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Background: Neonatal mortality is a significant contributor to infant mortality. Causes and predictors of neonatal death are known to vary in different settings and across different contexts. This study aimed to assess predictors, causes, and trends of neonatal mortality amongst neonates admitted to Nekemte Referral Hospital neonatal unit between 2010–2014. Methods: Retrospective data was collected for 2090 live born neonates admitted to the neonatal intensive care unit of Nekemte Referral Hospital by reviewing records between 2010 to 2014. Variables were collected from the neonatal registration book and patient card on the predictors, causes, and trends of neonatal death using a standard checklist developed by the World Health Organization (WHO). Data was analyzed using Epi info version 3.5.1, and SPSS version 25 for windows. The level of significance was set at P<0.05 with the corresponding confidence intervals at 95%. A logistic regression model was used for analysis and to control for confounders. Microsoft Excel 2007 was used to construct the trend analysis. Results: There were 183 deaths in the cohort equivalent to 8.8% of deaths among total admitted neonates during the study period. Early neonatal deaths accounted for 8% and late neonatal deaths accounted for 0.71% of deaths among total admitted neonates. Main predictors identified for an increased risk of neonatal mortality were; neonates from rural residents [AOR 1.35, (95% CI, 1.35–1.87)], birth order of greater than five [AOR 5.10, (95% CI, 1.15–22.63)], home delivery [AOR 3.41, (95% CI, 2.24–5.19)], very low birth weight [AOR 6.75, (95% CI, 3.63–12.54)] and low birth weight [AOR 2.81, (95% CI, 1.95–4.05)] and inability to cry at birth [AOR 2.21, (95% CI, 1.51–3.22)]. The trend analysis showed a sharp fall for the neonatal mortality over the last five years with a mean reduction of 16%. Conclusions: Data from the Nekemte Referral Hospital Neonatal Intensive Care Unit analysis revealed majority of the deaths were occurred during early neonatal period. The main predictors of neonatal mortality identified from this study needs strengthening an appropriate public health intervention through addressing antenatal care, curbing home delivery. [ABSTRACT FROM AUTHOR]

Background: One of the reported causes of high malnutrition rates in Burundi and Rwanda is children's inadequate dietary habits. The diet of children may be affected by individual characteristics and by the characteristics of the households and the communities in which they live. We used the minimum dietary diversity of children (MDD-C) indicator as a proxy of diet quality aiming at: 1) assess how much of the observed variation in MDD-C was attributed to community clustering, and 2) to identify the MDD-C associated factors. Methods: Data was obtained from the 2010 Demographic and Health Surveys of Burundi and Rwanda, from which only children 6 to 23 months from rural areas were analysed. The MDD-C was calculated according to the 2007 WHO/UNICEF guidelines. We computed the intra-class coefficient to assess the percentage of variation attributed to the clustering effect of living in the same community. And then we applied two-level logit regressions to investigate the association between MDD-C and potential risk factors following the hierarchical survey structure of DHS. Results: The MDD-C was 23% in rural Rwanda and 16% in rural Burundi, and a 29% of its variation in Rwanda and 17% in Burundi was attributable to community clustering. Increasing age and living standards were associated with higher MDD-C in both countries, and only in Burundi also increasing level of education of the mother's partner. In Rwanda alone, the increasing ages of the head of the household and of the mother at first birth were also positively associated with it. Despite the identification of an important proportion of the MDD-C variation due to clustering, we couldn't identify any community variable significantly associated with it. Conclusions: We recommend further research using hierarchical models, and to integrate dietary diversity in holistic interventions which take into account both the household's and the community's characteristics the children live in. [ABSTRACT FROM AUTHOR]

Hypoxia and angiogenesis are critical components in the progression of solid cancer, including gastric cancers (GCs). miR-382 has been identified as a hypoxia-induced miR (hypoxamiR), but the clinical significance in GCs has not been identified yet. To explore the clinical and prognostic importance of miR-382 in GCs, the surgical specimens of 398 patients with GCs in KNU hospital in Korea, the total of 183 patients was randomly selected using simple sampling methods and big data with 446 GCs and 45 normal tissues from the data portal () were analysed. Expression of miR-382 as well as miR-210, as a positive control hypoxamiR by qRT-PCR in histologically malignant region of GCs showed significantly positive correlation (R = 0.516, p<0.001). High miR-210 and miR-382 expression was significantly correlated with unfavorable prognosis including advanced GCs (AGC), higher T category, N category, pathologic TNM stage, lymphovascular invasion, venous invasion, and perinueral invasion, respectively (all p<0.05). In univariate analysis, high miR-210 expression was significantly associated with worse overall survival (OS) (p = 0.036) but not high miR-382. In paired 60 gastric normal and cancer tissues, miR-382 expression in cancer tissues was significantly higher than normal counterpart (p = 0.003), but not miR-210 expression. However, by increasing the patient number from the big data analysis, miR-210 as well as miR-382 expression in tumor tissues was significantly higher than the normal tissues. Our results suggest that miR-382, as novel hypoxamiR, can be a prognostic marker for advanced GCs and might be correlated with metastatic potential. miR-382 might play important roles in the aggressiveness, progression and prognosis of GCs. In addition, miR-382 give a predictive marker for progression of GCs compared to the normal or preneoplastic lesion. [ABSTRACT FROM AUTHOR]

The question of how self-driving cars should behave in dilemma situations has recently attracted a lot of attention in science, media and society. A growing number of publications amass insight into the factors underlying the choices we make in such situations, often using forced-choice paradigms closely linked to the trolley dilemma. The methodology used to address these questions, however, varies widely between studies, ranging from fully immersive virtual reality settings to completely text-based surveys. In this paper we compare virtual reality and text-based assessments, analyzing the effect that different factors in the methodology have on decisions and emotional response of participants. We present two studies, comparing a total of six different conditions varying across three dimensions: The level of abstraction, the use of virtual reality, and time-constraints. Our results show that the moral decisions made in this context are not strongly influenced by the assessment, and the compared methods ultimately appear to measure very similar constructs. Furthermore, we add to the pool of evidence on the underlying factors of moral judgment in traffic dilemmas, both in terms of general preferences, i.e., features of the particular situation and potential victims, as well as in terms of individual differences between participants, such as their age and gender. [ABSTRACT FROM AUTHOR]

The N-type Ca2+ channel (Cav2.2) is distributed in sympathetic nerves that innervate the tubules, the vessels, and the juxtaglomerular granular cells of the kidney. However, the role of N-type Ca2+ channels in renal disease remains unknown. To address this issue, Cav2.2 knockout mice were utilized. Immunoreactive Cav2.2 was undetectable in normal kidneys of C57BL/6N mice, but it became positive in the interstitial S100-positive nerve fibers after unilateral ureteral obstruction (UUO). There were no significant differences in mean blood pressure, heart rate, and renal function between wild-type littermates and Cav2.2-knockout mice at baseline, as well as after UUO. Cav2.2 deficiency significantly reduced the EVG-positive fibrotic area, alpha-SMA expression, the production of type I collagen, and the hypoxic area in the obstructed kidneys. The expression of tyrosine hydroxylase, a marker for sympathetic neurons, was significantly increased in the obstructed kidneys of wild-type mice, but not in Cav2.2-knockout mice. These data suggest that increased Cav2.2 is implicated in renal nerve activation leading to the progression of renal fibrosis. Blockade of Cav2.2 might be a novel therapeutic approach for preventing renal fibrosis. [ABSTRACT FROM AUTHOR]

Network coupled cells, such as astrocytes, regulate their cellular homeostasis via Ca2+ signals spread between the cells through gap junctions. Intracellular Ca2+ release is controlled by different signaling pathways that can be stimulated by ATP, glutamate and serotonin (5-HT). Based on our findings, all these pathways are influenced by inflammatory agents and must be restored to fully recover the Ca2+ signaling network. An ultralow concentration of the local anesthetic agent bupivacaine reduced 5-HT-evoked intracellular Ca2+ release, and an ultralow concentration of the phosphodiesterase-5 inhibitor sildenafil in combination with vitamin D3 reduced ATP-evoked intracellular Ca2+ release. Combinations of these three substances downregulated 5-HT-, glutamate- and ATP-evoked intracellular Ca2+ release to a more normal Ca2+ signaling state. Furthermore, inflammatory Toll-like receptor 4 expression decreased with a combination of these three substances. Substance P receptor neurokinin (NK)-1 expression was reduced by ultralow concentrations of bupivacaine. Here, bupivacaine and sildenafil (at extremely low concentrations) combined with vitamin D3 have potential anti-inflammatory properties. According to the present study, drug combinations at the right concentrations, especially extremely low concentrations of bupivacaine and sildenafil, affect different cellular biochemical mechanisms and represent a potential solution for downregulating inflammatory parameters, thereby restoring cells or networks to normal physiological homeostasis. [ABSTRACT FROM AUTHOR]

