CSF concentrations of NSE and tau were decreased in preeclampsia and there were no differences in plasma concentrations of NSE and tau between groups. For S100B, serum concentrations in preeclampsia were increased but there was no difference in CSF concentrations of S100B between women with preeclampsia and normal pregnancy.

NfL emerges as a promising circulating cerebral biomarker in preeclampsia and increased CSF concentrations point to a neuroaxonal injury in preeclampsia, even in the absence of clinically evident neurological complications.

NfL emerges as a promising circulating cerebral biomarker in preeclampsia and increased CSF concentrations point to a neuroaxonal injury in preeclampsia, even in the absence of clinically evident neurological complications.

To test the effectiveness of mid-regional pro-adrenomedullin (MR-proADM) in comparison to C-reactive protein (CRP), procalcitonin (PCT), D-dimer, lactate dehydrogenase (LDH) in predicting mortality in COVID-19-ICU-patients.

All consecutive COVID-19 adult patients admitted between March and June 2020 to the ICU of a referral, university hospital in Northern-Italy were enrolled. MR-proADM and routine laboratory test were measured within 48 hours from ICU admission, on day 3, 7 and 14. Survival curves difference with MR-proADM cut-off set to 1.8 nmol/L were tested using log-rank test. Predictive ability was compared using area under the curve and 95% confidence interval of different receiver-operating characteristics curves.

57 patients were enrolled. ICU and overall mortality were 54.4%. At admission, lymphocytopenia was present in 86% of patients; increased D-dimer and CRP levels were found in 84.2% and 87.7% of patients respectively, while PCT values > 0.5 μg/L were observed in 47.4% of patients. MR-decision-making. Further studies are needed to better explain the mechanisms responsible of the increase in MR-proADM in COVID-19 patients.

In COVID-19 ICU-patients, MR-proADM seems to have constantly higher values in non-survivor patients and predict mortality more precisely than other biomarkers. Repeated MR-proADM measurement may support a rapid and effective decision-making. Further studies are needed to better explain the mechanisms responsible of the increase in MR-proADM in COVID-19 patients.

Fibromyalgia (FM) and complex regional pain syndrome (CRPS) share many pathological mechanisms related to chronic pain and neuroinflammation, which may contribute to the multifactorial pathological mechanisms in both FM and CRPS. The aim of this study was to assess neuroinflammation in FM patients compared with that in patients with CRPS and healthy controls.

Neuroinflammation was measured as the distribution volume ratio (DVR) of [11C]-(R)-PK11195 positron emission tomography (PET) in 12 FM patients, 11 patients with CRPS and 15 healthy controls.

Neuroinflammation in FM patients was significantly higher in the left pre (primary motor cortex) and post (primary somatosensory cortex) central gyri (p < 0.001), right postcentral gyrus (p < 0.005), left superior parietal and superior frontal gyri (p < 0.005), left precuneus (p < 0.01), and left medial frontal gyrus (p = 0.036) compared with healthy controls. Furthermore, the DVR of [11C]-(R)-PK11195 in FM patients demonstrated decreased neuroinflFM. In addition, the identification of common and different critical regions related to abnormal neuroinflammation in FM, compared with patients with CRPS and healthy controls, may contribute to improved diagnosis and the development of effective medical treatment for patients with FM.

The burden of diabetes is considerable not only globally but also nationally within Korea. The Global Burden of Disease study derived the disability-adjusted life years (DALYs) of diabetes depending on its complications as individual severity using prevalence-based approach from 2017. Conversely, the Korean National Burden of Disease study based on an incidence-based approach does not incorporate the severity of diseases. This study aimed to simulate incidence-based DALYs of type 2 diabetes mellitus (T2DM), given diabetic complications as disease severity using a Markov model.

We developed a model with six Markov states, including incident and existing prevalent cases of diabetes and its complications and death. We assumed that diabetes and its complications would not be cured. The cycle length was one year, and the endpoint of the simulation was 100 years. A 5% discount rate was adopted in the analysis. Transition cases were counted by 5-year age groups above 30 years of age. Age- and sex-specific transition probabilities were calculated based on the incident rate.

The total DALY estimates of T2DM were 5,417 and 3,934 per 100,000 population in men and women, respectively. The years of life lost in men were relatively higher than those in women in most age groups except the 80-84 age group. The distribution of years lived with disability by gender and age group showed a bell shape, peaking in the 55-59 age group in men and 65-69 age group in women.

The burden of T2DM considering its complications was larger compared to the outcomes from previous studies, with more precise morbid duration using the Markov model.

