Fluorescent contaminants from plastic and rubber laboratory equipment.
Plastic and rubber laboratory apparatus contains materials that are extractable with water, aqueous solutions, and nonaqueous solvents. These extractable substances fluoresce under ultraviolet light and were found as contaminants in nutrient solution used for growing excised lemon fruit tissue in vitro. The source of these fluorescent contaminants has been removed by using all-glass laboratory equipment.


Angiographic assessment of biografts for femoropopliteal bypass.
A series of 257 femoropopliteal bypass procedures with a Biograft is analysed. The cumulative patency rate after 6 years is 64% for the whole series. This corresponds with a cumulative patency rate of 74% for AK cases and 44% for BK cases. Follow-up angiography to assess the morphology of the Biografts, was performed after 1 year and after 3-5 years. Angiography after 1 year (N = 126) showed few alterations: tortuosity in 3%, segmentation or wrinkling in 3%, slight diffuse dilatation in 4% and local stenosis in 2%. Angiography after 3-5 years (N = 82) revealed interesting changes. Besides tortuosity in 6% and segmentation in 29%, there were anastomotic aneurysms in 2%. Changes in the diameter of the body of the graft were remarkable and occurred in 46%. Diffuse regular or irregular dilatation, local ectasia or stenosis was found. Clinical implications are discussed.


Effect of multivitamin supplementation on the homocysteine and methylmalonic acid blood concentrations in women over the age of 60 years.
Deficiency of folic acid, vitamin B(6) and/or vitamin B(12) can result in elevated total plasma homocysteine concentrations (tHcy), which are considered to be a risk factor for vascular disease. Studies have shown that supplementation of the three vitamins can lower tHcy even in subjects with tHcy in the normal range. The aim of this study was to evaluate the effect of a 6 month supplementation with vitamin B(6), B(12) and folate on the concentrations of total plasma homocysteine and serum methylmalonic acid (MMA) of elderly women. The study was designed as a randomized placebo controlled double-blind trial, and 220 healthy women (aged 60-91 years) were involved. The vitamin and mineral capsule contained pyridoxine (3.4 mg), folic acid (400 microg) and cobalamin (9 microg) in addition to other micronutrients. Blood concentrations of folate, cobalamin, tHcy, MMA and the activity coefficient of erythrocyte alpha-aspartic aminotransferase (alpha-EAST) were measured at baseline and after 6 months of supplementation. Dietary intake was evaluated at the beginning and the end of the intervention by two 3-day diet records. Median concentrations of serum cobalamin, serum folate and erythrocyte folate increased significantly and tHcy and alpha-EAST activity (indicative of improved status of vitamin B(6)) coefficient decreased significantly in the supplemented group. Median MMA concentration of the supplemented group was significantly lower than that of the placebo group after the intervention. The vitamin supplementation had a greater decreasing effect on the tHcy concentration of volunteers with lower vitamin and higher tHcy initial concentrations. In a linear regression model, baseline tHcy, serum folate, age and alpha-EAST activity coefficient were significantly correlated with the change in tHcy. The change in MMA in the supplement group was significantly associated to the baseline MMA values. Our results show that a 6 month supplementation including physiological dosages of B vitamins improves the status of these nutrients and reduces tHcy in presumed healthy elderly women.


Non-random distribution of surface immunoglobulins on murine B lymphocytes.
An indirect labeling technique was used to map the surface immunoglobulin (Ig) on murine splenic B lymphocytes by freeze-etching. Cells were labeled first with fluorescein conjugates of monovalent (papain-digested) anti-Ig antibody followed by monovalent anti-fluorescein antibody coupled to ferritin. The technique avoids cross-linking and aggregation of surface Ig. Freeze-etched replicas of cells labeled at 4 degrees C, as well as of cells prefixed with paraformaldehyde showed that surface Ig was distributed in small clusters with interconnecting networks. The observed pattern was analyzed statistically by comparing it with the expected random (Poisson) distribution and shown to be non-random to a high degree of statistical significance. The deviation from randomness could be explained by the presence of clusters and relative excesses of bare membrane. Such an observed distribution of surface Ig suggests that this membrane macromolecule may be organized in a specific manner. The distribution may also play a role in the function of surface Ig as the antigen receptor on B lymphocytes.


Monoclonal antibody specific for avian sarcoma virus structural protein p27.
A hybridoma cell line which secretes antibody to the Rous sarcoma virus (RSV) structural protein p27 has been established. The hybrid resulted from the fusion of NS-1 myeloma cells with spleen cells from a Balb/c mouse which was immunized with RSV-transformed mouse cells. Antibodies produced by the hybrid clone immunoprecipitated p27 and gag precursor proteins (Pr180gag,pol, Pr76gag and Pr66gag) from [35S]methionine-labelled chicken embryo fibroblasts transformed by the Schmidt-Ruppin strain of RSV. When Schmidt-Ruppin virus was radioactively labelled with [35S]methionine, p27 was the only virus structural protein immunoprecipitated. Antibody production by the hybrid clone (designated 7-29-D6) has remained stable for longer than 12 months at a level of 50 micrograms IgG/ml medium. A highly sensitive method to determine the subclass specificity of monoclonal antibodies is described. In this procedure, the clone is incubated with [35S]-methionine, and radiolabelled antibody is precipitated with affinity-purified, subclass-specific rabbit anti-mouse serum and Staphylococcus aureus. The advantages of this procedure are discussed.


Very low microsatellite polymorphism and large heterozygote deficits suggest founder effects and cryptic structure in the parasite Perkinsus olseni.
Twelve microsatellite markers were used to characterize 130 clonal cultures of Perkinsus olseni derived from 30 clams from six different geographic locations. Only two loci were polymorphic in the four populations studied from Spanish coast (mean sample size = 31.2), and a third locus was variable in only two populations. In contrast, five parasites isolated from five clams from Japan and New Zealand showed variation at nine loci. Low genetic variation (2.08 ± 0.64 alleles per locus; mean genetic diversity: 0.101 ± 0.022), and very high F(IS) values (0.857 on average) were observed in Spanish populations. A total of 39 multilocus genotypes (MLGs) were identified in the whole sample (121 clonal isolates after excluding incomplete MLGs due to missing data). A three-level hierarchical analysis of molecular variance found significant levels of genetic variation within infrapopulations (all the parasites in a single host; Φ(IS) = 0.679) and among infrapopulations within the component population (all the parasites among a host population; Φ(SC) = 0.579). Differences among the component population from different geographic locations were not significant (Φ(CT) = 0.057). These results suggest that an important fraction of F(IS) is explained by the Wahlund effect, but also strong inbreeding within infrapopulations. Another explanation for the high F(IS) within infrapopulations is the presence of haploid and diploid stages in the clam. Although fully aquatic system provides many opportunities for mixing of parasites from different clams, results are consistent with the consideration of all P. olseni in a clam as a cohesive genetic unit (i.e., deme). If the parasite was introduced into the Spanish coast with the importation of infected clams from Asia and Oceania, the low microsatellite polymorphism could be reflecting founder effects in the recent evolutionary history of P. olseni. The loss of alleles would be intensified in a scenario structured in numerous demes because of recurrent founder effects at microgeographic level.


Anthraquinones as Potential Antibiofilm Agents Against Methicillin-Resistant Staphylococcus aureus.
Biofilms formed by methicillin-resistant Staphylococcus aureus (MRSA) are one of the contributing factors to recurrent nosocomial infection in humans. There is currently no specific treatment targeting on biofilms in clinical trials approved by FDA, and antibiotics remain the primary therapeutic strategy. In this study, two anthraquinone compounds isolated from a rare actinobacterial strain Kitasatospora albolonga R62, 3,8-dihydroxy-l-methylanthraquinon-2-carboxylic acid (1) and 3,6,8-trihydroxy-1-methylanthraquinone-2-carboxylic acid (2), together with their 10 commercial analogs 3-12 were evaluated for antibacterial and antibiofilm activities against MRSA, which led to the discovery of two potential antibiofilm anthraquinone compounds anthraquinone-2-carboxlic acid (6) and rhein (12). The structure-activity relationship analysis of these anthraquinones indicated that the hydroxyl group at the C-2 position of the anthraquinone skeleton played an important role in inhibiting biofilm formation at high concentrations, while the carboxyl group at the same C-2 position had a great influence on the antibacterial activity and biofilm eradication activity. The results of crystal violet and methyl thiazolyl tetrazolium staining assays, as well as scanning electron microscope and confocal scanning laser microscopy imaging of compounds 6 and 12 treatment groups showed that both compounds could disrupt preformed MRSA biofilms possibly by killing or dispersing biofilm cells. RNA-Seq was subsequently used for the preliminary elucidation of the mechanism of biofilm eradication, and the results showed upregulation of phosphate transport-related genes in the overlapping differentially expressed genes of both compound treatment groups. Herein, we propose that anthraquinone compounds 6 and 12 could be considered promising candidates for the development of antibiofilm agents.


[Method of early activation of patients after heart surgery].
Methods employed in an early activation of patients operated on a "closed" heart and under extracorporeal circulation are described. The authors began activating theri patients 2--3 hours after surgery and 16--20 hours therafter inst tuted a physical effort test (walking) over a distance of 50--100 m for 2.5--5 minutes). It was shown that the re-establisment of the hemodynamics indices, factors of external respiration and internal environment in patients managed post-operatively in accordance with the routine methods took much longer time than with the active method of managing the early post-operative period. The abolishment of a protracted hypodynamia regimen against the background of a quick normalizatiion of homesotasis is conducive to an earlier adaptation of patients to new conditions reduces the incidence of post-operative complications and curtails the patients' staty in hospital.


Developmentally Specific Associations Between CNR1 Genotype and Cannabis Use Across Emerging Adulthood.
Previous studies have found preliminary evidence for associations between common single-nucleotide polymorphisms (SNPs) in the cannabinoid receptor gene CNR1 and cannabis use and dependence. The present study examined a set of eight independent SNPs in or near CNR1 in relation to cannabis use measured longitudinally across emerging adulthood. Using latent growth curve modeling of 10 waves of longitudinal data spanning mean ages 18.4-23.8 years in a sample of non-Hispanic White individuals (n = 334), we tested if genotype at each CNR1 SNP was associated with both level and growth of cannabis use over time. Peer group drug use, a known correlate of individual use, was evaluated as a time-varying predictor of cannabis use and as a moderator of the relationship between SNPs and individual use. After correction for multiple comparisons, one SNP, rs806374, was significantly associated with individual differences in level-but not growth-of cannabis use over time, such that C carriers were more likely to use cannabis more frequently at study onset (around age 18). Peer drug use was a predictor of individual cannabis use that grew in terms of effect size with time, but did not significantly moderate the effect of rs806374 genotype. C carriers at rs806374 may be at specific risk for increased odds of use during the transition out of high school (around age 18). Future studies should investigate potential mechanisms at this developmental stage, including individual differences in subjective response, innate tolerance, reinforcement mechanisms, or general liability for substance misuse.