Background: In Sub-Saharan Africa, both HIV/AIDS and anemia have considerable public health problems. Anemia has an adverse effect on treatment outcome and it decreases the quality of life among adult HIV patients. This study was aimed to assess the prevalence of anemia and its associated factors among adult HIV positive patients in Wolaita Sodo University Teaching Referral Hospital. Method: Institution based cross-sectional study was conducted at Wolaita Sodo University Teaching Referral Hospital from 01 October to December 30, 2016. A randomly selected 411 adult people living with the human immunodeficiency virus were included in the study. A pre-tested questionnaire was used to collect data. Variables with P-value ≤0.25 in the bivariable logistic regression model were taken into multivariable logistic regression analysis along with 95% confidence interval and Odds Ratio was used to examine the association between anemia and independent variables. P˗value ≤ 0.05 was taken as statistically significant. Result: Prevalence of anemia in this study was 36.5% with 95% CI (32%-41%). Factors associated with anemia among adult people living with HIV/AIDS were individuals who lived with HIV ≥9years (AOR = 2.6, 95% CI:-1.03–6.59),years lived with HIV 5–8 years (AOR = 2.59, 95% CI:-1.02–6.57),CD4 count <200cells/ul (AOR = 4.2, 95%CI:-2.03–8.67), CD4 count200-350cells/ul(AOR = 1.82,95%CI:-1.01–3.26),infection with intestinal parasites (AOR = 2.04, 95% CI:-1.06–3.95), Participants with BMI <18.5kg/m2 (AOR = 2.96, 95%CI:-1.37–6.390),BMI 18.5-25kg/m2(AOR = 1.98, 95%CI:-1.11–3.56) and being HAART naïve (AOR = 2.23, 95% CI:- 1.16–4.28). Conclusion: Prevalence of anemia among this study participant was high. This may affect the treatment outcome, increases morbidity and mortality of the participants. So periodic screening of anemia, a routine checkup of nutritional status, CD4 count and examination for intestinal parasite are essential. [ABSTRACT FROM AUTHOR]

Cover crop suppression with glyphosate-based herbicides (GBHs) represents a common agricultural practice. The objective of this study was to compare rhizospheric microbial communities of A. sativa plants treated with a GBH relative to the mechanical suppression (mowing) in order to assess their differences and the potential implications for soil processes. Samples were obtained at 4, 10, 17 and 26 days post-suppression. Soil catabolic profiling and DNA-based methods were applied. At 26 days, higher respiration responses and functional diversity indices (Shannon index and catabolic evenness) were observed under glyphosate suppression and a neat separation of catabolic profiles was detected in multivariate analysis. Sarcosine and Tween 20 showed the highest contribution to this separation. Metabarcoding revealed a non-significant effect of suppression method on either alpha-diversity metrics or beta-diversity. Conversely, differences were detected in the relative abundance of specific bacterial taxa. Mesorhizobium sequences were detected in higher relative abundance in glyphosate-treated plants at the end of the experiment while the opposite trend was observed for Gaiella. Quantitative PCR of amoA gene from ammonia-oxidizing archaea showed a lower abundance under GBH suppression again at 26 days, while ammonia-oxidizing bacteria remained lower at all sampling times. Broad host range plasmids IncP-1β and IncP-1ε were exclusively detected in the rhizosphere of glyphosate-treated plants at 10 days and at 26 days, respectively. Overall, our study demonstrates differential effects of suppression methods on the abundance of specific bacterial taxa, on the physiology and mobile genetic elements of microbial communities while no differences were detected in taxonomic diversity. [ABSTRACT FROM AUTHOR]

Food intake may limit the ability of browsing mammals to gain body mass during the growing season when the leaves and stems of woody plants are most abundant. Moose are highly productive browsers with high demands for energy and nutrients, particularly during lactation. Using an indigestible marker, we estimated dry matter intake of free ranging adult female moose with and without calves over three growing seasons. During the same period, we analyzed forage quality. Intakes were highest in late spring (280 ± 19 g·kg-0.75·d-1) when forage quality peaked; however, intakes declined by 39% throughout the summer as temperatures increased and as acid detergent fiber content of browse increased. Digestibility of dry matter declined over summer from 71% to 57% among browse. Intakes were similar for moose with and without calves. Heat loads may impair the ability of moose to consume sufficient energy and nutrients. Warming and habitat change can adversely affect browser populations when poor forage qualities and low dry matter intakes combine to suppress digestible intakes of energy and nutrients. [ABSTRACT FROM AUTHOR]

Social scientists have been interested in measuring the prosperity, well-being, and quality of life of nations, which has resulted in a multiplicity of country-level indicators. However, little is known about the factor structure of these indicators. We explored the structure of quality of life, using country-level data on tens of subjective and objective indicators. Applying factor analysis, we identified three distinct factors that exhibited both overlap and complementarity. This structure was replicated in data from previous years and with a partially different set of variables. The first factor, ‘socio-economic progress’, is dominated by socio-political and economic indicators but also includes life satisfaction, which thus appears to reflect objective living conditions. The second factor, ‘psycho-social functioning’, consists of subjective indicators, such as eudaimonic well-being and positive affective states. The third, ‘negative affectivity’, comprises negatively-valenced affective states. The three macro-factors of societal quality of life demonstrated moderate intercorrelations and differential associations with cultural and ecological variables, providing support for their discriminant validity. Finally, country and regional rankings based on the three societal factors revealed a complex picture that cautions against over-reliance on any single indicator such as life satisfaction. The results underline the need for a broadly-based approach to the measurement of societal quality of life, and provide an empirically-derived multidimensional framework for conceptualizing and measuring quality of life and well-being at country level. This study is thus an initial empirical step towards systematizing the multiple approaches to societal quality of life. [ABSTRACT FROM AUTHOR]

Background: Postural orthostatic tachycardia syndrome is a disorder of the autonomic nervous system. Approximately 30% of patients experience orthostatic headaches. Orthostatic headaches also are a hallmark symptom in spontaneous intracranial hypotension. While the cause of orthostatic headaches in spontaneous intracranial hypotension can be linked to the cerebrospinal fluid loss at the spinal level and consecutively reduced intracranial pressure in the upright position, the cause of orthostatic headaches in postural orthostatic tachycardia syndrome still remains unknown. The present study examined orthostatic changes of intracranial pressure using dynamic ultrasound of the optic nerve and optic nerve sheath diameter in postural orthostatic tachycardia syndrome, spontaneous intracranial hypotension and healthy subjects. Methods: Data was obtained from postural orthostatic tachycardia syndrome patients with (n = 7) and without orthostatic headaches (n = 7), spontaneous intracranial hypotension patients (n = 5) and healthy subjects (n = 8). All participants underwent high-resolution transorbital ultrasound in the supine and upright position to assess optic nerve and optic nerve sheath diameter. Results: Group differences were found in percentage deviations when changing position of optic nerve sheath diameter (p < 0.01), but not regarding the optic nerve diameter. Pairwise comparisons indicated differences in optic nerve sheath diameter only between spontaneous intracranial hypotension and the other groups. No differences were found between postural orthostatic tachycardia syndrome patients with and without orthostatic headaches. Conclusion: This study shows that the size of the optic nerve sheath diameter dynamically decreases during orthostatic stress in spontaneous intracranial hypotension, but not in postural orthostatic tachycardia syndrome with or without orthostatic headaches, which indicates different underlying causes. [ABSTRACT FROM AUTHOR]

Cultivated watermelon (Citrullus lanatus) is one of the most important food crops in the Cucurbitaceae family. Diversification after domestication has led cultivated watermelons to exhibit diverse fruit flesh colors, including red, yellow, and orange. Recently, there has been increased interest in red-fleshed watermelons because they contain the antioxidant cis-isomeric lycopene. We performed whole genome resequencing (WGRS) of 24 watermelons with different flesh colors to identify single-nucleotide polymorphisms (SNPs) related to high lycopene content. The resequencing data revealed 203,894–279,412 SNPs from read mapping between inbred lines and the 97103 reference genome. In total, 295,065 filtered SNPs were identified, which had an average polymorphism information content of 0.297. Most of these SNPs were intergenic (90.1%) and possessed a transversion (Tv) rate of 31.64%. Overall, 2,369 SNPs were chosen at 0.5 Mb physical intervals to analyze genetic diversity across the 24 inbred lines. A neighbor-joining dendrogram and principal coordinate analysis (PCA) based on the 2,369 SNPs revealed that the 24 inbred lines could be grouped into high and low lycopene-type watermelons. In addition, we analyzed SNPs that could discriminate high lycopene content, red-fleshed watermelon from low lycopene, yellow or orange watermelon inbred lines. For validation, 19 SNPs (designated as WMHL1–19) were chosen randomly, and cleavage amplified polymorphic sequence (CAPS) markers were designed. Genotyping of the above 24 lines and 12 additional commercial cultivars using WMHL1–19 CAPS markers resulted in match rates of over 0.92 for most validated markers in correlation with the flesh color phenotypes. Our results provide valuable genomic information regarding the high lycopene content phenotype of red-fleshed cultivated watermelons, and the identified SNPs will be useful for the development of molecular markers in the marker-assisted breeding of watermelons with high lycopene content. [ABSTRACT FROM AUTHOR]

