High eccentric hip abduction strength reduces the risk of developing patellofemoral pain among novice runners initiating a self-structured running program: a 1-year observational study.
Observational prospective cohort study with 1-year follow-up. To investigate the relationship between eccentric hip abduction strength and the development of patellofemoral pain (PFP) in novice runners during a self-structured running regime. Recent research indicates that gluteal muscle weakness exists in individuals with PFP. However, current prospective research has been limited to the evaluation of isometric strength, producing inconsistent findings. Considering that hip muscles, including the gluteus maximus and medius, activate eccentrically to control hip and pelvic motion during weight-bearing activities such as running, the potential link between eccentric strength and PFP risk should be evaluated. Eight hundred thirty-two novice runners were included at baseline, and 629 participants were included in the final analysis. Maximal eccentric hip abduction strength was measured using a handheld dynamometer prior to initiating a self-structured running program. The diagnostic criteria to classify knee pain as PFP were based on a thorough clinical examination. Participants were followed for 12 months and training characteristics were gathered with a global positioning system. Results from the unadjusted generalized linear regression model for cumulative risk at 25 and 50 km indicated differences in cumulative risk of PFP between high strength, normal strength, and low strength (P<.05), with higher strength associated with reduced risk. Findings from this study indicate that, among novice runners, a level of peak eccentric hip abduction strength that is higher than normal may reduce the risk of PFP during the first 50 km of a self-structured running program.


[Collagen histomorphometric evaluation in uterin tissue samples before and after treatment of uterine fibroids with arterial embolization].
To analyze histomorphometric consequences of the uterine arteries embolization (UAE) in the uterine tissue, especially by collagen tissue quantification through uterine biopsy, before and after treatment of uterine leiomyoma. 15 patients with symptomatic leyomioma and/or infertility, submitted to UAE, participated in the study according to the study exclusion criteria, after having signed an informed consent. Uterine biopsy was performed in the secretory phase of the menstrual cycle, before and three months after the procedure, to evaluate the collagen. After the histological processing of the material, 3 micro slices were prepared, some of them dyed with hematoxiline-eosin (HE) and others with the specific dye for collagen fibers (Picrosirius red). Then, the slides were examined and interpreted, and the collagen quantified. The amount was calculated as the percent of the area composed by collagen, and the result expressed in mean+/-standard deviation (SD). Data has then been submitted to statistical analysis by Student's paired t test (p<0.05). The presence of smooth muscle cells was observed in the biopsies performed before the treatment, surrounded by a rich network of collagen fibers, which are part of the tumor, blood vessels and fibroblast nuclei. On the slides of biopsies performed after the treatment, it was observed the presence of widespread coagulation necrosis, vascular thrombosis, calcification and lymphoplasmocitary infiltration areas and clear reduction of the collagen component. The percentage of collagen fibers was higher in the pre-UAE group (84.07+/-1.41), than in the post-UAE (81.05+/-1.50) group, with p<0.0001, and 95% confidence interval (CI95%) from 2.080 to 3.827. The quantitative and qualitative collagen reduction clearly shows that the proposed treatment is efficient in reducing the tumoral mass, composed mainly by collagen fibers intermingled with neoplasic smooth muscle cells. Nevertheless, complementary studies are needed to investigate the functional and biological consequences of these histological changes.


Serological response of cattle following Brucella abortus strain 19 vaccination and simultaneous administration of levamisole.
The serological response of heifers to injection with Brucella abortus strain 19 vaccine and simultaneous administration of levamisole hydrochloride were compared with those of heifers inoculated with Brucella abortus strain 19 vaccine alone. The Rose Bengal, serum agglutination, complement fixation and Coombs' antibovine globulin tests were used to measure the humoral responses for a period of sixteen weeks after vaccination. The results indicated that antibody titres in the heifers injected with levamisole and the vaccine were moderately elevated. It was suggested that the heightened antibody titres were possibly mediated through helper T-cells and macrophages. The significance of using levamisole as an adjuvant with Brucella abortus strain 19 vaccine in cattle is briefly discussed.


NMDA receptor-mediated refinement of a transient retinotectal projection during development requires nitric oxide.
A transient ipsilateral retinotectal projection is normally eliminated during embryonic development of the chick visual system. Administration of the NMDA receptor antagonist 5-methyl-10, 11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) during the developmental period in which this projection normally disappears prevented its complete elimination. Previous studies showed that tectal cells express nitric oxide synthase during development, and blocking synthesis of nitric oxide also prevented elimination of the ipsilateral retinotectal projection. The effect of NMDA receptor blockade on nitric oxide synthase activity in tectal cells was assessed biochemically in chick embryos. Increasing concentrations of MK-801 resulted in a dose-dependent decrease in nitric oxide synthase activity. This result suggests that NMDA receptor activation can regulate nitric oxide synthase activity in the tectum. The degree of rescue of the ipsilateral retinotectal projection was compared in embryos treated either with MK-801 or with an inhibitor of nitric oxide synthesis, Nomega-nitro-L-arginine (L-NoArg). At comparable levels of inhibition of nitric oxide synthesis, no significant difference was observed in the degree of rescue mediated by NMDA receptor blockade or nitric oxide synthesis blockade. These results suggest that NMDA receptor-mediated elimination of the ipsilateral retinotectal projection is completely mediated via nitric oxide.


K-space linear Fourier domain mode locked laser and applications for optical coherence tomography.
We report on a Fourier Domain Mode Locked (FDML) wavelength swept laser source with a highly linear time-frequency sweep characteristic and demonstrate OCT imaging without k-space resampling prior to Fourier transformation. A detailed theoretical framework is provided and different strategies how to determine the optimum drive waveform of the piezo-electrically actuated optical bandpass-filter in the FDML laser are discussed. An FDML laser with a relative optical frequency deviation ??nu/nu smaller than 8 x10(-5) over a 100 nm spectral bandwidth at 1300 nm is presented, enabling high resolution OCT over long ranging depths. Without numerical time-to-frequency resampling and without spectral apodization a sensitivity roll off of 4 dB over 2 mm, 12.5 dB over 4 mm and 26.5 dB over 1 cm at 3.5 mus sweep duration and 106.6 dB maximum sensitivity at 9.2 mW average power is achieved. The axial resolution in air degrades from 14 to 21 mum over 4 mm imaging depth. The compensation of unbalanced dispersion in the OCT sample arm by an adapted tuning characteristic of the source is demonstrated. Good stability of the system without feedback-control loops is observed over hours.


Dose-dependent protection against or exacerbation of disease by a polylactide glycolide microparticle-adsorbed, alphavirus-based measles virus DNA vaccine in rhesus macaques.
Measles remains an important cause of vaccine-preventable child mortality. Development of a low-cost, heat-stable vaccine for infants under the age of 6 months could improve measles control by facilitating delivery at the time of other vaccines and by closing a window of susceptibility prior to immunization at 9 months of age. DNA vaccines hold promise for development, but achieving protective levels of antibody has been difficult and there is an incomplete understanding of protective immunity. In the current study, we evaluated the use of a layered alphavirus DNA/RNA vector encoding measles virus H (SINCP-H) adsorbed onto polylactide glycolide (PLG) microparticles. In mice, antibody and T-cell responses to PLG-formulated DNA were substantially improved compared to those to naked DNA. Rhesus macaques received two doses of PLG/SINCP-H delivered either intramuscularly (0.5 mg) or intradermally (0.5 or 0.1 mg). Antibody and T-cell responses were induced but not sustained. On challenge, the intramuscularly vaccinated monkeys did not develop rashes and had lower viremias than vector-treated control monkeys. Monkeys vaccinated with the same dose intradermally developed rashes and viremia. Monkeys vaccinated intradermally with the low dose developed more severe rashes, with histopathologic evidence of syncytia and intense dermal and epidermal inflammation, eosinophilia, and higher viremia compared to vector-treated control monkeys. Protection after challenge correlated with gamma interferon-producing T cells and with early production of high-avidity antibody that bound wild-type H protein. We conclude that PLG/SINCP-H is most efficacious when delivered intramuscularly but does not provide an advantage over standard DNA vaccines for protection against measles.


[Evaluation of erythrocyte basic ferritin in the diagnosis of anemia].
Erythrocyte basic ferritin (EF) concentration was determined in 64 normal subjects, 123 patients with anemia and 12 patients with leukopenia and thrombocytopenia. There was a significant difference between males and females. Other iron indices, including plasma iron (PI), total iron binding capacity (TIBC), zinc protoporphyrin (ZnPP) and plasma ferritin (PF) were also determined in all the subjects and bone marrow iron stain was determined in the 135 patients. The lowest EF concentration was seen in patients with iron deficiency anemia, being significantly lower than that in normal subjects. EF concentration in patients with iron deficiency erythropoiesis was also lower than that in normal subjects and at the same time significantly different from that in patients with iron deficiency anemia. EF concentration increased prior to PF concentration in patients with iron deficiency anemia who had been treated for a period of 1-8 weeks. EF concentration in patients with anemia of chronic diseases had a significant difference as compared with that in normal subjects and in patients with iron deficiency anemia, but EF concentration in those patients who were accompanied by iron deficiency was similar to that in patients with simple iron deficiency anemia. EF concentration in some iron overloaded patients (aplastic anemia, megaloblastic anemia, MDS etc.) was significantly higher than that in normal subjects. It was demonstrated that there was a good correlation between EF concentration and bone marrow sideroblastic iron in the rank correlation analysis of the iron indices in 135 patients (rs 0.893, P less than 0.01). PF concentration had the best correlation with marrow iron (rs 0.948, P less than 0.01).


RACK1, a potential target to decrease morphine reward in mice.
Morphine reexposure induces the decrease of receptor for activated C-kinase 1 protein (RACK1) levels in frontal cortex, and the increase of p-ERK (extracellular signal-regulated kinase) levels in mouse frontal cortex, striatum, hippocampus and nucleus accumbens (NAcc). Moreover, RACK1 is associated with the core kinases of the ERK pathway, Raf, MEK, and ERK. The purpose of this study is to investigate the effect of overexpression of RACK1 on the conditioned place preference (CPP) and the level of p-ERK in morphine reexposure mice. Mice were subcutaneously injected with morphine on the 2nd, 4th, 6th, and the 8th day, saline was delivered the next day. After mice showed place preference, RACK1 was administered by intraventricular injection 20 minutes after injection of morphine on the 11th, 13th, 15th, and 17th day. CPP was measured on the 18th day. It was found that morphine reexposured mice showed a decreased RACK1 level in the frontal cortex, striatum and an increased RACK1 level in hippocampus and NAcc, but this effect was reversed after administration of RACK1. In this study we demonstrated that RACK1 decreased p-ERK and erased CPP during reexposure of morphine and there was no an effect in reexposure saline mice. It strongly suggests that RACK1 may play a crucial role in morphine reexposured mice and the RACK1 has the potential to be a remedy to the morphine reward.