Contextual modulation of appearance-trait learning.
When we encounter a stranger for the first time, we spontaneously attribute to them a wide variety of character traits based on their facial appearance. There is increasing consensus that learning plays a key role in these first impressions. According to the Trait Inference Mapping (TIM) model, first impressions are the products of mappings between 'face space' and 'trait space' acquired through domain-general associative processes. Drawing on the associative learning literature, TIM predicts that first-learned associations between facial appearance and character will be particularly influential: they will be difficult to unlearn and will be more likely to generalise to novel contexts than appearance-trait associations acquired subsequently. The study of face-trait learning de novo is complicated by the fact that participants, even young children, already have extensive experience with faces before they enter the lab. This renders the study of first-learned associations from faces intractable. Here, we overcome this problem by using Greebles - a class of novel synthetic objects about which participants had no previous knowledge or preconceptions - as a proxy for faces. In four experiments (total N = 640) with adult participants we adapt classic AB-A and AB-C renewal paradigms to study appearance-trait learning. Our results indicate that appearance-trait associations are subject to contextual control, and are resistant to counter-stereotypical experience.


A Rare Opportunist, Morganella morganii, Decreases Severity of Polymicrobial Catheter-Associated Urinary Tract Infection.
Catheter-associated urinary tract infections (CAUTIs) are common hospital-acquired infections and frequently polymicrobial, which complicates effective treatment. However, few studies experimentally address the consequences of polymicrobial interactions within the urinary tract, and the clinical significance of polymicrobial bacteriuria is not fully understood. Proteus mirabilis is one of the most common causes of monomicrobial and polymicrobial CAUTI and frequently cocolonizes with Enterococcus faecalis, Escherichia coli, Providencia stuartii, and Morganella morganiiP. mirabilis infections are particularly challenging due to its potent urease enzyme, which facilitates formation of struvite crystals, catheter encrustation, blockage, and formation of urinary stones. We previously determined that interactions between P. mirabilis and other uropathogens can enhance P. mirabilis urease activity, resulting in greater disease severity during experimental polymicrobial infection. Our present work reveals that M. morganii acts on P. mirabilis in a contact-independent manner to decrease urease activity. Furthermore, M. morganii actively prevents urease enhancement by E. faecalis, P. stuartii, and E. coli Importantly, these interactions translate to modulation of disease severity during experimental CAUTI, predominantly through a urease-dependent mechanism. Thus, products secreted by multiple bacterial species in the milieu of the catheterized urinary tract can directly impact prognosis.


Community-acquired pneumonia.
This article presents a general approach to the patient with community-acquired pneumonia and details clinical and therapeutic features of the principal community-acquired pneumonias: pneumococcal pneumonia, mycoplasma pneumonia, and legionnaires disease.


A model for studying chronic reduction in uterine blood flow in pregnant sheep.
A model is described for the investigation of the effects of acute and chronic reduction in uterine blood flow in unanesthetized pregnant sheep. An externally adjustable vascular occluder has been designed to utilize the principles of a modified Goldblatt clamp. This occluder is made of nonbreakable plastic and is adjusted via a flexible cable encased in a sheath. The occluder has been tested in 17 pregnant sheep and has remained functional for periods up to 36 days, the length of implantation. This occluder has allowed graded reductions in uterine blood flow, which can be accurately and consistently reproduced. An example of flow reduction is shown in which uterine blood flow has been reduced by 24, 47, and 82% in late-term pregnant sheep. This method will allow the investigation of the effects of uterine hypoperfusion and fetal hypoxia in a precisely controlled unanesthetized pregnant sheep preparation.


Practical landmarks for visual field disability in glaucoma.
To assess whether mean deviation (MD) from automated perimetry is related to the visual field (VF) component for legal fitness to drive (LFTD) in glaucoma patients. Monocular 24-2 VFs of 2604 patients with bilateral VF damage were retrospectively investigated. Integrated visual fields were calculated and used as a surrogate to assess LFTD according to current UK driving licence criteria. The better eye MD (BEMD), worse eye MD (WEMD) and a measure utilising MD of both eyes were compared, to assess respective diagnostic capabilities to predict LFTD (using the integrated visual field surrogate test as the gold standard) and a 'Probability of Failure' (PoF) for various defect levels was calculated. BEMD appears to be a good predictor of the VF component for a patient's LFTD (receiver operating characteristic area under the curve: 96.2%); MDs from both eyes offered no significant extra diagnostic power (area under the curve: 96.4%). PoF for BEMD thresholds of ≤-10 dB and ≤-14 dB were 70 (95% CI 66% to 74%) and 92% (87% to 95%), respectively. There is a strong relationship between BEMD and a patient's LFTD. PoF values for LFTD associated with readily available MD values provide practical landmarks for VF disability in glaucoma.


[Attitudes of Brazilian pulmonologists toward nicotine dependence: a national survey].
Smoking is a medical condition, since there is drug dependence, and health professionals should treat it as a chronic disease. In order to understand the attitudes of Brazilian pulmonologists toward smokers, we conducted a national survey, using a questionnaire posted on the Internet, of 2,800 pulmonologists, 587 (21%) of whom completed and returned the questionnaires. We found that 3.2% of the respondents did not believe that smoking is a medical condition. Only 14.7% treated smokers, and 32.4% stated that they would refer smokers to another professional for treatment. These results suggest that Brazilian pulmonologists have insufficient knowledge of smoking cessation therapies.


Specific anion effects on water structure adjacent to protein monolayers.
Vibrational sum frequency spectroscopy (VSFS) was used to explore specific ion effects on interfacial water structure adjacent to a bovine serum albumin (BSA) monolayer adsorbed at the air/water interface. The subphase conditions were varied by the use of six different sodium salts and four different pH values. At pH 2 and 3, the protein layer was positively charged and it was found that the most chaotropic anions caused the greatest attenuation of water structure. The order of the salts followed an inverse Hofmeister series. On the other hand, when the protein layer was near its isoelectric point (pH 5), the most chaotropic anions caused the greatest increase in water structure, although the effect was weak. In this case, a direct Hofmeister series was obeyed. Finally, virtually no effect was observed when the protein layer was negatively charged with a subphase pH of 9. For comparison, similar experiments were run with positively charged, negatively charged, and zwitterionic surfactant monolayers. These experiments gave rise to nearly the identical results as the protein monolayer which suggested that specific anion effects are dominated by the charge state of the interfacial layer rather than its detailed chemical structure. In a final set of experiments, salt effects were examined with a monolayer made from an elastin-like polypeptide (ELP). The peptide consisted of 120 pentameric repeats of the sequence Val-Pro-Gly-Val-Gly. Data from this net neutral biopolymer followed a very weak, but direct Hofmeister series. This suggested that direct anion binding to the amide groups in the backbone of a polypeptide is quite weak in agreement with the BSA data. The results from the variously charged protein, surfactant, and polymer monolayers were compared with a modified Gouy-Chapman-Stern model. The agreement with this simple model was quite good.


Evidence on the Validity of a Comprehensive Health Risk Index and Implications for Ambulatory Care and Population Health Management.
A novel, comprehensive health risk index for adults has been validated and is now ready for use to improve the health of individuals and populations. This health risk index provides an estimate of the avoidable risk of death for adults 30 years or older. It includes 12 evidence-based clinical and behavioral risk factors and was validated on discrimination and calibration using the NHANES (National Health and Nutrition Examination Survey) and Framingham Heart Study cohorts. The results from both cohorts were consistent and similar. Discrimination was good, and calibration was acceptable but tended to overpredict mortality risk for females in the higher-risk deciles.


A stakeholder approach to community health management.
Although community health management has become an important issue for health care organizations, there is little information on the roles that they and other community institutions ought to play in this area. This article develops a stakeholder approach to community health management, identifies the set of community health stakeholders, determines their salience to health care organizations, discusses the strategies they use to influence organizational involvement in community health management, and examines the responses of health care organizations. Implications for community institutions, health care managers, and researchers are discussed.


Eelbrain, a Python toolkit for time-continuous analysis with temporal response functions.
Even though human experience unfolds continuously in time, it is not strictly linear; instead, it entails cascading processes building hierarchical cognitive structures. For instance, during speech perception, humans transform a continuously varying acoustic signal into phonemes, words, and meaning, and these levels all have distinct but interdependent temporal structures. Time-lagged regression using temporal response functions (TRFs) has recently emerged as a promising tool for disentangling electrophysiological brain responses related to such complex models of perception. Here we introduce the Eelbrain Python toolkit, which makes this kind of analysis easy and accessible. We demonstrate its use, using continuous speech as a sample paradigm, with a freely available EEG dataset of audiobook listening. A companion GitHub repository provides the complete source code for the analysis, from raw data to group level statistics. More generally, we advocate a hypothesis-driven approach in which the experimenter specifies a hierarchy of time-continuous representations that are hypothesized to have contributed to brain responses, and uses those as predictor variables for the electrophysiological signal. This is analogous to a multiple regression problem, but with the addition of a time dimension. TRF analysis decomposes the brain signal into distinct responses associated with the different predictor variables by estimating a multivariate TRF (mTRF), quantifying the influence of each predictor on brain responses as a function of time(-lags). This allows asking two questions about the predictor variables: 1) Is there a significant neural representation corresponding to this predictor variable? And if so, 2) what are the temporal characteristics of the neural response associated with it? Thus, different predictor variables can be systematically combined and evaluated to jointly model neural processing at multiple hierarchical levels. We discuss applications of this approach, including the potential for linking algorithmic/representational theories at different cognitive levels to brain responses through computational models with appropriate linking hypotheses.