DNA repair defects have been increasingly focused on as therapeutic targets. In hormone-positive breast cancer, XRCC1-deficient tumors have been identified and proposed as targets for combination therapies that damage DNA and inhibit DNA repair pathways. XRCC1 is a scaffold protein that functions in base excision repair (BER) by mediating essential interactions between DNA glycosylases, AP endonuclease, poly(ADP-ribose) polymerase 1, DNA polymerase β (POL β), and DNA ligases. Loss of XRCC1 confers BER defects and hypersensitivity to DNA damaging agents. BER defects have not been evaluated in triple negative breast cancers (TNBC), for which new therapeutic targets and therapies are needed. To evaluate the potential of XRCC1 as an indicator of BER defects in TNBC, we examined XRCC1 expression in the TCGA database and its expression and localization in TNBC cell lines. The TCGA database revealed high XRCC1 expression in TNBC tumors and TNBC cell lines show variable, but mostly high expression of XRCC1. XRCC1 localized outside of the nucleus in some TNBC cell lines, altering their ability to repair base lesions and single-strand breaks. Subcellular localization of POL β also varied and did not correlate with XRCC1 localization. Basal levels of DNA damage correlated with observed changes in XRCC1 expression, localization, and measure repair capacity. The results confirmed that XRCC1 expression changes indicate DNA repair capacity changes but emphasize that basal DNA damage levels along with protein localization are better indicators of DNA repair defects. Given the observed over-expression of XRCC1 in TNBC preclinical models and tumors, XRCC1 expression levels should be assessed when evaluating treatment responses of TNBC preclinical model cells. [ABSTRACT FROM AUTHOR]

Objectives: Aging is associated with low muscle mass and has been linked to adverse health outcomes. The objectives of this cross-sectional study were: (1) to describe anthropometry, body composition, appendicular skeletal muscle mass index (ASMI; appendicular skeletal muscle mass/height2), and prevalence of low ASMI in older people with normal nutritional status (Malnutrition Universal Screening Tool score = 0); (2) to determine factors associated with ASMI, and odds ratios of having low ASMI. Methods: SHIELD is a study of community-dwelling older people aged 65 years and above in Singapore. ASMI was determined using bioelectrical impedance analysis and low ASMI was defined as <7.0 kg/m2 for males and <5.7 kg/m2 for females (Asian Working Group for Sarcopenia, 2014). Results: A total of 400 older people (183 males and 217 females) took part in this study. The overall prevalence of low ASMI was 20.6% (15.5% in males and 24.9% in females). Females had significantly lower ASMI than males (P < 0.0001), age was inversely associated with ASMI (P = 0.0024) while BMI and calf circumference were positively associated with ASMI (both P < 0.0001) in the total cohort. In addition, ASMI was positively associated with bone mass in both genders (both P < 0.0001). After adjusting for covariates, the odds ratios of having low ASMI with every 1 year and 10 years increase in age were 1.13 (95% CI: 1.06, 1.20) and 3.36 (95% CI: 1.82, 6.21) respectively. Conclusions: The high prevalence of low ASMI in community-dwelling older people with normal nutritional status highlights the need for early screening. There was a strong inverse association between age and ASMI while BMI, calf circumference and bone mass were positively associated with ASMI. These findings will give further weight to the importance and development of public health strategies in maintaining and improving muscle health in this population group. [ABSTRACT FROM AUTHOR]

Prior research has found that places and people that are more economically disadvantaged have higher rates and risks, respectively, of sexually transmitted infections (STIs). Economic disadvantages at the level of places and people, however, are themselves influenced by economic policies. To enhance the policy relevance of STI research, we explore, for the first time, the relationship between state-level minimum wage policies and STI rates among women in a cohort of 66 large metropolitan statistical areas (MSAs) in the US spanning 2003–2015. Our annual state-level minimum wage measure was adjusted for inflation and cost of living. STI outcomes (rates of primary and secondary syphilis, gonorrhea and chlamydia per 100,000 women) were obtained from the CDC. We used multivariable hierarchical linear models to test the hypothesis that higher minimum wages would be associated with lower STI rates. We preliminarily explored possible socioeconomic mediators of the minimum wage/STI relationship (e.g., MSA-level rates of poverty, employment, and incarceration). We found that a $1 increase in the price-adjusted minimum wage over time was associated with a 19.7% decrease in syphilis rates among women and with an 8.5% drop in gonorrhea rates among women. The association between minimum wage and chlamydia rates did not meet our cutpoint for substantive significance. Preliminary mediation analyses suggest that MSA-level employment among women may mediate the relationship between minimum wage and gonorrhea. Consistent with an emerging body of research on minimum wage and health, our findings suggest that increasing the minimum wage may have a protective effect on STI rates among women. If other studies support this finding, public health strategies to reduce STIs among women should include advocating for a higher minimum wage. [ABSTRACT FROM AUTHOR]

Calibration of the molecular rate is one of the major challenges in marine population genetics. Although the use of an appropriate evolutionary rate is crucial in exploring population histories, calibration of the rate is always difficult because fossil records and geological events are rarely applicable for rate calibration. The acceleration of the evolutionary rate for recent coalescent events (or more simply, the time dependency of the molecular clock) is also a problem that can lead to overestimation of population parameters. Calibration of demographic transition (CDT) is a rate calibration technique that assumes a post-glacial demographic expansion, representing one of the most promising approaches for dealing with these potential problems in the rate calibration. Here, we demonstrate the importance of using an appropriate evolutionary rate, and the power of CDT, by using populations of the sandy beach amphipod Haustorioides japonicus along the Japanese coast of the northwestern Pacific Ocean. Analysis of mitochondrial sequences found that the most peripheral population in the Pacific coast of northeastern Honshu Island (Tohoku region) is genetically distinct from the other northwestern Pacific populations. By using the two-epoch demographic model and rate of temperature change, the evolutionary rate was modeled as a log-normal distribution with a median rate of 2.2%/My. The split-time of the Tohoku population was subsequently estimated to be during the previous interglacial period by using the rate distribution, which enables us to infer potential causes of the divergence between local populations along the continuous Pacific coast of Japan. [ABSTRACT FROM AUTHOR]

Introduction: Bexarotene, a retinoid X receptor agonist, improves cognition in murine models of Alzheimer’s disease (AD). This study evaluated the effects of bexarotene on pathological and electrophysiological changes in very old triple transgenic AD mice (3xTg-AD mice). Methods: 24-month-old 3xTg-AD mice were treated with bexarotene (100 mg/kg/day for 30 days). The Morris water maze was used to evaluate spatial memory; immunofluorescence and confocal microscopy were used to evaluate pathological changes; and in vivo electrophysiological recordings were used to evaluate basal transmission and plasticity in the commissural CA3-CA1 pathway. Results: In addition to cognitive improvement, bexarotene-treated 3xTg-AD mice were found to have 1) reductions of astrogliosis and reactive microglia both in cortex and hippocampus; 2) increased ApoE expression restricted to CA1; 3) increased number of cells co-labeled with ApoE and NeuN; 4) recovery of NeuN expression, suggesting neuronal protection; and, 5) recovery of basal synaptic transmission and synaptic plasticity. Discussion: These results indicate that bexarotene-induced improvement in cognition is due to multiple changes that contribute to recovery of synaptic plasticity. [ABSTRACT FROM AUTHOR]

Introduction: Cervical cancer imposes a substantial health burden worldwide including in Australia and is caused by persistent infection with one of 13 sexually transmitted high-risk human papillomavirus (HPV) types. The objective of this study was to assess the cost-effectiveness of adding a nonavalent new Gardasil-9® (9vHPV) vaccine to the national immunisation schedule in Australia across three different delivery strategies. Materials and methods: The Papillomavirus Rapid Interface for Modelling and Economics (PRIME) model was used to examine the cost-effectiveness of 9vHPV vaccine introduction to prevent HPV infection. Academic literature and anecdotal evidence were included on the demographic variables, cervical cancer incidence and mortality, treatment costs, and vaccine delivery costs. The incremental cost-effectiveness ratios (ICERs) were measured per disability-adjusted life years (DALYs) averted, using the heuristic cost-effectiveness threshold defined by the World Health Organisation (WHO). Analyses and data from international agencies were used in scenario analysis from the health system and societal perspectives. Results: The 9vHPV vaccination was estimated to prevent 113 new cases of cervical cancer (discounted) during a 20-year period. From the health system and societal perspectives, the 9vHPV vaccination was very cost-effective in comparison with the status quo, with an ICER of A$47,008 and A$44,678 per DALY averted, respectively, using the heuristic cost-effectiveness threshold level. Considering delivery strategies, the ICERs per DALY averted were A$47,605, A$46,682, and A$46,738 for school, health facilities, and outreach-based vaccination programs from the health system perspective, wherein, from the societal perspective, the ICERs per DALY averted were A$46,378, A$43,729, A$43,930, respectively. All estimates of ICERs fell below the threshold level (A$73,267). Conclusions: This cost-effectiveness evaluation suggests that the routine two-dose 9vHPV vaccination strategy of preadolescent girls against HPV is very cost-effective in Australia from both the health system and societal perspectives. If equally priced, the 9vHPV option is the most economically viable vaccine. Overall, this analysis seeks to contribute to an evidence-based recommendation about the new 9vHPV vaccination in the national immunisation program in Australia. [ABSTRACT FROM AUTHOR]

