Blood pressure and renal haemodynamic response to salt during the normal menstrual cycle.
The purpose of the present study was to evaluate prospectively blood pressure and the renal haemodynamic response to salt during the normal menstrual cycle. A total of 35 healthy normotensive young women not on oral contraceptives were enrolled; 17 were studied in the follicular phase and 18 in the luteal phase of the menstrual cycle. The women in each group were then randomly allocated to receive a low-sodium (40 mmol/day) or a high-sodium (250 mmol/day) diet for a 7-day period in two consecutive menstrual cycles. At the end of each dietary period, 24 h ambulatory blood pressure, urinary sodium excretion, plasma renin activity, plasma catecholamine levels and renal haemodynamics were measured. Our results show that the blood pressure response to salt is comparable during the luteal and the follicular phases of the normal menstrual cycle and is characterized by a salt-resistant pattern. In the kidney, effective renal plasma flow was significantly greater and the filtration fraction lower (P<0.05) after salt loading in women studied in the luteal phase compared with women investigated in the follicular phase. This study thus demonstrates that the female hormone status does not affect the blood pressure response to sodium in young normotensive women. However, in contrast with systemic haemodynamics, the renal response to salt varies during the normal menstrual cycle, suggesting that female sex hormones play a role (direct or indirect) in the regulation of renal haemodynamics.


Implications of humanitarian orthopaedic surgery in a combat zone: Operation Enduring Freedom and Iraqi Freedom experience.
The primary mission of deployed military orthopaedic surgeons in a combat zone is to treat musculoskeletal battlefield trauma and associated wartime injuries. The role of humanitarian surgical care during combat operations has not been defined. An anonymous online survey was sent to databases containing all U.S. military active-duty orthopaedic surgeons as well as to members of the Society of Military Orthopaedic Surgeons. Inclusion criteria for the study were defined as at least one deployment to Iraq (Operation Iraqi Freedom, OIF) or Afghanistan (Operation Enduring Freedom, OEF). Three hundred fifty-six invitations were sent with 107 orthopaedic surgeons completing the survey. Respondents reported approximately 3,000 humanitarian surgeries performed in the combat zone, with 70% to 80% involving chronic deformity and nonunion surgeries. Seventy-nine percent of the respondents believed that humanitarian surgery was a key component of the mission, improved skills (73%), benefited population (76%), and improved security (61%). A significant amount of humanitarian surgery in the combat zone has been performed in OEF/OIF.


Representation of collective electrical behavior of cardiac cell sheets.
The electrocardiogram (ECG) is a measure of the collective electrical behavior of the heart based on body surface measurements. With computational models or tissue preparations, various methods have been used to compute the pseudo-ECG (pECG) of bipolar and unipolar leads that can be given clinical interpretation. When spatial maps of transmembrane potential (V(m)) are available, pECG can be derived from a weighted sum of the spatial gradients of V(m). The concept of a lead field can be used to define sensitivity curves for different bipolar and unipolar leads and to determine an effective operating height for the bipolar lead position for a two-dimensional sheet of heart cells. The pseudo-vectorcardiogram (pVCG) is computed from orthogonal bipolar lead voltages, which are derived in this study from optical voltage maps of cultured monolayers of cardiac cells. Rate and propagation direction for paced activity, rotation frequency for reentrant activity, direction of the common pathway for figure-eight reentry, and transitions from paced activity to reentry can all be distinguished using the pVCG. In contrast, the unipolar pECG does not clearly distinguish among many of the different types of electrical activity. We also show that pECG can be rapidly computed by two geometrically weighted sums of V(m), one that is summed over the area of the cell sheet and the other over the perimeter of the cell sheet. Our results are compared with those of an ad hoc difference method used in the past that consists of a simple difference of the sum of transmembrane potentials on one side of a tissue sheet and that of the other.


The Role of Predictive Biomarkers in Endocervical Adenocarcinoma: Recommendations From the International Society of Gynecological Pathologists.
To review the scientific evidence related to predictive biomarkers in cervical adenocarcinoma (ADC). The authors reviewed the literature regarding predictive biomarkers in cervical ADC. There were several limitations: (1) there is an overlap between predictive and prognostic biomarkers, as the vast majority of patients are treated with anticancer strategies; (2) in many studies and clinical trials, cervical ADC patients are included in a large series of patients predominantly composed of cervical squamous cell carcinomas; and (3) in most of the studies, and clinical trials, there is no distinction between human papillomavirus (HPV)-associated and HPV-independent cervical ADCs, or between various histologic subtypes. Results obtained from a small group of studies confirm that cervical ADCs exhibit distinct molecular features as compared with squamous carcinomas, and that there are different molecular features between different types of cervical ADCs. Promising areas of interest include ERBB2 (HER2) mutations and PD-L1 expression as predictive biomarkers for anti-HER2 treatment and immunotherapy, respectively. To date, no definitive data can be obtained from the literature regarding predictive biomarkers for cervical ADC. Clinical trials specifically designed for endocervical ADC patients are required to elucidate the predictive value of HER2 mutations and PD-L1 expression. The distinction between HPV-associated and HPV-independent cervical ADCs as well as early involvement of pathologists in the design of future clinical trials are needed to identify new predictive biomarkers in cervical ADC.


Partial differential equation models in macroeconomics.
The purpose of this article is to get mathematicians interested in studying a number of partial differential equations (PDEs) that naturally arise in macroeconomics. These PDEs come from models designed to study some of the most important questions in economics. At the same time, they are highly interesting for mathematicians because their structure is often quite difficult. We present a number of examples of such PDEs, discuss what is known about their properties, and list some open questions for future research.


Red meat and poultry, cooking practices, genetic susceptibility and risk of prostate cancer: results from a multiethnic case-control study.
Red meat, processed and unprocessed, has been considered a potential prostate cancer (PCA) risk factor; epidemiological evidence, however, is inconclusive. An association between meat intake and PCA may be due to potent chemical carcinogens that are generated when meats are cooked at high temperatures. We investigated the association between red meat and poultry intake and localized and advanced PCA taking into account cooking practices and polymorphisms in enzymes that metabolize carcinogens that accumulate in cooked meats. We analyzed data for 1096 controls, 717 localized and 1140 advanced cases from the California Collaborative Prostate Cancer Study, a multiethnic, population-based case-control study. We examined nutrient density-adjusted intake of red meat and poultry and tested for effect modification by 12 SNPs and 2 copy number variants in 10 carcinogen metabolism genes: GSTP1, PTGS2, CYP1A2, CYP2E1, EPHX1, CYP1B1, UGT1A6, NAT2, GSTM1 and GSTT1. We observed a positive association between risk of advanced PCA and high intake of red meat cooked at high temperatures (trend P = 0.026), cooked by pan-frying (trend P = 0.035), and cooked until well-done (trend P = 0.013). An inverse association was observed for baked poultry and advanced PCA risk (trend P = 0.023). A gene-by-diet interaction was observed between an SNP in the PTGS2 gene and the estimated levels of meat mutagens (interaction P = 0.008). Our results support a role for carcinogens that accumulate in meats cooked at high temperatures as potential PCA risk factors, and may support a role for heterocyclic amines (HCAs) in PCA etiology.


The role of lipid dysregulation in gestational diabetes mellitus: Early prediction and postpartum prognosis.
Gestational diabetes mellitus (GDM) is a pathological condition during pregnancy characterized by impaired glucose tolerance, and the failure of pancreatic beta-cells to respond appropriately to an increased insulin demand. However, while the majority of women with GDM will return to normoglycemia after delivery, they have up to a seven times higher risk of developing type 2 diabetes during midlife, compared with those with no history of GDM. Gestational diabetes mellitus also increases the risk of multiple metabolic disorders, including non-alcoholic fatty liver disease, obesity, and cardiovascular diseases. Lipid metabolism undergoes significant changes throughout the gestational period, and lipid dysregulation is strongly associated with GDM and the progression to future type 2 diabetes. In addition to common lipid variables, discovery-based omics techniques, such as metabolomics and lipidomics, have identified lipid biomarkers that correlate with GDM. These lipid species also show considerable potential in predicting the onset of GDM and subsequent type 2 diabetes post-delivery. This review aims to update the current knowledge of the role that lipids play in the onset of GDM, with a focus on potential lipid biomarkers or metabolic pathways. These biomarkers may be useful in establishing predictive models to accurately predict the future onset of GDM and type 2 diabetes, and early intervention may help to reduce the complications associated with GDM.


Decisional support to prevent adverse drug reactions of long latency: pilot randomized controlled intervention for glucocorticoid-induced diabetes.
Long-term exposure to glucocorticoids can cause adverse drug reactions of long latency (ADRLLs), including glucocorticoid-induced diabetes mellitus (GID). Providers can monitor for GID using the glycosylated haemoglobin blood (HbA1C) test. This study examined the utility of decisional support to improve HbA1C-based screening for GID. US veterans were identified as chronic users of oral glucocorticoids (>120 days of oral glucocorticoids in the last 2 years). The primary care providers caring for these patients were the target of the intervention. Providers were randomized to receive automatic HbA1C orders for their patients receiving chronic glucocorticoid or usual care. This study was a pilot two-arm, group-randomized, controlled trial (n = 12 providers, n = 38 patients). Data collection occurred from 5 May 2013 until 10 January 2014. A pharmacist generated the order for an HbA1C through the electronic medical record. The time between the intervention start date and the date on which an HbA1C order was signed were compared using Cox proportional and hierarchical linear regression. The time to sign HbA1C orders (mean 12.0 days for the intervention arm; 104.0 days for control arm) was associated with significant differences favouring the intervention [HR (Hazard Ratio) 50.2, P < 0.001, confidence interval (CI) 6.3 to 398.7]. For the intervention group, 95% of orders were signed, whereas only 12% of control providers signed orders (odds ratio 150, P < 0.001, CI 12.4 to 1812.9). The results of this study strongly suggest that the clinical pharmacist-triggered order intervention is effective. This method of computerized decisional support may be useful in improving screening for GID and ADRLLs.