Mining host-pathogen protein interactions to characterize Burkholderia mallei infectivity mechanisms.
Burkholderia pathogenicity relies on protein virulence factors to control and promote bacterial internalization, survival, and replication within eukaryotic host cells. We recently used yeast two-hybrid (Y2H) screening to identify a small set of novel Burkholderia proteins that were shown to attenuate disease progression in an aerosol infection animal model using the virulent Burkholderia mallei ATCC 23344 strain. Here, we performed an extended analysis of primarily nine B. mallei virulence factors and their interactions with human proteins to map out how the bacteria can influence and alter host processes and pathways. Specifically, we employed topological analyses to assess the connectivity patterns of targeted host proteins, identify modules of pathogen-interacting host proteins linked to processes promoting infectivity, and evaluate the effect of crosstalk among the identified host protein modules. Overall, our analysis showed that the targeted host proteins generally had a large number of interacting partners and interacted with other host proteins that were also targeted by B. mallei proteins. We also introduced a novel Host-Pathogen Interaction Alignment (HPIA) algorithm and used it to explore similarities between host-pathogen interactions of B. mallei, Yersinia pestis, and Salmonella enterica. We inferred putative roles of B. mallei proteins based on the roles of their aligned Y. pestis and S. enterica partners and showed that up to 73% of the predicted roles matched existing annotations. A key insight into Burkholderia pathogenicity derived from these analyses of Y2H host-pathogen interactions is the identification of eukaryotic-specific targeted cellular mechanisms, including the ubiquitination degradation system and the use of the focal adhesion pathway as a fulcrum for transmitting mechanical forces and regulatory signals. This provides the mechanisms to modulate and adapt the host-cell environment for the successful establishment of host infections and intracellular spread.


Antibiotics for exacerbations of chronic obstructive pulmonary disease.
Many patients with an exacerbation of chronic obstructive pulmonary disease (COPD) are treated with antibiotics. However, the value of antibiotics remains uncertain as systematic reviews and clinical trials have shown conflicting results. To assess the effects of antibiotics in the management of acute COPD exacerbations on treatment failure as observed between seven days and one month after treatment initiation (primary outcome) and on other patient-important outcomes (mortality, adverse events, length of hospital stay). We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and other electronically available databases up to September 2012. Randomised controlled trials (RCTs) in people with acute COPD exacerbations comparing antibiotic therapy and placebo with a follow-up of at least seven days. Two review authors independently screened references and extracted data from trial reports. We kept the three groups of outpatients, inpatients and patients admitted to the intensive care unit (ICU) separate for benefit outcomes and mortality because we considered them to be clinically too different to be summarised in one group. We considered outpatients to have a mild to moderate exacerbation, inpatients to have a severe exacerbation and ICU patients to have a very severe exacerbation. Where outcomes or study details were not reported we requested missing data from the authors of the primary studies. We calculated pooled risk ratios (RR) for treatment failure, Peto odds ratios (OR) for rare events (mortality and adverse events) and weighted mean differences (MD) for continuous outcomes using fixed-effect models. We used GRADE to assess the quality of the evidence. Sixteen trials with 2068 participants were included. In outpatients (mild to moderate exacerbations), there was evidence of low quality that antibiotics did statistically significantly reduce the risk for treatment failure between seven days and one month after treatment initiation (RR 0.75; 95% CI 0.60 to 0.94; I(2) = 35%) but they did not significantly reduce the risk when the meta-analysis was restricted to currently available drugs (RR 0.80; 95% CI 0.63 to 1.01; I(2) = 33%). Evidence of high quality showed that antibiotics statistically significantly reduced the risk of treatment failure in inpatients with severe exacerbations (ICU not included) (RR 0.77; 95% CI 0.65 to 0.91; I(2) = 47%) regardless of whether restricted to current drugs. The only trial with 93 patients admitted to the ICU showed a large and statistically significant effect on treatment failure (RR 0.19; 95% CI 0.08 to 0.45; high-quality evidence).Evidence of low-quality from four trials in inpatients showed no effect of antibiotics on mortality (Peto OR 1.02; 95% CI 0.37 to 2.79). High-quality evidence from one trial showed a statistically significant effect on mortality in ICU patients (Peto OR 0.21; 95% CI 0.06 to 0.72). Length of hospital stay (in days) was similar in the antibiotics and placebo groups except for the ICU study where antibiotics statistically significantly reduced length of hospital stay (mean difference -9.60 days; 95% CI -12.84 to -6.36 days). One trial showed no effect of antibiotics on re-exacerbations between two and six weeks after treatment initiation. Only one trial (N = 35) reported health-related quality of life but did not show a statistically significant difference between the treatment and control group.Evidence of moderate quality showed that the overall incidence of adverse events was higher in the antibiotics groups (Peto OR 1.53; 95% CI 1.03 to 2.27). Patients treated with antibiotics experienced statistically significantly more diarrhoea based on three trials (Peto OR 2.62; 95% CI 1.11 to 6.17; high-quality evidence). Antibiotics for COPD exacerbations showed large and consistent beneficial effects across outcomes of patients admitted to an ICU. However, for outpatients and inpatients the results were inconsistent. The risk for treatment failure was significantly reduced in both inpatients and outpatients when all trials (1957 to 2012) were included but not when the analysis for outpatients was restricted to currently used antibiotics. Also, antibiotics had no statistically significant effect on mortality and length of hospital stay in inpatients and almost no data on patient-reported outcomes exist. These inconsistent effects call for research into clinical signs and biomarkers that help identify patients who benefit from antibiotics and patients who experience no effect, and in whom downsides of antibiotics (side effects, costs and multi-resistance) could be avoided.


Effect of phenol on conduction and synaptic transmission block.
The effect of phenol on nerve conduction and ganglionic synaptic transmission has been studied on sciatic nerve and on the VIIIth sympathetic ganglion of the frog. Ganglionic synaptic transmission block occurred at lower concentration than axonal conduction block. Both, conduction and synaptic transmission recovered in Ringer's solutions after 10 minutes. CaCl2 5.4 mM antagonized partially the axonal conduction block and EGTA in Ringer's solution without CaCl2 increased the effect of phenol on axonal conduction block on desheated sciatic nerve. Early in the experiments phenol had a weaker effect than procaine but at 10 minutes the effect of procaine became steady state and the effect of phenol continued to increase.


Anomalous origin of the right coronary artery with interarterial course: a mid-term follow-up of 28 cases.
Anomalous origin of the right coronary artery from the opposite sinus (right-ACAOS) with interarterial course (IAC) has been associated with increased risk of sudden cardiac death (SCD). Widespread use of coronary computed tomography angiography (CCTA) has led to increased recognition of this condition, even among healthy individuals. Our study sought to examine the prevalence, anatomical characteristics, and outcomes of right-ACAOS with IAC in patients undergoing CCTA for suspected coronary artery disease (CAD). We conducted a retrospective analysis of consecutive patients referred for CCTA at one tertiary hospital from January 2012 to December 2020. Patients exhibiting right-ACAOS with IAC were analyzed for cardiac symptoms and mid-term occurrence of first MACE (cardiac death, SCD, non-fatal myocardial infarction (MI) or revascularization of the anomalous vessel). CCTAs were reviewed for anatomical high-risk features and concomitant CAD. Among 10,928 patients referred for CCTA, 28 patients with right-ACAOS with IAC were identified. Mean age was 55 ± 17 years, 64% were male and 11 (39.3%) presented stable cardiac symptoms. Most patients had at least one high risk anatomical feature. During follow-up, there were no cardiac deaths or aborted SCD episodes and only 1 patient underwent surgical revascularization of the anomalous vessel. Right-ACAOS with IAC is an uncommon finding (prevalence of 0.26%). In a contemporary population of predominantly asymptomatic patients who survived this condition well into adulthood, most patients were managed conservatively with a low event rate. Additional studies are needed to support medical follow-up as the preferred option in this setting.


Management of adenocarcinoma arising in Barrett's esophagus.
Esophageal adenocarcinoma is a highly malignant tumor and, if not diagnosed at an early stage, carries a poor prognosis. Controversy exists over how to manage carcinoma of the esophagus confined to the mucosa and the extent of resection to cure disease that has extended beyond the mucosa. Similarly, there are differing opinions regarding the role of adjuvant chemotherapy and the efficacy of surgical resection for palliation. These issues are discussed as they pertain to the management of adenocarcinoma arising in Barrett's esophagus.


A literature review of treatment-specific clinical prediction models in patients with breast cancer.
Despite advances in the breast cancer treatment, significant variability in patient outcomes remain. This results in significant stress to patients and clinicians. Treatment-specific clinical prediction models allow patients to be matched against historical outcomes of patients with similar characteristics; thereby reducing uncertainty by providing personalised estimates of benefits, harms, and prognosis. To achieve this objective, models need to be clinical-grade with evidence of accuracy, reproducibility, generalizability, and be user-friendly. A structured search was undertaken to identify treatment-specific clinical prediction models for therapeutic or adverse outcomes in breast cancer using clinicopathological data. Significant gaps in the presence of validated models for available treatments was identified, along with gaps in prediction of therapeutic and adverse outcomes. Most models did not have user-friendly tools available. With the aim being to facilitate the selection of the best medicine for a specific patient and shared-decision making, future research will need to address these gaps.


Early microlesion of viral encephalitis confirmed by galectin-3 expression after a virus inoculation.
Galectin-3 is a β-galactosidase-binding lectin which is important in cell proliferation and apoptotic regulation. Encephalomyocarditis virus (EMCV), which includes the Enterovirus genus, can cause not only acute myocarditis but also neuronal degeneration of central nervous system in various animals including mice. The pathophysiological role of galectin-3 in central nervous system following acute viral infection is not fully understood. The goal of this study is to determine the localization and time-course of galectin-3 expression after acute viral inoculation with EMCV. Galectin-3 is up-regulated in degenerated lesions of brain area including cerebellum, hippocampus, thalamus and cerebral hemisphere, 96 h after EMCV inoculation. At the same time, Iba-1 positive microglia was morphologically activated within and around the focus of infection. Interestingly, in cerebellum, the microlesions containing a few galectin-3 cells were detected in the immediate-early phase of infection, as early as 48 h after EMCV inoculation. Thus, our results indicate that galectin-3 expression may be a key mediator between viral infection and neuronal degeneration in central nervous system including cerebellum. Furthermore, detection of galectin-3 might be an early diagnostic method for neuronal degeneration after virus infection.


