Unilateral spatial neglect: assessment and rehabilitation strategies.
Unilateral spatial neglect is one of the most striking disorders of cognition. Focal brain lesions, more commonly on the right, produce profound deficits in the awareness of contralateral self and space. This article reviews the assessment and current theoretical explanations of neglect, in light of rehabilitation. The presence of neglect is a predictor of poor functional recovery. No treatment protocols have been demonstrated to unequivocally aid the rehabilitation of these patients. However, based on a growing understanding of underlying mechanisms in the neglect syndrome, several promising treatment strategies have emerged. Group studies designed to establish the efficacy of these therapeutic options are urgently needed.


Sodium-Glucose Cotransporter 2 Inhibitors Potentially Prevent Atrial Fibrillation by Ameliorating Ion Handling and Mitochondrial Dysfunction.
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a novel class of glucose-lowering agents that significantly improve the prognosis of patients with type 2 diabetes (T2D) and heart failure. SGLT2i has recently been implicated in the treatment of atrial fibrillation (AF) with clinical data demonstrating that these agents decrease the incidence of AF events in patients with T2D. Fundamental findings have suggested that SGLT2i may alleviate atrial electrical and structural remodeling. The underlying mechanisms of SGLT2i are likely associated with balancing the sodium and calcium handling disorders and mitigating the mitochondrial dysfunction in atrial myocytes. This review illustrates the advances in understanding the underlying mechanisms of SGLT2i as an evolving treatment modality for AF.


Aerobic fitness and leisure physical activity as moderators of the stress-illness relation.
Exercise as a moderator of the stress-illness relation was examined by exploring leisure physical activity and aerobic fitness as potential "buffers" of the association between minor stress on physical and psychological symptoms in a sample of 135 college students. The goal was to gather information regarding the mechanisms by which exercise exhibits its buffering effects. Researchers have examined both physical activity and physical fitness in an attempt to demonstrate this effect; however, whether both of these components are necessary to achieve the protective effects against stress is unknown. This study examined engaging in leisure physical activity and having high aerobic fitness to determine if both were necessary for the stress-buffering effects or if one factor was more important than the other. Findings suggested a buffering effect for leisure physical activity against physical symptoms and anxiety associated with minor stress. This effect was not found with depression. Additionally, there was no moderating effect for aerobic fitness on physical or psychological symptoms. Collectively, the data suggested that participation in leisure physical activity as opposed to level of aerobic fitness is important to the stress-buffering effect of exercise. Implications for exercise prescription are discussed.


The Relationship Between Carotid Revascularization Procedural Volume and Perioperative Outcomes in Australia and New Zealand.
Carotid endarterectomy (CEA) and carotid artery stenting (CAS) prevent stroke in selected patients. However, each intervention carries a risk of perioperative complications including stroke or death (S/D). We aimed to determine the relationship between operator volume, hospital volume, and the perioperative risk of S/D in carotid revascularization in Australia and New Zealand. Retrospective analysis was performed on prospectively collected data extracted from the Australasian Vascular Audit between 2010 and 2017. Annual caseload volume was analyzed in quintiles (Q) using multivariate regression to assess its impact on perioperative S/D. Carotid endarterectomy procedures (n = 16 765) demonstrated higher S/D rates for lower-volume operators (2.21% for Q1-Q3 [1-17 annual cases] vs 1.76% for Q4-Q5 [18-61 annual cases]; odds ratio [OR]: 1.28; 95% CI: 1.001-1.64; P = .049). Carotid artery stenting procedures (n = 1350) also demonstrated higher S/D rates for lower-volume operators (2.63% for Q1-Q3 [1-11 annual cases] vs 0.37% for Q4-Q5 [12-31 annual cases]; OR: 6.11; 95% CI: 1.27-29.33; P = .024). No significant hospital volume-outcome effect was observed for either procedure. An inverse relationship was demonstrated between operator volume and perioperative S/D rates following CEA and CAS. Consideration of minimum operator thresholds, restructuring of services and networked referral pathways of care in Australia and New Zealand, would likely result in improved patient outcomes.


The beta/Gcd7 subunit of eukaryotic translation initiation factor 2B (eIF2B), a guanine nucleotide exchange factor, is crucial for binding eIF2 in vivo.
Eukaryotic translation initiation factor 2B (eIF2B) is the guanine nucleotide exchange factor (GEF) for eukaryotic translation initiation factor 2, which stimulates formation of the eIF2-GTP-Met-tRNA(i)(Met) ternary complex (TC) in a manner inhibited by phosphorylated eIF2 [eIF2(αP)]. While eIF2B contains five subunits, the ε/Gcd6 subunit is sufficient for GEF activity in vitro. The δ/Gcd2 and β/Gcd7 subunits function with α/Gcn3 in the eIF2B regulatory subcomplex that mediates tight, inhibitory binding of eIF2(αP)-GDP, but the essential functions of δ/Gcd2 and β/Gcd7 are not well understood. We show that the depletion of wild-type β/Gcd7, three lethal β/Gcd7 amino acid substitutions, and a synthetically lethal combination of substitutions in β/Gcd7 and eIF2α all impair eIF2 binding to eIF2B without reducing ε/Gcd6 abundance in the native eIF2B-eIF2 holocomplex. Additionally, β/Gcd7 mutations that impair eIF2B function display extensive allele-specific interactions with mutations in the S1 domain of eIF2α (harboring the phosphorylation site), which binds to eIF2B directly. Consistent with this, β/Gcd7 can overcome the toxicity of eIF2(αP) and rescue native eIF2B function when overexpressed with δ/Gcd2 or γ/Gcd1. In aggregate, these findings provide compelling evidence that β/Gcd7 is crucial for binding of substrate by eIF2B in vivo, beyond its dispensable regulatory role in the inhibition of eIF2B by eIF (αP).


Referral decisions based on a pre-hospital HEART score in suspected non-ST-elevation acute coronary syndrome: final results of the FamouS Triage study.
Although pre-hospital risk stratification of patients with suspected non-ST-elevation acute coronary syndrome (NSTE-ACS) by ambulance paramedics is feasible, it has not been investigated in daily practice whether referral decisions based on this risk stratification is safe and does not increase major adverse cardiac events (MACE). In Phase III of the FamouS Triage study, it was investigated whether referral decisions by ambulance paramedics based on a pre-hospital HEART score, is non-inferior to routine management. FamouS Triage Phase III is a non-inferiority study, comparing the occurrence of MACE before (Phase II) and after (Phase III) implementation of referral decisions based on a pre-hospital HEART score. In Phase II, all patients were risk-stratified and referred to the hospital; in Phase III, low-risk patients (HEART score ≤ 3) were not referred. Primary endpoint was MACE (acute coronary syndrome, revascularization, or death) within 45 days. A total of 1236 patients were included. Mean age was 63 years, 43% were female, 700 patients were included in the second phase and 536 in the third phase in which 149 low-risk patients (28%) were not transferred to the hospital. Occurrence of 45 days MACE was 16.6% in Phase II and 15.7% in Phase III (P = 0.67). Percentage MACE in low-risk patients was 2.9% in Phase II and 1.3% in Phase III. After adjustments for differences in baseline variables, the hazard ratio of 45 days MACE in Phase III was 0.88 (95% confidence interval 0.63-1.25) as compared to Phase II. Pre-hospital risk stratification of patients with suspected NSTE-ACS, avoiding hospitalization of a substantial number of low-risk patients, seems feasible and non-inferior to transferring all patients to the hospital.


Theoretical Investigation on the Hydrogen Evolution, Oxygen Evolution, and Oxygen Reduction Reactions Performances of Two-Dimensional Metal-Organic Frameworks Fe3(C2X)12 (X = NH, O, S).
Two-dimensional metal-organic frameworks (2D MOFs) inherently consisting of metal entities and ligands are promising single-atom catalysts (SACs) for electrocatalytic chemical reactions. Three 2D Fe-MOFs with NH, O, and S ligands were designed using density functional theory calculations, and their feasibility as SACs for hydrogen evolution reaction (HER), oxygen evolution reaction (OER), and oxygen reduction reaction (ORR) was investigated. The NH, O, and S ligands can be used to control electronic structures and catalysis performance in 2D Fe-MOF monolayers by tuning charge redistribution. The results confirm the Sabatier principle, which states that an ideal catalyst should provide reasonable adsorption energies for all reaction species. The 2D Fe-MOF nanomaterials may render highly-efficient HER, OER, and ORR by tuning the ligands. Therefore, we believe that this study will serve as a guide for developing of 2D MOF-based SACs for water splitting, fuel cells, and metal-air batteries.


Spatial navigation with horizontally spatialized sounds in early and late blind individuals.
Blind individuals often report difficulties to navigate and to detect objects placed outside their peri-personal space. Although classical sensory substitution devices could be helpful in this respect, these devices often give a complex signal which requires intensive training to analyze. New devices that provide a less complex output signal are therefore needed. Here, we evaluate a smartphone-based sensory substitution device that offers navigation guidance based on strictly spatial cues in the form of horizontally spatialized sounds. The system uses multiple sensors to either detect obstacles at a distance directly in front of the user or to create a 3D map of the environment (detection and avoidance mode, respectively), and informs the user with auditory feedback. We tested 12 early blind, 11 late blind and 24 blindfolded-sighted participants for their ability to detect obstacles and to navigate in an obstacle course. The three groups did not differ in the number of objects detected and avoided. However, early blind and late blind participants were faster than their sighted counterparts to navigate through the obstacle course. These results are consistent with previous research on sensory substitution showing that vision can be replaced by other senses to improve performance in a wide variety of tasks in blind individuals. This study offers new evidence that sensory substitution devices based on horizontally spatialized sounds can be used as a navigation tool with a minimal amount of training.


Role of Calcium in Phytochrome-Controlled Nyctinastic Movements of Albizzia lophantha Leaflets.
The involvement of Ca(2+) on phytochrome-controlled nyctinastic closure in Albizzia lophantha has been studied by testing the effect of the calcium ionophore 6S-[6alpha(2S(*),3S(*)),8beta(R(*)),9beta,11alpha]-5- methyl-amino)-2-[[3,9,11-trimethyl-8-[-1-methyl-2-oxo-2-(1H-pyrrol-2-yl) ethyl]-1,7-dioxaspiro[5.5]-undec-2yl] methyl]-4-benzoxazolecarboxylic acid (A23187) and the intracellular calcium antagonist 8-(diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8). An external supply of Ca(2+) or calcium ionophore A23187 to the Albizzia leaflets emulates the effect of red light irradiation and counteracts the inhibitory effect of far red light. The intracellular calcium antagonist TMB-8 supplied to Albizzia leaflets inhibits the effect of red light, but had no effect on far red irradiated plants. This suggests a dependence between phytochrome action and intracellular free Ca(2+). We suggest that calcium acts as a phytochrome messenger on control of ion fluxes that drive turgor changes in pulvinular motor cells.