Breastfeeding has a wide range of benefits for both infants and mothers. The identification of factors associated with exclusive breastfeeding (EBF) are important to increase the prevalence of EBF. The study aimed to determine the prevalence of EBF within the first six months and its associated factors in Kaiyuan, Yunnan Province, Southwest China. This cross-sectional study was conducted in Kaiyuan, a middle-sized city of Yunnan Province, Southwest China. Mothers of infants under twelve months were randomly selected for a face to face interview in four towns (two in urban areas and two in rural areas) in Kaiyuan. A structured questionnaire was applied for collection of sociodemographic information, mothers’ and infants’ health, and breastfeeding information. A 24-hour food recall survey was used to collect infant feeding information. A logistic regression analysis was performed to identify the factors independently associated with exclusive breastfeeding for infants up to six months of age. The number of 417 mothers with infants under six months was interviewed. The prevalence of EBF at six months was 27.34%. Logistic regression indicated that EBF within six months was more likely to be practiced by mothers who had higher average household income per year (OR = 2.09, 95% CI: 1.05–4.17 p = 0.037; OR = 1.85, 95% CI: 1.04–3.28 p = 0.037), and mothers who received breastfeeding information (OR = 2.46, (95%CI: 1.45–4.18, p = 0.0009). The prevalence of EBF in Kaiyuan, Southwest China is considerably lower than national and international recommendations. Yearly household income, and mothers who received breastfeeding information are associated with higher EBF prevalence. Breastfeeding information should be given to mothers in order to increase the prevalence of EBF. [ABSTRACT FROM AUTHOR]

Mouse models of mesial temporal lobe epilepsy recapitulate aspects of human epilepsy, which is characterized by neuronal network remodeling in the hippocampal dentate gyrus. Observational studies suggest that this remodeling is associated with altered Wnt pathway signaling, although this has not been experimentally examined. We used the well-characterized mouse intrahippocampal kainate model of temporal lobe epilepsy to examine associations between hippocampal neurogenesis and altered Wnt signaling after seizure induction. Tissue was analyzed using immunohistochemistry and confocal microscopy, and gene expression analysis was performed by RT-qPCR on RNA extracted from anatomically micro-dissected dentate gyri. Seizures increased neurogenesis and dendritic arborization of newborn hippocampal dentate granule cells in peri-ictal regions, and decreased neurogenesis in the ictal zone, 2-weeks after kainate injection. Interestingly, administration of the novel canonical Wnt pathway inhibitor XAV939 daily for 2-weeks after kainate injection further increased dendritic arborization in peri-ictal regions after seizure, without an effect on baseline neurogenesis in control animals. Transcriptome analysis of dentate gyri demonstrated significant canonical Wnt gene dysregulation in kainate-injected mice across all regions for Wnt3, 5a and 9a. Intriguingly, certain Wnt genes demonstrated differential patterns of dysregulation between the ictal and peri-ictal zones, most notably Wnt5B, 7B and DKK-1. Together, these results demonstrate regional variation in Wnt pathway dysregulation early after seizure induction, and surprisingly, suggest that some Wnt-mediated effects might actually temper aberrant neurogenesis after seizures. The Wnt pathway may therefore provide suitable targets for novel therapies that prevent network remodeling and the development of epileptic foci in high-risk patients. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) remains a morbid disease with poor prognosis and treatment that typically leaves patients with permanent damage to critical functions such as eating and talking. Currently only three targeted therapies are FDA approved for use in HNSCC, two of which are recently approved immunotherapies. In this work, we identify biological pathways involved with this disease that could potentially be targeted by current FDA approved cancer drugs and thereby expand the pool of potential therapies for use in HNSCC treatment. We analyzed 508 HNSCC patients with sequencing information from the Genomic Data Commons (GDC) database and assessed which biological pathways were significantly enriched for somatic mutations or copy number alterations. We then further classified pathways as either “light” or “dark” to the current reach of FDA-approved cancer drugs using the Cancer Targetome, a compendium of drug-target information. Light pathways are statistically enriched with somatic mutations (or copy number alterations) and contain one or more targets of current FDA-approved cancer drugs, while dark pathways are enriched with somatic mutations (or copy number alterations) but not currently targeted by FDA-approved cancer drugs. Our analyses indicated that approximately 35–38% of disease-specific pathways are in scope for repurposing of current cancer drugs. We further assess light and dark pathways for subgroups of patient tumor samples according to HPV status. The framework of light and dark pathways for HNSCC-enriched biological pathways allows us to better prioritize targeted therapies for further research in HNSCC based on the HNSCC genetic landscape and FDA-approved cancer drug information. We also highlight the importance in the identification of sub-pathways where targeting and cross targeting of other pathways may be most beneficial to predict positive or negative synergy with potential clinical significance. This framework is ideal for precision drug panel development, as well as identification of highly aberrant, untargeted candidates for future drug development. [ABSTRACT FROM AUTHOR]

Photorhabdus luminescens is an entomopathogenic bacterium found in symbiosis with the nematode Heterorhabditis. Dam DNA methylation is involved in the pathogenicity of many bacteria, including P. luminescens, whereas studies about the role of bacterial DNA methylation during symbiosis are scarce. The aim of this study was to determine the role of Dam DNA methylation in P. luminescens during the whole bacterial life cycle including during symbiosis with H. bacteriophora. We constructed a strain overexpressing dam by inserting an additional copy of the dam gene under the control of a constitutive promoter in the chromosome of P. luminescens and then achieved association between this recombinant strain and nematodes. The dam overexpressing strain was able to feed the nematode in vitro and in vivo similarly as a control strain, and to re-associate with Infective Juvenile (IJ) stages in the insect. No difference in the amount of emerging IJs from the cadaver was observed between the two strains. Compared to the nematode in symbiosis with the control strain, a significant increase in LT50 was observed during insect infestation with the nematode associated with the dam overexpressing strain. These results suggest that during the life cycle of P. luminescens, Dam is not involved the bacterial symbiosis with the nematode H. bacteriophora, but it contributes to the pathogenicity of the nemato-bacterial complex. [ABSTRACT FROM AUTHOR]

The purpose of this retrospective decisional analysis study is to develop the prediction model of suicidal ideation. We used a Decision Tree Analysis using SPSS 23.0 program to explore predictors of suicide thoughts for 12,015 Korean adults aged 19–98 years. As a result, the most powerful predictor of suicidal ideation was the level of depression. Of people who suspected depression (CESD-11>16), 32.6% experienced suicidal ideation, which is 12 times higher than that of total subjects. The group with the highest rate of suicidal ideation was people who experienced financial difficulties in depression-suspected group and the rate of suicidal thoughts in this group was 56.7%, which was the highest rate. However, in the non-depressive group, the satisfaction of family relationship was the strongest predictor of suicidal ideation. In the non-depressive group, the rate of suicidal thoughts of people with high level of family relationship satisfaction and high level of health satisfaction was 0.6%, which was the lowest rate. The contribution of this study was that it provided the combination of variables to predict the risk groups of adult suicide. This study suggests that researchers and clinicians should consider comprehensively depressive symptoms, family relationships, economic difficulties, and health status to prevent the suicide of adults. [ABSTRACT FROM AUTHOR]

How various types of focus differ with respect to exhaustivity has been a topic of enduring interest in language studies. However, most of the theoretical work explicating such associations has done so cross-linguistically, and little research has been done on how people process and respond to them during language comprehension. This study therefore investigates the associations between the concept of exhaustivity and three focus types in Chinese (wh, cleft, and only foci) using a trichotomous-response design in two experiments: a forced-choice judgment and a self-paced reading experiment, both with adult native speakers. Its results show that, whether engaged in conscious decision-making or an implicit comprehension process, the participants distinguished only-focus and cleft-focus from wh-focus clearly, and also that there are specific differences between only-focus and cleft-focus in conscious decision-making. This implies that, in terms of the relationship between exhaustivity and the focus types under investigation, cleft-focus and only-focus behave very similarly during language comprehension despite the existence of some fine distinctions between them. In other words, the potential linguistic levels that exhaustivity encodes in Chinese cleft-focus render it more similar to only-focus than to wh-focus. These results are broadly in line with the semantic account that distinguishes cleft from only-focus, i.e., that cleft encodes exhaustivity in not-at-issue presupposition and only-focus encodes exhaustivity in at-issue assertion, while both express semantically encoded exhaustivity, triggering robust language-processing patterns that differ from patterns of wh-focus in Chinese. [ABSTRACT FROM AUTHOR]