De novo Assembly of the Pokeweed Genome Provides Insight Into Pokeweed Antiviral Protein (PAP) Gene Expression.
Ribosome-inactivating proteins (RIPs) are RNA glycosidases thought to function in defense against pathogens. These enzymes remove purine bases from RNAs, including rRNA; the latter activity decreases protein synthesis in vitro, which is hypothesized to limit pathogen proliferation by causing host cell death. Pokeweed antiviral protein (PAP) is a RIP synthesized by the American pokeweed plant (Phytolacca americana). PAP inhibits virus infection when expressed in crop plants, yet little is known about the function of PAP in pokeweed due to a lack of genomic tools for this non-model species. In this work, we de novo assembled the pokeweed genome and annotated protein-coding genes. Sequencing comprised paired-end reads from a short-insert library of 83X coverage, and our draft assembly (N50 = 42.5 Kb) accounted for 74% of the measured pokeweed genome size of 1.3 Gb. We obtained 29,773 genes, 73% of which contained known protein domains, and identified several PAP isoforms. Within the gene models of each PAP isoform, a long 5' UTR intron was discovered, which was validated by RT-PCR and sequencing. Presence of the intron stimulated reporter gene expression in tobacco. To gain further understanding of PAP regulation, we complemented this genomic resource with expression profiles of pokeweed plants subjected to stress treatments [jasmonic acid (JA), salicylic acid, polyethylene glycol, and wounding]. Cluster analysis of the top differentially expressed genes indicated that some PAP isoforms shared expression patterns with genes involved in terpenoid biosynthesis, JA-mediated signaling, and metabolism of amino acids and carbohydrates. The newly sequenced promoters of all PAP isoforms contained cis-regulatory elements associated with diverse biotic and abiotic stresses. These elements mediated response to JA in tobacco, based on reporter constructs containing promoter truncations of PAP-I, the most abundant isoform. Taken together, this first genomic resource for the Phytolaccaceae plant family provides new insight into the regulation and function of PAP in pokeweed.


Histopathology of the spleen in T-cell large granular lymphocyte leukemia and T-cell prolymphocytic leukemia: a comparative review.
We review retrospectively the spleen histology in 8 patients with T-cell large granular lymphocyte (LGL) leukemia and 4 with T-cell prolymphocytic leukemia (T-PLL) to identify characteristic patterns of involvement and to distinguish such patterns from those described in other low grade B- and T-cell malignancies. Moderate splenic enlargement with red pulp expansion due to lymphocytic infiltration was characteristic of LGL leukemia. Abnormal lymphocytes expressed cytotoxic granule proteins and were consistently CD45RO and CD5 negative in contrast to normal red pulp T cells. This infiltration respected anatomic boundaries with encroachment but no invasion of white pulp areas. Unlike in hairy cell leukemia, the main differential diagnosis for red pulp lymphocytosis, the white pulp was not only preserved in T-cell LGL leukemia but showed germinal center hyperplasia with expansion of the mantle zones. By comparison, T-PLL spleens showed marked red pulp lymphoid infiltration by medium-sized cells with irregular nuclei and prominent eosinophilic nucleoli. T-PLL lymphocytes, unlike LGLs, were more invasive, infiltrating the spleen capsule as well as white pulp areas. T-cell prolymphocytes did not express cytotoxic granule proteins or NK-cell markers, were CD5+, CD45RO+ like normal spleen T cells, were CD2+, CD3+, CD45+, CD43+, TCRbeta+, but CD25-, CD30-, ALK-1-, TRAP-, DBA44-, and TdT-. Expression of CD4 and CD8 in these cells mirrored that of circulating T-PLL cells. These observations on the morphologic and immunohistochemical appearances of the spleen in T-cell LGL leukemia and T-PLL may aid diagnosis of these uncommon T-cell disorders, particularly T-cell LGL leukemia, where presentation may be cryptic and where unique pathognomonic features, are absent.


Practical considerations will ensure the continued success of pre-harvest biocontrol using non-aflatoxigenic Aspergillus flavus strains.
There is an important reason for the accelerated use of non-aflatoxigenic Aspergillus flavus to mitigate pre-harvest aflatoxin contamination… it effectively addresses the imperative need for safer food and feed. Now that we have decades of proof of the effectiveness of A. flavus as biocontrol, it is time to improve several aspects of this strategy. If we are to continue relying heavily on this form of aflatoxin mitigation, there are considerations we must acknowledge, and actions we must take, to ensure that we are best wielding this strategy to our advantage. These include its: (1) potential to produce other mycotoxins, (2) persistence in the field in light of several ecological factors, (3) its reproductive and genetic stability, (4) the mechanism(s) employed that allow it to elicit control over aflatoxigenic strains and species of agricultural importance and (5) supplemental alternatives that increase its effectiveness. There is a need to be consistent, practical and thoughtful when it comes to implementing this method of mycotoxin mitigation since these fungi are living organisms that have been adapting, evolving and surviving on this planet for tens-of-millions of years. This document will serve as a critical review of the literature regarding pre-harvest A. flavus biocontrol and will discuss opportunities for improvements.


Vitamin and mineral supplement use by older rural adults.
Vitamin and mineral supplement products are widely consumed by older adults. This study describes supplement product use in a multiethnic rural population, relates supplement usage to dietary nutrient intake, and determines predictors of supplement usage. Data are from a population-based sample of 130 community-dwelling adults aged 70 years and older in two rural North Carolina counties. The sample was 34% African American, 36% European American, and 30% Native American. Interviewer-administered semiquantitative food frequency questionnaires were used to obtain data on usual diet and supplement use. In-home interviews allowed verification of supplement composition. Intakes from diet and supplement products were examined for vitamins A, E, B6, C, folate, iron, zinc, and calcium. Of those who participated in the study, 47% reported using one or more supplement products. African Americans were significantly less likely to take supplements than Native Americans or European Americans. Based on dietary intakes, 65% of the participants were deficient (<2/3 recommended dietary allowance [RDA]) for at least one nutrient. The use of supplement products for the eight nutrients investigated was not related to dietary nutrient deficiency. For all nutrients investigated, except iron and calcium, a greater proportion of those without dietary deficiency took a supplement product than those with deficiency. Using logistic regression, ethnicity (European American and Native American), and gender (women) were significant predictors of supplement use. These findings suggest that although both dietary deficiencies of vitamins and minerals and supplement use are relatively high in this population, there is no association between supplement use and deficient dietary intakes for the eight nutrients examined. Health care providers should be aware that nutritional counseling and guidance on appropriate supplement usage is needed in this population.


Infusion Reactions After Receiving the Broadly Neutralizing Antibody VRC01 or Placebo to Reduce HIV-1 Acquisition: Results From the Phase 2b Antibody-Mediated Prevention Randomized Trials.
The antibody-mediated prevention (AMP) studies (HVTN 703/HPTN 081 and HVTN 704/HPTN 085) are harmonized phase 2b trials to assess HIV prevention efficacy and safety of intravenous infusion of anti-gp120 broadly neutralizing antibody VRC01. Antibodies for other indications can elicit infusion-related reactions (IRRs), often requiring premedication and limiting their application. We report on AMP study IRRs. From 2016 to 2018, 2699 HIV-uninfected, at-risk men and transgender adults in the Americas and Switzerland (704/085) and 1924 at-risk heterosexual women in sub-Saharan Africa (703/081) were randomized 1:1:1 to VRC01 10 mg/kg, 30 mg/kg, or placebo. Participants received infusions every 8 weeks (n = 10/participant) over 72 weeks, with 104 weeks of follow-up. Safety assessments were conducted before and after infusion and at noninfusion visits. A total of 40,674 infusions were administered. Forty-seven participants (1.7%) experienced 49 IRRs in 704/085; 93 (4.8%) experienced 111 IRRs in 703/081 (P < 0.001). IRRs occurred more frequently in VRC01 than placebo recipients in 703/081 (P < 0.001). IRRs were associated with atopic history (P = 0.046) and with younger age (P = 0.023) in 703/081. Four clinical phenotypes of IRRs were observed: urticaria, dyspnea, dyspnea with rash, and "other." Urticaria was most prevalent, occurring in 25 (0.9%) participants in 704/085 and 41 (2.1%) participants in 703/081. Most IRRs occurred with the initial infusion and incidence diminished through the last infusion. All reactions were managed successfully without sequelae. IRRs in the AMP studies were uncommon, typically mild or moderate, successfully managed at the research clinic, and resolved without sequelae. Analysis is ongoing to explore potential IRR mechanisms.


SARS-CoV-2 messenger RNA vaccine antibody response and reactogenicity in heart and lung transplant recipients.
While several studies have observed that solid organ transplant recipients experience diminished antibody responses to SARS-CoV-2 mRNA vaccination, data specific to heart and lung transplant (HT/LT) recipients remains sparse. US adult HT and LT recipients completed their vaccine series between January 7 and April 10, 2021. Reactogencity and SARS-CoV-2 anti-spike antibody were assessed after a priming dose (D1) and booster dose (D2). Modified Poisson regression with robust variance estimator was used to evaluate associations between participant characteristics and antibody development. Of 134 heart recipients, there were 38% non-responders (D1-/D2-), 48% booster responders (D1-/D2+), and 14% priming dose responders (D1+/D2+). Of 103 lung recipients, 64% were non-responders, 27% were booster responders, and 9% were priming dose responders. Lung recipients were less likely to develop antibodies (p < .001). Priming dose antibody response was associated with younger recipient age (p = .04), transplant-to-vaccination time ≥6 years (p < .01), and lack of anti-metabolite maintenance immunosuppression (p < .001). Pain at injection site was the most commonly reported reaction (85% after D1, 76% after D2). Serious reactions were rare, the most common being fatigue (2% after D1 and 3% after D2). No serious adverse events were reported. HT and LT recipients experienced diminished antibody response following vaccination; reactogenicity was comparable to that of the general population. LT recipients may exhibit a more impaired antibody response than HT recipients. While current recommendations are to vaccinate eligible candidates and recipients, further studies characterizing the cell-mediated immune response and clinical efficacy of these vaccines in this population are needed.