Clinical Outcome of Primary Total Hip Arthroplasty in Patients with Morbid Obesity-Retrospective and Prospective Follow-Up Studies.
Background and objective: There is a general clinical concern on the negative impact of obesity on surgical complications and functional outcomes. We hypothesized that the patients with morbid obesity are exceptionally prone to a significantly increased risk for surgical and short-term complications after primary total hip arthroplasty (THA). We aimed to identify the range of Body Mass Index (BMI) values of patients with a significant risk for lower functional improvement after THA. Materials and methods: In Stage 1 of the study, we conducted a retrospective comparative analysis of the rate of complications and functional outcomes in patients treated by primary THA, with normal weight (BMI 19-25, N = 1205) vs. Class 1 (BMI 26-34, N = 450), Class 2 (BMI 35-39, N = 183), and Class 3 (BMI ≥ 40, N = 47) obese patients. After the statistical similarity rates of complications and 6- and 12-month functional outcomes (by Harris Hip and SF-36 scores) were revealed in Class 1 patients and patients with normal BMI, we conducted the Stage 2 prospective study, by the same comparison protocol, on the cohorts of Class 2 (N = 29) and Class 3 (N = 16) patients compared to the Class 1 patients (N = 37) as controls. Results: Stage 1: There was no difference in surgical complications and function on 6- and 12-month postoperative follow-up (physical and mental) between Class 1 and patients with normal BMI (p > 0.05). Surgical complications were significantly higher in Class 2 (p < 0.05) and Class 3 (p < 0.001) patients. Functional activity on the 12-month follow-up increased significantly in all study groups, but in the Class 3 patients, the functional parameters were significantly lower (0.001). The mental health status on the follow-up was similar in all study groups. Stage 2 study revealed similar to the retrospective study comparison of parameters, except for the significantly lower mental health scores in Class 2 and Class 3 patients (p < 0.05) and functional scores in Class 3 patients (p < 0.05). Conclusion: Although the functional ability increased in all patients, it was significantly lower in Class 3 patients (with morbid obesity). Therefore, the patients with Class 1 and Class 2 obesity should be conceptionally distinguished from Class 3 patients in the decision-making process for a primary THA because of the less favorable functional and mental health improvement in those with morbid obesity (Class 3).


Extension and integration of the gene ontology (GO): combining GO vocabularies with external vocabularies.
Structured vocabulary development enhances the management of information in biological databases. As information grows, handling the complexity of vocabularies becomes difficult. Defined methods are needed to manipulate, expand and integrate complex vocabularies. The Gene Ontology (GO) project provides the scientific community with a set of structured vocabularies to describe domains of molecular biology. The vocabularies are used for annotation of gene products and for computational annotation of sequence data sets. The vocabularies focus on three concepts universal to living systems, biological process, molecular function and cellular component. As the vocabularies expand to incorporate terms needed by diverse annotation communities, species-specific terms become problematic. In particular, the use of species-specific anatomical concepts remains unresolved. We present a method for expansion of GO into areas outside of the three original universal concept domains. We combine concepts from two orthogonal vocabularies to generate a larger, more specific vocabulary. The example of mammalian heart development is presented because it addresses two issues that challenge GO; inclusion of organism-specific anatomical terms, and proliferation of terms and relationships. The combination of concepts from orthogonal vocabularies provides a robust representation of relevant terms and an opportunity for evaluation of hypothetical concepts.


Synapses/SynEx goes XML.
This paper describes the first approach to use the Extensible Markup Language (XML) as a data interchange/delivery format in the Synapses and SynEx healthcare environment. It will ease the semantic mapping between healthcare systems (server-server, server-client) and make them more interoperable.


Can accuracy of component alignment be improved with Oxford UKA Microplasty® instrumentation?
One factor in the long-term survivorship of unicompartmental knee arthroplasty is the accuracy of implantation. In addition to implant designs, the instrumentation has also evolved in the last three decades to improve the reproducibility of implant placement. There have been limited studies comparing mobile bearing unicompartmental knee arthroplasty with contemporary instrumentation and fixed bearing unicompartmental knee arthroplasty with conventional instrumentation. This study aims to determine whether the Microplasty instrumentation in Oxford unicompartmental knee arthroplasty allows the surgeon to implant the components more precisely and accurately. A total of 150 patients (194 knees) were included between April 2013 and June 2019. Coronal and sagittal alignment of the tibial and femoral components was measured on postoperative radiographs. Component axial rotational alignment was measured on postoperative computer tomography. The knee rotation angle was the difference between the femoral and tibial axial rotation. A rotational mismatch was defined as a knee rotation angle of > 10°. Statistical analysis was performed using Student t test and Mann-Whitney nonparametric test. A p value < 0.05 was considered statistically significant in each analysis. Between April 2013 to June 2019, 112 patients (150 knees) received Oxford unicompartmental knee arthroplasty, one patient (2 knees) had Journey unicompartmental knee arthroplasty, and 37 patients (42 knees) received Zimmer unicompartmental knee arthroplasty. All femoral components in the Oxford group were implanted within the reference range, compared with 36.6% in the fixed bearing group (p < 0.001). 88.3% of Oxford knees had tibial component falling within the reference range, whereas 56.1% of knees in the fixed bearing group fell within the reference range (p < 0.001). 97.5% of Oxford knees had tibial slope that fell within reference range, whereas 53.7% fell within range for fixed bearing group (p < 0.001). Femorotibial rotational mismatch of more than 10° was noted in 13.8% in Oxford group and 20.5% in fixed bearing group (p = 0.04). In conclusion, Microplasty instrumentation for Oxford mobile bearing unicompartmental knee arthroplasty is more accurate and precise compared to conventional fixed bearing unicompartmental knee arthroplasty in sagittal, coronal, and axial alignment. Prospective studies with long-term follow-up are warranted to investigate the clinical implications.


Do different neurons age differently? Direct genome-wide analysis of aging in single identified cholinergic neurons.
Aplysia californica is a powerful experimental system to study the entire scope of genomic and epigenomic regulation at the resolution of single functionally characterized neurons and is an emerging model in the neurobiology of aging. First, we have identified and cloned a number of evolutionarily conserved genes that are age-related, including components of apoptosis and chromatin remodeling. Second, we performed gene expression profiling of different identified cholinergic neurons between young and aged animals. Our initial analysis indicates that two cholinergic neurons (R2 and LPl1) revealed highly differential genome-wide changes following aging suggesting that on the molecular scale different neurons indeed age differently. Each of the neurons tested has a unique subset of genes differentially expressed in older animals, and the majority of differently expressed genes (including those related to apoptosis and Alzheimer's disease) are found in aging neurons of one but not another type. The performed analysis allows us to implicate (i) cell specific changes in histones, (ii) DNA methylation and (iii) regional relocation of RNAs as key processes underlying age-related changes in neuronal functions and synaptic plasticity. These mechanisms can fine-tune the dynamics of long-term chromatin remodeling, or control weakening and the loss of synaptic connections in aging. At the same time our genomic tests revealed evolutionarily conserved gene clusters associated with aging (e.g., apoptosis-, telomere- and redox-dependent processes, insulin and estrogen signaling and water channels).


O.R. custom packs: no easy answers.
The use of custom sterile packs continues to grow in popularity as hospitals look for different ways to reduce the cost of providing health care services. Mounting evidence appears to indicate, however, that the real beneficiaries of custom packs and the vendors themselves.


An algorithm for haplotype analysis.
This paper proposes an algorithm for haplotype analysis based on a Monte Carlo method. Haplotype configurations are generated according to the distribution of joint haplotypes of individuals in a pedigree given their phenotype data, via a Markov chain Monte Carlo algorithm. The haplotype configuration which maximizes this conditional probability distribution can thus be estimated. In addition, the set of haplotype configurations with relatively high probabilities can also be estimated as possible alternatives to the most probable one. This flexibility enables geneticists to choose the haplotype configurations which are most reasonable to them, allowing them to include their knowledge of the data under analysis.


From bed-blocking to delayed discharges: precursors and interpretations of a contested concept.
Delayed hospital discharges have been identified as a problem for the English National Health Service and have prompted several policy and service development responses in the last decade. However, bed-blocking is an issue surrounded by rival interpretations on how and why hospital delays occur and the way in which they are measured. To better understand this contested concept, this paper provides a brief description of the historical accounts that framed the emergence of delayed hospital discharges as a phenomenon. Three key features of the bed-blocking concept are also analysed: the reduction of patients' length of stay to improve efficiency, the intrinsic methodological difficulties of measuring hospital delays and the most common reasons for delayed discharges. A description of the characteristics of the patients frequently labelled as delayed discharge, their common traits and how these have been examined by previous research is also provided. Finally, this paper argues that the presence of hospital delays in a health system tends to be considered as an indicator of two possible system inefficiencies: a failure in the discharge planning process, which generally blames social services departments for not ensuring timely services, or a shortage of alternative forms of care for this group of patients.


Incidence, Nature, and Consequences of Oncologists' Experiences With Sexual Harassment.
The incidence and impact of workplace sexual harassment (SH) of oncologists requires rigorous characterization. Oncologists identified by ASCO's Research Survey Pool and social media outreach completed validated measures of SH (encompassing gender harassment, unwanted sexual attention, and sexual coercion) and four outcomes (mental health, job satisfaction, turnover intentions, and sense of workplace safety) over the previous year. Multivariable regression models assess the impact of SH on the four outcomes. Of 271 cisgender respondents (153 women and 118 men), 189 (70%) experienced SH in the past year alone by peers and/or superiors (80% of women v 56% of men, P < .0001). Specifically, 186 (69%) experienced gender harassment (79% of women, 55% of men, P < .0001), 45 (17%) unwanted sexual attention (22% of women, 9% of men, P = .005), and 7 (3%) sexual coercion (3% of women, 2% of men, P = .42). SH by patients and/or families in the past year was experienced by 143 (53% overall: 67% of women, 35% of men, P < .0001). Specifically, 141 (52%) experienced gender harassment (66% of women, 34% of men, P < .0001), 15 (6%) unwanted sexual attention (5% of women, 6% of men, P = .80), and 3 (1%) sexual coercion (1% of women, 1% of men, P = .72). Multivariable analysis showed that past-year SH by peers and/or superiors was significantly associated with decreased mental health (β = -0.45, P = .004), sense of workplace safety (β = -0.98, P < .001), and job satisfaction (β = -0.69, P = .001), along with increased turnover intentions (β = 0.93, P < .0001). Past-year SH by patients and/or families was significantly associated with decreased mental health (β = -0.41, P = .002), sense of workplace safety (β = -0.42, P = .014), and increased turnover intentions (β = 0.58, P = .0004). There were no significant interactions between the respondents' gender and the SH scores in any of the four outcome models, signifying no difference in impact between men and women oncologists. This study using validated measures of SH to systematically characterize oncologists' workplace experience demonstrates substantial incidence of SH in the previous one year alone and its impact on men and women oncologists, informing the need for and design of effective protective and preventive measures.


