Dexamethasone inhibits the effect of paclitaxel on human ovarian carcinoma xenografts in nude mice.
Recent studies showed that dexamethasone (DEX) could render cancer cells resistant to paclitaxel (PTX) induced apoptosis though an unknown mechanism. This study aimed to evaluate the influence of DEX pretreatment on the anti-tumor effect of PTX in an in vivo xenograft model with grafted ovarian cancer SKOV-3 cells innude mice. The xenograft procedure was performed, and the nude mice were grouped into four cohorts of ten that received the following treatments: Control group, DEX group, PTX group and DEX+PTX group. Individual treatments were administered once every three days for a total of 6 courses. The growth of tumors and the inhibition rates were measured. Changes in tissue morphology and cellular ultrastructure were observed using light and transmission electron microscopy. Immunohistochemistry was performed to examine the expression of Ki-67, Bcl-xL and cleaved caspase-3. Premedication with DEX reduced the inhibitory effect of PTX on tumor growth by approximately 20% compared to the PTX-only-treated group in the ovarian carcinoma xeno-grafted mice. Hematoxylin-eosin (H&E) staining revealed that significantly fewer cells exhibited vacuolization and apoptosis in the DEX + PTX group compared to the PTX group. Apoptotic characteristics including karyopyknosis, nuclear chromatin condensation along the nuclear membrane and aggregation were observed in both DEX+PTX and PTX groups under electron microscopy. However, these characteristics were less significant in the DEX+PTX group than those in the PTX group. The immunohistochemistry demonstrated that protein expression levels of Ki-67 and Bcl-xL were significantly increased, whereas cleaved caspase-3 decreased in the DEX+PTX group, compared to PTX group (p < 0.0125). DEX inhibits the therapeutic efficacy of PTX in a human ovarian carcinoma SKOV-3 xenograft model.


HIV knowledge, disclosure and sexual risk among pregnant women and their partners in rural South Africa.
Partner involvement has been deemed fundamental for the prevention of mother-to-child transmission (PMTCT) of HIV, although it remains difficult to achieve. This study aimed to explore the attitudes and behaviours of pregnant women and their partners who participated in a behavioural risk reduction intervention in six community health centres in the Mpumalanga province of South Africa. Qualitative methods only were used in this study. Women and their partners took part in four gender-concordant groups that addressed HIV, PMTCT, disclosure of HIV status and safer sex practices. The results indicate that men value and understand the importance of being involved in women's reproductive health, although some components of the PMTCT programme such as condom use were still met with some resistance. Participants demonstrated high levels of HIV- and sexually transmitted infection-related knowledge. Men lacked knowledge about PMTCT but were interested in acquiring information so that they could support their partners. All groups highlighted the emotional and physical benefits of disclosing one's HIV status. The involvement of men in antenatal care has the potential to prevent women from becoming infected with HIV both during pregnancy and post-partum when they are more vulnerable to infection and have a high risk of transmission to the infant. There is a need for interventions that focus on both increasing male involvement and promoting condom use during pregnancy.


Treatment of acute posttraumatic stress disorder with tricyclic antidepressants.
The diagnostic concept of posttraumatic stress disorder (PTSD) has long been recognized but usually applied in postwar circumstances. Recently developed criteria have allowed the disorder to be recognized in civilian patients having stress from such common insults as trauma, burns, or rape. Because PTSD may become chronic and difficult to treat if unrecognized, early intervention is desirable. In this report I describe three patients with acute PTSD who had favorable therapeutic response to tricyclic antidepressants. Although the use of the tricyclic agents in PTSD is rational because of their antianxiety and antidepressant properties, little has previously been said of their effectiveness in this disorder. These agents may provide an effective means of diminishing or preventing chronic PTSD.


High-intensity exercise to promote accelerated improvements in cardiorespiratory fitness (HI-PACE): study protocol for a randomized controlled trial.
African Americans have a disproportionate prevalence and incidence of type 2 diabetes compared with Caucasians. Recent evidence indicates that low cardiorespiratory fitness (CRF) level, an independent risk factor for type 2 diabetes, is also more prevalent in African Americans than Caucasians. Numerous studies in Caucasian populations suggest that vigorous exercise intensity may promote greater improvements in CRF and other type 2 diabetes risk factors (e.g., reduction of glucose/insulin levels, pulse wave velocity, and body fat) than moderate intensity. However, current evidence comparing health benefits of different aerobic exercise intensities on type 2 diabetes risk factors in African Americans is negligible. This is clinically important as African Americans have a greater risk for type 2 diabetes and are less likely to meet public health recommendations for physical activity than Caucasians. The purpose of the HI-PACE (High-Intensity exercise to Promote Accelerated improvements in CardiorEspiratory fitness) study is to evaluate whether high-intensity aerobic exercise elicits greater improvements in CRF, insulin action, and arterial stiffness than moderate-intensity exercise in African Americans. A randomized controlled trial will be performed on overweight and obese (body mass index of 25-45 kg/m2) African Americans (35-65 years) (n = 60). Participants will be randomly assigned to moderate-intensity (MOD-INT) or high-intensity (HIGH-INT) aerobic exercise training or a non-exercise control group (CON) for 24 weeks. Supervised exercise will be performed at a heart rate associated with 45-55% and 70-80% of VO2 max in the MOD-INT and HIGH-INT groups, respectively, for an exercise dose of 600 metabolic equivalents of task (MET)-minutes per week (consistent with public health recommendations). The primary outcome is change in CRF. Secondary outcomes include change in insulin sensitivity (measured via an intravenous glucose tolerance test), skeletal muscle mitochondrial oxidative capacity (via near-infrared spectroscopy), skeletal muscle measurements (i.e., citrate synthase, COX IV, GLUT-4, CPT-1, and PGC1-α), arterial stiffness (via carotid-femoral pulse wave velocity), body fat, C-reactive protein, and psychological outcomes (quality of life/exercise enjoyment). The anticipated results of the HI-PACE study will provide vital information on the health effects of high-intensity exercise in African Americans. This study will advance health disparity research and has the potential to influence future public health guidelines for physical activity. ClinicalTrials.gov identifier: NCT02892331 . Registered on September 8, 2016.


Effect of calcium and vitamin D supplementation on blood pressure: the Women's Health Initiative Randomized Trial.
Experimental and epidemiological studies suggest that calcium and vitamin D supplements may lower blood pressure. We examined the effect of calcium plus vitamin D supplementation on blood pressure and the incidence of hypertension in postmenopausal women. The Women's Health Initiative Calcium/Vitamin D Trial randomly assigned 36 282 postmenopausal women to receive 1000 mg of elemental calcium plus 400 IU of vitamin D3 daily or placebo in a double-blind fashion. Change in blood pressure and the incidence of hypertension were ascertained. Over a median follow-up time of 7 years, there was no significant difference in the mean change over time in systolic blood pressure (0.22 mm Hg; 95% CI: -0.05 to 0.49 mm Hg) and diastolic blood pressure (0.11 mm Hg; 95% CI: -0.04 to 0.27 mm Hg) between the active and placebo treatment groups. This null result was robust in analyses accounting for nonadherence to study pills and in baseline subgroups of interest, including black subjects and women with hypertension or high levels of blood pressure, with low intakes of calcium and vitamin D or low serum levels of vitamin D. In 17 122 nonhypertensive participants at baseline, the hazard ratio for incident hypertension associated with calcium/vitamin D treatment was 1.01 (95% CI: 0.96 to 1.06.) In postmenopausal women, calcium plus vitamin D3 supplementation did not reduce either blood pressure or the risk of developing hypertension over 7 years of follow-up.


Differentiation of the bovine dominant follicle from the cohort upregulates mRNA expression for new tissue development genes.
This study was designed to identify genes that regulate the transition from FSH- to LH-dependent development in the bovine dominant follicle (DF). Serial analysis of gene expression (SAGE) was used to compare the transcriptome of granulosa cells isolated from the most oestrogenic growing cohort follicle (COH), the newly selected DF and its largest subordinate follicle (SF) which is destined for atresia. Follicle diameter, follicular fluid oestradiol (E) and E:progesterone ratio confirmed follicle identity. Results show that there are 93 transcript species differentially expressed in DF granulosa cells, but only 8 of these encode proteins known to be involved in DF development. Most characterised transcripts upregulated in the DF are from tissue development genes that regulate cell differentiation, proliferation, apoptosis, signalling and tissue remodelling. Semiquantitative real-time PCR analysis confirmed seven genes with upregulated (P< or =0.05) mRNA expression in DF compared with both COH and SF granulosa cells. Thus, the new genes identified by SAGE and real-time PCR, which show enhanced mRNA expression in the DF, may regulate proliferation (cyclin D2; CCND2), prevention of apoptosis or DNA damage (growth arrest and DNA damage-inducible, beta; GADD45B), RNA synthesis (splicing factor, arginine/serine rich 9; SFRS9) and unknown processes associated with enhanced steroidogenesis (ovary-specific acidic protein; DQ004742) in granulosa cells of DF at the onset of LH-dependent development. Further studies are required to show whether the expression of identified genes is dysregulated when abnormalities occur during DF selection or subsequent development.


Prevalence of hepatitis B virus infection among pregnant women in Jos, Nigeria.
The study sought to determine the prevalence and risk factors associated with Hepatitis B surface antigenemia (HBsAg) positivity among pregnant women in Jos, Nigeria. This was a cross-sectional study carried out among the pregnant population in five healthcare facilities in Jos, between November 1, 2017 and April 30, 2018. Informed consent was obtained, and data on sociodemographic and risk factors for hepatitis B virus (HBV) infection were collected. Hepatitis B viral infection was assessed using the in vitro HBsAg diagnostic rapid kit (Acon Laboratories, USA). Descriptive statistics, Chi-square test, and logistic regression were performed to identify predictors of HBV infection in the study population. All statistical analyses were carried out on STATA version 15. Of the 3,238 women enrolled, 7.4% (241/3238) (95% confidence interval [CI] = 6.6% to 8.4%) were HBsAg positive. The absence of HBV vaccination (adjusted odds ratio [AOR] = 2.49; 95% CI = 1.49-4.09; P < 0.001), co-infection with HIV (AOR = 1.90; 95% CI = 1.18-3.08; P = 0.009), and higher parity (AOR = 1.37; 95% CI = 1.04-1.79; P = 0.024) were independently associated with HBV infection in pregnancy. The prevalence of HBV infection among pregnant women was high, especially among those without prior vaccination for HBV, those with HIV co-infection and higher parity.