Impact of delays and noise on dopamine signal transduction.
Dopamine is a critical neurotransmitter for the normal functioning of the central nervous system. Abnormal dopamine signal transmission in the brain has been implicated in diseases such as Parkinson's disease (PD) and schizophrenia, as well as in various types of drug addition. It is therefore important to understand the dopamine signaling dynamics in the presynaptic neuron of the striatum and the synaptic cleft, where dopamine synthesis, degradation, compartmentalization, release, reuptake, and numerous regulatory processes occur. The biochemical and biological processes governing this dynamics consist of interacting discrete and continuous components, operate at different time scales, and must function effectively in spite of intrinsic stochasticity and external perturbations. Not fitting into the realm of purely deterministic phenomena, the hybrid nature of the system requires special means of mathematical modeling, simulation and analysis. We show here how hybrid functional Petri-nets (HFPNs) and the software Cell Illustrator® facilitate computational analyses of systems that simultaneously contain deterministic, stochastic, and delay components. We evaluate the robustness of dopamine signaling in the presence of delays and noise and discuss implications for normal and abnormal states of the system.


Nuclear location of PLA2-I in proliferative cells.
We have previously demonstrated that pancreatic PLA2 (PLA2-I) stimulates the proliferation of UIII cells, a stromal cell line derived from normal rat uterus. In order to gain further insight into the mechanism of action of PLA2-I, we have investigated the intracellular processing of PLA2-I. Either highly proliferative or growth arrested UIII cells were analyzed. Growth arrested cells were obtained from a contact inhibited monolayer or from aristolochic acid-treated cultures. Using cellular fractionation, western blotting, immunocytochemistry and confocal microscopy, we demonstrate that endogenous PLA2-I was mainly located in the nucleus in highly proliferative cells whereas its location was cytoplasmic in non proliferative cells. When non confluent UIII cells were incubated with nanomolar amounts of exogenous PLA2-I, the enzyme was internalized and, in the majority of cells, appeared within the nucleus. Both internalization and nuclear location of exogenous PLA2-I were suppressed by the addition of aristolochic acid to the culture medium. Binding experiments performed on purified nuclear preparations showed the presence of specific cooperative binding sites for PLA2-I. Collectively our data suggest that the proliferative effect exerted by pancreatic PLA2 in UIII cells is mediated by a direct interaction of the enzyme at the nuclear level. Putative mechanisms and targets are discussed.


Ultrahigh surface area zirconium MOFs and insights into the applicability of the BET theory.
An isoreticular series of metal-organic frameworks (MOFs) with the ftw topology based on zirconium oxoclusters and tetracarboxylate linkers with a planar core (NU-1101 through NU-1104) has been synthesized employing a linker expansion approach. In this series, NU-1103 has a pore volume of 2.91 cc g(-1) and a geometrically calculated surface area of 5646 m(2) g(-1), which is the highest value reported to date for a zirconium-based MOF and among the largest that have been reported for any porous material. Successful activation of the MOFs was proven based on the agreement of pore volumes and BET areas obtained from simulated and experimental isotherms. Critical for practical applications, NU-1103 combines for the first time ultrahigh surface area and water stability, where this material retained complete structural integrity after soaking in water. Pressure range selection for the BET calculations on these materials was guided by the four so-called "consistency criteria". The experimental BET area of NU-1103 was 6550 m(2) g(-1). Insights obtained from molecular simulation suggest that, as a consequence of pore-filling contamination, the BET method overestimates the monolayer loading of NU-1103 by ∼16%.


Interplay between interdiffusion and shape transformations in nanoalloys evolving from core-shell to intermixed structures.
Nanoalloys are often grown or synthesized in non-equilibrium configurations whose further evolution towards equilibrium can take place through complex pathways. In this work, we consider bimetallic systems with tendency towards intermixing, namely AgAu, PtPd and AuCu. We analyze their evolution starting from non-equilibrium initial configurations, such as phase-separated core@shell ones, by means of molecular dynamics (MD) simulations. These systems present some differences, since AuCu bulk alloys make ordered phases at low temperature whereas AgAu and PtPd remain in solid solution. Moreover, Cu, Au and Ag have similar cohesive energies whereas Pt is much more cohesive than Pd. We consider both truncated octahedral and icosahedral initial shapes in the size range between 2 and 3 nm. For each AB system, we consider both A@B and B@A core@shell starting configurations. The evolution is characterized by monitoring the time-dependent degree of intermixing and the evolution of the shape. The simulations are performed up to temperatures close to the melting range. The approach to thermodynamic equilibrium is monitored by MD simulations and compared with the equilibrium chemical configurations obtained by Monte Carlo simulations.


[Resistance to hunger as an element of the adaptive strategy of malaria mosquito larva].
Mortality from starvation in larvae of malaria mosquito species Anopheles beklemishevi, A. messeae, and A. sinensis (Diptera, Culicidae) was compared. The results showed that the southern species. A. sinensis is more resistant to starvation and more competitive than A. messeae, the species with chromosome polymorphism. Mortality of larvae increased when they starved in groups. Starving A. messeae larvae with "southern" inversions (K-strategists) proved to be more viable than larvae with "northern" karyotypes (r-strategists). The relationship between resistance to starvation and selection strategies in malaria mosquito populations is discussed.


Long fusion from sacrum to thoracic spine for adult spinal deformity with sagittal imbalance: upper versus lower thoracic spine as site of upper instrumented vertebra.
Despite increasing numbers of patients with adult spinal deformity, it is unclear how to select the optimal upper instrumented vertebra (UIV) in long fusion surgery for these patients. The purpose of this study was to compare the use of vertebrae in the upper thoracic (UT) versus lower thoracic (LT) spine as the upper instrumented vertebra in long fusion surgery for adult spinal deformity. Patients who underwent fusion from the sacrum to the thoracic spine for adult spinal deformity with sagittal imbalance at a single medical center were studied. The patients with a sagittal vertical axis (SVA) ≥ 40 mm who had radiographs and completed the 12-item Short-Form Health Survey (SF-12) preoperatively and at final follow-up (≥ 2 years postoperatively) were included. Eighty patients (mean age of 61.1 ± 10.9 years; 69 women and 11 men) met the inclusion criteria. There were 31 patients in the UT group and 49 patients in the LT group. The mean follow-up period was 3.6 ± 1.6 years. The physical component summary (PCS) score of the SF-12 significantly improved from the preoperative assessment to final follow-up in each group (UT, 34 to 41; LT, 29 to 37; p = 0.001). This improvement reached the minimum clinically important difference in both groups. There was no significant difference in PCS score improvement between the 2 groups (p = 0.8). The UT group had significantly greater preoperative lumbar lordosis (28° vs 18°, p = 0.03) and greater thoracic kyphosis (36° vs 18°, p = 0.001). After surgery, there was no significant difference in lumbar lordosis or thoracic kyphosis. The UT group had significantly greater postoperative cervicothoracic kyphosis (20° vs 11°, p = 0.009). The UT group tended to maintain a smaller positive SVA (51 vs 73 mm, p = 0.08) and smaller T-1 spinopelvic inclination (-2.6° vs 0.6°, p = 0.06). The LT group tended to have more proximal junctional kyphosis (PJK), although the difference did not reach statistical significance. Radiographic PJK was 32% in the UT group and 41% in the LT group (p = 0.4). Surgical PJK was 6.4% in the UT group and 10% in the LT group (p = 0.6). Both the UT and LT groups demonstrated significant improvement in clinical and radiographic outcomes. A significant difference was not observed in improvement of clinical outcomes between the 2 groups.


Transient effect of nifedipine on pulmonary hypertension of systemic sclerosis.
A 64-year-old woman with systemic sclerosis and pulmonary hypertension underwent Swan-Ganz catheterization to test her response to the calcium channel blocker nifedipine. Pulmonary vascular resistance decreased from 2095 to 1333 dynes sec cm-5 with an initial dose of the drug. She developed tolerance to nifedipine within 12 h and subsequent doses had no effect on her pulmonary circulation. Our study confirms that acute administration of nifedipine reduces pulmonary vascular resistance in systemic sclerosis. However, an initial response to nifedipine does not predict benefit from continued administration of the drug.


Serp-2, a virus-derived apoptosis and inflammasome inhibitor, attenuates liver ischemia-reperfusion injury in mice.
Ischemia-reperfusion injury (IRI) is an antigen-independent, innate immune response to arterial occlusion and ischemia with subsequent paradoxical exacerbation after reperfusion. IRI remains a critical problem after vessel occlusion and infarction or during harvest and surgery in transplants. After transplant, liver IRI (LIRI) contributes to increased acute and chronic rejection and graft loss. Tissue loss during LIRI has been attributed to local macrophage activation and invasion with excessive inflammation together with hepatocyte apoptosis and necrosis. Inflammatory and apoptotic signaling are key targets for reducing post-ischemic liver injury.Myxomavirus is a rabbit-specific leporipoxvirus that encodes a suite of immune suppressing proteins, often with extensive function in other mammalian species. Serp-2 is a cross-class serine protease inhibitor (serpin) which inhibits the inflammasome effector protease caspase-1 as well as the apoptotic proteases granzyme B and caspases 8 and 10. In prior work, Serp-2 reduced inflammatory cell invasion after angioplasty injury and after aortic transplantation in rodents. In this report, we explore the potential for therapeutic treatment with Serp-2 in a mouse model of LIRI. Wildtype (C57BL/6 J) mice were subjected to warm, partial (70%) hepatic ischemia for 90 min followed by treatment with saline or Serp-2 or M-T7, 100 ng/g/day given by intraperitoneal injection on alternate days for 5 days. M-T7 is a Myxomavirus-derived inhibitor of chemokine-GAG interactions and was used in this study for comparative analysis of an unrelated viral protein with an alternative immunomodulating mechanism of action. Survival, serum ALT levels and histopathology were assessed 24 h and 10 days post-LIRI. Serp-2 treatment significantly improved survival to 85.7% percent versus saline-treated wildtype mice (p = 0.0135), while M-T7 treatment did not significantly improve survival (p = 0.2584). Liver viability was preserved by Serp-2 treatment with a significant reduction in serum ALT levels (p = 0.0343) and infarct scar thickness (p = 0.0016), but with no significant improvement with M-T7 treatment. Suzuki scoring by pathologists blinded with respect to treatment group indicated that Serp-2 significantly reduced hepatocyte necrosis (p = 0.0057) and improved overall pathology score (p = 0.0046) compared to saline. Immunohistochemistry revealed that Serp-2 treatment reduced macrophage infiltration into the infarcted liver tissue (p = 0.0197). Treatment with Serp-2, a virus-derived inflammasome and apoptotic pathway inhibitor, improves survival after liver ischemia-reperfusion injury in mouse models. Treatment with a cross-class immune modulator provides a promising new approach designed to reduce ischemia-reperfusion injury, improving survival and reducing chronic transplant damage.