Spontaneously resolving late-onset ocular myasthenia related to COVID-19. A case report.
Myasthenia gravis (MG) is the most common disease of the neuromuscular junction disorders with bimodal distribution of age, which is often under-estimated in the elderly. Some clinical cases show an association between MG and COVID-19, since molecular mimicry between SARS-CoV-2 and AChR proteins could be responsible for the onset of the disease. We report a 77-year-old woman who developed right eyelid ptosis five days after COVID-19 infection. Positive serum anti-acetylcholine receptor antibodies allowed the diagnosis of myasthenia gravis. It should be noted that there were no significant decremental changes on 3 Hz repetitive motor nerve stimulation study, even for the affected orbicularis oculi muscle. Clinical and pathophysiological data suggest that inflammation during COVID-19 could trigger an overproduction of autoantibodies previously present in the body at a subclinical level. This is the first case of COVID-19 infection complicated by myasthenia gravis, to the best of our knowledge, that resolves spontaneously.


Development of organic fertilizers from food market waste and urban gardening by composting in Ecuador.
Currently, the management of urban waste streams in developing countries is not optimized yet, and in many cases these wastes are disposed untreated in open dumps. This fact causes serious environmental and health problems due to the presence of contaminants and pathogens. Frequently, the use of specific low-cost strategies reduces the total amount of wastes. These strategies are mainly associated to the identification, separate collection and composting of specific organic waste streams, such as vegetable and fruit refuses from food markets and urban gardening activities. Concretely, in the Chimborazo Region (Ecuador), more than 80% of municipal solid waste is dumped into environment due to the lack of an efficient waste management strategy. Therefore, the aim of this study was to develop a demonstration project at field scale in this region to evaluate the feasibility of implanting the composting technology not only for the management of the organic waste fluxes from food market and gardening activities to be scaled-up in other developing regions, but also to obtain an end-product with a commercial value as organic fertilizer. Three co-composting mixtures were prepared using market wastes mixed with pruning of trees and ornamental palms as bulking agents. Two piles were created using different proportions of market waste and prunings of trees and ornamental palms: pile 1 (50:33:17) with a C/N ratio 25; pile 2: (60:30:10) with C/N ratio 24 and pile 3 (75:0:25) with C/N ratio 33), prepared with market waste and prunings of ornamental palm. Throughout the process, the temperature of the mixtures was monitored and organic matter evolution was determined using thermogravimetric and chemical techniques. Additionally, physico-chemical, chemical and agronomic parameters were determined to evaluate compost quality. The results obtained indicated that all the piles showed a suitable development of the composting process, with a significant organic matter decomposition, reached in a shorter period of time in pile 3. At the end of the process, all the composts showed absence of phytotoxicity and suitable agronomic properties for their use as organic fertilizers. This reflects the viability of the proposed alternative to be scaled-up in developing areas, not only to manage and recycle urban waste fluxes, but also to obtain organic fertilizers, including added value in economic terms related to nutrient contents.


[Epilepsy as a clinical and neurophysiological problem].
On the basis of both own investigations and publications the next basic aspects of epilepsy were discussed: a) a clinical one--definition of epilepsy, seizures' classification, children's and women's epilepsy, status epilepticus; b) a neurophysiological aspect--epileptic and antiepileptic mechanisms, the significance of slow EEG activity, interhemispheric interactions, influence of the seizures on brain homeostasis.


Numerical analysis of pulsing regimes near static borders of optically injected semiconductor lasers.
It is well known that semiconductor lasers under optical injection present rich, dynamic behavior. In this paper, we focus on pulsing regimes, which can be either exploited in a broad variety of applications or lead to undesired instabilities. In particular, we develop a multi-metric method to automatically identify pulsing regimes in the parameter space. We apply this method to extensive numerical simulations to show that these regimes occur in the vicinity of the static synchronization boundary. Furthermore, analyzing these pulsing regimes, we identify pulsations with repetition rates ranging from several megahertz up to more than 1 GHz. Finally, we analyze the effect of the linewidth enhancement factor and the slave-laser bias current, revealing that a linewidth enhancement factor of 3 and a higher bias current lead to broader regions of pulsation regimes.


The probabilistic nature of synaptic transmission at a mammalian excitatory central synapse.
The synaptic connection between single group I afferents and dorsal spinocerebellar tract (DSCT) neurons in the cat spinal cord has been studied in an attempt to gain insight into the mechanisms of excitatory synaptic transmission in the mammalian CNS. Fluctuations in the amplitude of single group I fiber EPSPs in DSCT neurons were examined using a numerical deconvolution procedure to reduce the effects of contaminating noise. In general, it was found that single fiber EPSPs fluctuate in peak amplitude between discrete levels separated by equal or quantal increments. Many previous studies have proposed simple binomial statistics as a general model of quantal synaptic transmission. In the present study we show that simple binomial statistics do not describe the fluctuations in amplitude of single group I fiber EPSPs in DSCT neurons. It is suggested that nonuniformities in the probability of transmitter release from release site to release site explain the failure of the binomial model to describe the EPSP fluctuation pattern at this synapse. Nonuniform quantal transmission is proposed as a more adequate description of excitatory synaptic transmission in the mammalian CNS.


Aromatase inhibitors and risk of cardiovascular events in breast cancer patients: a systematic review and meta-analysis.
Cardiovascular events (CVEs) was considered as one of the primary cause to reduce the quality of life in breast cancer patients with aromatase inhibitors (AIs) treatment, which has not been sufficiently addressed. The aim of this study was to assess the correlation between risk of CVEs and AIs in patients with breast cancer. Included studies were obtained from the databases of Embase, Pubmed, Cochrane Library, Clinical Trials.gov, and reference lists. The main outcome measures were overall incidence, odds ratios (ORs), and 95% confidence intervals (CIs). Furthermore, the association and the risk differences among different tumor types, AIs,ages,or treatment regimens were conducted. Fixed-effect or random-effect models were applied in the statistical analyses according to the heterogeneity. Our analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Seventeen studies, which included 44,411 subjects, were included in our analyses. The overall incidence of CVEs in AIs group was 13.02% (95% CI: 8.15-20.17%) and almost all of the high-grade CVEs occurred in patients treated with AIs. The pooled ORs of CVEs was 0.9940 (95% CI: 0.8545-1.1562). Under sub-group analysis, the incidence of CVEs related to exemestane was higher than that of controls (OR = 1.1564, 95% CI: 1.0656-1.2549), but no statistical differences in risk of CVEs were found in other sub-group analysis. No evidence of publication bias was found for incidence of CVEs in our meta-analysis by a funnel plot. These results suggest that patients with breast cancer treated with AIs do not have a significant risk of developing CVEs in comparison with the controls, and exemestane might not be considered as the alternative AI to the breast cancer patients from the perspective of CVEs. Further studies are recommended to investigate this association and the risk differences among different tumor types, AIs or treatment regimens.


Enhanced diffusion and magnetophoresis of paramagnetic colloidal particles in rotating magnetic fields.
Dispersions of paramagnetic colloids can be manipulated with external magnetic fields to assemble structures via dipolar assembly and control transport via magnetophoresis. For fields held steady in time, the dispersion structure and dynamic properties are coupled. This coupling can be problematic when designing processes involving field-induced forces, as particle aggregation competes against and hinders particle transport. Time-varying fields drive dispersions out-of-equilibrium, allowing the structure and dynamics to be tuned independently. Rotating the magnetic field direction using two biaxial fields is a particularly effective mode of time-variation and has been used experimentally to enhance particle transport. Fundamental transport properties, like the diffusivity and magnetophoretic mobility, dictate dispersions' out-of-equilibrium responses to such time-varying fields, and are therefore crucial to understand to effectively design processes utilizing rotating fields. However, a systematic study of these dynamic quantities in rotating fields has not been performed. Here, we investigate the transport properties of dispersions of paramagnetic colloids in rotating magnetic fields using dynamic simulations. We find that self-diffusion of particles is enhanced in rotating fields compared to steady fields, and that the self-diffusivity in the plane of rotation reaches a maximum value at intermediate rotation frequencies that is larger than the Stokes-Einstein diffusivity of an isolated particle. We also show that, while the magnetophoretic velocity of particles through the bulk in a field gradient decreases with increasing rotation frequency, the enhanced in-plane diffusion allows for faster magnetophoretic transport through porous materials in rotating fields. We examine the effect of porous confinement on the transport properties in rotating fields and find enhanced diffusion at all pore sizes. The confined and bulk values of the transport properties are leveraged in simple models of magnetophoresis through tortuous porous media.


Development and initial application of an in vitro model of apoptosis in rodent cholangiocytes.
Although histological data suggest that cholangiocytes die by apoptosis in human liver diseases, no information exists on the mechanisms of cholangiocyte apoptosis. Thus our aims were to establish an in vitro model of cholangiocyte apoptosis and to test the hypothesis that changes in intracellular ions would cause apoptosis in cholangiocytes by a protease-sensitive pathway. A large number of proapoptotic agents were ineffective in inducing apoptosis in rat or human cholangiocytes in culture; in contrast, beauvericin, a K+ ionophore, caused apoptosis in both cell lines, despite their expression of Bcl-2. Although beauvericin decreased intracellular K+ and increased intracellular Ca2+, abolishing the K+ gradient did not prevent beauvericin-induced apoptosis; in contrast, omission of extracellular Ca2+ inhibited apoptosis by 42%. The interleukin-1 beta-converting enzyme (ICE) family protease inhibitor, Z-Val-Ala-Asp chloromethylketone, inhibited apoptosis in a concentration-dependent manner. By Northern blot analysis, cholangiocytes expressed the mRNA for three members of the ICE protease family: ICE, ICE/ CED-3 homologue-1 (ICH-1), and cysteine protease P-32 (CPP-32). Cleavage of a substrate for CPP-32-like protease activity, but not a substrate for ICE and ICH-1, increased after beauvericin treatment. In summary, we have established an in vitro model of apoptosis in cholangiocytes. Our data suggest that beauvericin-induced apoptosis occurs by a Ca(2+)-dependent CPP-32 protease-sensitive pathway despite cholangiocyte expression of Bcl-2.