Primary ciliary dyskinesia diagnosis and management and its implications in America: a mini review.
Primary ciliary dyskinesia (PCD) is a rare genetic disorder that can result in significant morbidity and mortality if left untreated. Clinical manifestations of PCD include recurrent respiratory infections, laterality defects, and infertility, all of which arise from impaired or absent ciliary motility. Diagnostic approaches for PCD may include high-speed video microscopy, measurement of nasal nitric oxide levels, and genetic testing; however, no single definitive diagnostic test exists. The present study aims to highlight the lack of standardized diagnostic and treatment guidelines for PCD in Latin America (Central and South America, and the Caribbean). To this effect, we compared North American and European recommendations for the diagnosis and management of PCD and found that certain diagnostic tools and treatment options mentioned in these guidelines are not readily accessible in many Latin American countries. This review gathers disease information in North America, Europe, and Latin America organizing guideline results into tables for clarity and potential interventions. Management information for Latin America is inferred from case reports, as most findings are from North American recommendations and studies on PubMed, Google Scholar, and Scopus. Treatment and management information is based on North American and European standards.Among 5,774 publications reviewed, only 15 articles met the inclusion criteria (focused on PCD management, peer-reviewed, and located in America). No clinical guideline for PCD in Latin America was found, but recommendations on respiratory management from Colombia and Chile were discovered. The lack of guidelines in Latin America may originate from limited resources and research on the disease in those countries. PCD lacks documentation, research, and recommendations regarding its prevalence in Latin America, likely due to unfavorable economic conditions. This disadvantage results in limited access to diagnostic tests available in North America and Europe. The PICADAR score, discussed in this review, can be used in low-income nations as a screening tool for the disorder.


Output-sensitive 3D line integral convolution.
We propose an output-sensitive visualization method for 3D line integral convolution (LIC) whose rendering speed is largely independent of the data set size and mostly governed by the complexity of the output on the image plane. Our approach of view-dependent visualization tightly links the LIC generation with the volume rendering of the LIC result in order to avoid the computation of unnecessary LIC points: early-ray termination and empty-space leaping techniques are used to skip the computation of the LIC integral in a lazy-evaluation approach; both ray casting and texture slicing can be used as volume-rendering techniques. The input noise is modeled in object space to allow for temporal coherence under object and camera motion. Different noise models are discussed, covering dense representations based on filtered white noise all the way to sparse representations similar to oriented LIC. Aliasing artifacts are avoided by frequency control over the 3D noise and by employing a 3D variant of MIPmapping. A range of illumination models is applied to the LIC streamlines: different codimension-2 lighting models and a novel gradient-based illumination model that relies on precomputed gradients and does not require any direct calculation of gradients after the LIC integral is evaluated. We discuss the issue of proper sampling of the LIC and volume-rendering integrals by employing a frequency-space analysis of the noise model and the precomputed gradients. Finally, we demonstrate that our visualization approach lends itself to a fast graphics processing unit (GPU) implementation that supports both steady and unsteady flow. Therefore, this 3D LIC method allows users to interactively explore 3D flow by means of high-quality, view-dependent, and adaptive LIC volume visualization. Applications to flow visualization in combination with feature extraction and focus-and-context visualization are described, a comparison to previous methods is provided, and a detailed performance analysis is included.


Significance of Serum Polyunsaturated Fatty Acid Level Imbalance in Patients with Acute Venous Thromboembolism.
Polyunsaturated fatty acids (PUFAs) take part in various biological events linked to the pathogenesis of venous thromboembolism (VTE), including inflammation, endothelial dysfunction, and hypercoagulability. Several studies have demonstrated the association between PUFAs and the occurrence of VTE. However, the role of PUFAs in the pathogenesis of VTE remains unclear. We enrolled 45 patients with acute VTE and 37 age-, gender-, and body mass index-matched healthy volunteers to examine their PUFA levels. Serum omega 3 (eicosapentaenoic acid: EPA and docosahexaenoic acid: DHA) and omega 6 (dihomogammalinolenic acid: DGLA and arachidonic acid: AA) fatty acids levels were measured within 24 h of admission. Patients with VTE showed significantly higher AA and lower EPA levels, and lower EPA/AA ratios than the controls. Multivariate analysis revealed that AA was an independent marker for VTE. In addition, we divided the patients based on their median age (58 years old). The younger patients with VTE showed significantly lower EPA/AA levels than their age-matched controls, whereas older patients with VTE showed a significantly higher AA/DGLA levels than the older controls. High serum AA levels and low EPA levels are associated with the development of acute VTE, suggesting that the imbalance of PUFAs may be a potential therapeutic target for preventing acute VTE.


Choice of the levonorgestrel intrauterine device, etonogestrel implant or depot medroxyprogesterone acetate for contraception after aspiration abortion.
Women who have abortions are at high risk of contraception discontinuation and subsequent unintended pregnancy. The objective of this analysis was to identify factors associated with choice of highly effective, long-acting, progestin-only contraceptive methods after abortion. Women presenting for surgical abortion who selected the levonorgestrel intrauterine device (IUD), the progestin implant or the progestin injection (depot medroxyprogesterone acetate or DMPA) as their postabortion contraceptives were recruited to participate in a 1-year prospective cohort study. We used multivariable multinomial logistic regression to identify factors associated with choosing long-acting reversible contraceptives (IUD or implant) compared to DMPA. A total of 260 women, aged 18-45 years, enrolled in the study, 100 of whom chose the IUD, 63 the implant and 97 the DMPA. The women were 24.9 years old on average; 36% were black, and 29% were Latina. Fifty-nine percent had had a previous abortion, 66% a prior birth, and 55% were undergoing a second-trimester abortion. In multivariable analyses, compared with DMPA users, women who chose the IUD or the implant were less likely to be currently experiencing intimate partner violence (IPV); reported higher stress levels; weighed more; and were more likely to have finished high school, to have used the pill before and to report that counselors or doctors were helpful in making the decision (all significant at p<.05, see text for relative risk ratios and confidence intervals.) In addition, women who chose the IUD were less likely to be black (p<.01), and women who chose the implant were more likely to report that they would be unhappy to become pregnant within 6 months (p<.05) than DMPA users. A variety of factors including race/ethnicity, past contraceptive use, feelings towards pregnancy, stress and weight were different between LARC and DMPA users. Notably, current IPV was associated with choice of DMPA over the IUD or implant, implying that a desire to choose a hidden method may be important to some women and should be included in counseling. In contraceptive counseling, after screening for IPV, assessing patient's stress and taking a history about past contraceptive use, clinicians should discuss whether these factors might affect a patient's choice of method.


A Family Affair: Family Typologies of Problems and Midlife Well-Being.
Midlife adults are a "pivot" generation, responding to parents' and grown children's problems. Yet, some midlife adults may have families where multiple members suffer sorrows, whereas other midlife adults may have families with few problems. This study examined: (a) typologies of problems across generations and (b) associations between profiles of problems and midlife adults' well-being. Midlife adults (N = 633) reported their own, each parent's (n = 868), and grown child's (n = 1,785) physical (e.g., injury, cancer), psychological (e.g., anxiety, addiction), and lifestyle problems (e.g., divorce, job loss), and parents' functional disabilities. Midlife adults reported their own depressive symptoms. Latent profile analysis revealed four family typologies: (a) lowest problems across generations (n = 364), (b) offspring and midlife adult moderate problems, parent high physical problems and disability (n = 165), (c) offspring and parent moderate problems (n = 90), and (d) offspring highest problems (n = 14). Midlife adults in the lowest problems group (Profile a) reported higher income and fewer depressive symptoms than midlife adults in the other groups. Midlife adults cope with challenges when grown children or parents suffer problems, and their well-being may suffer as a result. In this study, regardless of the profile, higher problems in either generation were associated with more depressive symptoms for midlife adults.


Failure of demonstrated clinical efficacy of antibiotic-bonded continuous ambulatory peritoneal dialysis (CAPD) catheters.
Previous in vitro, in vivo, and a preliminary clinical report have demonstrated efficacy of noncovalently bonding antibiotics to the surface of continuous ambulatory peritoneal dialysis (CAPD) catheters in decreasing infectious complications. A larger prospective randomized clinical trial was completed. Eighty-six patients with chronic renal failure were enrolled in the study and randomized to receive either a surfactant treated or untreated control catheter. All catheters were soaked in cefoxitin at the time of insertion. Groups were comparable in terms of pre-existing illnesses, age, and gender. No differences were shown in the incidence of catheter-tract infections, peritonitis or mechanical complications. There was also no differences in microbiologic culture results. Therefore, it is concluded that this clinical trial did not demonstrate a reduction in catheter-related infectious complications by antibiotic bonding.


A Formidable Foe Is Sabotaging Your Results: What You Should Know about Biofilms and Wound Healing.
After reading this article, the participant should be able to: 1. Describe biofilm pathogenesis as it relates to problem wounds. 2. Understand the preclinical and clinical evidence implicating biofilm in problem wounds. 3. Explain the diagnostic and treatment challenges that biofilms create for problem wounds. 4. Demonstrate a basic understanding of emerging strategies aimed at counteracting these processes. Biofilm represents a protected mode of growth for bacteria, allowing them to evade standard diagnostic techniques and avoid eradication by standard therapies. Although only recently discovered, biofilm has existed for millennia and complicates nearly every aspect of medicine. Biofilm impacts wound healing by allowing bacteria to evade immune responses, prolonging inflammation and disabling skin barrier function. It is important to understand why problem wounds persist despite state-of-the-art treatment, why they are difficult to accurately diagnose, and why they recur. The aim of this article is to focus on current gaps in knowledge related to problem wounds, specifically, biofilm infection.


Observation of the χ_{b1}(3P) and χ_{b2}(3P) and Measurement of their Masses.
The χ_{b1}(3P) and χ_{b2}(3P) states are observed through their ϒ(3S)γ decays, using an event sample of proton-proton collisions collected by the CMS experiment at the CERN LHC. The data were collected at a center-of-mass energy of 13 TeV and correspond to an integrated luminosity of 80.0 fb^{-1}. The ϒ(3S) mesons are identified through their dimuon decay channel, while the low-energy photons are detected after converting to e^{+}e^{-} pairs in the silicon tracker, leading to a χ_{b}(3P) mass resolution of 2.2 MeV. This is the first time that the J=1 and 2 states are well resolved and their masses individually measured: 10513.42±0.41(stat)±0.18(syst) MeV and 10524.02±0.57(stat)±0.18(syst) MeV; they are determined with respect to the world-average value of the ϒ(3S) mass, which has an uncertainty of 0.5 MeV. The mass splitting is measured to be 10.60±0.64(stat)±0.17(syst) MeV.