Background: The association between sugar-sweetened beverage (SSB) consumption and colorectal cancer (CRC) risk remains unclear and published data are limited. Methods: The analytic cohort included 99,798 women, free of cancer at baseline, from the California Teachers Study, a longitudinal cohort comprised of 133,477 female teachers and administrators who were active or recently retired members of the California State Teachers Retirement System in 1995. SSB consumption constituted caloric soft drinks, sweetened bottled waters and teas, and fruit drinks, derived from a self-administered food frequency questionnaire. Consumption was divided into four categories: Rare or never, >rare/never to <1 serving/week, ≥1 serving/week to <1 serving/day, and ≥1 serving/day. CRC endpoints were based on annual linkage with California Cancer Registry, defined as first diagnosis of CRC, and classified following the Surveillance, Epidemiology, and End Results Program coding system. Multivariable-adjusted Cox proportional hazards models were used to generate hazard ratios (HR) and 95% confidence intervals (CI) for assessing the association between SSB consumption and incident CRC. Results: A total of 1,318 incident CRC cases were identified over 20 years of follow-up (54.5% proximal colon and 45.5% distal colorectum). Compared with rare/never consumers, the multivariable-adjusted HRs (95% CI) were 1.14 (0.86, 1.53) for total CRC; 1.11 (0.73, 1.68) for proximal colon; and 1.22 (0.80, 1.86) for distal colorectum cancers among women consuming ≥ 1 serving/day of SSBs. Conclusion: SSBs were not significantly associated with CRC risk. The biological effects of high SSB consumption make it important to continue to evaluate whether SSBs are associated with CRC. Additionally, future studies should further assess SSBs in large, racial/ethnically diverse cohorts of males and females, and, if feasible, address changes in SSB consumption over time. [ABSTRACT FROM AUTHOR]

Background and aims: Many countries lack resources to identify patients at risk of developing Type 2 diabetes mellitus (diabetes). We aimed to develop and validate a diabetes risk score based on easily accessible clinical data. Methods: Prospective study including 5277 participants (55.0% women, 51.8±10.5 years) free of diabetes at baseline. Comparison with two other published diabetes risk scores (Balkau and Kahn clinical, respectively 5 and 8 variables) and validation on three cohorts (Europe, Iran and Mexico) was performed. Results: After a mean follow-up of 10.9 years, 405 participants (7.7%) developed diabetes. Our score was based on age, gender, waist circumference, diabetes family history, hypertension and physical activity. The area under the curve (AUC) was 0.772 for our score, vs. 0.748 (p<0.001) and 0.774 (p = 0.668) for the other two. Using a 13-point threshold, sensitivity, specificity, positive and negative predictive values (95% CI) of our score were 60.5 (55.5–65.3), 77.1 (75.8–78.2), 18.0 (16.0–20.1) and 95.9 (95.2–96.5) percent, respectively. Our score performed equally well or better than the other two in the Iranian [AUC 0.542 vs. 0.564 (p = 0.476) and 0.513 (p = 0.300)] and Mexican [AUC 0.791 vs. 0.672 (p<0.001) and 0.778 (p = 0.575)] cohorts. In the European cohort, it performed similarly to the Balkau score but worse than the Kahn clinical [AUC 0.788 vs. 0.793 (p = 0.091) and 0.816 (p<0.001)]. Diagnostic capacity of our score was better than the Balkau score and comparable to the Kahn clinical one. Conclusion: Our clinically-based score shows encouraging results compared to other scores and can be used in populations with differing diabetes prevalence. [ABSTRACT FROM AUTHOR]

In nature, protozoa play a major role in controlling bacterial populations. This paper proposes a microfluidic device for the study of protozoa behaviors change due to their chemotactic response in the presence of bacterial cells. A three-channel microfluidic device was designed using a nitrocellulose membrane into which channels were cut using a laser cutter. The membrane was sandwiched between two glass slides; a Euglena suspension was then allowed to flow through the central channel. The two side channels were filled with either, 0.1% peptone as a negative control, or a Listeria suspension respectively. The membrane design prevented direct interaction but allowed Euglena cells to detect Listeria cells as secretions diffused through the nitrocellulose membrane. A significant number of Euglena cells migrated toward the chambers near the bacterial cells, indicating a positive chemotactic response of Euglena toward chemical cues released from Listeria cells. Filtrates collected from Listeria suspension with a series of molecular weight cutoffs (3k, 10k and 100k) were examined in Euglena chemotaxis tests. Euglena cells were attracted to all filtrates collected from the membrane filtration with different molecular weight cutoffs, suggesting small molecules from Listeria might be the chemical cues to attract protozoa. Headspace volatile organic compounds (VOC) released from Listeria were collected, spiked to 0.1% peptone and tested as the chemotactic effectors. It was discovered that the Euglena cells responded quickly to Listeria VOCs including decanal, 3,5- dimethylbenzaldehyde, ethyl acetate, indicating bacterial VOCs were used by Euglena to track the location of bacteria. [ABSTRACT FROM AUTHOR]

Background: Water Sanitation and Hygiene (WASH) in healthcare facilities is critical in the provision of safe and quality care. Poor WASH increases hospital-associated infections and contributes to the rise of antimicrobial resistance (AMR). It is therefore essential for governments and hospital managers to know the state of WASH in these facilities to set priorities and allocate resources. Methods: Using a recently developed survey tool and scoring approach, we assessed WASH across four domains in 14 public hospitals in Kenya (65 indicators) with specific assessments of individual wards (34 indicators). Aggregate scores were generated for whole facilities and individual wards and used to illustrate performance variation and link findings to specific levels of health system accountability. To help interpret and contextualise these scores, we used data from key informant interviews with hospital managers and health workers. Results: Aggregate hospital performance ranged between 47 and 71% with five of the 14 hospitals scoring below 60%. A total of 116 wards were assessed within these facilities. Linked to specific domains, ward scores varied within and across hospitals and ranged between 20% and 80%. At ward level, some critical indicators, which affect AMR like proper waste segregation and hand hygiene compliance activities had pooled aggregate scores of 45 and 35% respectively. From 31 interviews conducted, the main themes that explained this heterogenous performance across facilities and wards included differences in the built environment, resource availability, leadership and the degree to which local managers used innovative approaches to cope with shortages. Conclusion: Significant differences and challenges exist in the state of WASH within and across hospitals. Whereas the senior hospital management can make some improvements, input and support from the national and regional governments are essential to improve WASH as a basic foundation for averting nosocomial infections and the spread of AMR as part of safe, quality hospital care in Kenya. [ABSTRACT FROM AUTHOR]

Aquaculture of bivalve shellfish and seaweed represents a global opportunity to simultaneously advance coastal ecosystem recovery and provide substantive benefits to humanity. To identify marine ecoregions with the greatest potential for development of shellfish and seaweed aquaculture to meet this opportunity, we conducted a global spatial analysis using key environmental (e.g., nutrient pollution status), socioeconomic (e.g., governance quality), and human health factors (e.g., wastewater treatment prevalence). We identify a substantial opportunity for strategic sector development, with the highest opportunity marine ecoregions for shellfish aquaculture centered on Oceania, North America, and portions of Asia, and the highest opportunity for seaweed aquaculture distributed throughout Europe, Asia, Oceania, and North and South America. This study provides insights into specific areas where governments, international development organizations, and investors should prioritize new efforts to drive changes in public policy, capacity-building, and business planning to realize the ecosystem and societal benefits of shellfish and seaweed aquaculture. [ABSTRACT FROM AUTHOR]

Background: Since 2004, the President’s Emergency Plan for AIDS Relief (PEPFAR) has played a large role in Uganda’s HIV/AIDS response. To better target resources to high burden regions and facilities, PEPFAR planned to withdraw from 29% of previously-supported health facilities in Uganda between 2015 and 2017. Methods: We conducted a cross-sectional survey of 226 PEPFAR-supported health facilities in Uganda in mid-2017. The survey gathered information on availability, perceived quality, and access to HIV services before and after transition. We compare responses for facilities transitioned to those maintained on PEPFAR, accounting for survey design. We also extracted data from DHIS2 for the period October 2013–December 2017 on the number of HIV tests and counseling (HTC), number of patients on antiretroviral therapy (Current on ART), and retention on first-line ART (Retention) at 12 months. Using mixed effect models, we compare trends in service volume around the transition period. Results: There were 206 facilities that reported transition and 20 that reported maintenance on PEPFAR. Some facilities reporting transition may have been in a gap between implementing partners. The median transition date was September 2016, nine months prior to the survey. Transition facilities were more likely to discontinue HIV outreach following transition (51.6% vs. 1.4%, p<0.001) and to report declines in HIV care access (43.5% vs. 3.1%, p<0.001) and quality (35.6% vs. 0%, p<0.001). However, transition facilities did not differ in their trends in HIV service volume relative to maintenance facilities. Conclusions: Transition from PEPFAR resulted in facilities reporting worsening patient access and service quality for HIV care, but there is insufficient evidence to suggest negative impacts on volume of HIV services. Facility respondents’ perceptions about access and quality may be overly pessimistic, or they may signal forthcoming impacts. Unrelated to transition, declining retention on ART in Uganda is a cause for concern. [ABSTRACT FROM AUTHOR]

South Korea is ranked as 4th among 34 nations of the Organization for Economic Cooperation and Development with 102 deaths in road accidents per one million population. This paper aims to investigate the factors associated with road accidents in South Korea. The rainfall data of the Korea Meteorological Administration and road accidents data of Traffic Accident Analysis System of Korea Road Traffic Authority is analyzed for this purpose. In this connection, multivariate regression analysis and ratio analysis with the descriptive analysis are performed to uncover the catastrophic factors involved. In turn, the results reveal that traffic volume is the leading factor in road accidents. The limited road extension of 1.47% compared to the 4.14% per annum growth of the vehicles is resulting in road accidents at such a large scale. The increasing proportion of passenger cars accelerate road accidents as well. 56% of accidents occur by the infringement of safety driving violations. The drivers with higher driving experience tend to have a higher accident ratio. The collected data is analyzed in terms of gender, driver experience, type of violations and accidents as well as the associated time of the accidents when they happen. The results indicate that 36.29% and 53.01% of accidents happen by male drivers in the day and night time, respectively. 29.15% of crashes happen due to safety infringement and violations of 41 to 60 years old drivers. The results demonstrate that population density is associated with the accidents frequency and lower density results in an increased number of accidents. The necessity of the state-of-the-art regulations to govern the urban road traffic is beyond dispute, and it becomes even more crucial for citizens’ relief since in our daily lives road accidents are getting more diverse. [ABSTRACT FROM AUTHOR]