The burden of T2DM considering its complications was larger compared to the outcomes from previous studies, with more precise morbid duration using the Markov model.It is well established that leisure vacations markedly improve well-being, but that these effects are only of short duration. The present study aimed to investigate whether vacation effects would be more lasting if individuals practiced meditation during the leisure episode. Meditation is known to improve well-being durably, among others, by enhancing the mental faculty of mindfulness. In this aim, leisure vacations during which individuals practiced meditation to some extent were compared with holidays not including any formal meditation practice as well as with meditation retreats (characterized by intense meditation practice) utilizing a naturalistic observational design. Fatigue, well-being, and mindfulness were assessed ten days before, ten days after, and ten weeks after the stays in a sample of 120 individuals accustomed to meditation practices. To account for differences in the experience of these stays, recovery experiences were additionally assessed. Ten days after the stay, there were no differences except for an increase in mindfulness for those practicing meditation. Ten weeks after the stay, meditation retreats and vacations including meditation were associated with greater increases in mindfulness, lower levels of fatigue, and higher levels of well-being than an „ordinary” vacation during which meditation was not practiced. The finding suggests that the inclusion of meditation practice during vacation could help alleviate vacations’ greatest pitfall, namely the rapid decline of its positive effects.

Sex and gender differences in acute coronary syndrome (ACS) have been well studied in the western population. However, limited studies have examined the trends of these differences in a multi-ethnic Asian population.

To study the trends in sex and gender differences in ACS using the Malaysian NCVD-ACS Registry.

Data from 24 hospitals involving 35,232 ACS patients (79.44% men and 20.56% women) from 1st. Jan 2012 to 31st. Dec 2016 were analysed. Data were collected on demographic characteristics, coronary risk factors, anthropometrics, treatments and outcomes. Analyses were done for ACS as a whole and separately for ST-segment elevation myocardial infarction (STEMI), Non-STEMI and unstable angina. These were then compared to published data from March 2006 to February 2010 which included 13,591 ACS patients (75.8% men and 24.2% women).