Catalytic activity of palladium-doped silver dilute nanoalloys for formate oxidation from a theoretical perspective.
The large-scale practical application of formate oxidation reaction (FOR) catalysts is hindered by their low activity and high cost. Herein, for the first time, a series of Pd-doped Ag dilute nanoalloys is demonstrated to have high catalytic activity in FOR with reduced consumption of Pd metals through density functional theory calculations, where the effects of potential, solvent and spin on catalytic performance are discussed. The Pd1Ag(111) single-atom alloy (SAA) exhibits higher FOR catalytic activity as reflected by the low limiting potential of 0.026 eV for the direct association path and a value of 0.084 eV for the direct dissociation path, and the lowest activation energy of 0.774 eV for the rate-determining-step in the direct dissociation path compared with Pd2Ag(111) and Pd3Ag(111) dilute alloys. Pd1Ag(111) SAA exhibits an extremely narrow sharp peak in the partial density of states from -0.75 to -2.0 eV, which is due to the free-atom-like electronic structure of the single Pd atom. The isolated Pd single atom is more stable by -0.041 and -0.097 eV, respectively, than the aggregated Pd2 and Pd3 atom clusters on the Ag(111) surface, which verifies the potential application of Pd1Ag(111) SAA in experiments. Overall, this work further elucidates the theoretical profile of FOR and provides a new strategy for designing the catalytic reaction at the atomic level.


Incorporation of relative cerebral blood flow into CT perfusion maps reduces false 'at risk' penumbra.
The region defined as 'at risk' penumbra by current CT perfusion (CTP) maps is largely overestimated. We aimed to quantitate the portion of true 'at risk' tissue within CTP penumbra and to determine the parameter and threshold that would optimally distinguish it from false 'at risk' tissue, that is, benign oligaemia. Among acute stroke patients evaluated by multimodal CT (NCCT/CTA/CTP) we identified those that had not undergone endovascular/thrombolytic treatment and had follow-up NCCT. Maps of absolute and relative CBF, CBV, MTT, TTP and Tmax as well as summary maps depicting infarcted and penumbral regions were generated using the Intellispace Portal (Philips Healthcare, Best, Netherlands). Follow-up CT was automatically co-registered to the CTP scan and the final infarct region was manually outlined. Perfusion parameters were systematically analysed - the parameter that resulted in the highest true-negative-rate (ie, proportion of benign oligaemia correctly identified) at a fixed, clinically relevant false-negative-rate (ie, proportion of 'missed' infarct) of 15%, was chosen as optimal. It was then re-applied to the CTP data to produce corrected perfusion maps. Forty seven acute stroke patients met selection criteria. Average portion of infarcted tissue within CTP penumbra was 15%±2.2%. Relative CBF at a threshold of 0.65 yielded the highest average true-negative-rate (48%), enabling reduction of the false 'at risk' penumbral region by ~half. Applying a relative CBF threshold on relative MTT-based CTP maps can significantly reduce false 'at risk' penumbra. This step may help to avoid unnecessary endovascular interventions.


Multiple responses to administration of liposome-encapsulated hemoglobin (LEH): Effects on hematopoiesis and serum IL-6 levels.
Liposome-encapsulated hemoglobin (LEH) has been tested in animals as an oxygen-carrying red cell substitute and has been shown to be beneficial in the treatment of hemorrhagic shock. The effects of LEH on immune responses have not been studied thoroughly in any well-controlled model. Using a murine model, we evaluated nephrotoxicity and hepatotoxicity as well as immune function parameters following LEH administration. Following intravenous administration of LEH, 1) a serum spike of interleukin-6 (IL-6) occurred in mice at 4-8 hours, with no elevation of IL-1, tumor necrosis factor (TNF), or interferon-gamma (IFN-gamma); 2) the serum liver function enzymes SGOT (AST, aspartate aminotransferase) and SGPT (ALT, alanine aminotransferase) were elevated at 48 hours; 3) only a slight increase in serum antibody to bovine hemoglobin was observed; and 4) increased hematopoietic activity was observed in the spleen and bone marrow. The finding that only IL-6 but not the associated TNF, IL-1, or IFN-gamma is secreted in vivo following LEH administration is novel and may have significance in defining the mechanisms underlying specific adverse responses observed with LEH administration in animals.


Integrated communication support program for oncologists, caregivers and patients with rapidly progressing advanced cancer to promote patient-centered communication: J-SUPPORT 1904 study protocol for a randomised controlled trial.
Communication is an essential aspect of care for patients with progressive serious illnesses. This study aims to evaluate the efficacy of a new, integrated communication support program for oncologists, patients with rapidly progressing advanced cancer and their caregivers. The proposed integrated communication support programme is in the randomised control trial stage. It comprises a cluster of oncologists from comprehensive cancer centre hospitals in a metropolitan area in Japan. A total of 20 oncologists, 200 patients with advanced pancreatic cancer and the patients' caregivers are enrolled in this study as of the writing of this protocol report. Oncologists are randomly assigned to the intervention group (IG) or control group (CG). Patients and caregivers are allocated to the same group as their oncologists. The IG oncologists receive a 2.5-hour individual communication skills training, and patients and caregivers receive a half-hour coaching intervention to facilitate prioritising and discussing questions and concerns; the CG participants do not receive any training. Follow-up data will be collected quarterly for 6 months for a year and then annually for up to 3 years. The primary endpoint is the intergroup difference between before-intervention and after-intervention patient-centred communication behaviours during oncology visits. This study is conducted in accordance with the ethical guidelines for clinical studies published by Japan's Ministry of Education, Cultural, Sports, Science and Technology, the Ministry of Health, Labour and Welfare, and the ethical principles established for research on humans stipulated in the Declaration of Helsinki and further amendments thereto. The protocol was approved by the Institutional Review Board of National Cancer Center, Japan on 4 July 2018 (ID: 2017-474). This study is currently enrolling participants. Enrolment period ends 31 July 2020; estimated follow-up date is 31 March 2023. UMIN Clinical Trial Registry (UMIN000033612); pre-results.


Normal Components and Contaminants.
The pancreas is a retroperitoneal organ located in the duodenal loop with the posterior wall of the stomach overlying it and the left lobe of the liver lying anteriorly to it. Tissues from these organs, in addition to the lesion of interest within the pancreas, may be sampled during fine-needle aspiration (FNA) procedures. Therefore, it is important to recognize the cytology of normal benign components of the pancreas and potential contaminants in order to render a correct diagnosis and avoid pitfalls. Normal components of the pancreas include ductal epithelial cells, acinar cells, and islet cells. In addition to the normal pancreatic cells, it is not uncommon to encounter epithelial cells from the duodenal and gastric mucosa with endoscopic ultrasound-guided fine-needle aspiration. It is important to recognize these cells as benign and to distinguish them from a well-differentiated pancreatic adenocarcinoma. Besides these, mesothelial cells and hepatocytes and bile duct cells from the liver may be sampled as well. Here, the cytological features of normal components and contaminants are described in detail.


HIV transmission behaviors in jail/prison among puerto rican drug injectors in New York and Puerto Rico.
This study examined HIV risk behavior in jail/prison among Puerto Rican drug injectors in New York (NY, n = 300) and Puerto Rico (PR, n = 200), and its relationship with later drug and sex risk behaviors. During 3 years prior to interview, 66% of NY and 43% of PR samples were incarcerated at least once. While incarcerated, 5% of NY and 53% of PR injected drugs. Few reported engaging in sex inside jail/prison (5% in both sites). Of those who engaged in risk behaviors in jail/prison, almost all reported having unprotected sex and sharing injection equipment. The impact of jail/prison risk behaviors on risk behaviors after release differed between the two sites: they were more related to subsequent sex risk behaviors in NY, and subsequent injection risk behaviors in PR. The findings indicate a need for effective drug treatment programs inside jail/prisons to reduce HIV-related risk behaviors among drug injectors during incarceration and after release.


Sociocultural Influences on Moral Judgments: East-West, Male-Female, and Young-Old.
Gender, age, and culturally specific beliefs are often considered relevant to observed variation in social interactions. At present, however, the scientific literature is mixed with respect to the significance of these factors in guiding moral judgments. In this study, we explore the role of each of these factors in moral judgment by presenting the results of a web-based study of Eastern (i.e., Russia) and Western (i.e., USA, UK, Canada) subjects, male and female, and young and old. Participants (n = 659) responded to hypothetical moral scenarios describing situations where sacrificing one life resulted in saving five others. Though men and women from both types of cultures judged (1) harms caused by action as less permissible than harms caused by omission, (2) means-based harms as less permissible than side-effects, and (3) harms caused by contact as less permissible than by non-contact, men in both cultures delivered more utilitarian judgments (save the five, sacrifice one) than women. Moreover, men from Western cultures were more utilitarian than Russian men, with no differences observed for women. In both cultures, older participants delivered less utilitarian judgments than younger participants. These results suggest that certain core principles may mediate moral judgments across different societies, implying some degree of universality, while also allowing a limited range of variation due to sociocultural factors.


Membrane diffusing capacity and pulmonary capillary volume in rheumatoid disease.
In some patients with rheumatoid disease gas transfer across the lungs is abnormal. We measured the membrane component of gas transfer (Dm) and pulmonary capillary volume (Vc) in 48 patients with rheumatoid arthritis and in 48 normal volunteers matched for age, sex, and smoking habits. Volunteers had normal chest radiographs and normal forced expiratory volume in one second and vital capacity. There were no significant differences between the rheumatoid and control groups for Dm. Mean Vc in rheumatoid male smokers (64.0 ml, SD 16.5) was significantly lower than in control male smokers (76.3 ml, SD 18.0 p less than 0.05). In rheumatoid female smokers mean Vc (43.4 ml, SD 13.3) was significantly lower than in rheumatoid female non-smokers (58.4 ml, SD 15.4 p less than 0.01). There was no significant difference between rheumatoid and control female non-smokers (mean Vc 58.4 ml and 60.7 ml respectively). Significant differences in Vc in terms of per cent predicted normal were found between patients receiving corticosteroids and those not receiving corticosteroids or penicillamine (p less than 0.02) and between patients with nodules and those without (p less than 0.05). Patients with persistently low transfer factor for five years had a significantly lower Vc (p less than 0.02). There was no consistent correlation between Dm and Vc and dynamic compliance or static recoil pressure. It appears that the abnormality of transfer factor in rheumatoid disease previously demonstrated is caused by reduction of Vc. It seems that involvement of pulmonary blood vessels occurs in patients with nodules and is suppressed by treatment with corticosteroids.


