoing Parathyroidectomy.
Phosphate burden in chronic kidney disease (CKD) leads to elevated serum fibroblast factor-23 (FGF-23) levels, secondary hyperparathyroidism and chronic kidney disease-mineral bone disorder (CKD-MBD). However dissociated hyperphosphatemia and low serum FGF-23 concentrations have been observed in experimentally parathyoridectomized rats. The relationships between serum mineral, hormone, and bone metabolism may be altered in the presence of CKD. The aim of our study was to investigate whether a consistent relationship existed between serum FGF-23 levels, specific serum biochemical markers, and histomorphometric parameters of bone metabolism in a parathyroidectomized CKD animal model. Sprague Dawley rats were divided into 3 groups: parathyroidectomy (PTX) and CKD (PTX+CKD, 9 rats), CKD without PTX (CKD, 9 rats), and neither PTX nor CKD (sham-operated control, 8 rats); CKD was induced by partial nephrectomy. At 8 weeks after partial nephrectomy, serum biomarkers were measured. Bone histomorphometries of the distal femoral metaphyseal bone were analyzed. The mean serum FGF-23 levels and mean bone formation rate were the highest in the CKD group and the lowest in the PTX+CKD group. Bone volume parameters increased significantly in the PTX+CKD group. Pearson's correlation revealed that serum FGF-23 levels associated with those of intact parathyroid hormone, phosphate, collagen type I C-telopeptide, and calcium. Univariate linear regression showed that serum FGF-23 values correlated with bone formation rate, bone volume, and osteoid parameters. Stepwise multivariate regression analysis revealed that circulating FGF-23 values were independently associated with bone volume and thickness (β = -0.737; p < 0.001 and β = -0.526; p = 0.006, respectively). Serum parathyroid hormone levels independently correlated with bone formation rate (β = 0.714; p < 0.001) while collagen type I C-telopeptide levels correlated with osteoid parameter. Serum FGF-23 levels independently correlated with bone volume parameters in rats with experimentally induced CKD.


The HER2 I655V polymorphism and risk of breast cancer in women < age 40 years.
The HER2 gene controls cellular function and has prognostic significance in breast cancer. The I655V polymorphism was associated with increased risk of breast cancer in Chinese women under the age of 45 years and in women with a first-degree family history of the disease. These associations, however, have not been confirmed in several studies of older women. We conducted a population-based case-control-family study of the I655V polymorphism using 409 Australian women with breast cancer diagnosed before the age of 40 years and 299 controls frequency matched for age. The I655V polymorphism was more common in cases (P = 0.01). A recessive model, in which homozygotes were associated with an adjusted odds ratio of 2.8 (95% confidence interval 1.3-6.2; P = 0.005), gave the best fit under parsimony. Although the biological role of the I655V polymorphism is not known, large independent studies of early onset breast cancer are warranted to attempt to replicate this finding.


No. 329-Canadian Contraception Consensus Part 4 of 4 Chapter 9: Combined Hormonal Contraception.
To provide guidelines for health care providers on the use of contraceptive methods to prevent pregnancy and on the promotion of healthy sexuality. Overall efficacy of cited contraceptive methods, assessing reduction in pregnancy rate, safety, and side effects; the effect of cited contraceptive methods on sexual health and general well-being; and the availability of cited contraceptive methods in Canada. Medline and the Cochrane Database were searched for articles in English on subjects related to contraception, sexuality, and sexual health from January 1994 to December 2015 in order to update the Canadian Contraception Consensus published February-April 2004. Relevant Canadian government publications and position papers from appropriate health and family planning organizations were also reviewed. The quality of the evidence is rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Recommendations for practice are ranked according to the method described in this report. RECOMMENDATIONS.


Thermocatalytic CO2 Conversion over a Nickel-Loaded Ceria Nanostructured Catalyst: A NAP-XPS Study.
Despite the increasing economic incentives and environmental advantages associated to their substitution, carbon-rich fossil fuels are expected to remain as the dominant worldwide source of energy through at least the next two decades and perhaps later. Therefore, both the control and reduction of CO2 emissions have become environmental issues of major concern and big challenges for the international scientific community. Among the proposed strategies to achieve these goals, conversion of CO2 by its reduction into high added value products, such as methane or syngas, has been widely agreed to be the most attractive from the environmental and economic points of view. In the present work, thermocatalytic reduction of CO2 with H2 was studied over a nanostructured ceria-supported nickel catalyst. Ceria nanocubes were employed as support, while the nickel phase was supported by means a surfactant-free controlled chemical precipitation method. The resulting nanocatalyst was characterized in terms of its physicochemical properties, with special attention paid to both surface basicity and reducibility. The nanocatalyst was studied during CO2 reduction by means of Near Ambient Pressure X-ray Photoelectron Spectroscopy (NAP-XPS). Two different catalytic behaviors were observed depending on the reaction temperature. At low temperature, with both Ce and Ni in an oxidized state, CH4 formation was observed, whereas at high temperature above 500 °C, the reverse water gas shift reaction became dominant, with CO and H2O being the main products. NAP-XPS was revealed as a powerful tool to study the behavior of this nanostructured catalyst under reaction conditions.


Incidence and prevalence of ulcerative colitis in the upper Galilee, Northern Israel, 1967-1986.
An epidemiological study of ulcerative colitis was performed in the Upper Galilee, Israel, over a 20-yr period (1967-1986). The average annual incidence of ulcerative colitis was 2.23 per 100,000 population, and the prevalence on December 31, 1986, was 44.58 per 100,000. Considering the fact that strict steps were taken to include only definite cases, these figures are probably an underestimation. An increase of the average annual incidence from 0.88 in the period 1967-1976 to 3.79 in 1977-1986 was found. When the data were stratified according to ethnic groups, the highest average annual incidence and the highest point prevalence was found in Israeli-born Jews (6.9 and 138.2 per 100,000 population, respectively). When Jewish residence patterns were compared, the highest average annual incidence and point prevalence were found among Kibbutz members (5.52 and 110.39, respectively), and the lowest (1.94 and 38.76) among Moshav inhabitants. There were 10 Arab patients with an average annual incidence of 0.96 and a point prevalence of 19.27. There were 25 women and 28 men (female:male ratio of 0.89). Among the Jews, the female:male ratio was 1.04. Peak incidence was found in the 25- to 34-yr-old range. No second peak was noticed. Anemia was demonstrated in 66.6% of the women and 27.5% of the men in our study. We suggest that the increase in UC incidence and prevalence in Israeli and Asia/africa-born Jew and in Arabs in the Upper Galilee points toward environmental factors in the etiology of this disease.


A pilot randomized controlled trial comparing nutritious meal kits and no-prep meals to improve food security and diet quality among food pantry clients.
Food pantry clients have high rates of food insecurity and greater risk for and prevalence of diet-related diseases. Many clients face time, resource, and physical constraints that limit their ability to prepare healthy meals using foods typically provided by pantries. We compared two novel approaches to alleviate those barriers and encourage healthier eating: meal kits, which bundle ingredients with a recipe on how to prepare a healthy meal, and nutritious no-prep meals, which can be eaten after thawing or microwaving. Participants were adult pantry clients from a large food pantry in the Southern sector of Dallas, Texas. We conducted a repeated measures between-subjects study with 70 clients randomized to receive 14-days of meal kits (n=35) or no-prep meals (n=35). Participants completed questionnaires at baseline and twoweek follow-up on demographics, hedonic liking of study meals, perceived dietary quality, and food security. Two-way repeated measures analysis of variance was used to examine group and time effects, and group by time interactions. We also describe feasibility and satisfaction outcomes to inform future implementation. Sixty-six participants completed the study (94%). Participants were predominantly Hispanic or Latino(a) (63%) and African American or Black (31%) women (90%). There was a significant interaction on hedonic liking of study meals (ηp2=0.16, F(1,64)=11.78, p<.001), such that participants that received meal kits had greater improvements in hedonic liking over time than participants in the no-prep group. We observed significant improvements in perceived dietary quality (ηp2=0.36, F(1,64)=36.38, p<.001) and food security (ηp2=0.36, F(1,64)=36.38, p<.001) across both groups over time, but no between group differences or significant interactions indicating one intervention was more effective than the other. Program satisfaction was high across both groups, but higher among the meal kit group (ηp2=0.09, F(1,64)=6.28, p=.015). Results suggest nutritious meal kits and no-prep meals may be desirable nutrition intervention strategies for pantry clients and have potential to increase food security and perceived dietary quality in the short-term. Our findings are limited by a small sample and short follow-up. Future studies should continue to test both interventions, and include longer follow-up, objective measures of dietary quality, and relevant clinical outcomes. This trial was registered on 25/10/2022 on Clinicaltrials.gov, identifier: NCT05593510.