Minimally aortic valve surgery avoiding sternotomy.
Minimally invasive valve surgery, although still in its pioneer era, can open new horizons in cardiac surgery. Following that trend we started aortic valve surgery through a right anterior minithoracotomy using a novel approach under 3-D video-assistance in most of the cases. Aortic valve replacement avoiding sternotomy through a right thoracotomy was performed in seven patients (14% were female, average age: 58 years) There were five aortic stenoses and two aortic insufficiencies. In four patients we employed central aortic and right atrium cannulation and in three, femoral artery returns. Antegrade cardioplegia was used in all patients. The operative mortality was 0%, four patients received a mechanical aortic valve, two patients received a biological valve, and in one patient a decalcification of the valve was performed. The mean pump time was 110 min (70-146), the mean cross-clamp time was 72 min (52-95), the mean hospital stay was 7.7 days (4-11 days). One patient died 7 months after the operation of pulmonary insufficiency, the rest of the patients are alive and improved the clinical situation. This access produces an operative view adequate to safely perform aortic valve surgery. Therefore, removal of ribs or cartilage fragments is not necessary, which results in a less traumatic and less painful approach. Within this is a potential good approach for patients with sternal problems (radiation), redo in certain situations (example previous coronary surgery with LIMA open to LAD). Young patients are potential candidates for future coronary surgery as well as patients with long thoracic cavity and deep aortic plane.


Post-acne erythema treatment: A systematic review of the literature.
Post-acne erythema (PAE) is a common sequela of acne inflammation, and it refers to telangiectasia and erythematous lesions remaining after the acne treatment. Although some PAE lesions may improve over time, persisting PAE might be esthetically undesirable for patients. The efficacy of various treatment options for PAE has been investigated in many studies but there exists no gold standard treatment modality. In this study, we aimed to give a systematic literature review on various treatment options for PAE, the advantage of each modality, and compare their efficacy, safety, and feasibility. By using the selected keywords, we carried out a systematic search for articles published from the inception to 28 April 2021 in PubMed/Medline and Embase databases. Of the 5796 initially retrieved articles, 18 of them were fully eligible to be enrolled in our study. In this study, we found that light and laser-based devices were the most frequently used treatments for PAE. Generally, pulsed-dye lasers were the most commonly used laser devices for PAE. Neodymium:yttrium aluminum-garnet lasers were the second most commonly used modalities in treating PAE. Topical treatments such as oxymetazoline, tranexamic acid, and brimonidine tartrate are promising treatments in reducing PAE lesions. In our study, no severe side effects were found. In conclusion, both laser devices and topical agents seem to be effective for PAE lesions; however, further randomized clinical trials are needed in this field.


The nonequilibrium mechanism for ultrasensitivity in a biological switch: sensing by Maxwell's demons.
The Escherichia coli flagellar motor senses the intracellular concentration of the response regulator CheY-P and responds by varying the bias between its counterclockwise (CCW) and clockwise (CW) rotational states. The response is ultrasensitive with a large Hill coefficient (approximately 10). Recently, the detailed distribution functions of the CW and the CCW dwell times have been measured for different CW biases. Based on a general result on the properties of the dwell-time statistics for all equilibrium models, we show that the observed dwell-time statistics imply that the flagellar motor switch operates out of equilibrium, with energy dissipation. We propose a dissipative allosteric model that generates dwell-time statistics consistent with the experimental results. Our model reveals a general nonequilibrium mechanism for ultrasensitivity wherein the switch operates with a small energy expenditure to create high sensitivity. In contrast to the conventional equilibrium models, this mechanism does not require one to assume that CheY-P binds to the CCW and CW states with different affinities. The estimated energy consumption by the flagellar motor switch suggests that the transmembrane proton motive force, which drives the motor's rotation, may also power its switching. The existence of net transitional fluxes between microscopic states of the switch is predicted, measurement of these fluxes can test the nonequilibrium model directly. Both the results on the general properties of the dwell-time statistics and the mechanism for ultrasensitivity should be useful for understanding a diverse class of physical and biological systems.


Organ donation: who holds the key?
All health care providers must share the responsibility for educating health professionals and the lay public about the need for donor organs and the process of donation. PAs should become familiar with the procedures involved, including the protocol for diagnosing brain death, the criteria by which potential organ donors are identified, the maintenance of organs in vitro, and the methods of preserving procured organs for transplantation. PAs are urged to become active in procurement/transplantation programs at their institutions or by working with a procurement agency to establish a program if one does not already exist. In addition, PAs should become familiar with the laws that govern organ donations in their states.


Music Therapy Practice Status and Trends Worldwide: An International Survey Study.
The field of music therapy is growing worldwide. While there is a wealth of country-specific information available, only a few have databased workforce censuses. Currently, little to no descriptive data exists about the global development of the profession. The purpose of this study was to obtain descriptive data about current demographics, practice status, and clinical trends to inform worldwide advocacy efforts, training needs, and the sustainable development of the field. Music therapists (N = 2,495) who were professional members of organizations affiliated with the World Federation of Music Therapy (WFMT) served as a sample for this international cross-sectional survey study. A 30-item online questionnaire was designed, pilot tested by key partners, and translated into seven languages. Researchers and key partners distributed the online survey through e-mail invitations and social media announcements. Professional music therapists worldwide are well-educated, mature professionals with adequate work experience, who are confident in providing high-quality services primarily in mental health, school, and geriatric settings. Due to ongoing challenges related to recognition and government regulation of the field as an evidence-based and well-funded healthcare profession, most individuals work part-time music therapy jobs and feel underpaid. Yet, many music therapists have a positive outlook on the field's future. Continued research and advocacy efforts, as well as collaborations with lobbyists, business consultants, and credentialing/licensure experts to develop progressive strategies, will be crucial for global development and sustainability of the field.


Synthesis and Crosslinking of Polyether-Based Main Chain Benzoxazine Polymers and Their Gas Separation Performance.
The poly(ethylene glycol)-based benzoxazine polymers were synthesized via a polycondensation reaction between Bisphenol-A, paraformaldehyde, and poly(ether diamine)/(Jeffamine®). The structures of the polymers were confirmed by proton nuclear magnetic resonance spectroscopy (¹H-NMR), indicating the presence of a cyclic benzoxazine ring. The polymer solutions were casted on the glass plate and cross-linked via thermal treatment to produce tough and flexible films without using any external additives. Thermal properties and the crosslinking behaviour of these polymers were studied by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Single gas (H₂, O₂, N₂, CO₂, and CH₄) transport properties of the crosslinked polymeric membranes were measured by the time-lag method. The crosslinked PEG-based polybenzoxazine membranes show improved selectivities for CO₂/N₂ and CO₂/CH₄ gas pairs. The good separation selectivities of these PEG-based polybenzoxazine materials suggest their utility as efficient thin film composite membranes for gas and liquid membrane separation technology.


Glycoprotein receptor inhibitors in the management of acute coronary syndromes.
Coronary thrombosis and the risk of clinical adverse events remains high despite considerable advances in the management of acute coronary syndromes (ACS) with the combined use of aspirin, heparin, fibrinolytic therapy, and percutaneous coronary intervention (PCI). Platelet aggregation and thrombosis play a key role in the pathogenesis of unstable coronary syndromes. Over the past several years, multiple placebo-controlled trials involving more than 50,000 ACS patients have shown that blockade of the platelet receptor glycoprotein (GP) IIb/IIIa, the final pathway in platelet aggregation, reduces the incidence of ischemic complications among patients with ACS. Three agents (abciximab, eptifibatide, and tirofiban) are currently approved for use with aspirin and heparin in the management of ACS or during percutaneous coronary intervention. They have consistently been shown to reduce the incidence of death or myocardial infarction in the ACS population including the patients not routinely scheduled for early revascularization. They provide an augmented treatment effect among high-risk ACS patients, particularly those who have a baseline troponin-t-positive status. Recently published practice guidelines have recommended their use in high-risk patients with ACS and all those undergoing PCI.


Role of diesel exhaust particles in the induction of allergic asthma to low doses of soybean.
Exposure to environmental pollutants such as diesel exhaust particles (DEP) increases the risk of asthma and asthma exacerbation. However, the exact mechanisms inducing asthma to low doses of allergens remain poorly understood. The present study aimed to analyse the immunomodulatory effect of the inhalation of DEP in a mouse model exposed to non-asthmagenic doses of soybean hull extract (SHE). BALB/c ByJ mice were randomly divided into four experimental groups. Two groups received nasal instillations of saline and the other two groups received 3 mg ml-1 SHE during 5 days per week for 3 weeks. One group in each pair also received 150 μg of DEP in the same instillations 3 days per week. SHE-specific IgE levels, oxidative stress, leukocyte pattern and optical projection tomography (OPT) imaging studies were assessed. Inhalation of SHE and/or DEP increased levels of H2O2 in BAL, while coexposure to SHE and DEP increased SHE-specific IgE levels in serum. Inhalation of SHE alone increased eosinophils, B cells, total and resident monocytes and decreased levels of NK cells, while inhalation of DEP increased neutrophils and decreased total monocytes. Regarding dendritic cells (DC), the inhalation of SHE and/or DEP increased the total population, while the inhalation of SHE alone increased Th2-related DCs (CD11b + Ly6C-) and decreased tolerogenic DCs (CD11b-Ly6C-). However, coexposure to SHE and DEP increased oxidative stress-sensitive DCs (CD11b-Ly6C+) and decreased Th1-related DCs (CD11b + Ly6C+). As regards macrophages, inhalation of SHE and DEP decreased total and alveolar populations. DEP deposition in lung tissue did not differ between groups. Coexposure to DEP activates the asthmatic response to low doses of soy by triggering the immune response and oxidative stress.