A Transcriptional Regulatory Map of Iron Homeostasis Reveals a New Control Circuit for Capsule Formation in Cryptococcus neoformans.
Iron is essential for the growth of the human fungal pathogen Cryptococcus neoformans within the vertebrate host, and iron sensing contributes to the elaboration of key virulence factors, including the formation of the polysaccharide capsule. C. neoformans employs sophisticated iron acquisition and utilization systems governed by the transcription factors Cir1 and HapX. However, the details of the transcriptional regulatory networks that are governed by these transcription factors and connections to virulence remain to be defined. Here, we used chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) and transcriptome analysis (RNA-seq) to identify genes directly regulated by Cir1 and/or HapX in response to iron availability. Overall, 40 and 100 genes were directly regulated by Cir1, and 171 and 12 genes were directly regulated by HapX, under iron-limited and replete conditions, respectively. More specifically, we found that Cir1 directly controls the expression of genes required for iron acquisition and metabolism, and indirectly governs capsule formation by regulating specific protein kinases, a regulatory connection not previously revealed. HapX regulates the genes responsible for iron-dependent pathways, particularly under iron-depleted conditions. By analyzing target genes directly bound by Cir1 and HapX, we predicted the binding motifs for the transcription factors and verified that the purified proteins bind these motifs in vitro Furthermore, several direct target genes were coordinately and reciprocally regulated by Cir1 and HapX, suggesting that these transcription factors play conserved roles in the response to iron availability. In addition, biochemical analyses revealed that Cir1 and HapX are iron-containing proteins, implying that the regulatory networks of Cir1 and HapX may be influenced by the incorporation of iron into these proteins. Taken together, our identification of the genome-wide transcriptional networks provides a detailed understanding of the iron-related regulatory landscape, establishes a new connection between Cir1 and kinases that regulate capsule, and underpins genetic and biochemical analyses that reveal iron-sensing mechanisms for Cir1 and HapX in C. neoformans.


Sexual function in women with type 1 diabetes matched with a control group: depressive and psychosocial aspects.
Sexual dysfunction in women with diabetes, despite its important consequences to their quality of life, has been investigated only recently with conflicting results about its prevalence and association with complications and psychological factors. To assess the prevalence of the alteration of sexual function and the influence of metabolic control and psychological factors on female sexuality. Seventy-seven adult Italian women with type 1 diabetes, matched with a control group (n=77), completed questionnaires evaluating sexual function (Female Sexual Function Index, FSFI), depressive symptoms (Self-Rating Depression Scale, SRDS), social and family support (Multidimensional Scale of Perceived Social Support), and diabetes-related quality of life (Diabetes Quality of Life). Clinical and metabolic data were collected. Prevalence and magnitude of sexual dysfunction in terms of alteration of sexual functioning as measured by the FSFI scores. The prevalence of sexual dysfunction was similar in diabetes and control groups (33.8% vs. 39.0%, not significant), except for higher SRDS scores in the diabetes group (47.39 ± 11.96 vs. 43.82 ± 10.66; P=0.047). Diabetic patients with an alteration of sexual function showed a significantly higher SRDS score (53.58 ± 14.11 vs. 44.24 ± 9.38, P=0.004). Depression symptoms and good glycemic control (A1C<7.0%) were predictors of alteration of sexual function only in diabetic patients (odds ratio [OR]=1.082; 95% confidence interval [CI]: 1.028-1.140; OR=5.085; 95% CI: 1.087-23.789), since we have not found any significant predictor of sexual dysfunction in the control group. The prevalence of sexual dysfunction in our type 1 diabetes patients' sample is similar to those reported in other studies. Diabetic patients are similar to healthy people except for higher depression scores. Further studies are necessary to understand whether the correlation between an alteration of sexual function and good glycemic control may be related to the role of control as a mental attitude.


Energy optimization during walking involves implicit processing.
Gait adaptations, in response to novel environments, devices or changes to the body, can be driven by the continuous optimization of energy expenditure. However, whether energy optimization involves implicit processing (occurring automatically and with minimal cognitive attention), explicit processing (occurring consciously with an attention-demanding strategy) or both in combination remains unclear. Here, we used a dual-task paradigm to probe the contributions of implicit and explicit processes in energy optimization during walking. To create our primary energy optimization task, we used lower-limb exoskeletons to shift people's energetically optimal step frequency to frequencies lower than normally preferred. Our secondary task, designed to draw explicit attention from the optimization task, was an auditory tone discrimination task. We found that adding this secondary task did not prevent energy optimization during walking; participants in our dual-task experiment adapted their step frequency toward the optima by an amount and at a rate similar to participants in our previous single-task experiment. We also found that performance on the tone discrimination task did not worsen when participants were adapting toward energy optima; accuracy scores and reaction times remained unchanged when the exoskeleton altered the energy optimal gaits. Survey responses suggest that dual-task participants were largely unaware of the changes they made to their gait during adaptation, whereas single-task participants were more aware of their gait changes yet did not leverage this explicit awareness to improve gait adaptation. Collectively, our results suggest that energy optimization involves implicit processing, allowing attentional resources to be directed toward other cognitive and motor objectives during walking.


Cancer statistics for the US Hispanic/Latino population, 2021.
The Hispanic/Latino population is the second largest racial/ethnic group in the continental United States and Hawaii, accounting for 18% (60.6 million) of the total population. An additional 3 million Hispanic Americans live in Puerto Rico. Every 3 years, the American Cancer Society reports on cancer occurrence, risk factors, and screening for Hispanic individuals in the United States using the most recent population-based data. An estimated 176,600 new cancer cases and 46,500 cancer deaths will occur among Hispanic individuals in the continental United States and Hawaii in 2021. Compared to non-Hispanic Whites (NHWs), Hispanic men and women had 25%-30% lower incidence (2014-2018) and mortality (2015-2019) rates for all cancers combined and lower rates for the most common cancers, although this gap is diminishing. For example, the colorectal cancer (CRC) incidence rate ratio for Hispanic compared with NHW individuals narrowed from 0.75 (95% CI, 0.73-0.78) in 1995 to 0.91 (95% CI, 0.89-0.93) in 2018, reflecting delayed declines in CRC rates among Hispanic individuals in part because of slower uptake of screening. In contrast, Hispanic individuals have higher rates of infection-related cancers, including approximately two-fold higher incidence of liver and stomach cancer. Cervical cancer incidence is 32% higher among Hispanic women in the continental US and Hawaii and 78% higher among women in Puerto Rico compared to NHW women, yet is largely preventable through screening. Less access to care may be similarly reflected in the low prevalence of localized-stage breast cancer among Hispanic women, 59% versus 67% among NHW women. Evidence-based strategies for decreasing the cancer burden among the Hispanic population include the use of culturally appropriate lay health advisors and patient navigators and targeted, community-based intervention programs to facilitate access to screening and promote healthy behaviors. In addition, the impact of the COVID-19 pandemic on cancer trends and disparities in the Hispanic population should be closely monitored.


GR 20263, a new broad-spectrum cephalosporin with anti-pseudomonal activity.
GR 20263 is a new broad-spectrum injectable cephalosporin which is stable to most beta-lactamases. Its in vitro activities were of the same order as those of cefotaxime against most gram-negative bacteria, were clearly inferior to cefotaxime against Staphylococcus aureus, but were significantly more active against Pseudomonas aeruginosa. Against the 25 strains used, GR 20263 was significantly more active than any of the other agents tested: piperacillin, azlocillin, gentamicin, amikacin, and carbenicillin. GR 20263 protected mice against experimental infections with P. aeruginosa more effectively than other beta-lactam antibiotics; its general effectiveness in this test was comparable with gentamicin. Studies on human volunteers showed that it produces high, long-lasting blood levels, with much of the antibiotic being recovered in the urine. Intramuscular and intravenous injections were well tolerated by the volunteers, and there were no untoward side effects.


MS-based phenotypic characterization of a human blood protein from urinary waste products.
The urine proteome (urineome) has become an ideal biological fluid for biomarker study and detection due to its rich protein content as well as its ease and abundance in collection. Protein variation in human plasma has been linked to the presence of disease states in humans; however, it stands to reason that the same is true of the equally complex urineome. In this manuscript we present the combination of two proteomics technologies, mass spectrometric immunoassay and a bioreactive probe, for the detection and characterization of the protein variants of transthyretin (TTR) found in human urine. Coupling these two technologies we could precisely identify protein variants within a population of normal individuals. This is the first report of the detailed characterization of urinary TTR using this combination of proteomic analytical techniques, and demonstrates a novel non-invasive methodology for the routine analysis of this clinically significant urine protein target.


Halo-derivatised calix[4]tubes.
Halo functionalisation of calix[4]tubes has been investigated through both derivatisation of individual calix[4]arenes and calix[4]tubes, using classical synthetic methods, to allow preparation of a series of novel derivatives. The solution and solid state properties are in accordance with the constituent[4]arenes adopting flattened cone arrangements which on complexation with potassium simplify to a regular cone. Electrospray and 1H NMR studies, combined with molecular modelling have been used to ascertain the metal binding of this new series of cryptand like ionophores, demonstrating their retained selectivity for binding potassium over other Group 1 metals and the dependence on counter anion in the weak binding of silver.


Lipopolysaccharide Induced Opening of the Blood Brain Barrier on Aging 5XFAD Mouse Model.
The development of neurotherapeutics for many neurodegenerative diseases has largely been hindered by limited pharmacologic penetration across the blood-brain barrier (BBB). Previous attempts to target and clear amyloid-β (Aβ) plaques, a key mediator of neurodegenerative changes in Alzheimer's disease (AD), have had limited clinical success due to low bioavailability in the brain because of the BBB. Here we test the effects of inducing an inflammatory response to disrupt the BBB in the 5XFAD transgenic mouse model of AD. Lipopolysaccharide (LPS), a bacterial endotoxin recognized by the innate immune system, was injected at varying doses. 24 hours later, mice were injected with either thioflavin S, a fluorescent Aβ-binding small molecule or 30 nm superparamagnetic iron oxide (SPIO) nanoparticles, both of which are unable to penetrate the BBB under normal physiologic conditions. Our results showed that when pretreated with 3.0 mg/kg LPS, thioflavin S can be found in the brain bound to Aβ plaques in aged 5XFAD transgenic mice. Following the same LPS pretreatment, SPIO nanoparticles could also be found in the brain. However, when done on wild type or young 5XFAD mice, limited SPIO was detected. Our results suggest that the BBB in aged 5XFAD mouse model is susceptible to increased permeability mediated by LPS, allowing for improved delivery of the small molecule thioflavin S to target Aβ plaques and SPIO nanoparticles, which are significantly larger than antibodies used in clinical trials for immunotherapy of AD. Although this approach demonstrated efficacy for improved delivery to the brain, LPS treatment resulted in significant weight loss even at low doses, resulting from the induced inflammatory response. These findings suggest inducing inflammation can improve delivery of small and large materials to the brain for improved therapeutic or diagnostic efficacy. However, this approach must be balanced with the risks of systemic inflammation.