Immortalization of normal human oral keratinocytes with type 16 human papillomavirus.
Primary human oral keratinocytes were transformed by transfection with recombinant human papillomavirus type 16 (HPV-16) DNA, and two transformed cell lines named human oral keratinocytes-16A and -16B (HOK-16A and HOK-16B) were established. While normal cells and cells transfected with vector only exhibited a limited lifespan, the HOK-16A and HOK-16B lines demonstrated immortality and altered morphology from their normal counterpart. The HOK-16A and HOK-16B lines contained approximately 40 and approximately 25 copies of intact HPV-16 DNA as integrated form per cell respectively, and both cell lines expressed several viral specific poly(A+) RNAs. Notably these cell lines also overexpressed cellular myc proto-oncogene in comparison with the normal counterpart. However, the immortalized cell lines were not able to produce tumors in nude mice, indicating that the cells are partially transformed. The HOK-16A and HOK-16B lines are, therefore, useful for investigating the multistep molecular events of oral carcinogenesis.


Developing students' writing skills: an early intervention approach.
In what seems to be a universal situation, nurse educators are reading student papers and lamenting the fact that their students cannot write. The author explains a successful model of early intervention aimed at improving academic writing for new graduate students. The model and teaching strategies are helpful to nurse educators who struggle with the quality of their students' written work.


Association between type 1 diabetes mellitus and risk of epilepsy: A meta-analysis of observational studies.
A potential association between type 1 diabetes mellitus and subsequent epilepsy emerged in recent studies. This study aimed to evaluate the possible relationship between type 1 diabetes mellitus and epilepsy using meta-analysis. Pubmed, ISI Web of Knowledge, Embase and Cochrane Library were searched for potential studies of the association between type 1 diabetes mellitus and epilepsy from inception to February 1, 2017. Two investigators independently screened studies for inclusion and extracted related data; discrepancies were solved by consensus. Random effects model of Hazard Ratio (HR) was used to estimate the strength of association. We identified 13 papers from potentially relevant articles of which 3 cohort studies met the inclusion criteria. Random effects meta-analysis showed that type 1 diabetes mellitus was associated with an increased risk of epilepsy with HR = 3.29 (95% CI: 2.61-4.14; I2 = 0, p = 0.689). Similar results were observed in type 1 diabetes mellitus patents younger than 18-years-old with HR = 2.96 (95% CI: 2.28-3.84; I2 = 0, p = 0.571). Meta-analysis of 2 studies that adjusted for potential confounders yielded an increased risk of epilepsy with HR = 2.89 (95% CI: 2.26-3.70; I2 = 0, p = 0.831). The meta-analysis indicates that type 1 diabetes mellitus is associated with a statistically significant increased risk for epilepsy compared to those without type 1 diabetes mellitus.


Vaccine immunity to coccidioidomycosis occurs by early activation of three signal pathways of T helper cell response (Th1, Th2, and Th17).
We have previously reported that C57BL/6 mice vaccinated with a live, attenuated mutant of Coccidioides posadasii, referred to as the ΔT vaccine, are fully protected against pulmonary coccidioidomycosis. This model was used here to explore the nature of vaccine immunity during the initial 2-week period after intranasal challenge. Elevated neutrophil and eosinophil infiltration into the lungs of nonvaccinated mice contrasted with markedly reduced recruitment of these cells in vaccinated animals. The numbers of lung-infiltrated macrophages and dendritic cells showed a progressive increase in vaccinated mice and corresponded with reduction of the lung infection. Concentrations of selected inflammatory cytokines and chemokines were initially higher in lung homogenates of vaccinated mice but then generally decreased at 14 days postchallenge in correlation with containment of the organism and apparent dampening of the inflammation of host tissue. Profiles of cytokines detected in lung homogenates of ΔT-vaccinated mice were indicative of a mixed T helper 1 (Th1)-, Th2-, and Th17-type immune response, a conclusion which was supported by detection of lung infiltration of activated T cells with the respective CD4(+) gamma interferon (IFN-γ)(+), CD4(+) interleukin-5 (IL-5)(+), and CD4(+) IL-17A(+) phenotypes. While Th1 and Th2 immunity was separately dispensed of by genetic manipulation without loss of ΔT vaccine-mediated protection, loss of functional Th17 cells resulted in increased susceptibility to infection in immunized mice. Characterization of the early events of protective immunity to Coccidioides infection in vaccinated mice contributes to the identification of surrogates of immune defense and provides potential insights into the design of immunotherapeutic protocols for treatment of coccidioidomycosis.


Effect of antimacrophage serum on dermal tuberculin sensitivity and allergic pulmonary granuloma formation in rabbits.
Anti-rabbit alveolar macrophage goat serum (AMS), adsorbed of hemolysins and hemagglutinins, exhibited complement-dependent cytotoxicity for the following rabbit target cells: alveolar macrophages, thymocytes, and kidney (RK-13) cells. The intravenous injection of AMS, sufficient to reduce markedly the dermal tuberculin reaction in BCG-sensitized rabbits, did not suppress the development of BCG-induced chronic and accelerated pulmonary granulomas. These observations are discussed in relation to delayed sensitivity, allergic granuloma formation, and cell-associated immunity.


Effect of troglitazone on tumor growth and pulmonary metastasis development of the mouse osteosarcoma cell line LM8.
Osteosarcoma often develops micrometastases in the lung prior to diagnosis, causing a fatal outcome. Therefore, the prevention of pulmonary metastases is critical for the improvement of the prognosis of patients with osteosarcoma. The purpose of this study was to investigate whether troglitazone (TGZ) is considered as possible therapeutics in the treatment of growth and metastasis of osteosarcoma. LM8 cells were treated for 3 days with various concentrations of TGZ. The effect of TGZ on cell proliferation was determined by DNA measurement in the cultures and 5-bromo-2'-deoxyuridine incorporation study. The assay of cell invasion and motility was performed using either the Matrigel-coated cell culture inserts or the uncoated cell culture inserts in the invasion chambers. The effect of TGZ on Akt signaling was assessed by Western blot analysis of Akt and p-Akt. The effects of oral administration of either TGZ (TGZ group) or ethanol (control group) on the growth of primary tumor and the development of pulmonary metastasis were examined in nude mice implanted with LM8 cells on their backs. The expression and activity of matrix metalloproteinase 2 (MMP-2) within the tumor were determined by immunohistochemistry and zymography. The microvessel density (MVD) within the tumor was determined by immunohistochemistry for CD34. TGZ dose-dependently inhibits cell proliferation. TGZ-treated cells were less invasive and less motile than untreated cells. The activity of MMP-2 secreted by TGZ-treated cells was lower than that secreted by untreated cells. TGZ decreased the level of p-Akt. The primary tumor mass was smaller in the TGZ group than in the control group. The TGZ group had less metastatic tumors in the lung compared with the control group. The expression and activity of MMP-2 within the tumor of the TGZ group were lower than those of the control group. The MVD within the tumor of the TGZ group was lower than that of the control group. Inhibition of Akt signaling by TGZ may decrease the secretion of MMP-2, resulting in the decrease of invasiveness and motility in LM8 cells. Treatment of tumor-bearing mice with TGZ decreases the expression and activity of MMP-2 within the tumor, and inhibits primary tumor growth and pulmonary metastasis development. TGZ may offer a new approach in chemotherapy for osteosarcoma.


Is the positive association between middle-income and rich household wealth and adult sub-Saharan African women's overweight status modified by the level of education attainment? A cross-sectional study of 22 countries.
Previous studies show a positive association between household wealth and overweight in sub-Saharan African (SSA) countries; however, the manner in which this relationship differs in the presence of educational attainment has not been well-established. This study examined the multiplicative effect modification of educational attainment on the association between middle-income and rich household wealth and overweight status among adult females in 22 SSA countries. We hypothesized that household wealth was associated with a greater likelihood of being overweight among middle income and rich women with lower levels of educational attainment compared to those with higher levels of educational attainment. Demographic and Health Survey (DHS) data from 2006 to 2016 for women aged 18-49 years in SSA countries were used for the study. Overweight was defined as a body mass index (BMI) ≥ 25 kg/m2. Household wealth index tertile was the exposure and educational attainment, the effect modifier. Potential confounders included age, ethnicity, place of residence, and parity. Descriptive analysis was conducted, and separate logistic regression models were fitted for each of the 22 SSA countries to compute measures of effect modification and 95% confidence intervals. Analysis of credibility (AnCred) methods were applied to assess the intrinsic credibility of the study findings and guide statistical inference. The prevalence of overweight ranged from 12.6% in Chad to 56.6% in Swaziland. Eighteen of the 22 SSA countries had measures of effect modification below one in at least one wealth tertile. This included eight of the 12 low-income countries and all 10 middle income countries. This implied that the odds of overweight were greater among middle-income and rich women with lower levels of educational attainment than those with higher educational attainment. On the basis of the AnCred analysis, it was found that the majority of the study findings across the region provided some support for the study hypothesis. Women in higher wealth strata and with lower levels of educational attainment appear to be more vulnerable to overweight compared to those in the same wealth strata but with higher levels of educational attainment in most low- and middle- income SSA countries.


A novel method for measuring continuous dispersion spectrum of electro-optic coefficients of nonlinear materials.
We report, for the first time to our knowledge, a novel and simple method for measuring continuous dispersion spectrum of unclamped linear electro-optic (EO) coefficient using a white-light interferometry. This method detects phase changes of the interference patterns with and without an applied electric voltage, and allows a simultaneous measurement of wavelength and polarization dependent EO coefficients of birefringent materials. Both of the unclamped EO coefficients, r(13) (T) and r(33) (T), of a congruent LiNbO(3) (LN) crystal have been measured simultaneously with the method, and their continuous dispersion curves have been also obtained.


Claudin and occludin expression and function in the seminiferous epithelium.
Integral membrane proteins that contribute to function of the blood-testes barrier (BTB) in mice include claudins 3, 5 and 11 and occludin. Although claudin 11 is expressed throughout all stages of the seminiferous epithelial cycle, claudins 3 and 5 have specific expression at stage VIII. These differences in protein expression suggest that the interactions among, and functions of, these integral membrane proteins may shift over the course of the seminiferous epithelial cycle. Also, differences in expression among rodent species and men may make interpretation of studies across species challenging. This review will discuss the characteristics of claudins and occludin; the expression, regulation and function of these integral membrane proteins in the seminiferous epithelium; and how these properties relate to the unique features of BTB.