Topical antibiotics and intravitreal injections.
There is increasing evidence that topical antibiotics, given before and/or after intravitreal injections, are ineffective in preventing endophthalmitis and are possibly harmful. In addition to the lack of efficacy and increased development of resistant organisms, the use of topical antibiotics adds significantly to the cost of delivering intravitreal therapy. Despite this, in many countries, it is still common practice to use pre- and/or postinjection topical antibiotics. This review outlines the general principles of effective antibiotic prophylaxis, and the evidence regarding topical antibiotic use as a prophylactic measure for endophthalmitis following intravitreal injections. A key distinguishing feature of intravitreal injections from most other invasive procedures is the fact that they are often repeated on multiple occasions to the same eye. Given the lack of evidence to support topical antibiotics as an effective method of prophylaxis for postinjection endophthalmitis, it appears that more widespread education of ophthalmologists is required to avoid continued inappropriate use. Revision of drug labels in some jurisdictions, and amendment of local/professional society guidelines, may be required to assist in achieving this goal. Emphasis should be placed on antisepsis and aseptic technique, which are the major proven methods of endophthalmitis prevention, rather than antibiotics.


Solid-state reactions in binary molecular assemblies of F₁₆CuPc and pentacene.
Various phases of binary molecular assemblies of perfluorinated Cu-phthalocyanine (F₁₆CuPc) and pentacene were examined using scanning tunneling microscopy (STM). Alloying, solid solutions, phase separation, and segregation were observed in assemblies on monolayers according to the mixture ratios. The main driving force behind such molecular blending is CH-F hydrogen bonds. Lattice matching and molecular symmetry are other factors that determine the assembly configuration. A detailed understanding of such solid-state reactions provides a guideline to the construction of multilayered binary assemblies, where intermixing between molecules takes place when multiple layers are stacked.


DEVILS: a tool for the visualization of large datasets with a high dynamic range.
The number of grey values that can be displayed on monitors and be processed by the human eye is smaller than the dynamic range of image-based sensors. This makes the visualization of such data a challenge, especially with specimens where small dim structures are equally important as large bright ones, or whenever variations in intensity, such as non-homogeneous staining efficiencies or light depth penetration, becomes an issue. While simple intensity display mappings are easily possible, these fail to provide a one-shot observation that can display objects of varying intensities. In order to facilitate the visualization-based analysis of large volumetric datasets, we developed an easy-to-use ImageJ plugin enabling the compressed display of features within several magnitudes of intensities. The Display Enhancement for Visual Inspection of Large Stacks plugin (DEVILS) homogenizes the intensities by using a combination of local and global pixel operations to allow for high and low intensities to be visible simultaneously to the human eye. The plugin is based on a single, intuitively understandable parameter, features a preview mode, and uses parallelization to process multiple image planes. As output, the plugin is capable of producing a BigDataViewer-compatible dataset for fast visualization. We demonstrate the utility of the plugin for large volumetric image data.


Naive and effector CD4 T cells differ in their requirements for T cell receptor versus costimulatory signals.
We used naive CD4 cells and in vitro-derived Th1 and Th2 effectors from TCR transgenic mice to investigate the requirements of these subsets for TCR signaling and interactions with accessory molecules. Peptide Ag and immobilized anti-CD3 were used to provide different TCR signals. Anti-CD28 Ab or a panel of class II+ fibroblasts, expressing no accessory molecules or expressing intracellular adhesion molecule-1, B7-1, or both molecules, were used as APC or accessory cells (AC). An efficient naive T cell response required a strong TCR signal (high dose anti-CD3 or peptide) and high levels of multiple synergizing costimulatory signals, while effector cells responded efficiently to anti-CD3 alone. Addition of AC only slightly augmented the effector response. Effectors responded to lower doses of peptide than naive cells. However, when peptide-pulsed APC were used to stimulate effectors, requirements varied with the cytokine measured. The production of IL-4 did not require accessory molecules on APC. IL-2 production required interacting APC to express accessory molecules, but was little augmented by AC not presenting Ag, suggesting a requirement for noncostimulatory interactions. Proliferation of effectors closely paralleled IL-2 production. Production of IFN-gamma was intermediate in dependence on accessory molecules, and production of IL-5 was nearly as dependent as IL-2. These results establish major differences between the induction of naive and effector responses and document differential requirements for the induction of distinct cytokines, indicating that different cytokines may be produced depending on the context of effector restimulation.


Identification of a Membrane Binding Peptide in the Envelope Protein of MHV Coronavirus.
Coronaviruses (CoVs) are enveloped, positive sense, single strand RNA viruses that cause respiratory, intestinal and neurological diseases in mammals and birds. Following replication, CoVs assemble on intracellular membranes including the endoplasmic reticulum Golgi intermediate compartment (ERGIC) where the envelope protein (E) functions in virus assembly and release. In consequence, E potentially contains membrane-modifying peptides. To search for such peptides, the E coding sequence of Mouse Hepatitis Virus (MHV) was inspected for its amino acid conservation, proximity to the membrane and/or predicted amphipathic helices. Peptides identified in silico were synthesized and tested for membrane-modifying activity in the presence of giant unilamellar vesicles (GUVs) consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), sphingomyelin and cholesterol. To confirm the presence of membrane binding peptides identified in the context of a full-length E protein, the wild type and a number of mutants in the putative membrane binding peptide were expressed in Lenti-X-293T mammalian and insect cells, and the distribution of E antigen within the expressing cell was assessed. Our data identify a role for the post-transmembrane region of MHV E in membrane binding.


Ability of ankle-brachial index to detect lower-extremity atherosclerotic disease progression.
Accurate determination of progression of lower-extremity arterial occlusive disease (LEAOD) is required for natural history studies and evaluation of therapies for atherosclerosis. To determine if changes in the ankle-brachial index (ABI) correlated with progression of LEAOD as determined by arteriography or duplex scanning. In patients with prior suprainguinal or infrainguinal lower-extremity revascularization, progression of LEAOD in native arteries was determined by comparing a preoperative (baseline) arteriogram with late follow-up arteriography or duplex scanning. Superficial femoral and popliteal arteries were graded as having less than 50% stenosis, 50% to 99% stenosis, or as being occluded. Tibial arteries were graded as continuously patent or occluded. Operated and nonoperated extremities were included in the study. The baseline ABI was performed postoperatively and repeated at follow-up arteriography or duplex scanning. Progression of LEAOD by the ABI was defined as a decrease in the ABI of 0.15 or greater. Progression of LEAOD by imaging studies was defined as an increase in 1 category of stenosis. Extremities with suprasystolic pressures were excluded. Tertiary vascular surgical service. EXTREMITIES AND PATIENTS: One hundred ninety-three extremities were studied in 114 patients during a mean follow-up of 3.3 years. Seventy-two lower extremities (37.3%) showed progression of atherosclerosis by late follow-up arteriography or duplex scanning. Using the imaging studies as the criterion standard, the ABI had 102 true negatives, 29 true positives, 42 false negatives, and 20 false positives (sensitivity, 41%; specificity, 84%; positive predictive value, 59%; negative predictive value, 71%; and accuracy, 68%) for determining the progression of LEAOD. The ABI is relatively insensitive in identifying the progression of LEAOD as demonstrated by the use of imaging studies. In studies of natural history or therapy for atherosclerosis, imaging studies should be used in preference to the ABI to evaluate the progression of LEAOD accurately.