Taking photographs with a microscope.
We describe a simple, economical, and highly practical technique for taking digital photographs of specimens visualized through a light microscope. Most models of light microscope and compact digital camera, and even some cameraphones, can be used. The technique is quick to learn and can easily be performed in a resource-poor setting. It can be used to assist with diagnosis in remote areas and can be extremely useful for teaching.


GABA(B) receptors as potential therapeutic targets.
gamma-Aminobutyric acid-B (GABA(B)) receptors are broadly expressed in the nervous system and have been implicated in a wide variety of neurological and psychiatric disorders. To date the only GABA(B) drug on the market is the agonist baclofen (Lioresal((R))) that is used to treat severe spasticity of cerebral and spinal origin. In addition baclofen is effective in animal models for many central and peripheral disorders, but side-effects and the development of tolerance prohibited a more widespread use of this drug in man. Similarly GABA(B) antagonists show great therapeutic promise but their shortcomings, e.g. the lack of brain penetration or some proconvulsive potential, prevented clinical development. The cloning of GABA(B) receptors in 1997 revived interest in these receptors as drug targets. The long-awaited availability of the tools that were necessary to develop more selective and safer drugs stimulated an impressive activity in the field. The demonstration that GABA(B) receptors needed to heteromerize for function provided new insights into the structure of G-protein coupled receptors in general and enabled to identify allosteric GABA(B) drugs. Gene knockout mice revealed neuronal systems that are under tonic GABA(B) control and therefore best suited for therapeutic intervention. Significant advances were made in clarifying the relationship between GABA(B) receptors and the receptors for gamma-hydroxybutyrate (GHB), a drug of abuse. Here we provide and update on the molecular composition, the physiology and the pharmacology of GABA(B) receptors and discuss to what extent our current knowledge influences ongoing and future drug discovery efforts.


Measuring sensitivity to social distancing behavior during the COVID-19 pandemic.
Social distancing remains an effective nonpharmaceutical behavioral interventions to limit the spread of COVID-19 and other airborne diseases, but monitoring and enforcement create nontrivial challenges. Several jurisdictions have turned to "311" resident complaint platforms to engage the public in reporting social distancing non-compliance, but differences in sensitivity to social distancing behaviors can lead to a mis-allocation of resources and increased health risks for vulnerable communities. Using hourly visit data to designated establishments and more than 71,000 social distancing complaints in New York City during the first wave of the pandemic, we develop a method, derived from the Weber-Fechner law, to quantify neighborhood sensitivity and assess how tolerance to social distancing infractions and complaint reporting behaviors vary with neighborhood characteristics. We find that sensitivity to non-compliance is lower in minority and low-income neighborhoods, as well as in lower density areas, resulting in fewer reported complaints than expected given measured levels of overcrowding.


Boutons originating from the same axon do not participate equally in synaptic transmission.
Morphological changes in the synaptic boutons located on the ciliary neurons were observed following stimulation of the Edinger-Westphal nucleus (EWn). A reduction in the number of clear and dense core vesicles (DCVs) per unit area and an increased surface density of vacuoles were observed in boutons located proximal to the afferent axon. Only a slight reduction in the number of DCVs per unit area was observed on boutons located distally to the afferent axon. Several mechanisms are proposed to explain why all boutons do not participate equally in synaptic transmission.


Late Gadolinium Enhancement in Patients With Hypertrophic Cardiomyopathy and Preserved Systolic Function.
A high proportion of patients with hypertrophic cardiomyopathy (HCM) have evidence of late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR). This study sought to assess the incremental prognostic utility of LGE in patients with HCM. We studied 1,423 consecutive low-/intermediate-risk patients with HCM (age ≥18 years) with preserved left ventricular (LV) ejection fraction (mean age 66 ± 14 years, 60% men) who underwent transthoracic echocardiography (TTE) (including dimensions and LV outflow tract gradients) and CMR (including LGE as a % of LV mass) at our center between January 2008 and December 2015. The primary composite endpoint was sudden cardiac death (SCD) and appropriate implantable cardioverter-defibrillator discharge. The percent 5-year SCD risk score was calculated. The mean 5-year SCD risk score was 2.3 ± 2.0. Mean maximal LV outflow tract gradient (TTE) was 70 ± 55 mm Hg (median 74 mm Hg [interquartile range (IQR): 10 to 67 mm Hg]); indexed LV mass and LGE (both on CMR) were 91 ± 10 g/m2 and 8.4 ± 12% (IQR: 0% to 19%); 50% had LGE on CMR. Of these, 458 were nonobstructive and 965 were obstructive (of which 686 were underwent myectomy). At 4.7 ± 2.0 years of follow-up, 60 (4%) met the composite endpoint. On quadratic spline analysis, LGE ≥15% was associated with increased risk of composite events. In the obstructive subgroup, on competing risk regression analysis, ≥15% LGE (subhazard ratio: 3.04 [95% confidence interval: 1.48 to 6.10]) was associated with a higher rate and myectomy (subhazard ratio: 0.44 [95% confidence interval: 0.20 to 0.76]) was associated with a lower rate of composite endpoints (both p < 0.01). Similarly, sequential addition of LGE ≥15% and myectomy to % 5-year SCD risk score improved the log likelihood ratios from -227.85 to -219.14 (chi-square 17) and to -215.14 (chi-square 8; both p < 0.01). Association of %LGE with composite events was similar even in myectomy and nonobstructive subgroups. In low-/intermediate-risk adult patients with HCM (obstructive, myectomy, and nonobstructive subgroups) with preserved systolic function, %LGE was significantly associated with a higher rate of composite endpoint, providing incremental prognostic utility.


Extracorporeal treatment for thallium poisoning: recommendations from the EXTRIP Workgroup.
The EXtracorporeal TReatments In Poisoning (EXTRIP) workgroup was formed to provide recommendations on the use of extracorporeal treatment (ECTR) in poisoning. To test and validate its methods, the workgroup reviewed data for thallium (Tl). After an extensive search, the co-chairs reviewed the articles, extracted the data, summarized findings, and proposed structured voting statements following a predetermined format. A two-round modified Delphi method was chosen to reach a consensus on voting statements and RAND/UCLA Appropriateness Method to quantify disagreement. Blinded votes were compiled, returned, and discussed during a conference call. A second vote determined the final recommendations. Forty-five articles met inclusion criteria. Only case reports and case series were identified, yielding a very low quality of evidence for all recommendations. Data on 74 patients, including 11 who died, were abstracted. The workgroup concluded that Tl is slightly dialyzable and made the following recommendations: ECTR is recommended in severe Tl poisoning (1D). ECTR is indicated if Tl exposure is highly suspected on the basis of history or clinical features (2D) or if the serum Tl concentration is >1.0 mg/L (2D). ECTR should be initiated as soon as possible, ideally within 24-48 hours of Tl exposure (1D), and be continued until the serum Tl concentration is <0.1 mg/L for a minimal duration of 72 hours (2D). Despite Tl's low dialyzability and the limited evidence, the workgroup strongly recommended extracorporeal removal in the case of severe Tl poisoning.


Conformational entropy in molecular recognition by proteins.
Molecular recognition by proteins is fundamental to almost every biological process, particularly the protein associations underlying cellular signal transduction. Understanding the basis for protein-protein interactions requires the full characterization of the thermodynamics of their association. Historically it has been virtually impossible to experimentally estimate changes in protein conformational entropy, a potentially important component of the free energy of protein association. However, nuclear magnetic resonance spectroscopy has emerged as a powerful tool for characterizing the dynamics of proteins. Here we employ changes in conformational dynamics as a proxy for corresponding changes in conformational entropy. We find that the change in internal dynamics of the protein calmodulin varies significantly on binding a variety of target domains. Surprisingly, the apparent change in the corresponding conformational entropy is linearly related to the change in the overall binding entropy. This indicates that changes in protein conformational entropy can contribute significantly to the free energy of protein-ligand association.


Neonatal outcome using ultrathin fetoscope for laser coagulation in twin-to-twin-transfusion syndrome.
To improve neonatal outcome using ultrathin fetoscope for laser treatment of twin-to-twin transfusion syndrome. Retrospective cohort study of a series of 80 cases of twin-to-twin-transfusion syndrome prior to 26-weeks' gestation subjected to laser coagulation by means of a 1.0/1.2 mm fiber fetoscope with a sheath sectional area 2.65 mm(2)/3.34 mm(2) (n=27) and a 2.0 mm classic lens fetoscope with a sheath sectional area: 6.63 mm(2)/11.27 mm(2) (n=53). The survival rates of at least one twin in the compared groups were 94.4% (classic optic) and 100% (ultrathin optic), for both twins: 75.5% and 83.3%, respectively. By decreasing sheath diameter a pregnancy was prolonged by an average of 21.3 days (P=0.0045), with a resulting increase in the recipient's weight of 389 g (P=0.0049) and an increase in the donor's Apgar score. However, the intervention with ultrathin optic took 11 min longer (P=0.031). The reduction of the iatrogenic damage of the amniotic membrane using ultrathin fetoscope with a small sheath, significantly improves the neonatal outcome after laser treatment of twin-to-twin-transfusion syndrome. The operator should only commence working with the 1 mm fetoscope after the learning curve has been accomplished.