Current States and Future Trends in Safety Research of Construction Personnel: A Quantitative Analysis Based on Social Network Approach.
The construction industry is recognized as a high-risk industry given that safety accidents and personnel injuries frequently occur. This study provided a systematic and quantitative review of existing research achievements by conducting social network approach to identify current states and future trends for the occupational safety of construction personnel. A total of 250 peer-reviewed articles were collected to examine the research on safety issues of workers in construction industry. Social network approach was applied to analyze the interrelationship among authors, keywords, and citations of these articles using VOS viewer and CitNetExplorer. A knowledge structure map was drawn using main path analysis (MPA) towards the collected papers, which was implemented by Pajek. In line with the findings of social network analysis, five research groups, and six keyword themes were identified in accordance with the times of cooperation of researchers and correlation among keywords of the papers. Core papers were identified by using main path analysis for each research domain to represent the key process and backbone for the corresponding area. Based on the finding of the research, significant implications and insights in terms of current research status and further research trends were provided for the scholars, thus helping generate a targeted development plan for occupational safety in construction industry.


[Propylthiouracil in therapy of alcohol-induced liver damage?].
Propylthiouracil (Propycil Thyreostat) is presently being used in hyperthyroidism, thyroidectomy, and other diseases affecting thyroid gland metabolism. Canadian clinicians have published interesting reports showing that propylthiouracil can be used to successfully treat alcohol-induced liver damage. In two clinical trials (approximately 340 patients) it was shown that long-term treatment with propylthiouracil was associated with a significantly more favorable prognosis in cirrhosis of the liver and with a reduction in mortality. Preclinical studies suggest that alcohol abuse leads to a hypermetabolic status of the liver, which is similar to hyperthyroidism. The results of these studies suggest a rationale for the use of propylthiouracil in alcohol-induced liver cirrhosis.


Talking About Cancer and Meeting Peer Survivors: Social Information Needs of Adolescents and Young Adults Diagnosed with Cancer.
Limited research exists on the social information needs of adolescents and young adults (AYAs, aged 15-39 at diagnosis) with cancer. The Adolescent and Young Adult Health Outcomes and Patient Experiences (AYA HOPE) Study recruited 523 patients to complete surveys 6-14 months after cancer diagnosis. Participants reported information needs for talking about their cancer experience with family and friends (TAC) and meeting peer survivors (MPS). Multiple logistic regression was used to examine factors associated with each need. Approximately 25% (118/477) and 43% (199/462) of participants reported a TAC or MPS need respectively. Participants in their 20s (vs. teenagers) were more likely to report a MPS need (p=0.03). Hispanics (vs. non-Hispanic whites) were more likely to report a TAC need (p=0.01). Individuals who did not receive but reported needing support groups were about 4 and 13 times as likely to report TAC and MPS needs respectively (p<0.05). Participants reporting high symptom burden were more likely to report TAC and MPS needs (p<0.01), and those reporting fair/poor quality of care were more likely to report a TAC need (p<0.01). Those reporting that cancer had an impact on several key relationships with family and friends were more likely to report social information needs. Social information needs are higher in AYAs diagnosed in their 20s, in Hispanics, among those reporting high symptom burden and/or lower quality of care, and in individuals not in support groups. Efforts should be made to develop interventions for AYAs in most need of social information and support.


Topical fibronectin and aprotinin for keratectomy wound healing in rabbits.
We evaluated the effect of fibronectin (an adhesive protein) and aprotinin (a protease inhibitor) as single or combined topical therapies for primary healing and prevention of recurrent corneal epithelial defects in the rabbit keratectomy wound model. The biological activity of the prepared solutions of rabbit plasma fibronectin (0.6 g/L) was suggested by in vitro assays of rabbit corneal epithelial cell adhesion and gelatin-binding affinity. In the first experiment, we compared fibronectin, albumin (a control nonadhesive protein), and saline. In the second and third experiments, fibronectin supplemented with aprotinin, aprotinin alone, and saline were compared; aprotinin was used at concentrations of 40 and 1000 kallikrein inactivating units (KIU) per mililiter. Our results suggest that topical fibronectin, 0.6 g/L, as well as aprotinin at 40- and 1000-KIU/mL concentrations, given alone or in combination, neither promote corneal epithelial wound healing nor prevent recurrent corneal epithelial defects in rabbit keratectomy wounds.


[Effect of bacitracin and other drugs on the synthesis of the antibiotic itself (bacitracin) by a Bacillus licheniformis culture].
The type and level of resistance of Bac. licheniformis 1001 to the antibiotic produced by it, i. e. bacitracin and the effect of bacitracin and some other drugs on the culture variation with respect to the feature of the antibiotic production were studied. It was found that strain 1001 possessed an inducible resistance to its own antibiotic. In addition, a cross inducible resistance to bacitracin and penicillin was observed. The mutations of the resistance to bacitracin, as well as streptomycin, rifampicin and sulfaethidole had no effect on bacitracin production by strain 1001.


Oral Nucleos(t)ide Analogs Alone After Liver Transplantation in Chronic Hepatitis B With Preexisting rt204 Mutation.
There is currently limited data regarding the use of oral antiviral therapy alone without hepatitis B immune globulin for chronic hepatitis B patients with preexisting lamivudine (LAM) resistance (LAM-R) undergoing liver transplantation. This is a cohort study determining the effectiveness and long-term outcome in this group of patients. Fifty-seven consecutive chronic hepatitis B patients with preexisting rt204 LAM-R mutations or virological load refractory to LAM undergoing liver transplantation were included, with a median follow-up of 73 months. Fifty-five (96.5%) patients received a regimen that included the use of nucleotide analogs. The cumulative rate of hepatitis B surface antigen seroclearance at 1, 5, and 10 years was 82%, 88%, and 91%, respectively. At the time of transplantation, 39 (72%) patients had detectable hepatitis B virus (HBV) DNA, with a median of 4.5 log copies/mL. The cumulative rate of HBV undetectability was 91% at 1 year, increasing to 100% by 5 years. After 1 year of liver transplantation, over 90% of the patients had undetectable HBV DNA, and from 8 years onward, 100% had undetectable HBV DNA. The overall long-term survival was excellent, with a 12-year survival of 87%. There was no HBV-related graft loss, and no retransplantation or deaths due to HBV reactivation. Oral antiviral therapy alone without hepatitis B immune globulin is highly effective in preventing HBV reactivation and graft loss from recurrent hepatitis B after liver transplantation in patients with preexisting LAM resistance HBV. The long-term outcome was excellent, with survival of 87% at 12 years after transplantation, without any mortality related to HBV reactivation.


TRPM3.
Like most other members of the TRP family, the Trpm3 gene encodes proteins that form cation-permeable ion channels on the plasma membrane. However, TRPM3 proteins have several unique features that set them apart from the other members of this diverse family. The Trpm3 gene encodes for a surprisingly large number of isoforms generated mainly by alternative splicing. Only for two of the (at least) eight sites at which sequence diversity is generated the functional consequences have been elucidated, one leading to nonfunctional channels, the other one profoundly affecting the ionic selectivity. In the Trpm3 gene an intronic microRNA (miR-204) is co-transcribed with Trpm3. By regulating the expression of a multitude of genes, miR-204 increases the functional complexity of the Trpm3 locus. Over the past years, important progress has been made in discovering pharmacological tools to manipulate TRPM3 channel activity. These substances have facilitated the identification of endogenously expressed functional TRPM3 channels in nociceptive neurons, pancreatic beta cells, and vascular smooth muscle cells, among others. TRPM3 channels, which themselves are temperature sensitive, thus have been implicated in sensing noxious heat, in modulating insulin release, and in secretion of inflammatory cytokines. However, in many tissues where TRPM3 proteins are known to be expressed, no functional role has been identified for these channels so far. Because of the availability of adequate pharmacological and genetic tools, it is expected that future investigations on TRPM3 channels will unravel important new aspects and functions of these channels.


A role for semaphorin 3A signaling in the degeneration of hippocampal neurons during Alzheimer's disease.
Among the earliest invariant neuropathological changes in Alzheimer's disease (AD) is the degeneration of vulnerable hippocampal CA1 and subicular pyramidal neurons. Semaphorin 3A (Sema3A) is a secreted protein that functions in signaling growth cone collapse, chemorepulsion and neuronal apoptosis during early development of the central nervous system. In this report we show that accumulation of an internalized form of Sema3A is associated with degeneration of neurons in vulnerable fields of the hippocampus during AD. Accumulation of Sema3A overlaps the appearance of phosphorylated MAP1B and tau in many neurons, suggesting that Sema3A signaling at some level may be coupled to these previously identified cytoskeletal markers of neurodegeneration. Consistent with this, we isolated and partially characterized a multiprotein complex from the hippocampus of patients with AD that contains phosphorylated MAP1B, collapsin-response mediator protein 2 (CRMP-2), Plexins A1 and A2, and a processed form of Sema3A. A model is presented in which aberrant release of Sema3A from expressing neurons in the subiculum during AD results in the internalization and transport of Sema3A from this field to CA1. Within the context of the myriad of potential insults that contribute to Alzheimer's and other neurodegenerative diseases, the bioactivity of Sema3A may contribute either directly to neurodegeneration by inducing neuronal collapse, or indirectly by abrogating the recovery capabilities of adult neurons faced with these insults.