Effect of bacterial antagonists on lettuce: active biocontrol of Rhizoctonia solani and negligible, short-term effects on nontarget microorganisms.
The aim of this study was to assess the biocontrol efficacy against Rhizoctonia solani of three bacterial antagonists introduced into naturally Rhizoctonia-infested lettuce fields and to analyse their impact on the indigenous plant-associated bacteria and fungi. Lettuce seedlings were inoculated with bacterial suspensions of two endophytic strains, Serratia plymuthica 3Re4-18 and Pseudomonas trivialis 3Re2-7, and with the rhizobacterium Pseudomonas fluorescens L13-6-12 7 days before and 5 days after planting in the field. Similar statistically significant biocontrol effects were observed for all applied bacterial antagonists compared with the uninoculated control. Single-strand conformation polymorphism analysis of 16S rRNA gene or ITS1 fragments revealed a highly diverse rhizosphere and a less diverse endophytic microbial community for lettuce. Representatives of several bacterial (Alpha-, Beta- and Gammaproteobacteria, Firmicutes, Bacteriodetes), fungal (Ascomycetes, Basidiomycetes) and protist (Oomycetes) groups were present inside or on lettuce plants. Surprisingly, given that lettuce is a vegetable that is eaten raw, species of genera such as Flavobacterium, Burkholderia, Staphylococcus, Cladosporium and Aspergillus, which contain potentially human pathogenic strains, were identified. Analysis of the indigenous bacterial and endophytic fungal populations revealed only negligible, short-term effects resulting from the bacterial treatments, and that they were more influenced by field site, plant growth stage and microenvironment.


Toxicity of busulfan and cyclophosphamide (BU/CY2) in patients with hematologic malignancies.
Between July 1991 and January 1994, 52 patients with hematologic malignancies underwent BMT using BU/CY2 as conditioning regimen. Median patient age was 38 years. Eleven patients underwent autologous BMT, 22 HLA-identical allogeneic BMT, and 19 patients underwent a MUD or an allogeneic mismatched BMT. GVHD prophylaxis was with cyclosporine/methylprednisone in 26 patients; T cell depletion was used in 15 patients. VOD was observed in 7.5% of patients, IP in 12%, seizures in 4%. The overall incidence of grade II-IV acute GVHD was 35%. Delayed platelet engraftment was observed in seven of 11 patients who underwent autologous BMT. Graft failure was seen in seven of 19 (37%) patients who underwent MUD or allogeneic mismatched BMT. Six of the seven patients received T cell depletion as GVHD prophylaxis. BU/CY2 transplantation from an unrelated or family-mismatched donor with T cell depletion is associated with a high incidence of graft failure.


Expression of small interfering RNAs targeted against HIV-1 rev transcripts in human cells.
RNA interference (RNAi) is the process of sequence-specific, posttranscriptional gene silencing in animals and plants initiated by double-stranded (ds) RNA that is homologous to the silenced gene. This technology has usually involved injection or transfection of dsRNA in model nonvertebrate organisms. The longer dsRNAs are processed into short (19 25 nucleotides) small interfering RNAs (siRNAs) by a ribonucleotide protein complex that includes an RNAse III related nuclease (Dicer), a helicase family member, and possibly a kinase and an RNA-dependent RNA polymerase (RdRP). In mammalian cells it is known that dsRNA 30 base pairs or longer can trigger interferon responses that are intrinsically sequence-nonspecific, thus limiting the application of RNAi as an experimental and therapeutic agent. Duplexes of 21-nucleotide siRNAs with short 3' overhangs, however, can mediate RNAi in a sequence-specific manner in cultured mammalian cells. One limitation in the use of siRNA as a therapeutic reagent in vertebrate cells is that short, highly defined RNAs need to be delivered to target cells--a feat thus far only accomplished by the use of synthetic, duplex RNAs delivered exogenously to cells. In this report, we describe a mammalian Pol III promoter system capable of expressing functional double-stranded siRNAs following transfection into human cells. In the case of the 293 cells cotransfected with the HIV-1 pNL4-3 proviral DNA and the siRNA-producing constructs, we were able to achieve up to 4 logs of inhibition of expression from the HIV-1 DNA.


[Gonotrophic cycle of Leptoconops borealis (Diptera, Ceratopogonidae)].
Data are given concerning the gonotrophic cycle in fully engorged specimens of Leptoconops borealis, a mass blood sucker from the coast of the sea of Azov. In fully engorged females the repetition of gonotrophic cycles and degeneration of ovaries take place under the effect of Mermitoidea parasitism.


Controlling colloidal stability of silica nanoparticles during bioconjugation reactions with proteins and improving their longer-term stability, handling and storage.
Despite the potential of antibody-coated nanoparticles (Ab-NPs) in many biological applications, there are very few successful, commercially available examples in which the carefully engineered nanomaterial has made it beyond the laboratory bench. Herein we explore the robustness and cost of protein-nanoparticle conjugation. Using multivalent polyamidoamine (PAMAM) dendrimers and dextran as crosslinkers, it was possible to retain colloidal stability during (i) NP-linker binding and (ii) the subsequent conjugation reaction between linker-coated NPs and proteins to generate monodisperse Ab-NPs. This was attributed to the physicochemical properties of the linkers, which were inherited by the NPs and thus benefited colloidal stability. Attaching negatively charged, EDC/sulfo-NHS-activated PAMAM to the NPs contributed to overall negative charge of particles, and in turn led to high electrostatic attraction between the protein and PAMAM-coated NPs during the reaction conditions. In contrast, using an uncharged, EDC/NHS-activated PAMAM dendrimer led to NP aggregation and lower protein binding efficiency. Dextran as a cost-effective, uncharged macromolecule allowed for steric repulsions between neighbouring particles during protein binding, thus inducing NP stability in solution, and also produced monodisperse Ab-NPs. By freeze-drying Ab-NPs from a 1% BSA solution it is possible to reconstitute the solid-form colloid back to a stable state by adding solvent and simply shaking the sample vial by hand. The consequences of the different surface chemistries and freeze-drying stabilizers on the colloidal stability of the NPs were probed by dynamic light scattering. The performance of Ab-NPs was compared in a simple fluorescence linked immunoassay in whole serum. Interestingly, the signal-to-noise ratios were similar for Ab-NPs using PAMAM and dextran, despite dextran binding fewer Abs per NP. We believe this work provides researchers with the tools and strategies for reliably generating Ab-NPs that can be used for a variety of biological applications.


Perceived Well-Being, Social Support, and Self-Management Behavior among Women Experiencing Chemotherapy-Related Nausea and Vomiting in A Tertiary Hospital in Lahore, Pakistan.
The basic objective is to determine the level of the self-management behaviors (SMB), perceived well-being, and social support of patients in the outpatient settings at tertiary care hospital at Lahore Pakistan. It also explores if there is any significant relationship among all three variables. A descriptive-correlational study design has been used. The data have been collected at single setting of 32-bedded chemotherapy unit of a tertiary care hospital of Pakistan. The purposive sampling method has been employed. The IBM SPSS version 20 (IBM Corp., Armonk, NY, USA) has been utilized for statistical analyses. A total of 317 patients' data were analyzed. The average age of patients was 42 years, and they received chemotherapy for different cancers. It was revealed that the SMB, for example, taking anti-emetics on time, and applying physical and cognitive distractions, have strong association with psychological, social, physical, and emotional dimensions of the perceived well-being. Similar self-managing strategies have associations with the provision of social support from the health-care team, personal, and family side. To conclude, the most common self-care methods of women receiving chemo are pharmacological management, applying physical and cognitive distraction, executing relaxation measures to control chemo-induced nausea.


Predictors of Echinococcus multilocularis Prevalence in Definitive and Intermediate Hosts: A Meta-Analysis Approach.
Echinococcus multilocularis (EM) is a pathogenic and potentially fatal cestode causing human alveolar echinococcosis (AE). A meta-analysis was conducted using a generalized estimation equation approach (GEE) to assess the effect of taxonomic, environmental, and diagnostic variables on EM prevalence in different hosts. Red foxes ( Vulpes vulpes ) had significantly higher prevalence of EM than domestic dogs ( Canis lupus familiaris), with the diagnostic method playing an important factor in assessing prevalence. For intermediate hosts genera was significantly associated with EM prevalence, although there was some indication of publication bias in this dataset. This study also highlights the possible importance of temperature and precipitation to EM transmission. This implies the possibility of a changing climate affecting the future distribution of the parasite.


Perfectionism and self-consciousness in social phobia and panic disorder with agoraphobia.
Social phobics were compared to patients with panic disorder with agoraphobia and normal controls on perfectionism and self-consciousness. On concern over mistakes and doubts about action, social phobics scored higher than patients with panic disorder. Social phobics also demonstrated a higher level of public self-consciousness than patients with panic disorder and when this difference was controlled for the significant differences on perfectionism disappeared. Within each patient group, however, perfectionism was more robustly related to social anxiety than was public self-consciousness, which replicates the findings of Saboonchi and Lundh [Saboonchi, F. & Lundh, L. G. (1997). Perfectionism, self-consciousness and anxiety. Personality and Individual Differences, 22, 921-928.] from a non-clinical sample. The results are discussed in terms of public self-consciousness being a differentiating characteristic of the more severe kind of social anxiety which is typical of social phobia.


Implementation of dispersion models in the split-field-finite-difference-time-domain algorithm for the study of metallic periodic structures at oblique incidence.
We extend here the finite-difference-time-domain (FDTD) algorithm working in oblique incidence to dispersive media. The split-field method (SFM) is used and adapted for taking into account the metal dispersion. The additional equations to the FDTD algorithm are given. Instead of the 24 field components usually used in the SFM, 38 and 112 field components are needed to implement the cases of Drude and Drude-Lorentz dispersion models, respectively. Some tests are presented to validate our code as long as the angle of incidence is lower than 76 degrees in addition to an application dealing with enhanced transmission and showing original results.


