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Given Japan's unique social background, it is critical to understand the current risk factors for postpartum hemorrhage (PPH) to effectively manage the condition, especially among specific groups. Therefore, this study aimed to identify the current risk factors for PPH during planned cesarean section (CS) in Japan. This multicenter retrospective cohort study was conducted in two tertiary maternal-fetal medicine units in Fukushima, Japan and included 1,069 women who underwent planned CS between January 1, 2013, and December 31, 2022. Risk factors for PPH (of > 1000 g and > 1500 g) were assessed using multivariate logistic regression analysis, considering variables such as maternal age, parity, assisted reproductive technology (ART) pregnancy, pre-pregnancy body mass index (BMI), uterine myoma, placenta previa, gestational age at delivery, birth weight categories, and hypertensive disorders of pregnancy (HDP). Multivariate linear regression analyses were conducted to predict estimated blood loss during planned CS. ART pregnancy, a pre-pregnancy BMI of 25.0-29.9 kg/m2, and uterine myoma increased PPH risk at various levels. Maternal smoking increased the risk of >1500 g PPH (adjusted odds ratio: 3.09, 95% confidence interval [CI]: 1.16-8.20). Multivariate linear analysis showed that advanced maternal age (B: 83 g; 95% CI: 27-139 g), ART pregnancy (B: 239 g; 95% CI: 121-357 g), pre-pregnancy BMI of 25.0-29.9 kg/m2 (B: 74 g; 95% CI: 22-167 g), uterine myoma (B: 151 g; 95% CI: 47-256 g), smoking (B: 107 g; 95% CI: 13-200 g), and birth weight > 3,500 g (B: 203 g; 95% CI: 67-338 g) were associated with blood loss during planned CS. Considering a patient's clinical characteristic may help predict bleeding in planned CSs and help improve patient safety.

BackgroundUtilization of skilled birth attendance during home delivery of pregnant women is proven to reduce complications during and after childbirth. Though the utilization of skilled birth attendance (SBA) during home delivery has increased significantly in recent times, the rate of utilizing skilled birth attendance is still low in several regions across India. The objective of this study is to analyze the prevalence and to identify the determinants of the utilization of skilled birth attendance during home delivery of pregnant women in India.MethodsTo conduct this study, data and information from the Indian Demographic and Health Survey 2015-16 have been utilized. The sample size for this study is a weighted sample of 41,171 women. The sample consisted of women who had given a live birth in the three years preceding the survey. For women with more than one child, only the first live birth was considered. The binary logistic regression model and the log-binary logistic regression analysis have been applied as the adjusted odds ratios (AORs) with 95% confidence intervals for identifying the determinants of home-based skilled birth attendance during delivery. That allows us to select the most appropriate model for our study objective by ensuring that the determinants of skilled birth attendance for home delivery are accurately assessed based on the characteristics of the data.ResultsThe analyses show that only 18.8% of women had utilized skilled birth attendance during delivery. Women residing in urban areas are more likely to utilize skilled birth attendance during home delivery (AOR: 1.14; 95% CI: 1.08-1.20). Women having higher education levels are associated with increased use of SBA during home delivery (AOR: 1.15; 95% CI: 1.04-1.28). Exposure to media is associated with increased utilization of SBA (AOR: 1.17; 95% CI: 1.11-1.23). Overweight women are also more likely to avail the SBA during home delivery (AOR: 1.11; 95% CI: 1.03-1.19). Women belonging to affluent households have higher odds of utilizing skilled birth attendance (AOR: 1.41; 95% CI: 1.33-1.49). Having 3+ tetanus injections is associated with the utilization of SBA (AOR: 1.56; 95% CI: 1.43-1.69). Women having 4+ antenatal care visits were more likely to utilize SBA (AOR: 1.81; 95% CI: 1.71-1.92). Women belonging to the Hindu religion were 1.12 times more likely to utilize SBA (AOR: 1.12; 95% CI: 1.07-1.18). Women with 1 to 3 birth orders were 1.40 times more likely to utilize skilled birth attendance during home delivery (AOR: 1.40; 95% CI: 1.30-1.51).ConclusionThe percentage of women utilizing skilled birth attendance during home delivery is still very low which is a matter of serious concern. Several factors have been found to be associated with the utilization of SBA during home delivery in India. As skilled birth attendance has significant positive health outcomes for pregnant women and newborns, efforts to increase the rate of SBA utilization during home delivery should be undertaken.

Background: Differentiated service delivery models have been developed to accommodate the rising number of stable antiretroviral therapy clients and to maintain improvements in health outcomes and care retention. Ethiopia adopted the appointment spacing model and has had notable successes in implementing it. However, with the implementation of the six multi-month scripting/appointment spacing model in Ethiopia, little is known about the uptake and its associated factors. Therefore, this study aimed to assess the uptake and associated factors of the six multi-month scripting/appointment spacing differentiated service delivery model of care among stable clients on antiretroviral therapy in Southern Ethiopia. Methods: A hospital-based cross-sectional study was conducted among 419 stable clients on antiretroviral therapy in southern Ethiopia from June 22 to September 29, 2023. A systematic sampling technique was used to select the study participants. Using a structured questionnaire, socio-demographic, health service delivery, behavioral, and clinical-related data were collected. The collected data were entered into Epi Data version 3.1 and analyzed using Stata version 14. Variables with a P-value <0.05 in the multivariable logistic analysis were considered statistically significant. Multicollinearity and model fitness were checked using the variance inflation factor and the Hosmer and Lemeshow goodness of fit tests, respectively. Results: The uptake of the six multi-month scripting/appointment spacing differentiated service delivery model of care was 63.25% (95% confidence interval (CI): 58.61%, 67.88%). Missed appointment (Adjusted Odds Ratio (AOR): 1.91 (95% CI: 1.13, 3.25)), distance to antiretroviral therapy facility (AOR: 2.90 (95% CI: 1.67, 5.04)), duration on antiretroviral therapy (AOR: 2.21 (95% CI: 1.34, 3.64)), and intermediate social support (AOR: 2.02 (95% CI: 1.29, 3.17)) and strong social support (AOR: 2.71 (95% CI: 1.23, 5.97)) were factors significantly associated with the uptake. Conclusion: The uptake of six multi-month scripting/appointment spacing differentiated service delivery models of care was six out of ten clients on antiretroviral therapy. To further improve the uptake, a precise intervention on the identified associated factor is required. [ABSTRACT FROM AUTHOR]

PurposeCerebral vasospasm following aneurysmal subarachnoid hemorrhage (aSAH) is a significant complication associated with poor neurological outcomes. We present a novel, semi-automated pipeline, implemented in the open-source medical imaging analysis software ITK-SNAP, to segment subarachnoid blood volume from initial CT head (CTH) scans and use this to predict future radiological vasospasm.Methods42 patients were admitted between February 2020 and December 2021 to our tertiary neurosciences center, and whose initial referral CTH scan was used for this retrospective cohort study. Blood load was segmented using a semi-automated random forest classifier and active contour evolution implemented in ITK-SNAP. Clinical data were extracted from electronic healthcare records in order to fit models aimed at predicting radiological vasospasm risk.ResultsSemi-automated segmentations demonstrated excellent agreement with manual, expert-derived volumes (mean Dice coefficient = 0.92). Total normalized blood volume, extracted from CTH images at first presentation, was significantly associated with greater odds of later radiological vasospasm, increasing by approximately 7% for each additional cm3 of blood (OR = 1.069, 95% CI: 1.021-1.120; p < .005). Greater blood volume was also significantly associated with vasospasm of a higher Lindegaard ratio, of longer duration, and a greater number of discrete episodes. Total blood volume predicted radiological vasospasm with a greater accuracy as compared to the modified Fisher scale (AUC = 0.86 vs 0.70), and was of independent predictive value.ConclusionSemi-automated methods provide a plausible pipeline for the segmentation of blood from CT head images in aSAH, and total blood volume is a robust, extendable predictor of radiological vasospasm, outperforming the modified Fisher scale. Greater subarachnoid blood volume significantly increases the odds of subsequent vasospasm, its time course and its severity.