Long-Term Efficacy, Safety, and Pharmacokinetics of Drisapersen in Duchenne Muscular Dystrophy: Results from an Open-Label Extension Study.
Drisapersen induces exon 51 skipping during dystrophin pre-mRNA splicing and allows synthesis of partially functional dystrophin in Duchenne muscular dystrophy (DMD) patients with amenable mutations. This 188-week open-label extension of the dose-escalation study assessed the long-term efficacy, safety, and pharmacokinetics of drisapersen (PRO051/GSK2402968), 6 mg/kg subcutaneously, in 12 DMD subjects. Dosing was once weekly for 72 weeks. All subjects had a planned treatment interruption (weeks 73-80), followed by intermittent dosing (weeks 81-188). Subjects received a median (range) total dose of 5.93 (5.10 to 6.02) mg/kg drisapersen. After 177 weeks (last efficacy assessment), median (mean [SD]) six-minute walk distance (6MWD) improved by 8 (-24.5 [161]) meters for the 10 subjects able to complete the 6MWD at baseline (mean age [SD]: 9.5 [1.9] years). These statistics include 2 subjects unable to complete the test at later visits and who scored "zero". When only the 8 ambulant subjects at week 177 were taken into account, a median (mean [SD]) increase of 64 (33 [121]) meters in 6MWD was observed. Of 7 subjects walking ≥330 m at extension baseline, 5 walked farther at week 177. Of 3 subjects walking <330 m, 2 lost ambulation, while 1 declined overall but walked farther at some visits. Over the 188 weeks, the most common adverse events were injection-site reactions, raised urinary α1-microglobulin and proteinuria. Dystrophin expression was detected in all muscle biopsies obtained at week 68 or 72. Drisapersen was generally well tolerated over 188 weeks. Possible renal effects, thrombocytopenia and injection-site reactions warrant continued monitoring. Improvements in the 6MWD at 12 weeks were sustained after 3.4 years of dosing for most patients. For a small, uncontrolled study, the outcomes are encouraging, as natural history studies would anticipate a decline of over 100 meters over a 3-year period in a comparable cohort. ClinicalTrials.gov NCT01910649.


[Effect of expectancies on negative mood regulation].
The role of expectancies regarding negative mood regulation in improving the mood states of undergraduate students when they experience both negative and positive life events was investigated. In Study 1, a Japanese language scale for measuring expectancies for negative mood regulation (NMR scale) was developed. In Study 2, undergraduates (n = 95) completed the NMR scale twice within an interval of five-weeks. They also completed a self-rating depression scale and a scale of life events in interpersonal and achievement domains. The results indicated that participants with high NMR scores did not experience depression when they faced negative events, if they concurrently experienced positive life events. These results suggest that expectancies for negative mood regulation alleviate the negative mood states by using a mood regulation strategy moderated by positive life events, and predict the level of depression.


Van der Waals interactions: evaluations by use of a statistical mechanical method.
In this work the induced van der Waals interaction between a pair of neutral atoms or molecules is considered by use of a statistical mechanical method. With use of the Schrödinger equation this interaction can be obtained by standard quantum mechanical perturbation theory to second order. However, the latter is restricted to electrostatic interactions between dipole moments. So with radiating dipole-dipole interaction where retardation effects are important for large separations of the particles, other methods are needed, and the resulting induced interaction is the Casimir-Polder interaction usually obtained by field theory. It can also be evaluated, however, by a statistical mechanical method that utilizes the path integral representation. We here show explicitly by use of this method the equivalence of the Casimir-Polder interaction and the van der Waals interaction based upon the Schrödinger equation. The equivalence is to leading order for short separations where retardation effects can be neglected. In recent works [J. S. Høye, Physica A 389, 1380 (2010); Phys. Rev. E 81, 061114 (2010)], the Casimir-Polder or Casimir energy was added as a correction to calculations of systems like the electron clouds of molecules. The equivalence to van der Waals interactions indicates that the added Casimir energy will improve the accuracy of calculated molecular energies. Thus, we give numerical estimates of this energy including analysis and estimates for the uniform electron gas.


Valganciclovir for the Suppression of Epstein-Barr Virus Replication.
Epstein-Barr virus (EBV) causes infectious mononucleosis and can lead to lymphoproliferative diseases. We evaluated the effects of valganciclovir on oral EBV shedding in a randomized, double-blind, placebo-controlled study. Twenty-six men received oral valganciclovir or daily placebo for 8 weeks, followed by a 2-week "washout period" and then 8 weeks of the alternative treatment. Valganciclovir reduced the proportion of days with EBV detected from 61.3% to 17.8% (relative risk, 0.28; 95% confidence interval [CI], .21-.41; P < .001), and quantity of virus detected by 0.77 logs (95% CI, .62-.91 logs; P < .001). Further investigations into the impact of valganciclovir on EBV-associated diseases are needed.


Proteolytic activity of Aeromonas caviae.
Aeromonas strains produce a variety of virulence factors including proteases. Studies on the kinetics of growth of Aeromonas caviae NRRL B-966 and its proteases suggest that the proteolytic activities are produced throughout the growth phase, with peak level occurring at stationary phase. A. caviae synthesize both intracellular and extracellular proteases with the latter account for major portion of the total activity. Optimum pH for the A. caviae proteolytic activity is at 7.0. A. caviae produces a thermoresistant protease, whose activity is dependent on Mg++ and Ca++ ions. Inhibition of proteolytic activity by phenyl methyl sulfonyl fluoride suggest the presence of a serine protease in A. caviae. Nitrogenous compounds enhance the proteolytic activity while carbohydrates tested in this study inhibit the activity.


LC-ESI-MS/MS method for quantification of ambrisentan in plasma and application to rat pharmacokinetic study.
A sensitive high-performance liquid chromatography-positive ion electrospray tandem mass spectrometry method was developed and validated for the quantification of ambrisentan in plasma. The analyte and the internal standard (armodafinil) were extracted from plasma by acetonitrile precipitation and they were separated on a reversed-phase C(18) column with a gradient program. The MS acquisition was performed with multiple reaction monitoring mode using the respective [M + H](+) ions, m/z 379-347 for ambrisentan and m/z 274-167 for the IS. The assay exhibited a linear dynamic range of 1-2000 ng/mL for ambrisentan in plasma. Acceptable precision (<10%) and accuracy (100 ± 8%) were obtained for concentrations over the standard curve range. The method was successfully applied to quantify ambrisentan concentrations in a rodent pharmacokinetic study after a single oral administration of ambrisentan at 2.5 mg/kg to rats. Following oral administration the maximum mean concentration in plasma (C(max) ; 1197 ± 179 ng/mL) was achieved at 1.0 ± 0.9 h (T(max) ), and the area under the curve (AUC) was 6013 ± 997 ng h/mL. Therefore, development of such a simple and sensitive method in rat plasma should translate into a method for ambrisentan in human plasma for clinical trials.


Seasonal congestive heart failure mortality and hospitalisation trends, Quebec 1990-1998.
To describe seasonal congestive heart failure (CHF) mortality and hospitalisations in Quebec, Canada between 1990-1998 and compare trends in CHF mortality and morbidity with those in France. Population cohort study. Province of Quebec, Canada. Mortality data were obtained from the Quebec Death Certificate Registry and hospitalisation from the Quebec Med-Echo hospital discharge database. Cases with primary ICD-9 code 428 were considered cases of CHF. Monthly CHF mortality was higher in January, declined until September and then rose steadily (p<0.05). Hospital admissions for CHF declined from May until September (moving averages analysis p<0.0001). Seasonal mortality patterns observed in Quebec were similar to those observed in France. CHF mortality in Quebec is highest during the winter and declines in the summer, similar to observations in France and Scotland. This suggests that absolute temperatures may not necessarily be that important but increased CHF mortality is observed once environmental temperatures fall below a certain "threshold" temperature. Alternatively better internal heating and warmer clothing required for survival in Quebec may ameliorate mortality patterns despite colder external environments.


The community's tolerance of the mentally ill.
A survey of attitudes to mental illness was conducted in a quota sample of about 2000 subjects in Malvern and Bromsgrove. Factor analysis showed three main components - benevolence, authoritarianism, and fear of the mentally ill. Residents of Bromsgrove, which is served by a traditional mental hospital, were slightly more tolerant than those living in Malvern, which has a community-based service, and has seen the closure of two mental hospitals in its vicinity during the last 10 years. The main demographic determinants of tolerance are age, education, occupation, and acquaintance with the mentally ill.


[Combined effects of alpha-interferon and anticancer drugs against renal cell carcinoma].
The direct antitumor effects of combined administration of alpha-interferon and chemotherapeutic agents against the human tumor cell line derived from renal cell carcinoma were examined in vivo as xenograft in nude mice. The administration regimen was as follows: Human lymphoblastoid interferon (HLBI) was injected intramuscularly (1 x 10(5) IU/mouse/day) every day for 14 days. Peplomycin (PEP), adriamycin (ADM), or 5-fluorouracil (5-FU) was also administered at a dose of one third of their LD50. We evaluated the effect 20 days after initial administration using the ratio of mean tumor weight. Combined administration of HLBI and PEP or ADM was determined effective and inhibited tumor growth more strongly than HLBI alone or control. Furthermore, the histopathological examination suggested that the effect of combined administration was cytostatic rather than cytolytic.


Chronic hepatitis C and Crohn's disease: nosocomial infection treatment with PEG-interferon plus ribavirin.
We describe the case of a patient with a diagnosis of Crohn's disease and accidental infection during abdominal surgery by hepatitis C virus (HCV) who received combination therapy with pegylated interferon-alpha2b (1.5 microg/kg weekly) plus ribavirin (10.6 mg/kg daily) for histologically demonstrated chronic hepatitis C. After 48 weeks treatment, serum transaminase levels were normal and viremia (HCV RNA) was negative (end-of-treatment response); 24 weeks later (follow-up period), a sustained virological response was demonstrated. The tolerance to combination antiviral therapy was good, without intestinal symptoms of inflammatory bowel disease recurrence. We conclude that current antiviral therapies with immunomodulatory effects may be helpful and safe for patients with inflammatory bowel disease infected by hepatitis C virus.


Growing pains: are they due to increased growth during recumbency as documented in a lamb model?
The rate and patterns of longitudinal bone growth are affected by many different local and systemic factors; however, uncompromised growth is usually considered to be smoothly continuous, with predictable accelerations and decelerations over periods of months to years. The authors used implanted microtransducers to document bone growth in immature lambs. Bone length measurements were sampled every 167 seconds for 21 to 25 days. The authors show that at least 90% of bone elongation occurs during recumbency and almost no growth occurs during standing or locomotion. The authors hypothesize that growth may also occur in children during rest or sleep, thus supporting the concept of nocturnal growth and perhaps a relationship to growing pains.


Rheumatoid arthritis after Takayasu's arteritis.
The association of Takayasu's arteritis with other rheumatic disease is rare. We report a 37-year-old female who developed Takayasu's arteritis in her 20s and subsequently developed rheumatoid arthritis.