Regulation of glycolytic flux in ischemic preconditioning. A study employing metabolic control analysis.
Exact adjustment of the Embden-Meyerhof pathway (EMP) is an important issue in ischemic preconditioning (IP) because an attenuated ischemic lactate accumulation contributes to myocardial protection. However, precise mechanisms of glycolytic flux and its regulation in IP remain to be elucidated. In open chest pigs, IP was achieved by two cycles of 10-min coronary artery occlusion and 30-min reperfusion prior to a 45-min index ischemia and 120-min reperfusion. Myocardial contents in glycolytic intermediates were assessed by high performance liquid chromatographic analysis of serial myocardial biopsies under control conditions and IP. Detailed time courses of metabolite contents allow an in-depth description of EMP regulation during index ischemia using metabolic control analysis. IP reduced myocardial infarct size (control, 90.0 +/- 3.1 versus 5.05 +/- 2.1%; p < 0.001) and attenuated myocardial lactate accumulation (end-ischemic contents, 31.9 +/- 4.47 versus 10.3 +/- 1.26 micromol/wet weight, p < 0.0001), whereby a decrease in anaerobic glycolytic flux by at least 70% could constantly be observed throughout index ischemia. By calculation of flux:metabolite co-responses, the mechanisms of glycolytic regulation were investigated. The continuous deceleration of EMP flux in control myocadium could neither be explained on the basis of substrate availability nor be attributed to regulatory "key enzymes," as multisite regulation was employed for flux adjustment. In myocardium subjected to IP, an even pronounced deceleration of EMP flux during index ischemia was observed. Again, the adjustment of EMP flux was because of multisite modulation without any evidence for flux limitation by substrate availability or a key enzyme. However, IP changed the regulatory properties of most EMP enzymes, and some of these patterns could not be explained on the basis of substrate kinetics. Instead, other regulatory mechanisms, which have previously not yet been described for EMP enzymes, must be considered. These altered biochemical properties of the EMP enzymes have not yet been described.


Fenfluramine-induced hyperthermia and stimulation in the rabbit.
Fenfluramine produces dose-related hyperthermia and behavioral stimulation in rabbits following intravenous administration. Both responses were antagonized by pretreatment with cinanserin, cyproheptadine, or fluxetine. Methergoline likewise abolished the stimulatory effect of fenfluramine and produced a partial blockade of the hyperthermia. Haloperidol was ineffective as a fenfluramine antagonist. This study demonstrates that fenfluramine-induced hyperthermia and stimulation in the rabbit result from an indirect action upon serotonergic receptors.


Influences of self-beliefs, social support, and comfort in the university environment on the academic nonpersistence decisions of American Indian undergraduates.
This study investigated the influence of self-beliefs, social support, and comfort in the university environment on the academic nonpersistence decisions of 83 American Indian undergraduates. The self-belief construct comprised self-esteem and 2 dimensions of college-related self-efficacy. The social support cluster consisted of 3 variables: family support, friend support, and perception of being mentored. The 3rd cluster, comfort in the university environment, was measured by perceptions of university environment, cultural congruity, and college stress. Although each of the 3 constructs significantly accounted for academic nonpersistence decisions, social support was the strongest predictor, followed by comfort in the university environment, and then self-beliefs. Students who perceived being mentored were more likely to report decreased nonpersistence decisions. Similarly, students who had more positive perceptions of the university environment were more likely to make fewer nonpersistence decisions. Finally, higher self-esteem and greater college-related self-efficacy were associated with decreased nonpersistence decisions. Research-informed practice implications for increasing the academic persistence of American Indian students include fostering mentoring relationships and providing interventions to increase social support, self-esteem, and self-efficacy.


A comparative study of the effects of electrical stimulation and laser treatment on experimental wound healing in rats.
We investigated the effects of electrical stimulation (ES) and laser treatment on wound healing in rats. A randomized-controlled trial, conducted at the Experimental and Clinical Research Centre of Erciyes University (Kayseri, Turkey), divided 124 healthy female Swiss-Albino rats into four groups. A 6 cm linear incision was made at the dorsal skin of all rats. Group 1 was given a constant direct current of 300 microA for 30 min per day. The current was applied in negative polarity for the first 3 days and in positive polarity for the next 7 days. Group 3 received a full-contact, continuous gallium-arsenide (GaAs) laser therapy, with a wavelength of 904 nm, an energy density of 1 J/cm2, and an average power of 6 mW for 10 min per day. The remaining two groups (Groups 2 and 4) were considered the control groups and received sham treatment. All groups were treated for 10 days. Histopathologic and biochemical evaluations were conducted on 10 rats from each group on the 4th and 10th days, and wound breaking strength was measured for biomechanical evaluation on the 25th day of the study. Both ES and laser treatment proved significantly effective in the inflammatory phase compared with control groups (p < 0.05); however, the ES was even more effective than laser treatment, with more significant results (p < 0.05). In the proliferation and maturation phases, while ES and laser treatment were both found to be significantly effective treatment methods compared with the control groups, no statistically significant difference was observed between the two treatment groups (p > 0.05). Although ES and laser treatment both were effective in the maturation phase, increasing wound breaking strength compared with their control groups (p < 0.05), there was no statistically significant difference between the two treatment groups (p > 0.05). We conclude that ES and laser treatment both have beneficial effects during the inflammatory, proliferation, and maturation phases of a wound. Both ES and laser treatment can be used successfully in decubitis ulcers and chronic wounds, in combination with conventional therapies such as daily care and debridement of wounds; however, ES has more beneficial effects during the inflammatory phase in some parameters than laser treatment.


Consumption of Different Egg-Based Diets Alters Clinical Metabolic and Hematological Parameters in Young, Healthy Men and Women.
Eggs-particularly egg yolks-are a rich source of bioactive nutrients and dietary compounds that influence metabolic health, lipid metabolism, immune function, and hematopoiesis. We investigated the effects of consuming an egg-free diet, three egg whites per day, and three whole eggs per day for 4 weeks on comprehensive clinical metabolic, immune, and hematologic profiles in young, healthy adults (18-35 y, BMI < 30 kg/m2 or <30% body fat for men and <40% body fat for women, n = 26) in a 16-week randomized, crossover intervention trial. We observed that average daily macro- and micronutrient intake significantly differed across egg diet periods, including greater intake of choline during the whole egg diet period, which corresponded to increased serum choline and betaine without altering trimethylamine N-oxide. Egg white and whole egg intake increased serum isoleucine while whole egg intake reduced serum glycine-markers of increased and decreased risk of insulin resistance, respectively-without altering other markers of glucose sensitivity or inflammation. Whole egg intake increased a subset of large HDL particles (H6P, 10.8 nm) and decreased the total cholesterol:HDL-cholesterol ratio and % monocytes in female participants using combined oral contraceptive (COC) medication (n = 11) as compared to female non-users (n = 10). Whole egg intake further increased blood hematocrit whereas egg white and whole egg intake reduced blood platelet counts. Changes in clinical immune cell counts between egg white and whole egg diet periods were negatively correlated with several HDL parameters yet positively correlated with measures of triglyceride-rich lipoproteins and insulin sensitivity. Overall, the intake of whole eggs led to greater overall improvements in micronutrient diet quality, choline status, and HDL and hematologic profiles while minimally-yet potentially less adversely-affecting markers of insulin resistance as compared to egg whites.


Development and validation of disease-specific measures for choroidal melanoma: COMS-QOLS report No. 2.
To develop and validate scales measuring common concerns of patients with choroidal melanoma: perception of appearance, concern about cancer recurrence, and difficulty with vision-dependent activities requiring stereopsis or binocularity. Cross-sectional study within a randomized multicenter clinical trial. Eight-hundred forty-two of 1317 patients with choroidal melanoma enrolled in the Collaborative Ocular Melanoma Study (COMS) for medium-sized tumors and randomized to receive iodine 125 brachytherapy or enucleation were interviewed. Scale reliability was evaluated using Cronbach's alpha, and validity was investigated through correlation with existing scales and with data collected during COMS clinical examinations. All 3 proposed scales had good internal consistency reliability. The appearance and recurrence scales had low to moderate correlation with the 36-Item Short-Form Health Survey mental health scale (r = 0.26 and 0.31, respectively) and with the the Hospital Anxiety and Depression Scale depression (r = -0.22 and -0.19) and anxiety (r = -0.27 and -0.42) scales. Appearance scores were significantly associated with occurrence of appearance-altering complications and conditions, recurrence scores were associated with recent removal of the brachytherapy-treated eye, and stereopsis/binocularity scores were higher in patients with good visual acuity in both eyes than in those with good visual acuity in one eye and an enucleated fellow eye. All 3 proposed scales have good internal consistency, range, and SDs of measurement in the tested population. Based on clinical data, there is evidence of good construct validity for all 3 scales, although there also is evidence that the stereopsis/binocularity scale is sensitive to other aspects of vision in addition to stereopsis and binocularity. The appearance and recurrence scales capture clinically relevant information not available from standard mental health scales.


Distrust and the positive test heuristic: dispositional and situated social distrust improves performance on the Wason rule discovery task.
Feelings of distrust alert people not to take information at face value, which may influence their reasoning strategy. Using the Wason (1960) rule identification task, we tested whether chronic and temporary distrust increase the use of negative hypothesis testing strategies suited to falsify one's own initial hunch. In Study 1, participants who were low in dispositional trust were more likely to engage in negative hypothesis testing than participants high in dispositional trust. In Study 2, trust and distrust were induced through an alleged person-memory task. Paralleling the effects of chronic distrust, participants exposed to a single distrust-eliciting face were 3 times as likely to engage in negative hypothesis testing as participants exposed to a trust-eliciting face. In both studies, distrust increased negative hypothesis testing, which was associated with better performance on the Wason task. In contrast, participants' initial rule generation was not consistently affected by distrust. These findings provide first evidence that distrust can influence which reasoning strategy people adopt.


Modular and Tunable Alternative Surfactants for Biopharmaceuticals Provide Insights into Surfactant's Structure-Function Relationship.
Surface-induced aggregation of protein therapeutics is opposed by employing surfactants, which are ubiquitously used in drug product development, with polysorbates being the gold standard. Since poloxamer 188 is currently the only generally accepted polysorbate alternative, but cannot be ubiquitously applied, there is a strong need to develop surfactant alternatives for protein biologics that would complement and possibly overcome known drawbacks of existing surfactants. Yet, a severe lack of structure-function relationship knowledge complicates the development of new surfactants. Herein, we perform a systematic analysis of the structure-function relationship of three classes of novel alternative surfactants. Firstly, the mode of action is thoroughly characterized through tensiometry, calorimetry and MD simulations. Secondly, the safety profiles are evaluated through cell-based in vitro essays. Ultimately, we could conclude that the alternative surfactants investigated possess a mode of action and safety profile comparable to polysorbates. Moreover, the biophysical patterns elucidated here can be exploited to precisely tune the features of future surfactant designs.