BackgroundHousehold food insecurity is a major public health problem in Ethiopia despite the presence of various interventions implemented by the government. However, there is a dearth of evidence regarding the prevalence and responsible factors in Ethiopia, specifically in the South Ari district. This study, therefore, aimed to assess household food insecurity and associated factors in South Ari district, Southern Ethiopia.MethodsA community-based cross-sectional study was employed from March 11 to April 11, 2021, at South Ari district, Southern Ethiopia. A two-stage sampling technique was used to draw a sample of 717 households. Data were checked and entered into Epi-Data V3.2., and exported to SPSS V25.0 for data exploration and analysis. Variables with a p-value ResultThe prevalence of household food insecurity was 44.8% (95% CI: 41.1%, 48.5%). Larger family size (8 and above) (AOR = 1.91, 95% CI: 1.10, 3.30), high dependency ratio (AOR = 2.71, 95% CI: 1.67, 4.40), medium dependency ratio (AOR = 1.72, 95% CI: 1.13, 2.62), poor wealth index (AOR = 2.30, 95% CI: 1.53, 3.46), not using agricultural extension service (AOR = 2.25, 95% CI: 1.57, 3.23), and non-beneficiary of productive safety net program (AOR = 1.71, 95% CI: 1.01, 2.87) were factors significantly associated with household food insecurity.ConclusionsThe findings of this study showed a significant proportion of households were food insecure in South Ari District. Larger family size, high and medium dependency ratio, poor wealth index, not using agricultural extension service, and non-beneficiary of productive safety net program were significant risk factors associated with household food insecurity. Therefore, rigorous work is highly needed to enhance income-generating activities, strengthen agricultural productivity, expand the productive safety net program, and limit population pressure through improved family planning use.

Given Japan's unique social background, it is critical to understand the current risk factors for postpartum hemorrhage (PPH) to effectively manage the condition, especially among specific groups. Therefore, this study aimed to identify the current risk factors for PPH during planned cesarean section (CS) in Japan. This multicenter retrospective cohort study was conducted in two tertiary maternal-fetal medicine units in Fukushima, Japan and included 1,069 women who underwent planned CS between January 1, 2013, and December 31, 2022. Risk factors for PPH (of > 1000 g and > 1500 g) were assessed using multivariate logistic regression analysis, considering variables such as maternal age, parity, assisted reproductive technology (ART) pregnancy, pre-pregnancy body mass index (BMI), uterine myoma, placenta previa, gestational age at delivery, birth weight categories, and hypertensive disorders of pregnancy (HDP). Multivariate linear regression analyses were conducted to predict estimated blood loss during planned CS. ART pregnancy, a pre-pregnancy BMI of 25.0–29.9 kg/m2, and uterine myoma increased PPH risk at various levels. Maternal smoking increased the risk of >1500 g PPH (adjusted odds ratio: 3.09, 95% confidence interval [CI]: 1.16–8.20). Multivariate linear analysis showed that advanced maternal age (B: 83 g; 95% CI: 27–139 g), ART pregnancy (B: 239 g; 95% CI: 121–357 g), pre-pregnancy BMI of 25.0–29.9 kg/m2 (B: 74 g; 95% CI: 22–167 g), uterine myoma (B: 151 g; 95% CI: 47–256 g), smoking (B: 107 g; 95% CI: 13–200 g), and birth weight > 3,500 g (B: 203 g; 95% CI: 67–338 g) were associated with blood loss during planned CS. Considering a patient's clinical characteristic may help predict bleeding in planned CSs and help improve patient safety. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the impact of Chlamydia trachomatis (CT) infection on pregnancy outcome in pregnant Japanese women. We utilized the data from a nationwide birth cohort study, the Japan Environment and Children's Study (JECS), for this study. We enrolled 26,385 individuals who could refer to data on pregnancy outcomes and confounding factors, with data on CT. Binominal logistic regression models were used to determine whether pregnant women with CT positivity were at more risk of experiencing adverse pregnancy outcomes, preterm birth (PTB), preterm prelabor rupture of membrane (pPROM), low birth weight (LBW) infants, small for gestational age (SGA) births, or hypertensive disorders of pregnancy (HDP). After adjusting for maternal age, parity, marital status, smoking status, and education status, there were no significantly increased risks of PTB, pPROM, LBW infants, SGA, and HDP in the odds ratios. No significant increase in the risk of adverse pregnancy outcomes was observed in any of the subgroup analyses, which were limited to the pregnancy women in Fukushima prefecture, where CT screening could be confirmed at 28-30 weeks of gestation. We believe that the results of this study will make a significant contribution to the future of medical care for pregnant women in Japan. Our findings are important for medical practitioners to contribute to the future medical treatment of Japanese pregnant women, and also to contribute to pre-conception care for Japanese society as a whole, including pregnant women.

Background Vaccines are effective in preventing Coronavirus Disease 2019 (COVID-19). Vaccine hesitancy defined as delay of acceptance or refusal of the vaccine is a major barrier to effective implementation. Methods Participants were recruited statewide through an English and Spanish social media marketing campaign conducted by a local news station during a one-month period as vaccines were becoming available in Rhode Island (from December 21, 2020 to January 22, 2021). Participants completed an online survey about COVID-19 vaccines and vaccine hesitancy with constructs and items adopted from the Health Belief Model. Results A total of 2,007 individuals completed the survey. Eight percent (n = 161) reported vaccine hesitancy. The sample had a median age of 58 years (interquartile range [IQR]: 45, 67), were majority female (78%), White (96%), Non-Hispanic (94%), employed (58%), and reported an annual individual income of $50,000 (59%). COVID-19 vaccine hesitancy was associated with attitudes and behaviors related to COVID-19. A one unit increase in concern about COVID-19 was associated with a 69% (Adjusted Odds Ratio: 0.31, 95% CI: 0.26–0.37) decrease in vaccine hesitancy. A one-level increase in the likelihood of getting influenza vaccine was associated with a 55% (AOR: 0.45 95% CI: 0.41–0.50) decrease in vaccine hesitancy. Conclusions COVID-19 vaccine hesitancy was relatively low in a state-wide survey in Rhode Island. Future research is needed to better understand and tailor messaging related to vaccine hesitancy.