Gastric emptying (GE) can be either delayed or accelerated in diabetes mellitus (DM). However, most research has focused on delayed GE mediated by a chronic hyperglycemic condition in DM. As such, the function of GE in the early stages of DM is not well understood. Interstitial cells of Cajal (ICC) are pacemaker cells in the gastrointestinal tract. In the present study, we investigated changes in GE and ICC networks in the early stages of DM using a streptozotocin-induced type 1 diabetic mouse model. The changes in GE were measured by the 13C-octanoic acid breath test. ICC networks were immunohistochemically detected by an antibody for c-Kit, a specific marker for ICC. Our results showed that GE in type 1 DM was significantly accelerated in the early stages of DM (2–4 weeks after onset). In addition, acute normalization of blood glucose levels by a single administration of insulin did not recover normal GE. ICC networks of the gastric antrum were significantly increased in DM and were not affected by the acute normalization of blood glucose. In conclusion, our results suggest that GE is accelerated in the early stages of DM, and it is associated with increased ICC networks. This mechanism may help to clarify a link between the onset of DM and GE disorders. [ABSTRACT FROM AUTHOR]

Although there is good evidence to indicate a major role of intrinsic impairment of the contractile apparatus in muscle weakness seen in several pathophysiological conditions, the factors responsible for control of myofibrillar function are not fully understood. To investigate the role of mechanical load in myofibrillar function, we compared the skinned fiber force between denervated (DEN) and dexamethasone-treated (DEX) rat skeletal muscles with or without neuromuscular electrical stimulation (ES) training. DEN and DEX were induced by cutting the sciatic nerve and daily injection of dexamethasone (5 mg/kg/day) for 7 days, respectively. For ES training, plantarflexor muscles were electrically stimulated to produce four sets of five isometric contractions each day. In situ maximum torque was markedly depressed in the DEN muscles compared to the DEX muscles (-74% vs. -10%), whereas there was not much difference in the degree of atrophy in gastrocnemius muscles between DEN and DEX groups (-24% vs. -17%). Similar results were obtained in the skinned fiber preparation, with a greater reduction in maximum Ca2+-activated force in the DEN than in the DEX group (-53% vs. -16%). Moreover, there was a parallel decline in myosin heavy chain (MyHC) and actin content per muscle volume in DEN muscles, but not in DEX muscles, which was associated with upregulation of NADPH oxidase (NOX) 2, neuronal nitric oxide synthase (nNOS), and endothelial NOS expression, translocation of nNOS from the membrane to the cytosol, and augmentation of mRNA levels of muscle RING finger protein 1 (MuRF-1) and atrogin-1. Importantly, mechanical load evoked by ES protects against DEN- and DEX-induced myofibrillar dysfunction and these molecular alterations. Our findings provide novel insights regarding the difference in intrinsic contractile properties between DEN and DEX and suggest an important role of mechanical load in preserving myofibrillar function in skeletal muscle. [ABSTRACT FROM AUTHOR]

The physical simultaneity between two events can differ from our point of subjective simultaneity (PSS). Studies using simultaneity judgments (SJ) and temporal order judgments (TOJ) tasks have shown that whether two events are reported as simultaneous is highly context-dependent. It has been recently suggested that the interval between the two events in the previous trial can modulate judgments both in SJ and TOJ tasks, an effect named rapid recalibration. In this work, we investigated rapid recalibration in SJ and TOJ tasks and tested whether centering the range of presented intervals on perceived simultaneity modulated this effect. We found a rapid recalibration effect in TOJ, but not in SJ. Moreover, we found that centering the intervals on objective or subjective simultaneity did not change the pattern of results. Interestingly, we also found no correlations between an individual’s PSS in TOJ and in SJ tasks, which corroborates other studies in suggesting that these two psychophysical measures may capture different processes. [ABSTRACT FROM AUTHOR]

Ozenoxacin (OZN) belongs to a new generation of non-fluorinated quinolones for the topical treatment of skin infections which has shown to be effective in the treatment of susceptible and resistant Gram-positive cocci. The mutant prevention concentration (MPC) of ozenoxacin, levofloxacin and ciprofloxacin was determined in quinolone-susceptible and -resistant strains including methicillin-susceptible S. aureus, methicillin-resistant S. aureus, methicillin-susceptible S. epidermidis and methicillin-resistant S. epidermidis with different profile of mutation in the quinolone resistance determining regions (QRDR). The MPC value of OZN for the methicillin-susceptible S. aureus strain susceptible to quinolones, without mutations in QRDR, was 0.05 mg/L, being 280-fold lower than that observed with ciprofloxacin and levofloxacin. In methicillin-susceptible and–resistant S. aureus strains with mutations in the gyrA or/and grlA genes the MPC of OZN went from 0.1 to 6 mg/L, whereas the MPC of levofloxacin and ciprofloxacin was > 50 mg/L for the same strains. For methicillin-susceptible and–resistant S. epidermidis the results were similar to those abovementioned for S. aureus. According to our results, the MPC of OZN was far below the quantity of ozenoxacin achieved in the epidermal layer, suggesting that the in vivo selection of mutants, if it occurs, will take place at low frequency. Ozenoxacin is an excellent candidate for the treatment of bacterial infections caused by susceptible and quinolone-resistant staphylococci isolated usually from skin infections. [ABSTRACT FROM AUTHOR]

A number of studies carried out since the early ‘70s has investigated the effects of isolation on genetic variation within and among human populations in diverse geographical contexts. However, no extensive analysis has been carried out on the heterogeneity among genomes within isolated populations. This issue is worth exploring since events of recent admixture and/or subdivision could potentially disrupt the genetic homogeneity which is to be expected when isolation is prolonged and constant over time. Here, we analyze literature data relative to 87,815 autosomal single-nucleotide polymorphisms, which were obtained from a total of 28 European populations. Our results challenge the traditional paradigm of population isolates as structured as genetically (and genomically) uniform entities. In fact, focusing on the distribution of variance of intra-population diversity measures across individuals, we show that the inter-individual heterogeneity of isolated populations is at least comparable to the open ones. More in particular, three small and highly inbred isolates (Sappada, Sauris and Timau in Northeastern Italy) were found to be characterized by levels of inter-individual heterogeneity largely exceeding that of all other populations, possibly due to relatively recent events of genetic introgression. Finally, we propose a way to monitor the effects of inter-individual heterogeneity in disease-gene association studies. [ABSTRACT FROM AUTHOR]

Sepsis can be caused by malaria infection, but little is known about the utility of the quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA) and SOFA score in malaria. We conducted a prospective observational study from March 2013 to February 2017 to examine adults admitted with community-acquired infection in a tertiary-care hospital in Ubon Ratchathani, Northeast Thailand (Ubon-sepsis). Subjects were classified as having sepsis if they had a modified SOFA score ≥2 within 24 hours of admission. Serum was stored and later tested for malaria parasites using a nested PCR assay. Presence of severe malaria was defined using modified World Health Organization criteria. Of 4,989 patients enrolled, 153 patients (3%) were PCR positive for either Plasmodium falciparum (74 [48%]), P. vivax (69 [45%]), or both organisms (10 [7%]). Of 153 malaria patients, 80 were severe malaria patients presenting with sepsis, 70 were non-severe malaria patients presenting with sepsis, and three were non-severe malaria patients presenting without sepsis. The modified SOFA score (median 5; IQR 4–6; range 1–18) was strongly correlated with malaria severity determined by the number of World Health Organization severity criteria satisfied by the patient (Spearman’s rho = 0.61, p<0.001). Of 80 severe malaria patients, 2 (2.5%), 11 (14%), 62 (77.5%) and 5 (6%), presented with qSOFA scores of 0, 1, 2 and 3, respectively. Twenty eight-day mortality was 1.3% (2/153). In conclusion, qSOFA and SOFA can serve as markers of disease severity in adults with malarial sepsis. Patients presenting with a qSOFA score of 1 may also require careful evaluation for sepsis; including diagnosis of cause of infection, initiation of medical intervention, and consideration for referral as appropriate. [ABSTRACT FROM AUTHOR]