Reduction of Radiation Dose Received by Surgeons and Patients During Percutaneous Nephrolithotomy: A New Shielding Method.
Due to high prevalence of urolithiasis, endourologic interventions have increased for the treatment of patients with urinary stones. During fluoroscopy-guided percutaneous nephrolithotomy (PCNL), the surgeon and the patient are exposed to X-ray and its harmful effects. This study aimed to assess the reduction of the radiation dose received by surgeons and patients after using a new shielding method. In this study, the dose of radiation exposure by the surgeon and patient during PCNL under fluoroscopic procedure with conventional shielding methods was compared to a new shielding method designed by the researcher. For this purpose, shields and lead cones with a thickness of 0.5 mm were used. Also, to evaluate the dose of radiation received by surgeons and patients in different parts of the body, thermoluminescent dosimeters (TLD) were used. By using the new shielding method, a 37 ± 2% reduction was found in the dose exposure as compared to the conventional shielding method. The maximum reduction in radiation dose was specified to the surgeon's hands, while the lowest reduction in radiation dose was related to the surgeon's thyroid gland. The maximum and minimum reductions in radiation exposure for patients were specified to patients' feet and chest respectively. There is a significant difference between the total dose received by the surgeons and the patients following the use of the new shielding method and the standard shielding method. The new shielding method can reduce 37 ± 2% of the x-ray received by the patient and the surgeon during fluoroscopy-guided PCNL.


[The use of NMP22 Bladder-Chek for the diagnosis and follow-up bladder cancer].
The goal of this work is to evaluate the usefulness of NMP22 BladderChek in the diagnosis and follow-up of bladder cancer, comparing it with cystoscopy and urine cytology. Group 1: 109 asymptomatic patients on follow up for bladder cancer underwent cystoscopy, cytology and NMP22 BladderChek. Group 2:15 patients with history of hematuria underwent cystoscopy and NMP22 BladderChek. Group 1: 9 patients had tumor relapse. Sensitivity was 25% for NMP22 test, 50% for citology and 100% for cystoscopy Specificity was 91.1%, 94.1% and 95% respectively. Group 2: 12 patients had bladder cancer. The sensitivity was of 83.3% for NMP22 BladderChek and 100% for cystoscopy. The specificity was of 100% for NMP22 BladderChek and 66.7% for cystoscopy. The low sensitivity of NMP22 Bladder-Chek invalidates it as alternative method to cystoscopy in the follow-up of bladder cancer. But it can be recommended for screening in patients without history of bladder cancer but with an increased risk (smokers, patients with dysuria and hematuria).


[Evaluation of genetic variability of the Kamchatka crab Paralithodes camtschaticus (Tilesius) using allozyme markers].
Interspecific genetic variation in populations of red king crab Paralithodes camtschaticus Tilesius (Litholidae, Decapoda: Crustacea) was examined using allozyme markers. The activity of 57 enzymes and the general protein presumably encoded by 92 loci was detected. The level of allozyme variability was low: the expected heterozygosity and the proportion of polymorphic loci were respectively 0.027 +/- 0.008 and 6.5%. This level of heterozygosity is three times lower than the average value for 122 crustacean species (0.082 +/- 0.007). Although genetic variants were found at 22 loci, their frequencies were generally low: only in loci 6-Pgd, Alp-1, and Pep-1 did the frequencies of the most common alleles not exceed 0.9. All polymorphic loci except one had two alleles; the exception was 6-Pgd, which had three alleles. The possible reasons for the low level of allozyme variability in red king crab are discussed.


Phosphorus runoff: effect of tillage and soil phosphorus levels.
Continued inputs of fertilizer and manure in excess of crop requirements have led to a build-up of soil phosphorus (P) levels and increased P runoff from agricultural soils. The objectives of this study were to determine the effects of two tillage practices (no-till and chisel plow) and a range of soil P levels on the concentration and loads of dissolved reactive phosphorus (DRP), algal-available phosphorus (AAP), and total phosphorus (TP) losses in runoff, and to evaluate the P loss immediately following tillage in the fall, and after six months, in the spring. Rain simulations were conducted on a Typic Argiudoll under a corn (Zea mays L.)-soybean [Glycine max (L.) Merr.] rotation. Elapsed time after tillage (fall vs. spring) was not related to any form of P in runoff. No-till runoff averaged 0.40 mg L(-1) and 0.05 kg ha(-1) DRP and chisel-plow plots averaged 0.24 mg L(-1) and 0.02 kg ha(-1) DRP concentration and loads, respectively. The relationship between DRP and Bray P1 extraction values was approximated by a logistic function (S-shaped curve) for no-till plots and by a linear function for tilled plots. No significant differences were observed between tillage systems for TP and AAP in runoff. Bray P1 soil extraction values and sediment concentration in runoff were significantly related to the concentrations and amounts of AAP and TP in runoff. These results suggest that soil Bray P1 extraction values and runoff sediment concentration are two easily measured variables for adequate prediction of P runoff from agricultural fields.


Current status on the diagnosis and evaluation of pancreatic tumor in Asia with particular emphasis on the role of endoscopic ultrasound.
In Asia, the incidence of pancreatic cancer in some countries has been increasing. Owing to most cases being diagnosed late, prognosis for pancreatic cancer remains dismal. It is clear that the future for pancreatic cancer lies in early detection. While the possible presence of pancreatic masses is often first raised by non-invasive abdominal imaging, such as computerized tomography and magnetic resonance imaging, smaller lesions and locoregional lymph node metastases are often not detectable by these means. Endoscopic ultrasonography (EUS) offers a higher sensitivity (93-100%) for detection of small potentially curable pancreatic masses than other existing imaging modalities. It is also recommended for the evaluation of portal vein confluence, portal vein, celiac axis, and superior mesentric artery origin, and exclusion of resectability. Due to the closer proximity of EUS to the target structure, and lower rate of needle tract seeding, EUS-guided fine-needle aspiration of pancreatic mass is considered the most suitable tissue acquisition technique. Lastly, EUS also enables the performance of endoscopic interventions. Its performance can be further enhanced with newer techniques, including contrast-enhanced ultrasound and elastrography. It is anticipated that in the near future, molecular technologies may make it possible to detect microscopic amounts of cancer in tissue or blood, predict relapse and survival after therapy, as well as determine optimal therapy.


A Survey on Workplace Violence Experienced by Critical Care Physicians.
Workplace violence (WPV) has been defined as, "violent acts including physical assault and threats of assault directed toward personnel at work or on duty". Healthcare staff are at highest risk of WPV among the professionals and it is more common among the critical care services. Prevalence of WPV among doctors all over the world is around 56-80% and in Indian scenario, it is around 40.8-75%. There is scarcity of studies on WPV among doctors from India. To our knowledge, this is the first of its kind survey conducted to know about the incidence of WPV amongst critical care physicians in India. This survey was conducted after taking due ethical committee clearance amongst critical care physicians attending a critical care conference. The purpose of the study was informed to the participants and a pretested, self-administered, semi-structured questionnaire was distributed among them for their voluntary and anonymous response. Out of 160 delegates who were given the questionnaire, 118 responses were collected and their forms were analyzed. Maximum responses (84%) received were of age group 20-40 years. Seventy-two percent respondents experienced WPV during their work hours. Most common type of violence reported was verbal violence (67%). Sixty-five percent respondents reported that poor communication was the leading cause of WPV. Due to WPV, most of the respondents (60%) had to change their place and pattern of work. Proper communication (76%) was the most common measure among multiple measures suggested by respondents for avoiding WPV. Eighty-three (98%) respondents opined that conflict management should be part of regular curriculum in medical education. Improving the communication skills amongst critical care physicians, teaching doctors about conflict management in their regular curriculum of medical education, spreading awareness in public about patient rights and taking initiatives in propagating an idea to "Fight against the diseases and not against the doctors" are the key measures to combat WPV. Kumar NS, Munta K, Kumar JR, Rao SM, Dnyaneshwar M, Harde Y. A Survey on Workplace Violence Experienced by Critical Care Physicians. Indian J Crit Care Med 2019;23(7):295-301.


Small-bowel occlusion after operative laparoscopy: our experience and review of the literature.
Bowel complications as a consequence of laparoscopic surgery are usually due to direct injuries; on the other hand, bowel occlusion is a rarely described event. We have retrospectively analyzed our data in this field. Out of 2652 laparoscopies performed between July 1996 and March 2000, three cases of small-bowel occlusion were observed. Two cases were due to bowel hernia through a 5-mm trocar port incision, the third was a consequence of an adhesion between the ileum and lost fragment of myoma. Two cases were treated laparoscopically, while in the third a laparotomy was required. At the time of writing, all the patients are well after a mean follow-up of 6 months. It appears important to also perform closure of the fascia and peritoneum after a 5-mm trocar port incision where there has been extensive manipulation.


Characterization of hemin binding activity of Streptococcus pneumoniae.
Streptococcus pneumoniae is a causative agent of bacterial pneumonia, otitis media, meningitis, and bacteremia. It causes considerable morbidity and mortality throughout the world, especially among children, the elderly, and immunocompromised individuals. We have demonstrated previously that the growth of S. pneumoniae is limited under iron-depleted conditions and can be restored by the addition of either hemin or hemoglobin. In the present study, we showed that S. pneumoniae had the ability to bind hemin and that the level of hemin binding activity was not affected by supplementation of the growth medium with iron. Approximately 70 to 80% of the hemin binding activity was mediated by proteinase-resistant components, and the remainder was mediated by proteins. Hemin binding proteins were located in both soluble extract and envelope fractions of pneumococcal cells. By batch affinity chromatography, a major hemin binding polypeptide with an apparent molecular mass of 43 kDa was identified in the cell lysate of S. pneumoniae. Polyclonal antibodies against this polypeptide were raised. By immunoblot analysis, this hemin binding polypeptide was localized in the envelope and did not exhibit any variation in molecular weight among all serotypes tested. The subcellular distribution of hemin binding activity may have functional implications.


The impact of group singing on mood, coping, and perceived pain in chronic pain patients attending a multidisciplinary pain clinic.
This study explored the impact of group singing on mood, coping, and perceived pain in chronic pain patients attending a multidisciplinary pain clinic. Singers participated in nine 30-minute sessions of small group singing, while comparisons listened to music while exercising. A short form of The Profile of Mood States (POMS) was administered before and after selected singing sessions to assess whether singing produced short-term elevations in mood. Results indicated that pre to post difference scores were significantly different between singing and control groups for only one of the 15 mood variables (i.e., uneasy). To test the longer term impacts of singing the Profile of Mood States, Zung Depression Inventory, Pain Self-Efficacy Questionnaire, Pain Rating Self-Statement, and Pain Disability Questionnaire were administered immediately before and after the singing sessions. All inventories other than the POMS were re-administered 6 months later. One-way ANCOVAs indicated that participants who attended the singing sessions showed evidence of postintervention improvements in active coping, relative to those who failed to attend, when preintervention differences in active coping were controlled for. While the singing group showed marked improvements from pre to postintervention on all mood, coping, and perceived pain variables, these improvements were also observed among comparison participants. The results of this study suggest that active singing may have some benefits, in terms of enhancing active coping, though the limitations of the study and small effect sizes observed suggest that further research is required to fully explore such effects.