The large subunit of initiation factor aIF2 is a close structural homologue of elongation factors.
The heterotrimeric factor e/aIF2 plays a central role in eukaryotic/archaeal initiation of translation. By delivering the initiator methionyl-tRNA to the ribosome, e/aIF2 ensures specificity of initiation codon selection. The three subunits of aIF2 from the hyperthermophilic archaeon Pyrococcus abyssi could be overproduced in Escherichia coli. The beta and gamma subunits each contain a tightly bound zinc. The large gamma subunit is shown to form the structural core for trimer assembly. The crystal structures of aIF2gamma, free or complexed to GDP-Mg(2+) or GDPNP-Mg(2+), were resolved at resolutions better than 2 A. aIF2gamma displays marked similarities to elongation factors. A distinctive feature of e/aIF2gamma is a subdomain containing a zinc-binding knuckle. Examination of the nucleotide-complexed aIF2gamma structures suggests mechanisms of action and tRNA binding properties similar to those of an elongation factor. Implications for the mechanism of translation initiation in both eukarya and archaea are discussed. In particular, positioning of the initiator tRNA in the ribosomal A site during the search for the initiation codon is envisaged.


Choline acetyltransferase activity is increased in combined cultures of spinal cord and muscle cells from mice.
The activity of choline acetyltransferase was more than tenfold greater in combined cultures of spinal cord and muscle cells than in cultures of spinal cord cells alone. This increase was associated with the formation of functional neuromuscular junctions in culture. Counts of silver-stained cells and determinations of other enzyme activities indicated that the increased choline acetyltransferase activity was not due to nonspecific neuronal survival but reflected greater activity in the surviving neurons. Hence, muscle had a marked, highly specific trophic effect on the cholinergic neurons that innervated it.


New insight into clinical heterogeneity and inheritance diversity of FBLN5-related cutis laxa.
FBLN5-related cutis laxa (CL) is a rare disorder that involves elastic fiber-enriched tissues and is characterized by lax skin and variable systemic involvement such as pulmonary emphysema, arterial involvement, inguinal hernias, hollow viscus diverticula and pyloric stenosis. This type of CL follows mostly autosomal recessive (AR) and less commonly autosomal dominant patterns of inheritance. In this study, we detected a novel homozygous missense variant in exon 6 of FBLN5 gene (c.G544C, p.A182P) by using whole exome sequencing in a consanguineous Iranian family with two affected members. Our twin patients showed some of the clinical manifestation of FBLN5-related CL but they did not present pulmonary complications, gastrointestinal and genitourinary abnormalities. The notable thing about this monozygotic twin sisters is that only one of them showed ventricular septal defect, suggesting that this type of CL has intrafamilial variability. Co-segregation analysis showed the patients' parents and relatives were heterozygous for detected variation suggesting AR form of the CL. In silico prediction tools showed that this mutation is pathogenic and 3D modeling of the normal and mutant protein revealed relative structural alteration of fibulin-5 suggesting that the A182P can contribute to the CL phenotype via the combined effect of lack of protein function and partly misfolding-associated toxicity. We underlined the probable roles and functions of the involved domain of fibulin-5 and proposed some possible mechanisms involved in AR form of FBLN5-related CL. However, further functional studies and subsequent clinical and molecular investigations are needed to confirm our findings.


Diagnostic Utility of Measuring Cerebral Atrophy in the Behavioral Variant of Frontotemporal Dementia and Association With Clinical Deterioration.
The presence of atrophy on magnetic resonance imaging can support the diagnosis of the behavioral variant of frontotemporal dementia (bvFTD), but reproducible measurements are lacking. To assess the diagnostic and prognostic utility of 6 visual atrophy scales (VAS) and the Magnetic Resonance Parkinsonism Index (MRPI). In this diagnostic/prognostic study, data from 235 patients with bvFTD and 225 age- and magnetic resonance imaging-matched control individuals from 3 centers were collected from December 1, 1998, to September 30, 2019. One hundred twenty-one participants with bvFTD had high confidence of frontotemporal lobar degeneration (FTLD) (bvFTD-HC), and 19 had low confidence of FTLD (bvFTD-LC). Blinded clinicians applied 6 previously validated VAS, and the MRPI was calculated with a fully automated approach. Cortical thickness and subcortical volumes were also measured for comparison. Data were analyzed from February 1 to June 30, 2020. The main outcomes of this study were bvFTD-HC or a neuropathological diagnosis of 4-repeat (4R) tauopathy and the clinical deterioration rate (assessed by longitudinal measurements of Clinical Dementia Rating Sum of Boxes). Measures of cerebral atrophy included VAS scores, the bvFTD atrophy score (sum of VAS scores in orbitofrontal, anterior cingulate, anterior temporal, medial temporal lobe, and frontal insula regions), the MRPI, and other computerized quantifications of cortical and subcortical volumes. The areas under the receiver operating characteristic curve (AUROC) were calculated for the differentiation of participants with bvFTD-HC and bvFTD-LC and controls. Linear mixed models were used to evaluate the ability of atrophy measures to estimate longitudinal clinical deterioration. Of the 460 included participants, 296 (64.3%) were men, and the mean (SD) age was 62.6 (11.4) years. The accuracy of the bvFTD atrophy score for the differentiation of bvFTD-HC from controls (AUROC, 0.930; 95% CI, 0.903-0.957) and bvFTD-HC from bvFTD-LC (AUROC, 0.880; 95% CI, 0.787-0.972) was comparable to computerized measures (AUROC, 0.973 [95% CI, 0.954-0.993] and 0.898 [95% CI, 0.834-0.962], respectively). The MRPI was increased in patients with bvFTD and underlying 4R tauopathies compared with other FTLD subtypes (14.1 [2.0] vs 11.2 [2.6] points; P < .001). Higher bvFTD atrophy scores were associated with faster clinical deterioration in bvFTD (1.86-point change in Clinical Dementia Rating Sum of Boxes score per bvFTD atrophy score increase per year; 95% CI, 0.99-2.73; P < .001). Based on these study findings, in bvFTD, VAS increased the diagnostic certainty of underlying FTLD, and the MRPI showed potential for the detection of participants with underlying 4R tauopathies. These widely available measures of atrophy can also be useful to estimate longitudinal clinical deterioration.


Urine-based testing for Chlamydia trachomatis among young adults in a population-based survey in Croatia: feasibility and prevalence.
We assessed the feasibility of collecting urine samples for testing on genital Chlamydia trachomatis infection in a population-based survey, and prevalence of this infection among young people aged 18-25 in Croatia. In Croatia, as in the other countries of Eastern Europe, there is a lack of data on prevalence of C. trachomatis in the general population, including young adults. We sampled participants using a nationally representative, multi-stage stratified probability sample of young men and women. Detection of C. trachomatis DNA in urine samples was performed by using a real-time PCR assay COBAS® TaqMan® CT Test, v2.0. Overall, 1005 young adults participated in the behavioural part of the survey, and 27.9% men and 37.5% women who were sexually experienced agreed to provide urine samples for testing on C. trachomatis. Using multivariate analysis, women were significantly more likely to provide urine samples than men (aOR = 1.53, 95% CI 1.14-2.06) as were those who reported no condom use at last intercourse (aOR = 1.95, 95% CI 1.44-2.62). Prevalence of C. trachomatis infection among those who were sexually experienced was 7.3% in men and 5.3% in women. Population-based surveys that use probabilistic sampling are a feasible way to obtain population estimates of C. trachomatis prevalence among young adults in Croatia, but it is challenging to obtain an adequate response rate. The prevalence of C. trachomatis among young adults in Croatia found in this study was higher than that found in other European countries with similar survey response rates.


Extending access to essential services against constraints: the three-tier health service delivery system in rural China (1949-1980).
China has made remarkable progress in scaling up essential services during the last six decades, making health care increasingly available in rural areas. This was partly achieved through the building of a three-tier health system in the 1950s, established as a linked network with health service facilities at county, township and village level, to extend services to the whole population. We developed a Theory of Change to chart the policy context, contents and mechanisms that may have facilitated the establishment of the three-tier health service delivery system in rural China. We systematically synthesized the best available evidence on how China achieved universal access to essential services in resource-scarce rural settings, with a particular emphasis on the experiences learned before the 1980s, when the country suffered a particularly acute lack of resources. The search identified only three peered-reviewed articles that fit our criteria for scientific rigor. We therefore drew extensively on government policy documents, and triangulated them with other publications and key informant interviews. We found that China's three-tier health service delivery system was established in response to acute health challenges, including high fertility and mortality rates. Health system resources were extremely low in view of the needs and insufficient to extend access to even basic care. With strong political commitment to rural health and a "health-for-all" policy vision underlying implementation, a three-tier health service delivery model connecting villages, townships and counties was quickly established. We identified several factors that contributed to the success of the three-tier system in China: a realistic health human resource development strategy, use of mass campaigns as a vehicle to increase demand, an innovative financing mechanisms, public-private partnership models in the early stages of scale up, and an integrated approach to service delivery. An implementation process involving gradual adaptation and incorporation of the lessons learnt was also essential. China's 60 year experience in establishing a de-professionalized, community-based, health service delivery model that is economically feasible, institutionally and culturally appropriate mechanism can be useful to other low- and middle-income countries (LMICs) seeking to extend essential services. Lessons can be drawn from both reform content and from its implementation pathway, identifying the political, institutional and contextual factors shaping the three-tier delivery model over time.


Universal precautions: improving the knowledge of trained nurses.
Universal precautions relate to the management of blood-borne viruses such as human immunodeficiency virus (HIV) and hepatitis B and C. Advice on the transmission of blood-borne viruses and the precautionary measures used to reduce or eliminate cross-infection have been addressed by national and professional bodies. There is a significant amount of research which assesses trained nurses' knowledge of universal precautions and includes understanding of the transmission routes of blood-borne viruses and the measures required to prevent cross-infection. However, the majority of the literature indicates an incomplete knowledge among trained nurses of the principles and application of universal precautions. The ability of the trained nurse to fulfil his/her role as health educator, teacher and therefore effective infection control practitioner is questioned by the literature. This article discusses the role of education in improving the knowledge of trained nurses and considers the implementation of in-service training and preregistration education.