Background: The National Army of Colombia is present in all of the national territory, focused in sylvatic zones where they are exposed continually to potential risk of transmission of Trypanosoma cruzi, the etiological agent of the Chagas disease. People of this study were active personal that were born and lived during their first years in endemic areas of transmission through domiciled vectors as Rhodnius prolixus. Aim: The main aim of this study was to estimate the prevalence of Chagas disease in the active military population of the National Army, gathered in five departments. Methods: An observational and descriptive study with cross-sectional analysis was carried out. Blood sample each patient in order to apply serological diagnosis by two different Enzyme Linked ImmunoSorbent Assay tests, following the algorithm of National Institute of Health, Colombia. In cases of serum results with inconsistencies, a Hemagglutination Inhibition test and Indirect Immunofluorescence assay test were performed to solve inconclusiveness. Positive samples by two different tests were considered seropositive. Additionally, to each positive sample by at least one serological test, we did extraction of DNA for molecular diagnosis. Results: 295 serums were analyzed and two of them were positive in order to get a prevalence of 0.68%. Two samples analyzed by molecular diagnosis were negative. Conclusion: The prevalence was < 1% It is probable the infection in the seropositive individuals occurred before enlisting in the military service due to origin locations with transmission such as Casanare and Boyacá. These findings allow defining the prevention and control programs of chronic cases and reduction in the disease burden. [ABSTRACT FROM AUTHOR]

The isolated fossil remains of an allosauroid theropod from the Lower Cretaceous Khok Kruat Formation of Khorat, Thailand, are described in this study. Detailed observations support the establishment of a new allosauroid, Siamraptor suwati gen. et sp. nov. This new taxon is based on a composite cranial and postcranial skeleton comprising premaxilla, maxilla, jugal, surangular, prearticular, articular, vertebrae, manual ungual, ischium, tibia, and pedal phalanx. It is distinguished from other allosauroids by characters such as a jugal with straight ventral margin and dorsoventrally deep anterior process below the orbit, a surangular with a deep oval concavity at the posterior end of the lateral shelf and four posterior surangular foramina, a long and narrow groove along the suture between the surangular and the prearticular, an articular with a foramen at the notch of the suture with the prearticular, an anterior cervical vertebra with a pneumatic foramen (so-called ‘pleurocoel’) excavating parapophysis, and cervical and posterior dorsal vertebrae penetrated by a pair of small foramina bilaterally at the base of the neural spine. The presence of a huge number of camerae and pneumatopores in cranial and axial elements reveals a remarkable skeletal pneumatic system in this new taxon. Moreover, the phylogenetic analyses revealed that Siamraptor is a basal taxon of Carcharodontosauria, involving a new sight of the paleobiogeographical context of this group. Siamraptor is the best preserved carcharodontosaurian theropod in Southeast Asia, and it sheds new light on the early evolutionary history of Carcharodontosauria. [ABSTRACT FROM AUTHOR]

Big Five personality traits are assumed to be linked with attitudes toward own aging. Since both constructs have central importance for the aging process, it is surprising that to our knowledge no study so far comprehensively addressed their mutual connection over time. We used data from the ILSE study, a longitudinal study capturing personality and attitudes toward own aging at four measurement occasions, spanning 20 years and including two participant cohorts in midlife (n = 501; born 1950–52) and later life (n = 500; born 1930–32). Dual latent change score models showed that personality was longitudinally related to change in attitudes toward own aging: Lower Neuroticism, higher Conscientiousness, and higher Openness predicted more positive attitudes, whereas the direction of the effect for Extraversion varied by time. Furthermore, the role of personality seems to be confined to certain sensitive periods in midlife and early old age. Contrary to our expectations, attitudes toward own aging had only marginal longitudinal impact on the Big Five. Our results shed light on the developmental co-dynamics of personality and subjective perceptions of aging across the second half of the lifespan. [ABSTRACT FROM AUTHOR]

One hundred and twenty dogs were enrolled to value the effect of loading condition changes on left ventricular volumes before and 24-hours after the patent ductus arteriosus (PDA) occlusion by Amplatzer Canine Duct Occluder (ACDO) using standard echocardiography. The animals were divided in pure breed (n. 94) and mixed breed (n. 26); subsequently, the pure breed dogs were divided on the basis of the size of the breed of belonging in 3 groups (small size n. 36; medium size n. 8; large size n. 50). Moreover, the animals were divided in three classes based on their age: until 6 months; 6–12 months; over 12 months. A significant reduction of all the examined parameters (left ventricle internal diameter at end-diastole—LVIDd; left ventricle internal diameter at end-systole—LVIDs; end-diastolic volume—EDV; end-systolic volume—ESV; end-diastolic volume index—EDVI; end-systolic volume index—ESVI; fractional shortening—FS) was observed after ductal closure. Twenty-four hours after the closure, the evaluation of the relative percentage difference (RPD) of the echocardiographic parameters showed a significant reduction, higher in small size breed than in large size breed dogs. No significant difference related to breed size was observed only for RPD_FS variable. A significant interaction effect, between breed size and age classes, was observed only for RPD_EDVI (F = 3.39; p = 0.039). Until six months of age there was no significant difference in RPD_EDVI reduction, but over 6 months a significant reduction between small size and large size breed dogs at 24-hours from the occlusion was observed. In conclusion, our data seem to indicate that small breed dogs show a greater tolerance to congenital volume overload than large breed dogs, and this finding could be justify a delay of PDA closure in order to simplify the interventional procedure. [ABSTRACT FROM AUTHOR]

DNA methylation through the activity of cytosine-5-methyltransferases (C5-MTases) and DNA demethylases plays important roles in genome protection as well as in regulating gene expression during plant development and plant response to environmental stresses. In this study, we report on a genome-wide identification of six C5-MTases (SmelMET1, SmelCMT2, SmelCMT3a, SmelCMT3b, SmelDRM2, SmelDRM3) and five demethylases (SmelDemethylase_1, SmelDemethylase_2, SmelDemethylase_3, SmelDemethylase_4, SmelDemethylase_5) in eggplant. Gene structural characteristics, chromosomal localization and phylogenetic analyses are also described. The transcript profiling of both C5-MTases and demethylases was assessed at three stages of fruit development in three eggplant commercial F1 hybrids: i.e. ‘Clara’, ‘Nite Lady’ and ‘Bella Roma’, representative of the eggplant berry phenotypic variation. The trend of activation of C5-MTases and demethylase genes varied in function of the stage of fruit development and was genotype dependent. The transcription pattern of C5MTAses and demethylases was also assessed in leaves of the F1 hybrid ‘Nite Lady’ subjected to salt and drought stresses. A marked up-regulation and down-regulation of some C5-MTases and demethylases was detected, while others did not vary in their expression profile. Our results suggest a role for both C5-MTases and demethylases during fruit development, as well as in response to abiotic stresses in eggplant, and provide a starting framework for supporting future epigenetic studies in the species. [ABSTRACT FROM AUTHOR]

Background: People with advanced cancer experience multiple symptoms during their illness trajectory, which can fluctuate in intensity. Aim: To describe the course of self-reported quality of life, emotional functioning, physical functioning and symptom intensity over time in cancer patients receiving palliative care. Design: Longitudinal study with monthly assessments, using the EORTC QLQ-C15-PAL. Data were analysed (1) prospectively, from baseline to ≥8-month follow-up; and (2) retrospectively, by taking death as index date and comparing results from three cross-sectional subsamples at different stages of illness (time to death ≥6, 5–3 and 2–0 months). Linear mixed models were calculated. Setting/participants: A total of 1739 patients (mean age 66, 50% male) from 30 palliative care centers in 12 countries were included. Results: In prospective analyses, quality of life, functioning and symptoms–except nausea/vomiting–remained generally stable over time. In retrospective analyses, patients 2–0 months before death reported significantly lower quality of life and physical functioning scores than those 5–3 months before death, who in turn scored lower than those ≥6 months before death, suggesting progressive decline. Emotional functioning remained initially unchanged, but decreased in the last months. Pain, fatigue and appetite loss showed a stable increase in intensity towards death. Dyspnea, insomnia and constipation increased from 5–3 to 2–0 months before death. Nausea/vomiting only increased when comparing those ≥6 months before death with those 2–0 months before death. Conclusion: While the prospective approach showed predominantly stable patterns for quality of life, functioning and symptom severity throughout study duration, retrospective analyses indicated that deterioration was already apparent before the terminal phase and accelerated close to death. Our findings support the importance of early symptom identification and treatment in this population, and highlight the need for further studies to explore what characterizes those with either lower or higher symptom burden at different time points towards death. [ABSTRACT FROM AUTHOR]

Background: Understanding the cardiorespiratory factors related to the increase in oxygen consumption () during exercise is essential for improving cardiorespiratory fitness in individuals with stroke. However, cardiorespiratory factors related to the increase in during exercise in these individuals have not been examined using multivariate analysis. This study aimed to identify cardiorespiratory factors related to the increase in during a graded exercise in terms of respiratory function, cardiac function, and the ability of skeletal muscles to extract oxygen. Methods: Eighteen individuals with stroke (aged 60.1 ± 9.4 years, 67.1 ± 30.8 days poststroke) underwent a graded exercise test for the assessment of cardiorespiratory response to exercise. The increases in from rest to first threshold and that from rest to peak exercise were measured as a dependent variable. The increases in respiratory rate, tidal volume, minute ventilation, heart rate, stroke volume, cardiac output, and arterial-venous oxygen difference from rest to first threshold and those from rest to peak exercise were measured as the independent variables. Results: From rest to first threshold, the increases in arterial-venous oxygen difference (β = 0.711) and cardiac output (β = 0.572) were significant independent variables for the increase in (adjusted R2 = 0.877 p < 0.001). Similarly, from rest to peak exercise, the increases in arterial-venous oxygen difference (β = 0.665) and cardiac output (β = 0.636) were significant factors related to the increase in (adjusted R2 = 0.923, p < 0.001). Conclusion: Our results suggest that the ability of skeletal muscle to extract oxygen is a major cardiorespiratory factor related to the increase in during exercise testing in individuals with stroke. For improved cardiorespiratory fitness in individuals with stroke, the amount of functional muscle mass during exercise may need to be increased. [ABSTRACT FROM AUTHOR]