Deception, power, and self-differentiation in college students' romantic relationships: an exploratory study.
The relationships among deception, power, and self-differentiation in college students' romantic relationships were explored. As hypothesized, lower total deception scores were found to significantly predict higher self-differentiation scores. Both men and women reported that men held significantly more power in their relationships. A secondary analysis revealed that men were significantly more likely than women to indicate they would be inclined to use deceptive strategies. Counter to the hypotheses, a significant negative correlation was not detected between power scores and omission scores, and positive relationships between power scores and contradiction scores were not found.


IL-4-secreting secondary T follicular helper (Tfh) cells arise from memory T cells, not persisting Tfh cells, through a B cell-dependent mechanism.
Humoral immunity requires cross-talk between T follicular helper (Tfh) cells and B cells. Nevertheless, a detailed understanding of this intercellular interaction during secondary immune responses is lacking. We examined this by focusing on the response to a soluble, unadjuvanted, pathogen-derived Ag (soluble extract of Schistosoma mansoni egg [SEA]) that induces type 2 immunity. We found that activated Tfh cells persisted for long periods within germinal centers following primary immunization. However, the magnitude of the secondary response did not appear to depend on pre-existing Tfh cells. Instead, Tfh cell populations expanded through a process that was dependent on memory T cells recruited into the reactive LN, as well as the participation of B cells. We found that, during the secondary response, IL-4 was critical for the expansion of a population of plasmablasts that correlated with increased SEA-specific IgG1 titers. Additionally, following immunization with SEA (but not with an Ag that induced type 1 immunity), IL-4 and IL-21 were coproduced by individual Tfh cells, revealing a potential mechanism through which appropriate class-switching can be coupled to plasmablast proliferation to enforce type 2 immunity. Our findings demonstrate a pivotal role for IL-4 in the interplay between T and B cells during a secondary Th2 response and have significant implications for vaccine design.


[Combined treatment of lung cancer].
The results of surgical and combined treatment of 2025 cases of differentiated cancer of the lung are compared. There was no difference in treatment results for stages I-II. In stage III tumor treatment, preoperative radiotherapy or postoperative polychemotherapy were followed by relative increase in 5-year survival. When intrathoracic lymph nodes were involved, combined treatment including pre- or postoperative radiotherapy was a procedure of choice since it was followed by better end results.


Free Energy Profile Decomposition Analysis for QM/MM Simulations of Enzymatic Reactions.
In enzyme mechanistic studies and mutant design, it is highly desirable to know the individual residue contributions to the reaction free energy and barrier. In this work, we show that such free energy contributions from each residue can be readily obtained by postprocessing ab initio quantum mechanical molecular mechanical (ai-QM/MM) free energy simulation trajectories. Specifically, through a mean force integration along the minimum free energy pathway, one can obtain the electrostatic, polarization, and van der Waals contributions from each residue to the free energy barrier. Separately, a similar analysis procedure allows us to assess the contribution from different collective variables along the reaction coordinate. The chorismate mutase reaction is used to demonstrate the utilization of these two trajectory analysis tools.


Intraventricular early diastolic filling during acute myocardial ischemia, assessment by multigated color m-mode Doppler echocardiography.
Color M-mode Doppler echocardiography has been suggested as a new noninvasive technique for assessing left ventricular diastolic function. The present study investigated intraventricular filling pattern by color M-mode Doppler in patients during percutaneous transluminal coronary angioplasty (PTCA). In a dog model of myocardial ischemia, the color M-mode flow pattern was related to indices of global and regional myocardial function. From color M-mode images, the time difference (TD) between occurrence of peak velocity in the apical region and at the mitral tip was determined in 20 patients and eight anesthetized dogs during coronary occlusions. During PTCA, the timing of peak velocity was progressively delayed from mitral valve to apex. Consistent with this, the dog model showed delayed apical filling during coronary occlusion; TD increased from 18 +/- 4 to 71 +/- 9 milliseconds (P < .01). In the ischemic region, systolic shortening (sonomicrometry) decreased from 20 +/- 3% to -5 +/- 2% (p < .01). The one-third filling fraction decreased from 59 +/- 5% to 31 +/- 6% (P < .01) and correlated with TD (r = .85, P < .01). The time constant of isovolumic relaxation (tau) increased slightly and correlated with TD (r = .81, P < .01). Pacing tachycardia, caval constriction, and volume loading were performed to mimic the ischemia-induced changes in heart rate, stroke volume, and intracavitary filling pressure, respectively. There were no significant changes in TD or tau during these interventions. Color M-mode Doppler echocardiography showed a marked delay of apical peak filling velocity during PTCA. The experimental data suggest that this reflects retarded filling of the ischemic ventricle. Thus, color M-mode Doppler may provide a useful method for assessing diastolic dysfunction.


Evaluation of HiaureusTM Coagulase Confirmation Kit in Identification of Staphylococcus aureus.
Staphylococcus aureus is a facultative anaerobic Gram positive coccal bacterium whose incidence ranges to different infections. It is a cause of various uncomplicated skin infections, abscesses, septicaemia/bacteraemia, gastroenteritis, endocarditis, toxic shock syndrome and food intoxications. Various methods with varied time, sensitivities, specificities and costs are available, but may not be used as a reliable test for the identification and differentiation of S. aureus. Therefore, there is a need to evaluate newer tests. To compare the conventional tests with a commercial available kit for reliable, cost effective identification and confirmation of S. aureus. The current prospective study was conducted in the Department of Clinical Pathology, Haffkine Institute for a period of six months. A total of 341 clinical isolates of staphylococci isolated from pus, urine, blood culture and sterile body fluids were subjected to conventional tests like Tube Coagulase Test (TCT) using Rabbit Plasma (RP) and Human Plasma (HP), culture media such as Mannitol Salt Agar (MSA) and Deoxyribonuclease (DNase) media in parallel to HiaureusTM Coagulase Confirmation Kit (HACCK), a commercially available kit for identification of S. aureus. Amplification of the femA gene was used as a comparative reference point test to calculate the sensitivity, specificity and concordance values of the conventional tests. Amongst the coagulase based tests, HACCK was 100% sensitive and specific. The TCT using RP was 98.58% sensitive while TCT using HP was less sensitive (95.37%). A total of 100% specificity was observed for TCT using RP while TCT using HP was 96.68% specific. The MSA and DNase media were 97.86% vs 96.44% and 96.67% vs 91.67% sensitive and specific respectively. The combination tests had varying sensitivity and specificity ranges. The HACCK demonstrated 100% concordance with femA amplification and was labelled as an ideal perfect test (κ=1) with MSA as an alternative test for S. aureus identification. The HACCK can be used as an exclusive, reliable and cost effective test for identification of S. aureus. Alternatively, in view of the cost factor MSA either as a single test or in combination with TCT using HP could be used as screening tests and confirm discordant results with HACCK.


Predictive value of object relations for therapeutic alliance and outcome in psychotherapy for depression: an exploratory study.
The concept of object relations has been shown to be relevant for the process and outcome of psychodynamic psychotherapies. However, little is known about its relevance for the psychotherapeutic treatment of depression. In this study, we explored the predictive value of object relational functioning (ORF) for the therapeutic alliance and outcome of short-term psychodynamic supportive psychotherapy in patients with mild to moderately severe depression. The ORF of 81 patients was rated by using the Developmental Profile. The overall maturity of ORF measured at baseline was higher in patients who showed a better treatment response. In multiple regression analysis, the adaptive level of individuation appeared to be specifically predictive of outcome. Patients with a recurrent depression showed less mature levels of ORF, lower adaptive levels and a higher score on the symbiotic level. No association was found between ORF and therapeutic alliance during treatment. In contrast to the single measure of alliance early in therapy, the growth of the alliance was related to outcome. The study indicated the relevance of ORF for depression and established that it is distinctive from the actual therapeutic alliance.