Feasibility of northern Thai factory workers as participants in HIV vaccine trials.
To determine the feasibility of establishing a cohort of HIV-1 seronegative factory workers for potential HIV vaccine trials, and other HIV preventive interventions, we enroled and followed 499 male and female industrial workers in Lamphun Province, northern Thailand. A baseline demographic and HIV seroprevalence survey was conducted by a mobile team at worker's housing units in Lamphun Province in 1994. Follow-up HIV and syphilis incidence rates were measured 6 months later. The study was voluntary, anonymous, and included HIV pre- and post-test counseling, HIV and syphilis serology, and a self-administered fact sheet. A total of 106 men and 393 women were recruited. The median age was 22 years, and the mean 23.4 years. Educational levels were moderate; 41.9% had some secondary school and 23.6% had completed secondary school. HIV prevalence was 2.4% overall but differed by sex; among men it was 7/106, 6.6%, among women 5/393, 1.3%, OR = 5.49 (95% CI = 1.52, 20.39). Low educational levels were associated with HIV infection, OR = 7.2 (95% CI = 2.2, 23.4). Syphilis prevalence was 3.8%. Follow-up at 6 months was successful for 420/499 subjects, 84.2%, and varied by sex: 73/106 men, 68.9%, returned while 347/393 women, 88.3%, did so, RR = 1.21 (95% CI = 1.07, 1.37). There were 5 incident HIV-1 infections, a rate of 2.1/100 person years. The HIV seroconversion rate differed by sex, but not significantly; it was 4.1/100 person years for men and 1.5/100 person years for women. This population is largely young, female, and at considerable HIV risk. If follow-up could be improved, factory workers in northern Thailand could be an appropriate population in which to mount HIV preventive efficacy studies, including vaccine trials.


Measuring mass of nanoparticles and viruses in liquids with nanometer-scale pores.
Nanopores have recently been developed for the detection and physical characterization of nanoparticles, viruses, proteins, nucleic acids, and other macromolecules in liquids. The method provides the ability to rapidly estimate the size and electrical charge of analytes over a wide range of concentration, potentially with small sample volumes and low cost. Here, we use the technique to measure the mass of nanoparticles and viruses and their sedimentation. The analyte sedimentation-time measurement provides an estimate for the nanoparticle mass-density. We also show that the method can be used with samples at low concentration and in small volumes.


Potential of agroindustrial waste from olive oil industry for fuel ethanol production.
Olive pulp (OP) is a highly polluting semi-solid residue generated from the two-stage extraction processing of olives and is a major environmental issue in Southern Europe, where 80% of the world olive oil is produced. At present, OP is either discarded to the environment or combusted with low calorific value. In this work, utilization of OP as a potential substrate for production of bioethanol was studied. Enzymatic hydrolysis and subsequent glucose fermentation by baker's yeast were evaluated for OP from 10% to 30% dry matter (i.e., undiluted). Enzymatic hydrolysis resulted in an increase in glucose concentration by 75%, giving final glucose yields near 70%. Fermentation of undiluted OP hydrolysate (OPH) resulted in the maximum ethanol produced (11.2 g/L) with productivity of 2.1 g/L/h. Ethanol yields were similar for all tested OPH concentrations and were in the range of 0.49-0.51 g/g. Results showed that yeast could effectively ferment OPH even without nutrient addition, revealing the tolerance of yeast to OP toxicity. Because of low xylan (12.4%) and glucan (16%) content in OP, this specific type of OP is not a suitable material for producing only ethanol and thus, bioethanol production should be integrated with production of other value-added products.


Single-cell sequencing analysis related to sphingolipid metabolism guides immunotherapy and prognosis of skin cutaneous melanoma.
We explore sphingolipid-related genes (SRGs) in skin melanoma (SKCM) to develop a prognostic indicator for patient outcomes. Dysregulated lipid metabolism is linked to aggressive behavior in various cancers, including SKCM. However, the exact role and mechanism of sphingolipid metabolism in melanoma remain partially understood. We integrated scRNA-seq data from melanoma patients sourced from the GEO database. Through the utilization of the Seurat R package, we successfully identified distinct gene clusters associated with patient survival in the scRNA-seq data. Key prognostic genes were identified through single-factor Cox analysis and used to develop a prognostic model using LASSO and stepwise regression algorithms. Additionally, we evaluated the predictive potential of these genes within the immune microenvironment and their relevance to immunotherapy. Finally, we validated the functional significance of the high-risk gene IRX3 through in vitro experiments. Analysis of scRNA-seq data identified distinct expression patterns of 4 specific genes (SRGs) in diverse cell subpopulations. Re-clustering cells based on increased SRG expression revealed 7 subgroups with significant prognostic implications. Using marker genes, lasso, and Cox regression, we selected 11 genes to construct a risk signature. This signature demonstrated a strong correlation with immune cell infiltration and stromal scores, highlighting its relevance in the tumor microenvironment. Functional studies involving IRX3 knockdown in A375 and WM-115 cells showed significant reductions in cell viability, proliferation, and invasiveness. SRG-based risk signature holds promise for precise melanoma prognosis. An in-depth exploration of SRG characteristics offers insights into immunotherapy response. Therapeutic targeting of the IRX3 gene may benefit melanoma patients.


Hepatitis A virus cDNA and its RNA transcripts are infectious in cell culture.
A full-length cDNA copy of an attenuated, cell culture-adapted hepatitis A virus (HAV HM-175/7 MK-5) genome was constructed in the PstI site of plasmid vector pBR322. Transfection of monkey kidney cells with this plasmid failed to induce the production of hepatitis A virus (HAV). The HAV cDNA was excised from pBR322 and inserted, without the oligo(dG) X oligo(dC) tails, into an RNA transcription vector to yield plasmid pHAV/7. Transfection of monkey kidney cells with pHAV/7 DNA induced HAV infection. Transfection with RNA transcripts produced in vitro from pHAV/7 yielded about 10-fold more HAV than did transfection with pHAV/7 DNA. Marmosets inoculated with transfection-derived virus developed anti-HAV antibodies and had liver enzyme patterns that closely resembled the liver enzyme patterns seen in animals inoculated with virus from a comparable level of cell culture passage. Infectious RNA transcripts from HAV cDNA should be useful for studying the molecular basis of cell culture adaptation and attenuation as well as for studying specific viral functions.


Efficacy of prophylaxis and genotype-phenotype correlation in patients with severe Factor X deficiency in Iran.
We aimed to evaluate the effect of regular prophylaxis with a Factor X (FX) concentrate for patients with severe FXD in Iran and to assess the correlation of the genotype and phenotype in these patients. Ten patients with severe FXD (FX activity <1%) were enrolled and characterized during 2010-2011. Prophylaxis with 20 IU FX P Behring per kg body weight was administered once a week. FX levels, were monitored at baseline, 15 and 30 min, 1, 3, 6, 12, 24, 48, 72 and 96 h after starting prophylaxis. All patients were followed for 1 year. The mean age of the patients was 15 ± 7.8 years (age range of: 6-27 years). One patient had anaphylactic reaction after the first infusion, and the treatment was stopped. During one-year follow-up after starting prophylaxis, no bleeding symptoms occurred in any patient who tolerated and remained on the prophylaxis programme and all of them had a FX level of 1% or above. The maximum level of FX activity has been observed at 15 min after starting prophylaxis. A level of 1.5-3.5% was detected after 96 h. Homozygous mutations p.Arg40Thr (Arg-1Thr), p.Gly51Arg and p.Glu69Lys were detected in patients with intracranial haemorrhage. In our patients, significant decrease in symptoms without any complication after administration of FX, was demonstrated in all except one patient who had an anaphylactic reaction. It seems that the dose of 20 IU kg(-1) could be probably the best choice for patients with severe FXD, who require regular prophylaxis.


Hostilities faced by people on the frontlines of sexual and reproductive health and rights: a scoping review.
Frontline workers for sexual and reproductive health and rights (SRHR) provide life-changing and life-saving services to millions of people every year. From accompanying the pregnant, delivering babies and caring for the newborn to supporting those subjected to sexual violence; from treating debilitating infections to expanding contraceptive choices; from enabling access to safe abortion services to countering homophobia: all over the world frontline SRHR carers and advocates make it possible for so many more to experience dignity in sex, sexuality and reproduction. Yet they are also subjected to hostility for what they do, for whom they provide care, for where they work and for the issues they address. From ostracistion and harassment in the workplace to verbal threats and physical violence, hostilities can extend even into their private lives. In other words, as SRHR workers seek to fulfil the human rights of others, their own human rights are put at risk. Yet, as grave as that is, it is a reality largely undocumented and thus also underestimated. This scoping review sets out to marshal what is known about how hostilities against frontline SRHR workers manifest, against whom, at whose hands and in which contexts. It is based on review of six sources: peer-reviewed and grey literature, news reports, sector surveys, and consultations with sector experts and, for contrast, literature issued by opposition groups. Each source contributes a partial picture only, yet taken together, they show that hostilities against frontline SRHR workers are committed the world over-in a range of countries, contexts and settings. Nevertheless, the narratives given in those sources more often treat hostilities as 'one-off', exceptional events and/or as an 'inevitable' part of daily work to be tolerated. That works in turn both to divorce such incidents from their wider historical, political and social contexts and to normalise the phenomena as if it is an expected part of a role and not a problem to be urgently addressed. Our findings confirm that the SRHR sector at large needs to step-up its response to such reprisals in ways more commensurate with their scale and gravity.


Characterization of FtsH Essentiality in Streptococcus mutans via Genetic Suppression.
FtsH belongs to the AAA+ ATP-dependent family of proteases, which participate in diverse cellular processes and are ubiquitous among bacteria, chloroplasts, and mitochondria. FtsH is poorly characterized in most organisms, especially compared to other major housekeeping proteases. In the current study, we examined the source of FtsH essentiality in the human oral microbiome species Streptococcus mutans, one of the primary etiological agents of dental caries. By creating a conditionally lethal ftsH mutant, we were able to identify a secondary suppressor missense mutation in the vicR gene, encoding the response regulator of the essential VicRK two-component system (TCS). Transcriptomic analysis of the vicR (G195R) mutant revealed significantly reduced expression of 46 genes, many of which were located within the genomic island Tnsmu2, which harbors the mutanobactin biosynthetic gene cluster. In agreement with the transcriptomic data, deletion of the mutanobactin biosynthetic gene cluster suppressed ftsH essentiality in S. mutans. We also explored the role of FtsH in S. mutans physiology and demonstrated its critical role in stress tolerance, especially acid stress. The presented results reveal the first insights within S. mutans for the pleiotropic regulatory function of this poorly understood global regulator.