The circulating calcification inhibitors, fetuin-A and osteoprotegerin, but not matrix Gla protein, are associated with vascular stiffness and calcification in children on dialysis.
Vascular calcification occurs in the majority of patients with chronic kidney disease, but a subset of patients does not develop calcification despite exposure to a similar uraemic environment. Physiological inhibitors of calcification, fetuin-A, osteoprotegerin (OPG) and undercarboxylated-matrix Gla protein (uc-MGP) may play a role in preventing the development and progression of ectopic calcification, but there are scarce and conflicting data from clinical studies. We measured fetuin-A, OPG and uc-MGP in 61 children on dialysis and studied their associations with clinical, biochemical and vascular measures. Fetuin-A and OPG were higher and uc-MGP lower in dialysis patients than controls. In controls, fetuin-A and OPG increased with age. Fetuin-A showed an inverse correlation with dialysis vintage (P = 0.0013), time-averaged serum phosphate (P = 0.03) and hs-CRP (P = 0.001). Aortic pulse wave velocity (PWV) and augmentation index showed a negative correlation with fetuin-A while a positive correlation was seen with PWV and OPG. Patients with calcification had lower fetuin-A and higher OPG than those without calcification. On multiple linear regression analysis Fetuin-A independently predicted aortic PWV (P = 0.004, beta = -0.45, model R(2) = 48%) and fetuin-A and OPG predicted cardiac calcification (P = 0.02, beta = -0.29 and P = 0.014, ss = 0.33, respectively, model R(2) = 32%). This is the first study to define normal levels of the calcification inhibitors in children and show that fetuin-A and OPG are associated with increased vascular stiffness and calcification in children on dialysis. Higher levels of fetuin-A in children suggest a possible protective upregulation of fetuin-A in the early stages of exposure to the pro-calcific and pro-inflammatory uraemic environment.


Precise Manipulation and Patterning of Protein Crystals for Macromolecular Crystallography Using Surface Acoustic Waves.
Advances in modern X-ray sources and detector technology have made it possible for crystallographers to collect usable data on crystals of only a few micrometers or less in size. Despite these developments, sample handling techniques have significantly lagged behind and often prevent the full realization of current beamline capabilities. In order to address this shortcoming, a surface acoustic wave-based method for manipulating and patterning crystals is developed. This method, which does not damage the fragile protein crystals, can precisely manipulate and pattern micrometer and submicrometer-sized crystals for data collection and screening. The technique is robust, inexpensive, and easy to implement. This method not only promises to significantly increase efficiency and throughput of both conventional and serial crystallography experiments, but will also make it possible to collect data on samples that were previously intractable.


Fixational saccades during grating detection and discrimination.
We investigated the patterns of fixational saccades in human observers performing two classical perceptual tasks: grating detection and discrimination. First, participants were asked to detect a vertical or tilted grating with one of three spatial frequencies and one of four luminance contrast levels. In the second experiment, participants had to discriminate the spatial frequency of two supra-threshold gratings. The gratings were always embedded in additive, high- or low-contrast pink noise. We observed that the patterns of fixational saccades were highly idiosyncratic among participants. Moreover, during the grating detection task, the amplitude and the number of saccades were inversely correlated with stimulus visibility. We did not find a systematic relationship between saccade parameters and grating frequency, apart from a slight decrease of saccade amplitude during grating discrimination with higher spatial frequencies. No consistent changes in the number and amplitude of fixational saccades with performance accuracy were reported. Surprisingly, during grating detection, saccade number and amplitude were similar in grating-with-noise and noise-only displays. Grating orientation did not affect substantially saccade direction in either task. The results challenge the idea that, when analyzing low-level spatial properties of visual stimuli, fixational saccades can be adapted in order to extract task-relevant information optimally. Rather, saccadic patterns seem to be overall modulated by task context, stimulus visibility and individual variability.


[Sensitized photomodification by binary systems. I. Synthesis of oligonucleotide reagents, and the effect of their structure on the efficacy of target modification].
A highly effective sensitized photomodification of the target DNA by a binary system of oligonucleotide reagents complementary to adjacent regions of the target was accomplished. One of the oligonucleotides carries a photoregent p-azidotetrafluorobenzamide, and the other carries a pyrene sensitizer. Synthesis of the oligonucleotide derivatives was described. The rate and efficacy of the direct and sensitized target photomodifications depending on the location of the photoreagent and sensitizer at the 3'- and 5'-terminal phosphates and on the length of the linker between the sensitizer and addressed nucleotide were studied. The oligonucleotide derivatives with the photoreagent at the 3' terminus proved to be more effective (yield of the covalent adducts 70%). The rate of photomodification sensitized by UV light (365-390 nm) is 100-1500-fold higher than that of the direct site-specific modification and decreases with an increasing length of the linker. In all cases, modification occurs at the guanosine residue located near the photoreagent.


In vitro activity of new generation fluoroquinolones against genotypically distinct and indistinguishable Clostridium difficile isolates.
We compared the activities of ciprofloxacin and levofloxacin with those of the newer fluoroquinolones grepafloxacin, moxifloxacin, sparfloxacin and trovafloxacin against Clostridium difficile isolates. As there is good evidence of marked clonal spread of C. difficile, we studied both genotypically distinct (n = 26) and indistinguishable (n = 28) isolates as determined by random amplified polymorphic DNA and ribosomal spacer PCR fingerprinting. The indistinguishable strains examined represent the main UK epidemic C. difficile clone. For 17 of 54 strains (31%) we were unable to read MICs following inocula preparation using Mueller-Hinton broth. Using Schaedler's broth for inocula preparation 93% of strains had readable MICs, although geometric mean MICs were uniformly higher (2.5- to 5.4-fold) compared with results using Mueller-Hinton broth. Moxifloxacin and trovafloxacin, followed by grepafloxacin, were the most active fluoroquinolones tested and were 3- to 4-fold more active than older agents such as ciprofloxacin by both MIC methods. Unexpectedly, clonal C. difficile strains had markedly reduced susceptibility compared with the distinct strains to each of the fluoroquinolones tested. Clonal strains were more than seven-fold or 12- to 29-fold less susceptible (according to geometric mean MICs) than distinct strains to both moxifloxacin and trovafloxacin, depending on the MIC method used. It remains to be seen whether the enhanced activity of new fluoroquinolones such as moxifloxacin in comparison with other fluoroquinolones against C. difficile implies that these agents are unlikely to be associated with C. difficile infection. However, clinical use of new generation fluoroquinolones in elderly hospitalized patients where C. difficile is endemic requires further study, particularly given the reduced antibiotic susceptibility to all fluoroquinolones of the readily transmissible UK C. difficile clone.


Arsenic exposure in Indo Gangetic plains of Bihar causing increased cancer risk.
Reportedly, 300 million people worldwide are affected by the consumption of arsenic contaminated groundwater. India prominently figures amongst them and the state of Bihar has shown an upsurge in cases affected by arsenic poisoning. Escalated arsenic content in blood, leaves 1 in every 100 human being highly vulnerable to being affected by the disease. Uncontrolled intake may lead to skin, kidney, liver, bladder, or lung related cancer but even indirect forms of cancer are showing up on a regular basis with abnormal arsenic levels as the probable cause. But despite the apparent relation, the etiology has not been understood clearly. Blood samples of 2000 confirmed cancer patients were collected from pathology department of our institute. For cross-sectional design, 200 blood samples of subjects free from cancer from arsenic free pockets of Patna urban agglomeration, were collected. Blood arsenic levels in carcinoma patients as compared to sarcomas, lymphomas and leukemia were found to be higher. The geospatial map correlates the blood arsenic with cancer types and the demographic area of Gangetic plains. Most of the cancer patients with high blood arsenic concentration were from the districts near the river Ganges. The raised blood arsenic concentration in the 2000 cancer patients strongly correlates the relationship of arsenic with cancer especially the carcinoma type which is more vulnerable. The average arsenic concentration in blood of the cancer patients in the Gangetic plains denotes the significant role of arsenic which is present in endemic proportions. Thus, the study significantly correlates and advocates a strong relation of the deleterious element with the disease. It also underlines the need to address the problem by deciphering the root cause of the elevated cancer incidences in the Gangetic basin of Bihar and its association with arsenic poisoning.


Family history of prostate cancer and prostate cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study.
Prostate cancer family history has been associated with increased risk of the malignancy. Most prior studies have been retrospective and subject to recall bias, however, and data evaluating interactions with other important risk factors are limited. We examined the relationship between a family history of prostate cancer and prostate cancer risk in relation to body size, micronutrients and other exposures in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study cohort of Finnish male smokers. Family history of cancer information was self-reported once during the study in 1991, and anthropometry was measured by trained personnel. Among 19,652 men with complete data, 1,111 incident cases were identified during up to 12.3 years of follow-up. A first-degree family history of prostate cancer was associated with an overall relative risk (RR) of 1.91 (95% CI = 1.49-2.47) and a RR of 4.16 (95% CI = 2.67-6.49) for advanced disease (stage >or= 3), adjusted for age and trial intervention. Our data also suggest that to some degree, height, body mass index, and serum alpha-tocopherol and beta-carotene modify the family history and prostate cancer association, although the interactions were not statistically significant. Supplementation with vitamin E or beta-carotene did not modify the family history-prostate cancer association. This study provides additional evidence that family history is a significant risk factor for prostate cancer.


Glandulocalyx upatoiensis, a fossil flower of Ericales (Actinidiaceae/Clethraceae) from the Late Cretaceous (Santonian) of Georgia, USA.
Ericales are a major group of extant asterid angiosperms that are well represented in the Late Cretaceous fossil record, mainly by flowers, fruits and seeds. Exceptionally well preserved fossil flowers, here described as Glandulocalyx upatoiensis gen. & sp. nov., from the Santonian of Georgia, USA, yield new detailed evidence of floral structure in one of these early members of Ericales and provide a secure basis for comparison with extant taxa. The floral structure of several fossil specimens was studied by scanning electron microscopy (SEM), light microscopy of microtome thin sections and synchrotron-radiation X-ray tomographic microscopy (SRXTM). For direct comparisons with flowers of extant Ericales, selected floral features of Actinidiaceae and Clethraceae were studied with SEM. Flowers of G. upatoiensis have five sepals with quincuncial aestivation, five free petals with quincuncial aestivation, 20-28 stamens arranged in a single series, extrorse anther orientation in the bud, ventral anther attachment and a tricarpellate, syncarpous ovary with three free styles and numerous small ovules on axile, protruding-diffuse and pendant placentae. The calyx is characterized by a conspicuous indumentum of large, densely arranged, multicellular and possibly glandular trichomes. Comparison with extant taxa provides clear evidence for a relationship with core Ericales comprised of the extant families Actinidiaceae, Roridulaceae, Sarraceniaceae, Clethraceae, Cyrillaceae and Ericaceae. Within this group, the most marked similarities are with extant Actinidiaceae and, to a lesser degree, with Clethraceae. More detailed analyses of the relationships of Glandulocalyx and other Ericales from the Late Cretaceous will require an improved understanding of the morphological features that diagnose particular extant groups defined on the basis of molecular data.