Characterization of the Small RNA Transcriptome of the Marine Coccolithophorid, Emiliania huxleyi.
Small RNAs (smRNAs) control a variety of cellular processes by silencing target genes at the transcriptional or post-transcription level. While extensively studied in plants, relatively little is known about smRNAs and their targets in marine phytoplankton, such as Emiliania huxleyi (E. huxleyi). Deep sequencing was performed of smRNAs extracted at different time points as E. huxleyi cells transition from logarithmic to stationary phase growth in batch culture. Computational analyses predicted 18 E. huxleyi specific miRNAs. The 18 miRNA candidates and their precursors vary in length (18-24 nt and 71-252 nt, respectively), genome copy number (3-1,459), and the number of genes targeted (2-107). Stem-loop real time reverse transcriptase (RT) PCR was used to validate miRNA expression which varied by nearly three orders of magnitude when growth slows and cells enter stationary phase. Stem-loop RT PCR was also used to examine the expression profiles of miRNA in calcifying and non-calcifying cultures, and a small subset was found to be differentially expressed when nutrients become limiting and calcification is enhanced. In addition to miRNAs, endogenous small RNAs such as ra-siRNAs, ta-siRNAs, nat-siRNAs, and piwiRNAs were predicted along with the machinery for the biogenesis and processing of si-RNAs. This study is the first genome-wide investigation smRNAs pathways in E. huxleyi. Results provide new insights into the importance of smRNAs in regulating aspects of physiological growth and adaptation in marine phytoplankton and further challenge the notion that smRNAs evolved with multicellularity, expanding our perspective of these ancient regulatory pathways.


Ion recombination for ionization chamber dosimetry in a helical tomotherapy unit.
Ion recombination for ionization chambers in pulsed high-energy photon beams is a well-studied phenomenon. Despite this, the correction for ion recombination is often determined inaccurately due to the inappropriate combination of using a high polarizing voltage and the simple two-voltage method. An additional complication arises in new treatment modalities such as IMRT and tomotherapy, where the dosimetry of a superposition of many constituting fields becomes more relevant than of single static fields. For these treatment modalities, the irradiation of the ion chamber geometry can be instantaneously inhomogeneous and time dependent. This article presents a study of ion recombination in ionization chambers used for dosimetry in a helical tomotherapy beam. Models are presented for studying the recombination correction factors in a continuous beam, in pulsed large and small fields, and in helical fields. Measurements using Exradin A1SL, NE2571, and NE2611 type chambers and Monte Carlo simulations using PENELOPE are performed in support of these models. Initial recombination and charge multiplication are found to be the same in 60Co and in the pulsed high-energy photon beam for the chambers and operating voltages used in this study. Applying the two-voltage technique for the A1SL chamber at its recommended operating voltage of 300 V leads to an overestimation of the recombination. Operating at a voltage of 100 V yields larger but more accurate values for the recombination correction. The recombination correction measured for this chamber in the TomoTherapy HiArt unit is lower than the 1% applied in the routine dosimetry for this treatment unit. For a helical dose delivery with a small slice width, lateral electron scatter in the cavity makes that the recombination is smaller than for an open beam delivering the same total dose. In a Farmer type chamber, a helical delivery with a 1 cm slice field results in a time and spatially integrated volume recombination of 55% of that with a 2.5 cm slice field. The relative recombination corrections for different slice widths and different field offsets with respect to the chamber center obtained from the developed models are in good agreement with experimental data. Because of the presence of charge multiplication, it is more accurate to determine the recombination correction at lower operating voltages than are often applied using the two-voltage method. Models and experiments for partial irradiation conditions of the ion chamber show that resulting recombination corrections are reduced compared to those for an open field. A model for helical dose deliveries results in recombination corrections that get lower with smaller slice widths. This model could be adapted to any IMRT delivery where the ion chamber is instantaneously partial and/or inhomogeneously irradiated, and could provide a practical procedure to calculate the recombination for complex deliveries for which it is difficult to be measured.


Caterpillar Track Complexes in Template-Directed Synthesis and Correlated Molecular Motion.
Small alterations to the structure of a star-shaped template totally change its mode of operation. The hexapyridyl template directs the conversion of a porphyrin dimer to the cyclic hexamer, but deleting one pyridine site changes the product to the cyclic decamer, while deleting two binding sites changes the product to the cyclic octamer. This surprising switch in selectivity is explained by the formation of 2:1 caterpillar track complexes, in which two template wheels bind inside the nanoring. Caterpillar track complexes can also be prepared by binding the hexapyridyl template inside the 8- and 10-porphyrin nanorings. NMR exchange spectroscopy (EXSY) experiments show that these complexes exhibit correlated motion, in which the conrotatory rotation of the two template wheels is coupled to rotation of the nanoring track. In the case of the 10-porphyrin system, the correlated motion can be locked by binding palladium(II) dichloride between the two templates.


Clinical and laboratory biomarkers in the management of pancreatic adenocarcinoma.
Despite improvements in the health service and the available treatment means, the outcome of the majority of patients with advanced pancreatic adenocarcinoma, even in the Western world, is disappointing. This fact necessitates invention and development of clinical and laboratory biomarkers that help us detect early enough those patients who have the worst prognosis, and who may benefit or not from our treatments and individualize thus our management accordingly. In the 2012 American Society of Clinical Oncology (ASCO) Annual Meeting, four interesting scientific works on biomarkers in pancreatic cancer were presented. Two of them presented new clinical data such as the correlation of hand and foot skin reaction with the prognosis of patients treated with capecitabine based treatment (Abstract #4023), and the independent association of early presentation of venous thromboembolic events with poor survival (Abstract #4037). The other two significant abstracts focused on new potential predictive laboratory biomarkers, such as the association of the baseline levels of serum albumin to benefit from bevacizumab enriched treatment (Abstract #4039) and the likely correlation of high insulin growth factor 1 (IGF-1) tissue expression to better prognosis in patients treated with the IGF-1 receptor monoclonal antibody (mAb) MK-0646 (Abstract #4054).


In vivo transcription of ribosomal RNA in relation to the mitotic cycle in Physarum polycephalum.
We have investigated the transcription of ribosomal RNA in plasmodia of Physarum polycephalum by a combination of pulse-labelling with [3H]uridine and RNA:DNA hybridization. The DNA used for the hybridization was a HindIII restriction fragment (cloned in bacteriophage lambda) of Physarum ribosomal DNA that carries a substantial fraction of the rRNA genes, enabling the ribosomal transcripts in the newly synthesized RNA to be measured. We found that ribosomal RNA constituted about 40% of the pulse-labelled RNA at all times during the synchronous mitotic cycle.


Comparisons of the combined contributions of agonist binding frequency and intrinsic efficiency to receptor-mediated activation of adenylate cyclase.
A given overall level of beta-adrenergic receptor occupancy by agonist can involve either high or low turnover of occupancy with respect to individual receptors, depending on the binding properties of the particular agonist. It was recently demonstrated that, for epinephrine-stimulated adenylate cyclase activation in the S49 cell, a portion of the separation between the beta-adrenergic receptor binding curve and the cyclase response curves is dependent on high occupancy turnover (high binding frequency). By involving a larger number of receptors within a short period of time than are bound at any one instant, the effect of high binding frequency is to increase the rate of GTP-binding protein/adenylate cyclase activation over the rate that is observed when the mobility of the number of receptors occupied at any given instant is the rate-limiting factor. This phenomenon contributes to the normal dose-response curve for epinephrine, according to our analysis, but only in combination with the apparent high efficiency of the receptor in the epinephrine-bound state at cyclase activation. Here we examined the potential combination of the contributions of agonist binding frequency and intrinsic efficiency to the adenylate cyclase activation rate for four other beta-adrenergic agonists (isoproterenol, zinterol, metaproterenol, and dobutamine). This was done by a comparison of the response (1-min cAMP accumulation) between a point on the normal dose versus response curve (control) with the response under conditions in which the concentration of agonist-bound receptors was identical to control but the absolute number of receptors involved in maintaining that concentration was significantly reduced. In the experiments, the majority of the receptors were blocked by the beta-adrenergic antagonist propranolol, which has a relatively long occupancy half-life. The remaining receptors were occupied by agonist such that the concentration of bound receptors was identical to the control condition of low occupancy of the full complement of receptors in the absence of antagonist. Compared with control, the experimental condition was one in which agonist occupancy turnover was inhibited and the potential contribution of agonist binding frequency as a factor contributing to the cyclase activation rate was greatly reduced (producing a point on the receptor mobility-limited dose versus response curve). Isoproterenol and metaproterenol show evidence that their binding frequencies and the efficiency of the receptor when bound to them are of such a combination that the normal dose-response curves for these agonists contain a component that is dependent on the binding frequency.(ABSTRACT TRUNCATED AT 400 WORDS)


The anterior cerebellar vermis: essential involvement in classically conditioned bradycardia in the rabbit.
The effects of lesions of the cerebellum on the acquisition and retention of aversive Pavlovian conditioned bradycardia were examined in rabbits. Lesions of the anterior cerebellar vermis severely attenuated the acquisition of simple conditioned bradycardia without disrupting baseline heart rate (HR), or unconditioned HR responses. Also, lesions of the vermis performed after the acquisition of conditioned bradycardia eliminated evidence of prior conditioning. Bilateral lesions of the cerebellar hemispheres did not affect conditioned or unconditioned HR responses. These results were interpreted to indicate that anterior vermis lesions specifically disrupted part of an essential conditioned response pathway without interfering with the neural circuits that mediate unconditioned HR responding. These lesion data, coupled with recent electrophysiological evidence of learning-related changes in neuronal activity within the anterior vermis of the fear-conditioned rabbit, suggest that the anterior cerebellar vermis is critically involved in the acquisition and retention of this rapidly learned autonomic conditioned response.