Standardized image evaluation in patients with idiopathic normal pressure hydrocephalus: consistency and reproducibility.
Assess the agreement for two investigators between computed tomography (CT) and magnetic resonance imaging (MRI) for seven imaging features included in the iNPH Radscale, a radiological screening tool. The study included 35 patients with idiopathic normal pressure hydrocephalus (iNPH) who were treated surgically from 2011 to 2015 at Uppsala University Hospital with preoperative CT and MRI performed with maximum 3 months between scans. Seven features were assessed: Evans' index, temporal horn size, callosal angle, periventricular white matter changes, narrow high convexity sulci, focally enlarged sulci, and enlarged Sylvian fissures. All scans were assessed by two investigators who were blinded to each other's results and to clinical data. The agreement between CT and MRI was almost perfect for Evans' index, temporal horns, narrow sulci, and Sylvian fissures (kappa and intraclass correlation, 0.84-0.91, p ≤ 0.001). There was substantial to almost perfect agreement for callosal angle and focally enlarged sulci. The concordance between modalities was fair for changes in periventricular white matter. CT and MRI are equally good for assessing radiological signs associated with iNPH except for periventricular white matter changes, as MRI has superior soft tissue contrast. The other imaging features can be evaluated consistently, and assessments are reproducible independent of modality. Therefore, the iNPH Radscale is applicable to both CT and MRI and may become an important tool for standardized evaluation in the workup in patients with suspected iNPH.


Validated stability indicating RP-HPLC for quantitation of nitazoxanide in presence of its alkaline degradation products and their characterization by HPLC-tandem mass spectrometry.
A simple and sensitive stability indicating HPLC method was developed and validated for quantitative determination of Nitazoxanide (NTZ), a new antiprotozoal drug, in presence of degradation products generated under forced alkaline hydrolysis. Chromatographic separation was achieved on Inertsil C8-3 column (150 × 4.6 mm i.d.) using a mobile phase composed of acetonitrile: 50 mM ammonium acetate buffer (50:50, v/v, pH 5.0 adjusted with acetic acid) at a flow rate of 1 mL/min. Quantification was achieved with UV detection at 298 nm based on relative peak area. The method was linear over the concentration range of 0.8-50 µg/mL (r = 0.9999) with a limit of detection and quantification 0.0410 and 0.1242 µg/mL, respectively. The developed method has the requisite accuracy, selectivity, sensitivity and precision to assay NTZ in presence of its degradation products either in bulk powder or in pharmaceutical formulations. The degradation products were then identified by HPLC-MS/MS analysis using an electrospray ionization source and an ion trap analyzer.


The spatial control of Torso RTK activation: a C-terminal fragment of the Trunk protein acts as a signal for Torso receptor in the Drosophila embryo.
Regulated activation of receptor tyrosine kinases depends on both the presence of the receptors at the cell surface and on the availability of their ligands. In Drosophila, the torso tyrosine kinase receptor is distributed along the surface of the embryo but it is only activated at the poles by a diffusible extracellular ligand generated at each pole that is trapped by the receptor, thereby impeding further diffusion. Although it is known that this signal depends on the activity of several genes, such as torso-like and trunk, it is still unclear how is generated. The identification of the signal responsible for the torso receptor activation is an essential step towards understanding the mechanism that regulates the local restriction of torso signalling. Here we report that a fragment containing the carboxy-terminal 108 amino acids of the trunk protein retains trunk activity and is sufficient to activate torso signalling. We also show that this fragment bypasses the requirements for the other genes involved in the activation of the torso receptor. These results suggest that a cleaved form of the trunk protein acts as a signal for the torso receptor. We therefore propose that the restricted activation of the torso receptor is defined by the spatial control of the proteolytic processing of the trunk protein.


Transforming growth factor-beta1 induces junB mRNA accumulation, G1-phase arrest, and pRb dephosphorylation in human leukemia HL-60 cells.
Although TGF-beta1 unambiguously functions as a regulator of hematopoietic differentiation, its significance for the development of myeloid lineage is still questionable. In this study three components of early response to TGF-beta1 treatment were investigated in human promyelocytic leukemia HL-60 cells. Changes in junB mRNA accumulation and pRb dephosphorylation were accompained by accumulation of cells in G1 phase of the cell cycle. Time dependence of these changes may implicate mutual cooperation of the pRb and junB in the cell cycle control. It can be concluded that, although myeloid HL-60 cells are known to require rather complex cytokine stimulation to fully differentiate, they clearly possess the ability to respond to TGF-beta1.


Energy-Degeneracy-Driven Covalency in Actinide Bonding.
Evaluating the nature of chemical bonding for actinide elements represents one of the most important and long-standing problems in actinide science. We directly address this challenge and contribute a Cl K-edge X-ray absorption spectroscopy and relativistic density functional theory study that quantitatively evaluates An-Cl covalency in AnCl62- (AnIV = Th, U, Np, Pu). The results showed significant mixing between Cl 3p- and AnIV 5f- and 6d-orbitals (t1u*/t2u* and t2 g*/eg *), with the 6d-orbitals showing more pronounced covalent bonding than the 5f-orbitals. Moving from Th to U, Np, and Pu markedly changed the amount of M-Cl orbital mixing, such that AnIV 6d - and Cl 3p-mixing decreased and metal 5f - and Cl 3p-orbital mixing increased across this series.


Complete genome sequence of Mycobacterium immunogenum strain C14-1.MIM isolated from a hospitalized lung transplant recipient.
Mycobacterium immunogenum is a rapidly growing nontuberculous mycobacteria species that can cause healthcare-associated infections. We report the complete genome of C14-1.MIM, isolated via culture of a respiratory specimen obtained from a hospitalized lung transplant recipient. The circular chromosome contains 5,407,919 bp with a G + C content of 64.24% and 5,217 coding sequences.


Structure-activity relationships of receptor binding of 1,4-dihydropyridine derivatives.
The present study was undertaken to investigate binding activity of synthesized 1,4-dihydropyridine (1,4-DHP) derivatives (Compounds 1--124) to 1,4-DHP calcium channel antagonist receptors in rat brain. Sixteen 1,4-DHP derivatives inhibited specific (+)-[3H]PN 200-110 binding in rat brain in a concentration-dependent manner with IC50 value of 0.43 to 3.49 microM. Scatchard analysis revealed that compounds 54, 69, 85, like nifedipine, caused a significant increase in apparent dissociation constant (Kd) for (+)-[3H]PN 200-110, while compounds 68, 69 and 80 caused a significant decrease in maximal number of bindings sites (Bmax). These data suggest that compounds 68, 69 and 80 exert longer-acting antagonistic effects of 1,4-DHP receptors than compounds 54, 69 and 85. The structure-activity relationship study has revealed that 1) ester groups in 3- and 5-positions are the most effective, 2) the aryl group in the 4-position of 1,4-DHP ring is the basic requirement for optimal activity, 3) position and type of electron-withdrawing groups on phenyl group at position 4 would affect the receptor-binding activity. Furthermore, compound 58 exerted alpha1 receptor binding activity, being 1.6 times greater than 1,4-DHP receptors. Compounds 81, 84, 91, 94, 106, 108 and 109 showed significant binding of ATP-sensitive potassium (K ATP) channel, and the binding activities of compounds 81, 84, 108 and 109 were 1.6--3.8 times greater than the binding activity for 1,4-DHP receptors. Compounds 91 and 106 had similar binding activity for K ATP channel and 1,4-DHP receptors. In conclusion, the present study has shown that novel 1,4-DHP derivatives exert relatively high binding affinity to 1,4-DHP receptors and has revealed new aspect of structure-activity relationships of 1,4-DHP derivatives, especially hexahydroquinoline derivatives.


Research Note: Changes in chicken egg yolk metabolome during its formation.
The process of egg yolk formation involves the transport and uptake of a large number of small molecule metabolites. A qualitative and relative quantitative analysis of metabolites in the 3 formation periods of egg yolk was performed by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytical workflow. A total of 398 metabolites were identified, of which "amino acids and their metabolites", "lipid", and "organic acids and their derivatives" were the dominant egg yolk metabolite categories with the most metabolite species. The findings suggested that a number of amino acids, organic acids, nucleotides and their metabolites were deposited during follicular development to provide material support for later embryonic development. At the same time, some vitamins and carbohydrates were consumed during follicular development to support the normal development process. In addition, the small hierarchical follicle (SF) period may be a critical period for the regulation of the transport and deposition of some active ingredients. These results contribute to a comprehensive understanding of the nutrient deposition pattern and nutritional properties of egg yolk.


A survey of calpain inhibitors.
Calpain is unique among the cysteine protease family of enzymes in that it combines thiol protease activity with calmodulin-like activity. Despite its wide spread distribution the exact physiological function(s) of calpain is yet to be deciphered. The enzyme is however, implicated in a number of pathophysiological conditions. Due to the potential of calpain as a therapeutic target a number of inhibitors have been described for the enzyme. In this article we have grouped calpain inhibitors into those derived from natural sources, and those derived from chemical synthesis. Additionally, an overview of functional groups that have been used as warheads of calpain inhibitors is presented along with a discussion of the structure activity relationship studies of the address region of peptidyl calpain inhibitors. Recent work in this area has led to a better understanding of the structural requirements for tight binding of inhibitors to the active site of calpain. A discussion of peptidomimetic calpain inhibitors, nonpeptide calpain inhibitors, and selectivity of some calpain inhibitors are also presented. The recent disclosure of the crystal structure of a nonpeptide calpain inhibitor bound to a hydrophobic pocket on the calcium-binding domain of calpain has opened the door to future development of potent cell permeable nonpeptide calpain inhibitors.


Distributions of topological observables in inclusive three- and four-jet events in pp collisions at [Formula: see text][Formula: see text].
This paper presents distributions of topological observables in inclusive three- and four-jet events produced in pp collisions at a centre-of-mass energy of 7[Formula: see text] with a data sample collected by the CMS experiment corresponding to a luminosity of 5.1[Formula: see text]. The distributions are corrected for detector effects, and compared with several event generators based on two- and multi-parton matrix elements at leading order. Among the considered calculations, MadGraph interfaced with pythia6 displays the overall best agreement with data.