Inhibition of intestinal biotin absorption by chronic alcohol feeding: cellular and molecular mechanisms.
The water-soluble vitamin biotin is essential for normal cellular functions and its deficiency leads to a variety of clinical abnormalities. Mammals obtain biotin from exogenous sources via intestinal absorption, a process mediated by the sodium-dependent multivitamin transporter (SMVT). Chronic alcohol use in humans is associated with a significant reduction in plasma biotin levels, and animal studies have shown inhibition in intestinal biotin absorption by chronic alcohol feeding. Little, however, is known about the cellular and molecular mechanisms involved in the inhibition in intestinal biotin transport by chronic alcohol use. These mechanisms were investigated in this study by using rats and transgenic mice carrying the human full-length SLC5A6 5'-regulatory region chronically fed alcohol liquid diets; human intestinal epithelial Caco-2 cells chronically exposed to alcohol were also used as models. The results showed chronic alcohol feeding of rats to lead to a significant inhibition in carrier-mediated biotin transport events across jejunal brush border and basolateral membrane domains. This inhibition was associated with a significant reduction in level of expression of the SMVT protein, mRNA, and heterogenous nuclear RNA. Chronic alcohol feeding also inhibited carrier-mediated biotin uptake in rat colon. Studies with transgenic mice confirmed the above findings and further showed chronic alcohol feeding significantly inhibited the activity of SLC5A6 5'-regulatory region. Finally, chronic exposure of Caco-2 cells to alcohol led to a significant decrease in the activity of both promoters P1 and P2 of the human SLC5A6 gene. These studies identify for the first time the cellular and molecular parameters of the intestinal biotin absorptive processes that are affected by chronic alcohol feeding.


Disruption of sex pheromone communication in a nematode.
Males of Nippostrongylus brasiliensis, an intestinal parasite of rodents, were maintained in an environment permeated with pheromone produced by females of the species. After the males were removed from that environment, their subsequent ability to orient to a gradient of the pheromone emanating from living females was greatly reduced for periods up to 2 hours. This phenomenon might serve as the basis for a new, selective antihelminthic technique in which the premating communication between males and females is disrupted.


Mechanisms of dysfunction of the blood-brain barrier in critically ill patients: emphasis on the role of matrix metalloproteinases.
This paper aims to describe the physiological basis of the blood-brain barrier components and its properties. Additionally, the particular effects of metalloproteinases and their control over the extracellular matrix and its relationship with blood-brain barrier dysfunction are discussed. Finally, the role of metalloproteinases on changes in the central nervous system in critically ill patients is discussed.


Bilateral projections to the thalamus from individual neurons in the inferior colliculus.
The medial geniculate body (MG) receives a large input from the ipsilateral inferior colliculus (IC) and a smaller but substantial input from the contralateral IC. Both crossed and uncrossed inputs comprise a large percentage of glutamatergic cells and a smaller percentage of GABAergic cells. We used double labeling with fluorescent retrograde tracers to identify individual IC cells that project bilaterally to the MGs in adult guinea pigs. We also used immunohistochemistry for glutamic acid decarboxylase to distinguish GABAergic from glutamatergic cells that project bilaterally to the MG. We found cells in the IC that contained both retrograde tracers, indicating that they project bilaterally. Across cases, the bilaterally projecting cells constituted up to 37% of the cells that project to the ipsilateral MG and up to 73% of the cells that project to the contralateral MG. GABAergic cells averaged 20% of the bilaterally-projecting population. We conclude that a population of IC cells sends branching axonal projections to innervate the MG bilaterally. Most of the neurons in this population are glutamatergic, with a minority that are GABAergic. A mixed projection, with glutamatergic cells outnumbering GABAergic cells, originates from each of the major IC subdivisions (central nucleus, dorsal cortex, and lateral cortex). The bilaterally projecting cells are likely to serve functions different from the larger unilateral projections, perhaps synchronizing activity on the two sides of the auditory brain.


Recurrent uterine cancer after surgery: magnetic resonance imaging patterns and their changes after concomitant chemoradiation.
Our primary objective was to describe the magnetic resonance (MR) imaging patterns of recurrent uterine cancer after surgery and their changes following concurrent chemoradiation. The secondary objective was to identify MR imaging predictors of outcome. Twenty-two consecutive women with biopsy-proven recurrent uterine cancer after surgery (cervix 13 patients, endometrium nine patients) were enrolled in this prospective study. Inclusion criteria were MR imaging at diagnosis and during follow-up and eligibility for concurrent chemoradiation. MR images were assessed for signal intensity of the pelvic relapse on T2-weighted images, site of relapse and infiltration of adjacent organs. Pre- and posttreatment MR images were compared on the basis of the same criteria. The 3D volume of relapses after treatment was calculated, and tumour response to treatment was evaluated as complete, partial, no change or disease progression. Recurrences appeared hyperintense on T2-weighted images in 22/22 (100%) patients. Pelvic relapse site was vagina in 5/22 (23%), vaginal vault in 9/22 (41%), vaginal vault with extension to the pelvic wall in 5/22 (23%) and pelvic wall in 3/22 (13%). Infiltration of adjacent organs was detected in 9/22 (41%) patients. The mean volume of recurrences on pretreatment MR images was 38.83 cm(3). On posttreatment MR images, relapses appeared hypointense in 19/22 (86%) patients and hyperintense in 3/22 (14%). The mean volume of recurrences on posttreatment MR images was 18.01 cm(3). Complete response was seen in 11/22 (50%) patients, partial response in 8/22 (36%) and no change in 3/22 (14%). MR imaging can provide an evaluation of all parameters necessary for planning treatment and assessing response to treatment.


Hair analysis for abused drugs by capillary zone electrophoresis with field-amplified sample stacking.
The present paper describes the methodological optimisation and validation of a capillary zone electrophoresis method for the determination of morphine, cocaine and 3,4-methylenedioxymethamphetamine (MDMA) in hair, with injection based on field-amplified sample stacking. Diode array UV absorption detection was used to improve analytical selectivity and identification power. Analytical conditions: running buffer 100 mM potassium phosphate adjusted to pH 2.5 with phosphoric acid, applied potential 10 kV, temperature 20 degrees C, injection by electromigration at 10 kV for 10 s, detection by UV absorption at the fixed wavelength of 200 nm or by recording the full spectrum between 190 and 400 nm. Injection conditions: the dried hair extracts were reconstituted with a low-conductivity solvent (0.1 mM formic acid), the injection end of the capillary was dipped in water for 5 s without applying pressure (external rinse step), then a plug of 0.1 mM phosphoric acid was loaded by applying 0.5 psi for 10 s and, finally, the sample was injected electrokinetically at 10 kV for 10 s. Under the described conditions, the limit of detection was 2 ng/ml for MDMA, 8 ng/ml for cocaine and 6 ng/ml for morphine (with a signal-to-noise ratio of 5). The lowest concentration suitable for recording interpretable spectra was about 10-20-times the limit of detection of each analyte. The intraday and day-to-day reproducibility of migration times (n = 6), with internal standardisation, was characterised by R.S.D. values < or = 0.6%; peak area R.S.D.s were better than 10% in intraday and than 15% in day-to-day experiments. Analytical linearity was good with R2 better than 0.9990 for all the analytes.


Simulated job interview improves skills for adults with serious mental illnesses.
Adults with serious mental illnesses (e.g., Autism Spectrum Disorder [ASD], schizophrenia, post-traumatic stress disorder [PTSD]) often have difficulties obtaining employment. The Job Interview Training System with Molly Porter, developed in collaboration with Yale and Northwestern Universities and vocational rehabilitation specialists with funding from The National Institutes of Health (R43/44MH080496), allows learners to practice job interviews on computers in a stress free environment. The system includes user-driven educational materials, an interactive job application, a practice simulation with a fictional interviewer (Molly Porter), and extensive feedback. SIMmersion's PeopleSIM™ technology allows each conversation with Molly to provide a unique interview experience, enabling users to gain confidence while building skills. The on-screen coach provides insight during the conversation, and a comprehensive after-action review provides learners with feedback on the entire interview. In a randomized control trial, the system was proven effective at improving participants' interview skills and confidence. Ninety-six (96) unemployed adults with ASD (n=26), schizophrenia/other (n=37) or PTSD (n=33) were recruited. Participants were randomized into control (n=32) and experimental (n=64) conditions. The control group was "wait-listed" to receive training, and the experimental group used the training system with Molly Porter. Both groups completed pre- and post-intervention role-play interviews and self-assessment questionnaires. Analyses of covariance showed that the simulation provided a highly significant training effect, with experimental group participants scoring better in the role-play interviews and self-assessing higher than control group participants. By increasing skills and confidence, this system may ultimately reduce the length of unemployment for adults with mental illnesses.