Women were older and more likely to have diabetes mellitus, hypertension, dyslipidemia, previous heart failure and renal failure than men. Women remained less likely to retinued to have longer system delays, receive less aggressive pharmacotherapies and invasive treatments with poorer outcome. There is an urgent need for increased effort from all stakeholders if we are to narrow this gap.The aim of this study was to determine the abnormal hand and mouth behavior before actual swallowing for eating in elderly people with high risk of aspiration pneumonia. Ten elderly people with a diagnosis of aspiration pneumonia (EAP), 15 healthy elderly (HE) people, and 21 young adults (YA) were enrolled. The feeding time and the timing of the maximum distance between the upper and lower lips were extracted using a motion analyzer during self-feeding and assisted-feeding. The results showed that feeding time in EAP was significantly longer than that for the other groups in self- and assisted-feeding. In self-feeding, the timing of mouth-preparation in the EAP group was significantly earlier than that in the other groups; conversely, in assisted-feeding, the timing in EAP was significantly delayed. Our results indicate that abnormal preparation of mouth-shape and movement time of hand before actual swallowing in both self- and assisted-feeding may exist in elderly people with previous experience of aspiration pneumonia.The emergence of antibiotic resistance over the past several decades has given urgency to new antibacterial strategies that apply less selective pressure. A new class of anti-virulence compounds were developed that are active against methicillin-resistant Staphylococcus aureus (MRSA), by inhibiting bacterial virulence without hindering their growth to reduce the selective pressure for resistance development. One of the compounds CCG-211790 has demonstrated potent anti-biofilm activity against MRSA. This new class of anti-virulence compounds inhibited the gene expression of virulence factors involved in biofilm formation and disrupted the biofilm structures. In this study, the physicochemical properties of CCG-211790, including morphology, solubility in pure water or in water containing sodium dodecyl sulfate, solubility in organic solvents, and stability with respect to pH were investigated for the first time. Furthermore, a topical formulation was developed to enhance the therapeutic potential of the compound. The formulation demonstrated acceptable properties for drug release, viscosity, pH, cosmetic elegance and stability of over nine months.A minute thrombus can pass through a small type of interatrial communication, which can result in a stroke or transient ischemic attack and several associated symptoms. This study sought to investigate a new type of interatrial communication. Thirty-one hearts from embalmed adult cadavers were investigated. Each interatrial channels (IACs) was classified as either an open or obstructed channel according to the connection of each hole on the right and left surfaces of the interatrial septum. Open channels were found in two specimens (6.5%). Both open and obstructed IACs followed tortuous courses through the interatrial septum. On the right surface of the interatrial septum, the hole was usually found adjacent to the left border of the interatrial septum between the opening of the superior vena cava into the right atrium and the superior margin of the fossa ovalis. Conversely, holes on the left surface of the interatrial septum were usually found in the upper and middle parts adjacent to the left border of the interatrial septum. This novel finding is expected to support our understanding of the onset of possible symptoms such as stroke in the absence of classical atrial septal defects.During the development of a holometabolous insect such as Drosophila, specific group of cells in the larva survive during metamorphosis, unlike the other larval cells, and finally give rise to the differentiated adult structures. These cells, also known as Adult Progenitor Cells (APCs), maintain their multipotent capacity, differentially respond to hormonal and nutritional signals, survive the intrinsic and environmental stress and respond to the final differentiation cues. However, not much is known about the specific molecular mechanisms that account for their unique characteristics. Here we show that a specific Drosophila APC gene, headcase (hdc), has a dual role in the normal development of these cells. It acts at a systemic level by controlling the hormone ecdysone in the prothoracic gland and at the same time it acts locally as a tissue growth suppressor in the APC clusters, where it modulates the activity of the TOR pathway and promotes their survival by contributing in the regulation of the Unfolded Protein Response. We also show that hdc provides protection against stress in the APCs and that its ectopic expression in cells that do not usually express hdc can confer these cells with an additional stress protection. Hdc is the founding member of a group of homolog proteins identified from C. elegans to humans, where has been found associated with cancer progression. The finding that the Drosophila hdc is specifically expressed in progenitor cells and that it provides protection against stress opens up a new hypothesis to be explored regarding the role of the human Heca and its contribution to carcinogenesis.The outbreak of Coronavirus disease 2019(COVID-19) necessitated an abrupt transition from on campus, face-to-face sessions to online, distance learning in higher education institutions. The purpose of this study was to investigate the perceptions of postgraduate dental learners and instructors about the transition to distance learning, including the changes to the learning and teaching and its efficaciousness. A convergent mixed methods approach to research was utilized. All the instructors and postgraduate learners in a dental college were invited to participate in an online survey. Quantitative data was analyzed using descriptive and inferential analyses on SPSS for Windows version 25.0, and for the responses to the open-ended questions, multi-staged thematic analysis was utilized. Both groups of stakeholders learners and instructors, were satisfied with the rapid transition to distance learning due to COVID-19. Instructors were significantly more satisfied than the learners. The stakeholders adapted well to the change. The perception of the stakeholders regarding the case-based scenarios significantly influenced their level of satisfaction. As perceived by the stakeholders, the transition to distance learning entailed advantages and challenges. Going through the experience enabled the stakeholders to develop informed opinions of how best to sustain learning and teaching irrespective of how matters unfold in relation to the pandemic. In conclusion, the worldwide dental education community faced unprecedented challenges due to the onset of COVID-19. From a macro perspective, decision-makers must not miss out on the valuable opportunities, inherent in the experience, to reinforce curriculums, and maximize learning and teaching.The Phase II clinical trials aim to assess the therapeutic efficacy of a new drug. The therapeutic efficacy has been often quantified by response rate such as overall response rate or survival probability in the Phase II setting. However, there is a strong desire to use survival time, which is the gold standard endpoint for the confirmatory Phase III study, when investigators set the primary objective of the Phase II study and test hypotheses based on the median survivals. We propose a method for median event time test to provide the sample size calculation and decision rule of testing. The decision rule is simple and straightforward in that it compares the observed median event time to the identified threshold. Moreover, it is extended to optimal two-stage design for practice, which extends the idea of Simon’s optimal two-stage design for survival endpoint. We investigate the performance of the proposed methods through simulation studies. The proposed methods are applied to redesign a trial based on median event time for trial illustration, and practical strategies are given for application of proposed methods.Limited testing capacity for COVID-19 has hampered the pandemic response. Pooling is a testing method wherein samples from specimens (e.g., swabs) from multiple subjects are combined into a pool and screened with a single test. If the pool tests positive, then new samples from the collected specimens are individually tested, while if the pool tests negative, the subjects are classified as negative for the disease. Pooling can substantially expand COVID-19 testing capacity and throughput, without requiring additional resources. We develop a mathematical model to determine the best pool size for different risk groups, based on each group’s estimated COVID-19 prevalence. Our approach takes into consideration the sensitivity and specificity of the test, and a dynamic and uncertain prevalence, and provides a robust pool size for each group. For practical relevance, we also develop a companion COVID-19 pooling design tool (through a spread sheet). To demonstrate the potential value of pooling, we study COVID-19 screening using testing data from Iceland for the period, February-28-2020 to June-14-2020, for subjects stratified into high- and low-risk groups. We implement the robust pooling strategy within a sequential framework, which updates pool sizes each week, for each risk group, based on prior week’s testing data. Robust pooling reduces the number of tests, over individual testing, by 88.5% to 90.2%, and 54.2% to 61.9%, respectively, for the low-risk and high-risk groups (based on test sensitivity values in the range [0.71, 0.98] as reported in the literature). This results in much shorter times, on average, to get the test results compared to individual testing (due to the higher testing throughput), and also allows for expanded screening to cover more individuals. Thus, robust pooling can potentially be a valuable strategy for COVID-19 screening.Despite the high prevalence of potential drug-drug interactions in pediatric intensive care units, their clinical relevance and significance are unclear. We assessed the characteristics and risk factors of clinically relevant potential drug-drug interactions to facilitate their efficient monitoring in pediatric intensive care units. This retrospective cohort study reviewed the medical records of 159 patients aged less then 19 years who were hospitalized in the pediatric intensive care unit at Seoul National University Hospital (Seoul, Korea) for ≥3 days between August 2019 and February 2020. Potential drug-drug interactions were screened using the Micromedex Drug-Reax® system. Clinical relevance of each potential drug-drug interaction was reported with official terminology, magnitude of severity, and causality, and the association with the patient’s clinical characteristics was assessed. In total, 115 patients (72.3%) were exposed to 592 potential interactions of 258 drug pairs. In 16 patients (10.1%), 22 clractions according to the pediatric intensive care unit characteristics.