Epithelial protein lost in neoplasm (EPLIN) interacts with α-catenin and actin filaments in endothelial cells and stabilizes vascular capillary network in vitro.
Adherens junctions are required for vascular endothelium integrity. These structures are formed by the clustering of the homophilic adhesive protein VE-cadherin, which recruits intracellular partners, such as β- and α-catenins, vinculin, and actin filaments. The dogma according to which α-catenin bridges cadherin·β-catenin complexes to the actin cytoskeleton has been challenged during the past few years, and the link between the VE-cadherin·catenin complex and the actin cytoskeleton remains unclear. Recently, epithelial protein lost in neoplasm (EPLIN) has been proposed as a possible bond between the E-cadherin·catenin complex and actin in epithelial cells. Herein, we show that EPLIN is expressed at similar levels in endothelial and epithelial cells and is located at interendothelial junctions in confluent cells. Co-immunoprecipitation and GST pulldown experiments provided evidence that EPLIN interacts directly with α-catenin and tethers the VE-cadherin·catenin complex to the actin cytoskeleton. In the absence of EPLIN, vinculin was delocalized from the junctions. Furthermore, suppression of actomyosin tension using blebbistatin triggered a similar vinculin delocalization from the junctions. In a Matrigel assay, EPLIN-depleted endothelial cells exhibited a reduced capacity to form pseudocapillary networks because of numerous breakage events. In conclusion, we propose a model in which EPLIN establishes a link between the cadherin·catenin complex and actin that is independent of actomyosin tension. This link acts as a mechanotransmitter, allowing vinculin binding to α-catenin and formation of a secondary molecular bond between the adherens complex and the cytoskeleton through vinculin. In addition, we provide evidence that the EPLIN clutch is necessary for stabilization of capillary structures in an angiogenesis model.


Relationship between neck acceleration and muscle activation in people with chronic neck pain: Implications for functional disability.
Previous study has found that people with chronic neck pain moved with a consistently compromised acceleration/deceleration at their cervical and thoracic spines. This study examined the strength of the association between the electromyographic activities and the acceleration/deceleration of the cervical and thoracic spine, and its correlation with the functional disabilities in individuals with neck pain. Time history of the cervical and thoracic acceleration/deceleration and EMG activity was acquired in thirty-four subjects with chronic neck pain and thirty-four age- and gender-matched asymptomatic subjects during active neck movements. The strength of the association between the electromyographic activity of spinal muscles and the cervical and thoracic acceleration/deceleration was determined using cross-correlation method. Relationship between the strength of this association and the severity of the functional disabilities in neck pain group was examined using correlation analysis. The strength of the association between cervical and thoracic acceleration/deceleration and electromyographic activities was significantly lower in neck pain group. Significant negative correlations were found between the functional disability level and the strength of this defined association in the symptomatic group. The compromised capability of the spinal muscles to produce acceleration/deceleration in the neck pain group may imply an impaired electromechanical coupling of these spinal muscles when performing neck movements. Significant negative correlation of the degree of functional disabilities suggests that the present approach can be used as an objective and specific evaluation of the dynamic performance of the spinal muscles and its relationship with the functional disabilities in neck pain subjects.


Sodium currents during differentiation in a human neuroblastoma cell line.
The electrophysiological properties of a human neuroblastoma cell line, LA-N-5, were studied with the whole-cell configuration of the patch clamp technique before and after the induction of differentiation by retinoic acid, a vitamin A metabolite. Action potentials could be elicited from current clamped cells before the induction of differentiation, suggesting that some neuroblasts of the developing sympathetic nervous system are excitable. The action potential upstroke was carried by a sodium conductance, which was composed of two types of sodium currents, described by their sensitivity to tetrodotoxin (TTX) as TTX sensitive and TTX resistant. TTX-sensitive and TTX-resistant sodium currents were blocked by nanomolar and micromolar concentrations of TTX, respectively. The voltage sensitivity of activation and inactivation of TTX-resistant sodium current is shifted -10 to -30 mV relative to TTX-sensitive sodium current, suggesting that TTX-resistant sodium current could play a role in the initiation of action potentials. TTX-sensitive current comprised greater than 80% of the total sodium current in undifferentiated LA-N-5 cells. The surface density of total sodium current increased from 24.9 to 57.8 microA/microF after cells were induced to differentiate. The increase in total sodium current density was significant (P less than 0.05). The surface density of TTX-resistant sodium current did not change significantly during differentiation, from which we conclude that an increase in TTX-sensitive sodium current underlies the increase in total current.


[Morphofunctional elements of the pathogenesis of acute pancreatitis].
Nineteen patients with acute pancreatitis were examined for the activity of LDH, NADH-tetrazolium oxidoreductase, acid phosphatase, the content of calcium salts, cAMP and cGMP in biopsy tissue of the pancreas; pancreatic enzymes and bicarbonates in the duodenal contents and pancreatic juice. The activity of enzymes participating in oxidative metabolism in epithelial cells of the intact pancreas appeared elevated. During the development of destructive changes in the pancreatic parenchyma, the processes of intracellular oxidation get inhibited, the enzymes go out into the intercellular space, calcium transport gets impaired, and acid phosphatase is activated. It has been found that in acute destructive pancreatitis, primarily impaired are epithelial cells of the islets, followed by the impairment of the epithelium of the acini and at the last moment of that of the excretory ducts. The data obtained enable one to regard cyclonucleotides, calcium, pancreatic enzymes and lysosomal hydrolases as pathogenetic elements of acute pancreatitis.


Mental health, family function and obesity in African-American women.
African-American women are disproportionately affected by obesity and its related diseases. How psychological and psychosocial factors that affect this population differ across weight categories remains poorly understood. To determine whether poor mental health and family functioning are associated with obesity in African-American women. African-American women patients aged 21-65 years were interviewed at three primary care centers. Four well-established assessment tools were used to measure general mental and physical health status, family functioning, depressive symptoms and anxiety levels. Demographics, health behaviors and family and personal histories of overweight were assessed. Among 113 patients, after controlling for age and parity, obese women had significantly higher anxiety levels, poorer perception of their physical health, more often were overweight as a child, had overweight parents or siblings and experienced more psychosocial problems in their family growing up, compared to overweight and normal weight women. The observed findings of poor mental health, perception of physical health and family function in obese African-American women support a need for clinical attention and further study.


Ca²⁺ sensitization of cardiac myofilament proteins contributes to exercise training-enhanced myocardial function in a porcine model of chronic occlusion.
Exercise training has been shown to improve cardiac dysfunction in both patients and animal models of coronary artery disease; however, the underlying cellular and molecular mechanisms have not been completely understood. We hypothesized that exercise training would improve force generation in the myocardium distal to chronic coronary artery occlusion via altered intracellular Ca(2+) concentration ([Ca(2+)](i)) cycling and/or Ca(2+) sensitization of myofilaments. Ameroid occluders were surgically placed around the proximal left circumflex coronary artery of adult female Yucatan pigs. Twenty-two weeks postoperatively, the myocardium was isolated from nonoccluded (left anterior descending artery dependent) and collateral-dependent (formerly left circumflex coronary artery dependent) regions of sedentary (pen confined) and exercise-trained (treadmill run, 5 days/wk for 14 wk) pigs. Force measurements in myocardial strips showed that the percent change in force at stimulation frequencies of 3 and 4 Hz relative to 1 Hz was significantly higher in exercise-trained pigs compared with sedentary pigs. β-Adrenergic stimulation with dobutamine significantly improved force kinetics in myocardial strips of sedentary but not exercise-trained pigs at 1 Hz. Additionally, time to peak and half-decay of intracellular Ca(2+) (340-to-380-nm fluoresence ratio) responses at 1 Hz were significantly decreased in the collateral-dependent region of exercise-trained pigs with no difference in peak [Ca(2+)](i) between groups. Furthermore, the skinned myocardium from exercise-trained pigs showed an increase in Ca(2+) sensitivity compared with sedentary pigs. Immunoblot analysis revealed that the relative levels of cardiac troponin T and β(1)-adrenergic receptors were decreased in hearts from exercise-trained pigs independent of occlusion. Also, the ratio of phosphorylated to total myosin light chain-2, basal phosphorylation levels of cardiac troponin I (Ser(23) and Ser(24)), and cardiac myosin binding protein-C (Ser(282)) were unaltered by occlusion or exercise training. Thus, our data demonstrate that exercise training-enhanced force generation in the nonoccluded and collateral-dependent myocardium was associated with improved Ca(2+) transients, increased Ca(2+) sensitization of myofilament proteins, and decreased expression levels of β(1)-adrenergic receptors and cardiac troponin T.