The complex experience of psoriasis related skin pain: a qualitative study.
Background and aims Psoriasis is a common chronic skin condition, causing skin lesions with thickened and scaling skin, as well as erythema and inflammation that may involve painful sores, cracks, and pustules. Previously psoriasis was regarded as a painless skin condition. However, over the past decade studies show that skin pain is a frequently reported and bothersome symptom in patients with psoriasis. There is however a lack of rich narratives describing the experience of skin pain in these patients. The aims of this qualitative study were therefore to explore in depth how patients experience psoriasis-related skin pain, and how they deal with it. Methods Thirteen patients with psoriasis were recruited from a dermatology ward and outpatient clinic. One of the investigators (TML) performed individual, semi-structured interviews at an undisturbed room in the hospital. Interviews were thematically analyzed using the method of Systematic Text Condensation as described by Malterud (2012). Results Three main themes were identified from the interviews. First, the skin pain experience was complex. Patients used a variety of adjectives and metaphors to describe their pain, and their skin was sensitive to stimuli of every-day activities. Itch was a common cosymptom, and could both mask pain but also cause severe pain due to excessive scratching and damage to the skin. Second, skin pain had a negative impact on patients' life. Skin pain reduced their physical activity level, impaired their sleep, and made them irritable, depressed, unconcentrated on tasks, as well as withdrawn from other people and social activities. Third, patients dealt with their skin pain in various ways. Although some took action to relieve the pain and distract themselves from pain, most of the patients applied maladaptive and passive coping strategies such as put up with it, avoid painful activities, become fearful or trivialize their pain. Conclusions The experience of psoriasis related skin pain is complex. The pain has a major negative impact on patients' life in terms of physical, emotional, cognitive, and social functions. Patients use a variety of adaptive but most frequently maladaptive coping strategies in order to deal with their skin pain. Implications This study provides new and in-depth knowledge on psoriasis related skin pain. This information is valuable for further work on pain assessment tools and pain management recommendations customized for skin pain experienced by patients with psoriasis.


Stromal disrupting effects of nab-paclitaxel in pancreatic cancer.
Nab-paclitaxel and gemcitabine have demonstrated a survival benefit over gemcitabine alone in advanced pancreatic cancer (PDA). This study aimed to investigate the clinical, biological, and imaging effects of the regimen in patients with operable PDA. Patients with operable PDA received two cycles of nab-paclitaxel and gemcitabine before surgical resection. FDG-PET and CA19.9 tumour marker levels were used to measure clinical activity. Effects on tumour stroma were determined by endoscopic ultrasound (EUS) elastography. The collagen content and architecture as well as density of cancer-associated fibroblasts (CAFs) were determined in the resected surgical specimen and compared with a group of untreated and treated with conventional chemoradiation therapy controls. A co-clinical study in a mouse model of PDA was conducted to differentiate between the effects of nab-paclitaxel and gemcitabine. A total of 16 patients were enrolled. Treatment resulted in significant antitumour effects with 50% of patients achieving a >75% decrease in circulating CA19.9 tumour marker and a response by FDG-PET. There was also a significant decrement in tumour stiffness as measured by EUS elastography. Seven of 12 patients who completed treatment and were operated had major pathological regressions. Analysis of residual tumours showed a marked disorganised collagen with a very low density of CAF, which was not observed in the untreated or conventionally treated control groups. The preclinical co-clinical study showed that these effects were specific of nab-paclitaxel and not gemcitabine. These data suggest that nab-paclitaxel and gemcitabine decreases CAF content inducing a marked alteration in cancer stroma that results in tumour softening. This regimen should be studied in patients with operable PDA.


Lens induction by Pax-6 in Xenopus laevis.
Despite extensive study following the pioneering work of Spemann on lens development (Spemann, H. (1901) Verh. Anat. Ges. 15, 61-79) and the subsequent establishment of the concept of embryonic induction, the molecular mechanism of vertebrate lens induction remains largely unknown. Here we report that in Xenopus expression of Pax-6 results in lens formation in a cell autonomous manner. In animal cap experiments, Pax-6 induced expression of the lens-specific marker beta B1-crystallin without inducing the general neural marker NCAM. Ectopic Pax-6 expression also resulted in the formation of ectopic lenses in whole embryos as well as in animal cap explants indicating that in vertebrates, as well as Drosophila (Halder, G., Callaerts, P., and Gehring, W.J. (1995) Science 267, 1788-1792), Pax-6 can direct the development of major components of the eye. Interestingly, ectopic lenses formed in whole embryos without association with neural tissue. Treatments giving rise to anterior neural tissue in animal cap explants resulted in the expression of both beta B1-crystallin and Pax-6. Given the ability of Pax-6 to direct lens formation, we propose that the establishment of Pax-6 expression in the presumptive lens ectoderm during normal development is likely to be a critical response of lens-competent ectoderm to early lens inducers.


Effects of irradiated tumor vaccine and infusion of granulocyte-macrophage colony-stimulating factor and interleukin-12 on established gliomas in rats.
We investigated granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-12 (IL-12) infused into the injection site of irradiated tumor vaccine (TV) as therapy for gliomas. Rats with subcutaneous RT-2 gliomas were treated with irradiated TV and/or subcutaneous infusion of GM-CSF and/or IL-12 via osmotic minipump 5 days after tumor-cell inoculation. Cytotoxic T lymphocyte (CTL) and natural killer (NK) cell activity were analyzed to investigate immune responses. Rats with intracerebral gliomas were treated with irradiated TV and infused GM-CSF/IL-12 3 days after tumor-cell inoculation. Tumor growth rates and animal survival were followed. Survivors were re-challenged with wild-type RT-2 cells subcutaneously or intracerebrally to study long-term anti-tumor immunity. Rats with subcutaneous gliomas treated with GM-CSF and IL-12 or TV plus GM-CSF or IL-12 did not have increased survival rate (P>0.2), but did have prolonged survival time (P<0.05); in contrast, rats treated with TV plus GM-CSF/IL-12 had increased survival rate (P<0.05) and prolonged survival time (P<0.05) compared with controls. These treatment strategies showed enhanced CTL and NK cell activities. Rats with intra-cerebral gliomas treated with TV plus GM-CSF/IL-12 did not have increased survival rate (P=0.11), but did have prolonged survival time (P<0.0001). Survivors in each group were re-challenged with wild-type RT-2 cells, and all had long-term survival. Irradiated TV plus continuous localized infusion of GM-CSF/IL-12 may induce a tumor-specific anti-tumor immune response on established subcutaneous or intra-cerebral gliomas, and such a treatment strategy deserves consideration as adjuvant treatment for glioma.


Fiber architecture of the intrinsic muscles of the shoulder and arm in semiterrestrial and arboreal guenons.
The internal organization of myofibers and connective tissues has important physiologic implications for muscle function and for naturalistic behavior. In this study of forelimb muscle morphology and primate locomotion, fiber architecture is examined in the intrinsic muscles of the shoulder (musculi deltoideus, infraspinatus, supraspinatus, subscapularis, teres major, and t. minor) and arm (m. coracobrachialis, biceps brachii, brachialis, and triceps brachii) in the semiterrestrial vervets (Chlorocebus aethiops) and arboreal red-tailed guenons (Cercopithecus ascanius). Wet weights and lengths of whole muscles, lengths of fasciculi and their associated proximal and distal tendons, and angles of pinnation were measured to estimate morphologic correlates of physiologic properties of individual muscles: force, velocity/excursion, energy expense, and relative isometric or isotonic contraction. Neither mean total-shoulder:total-arm ratios for muscle mass nor total reduced physiological cross-sectional area exhibited significant (P < 0.05) interspecific differences, thus emphasizing the importance of fine-tuning musculoskeletal analyses by the data collected here. The results generally support those previously published for quadriceps femoris and triceps surae of the hind limb in these species (Anapol and Barry [1996] Am. J. Phys. Anthropol. 99:429-447). The fiber architecture of the semiterrestrial vervets is largely suited for higher velocity while running on the ground. By contrast, the architectural configuration of red-tailed monkeys implies relatively isometric muscle contraction and passive storage of elastic strain energy for exploitation of the compliant canopy, where substrate components are situated beneath the sagittal plane of the animal. With respect to relative distribution of maximum potential force output among muscles of either shoulder or arm groups in these otherwise hind limb-dominated quadrupedal primates, statistically significant interspecific differences are best interpreted in light of braking, climbing, and, for vervets, the transition between ground and canopy. The interspecific differences shown here for the intrinsic muscles of the shoulder and arm underscore the significance of intramuscular morphology in reconciling structure and function with regard to locomotor behavior. Its analysis and interpretation lend support to consideration of "semiterrestrial" as a bona fide locomotor category uniquely different from what is practiced by dedicated arboreal and terrestrial quadrupeds that occasionally visit the habitat of one another. Data from a more committed terrestrial species would clarify this enigma.


Comparing decision-support systems in adopting sustainable intensification criteria.
Sustainable intensification (SI) is a multifaceted concept incorporating the ambition to increase or maintain the current level of agricultural yields while reduce negative ecological and environmental impacts. Decision-support systems (DSS) that use integrated analytical methods are often used to support decision making processes in agriculture. However, DSS often consist of set of values, objectives, and assumptions that may be inconsistent or in conflict with merits and objectives of SI. These potential conflicts will have consequences for adoption and up-take of agricultural research, technologies and related policies and regulations such as genetic technology in pursuit of SI. This perspective paper aimed at comparing a number of frequently used socio-economic DSS with respect to their capacity in incorporating various dimensions of SI, and discussing their application to analyzing farm animal genetic resources (FAnGR) policies. The case of FAnGR policies was chosen because of its great potential in delivering merits of SI. It was concluded that flexible DSS, with great integration capacity with various natural and social sciences, are needed to provide guidance on feasibility, practicality, and policy implementation for SI.


Net financial gain or loss from vaccination in pediatric medical practices.
The goal was to determine the net return (gain or loss after costs were subtracted from revenues) to private pediatric medical practices from investing time and resources in vaccines and vaccination of their patients. A cross-sectional survey of a convenience sample of private medical practices requested data on all financial and capacity aspects of the practices, including operating expenses; labor composition and wages/salaries; private- and public-purchase vaccine orders and inventories; Medicaid and private insurance reimbursements; patient population; numbers of providers; and numbers, types, and lengths of visits. Costs were assigned to vaccination visits and subtracted from reimbursements from public- and private-pay sources to determine net financial gains/losses from vaccination. Thirty-four practices responded to the survey. More than one half of the respondents broke even or suffered financial losses from vaccinating patients. With greater proportions of Medicaid-enrolled patients served, greater financial loss was noted. On average, private insurance vaccine administration reimbursements did not cover administration costs unless a child received > or = 3 doses of vaccine in 1 visit. Finally, wide ranges of per-dose prices paid and reimbursements received for vaccines indicated that some practices might be losing money in purchasing and delivering vaccines for private-pay patients if they pay high purchase prices but receive low reimbursements. We conclude that the vaccination portion of the business model for primary care pediatric practices that serve private-pay patients results in little or no profit from vaccine delivery. When losses from vaccinating publicly insured children are included, most practices lose money.