Infection with the SARS-CoV2 virus can vary from asymptomatic, or flu-like with moderate disease, up to critically severe. Severe disease, termed COVID-19, involves acute respiratory deterioration that is frequently fatal. To understand the highly variable presentation, and identify biomarkers for disease severity, blood RNA from COVID-19 patient in an intensive care unit was analyzed by whole transcriptome RNA sequencing. Both SARS-CoV2 infection and the severity of COVID-19 syndrome were associated with up to 25-fold increased expression of neutrophil-related transcripts, such as neutrophil defensin 1 (DEFA1), and 3-5-fold reductions in T cell related transcripts such as the T cell receptor (TCR). The DEFA1 RNA level detected SARS-CoV2 viremia with 95.5% sensitivity, when viremia was measured by ddPCR of whole blood RNA. Purified CD15+ neutrophils from COVID-19 patients were increased in abundance and showed striking increases in nuclear DNA staining by DAPI. Concurrently, they showed >10-fold higher elastase activity than normal controls, and correcting for their increased abundance, still showed 5-fold higher elastase activity per cell. Despite higher CD15+ neutrophil elastase activity, elastase activity was extremely low in plasma from the same patients. Collectively, the data supports the model that increased neutrophil and decreased T cell activity is associated with increased COVID-19 severity, and suggests that blood DEFA1 RNA levels and neutrophil elastase activity, both involved in neutrophil extracellular traps (NETs), may be informative biomarkers of host immune activity after viral infection.

Ritodrine hydrochloride is used for pregnancy prolongation and intrauterine fetal resuscitation. However, its clinical significance in intraamniotic inflammation during preterm labor and intrauterine fetal distress is unclear. We investigated the effects of maternal ritodrine hydrochloride administration (MRA; 200 μg/min for 2 h, followed by 800 μg/min for 2 h after 24 h) on fetal physiological parameters. For this purpose, we used chronically instrumented pregnant sheep at 113-119 d (term = 145 d) of gestation without (Group 1, n = 5) and with (Group 2, n = 5) intraamniotic inflammation induced by lipopolysaccharide injection into the amniotic cavity. The changes in fetal heart rate (FHR) and short-term variability (STV) and long-term variability (LTV) in FHR, fetal blood pressure, and fetal arterial blood gas (FABG) values were measured before and at 1 and 2 h after initiating MRA. Before MRA, all parameters were similar between Groups 1 and 2; however, there was significantly higher STV in Group 2 than in Group 1 before MRA at 800 μg/min, significantly higher partial arterial pressure of carbon dioxide in FABG in Group 2 than in Group 1 before MRA at 200 μg/min, and significantly lower blood glucose (BG) in Group 2 than in Group 1 before MRA at 800 μg/min. One hour after MRA, the FHR, STV, and LTV were significantly higher at 800 μg/min than those at the baseline in Group 1, as determined by the Friedman test; however, no significant difference was observed in Group 2. Additionally, the FABG pH significantly decreased 1 h after MRA at 800 μg/min in Group 2, whereas FABG lactate and BG significantly increased 2 h after MRA at 800 μg/min in Groups 1 and 2. Thus, short-term MRA at 800 μg/min increased the FHR, STV, and LTV significantly; these values were further modified under intraamniotic inflammation.

Uptake of modified lipoproteins by macrophages turns them into foam cells, the hallmark of the atherosclerotic plaque. The initiation and progression of atherosclerosis have been associated with mitochondrial dysfunction. It is known that aggregated low-density lipoproteins (agLDL) induce massive cholesterol accumulation in macrophages in contrast with native LDL (nLDL) and oxidized LDL (oxLDL). In the present study we aimed to assess the effect of agLDL on the mitochondria and ER function in macrophage-derived foam cells, in an attempt to estimate the potential of these cells, known constituents of early fatty streaks, to generate atheroma in the absence of oxidative stress. Results show that agLDL induce excessive accumulation of free (FC) and esterified cholesterol in THP-1 macrophages and determine mitochondrial dysfunction expressed as decreased mitochondrial membrane potential and diminished intracellular ATP levels, without generating mitochondrial reactive oxygen species (ROS) production. AgLDL did not stimulate intracellular ROS (superoxide anion or hydrogen peroxide) production, and did not trigger endoplasmic reticulum stress (ERS) or apoptosis. In contrast to agLDL, oxLDL did not modify FC levels, but stimulated the accumulation of 7-ketocholesterol in the cells, generating oxidative stress which is associated with an increased mitochondrial dysfunction, ERS and apoptosis. Taken together, our results reveal that agLDL induce foam cells formation and mild mitochondrial dysfunction in human macrophages without triggering oxidative or ERS. These data could partially explain the early formation of fatty streaks in the intima of human arteries by interaction of monocyte-derived macrophages with non-oxidatively aggregated LDL generating foam cells, which cannot evolve into atherosclerotic plaques in the absence of the oxidative stress.

We describe the first reported intergeneric, which naturally occurs between two subspecies belonging to different genera, Dactylorhiza fuchsii subsp. sooana (genus Dactylorhiza) and Pseudorchis albida subsp. tricuspis (genus Pseudorchis), as × Pseudorhiza nieschalkii (Senghas) P.F.Hunt nothosubsp. siculorum H.Kertész & N.Anghelescu, 2020. The hybrid was found and digitally photographed for the first time by Hajnalka Kertész in June, 2020, within Terra Siculorum, in one of the Natura 2000 protected areas, known as Harghita Mădăraș, ROSCI00090. Following detailed morphometric analysis using 67 characters and molecular karyological analyses, we identified this unique specimen as an intergeneric hybrid, new to science. The hybrid, an F1 generation plant, most likely representing a single intergeneric pollination event, is phenotypically intermediate between its parental species in most of the characters scored, but it significantly closely resembles Pseudorchis albida subsp. tricuspis parent. Since several individuals of the parental species occurred in near proximity, within 1-10 meters distance, we suggest that the production of this hybrid required a minimum travel distance of ca 1-10 meters, by the pollinators and frequent exchange of pollen between the parental species was very likely. The parental species and the hybrid, which display a considerable synchronicity in their flowering time, overlap in the pollinator community, sharing various species of Hymenopterans and Dipterans, very abundant in the heathland. This Terra Siculorum hybrid is thus best described as a rarely occurring intergeneric hybrid that shows strong Pseudorchis albida subsp. tricuspis parental dominance in inheritance patterns.