Contrastive study for coadsorption of copper and two dihydroxybenzene isomers by a multi-amine modified resin.
Coadsorption of Cu(II) and two dihydroxybenzene isomers (hydroquinone, HQ and catechol, CAT) onto a multi-amine modified resin (CEAD) were comparatively studied. The presence of Cu(II) promoted adsorption of both HQ and CAT by a maximum of 25.8% and 41.6%, respectively. However, two diphenols exerted a very different influence on Cu(II) uptake. Higher concentrations of HQ consistently suppressed Cu(II) adsorption while the coexistence of CAT facilitated it, especially at lower CAT concentrations. The interactions among solutes and adsorbents were revealed by means of kinetic tracking, sequential adsorption experiments, and characterizations/calculations (FTIR, XPS, MINTEQ and DFT). Cu(II) and HQ/CAT competed for amine sites with the order of adsorption affinity as HQ > Cu(II) > CAT. The bridging effect of Cu(II) forming ternary complexes (amine-Cu-CAT/HQ) on the resin phase was the dominant mechanism for the enhanced adsorption of diphenols. The [Cu-CAT] complex species showed a lower affinity to bind directly to amine sites compared with free Cu2+. Instead, the complex could be attracted by the polyphenyl matrix of CEAD, contributing to the increase of Cu(II) adsorption. Additionally, Cu(II) and diphenols were successively recovered, and CEAD could be stably reused. The findings will guide adsorbent applications and the environmental fate of concurrent heavy metals and phenolic compounds.


Comparison of Incidence of Urinary Tract Infection in Diabetic vs Non-Diabetic and Associated Pathogens.
Introduction Urinary tract infections (UTIs) are common in low socioeconomic country like Pakistan. There are various factors responsible for UTI, one major factor being diabetes. This study aims to compare diabetic and non-diabetic patients, for gender association, symptoms, and organisms, with UTI. Methods This cross-sectional study was conducted in the medicine ward of tertiary care hospital in Pakistan from January 2019 to December 2019. For urine analysis, freshly voided 5-10 ml of clean midstream urine specimens was collected in a sterile container. Samples were sent to the lab immediately, A colony count of ≥105 CFU/ml was considered for the diagnosis of UTI. Culture was done if UTI was diagnosed. Results The overall incidence of UTI in participants of the diabetic group was significantly higher than those in the non-diabetic group (13.67% vs 6.40%; P=0.004). Escherichia coli was the most common organism in both the diabetic and non-diabetic groups (60% vs 72%; P=0.73). Frequency of Klebsiella was considerably higher in the participants of diabetes but it was not significant (23.3% vs 11.1%; P=0.29). Conclusion UTI was significantly higher in the diabetic population compared to the non-diabetic population. Since diabetes is prevalent in Pakistan, care of diabetes should include reducing the risk factors for UTI.


Small angle X-ray scattering study of S100 proteins.
Small-angle X-ray scattering of both S100b and a mixture of S100a and S100ao (S100a,ao) was measured over a protein concentration range of 1.5 to 10.0 mg/ml. The addition of trifluoroperazine (TFP) to S100 solutions suppressed higher aggregation under the conditions studied. In the presence of TFP (1 mol TFP/mol of protein dimer), the radius of gyration of S100b and S100a,ao is found to be 19.5 +/- 0.3A and 20.2 +/- 0.3A, respectively, indicating that most S100 proteins may exist as dimers under the conditions studied. The observed difference (0.7 +/- 0.3A) in the radius of gyration between S100b and S100a,ao indicates that these dimers have different, asymmetrical shapes.


The Effect of Porcelain Firing on Electrochemical Behavior of a Dental Alloy in Hydrogen Peroxide.
The aim of this study was to evaluate changes in electrochemical corrosion properties of porcelain firing simulated nickel-chromium dental casting alloy exposed to a 10% hydrogen peroxide bleaching agent. The electrochemical corrosion behavior of a Ni-Cr alloy was evaluated by cyclic polarization test in the aerated electrolyte (pH = 6.5). Test groups were produced in as-cast (group 1, control group) and simulated porcelain firing (group 2: heat-treated/mean value; group 3: heat-treated/cycle) conditions. Scanning electron microscopy (SEM) was also used to examine the alloy surfaces before and after the corrosion test. The ranking of the groups with respect to Ecorr and Icorr was as follows: 1, 2, 3 and 3, 1, 2, respectively. Group 3 exhibited the greatest and group 2 displayed the least corrosion tendencies. An increase in corrosion rates was observed after heat treatment/cycle state. Post-corrosion SEM photographs were also consistent with the test results. Within the parameters of this study, a single heat treatment is insufficient to cause upheaval in corrosion behavior of a Ni-Cr alloy subjected to 10% hydrogen peroxide.


Resolution 64/85, 1985.
This Resolution provides that the Argentine social program on behalf of women and the family has the following objectives: to study the situation of women and the family in the legal, labor, educational, cultural, health and socioeconomic areas; to collect information and documentation regarding women and the family for use in the establishment of a data bank capable of serving as a basis for the formulation of programs and standards designed to achieve the full involvement of women in social planning; to prepare reports and support measures contributing to the elimination of existing discrimination against women in society; to promote the involvement of women in organized community activities aimed at improving the quality of life of the population; to promote the technical and occupational training of women in accordance with their psychosocial characteristics and the requirements of the labor market; to promote, in the communication media, a change in the image of women more in keeping with their actual role at the present time; to develop basic, nontraditional support services for women designed to bring about improvements in the conditions of family and occupational life and to eliminate instances of social discrimination against women; and to coordinate and monitor activities of promotion, prevention, or treatment on behalf of families in critical situations or vulnerability due to their socioeconomic circumstances.


[HLA typing in extrinsic allergic alveolitis].
The present conceptions about the genetic mechanisms in the predisposition to extrinsic allergic alveolitis are summarized in a review. The major complex of histocompatibility is shortly characterized and the method of HLA-typing is described. The own results of HLA-typing in poultry farm workers are compared with the data from the literature on patients with pigeon-, budgerigar-keepers-disease and farmer's lung. Persons with HLA-B8- or/and DR3-antigens seem to be predisposed to extrinsic allergic alveolitis. The importance of the investigations for the preventive medicine is stressed.


Molecular cloning, developmental expression, and cellular localization of the 70-kDa RPA-1 subunit of Drosophila melanogaster.
Replication protein A (RPA) is a highly conserved multifunctional heterotrimeric complex, involved in DNA replication, repair, recombination, and possibly transcription. Here, we report the cloning of the gene that codes for the largest subunit of the Drosophila melanogaster RPA homolog, dmRPA70. In situ hybridization showed that dmRPA70 RNA is present in developing embryos during the first 16 cycles. After this point, dm-RPA70 expression is downregulated in cells that enter a G1 phase and exit the mitotic cycle, becoming restricted to brief bursts of accumulation from late G1 to S phase. This pattern of regulated expression is also observed in the developing eye imaginal disc. In addition, we have shown that the presence of cyclin E is necessary and sufficient to drive the expression of dmRPA70 in embryonic cells arrested in G1 but is not required in tissues undergoing endoreduplication. Immunolocalization showed that in early developing embryos, the dmRPA70 protein associates with chromatin from the end of mitosis until the beginning of the next prophase in a dynamic speckled pattern that is strongly suggestive of its association with replication foci.


Leukotriene receptor antagonism and augmentation of beta-receptor-mediated events by LY171883.
LY171883, (1-[2-hydroxy-3-propyl-4-[4(1H-tetrazol-5-yl)butoxy)phenyl]etha none), a leukotriene (LT) D4/E4 receptor antagonist, was assessed in comparison with two well known phosphodiesterase inhibitors, isobutylmethyl-xanthine (IBMX) and theophylline, for its ability to augment beta-receptor-mediated responses. Relaxation of carbachol-contracted guinea-pig trachea by isoprenaline was enhanced by the three agents in a dose-dependent manner. A two-fold enhancement of isoprenaline-induced smooth muscle relaxation was produced by 2.5 microM IBMX, 28 microM LY171883, or 140 microM theophylline. Similar concentrations of IBMX or theophylline did not antagonize LTE4-induced tracheal contractions; LY171883 totally inhibited the response and had significant LTE4 receptor antagonist activity even at 10-fold lower concentrations. Antigen-induced release of histamine and LTC4 from guinea-pig lung was reduced by isoprenaline. Prior treatment with LY171883, IBMX, or theophylline did not enhance this action. Isoprenaline reduced histamine-induced bronchospasm in anaesthetized guinea-pigs. LY171883, 30 mg kg-1, or IBMX, 1 mg kg-1, did not affect the isoprenaline-induced decrease in the histamine response. IBMX, 3 mg kg-1, and theophylline, 30 mg kg-1, augmented the isoprenaline-induced bronchodilation. LTE4-induced bronchoconstriction was not affected by IBMX or theophylline whereas LY171883 antagonized this response at doses as low as 3 mg kg-1. Therefore, in both in-vitro and in-vivo test systems, LY171883 functioned primarily as a leukotriene receptor antagonist with minimal pharmacological activity attributable to its ability to potentiate isoprenaline.


A novel approach for directing transgene expression in Drosophila: T2A-Gal4 in-frame fusion.
In Drosophila, the Gal4-UAS system permits a transgene to be expressed in the same pattern as a gene of interest by placing the Gal4 transcription factor under control of the gene's DNA regulatory elements. If these regulatory elements are not known, however, expression of Gal4 in the desired pattern may be difficult or impossible. To solve this problem, we have developed a method for co-expressing Gal4 with the endogenous gene by exploiting the "ribosomal skipping" mechanism of the viral T2A peptide. This method requires explicit knowledge only of the endogenous gene's open reading frame and not its regulatory elements.


Aural-pharyngeal polyps associated with Cryptosporidium infection in three iguanas (Iguana iguana).
Cryptosporidium spp. infection was associated with aural-pharyngeal polyps in three iguanas (Iguana iguana). All iguanas were presented for masses protruding from the ear canal, and the disease was characterized by a chronic clinical course. The masses consisted of nests of cystic glands surrounded by abundant fibrous connective tissue and lined by hyperplastic cuboidal to pseudostratified columnar epithelium that was moderately to heavily colonized by cryptosporidial organisms. Electron microscopy revealed that the majority of organisms were trophozoites.