T cell-mediated induction of thymic stromal lymphopoietin in differentiated human primary bronchial epithelial cells.
Inhaled peptide challenge has been shown to induce T cell-mediated, isolated late asthmatic reaction (LAR), characterized by recruitment of CD4(+) T cells and increased levels of thymus and activation-regulated chemokine (TARC; CCL17). Epithelial-derived thymic stromal lymphopoietin (TSLP) has been shown to modulate dendritic cell function to promote TH 2 responses via CCL17 production. To elucidate the mechanisms involved in allergen-specific T cell-induced LAR and recruitment of CD4(+) T cells by examining the effects of T cell-derived factors on the induction of TSLP in primary bronchial epithelial cells (PBEC). PBEC grown at air-liquid interface from healthy individuals and patients with asthma were stimulated with double-stranded RNA (dsRNA) or supernatants from activated allergen-specific T cells. TSLP was measured in PBEC culture supernatants. Neutralizing antibodies and signalling inhibitors were used to examine the mechanisms responsible for the induction of epithelial-derived TSLP. The functional activity of PBEC-derived TSLP was measured using a bioassay involving the induction of CCL17 production from monocyte-derived dendritic cells (moDC). Both dsRNA and allergen-specific T cells induced enhanced TSLP secretion from asthmatic PBEC compared to healthy PBEC. Activated PBEC culture supernatant induced TSLP-dependent CCL17 production from moDC in a manner related to clinical asthmatic status. IL-1β, IL-6, and CXCL8, rather than TH 2 cytokines (IL-4/5/13), appeared to be the principle mediators of allergen-specific T cell-dependent induction of epithelial-derived TSLP, which was regulated by the MEK, MAPK, and NFκB pathways. Our data reveal a novel effect of allergen-specific T cells as a positive regulator of TSLP production by epithelial cells, suggesting T cell-airway epithelium interactions that may lead to maintenance and amplification of allergic inflammation. TSLP is currently a candidate for therapeutic intervention in asthma, but the factors that drive TSLP expression (T cell-derived factors) may be equally relevant in the treatment of allergic inflammation.


Confocal microscopic characterization of wound repair after photorefractive keratectomy.
Development of postoperative corneal haze and regression of refractive effect are unfavorable clinical complications of excimer laser photorefractive keratectomy (PRK). Although exact mechanisms remain to be elucidated, these outcomes have been attributed to post-PRK corneal wound healing. The purpose of this study was to evaluate corneal wound repair quantitatively after PRK in a rabbit model using a newly developed in vivo technique, termed confocal microscopy through focusing (CMTF). Twelve rabbit corneas received a monocular, 6-mm diameter, 9.0-diopter PRK myopic correction. Animals were evaluated sequentially up to 6 months after surgery by in vivo CMTF, which uses an image-intensity depth profile to measure epithelial and stromal thickness and uses corneal light reflectivity as an objective estimate of corneal haze. At differing temporal intervals, in vivo morphology was correlated with ex vivo histology using fluorescence microscopy. One week after PRK, an acellular layer of 86 +/- 24 microns was found anteriorly in the remaining stroma, which demonstrated surgically induced keratocyte death. Underlying keratocytes became activated and migrated toward the wound bed; repopulation was completed within 3 weeks. One week after PRK, there was a significant increase (P < 0.001) in light reflections detected from the photoablated stromal surface (1745 +/- 262 U) and from the underlying activated fibroblasts (713 +/- 607 U). Corneal reflectivity peaked at 3 weeks (4648 +/- 1263 U) and decreased linearly to 889 +/- 700 U by 6 months after the PRK; this corresponded to a reflectivity six times greater than the level seen in unoperated corneas. Two weeks after PRK, initial corneal edema had resolved, revealing an actual ablation depth (maximal stromal thinning) of 118 +/- 8 microns. Starting at 2 weeks after surgery, the stroma underwent gradual rethickening that reached 98% of the preoperative thickness at 6 months after PRK; at that time, only 6% of the initial photoablation depth persisted. By contrast, the central corneal epithelium showed no significant postoperative hyperplasia. Rabbit corneas treated by PRK showed a remarkable stromal wound-healing response that ultimately led to the restoration of the original stromal thickness by 6 months after surgery, demonstrating complete regression of the initial photoablative effect. Additionally, corneal wound healing was associated with increased light reflections from both the photoablated stromal surface and the activated wound-healing keratocytes underlying this area. Based on these findings, the authors hypothesize that the development of clinically observed corneal haze in PRK patients may be related, in part, to activation of corneal keratocytes and to putative changes in the extracellular matrix.


p14ARF interacts with the focal adhesion kinase and protects cells from anoikis.
The ARF protein functions as an important sensor of hyper-proliferative stimuli restricting cell proliferation through both p53-dependent and -independent pathways. Although to date the majority of studies on ARF have focused on its anti-proliferative role, few studies have addressed whether ARF may also have pro-survival functions. Here we show for the first time that during the process of adhesion and spreading ARF re-localizes to sites of active actin polymerization and to focal adhesion points where it interacts with the phosphorylated focal adhesion kinase. In line with its recruitment to focal adhesions, we observe that hampering ARF function in cancer cells leads to gross defects in cytoskeleton organization resulting in apoptosis through a mechanism dependent on the Death-Associated Protein Kinase. Our data uncover a novel function for p14ARF in protecting cells from anoikis that may reflect its role in anchorage independence, a hallmark of malignant tumor cells.


Poor oral health, a potential new geriatric syndrome.
This article presents a brief introduction to the medical aspects of ageing and age-related diseases, and to some geriatric syndromes, followed by a discussion on their impact on general and oral healthcare provision to community-dwelling older people. Recent investigations suggest that inflammation constitutes a biological foundation of ageing and the onset of age-related diseases. Multimorbidity and polypharmacy, together with alterations in pharmacokinetics and pharmacodynamics, make older people at risk of adverse medication reactions. A side effect of several medications is causing xerostomia and hyposalivation, and both the type and number of medications used are relevant. New options of general healthcare provision to community-dwelling older people are the use of mobility aids and assistive technology devices, domiciliary health care, respite care and telecare. Their oral health status may be jeopardised by frailty, disability, care dependency and limited access to professional oral health care. Recommendations for improvement are the following: better integrating oral health care into general health care, developing and implementing an oral healthcare guideline, providing customised oral hygiene care aids, domiciliary oral healthcare provision, visiting dental hygienists and/or nurses, oral hygiene telecare, easily and safely accessible dental offices, transforming dentistry into medical oral health care and upgrading dentists to oral physicians. In case oral healthcare providers do not take the responsibility of persuading society of the importance of adequate oral health, weakened oral health of community-dwelling older people will become a potential new geriatric syndrome.


Expression of p63 and Bcl-2 in Malignant Thyroid Tumors and their Correlation with other Diagnostic Immunocytochemical Markers.
Bcl-2 is a marker recently studied in thyroid tumours and proposed to have prognostic significance. p63 is expressed in a proportion of papillary thyroid carcinoma cases and may have a role in tumour progression. To study expression of Bcl2 and p63 in thyroid tumours and correlation of Bcl-2 with diagnostic markers including Thyroglobulin, Calcitonin and Carcinoembryonic antigen. Cytology smears of 35 cases of thyroid cancer were studied over a period of 18 months. In 20 cases histopathology was available. Immunocytochemistry for Bcl-2 and p63 was done, and diagnostic markers were applied as and when required. p63 showed focal nuclear expression in 46.1% of papillary thyroid carcinoma cases, and was negative in all other tumours. Bcl-2 was positive in 88.9% of follicular carcinomas, 100% of papillary carcinomas and 83.3% of medullary carcinoma cases, and showed focal weak expression in 40% of Anaplastic Carcinoma (ATC) cases, thereby signifying down regulation (p-value = 0.001). There was significant down regulation of Thyroglobulin (Tg) in ATC vs well differentiated follicular derived tumours (p-value ≤ 0.016). Positive correlation was noted between expression of Bcl-2 and Calcitonin (0.93) and Bcl-2 and Carcinoembryonic Antigen (CEA) (0.89), and weak positive correlation (0.65) between Tg and Bcl-2. Bcl-2 is downregulated in anaplastic carcinomas as compared to well differentiated thyroid tumours, and shows correlation with differentiation associated tumour antigens. Thus, loss of Bcl-2 was associated with loss of differentiation in thyroid tumours. Anaplastic carcinoma as such is associated with worse prognosis and loss of Bcl-2 may be partly responsible for the same. p63 is specific but less sensitive marker for PTC. Further studies are required to determine the role of Bcl-2 and p63 in thyroid tumours.


Focus on Notoginsenoside R1 in Metabolism and Prevention Against Human Diseases.
Notoginsenoside (NG)-R1 is one of the main bioactive compounds from Panax notoginseng (PN) root, which is well known in the prescription for mediating the micro-circulatory hemostasis in human. In this article, we mainly discuss NG-R1 in metabolism and the biological activities, including cardiovascular protection, neuro-protection, anti-diabetes, liver protection, gastrointestinal protection, lung protection, bone metabolism regulation, renal protection, and anti-cancer. The metabolites produced by deglycosylation of NG-R1 exhibit higher permeability and bioavailability. It has been extensively verified that NG-R1 may ameliorate ischemia-reperfusion (IR)-induced injury in cardiovascular and neuronal systems mainly by upregulating the activity of estrogen receptor α-dependent phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and nuclear factor erythroid-2-related factor 2 (NRF2) pathways and downregulating nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. However, no specific targets for NG-R1 have been identified. Expectedly, NG-R1 has been used as a main bioactive compound in many Traditional Chinese Medicines clinically, such as Xuesaitong, Naodesheng, XueShuanTong, ShenMai, and QSYQ. These suggest that NG-R1 exhibits a significant potency in drug development.