Background Emerging worldwide in the past decade, there has been a significant increase in multidrug-resistant bacteria from serious nosocomial infections, especially carbapenemase-producing Gram-negative bacilli that have emerged worldwide. The objective of this study is to investigate carbapenem resistance in Gram-negative bacilli bacteria using phenotypic detection, antimicrobial resistance profiles and genotypic characterisation methods. Methods 200 Gram-negative bacilli isolates were collected from different clinical specimens. All clinical samples were exposed to isolation and identification of significant pathogens applying bacteriological examination and an automated Vitek-2 system. The isolates were subjected to susceptibility tests by the Vitek-2 automated system and those isolates that were resistant to beta-lactam drugs, including carbapenems, third-generation cephalosporines or cefoxitin, were selected for phenotyping using Carba plus disc system assay for detection of carbapenemase-producing isolates. These isolates were further confirmed by molecular detection. PCR was used for the detection carbapenem-resistant genes (OXA-48, IMP, NDM, VIM, and KPC). Results 110 (55%) of 200 Gram-negative bacilli were identified as beta-lactam-resistant isolates. The frequency of carbapenem-resistant isolates was calculated to be 30.9% (n = 34/110). A collection totalling 65/110 (59%) isolates were identified as carbapenemase producers by phenotypic method. Moreover, among the 65 carbapenemase-producing Gram-negative isolates with a positive phenotype-based result, 30 (46%), 20 (30%) and 18 (27%) isolates were positive for OXA-48, KPC and MBL enzymes, respectively, as well as the production of 27% of AmpC with porin loss. Tigecycline was the most effective antibiotic that affected 70% of MDR isolates, but high rates of resistance were detected to other tested antimicrobials. Of interest, a high incidence of MDR, XDR and PDR profiles were observed among all carbapenemase-producing isolates. 36% (24/65) of the tested isolates were MDR to 3 to 5 antimicrobial classes. 29% (17/65) of the recovered isolates were XDR to 6 to 7 antimicrobial classes. Alarmingly, 24% (16/65) of isolates displayed PDR to all the tested 8 antimicrobial classes. Genotype assay, including 53 phenotypically confirmed carbapenemase-producing isolates of Gram-negative bacilli, found 51(96%) isolates were harbouring one or more genes. The most common carbapenemase gene was blaNDM 83% (44/53) followed by blaOXA-48 75% (40/53), blaVIM 49% (26/53) and blaIMP 43% (23/53), while the gene blaKPC was least frequent 7% (4/53). 92% (46/51) of isolates were involved in the production of more than one carbapenemase gene. Conclusion This study demonstrated the emergence of carbapenemase-producing Gram-negative pathogens implicated in healthcare-related infections. Accurate identification of carbapenem-resistant bacterial pathogens is essential for patient treatment, as well as the development of appropriate contamination control measures to limit the rapid spread of pathogens. Tigecycline exhibited potent antimicrobial activity against MDR, XDR and PDR-producing strains that establish a threatening alert which indicates the complex therapy of infections caused by these pathogens.

ObjectivePlacental abruption is a significant obstetric complication that affects both maternal and neonatal mortality and morbidity. The present study examined the effect of maternal age on the incidence of placental abruption.MethodsWe used data of singleton pregnancies from the Japan Environment and Children's Study, which was a prospective birth cohort study conducted between January 2011 and March 2014 across 15 regional centers in Japan. A multiple regression model was used to identify whether maternal age (ResultsA total of 94,410 Japanese women (93,994 without placental abruption and 416 with placental abruption) were recruited. Herein, 764, 8421, 25915, 33517, and 25793 women were aged ConclusionsIn the Japanese general population, besides advanced maternal age, teenage pregnancy was associated with placental abruption. Recently, the mean maternal age has been changing in Japan. Therefore, it is important for obstetric care providers to provide proper counseling to young women based on up-to-date evidence.

In the last decade, carbon nanotube growth substrates have been used to investigate neurons and neuronal networks formation in vitro when guided by artificial nano-scaled cues. Besides, nanotube-based interfaces are being developed, such as prosthesis for monitoring brain activity. We recently described how carbon nanotube substrates alter the electrophysiological and synaptic responses of hippocampal neurons in culture. This observation highlighted the exceptional ability of this material in interfering with nerve tissue growth. Here we test the hypothesis that carbon nanotube scaffolds promote the development of immature neurons isolated from the neonatal rat spinal cord, and maintained in vitro. To address this issue we performed electrophysiological studies associated to gene expression analysis. Our results indicate that spinal neurons plated on electro-conductive carbon nanotubes show a facilitated development. Spinal neurons anticipate the expression of functional markers of maturation, such as the generation of voltage dependent currents or action potentials. These changes are accompanied by a selective modulation of gene expression, involving neuronal and non-neuronal components. Our microarray experiments suggest that carbon nanotube platforms trigger reparative activities involving microglia, in the absence of reactive gliosis. Hence, future tissue scaffolds blended with conductive nanotubes may be exploited to promote cell differentiation and reparative pathways in neural regeneration strategies.

Systemic lupus erythematosus, simply known as lupus, is associated with adverse obstetric outcomes. This study evaluated the incidence of preterm births (before 37 and 34 weeks), low birthweight infants (

IntroductionA large proportion of patients with COVID-19 develop acute kidney injury (AKI). While the most severe of these cases require renal replacement therapy (RRT), little is known about their clinical course.MethodsWe describe the clinical characteristics of COVID-19 patients in the ICU with AKI requiring RRT at an academic medical center in New York City and followed patients for outcomes of death and renal recovery using time-to-event analyses.ResultsOur cohort of 115 patients represented 23% of all ICU admissions at our center, with a peak prevalence of 29%. Patients were followed for a median of 29 days (2542 total patient-RRT-days; median 54 days for survivors). Mechanical ventilation and vasopressor use were common (99% and 84%, respectively), and the median Sequential Organ Function Assessment (SOFA) score was 14. By the end of follow-up 51% died, 41% recovered kidney function (84% of survivors), and 8% still needed RRT (survival probability at 60 days: 0.46 [95% CI: 0.36-0.56])). In an adjusted Cox model, coronary artery disease and chronic obstructive pulmonary disease were associated with increased mortality (HRs: 3.99 [95% CI 1.46-10.90] and 3.10 [95% CI 1.25-7.66]) as were angiotensin-converting-enzyme inhibitors (HR 2.33 [95% CI 1.21-4.47]) and a SOFA score >15 (HR 3.46 [95% CI 1.65-7.25).Conclusions and relevanceOur analysis demonstrates the high prevalence of AKI requiring RRT among critically ill patients with COVID-19 and is associated with a high mortality, however, the rate of renal recovery is high among survivors and should inform shared-decision making.

The development of positive attitudes toward science is one of the main priorities in science education. However, there is a lack of reliable and valid instruments to measure Spanish-speaking elementary students' attitudes towards school science. In this study, the translation and validation of the Spanish School-Science Attitude Survey (S-SSAS) is reported. The instrument was administered to 643 students enrolled in 3rd to 6th elementary grades. Psychometric evaluation of the S-SSAS provided sound evidence for validity (face, content, construct and criterion) and reliability (internal consistency and temporal stability). Content validity was confirmed through a panel of experts who reached great consensus in linking items to attitudinal constructs, with an ICC = .956. Think-aloud interviews confirmed that students have easily understood and correctly interpreted all items included, thus providing face validity for the S-SSAS. Consistent with theoretical expectations, predictive validity ranged between -.334 to 543 and concurrent validity was examined through S-SSAS correlation with two external measures of conceptual convergence that ranged from.301 to .560, thus confirming criterion validity. Construct validity was assessed by obtaining consistent results with the original scale in terms of reporting no statistically significant differences in attitudinal profiles towards school science between girls and boys and between students from urban and rural schools. Cronbach αfor the entire scale was .704, with item-total correlation ranging from .243 to .560, which reports acceptable internal consistency. Temporal stability with a 10-days span was good, with ICC = .873 and r = .464-790. Taken together, these results indicate that the Spanish single-items School-Science Attitude Survey is easy to administer and equally interpreted by both girls and boys enrolled in rural and urban elementary schools, thus being a valid and reliable instrument for measuring attitudes towards school science.