An ENU-induced mutation in the Ankrd11 gene results in an osteopenia-like phenotype in the mouse mutant Yoda.
The mechanisms that regulate bone mass are important in a variety of complex diseases such as osteopenia and osteoporosis. Regulation of bone mass is a polygenic trait and is also influenced by various environmental and lifestyle factors, making analysis of the genetic basis difficult. As an effort toward identifying novel genes involved in regulation of bone mass, N-ethyl-N-nitrosourea (ENU) mutagenesis in mice has been utilized. Here we describe a mouse mutant termed Yoda that was identified in an ENU mutagenesis screen for dominantly acting mutations. Mice heterozygous for the Yoda mutation exhibit craniofacial abnormalities: shortened snouts, wider skulls, and deformed nasal bones, underlined by altered morphology of frontonasal sutures and failure of interfrontal suture to close. A major feature of the mutant is reduced bone mineral density. Homozygosity for the mutation results in embryonic lethality. Positional cloning of the locus identified a missense mutation in a highly conserved region of the ankyrin repeat domain 11 gene (Ankrd11). This gene has not been previously associated with bone metabolism and, thus, identifies a novel genetic regulator of bone homeostasis.


Genetic counselling in multiple sclerosis: risks to sibs and children of affected individuals.
Genetic factors are recognized as having important roles in both the overall etiology and the familial aggregation of multiple sclerosis (MS), leading to increased requests for genetic counselling. This paper is designed to provide familial risk data in a practical format for use during genetic counselling for MS. Depending on the amount of genetic sharing among family members, the relative risk of MS compared with that for the general population can range from 1 (adopted sibs and children of the MS proband, with whom they share no genetic material) to 190 (monozygotic co-twins of MS patients, with whom they share 100% of their genetic material). When counselling full sibs of MS patients, risks can be better calculated if information is available on the age of MS onset in the patient and whether or not one parent has MS.


Allium hookeri root extract regulates asthmatic changes through immunological modulation of Th1/Th2‑related factors in an ovalbumin‑induced asthma mouse model.
In 2013, WHO estimated that approximately 235 million people suffered from asthma worldwide. Asthma is a hyper responsive disorder, which is related to an imbalance between the T‑helper type 1 and 2 cells (henceforth, Th1 and Th2, respectively). Allium hookeri is a plant that is widely used for culinary purposes and also in traditional Asian medicine. The present study was conducted to elucidate the anti‑asthmatic effects and mechanism of action of A. hookeri root extracts (AHRE) in an ovalbumin (OVA)‑induced asthma mouse model. The mice were divided into five groups, namely, the control, the OVA‑treated group, the dexamethasone‑treated group, the 30 mg/kg AHRE‑treated group, and the 300 mg/kg AHRE‑treated group. The total WBC count and the differential cell count in the bronchoalveolar fluid, the level of serum IgE, the histopathological changes in the lung, and changes in the cell surface molecules, the asthma‑related cytokine levels, and Th cell transcription factors were evaluated. AHRE significantly ameliorated asthmatic changes, such as the total WBC count, eosinophil count, and the level of IgE; in addition, it reduced mucus hypersecretion, epithelial hyperplasia, and eosinophil infiltration in the lungs. AHRE significantly inhibited the expression of CD68+ cells and MHC class II+ molecules, Th1 cell transcription factor (T‑bet) activation, Th2 cell transcription factor (GATA‑3) activation, and TNF‑α in the lung tissue. Furthermore, it suppressed cell surface molecules, such as CD4+and CD8+; Th1‑related cytokines, such as IFN‑γ and IL‑12p40; Th2‑related cytokines, such as IL‑4 and IL‑5; and Th17‑related cytokines, such as IL‑6 and TNF‑α, in a dose‑dependent manner. Thus, AHRE may be considered a promising anti‑asthmatic drug.


Child-care use and the association with body mass index and overweight in children from 7 months to 2 years of age.
Studies regarding the association of child-care use with body mass index (BMI), overweight or obesity development show contradictory results. This study examined the relationship between child-care use and BMI z-scores and overweight, as well as associates of child-care use in children up to 2 years old. Longitudinal data originated from the Dutch KOALA Birth Cohort Study. Questionnaires assessed child-care use at ages 7 months and 1 and 2 years (N=2396). Height and weight assessed at 1 and 2 years were used to calculate BMI z-scores. Overweight was defined as a BMI z-score of ≥85th percentile. The influence of child-care use on weight development was tested using backward linear and logistic regression analyses. Outcomes were: (1) BMI z-score at 1 and 2 years; (2) change in BMI z-score between 1 and 2 years; (3) overweight vs non-overweight at 1 and 2 years; and (4) change from normal weight to overweight vs remaining normal weight between 1 and 2 years. The association between child-care use and parental background characteristics was tested using backward logistic regression analyses. Child-care use (no/yes) at 1 and 2 years positively predicted BMI z-scores at age 2 years, as well as change in BMI z-score between 1 and 2 years. These associations were adjusted for various covariates (for example, parental working hours). Furthermore, child-care use significantly increased the odds of being overweight at age 1 year. There were few differences in BMI or overweight between intensive (>16 h per week) and limited child-care use (≤16 h). Child-care use was positively associated with various parental characteristics, including parental working hours and maternal educational level. The findings suggest a small influence of child-care use on weight development in very young children. The child-care setting could have an important role in preventive interventions against overweight and obesity development in young children.


Organophosphate Ester Transport, Fate, and Emissions in Toronto, Canada, Estimated Using an Updated Multimedia Urban Model.
Organophosphate esters (OPEs), used as flame retardants and plasticizers, occur at relatively high concentrations in urban air and surface waters. We tested the hypothesis that some OPEs could be considered persistent and mobile organic compounds (PMOCs), using the poly parameter linear free energy relationship-modified Multimedia Urban Model (ppLFER-MUM) in Toronto, Canada, as a case study. Modeled air emissions of ∑6OPEs of 3300 (190-190 000) kg yr-1 were 10-100 times higher than emissions of polychlorinated biphenyls (∑5PCBs) and polybrominated diphenyl ethers (∑5PBDEs). Model results suggested that measured ∑6OPE stream concentrations of ∼2000 ng L-1 originate from emissions to urban air transferred to water mostly via precipitation. Water transport removed 7-28% of total air inputs compared to 0.1-10% for PCBs and 2-10% for PBDEs. Chlorinated OPEs were efficiently transported via surface water due to their persistence and high solubility. Loadings of ∑6OPEs to Lake Ontario from wastewater treatment plants, streams, and atmospheric deposition were 70%, 18%, and 13%, respectively, of ∑6OPE loadings of 3100 (1200-45 000) kg yr-1. Our results support the hypothesis that three chlorinated OPEs, tris(2-chloroethyl)phosphate phosphate (TCEP), tris(chloroisopropyl)phosphate (TCiPP), and tris(1,3-dichloroisopropyl)phosphate (TDCiPP), fit the profile of PMOCs due to their mobility and persistence in surface waters.


Impact of disability on families: grandparents' perspectives.
Caring for a child with a disability can be a unique and challenging experience, with families often relying on informal networks for support. Often, grandparents are key support resources, yet little is known about their roles and experiences. Reporting on data collected in a larger Australian study, this article explores grandparents' experiences of caring for a child with a disability and the impact on their family relationships and quality of life. A qualitative purposive sampling design was utilised; semi-structured interviews were conducted with 22 grandparents (17 women, 5 men) of children with a disability. Grandparents ranged in age from 55 to 75 years old and lived within a 90-min drive of Brisbane, Australia. Interviews were transcribed and responses analysed using a thematic approach, identifying categories, themes and patterns. Four key themes characterised grandparents' views about their role in the family: holding own emotions (decision to be positive), self-sacrifice (decision to put family needs first), maintaining family relationships (being the 'go-between') and quality of life for family in the future (concerns about the future). Grandparents are central to family functioning and quality of life, but this contribution comes with a significant cost to their own personal well-being. Implications for policy, practice and research are discussed, particularly grandparents' fear that their family could not cope without their support.