Isolation and characterization of two genes, waaC (rfaC) and waaF (rfaF), involved in Pseudomonas aeruginosa serotype O5 inner-core biosynthesis.
Recent studies have provided evidence to implicate involvement of the core oligosaccharide region of Pseudomonas aeruginosa lipopolysaccharide (LPS) in adherence to host tissues. To better understand the role played by LPS in the virulence of this organism, the aim of the present study was to clone and characterize genes involved in core biosynthesis. The inner-core regions of P. aeruginosa and Salmonella enterica serovar Typhimurium are structurally very similar; both contain two main chain residues of heptose linked to lipid A-Kdo2 (Kdo is 3-deoxy-D-manno-octulosonic acid). By electrotransforming a P. aeruginosa PAO1 library into Salmonella waaC and waaF (formerly known as rfaC and rfaF, respectively) mutants, we were able to isolate the homologous heptosyltransferase I and II genes of P. aeruginosa. Two plasmids, pCOREc1 and pCOREc2, which restored smooth LPS production in the waaC mutant, were isolated. Similarly, plasmid pCOREf1 was able to complement the Salmonella waaF mutant. Sequence analysis of the DNA insert of pCOREc2 revealed one open reading frame (ORF) which could code for a protein of 39.8 kDa. The amino acid sequence of the deduced protein exhibited 53% identity with the sequence of the WaaC protein of S. enterica serovar Typhimurium. pCOREf1 contained one ORF capable of encoding a 38.4-kDa protein. The sequence of the predicted protein was 49% identical to the sequence of the Salmonella WaaF protein. Protein expression by the Maxicell system confirmed that a 40-kDa protein was encoded by pCOREc2 and a 38-kDa protein was encoded by pCOREf1. Pulsed-field gel electrophoresis was used to determine the map locations of the cloned waaC and waaF genes, which were found to lie between 0.9 and 6.6 min on the PAO1 chromosome. Using a gene-replacement strategy, we attempted to generate P. aeruginosa waaC and waaF null mutants. Despite multiple attempts to isolate true knockout mutants, all transconjugants were identified as merodiploids.


Outcome of the extremely low birth weight infants (less than 999 grams): what messages are we getting?
The outcome of the extremely low birth weight (less than 1,000g or ELBW) babies continues to improve. More ELBW babies are surviving, though some of them may have various degrees of impairment or disability. The chance of dying or surviving with a major disability or cerebral palsy declines significantly in recent years in the developed countries. The implication of these findings is that application of neonatal care does not increase the risk of disabled survival as has been often feared but promoted normal survival. Great effort has been put in to achieve good results and better outcome. Developing countries however, will face a problem of achieving similar results because of limited resources or priority of allocation of limited resources, inadequate facilities, lower socio-economic status, poor home environment and lack of follow-up services, training and rehabilitation set-ups or intervention programme. What is the relevance of these good results in relation to the developing or third world countries? The limit of viability may have to be redefined. Nevertheless, it should be the aim to lower the mortality of these high risk babies and to reduce complications and morbidity of the survivors. Maintenance and control of body temperature, control of infections, blood sugar monitoring, antenatal steroids for the mother in premature labour, resuscitation at birth or even simple nasal continuous positive airway pressure (CPAP) should come a long way in fulfilling these goals. Those ELBW children who survive without neurological damage may have learning difficulties. It is necessary to find out the reasons for that such as the impact of the home environment on mental development. Do the children have a good background conducive for learning? Are there establishments for intervention programme in the community for these high risk children? The ratio of neonatal beds per 1,000 deliveries may have to be reviewed now that more ELBW infants are staying in the hospital for a longer period, and surviving.


secD, a new gene involved in protein export in Escherichia coli.
New mutants of Escherichia coli altered in protein export were identified in phoA-lacZ and lamB-lacZ gene fusion strains by searching for mutants that showed an altered lactose phenotype. Several mutations mapped in a new gene, secD. These mutants were, in general, cold sensitive for growth, and the mutations led to an accumulation of precursor of exported proteins. The secD gene is closely linked to tsx on the E. coli chromosome, but separable from another gene proposed to be involved in export, ssaD, which maps nearby. A plasmid carrying secD+ was identified and used to show that the mutations are recessive. The secD gene may code for a component of the cellular export machinery.


A Combined Experimental-Computational Investigation to Uncover the Puzzling (Chiro-)optical Response of Pyridocyclophanes: One- and Two-Photon Spectra.
A combined experimental-computational analysis of the one- and two-photon absorption (OPA, TPA) and the electronic circular dichroism (ECD) of complex chiral shape-persistent (2,6)-pyrido[142 ]allenoacetylenic cyclophane, (P,P,P,P)-MC[142 ] enantiomers, sheds light on the origin of their peculiar spectral signatures. The study on MC[142 ], which is represented in solution by three possible conformers, indicates that two of them (chair and twist) are the prevalent conformers at room temperature; the population ratio depending on the solvent. The complex shape of the red-edge of the UV and ECD spectra is qualitatively reproduced by using vibronic calculations and assigned to progressions on the ethynyl stretchings observable only in the chair and twist conformers. The picture arising from the analysis of the linear spectra is confirmed by two-photon spectroscopies, showing that they constitute valuable tools for the exploration of high-energy electronic transitions in pyridoallenoacetylenic cyclophanes. Discrepancies among computed and experimental spectra point out that an accurate description of such complex systems with a large delocalized π framework and a dense manifold of electronic excited state remains a challenge for theoretical models.


Pressure-relaxation studies of pyrene-labelled actin and myosin subfragment 1 from rabbit skeletal muscle. Evidence for two states of acto-subfragment 1.
We have used actin labelled at Cys-374 with N-(1-pyrenyl)iodoacetamide [Kouyama & Mihashi (1981) Eur. J. Biochem. 114, 33-38] to monitor pressure-induced relaxations of acto-myosin subfragment 1. This label greatly increases the sensitivity of measurement of dissociated actin and reveals the presence of two relaxations. The experimental data can be fitted by a model in which actin binds subfragment 1 relatively weakly (K = 5.9 X 10(4) M-1) and then isomerizes to a more tightly bound complex (K = 1.7 X 10(7) M-1). This directly observed isomerization supports the model of Geeves, Goody & Gutfreund [(1984) J. Muscle Res. Cell. Motil. 5, 351-361]. The rate of the isomerization is too high to be observed in the pressure-jump apparatus (less than 200 microseconds), but analysis of the amplitudes allows estimation of the equilibrium constant of the isomerization as 280 (20 degrees C, 0.1 M-KCl, pH 7). The equilibrium is sensitive to temperature, pressure, ionic strength and the presence of ethylene glycol. The pressure-sensitivity of the isomerization suggests a significant conformational change of the acto-myosin subfragment 1 complex.


Prior infection of chickens with H1N1 or H1N2 avian influenza elicits partial heterologous protection against highly pathogenic H5N1.
There is a critical need to have vaccines that can protect against emerging pandemic influenza viruses. Commonly used influenza vaccines are killed whole virus that protect against homologous and not heterologous virus. Using chickens we have explored the possibility of using live low pathogenic avian influenza (LPAI) A/goose/AB/223/2005 H1N1 or A/WBS/MB/325/2006 H1N2 to induce immunity against heterologous highly pathogenic avian influenza (HPAI) A/chicken/Vietnam/14/2005 H5N1. H1N1 and H1N2 replicated in chickens but did not cause clinical disease. Following infection, chickens developed nucleoprotein and H1 specific antibodies, and reduced H5N1 plaque size in vitro in the absence of H5 neutralizing antibodies at 21 days post infection (DPI). In addition, heterologous cell mediated immunity (CMI) was demonstrated by antigen-specific proliferation and IFN-γ secretion in PBMCs re-stimulated with H5N1 antigen. Following H5N1 challenge of both pre-infected and naïve controls chickens housed together, all naïve chickens developed acute disease and died while H1N1 or H1N2 pre-infected chickens had reduced clinical disease and 70-80% survived. H1N1 or H1N2 pre-infected chickens were also challenged with H5N1 and naïve chickens placed in the same room one day later. All pre-infected birds were protected from H5N1 challenge but shed infectious virus to naïve contact chickens. However, disease onset, severity and mortality was reduced and delayed in the naïve contacts compared to directly inoculated naïve controls. These results indicate that prior infection with LPAI virus can generate heterologous protection against HPAI H5N1 in the absence of specific H5 antibody.


Cool Crosslinking: Riboflavin at 4°C for Pain Management After Crosslinking for Keratoconus Patients, A Randomized Clinical Trial.
To explore corneal cooling as a method of pain management in corneal-accelerated collagen cross-linking. This was a prospective and interventional randomized clinical trial registered in the National Institutes of Health Clinical Trials through the identifier NCT030760770. The research was conducted at the Institute of Ophthalmology "Conde de Valenciana." A total of 98 patients were randomly assigned to one of the following 2 groups: cold riboflavin (4°C) group or control group (riboflavin at room temperature). The inclusion criteria were patients of any sex, older than 18 years of age with keratoconus diagnosis who needed management with cross-linking in both eyes because of the evidence of progression. The exclusion criteria were patients who had cross-linking without epithelial debridement, unilateral cross-linking, or any other ocular pathologies besides keratoconus and any cognitive incapacity that would make the understanding of the pain test difficult. The main outcome measures were pain, tearing, photophobia, foreign body sensation, and irritation. At 2 hours post-op, pain in the case and control groups was 3.80 ± 3.00 and 8.08 ± 2.21 (P < 0.05), tearing was 1.56 ± 1.96 and 8.29 ± 2.42 (P < 0.05), photophobia was 5.44 ± 3.57 and 7.83 ± 2.64 (P < 0.05), foreign body sensation was 2.20 ± 2.78 and 6.54 ± 2.73 (P < 0.05), and irritation was 3.48 ± 2.98 and 6.79 ± 3.00 (P < 0.05), respectively. A statistical significant difference was maintained in pain values on day 1 (2.79 ± 3.09 and 4.91 ± 3.27 [P < 0.05]), 2 (2.54 ± 2.41 and 4.00 ± 2.43 [P < 0.05]), and 4 (0.45 ± 0.76 and 1.22 ± 1.67 [P < 0.05]). This study demonstrated that pain and associated symptoms decreased significantly in the riboflavin 4°C group.


Virulence profiling and quantification of verocytotoxin-producing Escherichia coli O145:H28 and O26:H11 isolated during an ice cream-related hemolytic uremic syndrome outbreak.
In September-October 2007, a mixed-serotype outbreak of verocytotoxin-producing Escherichia coli (VTEC) O145:H28 and O26:H11 occurred in the province of Antwerp, Belgium. Five girls aged between 2 and 11 years developed hemolytic uremic syndrome, and seven other coexposed persons with bloody diarrhea were identified. Laboratory confirmation of O145:H28 infection was obtained for three hemolytic uremic syndrome patients, one of whom was coinfected with O26:H11. The epidemiological and laboratory investigations revealed ice cream as the most likely source of the outbreak. The ice cream was produced at a local dairy farm using pasteurized milk. VTEC of both serotypes with indistinguishable pulsed-field gel electrophoresis patterns were isolated from patients, ice cream, and environmental samples. Quantitative analysis of the ice cream indicated concentrations of 2.4 and 0.03 CFU/g for VTEC O145 and O26, respectively. Virulence typing revealed that the repertoire of virulence genes carried by the O145:H28 outbreak strain was comparable to that of O157 VTEC and more exhaustive as compared to the O26:H11 outbreak strain and nonrelated clinical strains belonging to these serotypes. Taken together, these data suggest that O145:H28 played the most important role in this outbreak.