The Ligurian Sea is one of the most studied Mediterranean basins. Since the beginning of the last century, many research expeditions have characterized its benthic and pelagic fauna through scuba diving and trawl surveys. However, a large knowledge gap exists about the composition of benthic communities extending into the so-called mesophotic or twilight depth range, currently under intense pressure from commercial and recreational fishing. A series of visual surveys, carried out by means of remotely operated vehicles between 2012 and 2018, were conducted along the Ligurian deep continental shelf and shelf break, between 30 and 210 m depth, in order to characterize the main benthic biocoenoses dwelling at this depth range and to determine the most relevant environmental factors that explain their spatial distribution. Deep circalittoral communities of the Ligurian Sea were represented by a mixture of species belonging to the deepest extension of shallow-water habitats and deep circalittoral ones. Twelve major biocoenoses were identified, each one characterized by specific preferences in depth range, substrate type and seabed slope. Those biocoenoses included gorgonian and hydrozoan forests, dense keratose sponge grounds, Dendrophyllia cornigera gardens, bryozoan beds and soft-bottom meadows of sabellid polychaetes and soft-corals. Other less common aggregations included six forests of black corals and two populations of Paramuricea macrospina. A georeferenced database has been created in order to provide information to managers and stakeholders about the location of the identified communities and high-diversity areas, aiming to facilitate sustainable long-term conservation of the Ligurian benthic ecosystem.

Lebiasinidae is a small fish family composed by miniature to small-sized fishes with few cytogenetic data (most of them limited to descriptions of diploid chromosome numbers), thus preventing any evolutionary comparative studies at the chromosomal level. In the present study, we are providing, the first cytogenetic data for the red spotted tetra, Copeina guttata, including the standard karyotype, C-banding, repetitive DNA mapping by fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH), providing chromosomal patterns and novel insights into the karyotype differentiation of the family. Males and females share diploid chromosome number 2n = 42 and karyotype composed of 2 metacentric (m), 4 submetacentric (sm) and 36 subtelocentric to acrocentric (st-a) chromosomes. Blocks of constitutive heterochromatin were observed in the centromeric and interstitial regions of several chromosomes, in addition to a remarkably large distal block, heteromorphic in size, which fully corresponded with the 18S rDNA sites in the fourth chromosomal pair. This overlap was confirmed by 5S/18S rDNA dual-color FISH. On the other hand, 5S rDNA clusters were situated in the long and short arms of the 2nd and 15th pairs, respectively. No sex-linked karyotype differences were revealed by male/female CGH experiments. The genomic probes from other two lebiasinid species, Lebiasina melanoguttata and Pyrrhulina brevis, showed positive hybridization signals only in the NOR region in the genome of C. guttata. We demonstrated that karyotype diversification in lebiasinids was accompanied by a series of structural and numeric chromosome rearrangements of different types, including particularly fusions and fissions.

A lot of daily activities are conducted in a sedentary posture. This includes a thermal interaction between the human and the seat that has implications on thermal perception and comfort. These interactions are investigated by simulating heat and mass transfer, thus, reducing a need for costly and time demanding subject studies. However, it is not clear, from the available literature, what portion of the body surface area is actually affected by the seat with respect to human anthropometry. The aim of this study was to develop a predicting function of the seat contact area based on anthropometric parameters. The results showed strong linear correlation between the contact area obtained by printing a body silhouette on paper placed at the seat and body weight, height, body surface area, and body mass index. The body surface area and the body weight were identified as the best predictors for the contact area.

Detailed clonal phenotypic/genotypic analyses explored viral-escape mechanisms during maraviroc-based therapy in highly treatment-experienced participants from the MOTIVATE trials. To allow real-time assessment of samples while maintaining a blind trial, the first 267 enrolled participants were selected for evaluation. At failure, plasma samples from 20/50 participants (16/20 maraviroc-treated) with CXCR4-using virus and all 38 (13 maraviroc-treated) with CCR5-tropic virus were evaluated. Of those maraviroc-treated participants with CXCR4-using virus at failure, genotypic and phenotypic clonal tropism determinations showed >90% correspondence in 14/16 at Day 1 and 14/16 at failure. Phylogenetic analysis of clonal sequences detected pre-treatment progenitor CXCR4-using virus, or on-treatment virus highly divergent from the Day 1 R5 virus, excluding possible co-receptor switch through maraviroc-mediated evolution. Re-analysis of pre-treatment samples using the enhanced-sensitivity Trofile® assay detected CXCR4-using virus pre-treatment in 16/20 participants failing with CXCR4-using virus. Post-maraviroc reversion of CXCR4-use to CCR5-tropic occurred in 7/8 participants with follow-up, suggesting selective maraviroc inhibition of CCR5-tropic variants in a mixed-tropic viral population, not emergence of de novo mutations in CCR5-tropic virus, as the main virologic escape mechanism. Maraviroc-resistant CCR5-tropic virus was observed in plasma from 5 treated participants with virus displaying reduced maximal percent inhibition (MPI) but no evidence of IC50 change. Env clones with reduced MPI showed 1-5 amino acid changes specific to each V3-loop region of env relative to Day 1. However, transferring on-treatment resistance-associated changes using site-directed mutagenesis did not always establish resistance in Day 1 virus, and key 'signature' mutation patterns associated with reduced susceptibility to maraviroc were not identified. Evolutionary divergence of the CXCR4-using viruses is confirmed, emphasizing natural selection not influenced directly by maraviroc; maraviroc simply unmasks pre-existing lineages by inhibiting the R5 virus. For R5-viral failure, resistance development through drug selection pressure was uncommon and manifested through reduced MPI and with virus strain-specific mutational patterns.

Galium verum is a well-known medicinal plant which is used in various pathologies. G. verum extracts are characterized here using chromatography, where among the rich pool of phenolic acids of flavonoids two known anti-stress modulators, chlorogenic acid and rutin are identified in high quantities. Additionally, the extracts are characterized using a series of in vitro assays (EPR, DPPH, TPC and TEAC). Considering the chemical findings, the potential beneficial effects of the G. verum extract are explored here in a living organism exposed to stress induced oxidative damages. Thus, the biochemical-modulatory and antioxidant roles of two doses of G. verum extract are examined in animals exposed to acute restraint and dark stress (S). The animals were divided in groups [control, S, SG1 (exposed to 25 mg G. verum extract), SG2 (50 mg extract)]. Increased levels of lipid peroxidation (TBARS from 4.43 to 8.06 nmol/mL), corticosterone from 0.43 to 1.96 μg/dL and epinephrine from 44.43 to 126.7 μg/mL, as well as decreased antioxidant enzymes activities (SOD/CAT) were observed in the S group. The G. verum extract afforded a near-normal equilibrium within the biochemical parameters of animals exposed to RS, by reducing oxidative damage (TBARS at a 3.73 nmol/mL; CS at 0.90 μg/dL; EP at 63.72 μg/mL) and by restoring the antioxidant balance.