Hapten contact hypersensitivity (CHS) elicits a well-documented inflammation response that can be used to illustrate training of immune cells through hapten-specific CHS memory. The education of hapten-specific memory T cells has been well-established, recent research in mice has expanded the “adaptive” characteristic of a memory response from solely a function of the adaptive immune system, to innate cells as well. To test whether similar responses are seen in a non-rodent model, we used hapten-specific CHS to measure the ear inflammation response of outbred pigs to dinitrofluorobenzene (DNFB), oxazolone (OXA), or vehicle controls. We adapted mouse innate memory literature protocols to the domestic pig model. Animals were challenged up to 32 days post initial sensitization exposure to the hapten, and specific ear swelling responses to this challenge were significant for 7, 21, and 32 days post-sensitization. We established hapten-specific CHS memory exists in a non-rodent model. We also developed a successful protocol for demonstrating these CHS responses in a porcine system. [ABSTRACT FROM AUTHOR]

Nigeria has a plural legal system in which various sources of law govern simultaneously. Inconsistent and conflicting legal frameworks can reinforce pre–existing health disparities in sexual and reproductive health (SRH). While previous studies indicate poor SRH outcomes for Nigerian women and girls, particularly in Northern states, the relationship between customary and religious law (CRL) and SRH has not been explored. We conducted a state-level ecological study to examine the relationship between CRL and SRH outcomes among women in 36 Nigerian states and the Federal Capital Territory of Abuja (n = 37), using publicly available Demographic and Health Survey data from 2013. Indicators were guided by published research and included contraception use among married women, total fertility rate, median age at first birth, receipt of antenatal care, delivery location, and comprehensive knowledge of HIV. To account for economic differences between states, crude linear regression models were compared to a multivariable model, adjusting for per capita GDP. All SRH outcomes, except comprehensive knowledge of HIV, were statistically significantly more negative in CRL states compared to non–CRL states, even after accounting for state–level GDP. In CRL states in 2013, compared to non–CRL states, the proportion of married women who used any method of contraception was 22.7 percentage points lower ([95% CI: −15.78 –−29.64], p<0.001), a difference that persisted in a model adjusting for per capita GDP (b[adj] = −16.15, 95% CI: [−8.64 –−23.66], p<0.001.). While this analysis of retrospective state-level data found robust associations between CRL and poor SRH outcomes, future research should incorporate prospective individual-level data to further elucidate these findings. [ABSTRACT FROM AUTHOR]

Background: Since 1990, the world’s homicide rate has declined by nearly 20%. While prior research has documented parallel homicide declines across many individual countries, the causes of a shared international homicide decline remain unknown. Drawing on a worldwide process of population ageing, and on research linking age to criminal activity, this study investigates the contribution of global demographic shifts to the international homicide decline. Methods: We draw from (1) a High Coverage Sample of 126 countries since 1990, and (2) a Long Series Sample of 26 countries since 1960 and utilize fixed-effect regressions to evaluate the impact of age structure on homicide trends. In addition, we use a quantile regression to explore variations in the relationship between age structure and homicide conditional on homicide levels. Findings: Results using the High Coverage Sample suggest no relationship between age structure and homicide. However, results from the Long Series Sample suggest that changes in the relative size of countries’ youth population is a major predictor of homicide trends since 1960. In exploring this divergence, we find that the influence of age structure on homicide becomes less evident as other risk factors for violence gain prominence. Thus, while high homicide countries had the most to gain from falling homicide rates, the safety benefits of an ageing population have been concentrated among the least violent countries. Interpretation: While the homicide declines of individual countries have often been attributed to domestic policies, the universality of international homicide trends suggests the influence of broader global phenomenon. We find that countries’ homicide trends are strongly associated with changes in the size of their youth populations, particularly where there are few competing criminogenic forces. Based on these results, we propose an explanation for the international homicide decline, while highlighting the importance of demographic patterns in explaining homicide trends. [ABSTRACT FROM AUTHOR]

Background: Previous studies of radiological damage in rheumatoid arthritis (RA) have used candidate-gene approaches, or evaluated single genome-wide association studies (GWAS). We undertook the first meta-analysis of GWAS of RA radiological damage to: (1) identify novel genetic loci for this trait; and (2) test previously validated variants. Methods: Seven GWAS (2,775 RA cases, of a range of ancestries) were combined in a meta-analysis. Radiological damage was assessed using modified Larsen scores, Sharp van Der Heijde scores, and erosive status. Single nucleotide polymophsim (SNP) associations with radiological damage were tested at a single time-point using regression models. Primary analyses included age and disease duration as covariates. Secondary analyses also included rheumatoid factor (RF). Meta-analyses were undertaken in trans-ethnic and European-only cases. Results: In the trans-ethnic primary meta-analysis, one SNP (rs112112734) in close proximity to HLA-DRB1, and strong linkage disequilibrium with the shared-epitope, attained genome-wide significance (P = 4.2x10-8). In the secondary analysis (adjusting for RF) the association was less significant (P = 1.7x10-6). In both trans-ethnic primary and secondary meta-analyses 14 regions contained SNPs with associations reaching P<5x10-6; in the European primary and secondary analyses 13 and 10 regions contained SNPs reaching P<5x10-6, respectively. Of the previously validated SNPs for radiological progression, only rs660895 (tagging HLA-DRB1*04:01) attained significance (P = 1.6x10-5) and had a consistent direction of effect across GWAS. Conclusions: Our meta-analysis confirms the known association between the HLA-DRB1 shared epitope and RA radiological damage. The lack of replication of previously validated non-HLA markers highlights a requirement for further research to deliver clinically-useful prognostic genetic markers. [ABSTRACT FROM AUTHOR]

Purpose: To investigate if there are differences in macular capillaries between black and white subjects using optical coherence tomography angiography (OCTA) and identify potential factors underlying the epidemiologically-based higher vulnerability of black populations to diabetic retinopathy (DR). Methods: This prospective, observational cross-sectional study included 93 eyes of 47 healthy subjects with no medical history and ocular history who self-identified as black or white and were matched for age, sex, refractive error, and image quality. Subjects underwent OCTA imaging (RTVue-XR Avanti) of the superficial (SCP) and deep (DCP) capillary plexuses and choriocapillaris. AngioAnalytics was used to analyze vessel density (VD) and choriocapillaris % blood flow area (BFA) in the 1mm-diameter fovea, parafovea, and 3mm-diameter circular area including the fovea and parafovea (3x3mm image). Foveal avascular zone (FAZ) was also analyzed. Linear mixed models were used to evaluate for differences between the study groups. Results: Compared to the white subjects in this study, black subjects were found to have: lower foveal VD in the SCP (p<0.05); lower VD in the parafovea and in the 3x3mm image in the DCP (p<0.05); larger FAZ in SCP and DCP (p<0.05); and decreased choriocapillary BFA in the area underlying the fovea, parafovea, and 3x3mm image (p<0.05). Conclusion: In our study, our black subjects had decreased macular capillary vasculature compared to matched white subjects, even in early adulthood and the absence of any systemic or ocular conditions. To our knowledge, this is the first report showing that retinal and choriocapillary vascular differences may contribute to racial disparities in vulnerability to DR. [ABSTRACT FROM AUTHOR]

Candida auris is an invasive and multidrug-resistant ascomycetous yeast that is under global surveillance. All clinical cases of C. auris infection diagnosed from 1997 to 2019 in Japan were non-invasive and sporadic otitis media cases. In the present study, we performed whole-genome sequencing of seven C. auris strains isolated from patients with otitis media in Japan, all of which belonged to clade II. Comparative genome analysis using the high-quality draft genome sequences JCM 15448T revealed that single nucleotide variations (SNVs), clade-specific accessory genes, and copy number variations (CNVs) were identified in each C. auris clade. A total of 61 genes involved in cell wall and stress response-related functions was absent in clade II, and the pattern of conserved CNVs in each clade was more stable in clade II than in other clades. Our data suggest that the genomic structural diversity is stable in C. auris isolated from each biogeographic location, and Japanese strains isolated from patients with otitis media might belong to an ancestral type of C. auris. One Japanese strain, TWCC 58362, with reduced susceptibility to fluconazole, exhibited no mutation in ergosterol biosynthesis-related genes (ERG). However, TWCC 58362-specific variations, including SNVs, indels, and CNVs were detected, suggesting that gene duplication events in C. auris might contribute to antifungal drug resistance. Taken together, we demonstrated that genomic structural variations in C. auris could correlate to geographical dissemination, epidemiology, lesions in the host, and antifungal resistance. [ABSTRACT FROM AUTHOR]