Lessons learned from the analysis of 200 laparoscopic sigmoid resections for diverticulitis.
Since the beginning of laparoscopic surgery indications for laparoscopic colon resections are still discussed controversively. In the latest studies benefit for laparoscopic approach is reported. The aim of this study was to evaluate the feasibility of laparoscopic sigmoid resections for diverticulitis regarding conversion rate, operation time and intraoperative and postoperative complications, and defining strategies to prevent complications. Out of a prospective database with all laparoscopic colon resection between May 1999 and January 2008 the patients with laparoscopic sigmoid resection for diverticulitis were analyzed. Preoperative diagnosis was made by abdominal computed tomography with irrigoscopy and/or endoscopy. Indications for laparoscopic sigmoid resections were diverticulitis as an early elective or elective operation and selected cases with perforated diverticulitis. Between May 1999 and January 2008, 200 patients (97 women, 103 men) were operated by laparoscopy for diverticulitis. Mean age at surgery was 59 years (range: 27 to 86); mean preoperative body mass index was 27.2 kg/m2 (range: 20 to 38). Mean operating time was 121 minutes (range: 60 to 239). Operating time was reduced due to experience and dropped from a mean of 150 minutes for the first 50 patients, 115 minutes for the second, 110 minutes for the third, and 107 minutes for the last 50 patients (P<0.05). Conversion rate was 1.5%, total morbidity rate was 19%, and reoperation rate was 6%. Laparoscopic sigmoid resections for diverticulitis can be performed with great safety and low conversion rate. Several adjustments in operation technique and perioperative management had to be done to achieve a complication rate and conversion rate at an acceptable low level.


Reduction of cell proliferative activities of gastric stump adenomatous hyperplasias after bile reflux diversion in rats.
Previously we reported the majority of lesions induced by bile reflux, in the absence of chemical carcinogens, in the rat remnant stomach to consist primarily of gastric type and secondarily of intestinal type cells, and that they are reversible after diversion of bile reflux. The present study was designed to evaluate changes in proliferative activities in cells of each type under these conditions. The frequency of adenomatous hyperplasia (AH) induced in the gastric stump mucosa by duodenal content reflux after Billroth II partial gastrectomy (BII) increased until the 54th week of the experiment. Roux-en-Y (RY) surgical procedure which prevents duodenal reflux performed at the 24th or 36th week after BII led to a decrease in AH. Cell content of the lesions was analyzed using routine H&E staining, immunohistochemical staining for pepsinogen isoenzyme 1 and histochemical procedures for mucins (paradoxical concanavalin A, galactose oxidase Schiff and sialidase galactose oxidase Schiff reactions) and proliferation in each compartment evaluated by an immunohistochemical method using bromodeoxyuridine (BrdU) and a monoclonal antibody against BrdU. At the 54th week the number of BrdU-labeled cells per normal pyloric column was significantly (P < 0.05) increased to 10.63/pit after the BII operation, while it diminished to 5.23/pit after RY diversion, this being the same level as with the RY procedure alone. AH maintained a high rate of BrdU incorporation at 12.7% after BII operation, which was also significantly reduced (P < 0.01) to 7.0% by the RY surgery. The intestinal type cell showed highest (22.2%), the surface mucous type cell showed the next (16.5%) and the pyloric gland type cell showed lowest (5.2%) BrdU labeling indices after BII operation. All the cell types in AH showed similar proportional decreases in BrdU incorporation after RY diversion. Thus surgical intervention reverses the cell proliferation caused by bile reflux in the gastric stump.


A thermodynamic study of unusually stable RNA and DNA hairpins.
About 70% of the RNA tetra-loop sequences identified in ribosomal RNAs from different organisms fall into either (UNCG) or (GNRA) families (where N = A, C, G, or U; and R = A or G). RNA hairpins with these loop sequences form unusually stable tetra-loop structures. We have studied the RNA hairpin GGAC(UUCG)GUCC and several sequence variants to determine the effect of changing the loop sequence and the loop-closing base pair on the thermodynamic stability of (UNCG) tetra-loops. The hairpin GGAG(CUUG)CUCC with the conserved loop G(CUUG)C was also unusually stable. We have determined melting temperatures (Tm), and obtained thermodynamic parameters for DNA hairpins with sequences analogous to stable RNA hairpins with (UNCG), C(GNRA)G, C(GAUA)G, and G(CUUG)C loops. DNA hairpins with (TTCG), (dUdUCG), and related sequences in the loop, unlike their RNA counterparts, did not form unusually stable hairpins. However, DNA hairpins with the consensus loop sequence C(GNRA)G were very stable compared to hairpins with C(TTTT)G or C(AAAA)G loops. The C(GATA)G and G(CTTG)C loops were also extra stable. The relative stabilities of the unusually stable DNA hairpins are similar to those observed for their RNA analogs.


Histaminergic and non-histaminergic elicited itch is attenuated in capsaicin-evoked areas of allodynia and hyperalgesia: A healthy volunteer study.
Chronic pain patients with sensitization may exhibit decreased sensitivity to normally pruritogenic sensory stimuli and moreover occasionally perceive these as painful. This study explored the relationship between itch and pain, by evaluating histaminergic and non-histaminergic itch evoked in capsaicin-induced allodynic and hyperalgesic areas. In 28 healthy volunteers, capsaicin (100 μg/0.1 mL) was injected intradermally in the volar forearm to establish secondary dysesthesias. After the capsaicin-induced pain subsided, the areas of allodynia and hyperalgesia were mapped and itch was provoked inside these areas by histamine (10 mg/mL) and cowhage (25-40 spicules). The evoked itch and pain were recorded on a visual analogue scale (VAS 0-10 cm). Contralateral injection of 0.1 mL isotonic saline served as a control. Histaminergic and non-histaminergic evoked itch were significantly decreased when provoked in allodynic skin (p < 0.05). The area-under-the-curve of the evoked itch was reduced -43% from 18.0 ± 2.6 cm10 min in normal skin to 10.3 ± 1.8 cm10 min in allodynic skin (p < 0.01) for cowhage and -56% from 20.0 ± 3.5 cm10 min in normal skin to 8.8 ± 2.3 cm10 min allodynic skin (p < 0.001) for histamine. The pain responses to the pruritogens were not significantly altered between the areas of allodynia and normal skin (p > 0.1). An additional experiment showed that pinprick hyperalgesia in the absence of allodynia was sufficient to evoke the observed reduced sensitivity to itch stimuli. Cutaneous sensitization (secondary allodynia and hyperalgesia) reduced itch responses regardless of the type of itch model applied and without attenuation of the associated pruritogen-induced pain responses. This could explain the decreased sensitivity to itch provocations previously observed in patients with chronic pain. This study shows that the neuronal sensitization processes underlying the development secondary hyperalgesia involve significant gating of histaminergic as well as non-histaminergic pruriceptive transmission. Because these itch provocations normally target specific subpopulations of C-nociceptors they could be of relevance for exploratory purposes in pain patients.


Significance of ectodomain cysteine boxes 2 and 3 for the activation mechanism of the thyroid-stimulating hormone receptor.
Recently, we identified constitutively activating mutations at positions Asp-403, Glu-404, and Asn-406 in the third extracellular cysteine box (C-b3) of the thyroid-stimulating hormone receptor. We hypothesized that this region could act as a molecular interface between the extracellular and serpentine domain. In this study we present a model for properties of potential interaction partners for this region. Moreover, we show that Pro-400 and Pro-407 adjacent to this epitope are also important for stabilizing the partially active, basal conformation of the wild-type (WT) thyroid-stimulating hormone receptor. Furthermore, the mutation K291A in the second extracellular cysteine box (C-b2) was identified as a new constitutively activating mutation that releases the basal conformation of the WT receptor like the known tryptic cleavage in its close vicinity. Taken together, we provide an activation scenario at the C-b2/C-b3 unit. Three anchor fragments (anchors I-III) most likely constrain the basal conformation. The three anchor fragments are tightly packed. A disulfide bridge holds the C-b2/C-b3 portions in close positions. Independent of the type of conformational interference such as side chain modifications, tryptic cleavage, or hormone stimulation that act on the constrained C-b2/C-b3 WT conformation, it will always release one of the anchor fragments. Subsequently, this results in a conformational displacement of the C-b2/C-b3 portions relative to each other, inducing receptor activation.


The in situ architecture of Escherichia coli ribosomal RNA derived by electron spectroscopic imaging and three-dimensional reconstruction.
The structures of the large and small ribosomal subunits of Escherichia coli were reconstructed using spectroscopic electron microscopy and quaternion-assisted angular reconstitution to resolutions of better than 4 nm. In addition, the distributions of phosphorus within these complexes were reconstructed. The three-dimensional reconstruction of the distribution of this atomic element is an extension of microanalysis (in two dimensions) for phosphorus identification and mapping, as a signature of the arrangement of the phosphate backbones of the constituent ribosomal RNAs. The results on both the phosphorus reconstructions and the total reconstructions (protein and ribosomal RNA) reveal several passageways through both subunits. The structures correspond favourably with other independent reconstructions of the whole E. coli ribosome from cryoelectron micrographs and their accompanying models of translation (Frank et al., Nature, 376, 441-444, 1995; Stark et al., Structure, 3, 815-821, 1995). The overall reconstructions in conjunction with the phosphorus (rRNA) distributions are the first to be achieved synchronously for this nucleoprotein complex.


Deep tissue hypersensitivity to pressure pain in individuals with unilateral acute inversion ankle sprain.
The objective of this study was to investigate whether pressure hypersensitivity over deep tissues is a feature of acute inversion ankle sprain. This is a cross-sectional study. No study has previously investigated peripheral and central sensitization mechanisms in a clinical acute pain model such as inversion ankle sprain. Twenty individuals with unilateral inversion ankle sprain (10 women/10 men, age: 31 ± 7 years) and 19 comparable healthy controls (11 women/8 men, age: 30 ± 6 years) participated in this study. Pressure pain thresholds (PPTs) over anterior talofibular, calcaneofibular, and deltoid ligaments; the lateral and medial malleolus; the tibialis anterior muscle; second metacarpal; and median, radial, and ulnar nerves were bilaterally assessed. The analysis of variance (ANOVA) revealed that PPT levels over the affected anterior talofibular (P = 0.048) and calcaneofibular (P = 0.002) ligaments, and over the affected lateral malleolus (P < 0.001) were lower compared with the non-affected side within patients and both sides in controls. The patients also showed bilateral lower PPT levels over the deltoid ligament than controls (P < 0.05). No significant differences for PPT over the medial malleolus; the second metacarpal; the tibialis anterior muscle; and the median, ulnar, radial nerves were found. Significant negative correlations between intensity of ongoing pain and PPT over the anterior talofibular and deltoid ligaments were found: the higher the pain intensity, the lower the PPT. This study showed the presence of localized pressure pain hypersensitivity over ankle ligaments in patients with unilateral acute inversion ankle sprain, confirming the presence of localized peripheral sensitization.