During the last decade, the incidence and mortality rates of ST-elevation myocardial infarction (STEMI) has been steadily increasing in young women but not in men. Environmental variables that contribute to cardiovascular events in women remain ill-defined.A total of 2199 consecutive patients presenting with acute ST-elevation myocardial infarction (STEMI, 25.8% women, mean age 62.6±12.4 years) were admitted at the Montreal Heart Institute between June 2010 and December 2014. Snow fall exceeding 2cm/day was identified as a positive predictor for STEMI admission rates in the overall population (RR 1.28, 95% CI 1.07-1.48, p = 0.005), with a significant effect being seen in men (RR 1.30, 95% CI 1.06-1.53, p = 0.01) but not in women (p = NS). An age-specific analysis revealed a significant increase in hospital admission rates for STEMI in younger women ≤55 years, (n = 104) during days with higher outside temperature (p = 0.004 vs men ≤55 years) and longer daylight hours (p = 0.0009 vs men ≤55 years). Accordingly, summer season, increased outside temperature and sunshine hours were identified as strong positive predictors for STEMI occurrence in women ≤55 years (RR 1.66, 95% CI 1.1-2.5, p = 0.012, RR 1.70, 95% CI 1.2-2.5, p = 0.007, and RR 1.67, 95% CI 1.2-2.5, p = 0.011, respectively), while an opposite trend was observed in men ≤55 years (RR for outside temperature 0.8, 95% CI 0.73-0.95, p = 0.01).The impact of environmental variables on STEMI is age- and sex-dependent. Higher temperature may play an important role in triggering such acute events in young women.

Purpose: Cerebral vasospasm following aneurysmal subarachnoid hemorrhage (aSAH) is a significant complication associated with poor neurological outcomes. We present a novel, semi-automated pipeline, implemented in the open-source medical imaging analysis software ITK-SNAP, to segment subarachnoid blood volume from initial CT head (CTH) scans and use this to predict future radiological vasospasm. Methods: 42 patients were admitted between February 2020 and December 2021 to our tertiary neurosciences center, and whose initial referral CTH scan was used for this retrospective cohort study. Blood load was segmented using a semi-automated random forest classifier and active contour evolution implemented in ITK-SNAP. Clinical data were extracted from electronic healthcare records in order to fit models aimed at predicting radiological vasospasm risk. Results: Semi-automated segmentations demonstrated excellent agreement with manual, expert-derived volumes (mean Dice coefficient = 0.92). Total normalized blood volume, extracted from CTH images at first presentation, was significantly associated with greater odds of later radiological vasospasm, increasing by approximately 7% for each additional cm3 of blood (OR = 1.069, 95% CI: 1.021–1.120; p <.005). Greater blood volume was also significantly associated with vasospasm of a higher Lindegaard ratio, of longer duration, and a greater number of discrete episodes. Total blood volume predicted radiological vasospasm with a greater accuracy as compared to the modified Fisher scale (AUC = 0.86 vs 0.70), and was of independent predictive value. Conclusion: Semi-automated methods provide a plausible pipeline for the segmentation of blood from CT head images in aSAH, and total blood volume is a robust, extendable predictor of radiological vasospasm, outperforming the modified Fisher scale. Greater subarachnoid blood volume significantly increases the odds of subsequent vasospasm, its time course and its severity. [ABSTRACT FROM AUTHOR]

This study aimed to predict recurrence after coil embolization of unruptured cerebral aneurysms with computational fluid dynamics (CFD) using porous media modeling (porous media CFD).A total of 37 unruptured cerebral aneurysms treated with coiling were analyzed using follow-up angiograms, simulated CFD prior to coiling (control CFD), and porous media CFD. Coiled aneurysms were classified into stable or recurrence groups according to follow-up angiogram findings. Morphological parameters, coil packing density, and hemodynamic variables were evaluated for their correlations with aneurysmal recurrence. We also calculated residual flow volumes (RFVs), a novel hemodynamic parameter used to quantify the residual aneurysm volume after simulated coiling, which has a mean fluid domain > 1.0 cm/s.Follow-up angiograms showed 24 aneurysms in the stable group and 13 in the recurrence group. Mann-Whitney U test demonstrated that maximum size, dome volume, neck width, neck area, and coil packing density were significantly different between the two groups (P < 0.05). Among the hemodynamic parameters, aneurysms in the recurrence group had significantly larger inflow and outflow areas in the control CFD and larger RFVs in the porous media CFD. Multivariate logistic regression analyses demonstrated that RFV was the only independently significant factor (odds ratio, 1.06; 95% confidence interval, 1.01-1.11; P = 0.016).The study findings suggest that RFV collected under porous media modeling predicts the recurrence of coiled aneurysms.

While there is strong evidence that regular participation in physical activity (PA) brings numerous health benefits to older adults, and interventions to effectively promote PA are being developed and tested, the characteristics and components of the most effective interventions remain unclear. This systematically conducted review of systematic reviews evaluated the effects and characteristics of PA promotion interventions aimed at community dwelling people over 50 years old.Major databases were searched for reviews from January 1990 to May 2015. TIDieR guidelines aided data extraction and the ROBIS tool was used to assess the risk of bias. Primary outcomes were objective and self-reported levels of PA. Indicators of psychological wellbeing and participation rates were secondary outcomes.Of 1284 records identified, 19 reviews met inclusion criteria and eight included meta-analyses. Interventions typically incorporated behaviour change techniques (BCTs) and were delivered as face-to-face, remote, group, individual or as combined interventions. Despite their heterogeneity, interventions often resulted in sustained improvements in PA over the study period, typically at 12 months, and led to improvements in general wellbeing. However, ways to ensure effective maintenance beyond one year are unclear. Certain intervention components were more clearly associated with positive effects (e.g. tailoring promotion strategy with combination of cognitive and behavioural elements, low to moderate intensity activity recommended). We found no evidence that certain other intervention characteristics were superior in achieving positive outcomes (e.g. mode of delivery, setting, professional background of the intervention provider, type of PA recommended).The evidence suggests that interventions to promote PA among older adults are generally effective but there is uncertainty around the most beneficial intervention components. There are indications that purely cognitive strategies and BCTs might be less suitable for older adults than motivators more meaningful to them, including social and environmental support, and enjoyment coming from being physically active. A whole system-oriented approach is required that is tailored to meet the needs of older adults and aligned with social, individual and environmental factors.

It has been largely proved that while judging a force humans mainly rely on the motor commands produced to interact with that force (i.e., sense of effort). Despite of a large bulk of previous investigations interested in understanding the contributions of the descending and ascending signals in force perception, very few attempts have been made to link a measure of neural output (i.e., EMG) to the psychophysical performance. Indeed, the amount of correlation between EMG activity and perceptual decisions can be interpreted as an estimate of the contribution of central signals involved in the sensation of force. In this study we investigated this correlation by measuring the muscular activity of eight arm muscles while participants performed a quasi-isometric force detection task. Here we showed a method to quantitatively describe muscular activity ("muscle-metric function") that was directly comparable to the description of the participants' psychophysical decisions about the stimulus force. We observed that under our experimental conditions, muscle-metric absolute thresholds and the shape of the muscle-metric curves were closely related to those provided by the psychophysics. In fact a global measure of the muscles considered was able to predict approximately 60% of the perceptual decisions total variance. Moreover the inter-subjects differences in psychophysical sensitivity showed high correlation with both participants' muscles sensitivity and participants' joint torques. Overall, our findings gave insights into both the role played by the corticospinal motor commands while performing a force detection task and the influence of the gravitational muscular torque on the estimation of vertical forces.