Effect of nafazatrom on platelet function and release: relationship to symptomatic episodes in patients with peripheral vascular disease.
We studied the effect of nafazatrom on plasma prostacyclin (PGI2) levels, platelet function, and thromboxane B2 (TxB2), and 12-hydroxy-eicosatetraenoic acid (12-HETE) production and clinical improvement in 12 patients with peripheral vascular disease (PVD) by means of a double-blind crossover trial of placebo, 800 or 1600 mg of nafazatrom four times daily for 1 week, with intervening 2-week washout periods. Plasma PGI2 levels were measured as 6-keto-PGF1 alpha by radioimmunoassay. Platelet function ex vivo was measured as collagen and adenosine diphosphate (ADP)-induced platelet aggregation, release of 12-HETE and thromboxane A2 (measured as TxB2), and was determined by high-pressure liquid chromatography (HPLC) and radioimmunoassay, respectively. The plasma 6-keto-PGF1 alpha levels were unaffected by nafazatrom treatment (p greater than 0.25). Nafazatrom treatment had no effect on TxB2 production, but significantly altered the production of the platelet 12-HETE (p less than 0.05). There was a significant association between the changes in 12-HETE production and clinical improvement. These results suggest that the mechanism of action of nafazatrom is in part related to the inhibition of platelet function via the lipoxygenase pathway, independent of PGI2 stimulation.


Phosphorylation of both phosphoacceptor sites in the HIV-1 Vpu cytoplasmic domain is essential for Vpu-mediated ER degradation of CD4.
Human immunodeficiency virus type 1 (HIV-1) Vpu is phosphorylated at two serine residues (Ser52 and Ser56) present within the acidic dodecapeptide region of the 54-aa cytoplasmic domain. Previous experiments have shown that Vpu phosphorylation is critical for the degradation of CD4 in the endoplasmic reticulum. In this study, we carried out experiments to elucidate the role of individual phosphoacceptor sites in CD4 proteolysis. We show here that acidic amino acids could not functionally substitute for phosphoserines in Vpu that is capable of inducing the degradation of CD4. Our studies have further revealed that phosphorylation of either of the two phosphoacceptor sites is not sufficient to generate a functional Vpu protein. When tested for functional complementation, inactive phosphorylation-proficient Vpu mutants failed to generate Vpu proteins that had the ability to induce the degradation of Vpu-sensitive glycoproteins. The failure to complement was not due to assembly defects in the Vpu protein as unphosphorylated Vpu formed oligomeric complexes in the cell. We also showed that Vpu expression inhibits protein transport in a phosphorylation-dependent manner. Our studies have thus revealed that both phosphoserines in Vpu are critical participants in a pathway that leads to the proteolysis of CD4 in the ER and that these phosphoserines should be present on the same subunit of the Vpu protein.


Cellular responses to compound stress induced by atmospheric-pressure plasma in fission yeast.
The stress response is one of the most fundamental cellular processes. Although the molecular mechanisms underlying responses to a single stressor have been extensively studied, cellular responses to multiple stresses remain largely unknown. Here, we characterized fission yeast cellular responses to a novel stress inducer, non-thermal atmospheric-pressure plasma. Plasma irradiation generates ultraviolet radiation, electromagnetic fields and a variety of chemically reactive species simultaneously, and thus can impose multiple stresses on cells. We applied direct plasma irradiation to fission yeast and showed that strong plasma irradiation inhibited fission yeast growth. We demonstrated that mutants lacking sep1 and ace2, both of which encode transcription factors required for proper cell separation, were resistant to plasma irradiation. Sep1-target transcripts were downregulated by mild plasma irradiation. We also demonstrated that plasma irradiation inhibited the target of rapamycin kinase complex 1 (TORC1). These observations indicate that two pathways, namely the Sep1-Ace2 cell separation pathway and TORC1 pathway, operate when fission yeast cope with multiple stresses induced by plasma irradiation.


Dissection of the nucleotide cycle of B. subtilis DNA gyrase and its modulation by DNA.
DNA topoisomerases catalyze the inter-conversion of different topological forms of DNA. While all type II DNA topoisomerases relax supercoiled DNA, DNA gyrase is the only enyzme that introduces negative supercoils into DNA at the expense of ATP hydrolysis. We present here a biophysical characterization of the nucleotide cycle of DNA gyrase from Bacillus subtilis, both in the absence and presence of DNA. B. subtilis DNA gyrase is highly homologous to its well-studied Escherichia coli counterpart, but exhibits unique mechanistic features. The active heterotetramer of B. subtilis DNA gyrase is formed by mixing the GyrA and GyrB subunits. GyrB undergoes nucleotide-induced dimerization and is an ATP-operated clamp. The intrinsic ATPase activity of gyrase is stimulated tenfold in the presence of plasmid DNA. However, in contrast to the E. coli homolog, the rate-limiting step in the nucleotide cycle of B. subtilis GyrB is ATP hydrolysis, not product dissociation or an associated conformational change. Furthermore, there is no cooperativity between the two DNA and ATP binding sites in B. subtilis DNA gyrase. Nevertheless, the enzyme is as efficient in negative supercoiling as the E. coli DNA gyrase. Our results provide evidence that the evolutionary goal of efficient DNA supercoiling can be realized by similar architecture, but differences in the underlying mechanism. The basic mechanistic features are conserved among DNA gyrases, but the kinetics of individual steps can vary significantly even between closely related enzymes. This suggests that each topoisomerase represents a different solution to the complex reaction sequence in DNA supercoiling.


The use of whole genome amplification to study chromosomal changes in prostate cancer: insights into genome-wide signature of preneoplasia associated with cancer progression.
Prostate cancer (CaP) is a disease with multifactorial etiology that includes both genetic and environmental components. The knowledge of the genetic basis of CaP has increased over the past years, mainly in the pathways that underlie tumourigenesis, progression and drug resistance. The vast majority of cases of CaP are adenocarcinomas that likely develop through a pre-malignant lesion and high-grade prostatic intraepithelial neoplasia (HPIN). Histologically, CaP is a heterogeneous disease consisting of multiple, discrete foci of invasive carcinoma and HPIN that are commonly interspersed with benign glands and stroma. This admixture with benign tissue can complicate genomic analyses in CaP. Specifically, when DNA is bulk-extracted the genetic information obtained represents an average for all of the cells within the sample. To minimize this problem, we obtained DNA from individual foci of HPIN and CaP by laser capture microdissection (LCM). The small quantities of DNA thus obtained were then amplified by means of multiple-displacement amplification (MDA), for use in genomic DNA array comparative genomic hybridisation (gaCGH). Recurrent chromosome copy number abnormalities (CNAs) were observed in both HPIN and CaP. In HPIN, chromosomal imbalances involving chromosome 8 where common, whilst in CaP additional chromosomal changes involving chromosomes 6, 10, 13 and 16 where also frequently observed. An overall increase in chromosomal changes was seen in CaP compared to HPIN, suggesting a universal breakdown in chromosomal stability. The accumulation of CNAs, which occurs during this process is non-random and may indicate chromosomal regions important in tumourigenesis. It is therefore likely that the alterations in copy number are part of a programmed cycle of events that promote tumour development, progression and survival. The combination of LCM, MDA and gaCGH is ideally suited for the identification of CNAs from small cell clusters and may assist in the discovery of potential genomic markers for early diagnosis, or identify the location of tumour suppressor genes (TSG) or oncogenes previously unreported in HPIN and CaP.


Nutritional factors influencing infections in preterm infants.
In contrast with clinical studies in term infants or older children, it is very difficult to investigate possible immunoregulatory effects of a novel infant formula composition in preterm infants. This is mainly because of the multicausal origin of infections in this high-risk population that is usually admitted to the neonatal intensive care unit. Possible effects of nutrition composition on onset and incidence of nosocomial infections in these very small infants have to be compared with infections that may have originated in utero. The development of the gastrointestinal tract may be inhibited after severe intrauterine growth retardation, leading to functional impairment of the gut shortly after birth. This may be related to the onset of necrotizing enterocolitis of the newborn. However, this disease in very small preterm infants is possibly also related to the initiation of oral feeding and/or the amount of feeding. Specific infection risks of neonatal intensive care as a result of invasive techniques such as artificial ventilation or total parenteral nutrition using indwelling umbilical and/or Silastic lines and so-called "all-in-one" mixtures may influence the incidence of infections. Widespread use of intravenous antibiotics in the neonatal intensive care unit may create an even larger infection risk. Investigation of possible immunomodulatory effects of factors such as prebiotics and probiotics added to the nutrition of preterm infants should always be considered along with other nutritional factors known to influence the immature immune system.