Comparative analysis of prevalence, risk factors, and molecular epidemiology of antibiotic-associated diarrhea due to Clostridium difficile, Clostridium perfringens, and Staphylococcus aureus.
We prospectively studied the comparative epidemiology and risk factors for Clostridium difficile, Clostridium perfringens, and Staphylococcus aureus antibiotic-associated diarrhea (AAD). Four thousand six hundred fifty-nine inpatient fecal specimens (11 months) were tested for C. difficile cytotoxin, C. perfringens enterotoxin, and S. aureus by Vero cell assay, enzyme-linked immunosorbent assay, and growth on fresh blood agar, respectively. Two distinct age-, sex-, and location-matched control patient groups were used for multivariate logistic regression risk factor analyses: symptomatic patients who were AAD pathogen negative and asymptomatic patients with histories of recent antimicrobial therapy. All AAD pathogen isolates were DNA fingerprinted. In AAD cases, the prevalences of C. difficile cytotoxin, C. perfringens enterotoxin, and S. aureus were 12.7%, 3.3%, and 0.2%, respectively (15.8% overall). Age of >70 years was a common risk factor. Other risk factors for infective AAD and C. difficile AAD included length of hospital stay and use of feeding tubes (length of stay odds ratios [OR], 1.017 and 1.012; feeding tube OR, 1.864 and 2.808). Female gender and use of antacids were significantly associated with increased risk of C. perfringens AAD (OR, 2.08 and 2.789, respectively), but unlike what was found for C. difficile AAD, specific antibiotic classes were not associated with increased risk. A limited number of genotypes caused the majority of C. difficile and C. perfringens AAD cases. Similar to what was found for C. difficile AAD, there was epidemiological evidence of C. perfringens AAD case clustering and reinfection due to different strains. C. difficile AAD was approximately 4 and 60 times more common than C. perfringens AAD and S. aureus AAD, respectively. Risk factors for these AAD pathogens differed, highlighting the need to define specific control measures. There is evidence of nosocomial transmission in cases of C. perfringens AAD.


Lack of strong immune selection pressure by the immunodominant, HLA-A*0201-restricted cytotoxic T lymphocyte response in chronic human immunodeficiency virus-1 infection.
Despite detailed analysis of the HIV-1-specific cytotoxic T lymphocyte response by various groups, its relation to viral load and viral sequence variation remains controversial. We analyzed HLA-A*0201 restricted cytotoxic T lymphocyte responses in 17 HIV-1-infected individuals with viral loads ranging from < 400 to 221,000 HIV RNA molecules per milliliter of plasma. In 13 out of 17 infected subjects, CTL responses against the SLYNTVATL epitope (p17 Gag; aa 77-85) were detectable, whereas two other HLA-A*0201 restricted epitopes (ILKEPVHGV, IV9; and VIYQYMDDL, VL9) were only recognized by six and five individuals out of 17 individuals tested, respectively. Naturally occurring variants of the SL9 epitope were tested for binding to HLA-A*0201 and for recognition by specific T cell clones generated from five individuals. Although these variants were widely recognized, they differed by up to 10,000-fold in terms of variant peptide concentrations required for lysis of target cells. A comparison of viral sequences derived from 10 HLA-A*0201-positive individuals to sequences obtained from 11 HLA-A*0201-negative individuals demonstrated only weak evidence for immune selective pressure and thus question the in vivo efficacy of immunodominant CTL responses present during chronic HIV-1 infection.


Smoking and abdominal fat in blood donors.
To assess the association between smoking and abdominal fat among male blood donors. This was a cross-sectional study involving 1,235 adult male blood donors (age, 20-59 years) in the city of Cuiabá, Brazil. Socioeconomic, demographic, and anthropometric data, as well as information on the lifestyle of the participants, were collected. In this study, waist circumference and waist-to-hip ratio were used as markers of abdominal fat. The association between these two markers and smoking was analyzed by multiple linear regression in separate models, adjusted for potential confounders. Of the 1,235 respondents, 273 (22.1%) reported being smokers, and, of those, 99 (36.3%) reported smoking more than 15 cigarettes per day. The average body mass index was lower among smokers than among nonsmokers (p < 0.001). In the multiple linear regression analyses, smoking was associated with waist circumference and waist-to-hip ratio for smokers of 6-10 cigarettes/day and of > 11 cigarettes/day. In our sample, smoking was positively associated with indicators of abdominal fat, regardless of potential confounding factors, including the consumption of alcoholic beverages.


Uncovering extensive post-translation regulation during human cell cycle progression by integrative multi-'omics analysis.
Analysis of high-throughput multi-'omics interactions across the hierarchy of expression has wide interest in making inferences with regard to biological function and biomarker discovery. Expression levels across different scales are determined by robust synthesis, regulation and degradation processes, and hence transcript (mRNA) measurements made by microarray/RNA-Seq only show modest correlation with corresponding protein levels. In this work we are interested in quantitative modelling of correlation across such gene products. Building on recent work, we develop computational models spanning transcript, translation and protein levels at different stages of the H. sapiens cell cycle. We enhance this analysis by incorporating 25+ sequence-derived features which are likely determinants of cellular protein concentration and quantitatively select for relevant features, producing a vast dataset with thousands of genes. We reveal insights into the complex interplay between expression levels across time, using machine learning methods to highlight outliers with respect to such models as proteins associated with post-translationally regulated modes of action. We uncover quantitative separation between modified and degraded proteins that have roles in cell cycle regulation, chromatin remodelling and protein catabolism according to Gene Ontology; and highlight the opportunities for providing biological insights in future model systems.


Mirau correlation microscope.
We have constructed a correlation microscope based on the Mirau interferometer configuration using a thin silicon nitride film beam splitter. This microscope provides the amplitude and phase information for the reflected signal from a sample located on the microscope-object plane. The device is remarkably insensitive to vibrations and is self-correcting for spherical and chromatic range aberrations of the objective. An imaging theory for the correlation microscope has been derived, which predicts accurately both the transverse resolution at a sharp edge and the range resolution for a perfect plane reflector. The range resolution is slightly better than that for a scanning optical microscope using a lens with the same aperture.


Treatment choice in the presence of conflicting information: The role of physician likeability in the choice of non-proven therapies against conventional treatment.
Research on why patients sometimes choose non-proven therapies (NPT) instead of conventional treatments is limited. We investigated how physician likeability influences the choice of NPT instead of conventional treatment. In an experiment with three medical scenarios, participants (N = 384) consulted two physicians who gave conflicting recommendations: The first physician recommended a conventional treatment and the second one recommended a NPT. We manipulated the likeability of the first physician, who was either likeable or unlikeable. Using mediation analyses, we explored how the effect of likeability was channelled and whether time pressure influenced treatment choice. Participants chose the NPT more often (OR = 1.43, 95% CI [1.03-2.00]), had more positive affective responses, and perceived more benefit from NPT when the conventional treatment was recommended by an unlikeable (vs. likeable) physician. Time pressure had no effect on treatment choice. Physicians' likeability might play an important role in treatment choice in the presence of conflicting information. Providers should be cognizant that poor communication might push patients to prefer the advice of more likeable physicians, even when they prescribe NPT instead of conventional treatment.


Use of a geographic information system to map cases of measles in real-time during an outbreak in Dublin, Ireland, 2011.
In 2011, there was a large measles outbreak in Dublin. Nationally 285 cases were notified to the end of December 2011, and 250 (88%) were located in the Dublin region. After the first case was notified in week 6, numbers gradually increased, with 25 notified in June and a peak of 53 cases in August. Following public health intervention including a measles-mumps-rubella (MMR) vaccination campaign, no cases were reported in the Dublin region in December 2011. Most cases (82%) were children aged between 6 months and 14 years, and 46 cases (18%) were under 12 months-old. This is the first outbreak in Dublin to utilise a geographic information system for plotting measles cases on a digital map in real time. This approach, in combination with the analysis of case notifications, assisted the department of public health in demonstrating the extent of the outbreak. The digital mapping documented the evolution of two distinct clusters of 87 (35%) cases. These measles cases were infected with genotype D4-Manchester recently associated with large outbreaks across Europe. The two clusters occurred in socio-economically disadvantaged areas and were attributable to inadequate measles vaccination coverage due in part to the interruption of a school-based MMR2 vaccination programme.


Prevention and reversal of selenite-induced cataracts by N-acetylcysteine amide in Wistar rats.
The present study sought to evaluate the efficacy of N-acetylcysteine amide (NACA) eye drops in reversing the cataract formation induced by sodium selenite in male Wistar rat pups. Forty male Wistar rat pups were randomly divided into a control group, an N-acetylcysteine amide-only group, a sodium selenite-induced cataract group, and a NACA-treated sodium selenite-induced cataract group. Sodium selenite was injected intraperitoneally on postpartum day 10, whereas N-acetylcysteine amide was injected intraperitoneally on postpartum days 9, 11, and 13 in the respective groups. Cataracts were evaluated at the end of week 2 (postpartum day 14) when the rat pups opened their eyes. N-acetylcysteine amide eye drops were administered beginning on week 3 until the end of week 4 (postpartum days 15 to 30), and the rats were sacrificed at the end of week 4. Lenses were isolated and examined for oxidative stress parameters such as glutathione, lipid peroxidation, and calcium levels along with the glutathione reductase and thioltransferase enzyme activities. Casein zymography and Western blot of m-calpain were performed using the water soluble fraction of lens proteins. Morphological examination of the lenses in the NACA-treated group indicated that NACA was able to reverse the cataract grade. In addition, glutathione level, thioltransferase activity, m-calpain activity, and m-calpain level (as assessed by Western blot) were all significantly higher in the NACA-treated group than in the sodium selenite-induced cataract group. Furthermore, sodium selenite- injected rat pups had significantly higher levels of malondialdehyde, glutathione reductase enzyme activity, and calcium levels, which were reduced to control levels upon treatment with NACA. The data suggest that NACA has the potential to significantly improve vision and decrease the burden of cataract-related loss of function. Prevention and reversal of cataract formation could have a global impact. Development of pharmacological agents like NACA may eventually prevent cataract formation in high-risk populations and may prevent progression of early-stage cataracts. This brings a paradigm shift from expensive surgical treatment of cataracts to relatively inexpensive prevention of vision loss.