Mosquitoes in the Culex pipiens complex are considered to be involved in the transmission of a range of pathogens, including West Nile virus (WNV). Although its taxonomic status is still debated, the complex includes species, both globally distributed or with a more limited distribution, morphologically similar and characterised by different physiological and behavioural traits, which affect their ability as vectors. In many European countries, Cx. pipiens and its sibling species Culex torrentium occur in sympatry, exhibiting similar bionomic and morphological characters, but only Cx. pipiens appears to play a vector role in WNV transmission. This species consists of two biotypes, pipiens and molestus, which can interbreed when in sympatry, and their hybrids can act as WNV-bridge vectors, due to intermediate ecological features. Considering the yearly WNV outbreaks since 2008 and given the morphological difficulties in recognising species and biotypes, our aim was to molecularly identify and characterised Cx. pipiens and Cx. torrentium in Italy, using recently developed molecular assays. Culex torrentium was not detected; as in other European countries, the pipiens and molestus biotypes were widely found in sympatry with hybrids in most environments. The UPGMA cluster analysis applied to CQ11 genotypic frequencies mainly revealed two groups of Cx. pipiens populations that differed in ecological features. The high propensity of the molestus biotype to exist in hypogean environments, where the habitat's physical characteristics hinder and preclude the gene flow, was shown. These results confirmed the CQ11 assay as a reliable diagnostic method, consistent with the ecological and physiological aspects of the populations analysed. Since the assessment of the actual role of three biotypes in the WNV circulation remains a crucial point to be elucidated, this extensive molecular screening of Cx. pipiens populations can provide new insights into the ecology of the species and may give useful indications to plan and implement WNV surveillance activities in Italy.

OBJECTIVE:To verify whether body mass index (BMI) classification proposed by the Institute of Medicine (IOM) is valid in Japanese women. METHOD:A study was conducted in 97,157 women with singleton pregnancies registered in the Japan Society of Obstetrics and Gynecology (JSOG) Successive Pregnancy Birth Registry System between January 2013 and December 2013, to examine pregnancy outcomes in four groups stratified by pre-pregnancy BMI category according to the 2009 criteria recommended by the Institute of Medicine (IOM). The groups comprised 17,724 underweight women with BMI

Despite our knowledge of the protective role of antibodies passed to infants through breast milk, our understanding of immunity transfer via maternal leukocytes is still limited. To emulate the immunological interface between the mother and her infant while breast-feeding, we used murine pups fostered after birth onto MHC-matched and MHC-mismatched dams. Overall, data revealed that: 1) Survival of breast milk leukocytes in suckling infants is possible, but not significant after the foster-nursing ceases; 2) Most breast milk lymphocytes establish themselves in specific areas of the intestine termed Peyer's patches (PPs); 3) While most leukocytes in the milk bolus were myeloid cells, the majority of breast milk leukocytes localized to PPs were T lymphocytes, and cytotoxic T cells (CTLs) in particular; 4) These CTLs exhibit high levels of the gut-homing molecules α4β7 and CCR9, but a reduced expression of the systemic homing marker CD62L; 5) Under the same activation conditions, transferred CD8 T cells through breast milk have a superior capacity to produce potent cytolytic and inflammatory mediators when compared to those generated by the breastfed infant. It is therefore possible that maternal CTLs found in breast milk are directed to the PPs to compensate for the immature adaptive immune system of the infant in order to protect it against constant oral infectious risks during the postnatal phase.

A series of hemoglobin-based oxygen carrier candidates (HBOC), previously noted for their differences in prooxidative and physiological reactivity, were compared in terms of the negative effects displayed upon injection in Wistar rats. At the concentrations tested, antioxidant strategies based on albumin as well as based on rubrerythrin appear to offer observable physiological advantages.

The Eastern European Grey cattle are regarded as the direct descendants of the aurochs (Bos taurus primigenius). Nowadays in Romania, less than 100 Grey animals are being reared and included in the national gene reserve. We examined the genetic diversity among Romanian Grey, Brown, Spotted and Black and White cattle breeds, with a particular focus on Romanian Grey through the use of (i) 11 bovine specific microsatellite markers on 83 animals and (ii) 638 bp length of mitochondrial DNA (mtDNA) D-loop region sequence data from a total of 81 animals. Both microsatellite and mtDNA analysis revealed a high level of genetic variation in the studied breeds. In Romanian Grey a total of 100 alleles were found, the mean number of observed alleles per locus was 9.091; the average observed heterozygosity was 0.940; the Wright's fixation index (FIS) was negative (-0.189) and indicates that there is no inbreeding and no selection pressure. MtDNA analysis revealed 52 haplotypes with 67 variable sites among the Romanian cattle breeds without any insertion or deletion. Haplotype diversity was 0.980 ± 0.007 and ranged from 0.883 ± 0.056 (Brown) to 0.990 ± 0.028 (Spotted and Black and White). The highest genetic variability of the mtDNA was recorded in the Grey breed, where 18 haplotypes were identified. The most frequent mtDNA D-loop region belonged to T3 haplogroup (80.247%), which was found across all studied breeds, while T2 haplotypes (16.049%) was only found in Grey, Spotted and Black and White genotypes. The T1 haplotypes (3.704%) were found in the Grey and Spotted. The current results contribute to the general knowledge on genetic diversity found in Eastern European cattle breeds and could prove a valuable tool for the conservation efforts of animal genetic resources (FAnGR).

The genotype-phenotype correlation of MEFV remains unclear for the familial Mediterranean fever (FMF) patients, especially without canonical MEFV mutations in exon 10. The risk of FMF appeared to be under the influence of other factors in this case. The contribution of HLA polymorphisms to the risk of FMF was examined as strong candidates of modifier genes.Genotypes of HLA-B and -DRB1 loci were determined for 258 mutually unrelated Japanese FMF patients, who satisfied modified Tel-Hashomer criteria, and 299 healthy controls. The effects of carrier status were evaluated for the risk of FMF by odds ratio (OR). The HLA effects were also assessed for clinical forms of FMF, subsets of FMF with certain MEFV genotypes and responsiveness to colchicine treatment.The carriers of B*39:01 were increased in the patients (OR = 3.25, p = 0.0012), whereas those of DRB1*15:02 were decreased (OR = 0.45, p = 0.00050), satisfying Bonferroni's correction for multiple statistical tests (n = 28, p

Several ubiquitin-binding zinc fingers (UBZs) have been reported to preferentially bind K63-linked ubiquitin chains. In particular, the UBZ domain of FAAP20 (FAAP20-UBZ), a member of the Fanconi anemia core complex, seems to recognize K63-linked ubiquitin chains, in order to recruit the complex to DNA interstrand crosslinks and mediate DNA repair. By contrast, it is reported that the attachment of a single ubiquitin to Rev1, a translesion DNA polymerase, increases binding of Rev1 to FAAP20. To clarify the specificity of FAAP20-UBZ, we determined the crystal structure of FAAP20-UBZ in complex with K63-linked diubiquitin at 1.9 Å resolution. In this structure, FAAP20-UBZ interacts only with one of the two ubiquitin moieties. Consistently, binding assays using surface plasmon resonance spectrometry showed that FAAP20-UBZ binds ubiquitin and M1-, K48- and K63-linked diubiquitin chains with similar affinities. Residues in the vicinity of Ala168 within the α-helix and the C-terminal Trp180 interact with the canonical Ile44-centered hydrophobic patch of ubiquitin. Asp164 within the α-helix and the C-terminal loop mediate a hydrogen bond network, which reinforces ubiquitin-binding of FAAP20-UBZ. Mutations of the ubiquitin-interacting residues disrupted binding to ubiquitin in vitro and abolished the accumulation of FAAP20 to DNA damage sites in vivo. Finally, structural comparison among FAAP20-UBZ, WRNIP1-UBZ and RAD18-UBZ revealed distinct modes of ubiquitin binding. UBZ family proteins could be divided into at least three classes, according to their ubiquitin-binding modes.