Do women exhibit greater differences in established and novel risk factors between diabetes and non-diabetes than men? The British Regional Heart Study and British Women's Heart Health Study.
Type 2 diabetes is associated with greater relative risk of CHD in women than in men, which is not fully explained by conventional cardiovascular risk factors. We assessed whether cardiovascular risk factors including more novel factors such as markers of insulin resistance, inflammation, activated coagulation and endothelial dysfunction differ more between diabetic and non-diabetic women than between diabetic and non-diabetic men, and the role of insulin resistance. A cross-sectional study of non-diabetic and diabetic men and women (n = 7,529) aged 60-79 years with no previous myocardial infarction who underwent an examination was conducted. Measurements of anthropometry, blood pressure and fasting measurements of lipids, insulin, glucose and haemostatic and inflammatory markers were taken. Non-diabetic women tended to have more favourable risk factors and were less insulin resistant than non-diabetic men, but this was diminished in the diabetic state. Levels of waist circumference, BMI, von Willebrand factor (VWF), WBC count, insulin resistance (HOMA-IR), diastolic blood pressure, HDL-cholesterol, tissue plasminogen activator (t-PA) and factor VIII differed more between diabetic and non-diabetic women than between diabetic and non-diabetic men (test for diabetes × sex interaction p < 0.05). The more adverse effect of diabetes on these risk markers in women was associated with, and thereby largely attenuated by, insulin resistance. The greater adverse influence of diabetes per se on adiposity and HOMA-IR and downstream blood pressure, lipids, endothelial dysfunction and systemic inflammation in women compared with men may contribute to their greater relative risk of coronary heart disease.


Entorhinal cortex of the monkey: IV. Topographical and laminar organization of cortical afferents.
The nonhuman primate entorhinal cortex is the primary interface for information flow between the neocortex and the hippocampal formation. Based on previous retrograde tracer studies, neocortical afferents to the macaque monkey entorhinal cortex originate largely in polysensory cortical association areas. However, the topographical and laminar distributions of cortical inputs to the entorhinal cortex have not yet been comprehensively described. The present study examines the regional and laminar termination of projections within the entorhinal cortex arising from different cortical areas. The study is based on a library of 51 (3)H-amino acid injections that involve most of the afferent regions of the entorhinal cortex. The range of termination patterns was broad. Some areas, such as the medial portion of orbitofrontal area 13 and parahippocampal areas TF and TH, project widely within the entorhinal cortex. Other areas have a more focal and regionally selective termination. The lateral orbitofrontal, insular, anterior cingulate, and perirhinal cortices, for example, project only to rostral levels of the entorhinal cortex. The upper bank of the superior temporal sulcus projects mainly to intermediate levels of the entorhinal cortex, and the parietal and retrosplenial cortices project to caudal levels. The projections from some of these cortical regions preferentially terminate in the superficial layers (I-III) of the entorhinal cortex, whereas others project more heavily to the deep layers (V-VI). Thus, some of the cortical inputs may be more influential on the cortically directed outputs of the hippocampal formation or on gating neocortical information flow into the other fields of the hippocampal formation rather than contributing to the perforant path inputs to other hippocampal fields.


Proposal and Validation of a Simple Grading Scale (TRANSSPHER Grade) for Predicting Gross Total Resection of Nonfunctioning Pituitary Macroadenomas After Transsphenoidal Surgery.
A simple, reliable grading scale to better characterize nonfunctioning pituitary adenomas (NFPAs) preoperatively has potential for research and clinical applications. To develop a grading scale from a prospective multicenter cohort of patients that accurately and reliably predicts the likelihood of gross total resection (GTR) after transsphenoidal NFPA surgery. Extent-of-resection (EOR) data from a prospective multicenter study in transsphenoidal NFPA surgery were analyzed (TRANSSPHER study; ClinicalTrials.gov NCT02357498). Sixteen preoperative radiographic magnetic resonance imaging (MRI) tumor characteristics (eg, tumor size, invasion measures, tumor signal characteristics, and parameters impacting surgical access) were evaluated to determine EOR predictors, to calculate receiver-operating characteristic curves, and to develop a grading scale. A separate validation cohort (n = 165) was examined to assess the scale's performance and inter-rater reliability. Data for 222 patients from 7 centers treated by 15 surgeons were analyzed. Approximately one-fifth of patients (18.5%; 41 of 222) underwent subtotal resection (STR). Maximum tumor diameter > 40 mm; nodular tumor extension through the diaphragma into the frontal lobe, temporal lobe, posterior fossa, or ventricle; and Knosp grades 3 to 4 were identified as independent STR predictors. A grading scale (TRANSSPHER grade) based on a combination of these 3 features outperformed individual variables in predicting GTR (AUC, 0.732). In a validation cohort, the scale exhibited high sensitivity and specificity (AUC, 0.779) and strong inter-rater reliability (kappa coefficient, 0.617). This simple, reliable grading scale based on preoperative MRI characteristics can be used to better characterize NFPAs for clinical and research purposes and to predict the likelihood of achieving GTR.


Active aging promotion: results from the vital aging program.
Active aging is one of the terms in the semantic network of aging well, together with others such as successful, productive, competent aging. All allude to the new paradigm in gerontology, whereby aging is considered from a positive perspective. Most authors in the field agree active aging is a multidimensional concept, embracing health, physical and cognitive fitness, positive affect and control, social relationships and engagement. This paper describes Vital Aging, an individual active aging promotion program implemented through three modalities: Life, Multimedia, and e-Learning. The program was developed on the basis of extensive evidence about individual determinants of active aging. The different versions of Vital Aging are described, and four evaluation studies (both formative and summative) are reported. Formative evaluation reflected participants' satisfaction and expected changes; summative evaluations yielded some quite encouraging results using quasi-experimental designs: those who took part in the programs increased their physical exercise, significantly improved their diet, reported better memory, had better emotional balance, and enjoyed more cultural, intellectual, affective, and social activities than they did before the course, thus increasing their social relationships. These results are discussed in the context of the common literature within the field and, also, taking into account the limitations of the evaluations accomplished.


Inflammatory Marker Predicts Outcome of Oral Squamous Cell Carcinoma Receiving Chemo-Radiotherapy.
Inflammation is involved in the progression of oral squamous cell carcinoma. We therefore postulate that a blood-based inflammatory marker, the neutrophil-to-lymphocyte ratio, could help to predict the prognosis in patients with oral squamous cell carcinoma receiving chemo-radiotherapy, and build a prognostic nomogram. In 111 cases of oral squamous cell carcinoma, several baseline variables, including inflammatory markers and lactate dehydrogenase, were measured within the week of chemo-radiotherapy initiation as predictors of mortality and separate risk scores were developed. Dichotomized neutrophil-to-lymphocyte ratio was found to be associated with AJCC stage (p<0.001). Patients with oral squamous cell carcinoma with a low neutrophil-to-lymphocyte ratio survived longer than those with a high neutrophil-to-lymphocyte ratio (overall survival HR=2.39, 95% CI 1.24-4.61, p=0.009). The Harrell's concordance (C)-statistic of the nomogram was 0.74 and the calibration curve demonstrated the goodness of fit. The inflammatory marker neutrophil-to-lymphocyte ratio, obtained before chemo-radiotherapy, was an independent factor of survival prediction for oral squamous cell carcinoma. The nomogram incorporating immunological markers could more accurately predict individualized survival probability than the existing models. These findings are significant for the creation of personalized treatment strategies in the clinical setting.


Renal calcium phosphate and oxalate deposition in prolonged vitamin B6 deficiency: studies on a rat model of urolithiasis.
To determine the effect on kidney oxalate-salt deposition of a prolonged diet which induced vitamin B6 deficiency in adult rats, as there are reports of the pathogenic involvement of vitamin B6 deficiency in the formation of renal calcium oxalate calculi. The study comprised 24 6-month-old male albino Wistar rats; 12 were fed with a purified vitamin B6-deficient diet and the others provided with the same diet but supplemented with 6 mg/kg of vitamin B6. After 12 weeks, all rats were killed, and their kidneys fixed in formalin and routinely processed to paraffin for morphological examination; some fragments were fixed in glutaraldehyde and prepared for ultrastructural examination. From each rat consecutive sections of both kidneys were cut and stained with haematoxylin and eosin, periodic-acid Schiff, Sirius red and the Von Kossa method for calcium. Sections were examined in polarized light and by electron microscopy. The histopathological and ultrastructural features of the kidney of vitamin B6-deficient rats were those of tubular-interstitial nephritis, characterized by tubular atrophy, interstitial fibrosis and chronic inflammatory infiltration. Oxalate and phosphate crystals were present in the papillary and parenchymal connective tissue. Ultrastructural features confirmed severe tubular epithelial lesions and the presence of an interstitial and intraepithelial inflammatory infiltrate; there was mild interstitial fibrosis. None of these features were apparent in the kidney of control rats. Histopathological and ultrastructural data indicate that a prolonged vitamin B6-deficient diet may contribute to the formation and deposition of calcium phosphate and oxalate crystals, which lead to severe damage of the renal parenchyma. This phenomenon may occur not only in growing rats, which have more active protein metabolism and consequently higher vitamin B6 requirements, but also in adult rats.


Stressful Life Changes and Their Relationship to Nutrition-Related Health Outcomes Among US Army Soldiers.
Stressful life changes may tax people's adaptive capacity. We sought to determine if and when experiences of stressful life changes were associated with increased odds of adverse nutrition-related health outcomes among US Army soldiers relative to those who did not experience the same stressful life change. An additional aim was to determine which stressful life changes had the greatest association with these outcomes and if there were gender differences in the magnitude of the associations. Stressful life changes studied included: changes in marital status, combat deployment or return from deployment, relocation, adding a child, change in rank, change in occupation, and development of a physical limitation to duty. Using longitudinal data from the Stanford Military Data Repository, which represents all active-duty soldiers aged 17-62 between 2011 and 2014 (n = 827,126), we employed an event history analysis to examine associations between stressful life changes and a subsequent diagnosis of hyperlipidemia, substantial weight gain, and weight-related separation from the Army. Marriage was associated with an increase in the odds of substantial weight gain 3 months later for both men and women. Developing a physical duty limitation was associated with an increase in the odds of a hyperlipidemia diagnosis 2 months later for both men and women, as was substantial weight gain 2 months later. Stressful life changes were also associated with increased odds of nutrition-related health outcomes, although we found gender differences in the magnitude of the associations. Findings could be used to mitigate the effects of stress on health by health professionals.


From SARS to the Omicron variant of COVID-19: China's policy adjustments and changes to prevent and control infectious diseases.
The COVID-19 pandemic has been the biggest public health crisis in a century. Since it was initially reported in 2019, the duration and intensity of its impacts are still in serious question around the world, and it is about to enter its third year. The first public health revolution failed to achieve its ultimate targets, as previously contained infectious diseases seem to have returned, and new infectious diseases continue to emerge. The prevention and control of infectious diseases is still a public health priority worldwide. After SARS, China adjusted a series of its infectious disease policies. In order to ensure the effectiveness and implementation of prevention and control interventions, the government should integrate the concept of public health. Perhaps we need a global public health system at the government level to fight the potential threat of infectious disease. This system could include multifaceted strategies, not just specific prevention and control interventions, and it could also be a comprehensive system to ensure unimpeded communication and cooperation as well as sustainable development.