RECQ-like helicases Sgs1 and BLM regulate R-loop-associated genome instability.
Sgs1, the orthologue of human Bloom's syndrome helicase BLM, is a yeast DNA helicase functioning in DNA replication and repair. We show that SGS1 loss increases R-loop accumulation and sensitizes cells to transcription-replication collisions. Yeast lacking SGS1 accumulate R-loops and γ-H2A at sites of Sgs1 binding, replication pausing regions, and long genes. The mutation signature of sgs1Δ reveals copy number changes flanked by repetitive regions with high R-loop-forming potential. Analysis of BLM in Bloom's syndrome fibroblasts or by depletion of BLM from human cancer cells confirms a role for Sgs1/BLM in suppressing R-loop-associated genome instability across species. In support of a potential direct effect, BLM is found physically proximal to DNA:RNA hybrids in human cells, and can efficiently unwind R-loops in vitro. Together, our data describe a conserved role for Sgs1/BLM in R-loop suppression and support an increasingly broad view of DNA repair and replication fork stabilizing proteins as modulators of R-loop-mediated genome instability.


High number of kinome-mutations in non-small cell lung cancer is associated with reduced immune response and poor relapse-free survival.
Lung cancer is the leading cause of cancer related death, and the past years' improved insight into underlying molecular events has significantly improved outcome for specific subsets of patients. In particular, several new therapies that target protein kinases have been implemented, and many more are becoming available. We have investigated lung cancer specimens for somatic mutations in a targeted panel of 612 human genes, the majority being protein kinases. The somatic mutation profiles were correlated to profiles of immune cell infiltration as well as relapse-free survival. Targeted deep sequencing was performed on 117 tumour/normal pairs using the SureSelect Human Kinome kit (Agilent Technologies), with capture probes targeting 3.2 Mb of the human genome, including exons and untranslated regions of all known kinases, kinase receptors and selected cancer-related genes (612 genes in total). CD8 staining was determined using Ventana Benchmark. Survival analyses were performed using SPSS. The number of mutations per sample ranged from 0 to 50 (within the 612 genes tested), with a median of nine. The prognosis was worse for patients with more than the median number of mutations. A significant correlation was found between mutations in one of selected DNA-repair genes and the total number of mutations in that tumour (p < 0.001). There was a significant inverse correlation between the number of infiltrating stromal CD8+ lymphocytes and the presence of EGFR mutations.


Dual Poisson-Disk Tiling: an efficient method for distributing features on arbitrary surfaces.
This paper introduces a novel surface-modeling method to stochastically distribute features on arbitrary topological surfaces. The generated distribution of features follows the Poisson disk distribution, so we can have a minimum separation guarantee between features and avoid feature overlap. With the proposed method, we not only can interactively adjust and edit features with the help of the proposed Poisson disk map, but can also efficiently re-distribute features on object surfaces. The underlying mechanism is our dual tiling scheme, known as the Dual Poisson-Disk Tiling. First, we compute the dual of a given surface parameterization, and tile the dual surface by our specially-designed dual tiles; during the pre-processing, the Poisson disk distribution has been pre-generated on these tiles. By dual tiling, we can nicely avoid the problem of corner heterogeneity when tiling arbitrary parameterized surfaces, and can also reduce the tile set complexity. Furthermore, the dual tiling scheme is non-periodic, and we can also maintain a manageable tile set. To demonstrate the applicability of this technique, we explore a number of surface-modeling applications: pattern and shape distribution, bump-mapping, illustrative rendering, mold simulation, the modeling of separable features in texture and BTF, and the distribution of geometric textures in shell space.


STEM the bullying: An empirical investigation of abusive supervision in academic science.
Academic bullying is a topic of significant interest of late, with high profile cases featured in scientific journals. Our aim is to document the nature and extent of academic bullying behaviors, examining who are the primary targets and perpetrators as well as the responses to and outcomes of bullying. We developed a cross-sectional global survey aimed primarily at those in academic science institutions. The survey was administered via Qualtrics and data were collected (between November 2019 and July 2021) from 2006 individuals whose participation was solicited through various means including advertisements in Science and Nature magazines and the American Chemical Society. Among the 2006 survey participants, the majority of targets were graduate students or postdocs. An overwhelming proportion of participants reported either experiencing (84%) or witnessing (59%) abusive supervision, or both (49%). While a majority of perpetrators were male, they were proportionately no more likely to abuse than females. Perpetrators were more likely from the highest-ranked institutions and they were most likely PIs. Females were more likely to report being bullied but their scores on the Tepper abusive supervision scale and the contextual behavior checklist we developed were not greater than male targets. Male targets actually reported higher levels of certain bullying behaviors. While international scholars were no more likely to report being bullied, the severity of the behaviors they reported was significantly greater. Targets (64%) were most likely to use avoidant tactics (not reporting and relying on family/friends for support) in response to bullying due to fear of retaliation (61%). The small percentage that did report the abuse (29%) overwhelmingly reported unfair and biased (58%) outcomes. Additional qualitative analysis of open-ended comments revealed similar patterns. We also noticed that the COVID-19 pandemic has exacerbated academic bullying and changed the patterns of behaviors possibly due to the remote nature of interactions. Open-ended responses from targets are analyzed with examples provided. Our results elucidated the various forms of abuse, the most likely perpetrators and targets, as well as the typical reactions of targets and witnesses. We investigated the results of targets' actions following chronic bullying. Our findings highlight the domain, extent, and dynamics of academic bullying to hopefully motivate the scientific community to take action.


Vascular access and patient outcomes in hemodialysis: questions answered in recent literature.
Hemodialysis is not possible without access to the vascular system to provide an adequate and reliable source of blood flow through the hemodialyzer. Since maintenance hemodialysis therapy became a reality in the latter half of the twentieth century, no vascular access has exceeded the success and reliability of arteriovenous fistulae (AVF). They have the lowest infection and thrombosis rates, have the longest patency rates, and are associated with the best morbidity and mortality outcomes of any access modality. In the United States, the majority of patients starting hemodialysis do not have a primary AVF, which may explain why vascular access complications represent almost 20% of the total spending for hemodialysis. In addition, as much as 50% of hospitalization costs for end-stage renal disease are related to access issues. Every effort must be directed in the U.S. as well as elsewhere to promote the use of AVF whenever possible. In some European countries, more than 90% of patients have AVF as their hemodialysis access when nephrologists perform placement of vascular access. Already, some programs in the U.S. have recognized the need for trained nephrologists to provide these services. U.S. interventional nephrologists should be given the opportunity to learn AVF placement procedures to emulate their European counterparts, and thus improve U.S. dialysis outcomes.


Force-time curve characteristics and hormonal alterations during an eleven-week training period in elite women weightlifters.
The purpose of this investigation was to study the effects of an 11-week training period performed by female weightlifters. Two weeks before this investigation, baseline measures for total testosterone, cortisol, and testosterone:cortisol ratio were collected. The 11-week training program consisted of the core exercises (i.e., clean, clean and jerk, and snatch) and other supplemental exercises (i.e., clean pull, snatch pull, squat, and front squat). Hormonal, isometric, and dynamic middle thigh pull force-time curve characteristics were assessed biweekly throughout the duration of the investigation, whereas volume load and training intensity were assessed weekly throughout the investigation. The testosterone:cortisol ratio of the baseline (1.19 +/- 0.64) was significantly different from the ratio of weeks 1 (0.67 +/- 0.36) and 9 (0.94 +/- 0.66). When the week-to-week values were compared, week 1 (0.67 +/- 0.36) was significantly different (P < 0.05; eta = 0.84) from week 3 (1.06 +/- 0.54). A very strong correlation (r = -0.83; r = 0.69) was found between the percentage change of the testosterone:cortisol ratio and volume load from weeks 1 to 11. Moderate to very strong correlations were noted between the percentage change in volume load and isometric peak force, peak force during the 30% isometric peak force trial, and peak force during the 100-kg trial during the 11 weeks of training. The primary finding of this study was that alterations in training volume load can result in concomitant changes in the anabolic-to-catabolic balance, as indicated by the testosterone:cortisol ratio, and the ability to generate maximal forces.


A survey of medical researchers indicates poor awareness of research data management processes and a role for data librarians.
The European Parliament's directive on open data indicates the direction to follow for all public institutions in Europe. The portal Polish Platform of Medical Research (PPM) required more information about researcher attitudes and training requirements for strategic planning. The aim was to assess (1) the status of knowledge about research data management among medical researchers in Poland, and (2) their attitudes towards data sharing. This knowledge may help to inform a training program and adapt PPM to the requirements of researchers. The authors circulated an online survey and received responses from 603 researchers representing medical sciences and related disciplines. The survey was conducted in 2019 at seven Polish medical universities and at the Nofer Institute of Occupational Medicine. Analysis used descriptive statistics. Data sharing was not widespread (55.7% only shared with their research team, 9.8% had shared data on an open access basis). Many cited possible benefits of research data sharing but were concerned about drawbacks (e.g. fraud, plagiarism). Polish medical scientists, like many researchers, are not aware of the processes required for safe data preparation for sharing. Academic libraries should develop roles for data librarians to help train researchers. Fears about the dangers of data sharing need to be overcome before researchers are willing to share their own research data.


Trypsin-like proteinase and its endogenous inhibitor from Yersinia pseudotuberculosis. Biological activity.
A trypsin-like proteinase (YPTP) and its endogenous inhibitor (ITYP) were isolated from the culture filtrate of the pathogenic bacterium Yersinia pseudotuberculosis, and their biological activities were studied. YPTP was found to be highly toxic for random-bred white mice. Under in vitro conditions the proteolytic enzyme destroyed protective proteins of the immune system of the animals--IgG, IgA, and proteins of the complement system (CIq, C3, and C5)--and, consequently, was a pathogenetic factor in yersinioses. The inhibitor ITYP was shown to manifest antibacterial activity against virulent forms of Yersinia pseudotuberculosis, Escherichia coli, and Salmonella typhimurium. The ITYP preparation was harmless and nontoxic.