The pathogenesis of chronic inflammation in experimental antigen-induced arthritis. II. Preferential localization of antigen-antibody complexes to collagenous tissues.
In an experimental arthritis induced by injection of bovine serum albumin or egg albumin into the joints of previously immunized animals, it has been demonstrated that the major portion of the radioactively labeled antigens injected was localized to avascular collagenous tissues in the joint, i.e., articular cartilage, menisci, and intra-articular ligaments. The antigens were partially eluted from the tissues with 5 M guanidine solution, but not with acid buffers or by 3 M magnesium chloride. The radioactive material eluted with guanidine was at least 80% precipitable by specific antisera. The radioactively labeled-inducing antigen was identified on the surface of articular collagenous tissues from arthritic joints by radioautography and immunofluorescence. Rabbit immunoglobulin and C3 were demonstrated in the same sites by immunofluorescence. The presence of specific antibody in collagenous tissues was demonstrated by the selective in vitro binding of (125)I-labeled-inducing antigen to menisci from arthritic joints of immunized animals. The evidence obtained indicates that in this model of chronic arthritis, the inducing antigen persists for long periods of time in the form of immune complexes in the surface layers of the intra-articular collagenous tissue. The antigen retained in this form may be responsible for the chronicity of the synovitis by serving as a direct stimulus for the maintenance of prolonged antibody synthesis in the synovium and by providing a source of complement-fixing antigen-antibody complexes for the mediation of joint inflammation.


Detection of microsatellite alterations in plasma DNA of malignant mucosal melanoma using whole genome amplification.
Malignant mucosal melanoma (MMM) still has the poorest prognosis. There is a paucity of molecular biological studies on MMM of the head and neck. We investigated free-circulating DNA microsatellites with loss of heterozygosity (LOH) in the blood of MMM patients. Cancer-related DNA is found in plasma, with cancer patients showing a higher level of free-circulating DNA than normal subjects. However, it is difficult to obtain sufficient amounts of such DNA for PCR analysis. We have searched for ways to improve all stages of such research, and detected new microsatellite alterations by triplicated whole genome amplification (WGA) and triplicated PCR amplification. In order to achieve a better understanding of the extent of the alterations affecting chromosomes we determined the occurrence of LOH at the following gene loci: D1S243, D6S311, D9S161, and D19S246; only 4 out of the 20 microsatellite markers usually used in MMM were used in this study. We determined LOH in 17 MMM patients.It was possible to confirm LOH on at least one marker in 12 (70.6%) out of the 17 patients. Metastasis or recurrence was confirmed in 3 (17.6%) out of the 17 patients, and all of them were found to have LOH. LOH at microsatellite markers D1S243, D6S311, D9S161 and D19S246 in the plasma of these patients statistically correlated with MMM.The results of this study suggest that these loci are suitable for identifying cancerrelated DNA of MMM, and that analysis of LOH in plasma DNA released into the circulation may be useful as a screening tool.


Psychiatric disorders with onset in the preschool years: II. Correlates and predictors of stable case status.
To examine the correlates and predictors of stability and change in psychiatric disorder occurring among preschool children in a nonpsychiatric, primary care pediatric sample. Five hundred ten children aged 2 through 5 years were enrolled; 344 participated in a third wave of data collection 42 through 48 months later. Consensus diagnoses were assigned using best-estimate procedures; variables of maternal psychopathology, family climate, and life stresses were the correlates/predictors studied. For children who were cases initially, family cohesion predicted diagnostic stability. Among initial noncases, those remaining noncases experienced increased family cohesion; for those who later became cases, family cohesion declined. Negative life events declined when children were consistently noncases. Children who were initially noncases but were cases at the two subsequent waves had the highest levels of maternal negative affect. Predictors at wave 1 for wave 2 cases status included lower socioeconomic status, less family cohesiveness, and greater family inhibition/control. Wave 2 correlates of wave 2 status included older children and negative life events. Wave 2 predictors of wave 3 status included being older, while wave 3 correlates of wave 3 case status included older children and higher maternal negative affect. Family context contributes to the maintenance and onset of problems beginning in the preschool years.


[Distribution of HLA antigens in patients with hypertension].
An immunogenetic study of 71 patients with essential hypertension associated with no signs of heart or renal failure, and 276 normal Russian male residents of Moscow demonstrated a significantly increased frequency of antigens HLA-B13 (p less than 0.01) and HLA-B22 (p less than 0.05), as well as HLA-A11 (p less than 0.05), in the hypertensive sample. Aggravated heredity (familial hypertension) was established in 64% of hypertensive carriers of antigens HLA-B13 and HLA-B22.


Phenomenological network models: Lessons for epilepsy surgery.
The current opinion in epilepsy surgery is that successful surgery is about removing pathological cortex in the anatomic sense. This contrasts with recent developments in epilepsy research, where epilepsy is seen as a network disease. Computational models offer a framework to investigate the influence of networks, as well as local tissue properties, and to explore alternative resection strategies. Here we study, using such a model, the influence of connections on seizures and how this might change our traditional views of epilepsy surgery. We use a simple network model consisting of four interconnected neuronal populations. One of these populations can be made hyperexcitable, modeling a pathological region of cortex. Using model simulations, the effect of surgery on the seizure rate is studied. We find that removal of the hyperexcitable population is, in most cases, not the best approach to reduce the seizure rate. Removal of normal populations located at a crucial spot in the network, the "driver," is typically more effective in reducing seizure rate. This work strengthens the idea that network structure and connections may be more important than localizing the pathological node. This can explain why lesionectomy may not always be sufficient.


A review of chemical signaling pathways in the quorum sensing circuit of Pseudomonas aeruginosa.
Pseudomonas aeruginosa, an increasingly common competitive and biofilm organism in healthcare infection with sophisticated, interlinked and hierarchic quorum systems (Las, Rhl, PQS, and IQS), creates the greatest threats to the medical industry and has rendered prevailing chemotherapy medications ineffective. The rise of multidrug resistance has evolved into a concerning and potentially fatal occurrence for human life. P. aeruginosa biofilm development is assisted by exopolysaccharides, extracellular DNA, proteins, macromolecules, cellular signaling and interaction. Quorum sensing is a communication process between cells that involves autonomous inducers and regulators. Quorum-induced infectious agent biofilms and the synthesis of virulence factors have increased disease transmission, medication resistance, infection episodes, hospitalizations and mortality. Hence, quorum sensing may be a potential therapeutical target for bacterial illness, and developing quorum inhibitors as an anti-virulent tool could be a promising treatment strategy for existing antibiotics. Quorum quenching is a prevalent technique for treating infections caused by microbes because it diminishes microbial pathogenesis and increases microbe biofilm sensitivity to antibiotics, making it a potential candidate for drug development. This paper examines P. aeruginosa quorum sensing, the hierarchy of quorum sensing mechanism, quorum sensing inhibition and quorum sensing inhibitory agents as a drug development strategy to supplement traditional antibiotic strategies.