Comparison of the microdrop and minimum volume cooling methods for vitrification of porcine in vitro-produced zygotes and blastocysts after equilibration in low concentrations of cryoprotectant agents.
We compared the efficacy of the microdrop and minimum volume cooling (MVC) methods for the vitrification of in vitro-produced porcine zygotes and blastocysts after equilibration in low concentrations of cryoprotectant agents. Zygotes and blastocysts were equilibrated in 2% (v/v) ethylene glycol and 2% (v/v) propylene glycol for 13-15 min. Then, they were vitrified in a medium comprised of 17.5% ethylene glycol, 17.5% propylene glycol, 0.3 M sucrose, and 50 mg/ml polyvinylpyrrolidone either by either dropping them directly into liquid nitrogen (microdrop method) or placing them on Cryotop sheets in a minimum volume of medium and plunging into liquid nitrogen (MVC method). Both zygotes and blastocysts were successfully vitrified. For the vitrification of zygotes, the MVC and microdrop methods were equally effective; however, for blastocyst vitrification, MVC was superior. For both methods, the vitrification of zygotes produced higher-quality embryos than the vitrification of blastocysts.


Plasma amino acids and tissue methionine levels in fruit bats (Rousettus aegyptiacus) with nitrous oxide-induced vitamin B12 deficiency.
The effect of methylcobalamin inactivation by the gas nitrous oxide on plasma amino acid and tissue methionine levels in fruit bats (Rousettus aegyptiacus) was examined. Animals exposed to N2O-oxygen (1:1, v/v) for 90 min daily received a fruit diet with or without methionine or betaine supplements. Exposure and diets were continued for up to 17 weeks or until neurological impairment and muscular weakness was established. All the groups exposed to N2O had significantly lower liver, brain and plasma methionine concentrations except the methionine-supplemented animals which showed significantly raised levels. Plasma homocysteine, which was absent in controls, was present in all the N2O-exposed groups. Betaine supplementation resulted in reduced accumulation of homocysteine in plasma. However, plasma and liver methionine levels were only slightly increased compared with animals on the basal diet, and brain methionine levels were the lowest of all the groups studied. These results support the hypothesis that reduced methionine synthesis is an important contributor to the development of neurological impairment in this species and suggest that dietary supplementation with the methionine precursor betaine cannot replace the loss of vitamin B12-dependent methionine synthesis.


spolTools: online utilities for analyzing spoligotypes of the Mycobacterium tuberculosis complex.
spolTools is a collection of online programs designed to manipulate and analyze spoligotype datasets of the Mycobacterium tuberculosis complex. These tools are integrated into a repository currently containing 1179 spoligotypes and 6278 isolates across 30 datasets. Users can search this database to export for external use or to pass on to the integrated tools. These tools include the computation of basic population genetic quantities, the visualization of clusters of spoligotype patterns based on an estimated evolutionary history and a procedure to predict emerging strains - genotypes associated with elevated transmission.


Relaxin treatment reduces angiotensin II-induced vasoconstriction in pregnancy and protects against endothelial dysfunction†.
The peptide relaxin has gained considerable attention as a new vasoactive drug, largely through its beneficial therapeutic effects in cardiovascular disease. In this study, we tested the hypothesis that relaxin treatment alleviates systemic vascular dysfunction characteristic of hypertensive diseases of pregnancy. We investigated vascular effects and mechanisms of relaxin action in (i) pregnant relaxin-deficient (Rln-/-) mice with enhanced responses to angiotensin II (AngII) and (ii) arteries pre-incubated ex vivo in trophoblast conditioned media (TCM) to induce endothelial dysfunction. Pregnant Rln-/- mice received 0.5 μg/h recombinant human H2 relaxin (rhRLX: n = 5) or placebo (20 nM sodium acetate; n = 7) subcutaneously via osmotic minipumps for 5 days prior to gestational day 17.5. This treatment protocol significantly reduced AngII-mediated contraction of mesenteric arteries and increased plasma 6-keto prostaglandin F1α. These vascular effects were endothelium independent and likely involve smooth muscle-derived vasodilator prostanoids. In the second study, mesenteric arteries were incubated ex vivo for 24 h at 37°C in TCM, which contained high levels of soluble Flt-1 (>20 ng/ml) and soluble Eng (>1 ng/ml). TCM incubation caused significant reduction in endothelium-dependent relaxation and increased sensitivity to AngII. Co-incubation of arteries with rhRLX for 24 h (n = 6-16/treatment) prevented endothelial dysfunction but had no effect on AngII-mediated contraction. In conclusion, relaxin treatment prevents and/or reverses vascular dysfunction in mesenteric arteries, but acts through different vascular pathways depending on duration of relaxin treatment and type of vascular dysfunction. Overall, our data suggest that relaxin is a potential therapeutic to alleviate maternal systemic vascular dysfunction associated with hypertensive diseases in pregnant women.


Effects of oxygen on biodegradation of benzoate and 3-chlorobenzoate in a denitrifying chemostat.
A mixed microbial culture degraded a mixture of benzoate (863 mg/L), 3-chlorobenzoate (3-CB) (69.7 mg/L), and pyruvate (244 mg/L) under denitrifying conditions in a chemostat. Biodegradation under denitrifying conditions was stable, complete (effluent concentrations below detection limits), and proceeded without the production of toxic intermediates like chlorocatechols. The addition of oxygen at mass input rates of 6.2%, 15.5%, and 43.9% of the mass input rate of chemical oxygen demand (COD) (337 mg COD/h) did not induce the synthesis of aerobic biodegradation pathways and thus did not disrupt biodegradation. Rather, the oxygen was used as a terminal electron acceptor, displacing a stoichiometric amount of nitrate, leading to microaerobic conditions (dissolved oxygen concentration <0.050 mg/L) in which oxygen utilization and denitrification occurred simultaneously. The reduction of nitrate occurred fully to N(2) gas with no accumulation of nitrite, nitrous oxide, or nitric oxide, although the ability of the culture to transfer electrons to the nitrogen oxides decreased as the oxygen input was increased. The anoxic benzoate uptake capability was unaffected by the increase in oxygen addition, but the anoxic 3-CB uptake capability increased, as did the level of benzoyl-CoA reductase in the cells.


Prediction of protein long-range contacts using an ensemble of genetic algorithm classifiers with sequence profile centers.
Prediction of long-range inter-residue contacts is an important topic in bioinformatics research. It is helpful for determining protein structures, understanding protein foldings, and therefore advancing the annotation of protein functions. In this paper, we propose a novel ensemble of genetic algorithm classifiers (GaCs) to address the long-range contact prediction problem. Our method is based on the key idea called sequence profile centers (SPCs). Each SPC is the average sequence profiles of residue pairs belonging to the same contact class or non-contact class. GaCs train on multiple but different pairs of long-range contact data (positive data) and long-range non-contact data (negative data). The negative data sets, having roughly the same sizes as the positive ones, are constructed by random sampling over the original imbalanced negative data. As a result, about 21.5% long-range contacts are correctly predicted. We also found that the ensemble of GaCs indeed makes an accuracy improvement by around 5.6% over the single GaC. Classifiers with the use of sequence profile centers may advance the long-range contact prediction. In line with this approach, key structural features in proteins would be determined with high efficiency and accuracy.


Associations of Weight Gain From Early to Middle Adulthood With Major Health Outcomes Later in Life.
Data describing the effects of weight gain across adulthood on overall health are important for weight control. To examine the association of weight gain from early to middle adulthood with health outcomes later in life. Cohort analysis of US women from the Nurses' Health Study (1976-June 30, 2012) and US men from the Health Professionals Follow-Up Study (1986-January 31, 2012) who recalled weight during early adulthood (at age of 18 years in women; 21 years in men), and reported current weight during middle adulthood (at age of 55 years). Weight change from early to middle adulthood (age of 18 or 21 years to age of 55 years). Beginning at the age of 55 years, participants were followed up to the incident disease outcomes. Cardiovascular disease, cancer, and death were confirmed by medical records or the National Death Index. A composite healthy aging outcome was defined as being free of 11 chronic diseases and major cognitive or physical impairment. A total of 92 837 women (97% white; mean [SD] weight gain: 12.6 kg [12.3 kg] over 37 years) and 25 303 men (97% white; mean [SD] weight gain: 9.7 kg [9.7 kg] over 34 years) were included in the analysis. For type 2 diabetes, the adjusted incidence per 100 000 person-years was 207 among women who gained a moderate amount of weight (≥2.5 kg to <10 kg) vs 110 among women who maintained a stable weight (weight loss ≤2.5 kg or gain <2.5 kg) (absolute rate difference [ARD] per 100 000 person-years, 98; 95% CI, 72 to 127) and 258 vs 147, respectively, among men (ARD, 111; 95% CI, 58 to 179); hypertension: 3415 vs 2754 among women (ARD, 662; 95% CI, 545 to 782) and 2861 vs 2366 among men (ARD, 495; 95% CI, 281 to 726); cardiovascular disease: 309 vs 248 among women (ARD, 61; 95% CI, 38 to 87) and 383 vs 340 among men (ARD, 43; 95% CI, -14 to 109); obesity-related cancer: 452 vs 415 among women (ARD, 37; 95% CI, 4 to 73) and 208 vs 165 among men (ARD, 42; 95% CI, 0.5 to 94). Among those who gained a moderate amount of weight, 3651 women (24%) and 2405 men (37%) achieved the composite healthy aging outcome. Among those who maintained a stable weight, 1528 women (27%) and 989 men (39%) achieved the composite healthy aging outcome. The multivariable-adjusted odds ratio for the composite healthy aging outcome associated with moderate weight gain was 0.78 (95% CI, 0.72 to 0.84) in women and 0.88 (95% CI, 0.79 to 0.97) in men. Higher amounts of weight gain were associated with greater risks of major chronic diseases and lower likelihood of healthy aging. In these cohorts of health professionals, weight gain during adulthood was associated with significantly increased risk of major chronic diseases and decreased odds of healthy aging. These findings may help counsel patients regarding the risks of weight gain.