Structural phase transition of magnetic [Ni(dmit)2]- salts induced by supramolecular cation structures of (M+)([12]crown-4)2.
Sandwich-type supramolecular cation structures of (M(+))([12]crown-4)(2) complexes (M(+) = Li(+), Na(+), K(+), and Rb(+)) were introduced as countercations to the [Ni(dmit)(2)](-) anion, which bears an S = (1)/(2) spin, to form novel magnetic crystals (dmit(2-) = 2-thione-1,3-dithiole-4,5-dithiolate). The zigzag arrangement of Li(+)([12]crown-4)(2) cations in Li(+)([12]crown-4)(2)[Ni(dmit)(2)](-) salt induced weak intermolecular interactions of [Ni(dmit)(2)](-) dimers, whose magnetic spins were isolated from each other. The molecular arrangements of cations and anions in M(+)([12]crown-4)(2)[Ni(dmit)(2)](-) salts (M(+) = Na(+), K(+), and Rb(+)) were isostructural to each other. In the case of Na(+)([12]crown-4)(2)[Ni(dmit)(2)](-), the space group C2/m changed to C2/c with a lowering in temperature from 298 to 100 K. This structural change occurred at 222.5 K as a first-order phase transition. The space group C2/m (T = 298 K) in the salt K(+)([12]crown-4)(2)[Ni(dmit)(2)](-) also changed to C2/c (T = 100 K), which transition occurred at 270 K. Crystal structural analyses at 298 and 100 K revealed changes in both supramolecular cation conformation and [Ni(dmit)(2)](-) anion arrangements. The transition from C2/m to C2/c crystals generated a dipole moment in the Na(+)([12]crown-4)(2) and K(+)([12]crown-4)(2) structures, which were reconstructed to cancel the net dipole moment of the C2/c crystals. These cation transformations led to changes in intermolecular interactions between the [Ni(dmit)(2)](-) anions via structural rearrangements. The crystal structure of C2/c was stabilized in Rb(+)([12]crown-4)(2)[Ni(dmit)(2)](-) at 298 K. The [Ni(dmit)(2)](-) configuration in these salts with the C2/c space group was a one-dimensional uniform chain, which showed the temperature-dependent magnetic susceptibility of a one-dimensional linear Heisenberg antiferromagnetic chain.


Influenza infection in neutropenic adults.
While lymphopenia is a well-defined risk factor for severe influenza, the effect of neutropenia is unknown. This was a retrospective single centre study of adult patients with documented neutropenia and influenza between 2005 and 2013. Forty patients were included with a median follow-up of 2 years (IQR 0.8-4.0). Median ANC at influenza diagnosis was 0.3 × 109/L (IQR 0.1-0.4 × 109/L). Outcomes included hospitalization (N = 28, 70%), pneumonia (N = 9, 23%), ICU admission (N = 9, 23%) and mechanical ventilation (N = 7, 18%). Three deaths (7.5%) were attributed to influenza, all of whom had lower respiratory tract infection (LRTI). Patients with LRTI (N = 18, 45%) also had a higher 30-day mortality (37 versus 0%) and 90-day mortality (42 versus 0%) than those with upper respiratory tract infection. In summary, neutropenic patients have high rates of influenza complications. Our study highlights the need for early diagnosis and aggressive management of influenza in this population.


Approaches to Research Determination of Late Acute Cellular Rejection in Pediatric Liver Transplant Recipients.
A central pathology or site reading of biopsy slides is used in liver transplant clinical trials to determine rejection. We evaluated interrater reliability of readings of "rejection or not" using digitized slides from the Medication Adherence in Children who had a Liver Transplant (MALT) study. Four masked experienced pathologists read the digitized slides and then reread them after a study-specific histologic endpoint development program. Agreement was expressed throughout as a Kappa or Fleiss Kappa statistic (ҡ). A ҡ > 0.6 was predefined as desirable. Readings were correlated with immunosuppressant adherence (the Medication Level Variability Index, [MLVI]), and maximal liver enzyme levels during the study period. Interrater agreement between site and central review in MALT, and between 4 pathologists later on, was low (ҡ = 0.44, Fleiss ҡ = 0.41, respectively). Following the endpoint development program, agreement improved and became acceptable (ҡ = 0.71). The final reading was better-aligned with maximal gamma-glutamyl transferase levels and MLVI as compared with the original central reading. We found substantial disagreement between experienced pathologists reading the same slides. A unique study-specific procedure improved interrater reliability to the point it was acceptable. Such a procedure may be indicated to increase reliability of histopathologic determinations in future research, and perhaps also clinically.


Antidepressant medication prevents suicide in depression.
Ecological studies have demonstrated a substantial decrease in suicide in parallel with an increasing use of antidepressants. To investigate on the individual level the hypothesis that antidepressant medication was a causal factor. Data on the toxicological detection of antidepressants in 18 922 suicides in Sweden 1992-2003 were linked to registers of psychiatric hospitalization as well as registers with sociodemographic data. The probability for the toxicological detection of an antidepressant was lowest in the non-suicide controls, higher in suicides, and even higher in suicides that had been psychiatric in-patients but excluding those who had been in-patients for the treatment of depression. The finding that in-patient care for depression did not increase the probability of the detection of antidepressants in suicides is difficult to explain other than by the assumption that a substantial number of depressed individuals were saved from suicide by postdischarge treatment with antidepressant medication.


An introduced competitor elevates corticosterone responses of a Native Lizard (Varanus varius).
Glucocorticoid hormone profiles are increasingly used as physiological markers to infer the strength of species interactions that can influence fitness and ensuing population dynamics of animals. Here we investigated two aims. First, we measured the effect of a 90-min capture stress protocol on the plasma corticosterone responses of a large native Australian lizard, the lace monitor (Varanus varius). Second, we compared the basal and postcapture stress corticosterone responses of lace monitors in habitats where they were exposed to high or low densities of the European red fox (Vulpes vulpes), an introduced competitor. Lace monitors responded to the capture stress protocol by significantly increasing plasma levels of corticosterone above basal at 45- and 90-min-postcapture blood-sampling intervals. In habitats with high fox densities, lace monitors produced a significantly greater basal and capture-stress-induced corticosterone response compared to individuals in low-fox density habitat. A significant interaction among fox density, time postcapture, and body condition was also found to influence plasma corticosterone values. These results suggest competition with red fox, perhaps via nutritional stress and increased hypersensitivity of the adrenocortical axis in lizards. At present, without further research, we do not understand whether such responses mediate lizard fitness or whether they have adaptive or maladaptive consequences for lizard populations in response to red fox competition. Nevertheless, our results help broaden understanding of the physiological implications arising from species interactions and specifically how introduced competitors could mediate diverse impacts on native biodiversity.


The role of AV2 ("precoat") and coat protein in viral replication and movement in tomato leaf curl geminivirus.
We analyzed various mutants of tomato leaf curl virus-India to investigate the role of ORFs AV3, AV2, and coat protein (CP) in viral replication, movement, and symptom development. The results of these studies indicate that ORF AV3 does not encode a protein. Plants inoculated with infectious DNA which contained deletions in AV2 developed very mild symptoms and accumulated only low levels of both single-stranded (ss) and double-stranded (ds) viral DNA, whereas inoculated protoplasts accumulated both ss and dsDNA to wild-type levels, showing that AV2 is required for efficient viral movement. However, both plants and protoplasts inoculated with substitution, frameshift, and other similar mutations in AV2 accumulated low levels of viral DNA. The low levels of accumulation of DNA of these mutants were apparently not due to a defect in AV2 synthesis. Mutations in the CP caused a marked decrease in ssDNA accumulation in plants and protoplasts while increasing dsDNA accumulation in protoplasts. Mutations in both AV2 and CP behaved like AV2 mutants in plants and like CP mutants in protoplasts. The results demonstrated that multiple functions provided by AV2, BV1, BC1 are essential for viral movement, and that changes in A-component virion-sense mRNA structure or translation affect viral replication.


Flower pollination algorithm parameters tuning.
The flower pollination algorithm (FPA) is a highly efficient metaheuristic optimization algorithm that is inspired by the pollination process of flowering species. FPA is characterised by simplicity in its formulation and high computational performance. Previous studies on FPA assume fixed parameter values based on empirical observations or experimental comparisons of limited scale and scope. In this study, a comprehensive effort is made to identify appropriate values of the FPA parameters that maximize its computational performance. To serve this goal, a simple non-iterative, single-stage sampling tuning method is employed, oriented towards practical applications of FPA. The tuning method is applied to the set of 28 functions specified in IEEE-CEC'13 for real-parameter single-objective optimization problems. It is found that the optimal FPA parameters depend significantly on the objective functions, the problem dimensions and affordable computational cost. Furthermore, it is found that the FPA parameters that minimize mean prediction errors do not always offer the most robust predictions. At the end of this study, recommendations are made for setting the optimal FPA parameters as a function of problem dimensions and affordable computational cost.


Three-Stream Convolutional Neural Network for Depression Detection with Ocular Imaging.
Depression is a prevalent and severe mental disorder that significantly affects both mind and body, leading to persistent feelings of sadness, despair, and impaired functionality. Diagnosis of depression primarily relies on clinical assessment and observation of symptoms. However, due to the lack of objective indicators, the experience and skills of doctor may lead to misdiagnosis. Current researches indicate that eye movement patterns and pupil dilation can serve as potential biomarkers for emotional and cognitive dysregulation in individuals with depression. However, most studies are based on manually extracted eye movement features, overlooking a significant portion of information available in ocular imaging. This paper proposes Three-Stream Convolutional Neural Network (TSCNN) for detecting depression, leveraging both spatio-temporal information of raw ocular imaging and paradigmatic semantic features. We suggest using optical flow with different sampling intervals to capture temporal features. In the third stream, we employ an encoder to learn semantic information from paradigm images and use it as prior knowledge. Finally, we utilize a fully connected network for classification, achieving an accuracy of 79.3% on our self-collected dataset. The proposed method may demonstrate significant clinical utility in the future.