HTLV-1 and -2 envelope SU subdomains and critical determinants in receptor binding.
Human T-cell leukemia virus (HTLV) -1 and -2 are deltaretroviruses that infect a wide range of cells. Glut1, the major vertebrate glucose transporter, has been shown to be the HTLV Env receptor. While it is well established that the extracellular surface component (SU) of the HTLV envelope glycoprotein (Env) harbors all of the determinants of interaction with the receptor, identification of SU subdomains that are necessary and sufficient for interaction with the receptor, as well as critical amino acids therein, remain to be precisely defined. Although highly divergent in the rest of their genomes, HTLV and murine leukemia virus (MLV) Env appear to be related and based on homologous motifs between the HTLV and MLV SU, we derived chimeric HTLV/MLV Env and soluble HTLV-1 and -2 truncated amino terminal SU subdomains. Using these SU constructs, we found that the 183 and 178 amino terminal residues of the HTLV-1 and -2 Env, respectively, were sufficient to efficiently bind target cells of different species. Binding resulted from bona fide interaction with the HTLV receptor as isolated SU subdomains specifically interfered with HTLV Env-mediated binding, cell fusion, and cell-free as well as cell-to-cell infection. Therefore, the HTLV receptor-binding domain (RBD) lies in the amino terminus of the SU, immediately upstream of a central immunodominant proline rich region (Env residues 180 to 205), that we show to be dispensible for receptor-binding and interference. Moreover, we identified a highly conserved tyrosine residue at position 114 of HTLV-1 Env, Tyr114, as critical for receptor-binding and subsequent interference to cell-to-cell fusion and infection. Finally, we observed that residues in the vicinity of Tyr114 have lesser impact on receptor binding and had various efficiency in interference to post-binding events. The first 160 residues of the HTLV-1 and -2 mature cleaved SU fold as autonomous domains that contain all the determinants required for binding the HTLV receptor.


mtDNA and Y-chromosome diversity in Aymaras and Quechuas from Bolivia: different stories and special genetic traits of the Andean Altiplano populations.
Two Bolivian samples belonging to the two main Andean linguistic groups (Aymaras and Quechuas) were studied for mtDNA and Y-chromosome uniparental markers to evaluate sex-specific differences and give new insights into the demographic processes of the Andean region. mtDNA-coding polymorphisms, HVI-HVII control regions, 17 Y-STRs, and three SNPs were typed in two well-defined populations with adequate size samples. The two Bolivian samples showed more genetic differences for the mtDNA than for the Y-chromosome. For the mtDNA, 81% of Aymaras and 61% of Quechuas presented haplogroup B2. Native American Y-chromosomes were found in 97% of Aymaras (89% hg Q1a3a and 11% hg Q1a3*) and 78% of Quechuas (100% hg Q1a3a). Our data revealed high diversity values in the two populations, in agreement with other Andean studies. The comparisons with the available literature for both sets of markers indicated that the central Andean area is relatively homogeneous. For mtDNA, the Aymaras seemed to have been more isolated throughout time, maintaining their genetic characteristics, while the Quechuas have been more permeable to the incorporation of female foreigners and Peruvian influences. On the other hand, male mobility would have been widespread across the Andean region according to the homogeneity found in the area. Particular genetic characteristics presented by both samples support a past common origin of the Altiplano populations in the ancient Aymara territory, with independent, although related histories, with Peruvian (Quechuas) populations.


[Inhibition by propranolol of the ouabain binding to myocardium].
The amount of ouabain bound to an enriched fraction of heart or kidney medulla is reduced by propranolol. The inhibitory effect is greater under conditions in which complex II formation is promoted. Similar concentrations of propranolol are able to produce a reduction in Na+, K+-ATPase activity, by reduction of the number of active sites without changes in ionic affinity. The lack of stereospecificity and the high concentrations (greater than 10(-4)M) required indicate that this effect is independent of beta adrenergic blockade. Effectiveness reduction of cardiac glycosides in the presence of propranolol could be due to inhibition of drug interaction with its receptor.


[USE OF ENDOGENOUS MARKER CYSTATIN C FOR EARLY DETECTION OF RENAL IMPAIRMENT IN PATIENTS WITH COMBINED TRAUMA].
Combined trauma ranks high among all traumatic injuries. It is supposed to be one of three leading causes of death in general population and the most frequent cause of death among 40 year olds. Combined trauma mortality rates in Russia amount to 59-65 per 100,000 population and the number of years of life lost due to combined trauma is 15-25. High traumatic injury rates with large percentage of multiple injuries, high mortality and disability rates make combined trauma a high priority problem. The aim of this study was to demonstrate the feasibility of detecting early impairment of renal function in patients with combined trauma. The serum cystatin C levels and blood chemistry values were evaluated in 40 patients with combined trauma. Most of combined trauma patients in the study group were found to have normal creatinine values (36 patients). In 55% of the patients the serum cystatin C was increased to greater than 30% above normal values. The serum cystatin C levels peaked within the first 3 days after injury and then decreased gradually. In 27% of patients high levels of the serum cystatin C remained elevated after 1 week following trauma. In 61% of patients diagnosed as having renal contusion the serum cystatin C levels were above normal values. Decreased levels of GFR measured by Rehberg's test were detected in only 4 patients, while estimated by Hock's formula - in 22 patients.


Beet poleroviruses: close friends or distant relatives?
SUMMARY Taxonomy: There are three members of the genus Polerovirus (family Luteoviridae) that induce yellowing of sugar beet: Beet mild yellowing virus (BMYV), Beet chlorosis virus (BChV) and Beet western yellows virus-USA (BWYV-USA, Fig. 1). Non-beet-infecting isolates of BWYV found particularly within Europe have now been re-named Turnip yellows virus (TuYV). Species-specific antibodies are unavailable, but the viruses can be distinguished by RT-PCR using primers specifically designed to the 5' end of their respective genomes. Physical properties: The isometric virus particles are approximately 26 nm in diameter and the genome consists of a single strand of positive sense RNA that utilizes almost all known plant virus gene expression strategies (initiation bypass, translational frameshifting and readthrough, synthesis of subgenomic RNA and proteolytic processing). Many members of the Chenopodiaceae are susceptible, including commercial crops of sugar beet (Beta vulgaris), red beet and spinach. Experimental hosts include Montia perfoliata, Nicotiana benthamiana and Arabidopsis thaliana. Sugar beet infected with beet poleroviruses show patches of chlorosis on the older leaves 4-6 weeks post-infection; these areas expand until the whole leaf becomes yellow and older leaves then tend to thicken and become brittle. Beet poleroviruses are transmitted in a persistent (circulative, non-propagative) manner by several different aphid species, Myzus persicae being the most important vector.


Acceptability of Couples' Voluntary HIV Testing Among HIV-infected Patients in Care and Their HIV-negative Partners in the United States.
Couples' voluntary HIV counseling and testing (CHTC) is an HIV risk reduction strategy not widely available in the US. We assessed willingness to participate in CHTC among US HIV-infected clinic patients via tablet-based survey and among HIV-negative persons with HIV-infected partners in care via mixed-method phone interviews. Most of the N=64 HIV-infected partners surveyed were men (89%), on antiretroviral treatment (ART) (92%), and many self-identified homosexual (62%). We observed high levels of willingness to participate in CHTC (64%) among HIV-infected partners. Reasons for not wanting to participate included perceived lack of need (26%), desire to self-disclose their status (26%), and fear of being asked sensitive questions with their partner present (17%). HIV-infected partners were interested in discussing ART (48%), other sexually transmitted infections (STIs) (44%), and relationship agreements like monogamy (31%) during CHTC sessions. All N=15 HIV-negative partners interviewed were men, most identified as homosexual (73%), and about half (54%) reported consistent condom use with HIV-infected partners. We observed high levels of willingness to participate in CHTC (87%) among HIV-negative partners, who were also interested in discussing ART (47%), other STIs (47%), mental health services (40%), and relationship agreements (33%). Most negative partners (93%) indicated that they believed their HIV-infected partner was virally suppressed, but in the event that they were not, many (73%) were willing to take pre-exposure prophylaxis (PrEP). These results indicate that CHTC for serodiscordant couples is acceptable and should emphasize aspects most pertinent to these couples, such as discussion of ART/PrEP, STIs, and relationship agreements.


Cervicofacial necrotizing fasciitis. A devastating complication of blepharoplasty.
We report a case of cervicofacial necrotizing fasciitis that developed after blepharoplasty, an occurrence that, to our knowledge, has not previously been reported in the medical literature. A patient who presented to our institution 3 days after undergoing blepharoplasty of the upper eyelid was diagnosed as having fulminant fasciitis involving extensive areas of the face, scalp, and neck. We review the case in detail and discuss clinical and radiological clues to diagnosis, surgical and medical management, wound care, and subsequent scar contracture. This case emphasizes the need for individualized, appropriate postoperative care and for an awareness of this rare, potentially fatal complication. Early recognition and aggressive treatment of cervicofacial fasciitis can arrest its rapid progression and prevent devastating sequelae.