The presence of outliers in financial asset returns is a frequently occurring phenomenon which may lead to unreliable mean-variance optimized portfolios. This fact is due to the unbounded influence that outliers can have on the mean returns and covariance estimators that are inputs in the optimization procedure. In this paper we present robust estimators of mean and covariance matrix obtained by minimizing an empirical version of a pseudodistance between the assumed model and the true model underlying the data. We prove and discuss theoretical properties of these estimators, such as affine equivariance, B-robustness, asymptotic normality and asymptotic relative efficiency. These estimators can be easily used in place of the classical estimators, thereby providing robust optimized portfolios. A Monte Carlo simulation study and applications to real data show the advantages of the proposed approach. We study both in-sample and out-of-sample performance of the proposed robust portfolios comparing them with some other portfolios known in literature.

Inflammation is crucially involved in the development of carotid plaques. We examined the relationship between plaque vulnerability and inflammatory biomarkers using intraoperative blood and tissue specimens. We examined 58 patients with carotid stenosis. Following carotid plaque magnetic resonance imaging, 41 patients underwent carotid artery stenting (CAS) and 17 underwent carotid endarterectomy (CEA). Blood samples were obtained from the femoral artery (systemic) and common carotid artery immediately before and after CAS (local). Seventeen resected CEA tissue samples were embedded in paraffin, and histopathological and immunohistochemical analyses for IL-6, IL-10, E-selectin, adiponectin, and pentraxin 3 (PTX3) were performed. Serum levels of IL-6, IL-1β, IL-10, TNFα, E-selectin, VCAM-1, adiponectin, hs-CRP, and PTX3 were measured by multiplex bead array system and ELISA. CAS-treated patients were classified as stable plaques (n = 21) and vulnerable plaques (n = 20). The vulnerable group showed upregulation of the proinflammatory cytokines (IL-6 and TNFα), endothelial activation markers (E-selectin and VCAM-1), and inflammation markers (hs-CRP and PTX3) and downregulation of the anti-inflammatory markers (adiponectin and IL-10). PTX3 levels in both systemic and intracarotid samples before and after CAS were higher in the vulnerable group than in the stable group. Immunohistochemical analysis demonstrated that IL-6 was localized to inflammatory cells in the vulnerable plaques, and PTX3 was observed in the endothelial and perivascular cells. Our findings reveal that carotid plaque vulnerability is modulated by the upregulation and downregulation of proinflammatory and anti-inflammatory factors, respectively. PTX3 may thus be a potential predictive marker of plaque vulnerability.

Two studies examined how effort invested in a task shapes the affective predictions related to potential success in that task, and the mechanism underlying this relationship. In Study 1, PhD students awaiting an editorial decision about a submitted manuscript estimated the effort they had invested in preparing that manuscript for submission and how happy they would feel if it were accepted. Subjective estimates of effort were positively related to participants' anticipated happiness, an effect mediated by the higher perceived quality of one's work. In other words, the more effort one though having invested, the happier one expected to feel if it were accepted, because one expected a higher quality manuscript. We replicated this effect and its underlying mediation in Study 2, this time using an experimental manipulation of effort in the context of creating an advertising slogan. Study 2 further showed that participants mistakenly thought their extra efforts invested in the task had improved the quality of their work, while independent judges had found no objective differences in quality between the outcomes of the high- and low-effort groups. We discuss the implications of the relationship between effort and anticipated emotions and the conditions under which such relationship might be functional.

The EPH receptor tyrosine kinases and their cell-bound ligands, the ephrins, have been shown to be associated with cancer development and progression. In this study, mRNA and protein expression of the receptors EPHA1 and EPHA2 as well as of their ligand EFNA1 and their prognostic relevance in clear cell renal cell carcinoma was evaluated. Gene expression was measured in 75 cryo-preserved primary tumors and matched non-malignant renal specimens by quantitative PCR. Protein expression was analyzed by immunohistochemistry on tissue microarrays comprising non-malignant, primary tumors and metastatic renal tissues of 241 patients. Gene and protein expression of all three factors was altered in tumor specimens with EPHA1 and EPHA2 being generally diminished in tumors compared to normal renal tissue, whereas EFNA1 was commonly elevated. A positive EPHA1 and EPHA2 protein staining as well as a low EFNA1 protein level were significantly linked to more aggressive tumor features, but only a positive EPHA1 immunoreactivity was significantly associated with poor survival. In subgroup analyses, EPHA1 and EPHA2 protein levels were significantly higher in metastatic than in primary lesions. Patients with EPHA1/EPHA2-positive tumors or with tumors with positive EPHA1 and low EFNA1 immunoreactivity had the shortest survival rates compared to the respective other combinations. In a multivariate model, EPHA1 was an independent prognostic marker for different survival endpoints. In conclusion, an impaired EPH-ephrin signaling could contribute to the pathogenesis and progression of clear cell renal cell carcinoma.

This study aimed to investigate the impact of Chlamydia trachomatis (CT) infection on pregnancy outcome in pregnant Japanese women. We utilized the data from a nationwide birth cohort study, the Japan Environment and Children's Study (JECS), for this study. We enrolled 26,385 individuals who could refer to data on pregnancy outcomes and confounding factors, with data on CT. Binominal logistic regression models were used to determine whether pregnant women with CT positivity were at more risk of experiencing adverse pregnancy outcomes, preterm birth (PTB), preterm prelabor rupture of membrane (pPROM), low birth weight (LBW) infants, small for gestational age (SGA) births, or hypertensive disorders of pregnancy (HDP). After adjusting for maternal age, parity, marital status, smoking status, and education status, there were no significantly increased risks of PTB, pPROM, LBW infants, SGA, and HDP in the odds ratios. No significant increase in the risk of adverse pregnancy outcomes was observed in any of the subgroup analyses, which were limited to the pregnancy women in Fukushima prefecture, where CT screening could be confirmed at 28−30 weeks of gestation. We believe that the results of this study will make a significant contribution to the future of medical care for pregnant women in Japan. Our findings are important for medical practitioners to contribute to the future medical treatment of Japanese pregnant women, and also to contribute to pre-conception care for Japanese society as a whole, including pregnant women. [ABSTRACT FROM AUTHOR]