ReseqChip: automated integration of multiple local context probe data from the MitoChip array in mitochondrial DNA sequence assembly.
The Affymetrix MitoChip v2.0 is an oligonucleotide tiling array for the resequencing of the human mitochondrial (mt) genome. For each of 16,569 nucleotide positions of the mt genome it holds two sets of four 25-mer probes each that match the heavy and the light strand of a reference mt genome and vary only at their central position to interrogate all four possible alleles. In addition, the MitoChip v2.0 carries alternative local context probes to account for known mtDNA variants. These probes have been neglected in most studies due to the lack of software for their automated analysis. We provide ReseqChip, a free software that automates the process of resequencing mtDNA using multiple local context probes on the MitoChip v2.0. ReseqChip significantly improves base call rate and sequence accuracy. ReseqChip is available at http://code.open-bio.org/svnweb/index.cgi/bioperl/browse/bioperl-live/trunk/Bio/Microarray/Tools/. ReseqChip allows for the automated consolidation of base calls from alternative local mt genome context probes. It thereby improves the accuracy of resequencing, while reducing the number of non-called bases.


In vivo expression of exoprotein synthesis with a Sae mutant of Staphylococcus aureus.
The expression of exoprotein synthesis of Staphylococcus aureus Sae mutant RC121 and its parental strain was studied under in vivo growth conditions. Cultures of both strains were inoculated into dialysis sacs implanted in sheep peritoneum. Results indicated that similar to in vitro grown mutant cells, Sae mutant RC121 shows diminished synthesis of alpha- and beta-hemolysin, coagulase, DNase and protein A. However, in vitro and in vivo grown mutant cultures showed different exoprotein profiles in SDS-PAGE; some bands from in vivo mutant cultures were diminished or missing and others appeared as more concentrated, when compared with the pattern of the in vivo grown parental strain, while all the exoprotein bands from the in vitro cultures of the mutant were diminished or missing as compared to the in vitro grown parental strain. The virulence of the Sae mutant, assayed by intraperitoneal injection in mice, was lower than that of the parental strain after both in vivo and in vitro growth conditions.


[Character and reasons for change in mitochondrial ATP content during auto-oscillation of ion currents].
The changes in the adenosine triphosphate content in the course of ionic flux oscillations in mitochondria were estimated by using the chemiluminescence method. The ATP concentration changes were shown to be of cyclic character; the oscillations in the ATP content were shifted by 180 degrees C against those of K+ fluxes. The oligomycin-induced oxidative phosphorylation blocking changed (but did not eliminate) the oscillational character of the ATP content in mitochondrial suspensions. It was concluded that substrate phosphorylation is the source of ATP under conditions of oxidative phosphorylation inhibition. Incubation of mitochondria in the presence of exogenous ATP led to suppression of ionic flux oscillations.


Low cost nitrogen laser design for dye laser pumping.
A pulsed cross-field molecular nitrogen laser (3371 A) has been simply constructed from two plate glass strips 5 cm by 1.2 m. During operation twenty 500-pF capacitors evenly spaced along the channel arecharged from a 0.012-microF storage capacitor by a thyratron at up to 30 Hz. This distributed charge is available for discharge when the gas breakdown starts. The flowing gas laser produces a 160-kW, 10-nsec (full-width half-maximum) light pulse when operated at 15 kV and at a pressure of 20 Torr. The laser has successfully pumped a tunable dye laser.


Phytoconstituents from Adenanthera pavonina L. as antioxidants and inhibitors of inducible TNF-α production in BV2 cells.
Adenanthera pavonina L. has been used traditionally to relieve inflammation. This study aimed to expand the phytochemical knowledge of A. pavonina and evaluate its constituents for their antioxidant and anti-inflammatory potentials as tumor necrosis factor alpha (TNF-α) inhibitors. The antioxidant activity was evaluated using the DPPH radical scavenging assay, and the inhibition of TNF-α was assessed through ELISA and qRT-PCR techniques. Interestingly, five previously undescribed metabolites, including a pentadienoic acid derivative, a triterpenoid glycoside, and three tamarixetin glycosides, were identified alongside seven known compounds. Most compounds evaluated had higher DPPH radical scavenging capabilities than the standard, trolox. Tamarixetin 3-O-(α-ʟ-rhamnopyranosyl)-(1→2)-β-ᴅ-galactopyranoside (11), a previously undescribed compound, was the most effective at suppressing TNF-α protein and m-RNA levels. Other flavonoid glycosides, quercetin 3-O-(α-ʟ-rhamnopyranosyl-(1→2)-β-ᴅ-xylopyranoside (4), isovitixin (5), and quercetin-3-O-[α-ʟ-rhamnopyranosyl-(1→2)]-[α-ʟ-rhamnopyranosyl-(1→6)]-β-ᴅ-galactopyranoside (9), also significantly lowered TNF-α production.


Does venous function deteriorate in patients waiting for varicose vein surgery?
We have looked at the deterioration in the condition of the lower limbs in a group of 36 patients who were waiting for a median time of 20 months for varicose vein surgery, using clinical examination, colour Duplex scanning and photoplethysmograph (95% refilling times). We found a significant deterioration in this group of patients, with four limbs initially unaffected developing reflux on Duplex scanning, of which three had clinical varicose veins (all four were offered surgery), and of the initial 56 involved limbs, 10 further sources of reflux were found (18%), necessitating alteration of the initial planned surgical procedure. No patient developed deep venous insufficiency or ulceration while on the waiting list, although there was one new case of lipodermatosclerosis. However, had surgery been undertaken after the first assessment, 14 patients (25%) would potentially have required further surgery, although accepting this as justification for allowing patients to wait takes no account of patients suffering or quality of life while waiting for operation.


Persistent Opioid Use Among Patients with Urolithiasis: A Population based Study.
Urolithiasis can result in acute, short-lived pain for which opioids are often prescribed. The risk of persistent opioid use following an initial presentation for urolithiasis is unknown. To describe rates of opioid prescription and identify risk factors for persistent opioid use among patients with urolithiasis. This was a population-based study of all patients diagnosed with urolithiasis in Ontario between 2013 and 2017 using administrative databases. The primary outcome was persistent opioid use, defined as dispensing of opioids between 91 and 180 d after presentation. Multivariable logistic regression and Cox proportional hazard models were used to identify factors associated with outcomes. Of 101 896 previously opioid-naïve patients, 66% were prescribed opioids at diagnosis and 41% of those were dispensed more than 200 oral morphine equivalents (OMEs). For those patients prescribed opioids, 9% had continued use. In adjusted analysis, the number of health care visits and having a stone intervention were associated with a higher risk of persistent opioid use (p< 0.0001). Total OME dispensed at presentation was highly associated with persistent use: for >300 OME the odds ratio (OR) was 1.59 (95% confidence interval [CI] 1.41-1.79). Among those who had an intervention, the number and type of procedure were also associated with persistent use: the OR for shockwave lithotripsy compared to ureteroscopy was 1.65 (95% CI 1.42-1.92). This study is limited by the accuracy of the diagnostic and procedural administrative codes available. The majority of urolithiasis patients were prescribed opioids and 9% of previously opioid-naïve patients exhibited persistent opioid use 91-180 d after their initial urolithiasis visit. In this study we found that 9% of patients prescribed opioids at presentation for kidney stones filled an additional prescription 3-6 mo later. Risk factors for this continued use included a higher dose of opioids prescribed in the initial period and the type of kidney stone surgery.


Re-differentiation of human articular chondrocytes is not enhanced by a rotary bioreactor system.
ACI is the most widely used cell-based surgical procedure for the repair of articular cartilage defects. The method is based on in vitro chondrocyte cultivation. Two different culture conditions, rotating-wall-vessel bioreactor and static culture, were assessed by their effect on the re-differentiation potential of human articular chondrocytes seeded into a hydrogel scaffold. Gene expression analysis of the tissue-engineered construct revealed no significant difference between the tested systems.


Recent developments in melanoma epidemiology, 1993.
Recent work on melanoma epidemiology up to and including the Third International Conference in 1993 shows that in several countries mortality trends have stabilized or are decreasing, although incidence continues to increase. Despite specific attention, evidence for a role of factors other than sun and ultraviolet exposure is weak. The established aetiological factors are sun exposure, particularly intermittent exposure, and exposure to artificial sources of ultraviolet radiation. Acquired naevi are also related to sun exposure and may be a useful biological marker, as may be mutations such as p53. Evidence for the effectiveness of educational efforts to reduce sun exposure of populations is now provided by Australian work, and studies in Scotland demonstrate the effectiveness of public education in early diagnosis. A major unresolved issue is the value or otherwise of population screening, and systematic trails are required.


The Trojan horse - neuroinflammatory impact of T cells in neurodegenerative diseases.
Neuronal degeneration is a common mechanism of many neurological diseases including Parkinson's disease (PD), Alzheimer's disease (AD), and Multiple Sclerosis (MS). While AD and PD are classical neurodegenerative diseases, the primary pathology in MS is driven by autoimmune inflammation, attacking oligodendrocytes and thereby inducing neurodegeneration. In AD and PD, immune cells are also considered to play an important role in the disease progression. While the role of local central nervous system (CNS) innate immune cells is well described, a potential influence of adaptive immune cells in PD and AD is not yet fully understood.Here, we aim to summarize findings concerning adaptive immune cells in PD pathogenesis and compare them to AD and MS. In the first part, we focus on disease-specific alterations of lymphocytes in the circulating blood. Subsequently, we describe what is known about CNS-infiltrated lymphocytes and mechanisms of their infiltration. Finally, we summarize published data and try to understand the mechanisms of how lymphocytes contribute to neurodegeneration in PD, AD, and MS.Lymphocytes are critically involved in the pathogenesis of MS, and clarifying the role of lymphocytes in PD and AD pathogenesis might lead to an identification of a common signature of lymphocytes in neurodegeneration and thus pave the road towards novel treatment options.


Safe Practices for Medication Administration via Enteral Tubes.
Medication errors are possible when drugs are given through enteral feeding tubes.The Institute for Safe Medication Practices has suggested strategies for reducing the common errors that can occur through use of this route of administration.


Efficacy of Shexiang Baoxin Pills for the treatment of unstable angina pectoris: Protocol of systemic review and meta-analysis.
Shexiang Baoxin Pills (SBP) is widely used for the treatment of unstable angina pectoris (UAP) in China. However, the clinical evidence on the efficacy of SBP for the treatment of UAP is not well concluded. Seven electronic databases will be searched for eligible studies: MEDLINE, EMBASE, The Cochrane Library, Wanfang database, Chinese National Knowledge Infrastructure database, VIP database, and Chinese Biological and Medicine database. Data of included studies will be extracted, and quality will be evaluated. Data synthesis will be performed using RevMan software. Subgroup analysis and sensitivity analysis will also be carried out. Publication bias will be evaluated using funnel plot if included studies are sufficient. This systemic review and meta-analysis will provide synthesized result of clinical efficacy of SBP for the treatment of UAP. This systemic review and meta-analysis will provide high-quality evidence on the clinical efficacy of SBP for the treatment of UAP. PEROSPERO CRD42019124668.


Roles of support materials in 3D bioprinting - Present and future.
Bioprinting has been introduced as a new technique in tissue engineering for more than a decade. However, characteristics of bioprinted part are still distinct from native human tissue and organ in terms of both shape fidelity and functionality. Recently, the combination of at least two hydrogels or "multi-materials/multi-nozzles" bioprinting enables simultaneous deposition of both model and support materials, thus advancing the complexity of bioprinted shapes from 2.5D lattice into micro-channeled 3D structure. In this article, a perspective on the roles of second bioinks or support materials is presented and future outlook of sacrificial materials is discussed.


Efficacy of AloeVera Cream in the Treatment of Paederus Dermatitis in Mice.
Dermatitis caused by Paederus beetle involves many people around the world, especially Iran. The symptoms include redness, itching and severe irritation. This study evaluated the effectiveness of the Aloevera cream on the treatment of dermatitis caused by Paederus beetles. Forty male 6-8 weeks BALB/C mice were randomly divided into four groups of 10 mice. After removing the mice's back hair, the backs of mice were marked by a circle with a diameter of 3 mm. The Paederus beetles were collected from Babol in Mazandaran Province, northern Iran and transferred to the animal lab of Aja University of Medical Sciences, Tehran, Iran. The end of abdominal segment Paederus was cut with scissors and hemolymph content was pushed by forceps on the circle. Only hemolymph of one Paederus applied to the back of each mouse. Groups 1, 2, 3 and 4 were treated with the base (vehicle), dexamethasone 0.1%, Aloevera 0.5% and Aloevera 2% creams respectively. After 2 days, dermatitis appeared. Then the mentioned creams were applied on the mice once a day. The wound area was measured every day. Dermatitis surface area under curve (AUC) of each mouse was calculated for 17 days after induction of dermatitis. Statistical analysis of ANOVA was used. Application of Aloevera 0.5% and 2% significantly reduced the healing duration and dermatitis area in comparison with the vehicle and dexamethasone cream (P< 0.05). But dexamethasone had no significant effect on the healing of dermatitis as compared to vehicle. Aloevera may clinically effective in the treatment of Paederus dermatitis.


Case management in mental health.
Despite the growing popularity of case management in caring for clients' multiple needs, the concept of case management and its relationship to social work are yet to be defined clearly. To help shed light on the subject, this article reports on a survey of 403 case managers in community mental health centers in Georgia that examined how workers' educational level, professional identification, and demographic characteristics influenced their performance of case management tasks.


Effect of tree nuts on glycemic outcomes in adults with type 2 diabetes mellitus: a systematic review.
The objective of this review was to synthesize the best available research evidence regarding the effectiveness of tree nuts on glycemic outcomes in adults with type 2 diabetes mellitus. There has been an increase in the use of complementary therapy, particularly botanical products, for management of type 2 diabetes mellitus. It has been reported that increasing mono- and polyunsaturated fatty acids in diet effectively lowers the risk of development of type 2 diabetes mellitus. Hence, it was hypothesized that consumption of nuts, which are high in polyunsaturated fatty acids and mono-unsaturated fatty acids, may aid in preventing diabetes and reducing levels of blood glucose by reducing glycemic load by displacing dietary carbohydrates present in diet. This systematic review included randomized controlled trials that compared the consumption of any type and form of tree nut with a placebo or any other intervention in adults with type 2 diabetes mellitus. Trials were included if they measured fasting blood glucose, postprandial blood glucose, and/or glycated hemoglobin. Trials that assessed triglyceride levels and weight postintervention were also considered for inclusion. Trials were restricted to the English language. A three step search of PubMed, CINAHL, Embase, Trip database, and Cochrane Central Register of Controlled Trials (CENTRAL) was done in July 2019. To find unpublished studies, ClinicalTrials.gov and Google Scholar were searched. Studies from the search were reviewed against the inclusion criteria by two reviewers. The JBI critical appraisal checklist for randomized controlled trials was used to assess the potential studies for methodological quality. A meta-analysis and subgroup analysis was conducted among trials with the same type of intervention and outcome measures. Results are presented in a narrative format where statistical pooling was not possible. Fifteen trials were included with a total sample size of 667. Consumption of pistachios demonstrated a significant reduction in triglyceride levels (mmol/L) at three month or earlier follow-up (mean difference [MD] -0.28; confidence interval -0.33, -0.23; P <0.00001). The meta-analysis including all tree nuts combined showed reduction in both fasting blood glucose and glycated hemoglobin (MD -0.26 mmol/L and -0.11% respectively) at three month or earlier follow-up. The subgroup analysis demonstrated MD of -0.45, -0.16, and -0.90 mmol/L in fasting blood glucose following ingestion of walnuts, almonds, and hazelnuts, respectively, and -0.17% in glycated hemoglobin following ingestion of walnuts at three month or earlier follow-up. Although not clinically significant, these figures give an indication that further research with larger sample sizes and longer follow-up may show encouraging results. The authors found that pistachio consumption for three months or less significantly reduced triglyceride levels. Other tree nuts (walnuts, almonds, and hazelnuts) reduced fasting blood glucose and glycated hemoglobin levels by varying degrees. Further robust randomized controlled trials with power calculation-based sample size, comparing same type, dose, and method of nut intervention, will provide more evidence. For now, clinical decisions should be based on standard practice local guidelines. PROSPERO CRD42019133558.


Insulin receptor signaling and sarco/endoplasmic reticulum calcium ATPase in beta-cells.
Glucose is the main physiological secretagogue for insulin secretion by pancreatic beta-cells, and the major biochemical mechanisms involved have been elucidated. In particular, an increase in intracellular calcium is important for insulin exocytosis. More recently, it has become apparent that the beta-cell also has many of the elements of the insulin receptor signal transduction pathway, including the insulin receptor and insulin receptor substrate (IRS) proteins 1 and 2. Studies with transgenic models have shown that the beta-cell-selective insulin receptor knockout and the IRS-1 knockout lead to reduced glucose-induced insulin secretion. Overexpression of the insulin receptor and IRS-1 in beta-cells results in increased insulin secretion and increased cytosolic Ca(2+). We have thus postulated the existence of a novel autocrine-positive feedback loop of insulin on its own secretion involving interaction with the insulin receptor signal transduction pathway and regulation of intracellular calcium homeostasis. Our current working hypothesis is that this glucose-dependent interaction occurs at the level of IRS-1 and the sarco(endo)plasmic reticulum calcium ATPase, the calcium pump of the endoplasmic reticulum.


Developing an Ethics Framework for Allocating Remdesivir in the COVID-19 Pandemic.
On May 1, 2020, the US Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) to allow use of the antiviral drug remdesivir to treat patients with severe coronavirus disease-2019 (COVID-19). Remdesivir is an investigational drug studied in clinical trials for COVID-19 and is available to children and pregnant women through compassionate-use access but is not yet FDA approved. In early May, the US Department of Health and Human Services began to distribute remdesivir, donated by Gilead Sciences, Inc., to hospitals and state health departments for emergency use; multiple shipments have since been distributed. This process has raised questions of how remdesivir should be allocated. The Minnesota Department of Health has collaborated with the Minnesota COVID Ethics Collaborative and multiple clinical experts to issue an Ethical Framework for May 2020 Allocation of Remdesivir in the COVID-19 Pandemic. The framework builds on extensive ethical guidance developed for public health emergencies in Minnesota before the COVID-19 crisis. The Minnesota remdesivir allocation framework specifies an ethical approach to distributing the drug to facilities across the state and then among COVID-19 patients within each facility. This article describes the process of developing the framework and adjustments in the framework over time with emergence of new data, analyzes key issues addressed, and suggests next steps. Sharing this framework and the development process can encourage transparency and may be useful to other states formulating and refining their approach to remdesivir EUA allocation.


A review of the physiological significance of hypertonic body fluids on feed intake and ruminal function: salivation, motility and microbes.
Mechanisms exist in the ruminant to detect changes in osmolality and volume of plasma during feeding to maintain fluid and electrolyte homeostasis. Feed intake during a meal can be limited by the rise in osmolality of ruminal fluid, which is sensed in the wall of the rumino-reticulum. Ruminal microbes appear to be resilient to the short-term changes in ruminal fluid tonicity, but in vitro growth rates are inhibited when the tonicity of the culture medium is increased beyond physiological levels. Although mixing contractions of the rumen are not inhibited by the normal increases in tonicity of ruminal fluid, time to first rumination is increased. This aspect of motility requires further research. The tonicity of plasma increases toward the end of a large meal as a consequence primarily of absorption of VFA and Na+ from the rumen and fluid shifts into the gut. This hypertonicity is sensed centrally to inhibit parotid secretion by a reduction in the parasympathetic stimulation to the gland. Increases in animal production may result from future research directed toward developing ways of counteracting these negative effects of hypertonicity in body fluids on feed intake and ruminal function.


[Pharmacokinetic studies on the penetration of azlocillin and mezlocillin into bone and tissue fluid (author's transl)].
During and after hip replacement arthroplasty antimicrobial concentrations in serum, bone and tissue-fluid were determined microbiologically using agar diffusion assay technique after 15-min infusion of 5 g 6-[D-2-(2-oxoimidazolidine-1-carboxamido)-2-phenylacetamido] - penicillanic acid (azlocillin) and 5 g 6-[D-2-(3-methylsulfonyl-2-oxoimidazolin-1-ylcarboxamido)-2-phenylacetamido]-penicillanic acid (mezlocillin) and after i.v. bolus injection of 2 g mezlocillin. Serum pharmacokinetic data on the individual patients are computer derived using a modified open two-compartment model. The geometric mean of bone level determinations at defined intervals with deviation factor are presented. These results are related to the organic bone compartment and are expressed in mg/l. From the tissue fluid-concentration curve, peak concentration CP and its time were calculated. The time for which one-fourth of the peak concentration CP 1/4 was maintained in tissue fluid was determined graphically. This concentration is compared with the cumulative minimum inhibitory concentrations of representative bacteria causing bone and joint infections. These results are focused as criteria of valuation of antimicrobial chemotherapy.