COVID-19 complications can include neurological, psychiatric, psychological, and psychosocial impairments. Little is known on the consequences of SARS-COV-2 on cognitive functions of patients in the sub-acute phase of the disease. We aimed to investigate the impact of COVID-19 on cognitive functions of patients admitted to the COVID-19 Rehabilitation Unit of the San Raffaele Hospital (Milan, Italy).

87 patients admitted to the COVID-19 Rehabilitation Unit from March 27th to June 20th 2020 were included. Patients underwent Mini Mental State Evaluation (MMSE), Montreal Cognitive Assessment (MoCA), Hamilton Rating Scale for Depression, and Functional Independence Measure (FIM). Data were divided in 4 groups according to the respiratory assistance in the acute phase Group1 (orotracheal intubation), Group2 (non-invasive ventilation using Biphasic Positive Airway Pressure), Group3 (Venturi Masks), Group4 (no oxygen therapy). Follow-ups were performed at one month after home-discharge.

Out of the 87 patients (subacute phase of the disease, and show the need for long-term psychological support and treatment of post-COVID-19 patients.

Patients with severe functional impairments had important cognitive and emotional deficits which might have been influenced by the choice of ventilatory therapy, but mostly appeared to be related to aging, independently of FIM scores. These findings should be integrated for correct neuropsychiatric assistance of COVID-19 patients in the subacute phase of the disease, and show the need for long-term psychological support and treatment of post-COVID-19 patients.The purpose of this study was to identify performance measures of racially underrepresented minority (RUM) Ph.D. trainees who needed additional training initiatives to assist with completing the UAMS biomedical science degree. A sample of 37 trainees in the 10-year NIH-NIGMS funded Initiative for Maximizing Student Development (IMSD) program at the University of Arkansas for Medical Sciences (UAMS) were examined. Descriptive statistics and correlations examined process measures (GRE scores, GPAs, etc.) and outcome measures (time-to-degree, publications, post-doctoral fellowship, etc.) While differences were found, there were no statistically significant differences between how these two groups (Historically Black Colleges and Universities (HBCUs) and Predominately White Institutions (PWIs)) of students performed over time as Ph.D. students. Graduates who scored lower on the verbal section of the GRE also had a higher final graduate school grade point average in graduates who received their undergraduate training from HBCUs. Of the graduates who received their undergraduate training from PWIs, graduates who scored lower on the quantitative section of the GRE had higher numbers of publications. These findings stimulate the need to 1) reduce reliance on the use of the GRE in admission committee decisions, 2) identify psychometrically valid indicators that tailored to assess outcome variables that are relevant to the careers of biomedical scientists, and 3) ensure the effective use of the tools in making admission decisions.

Exclusive breastfeeding promotes beneficial modifications on the microbiota of cesarean born infants, but little is known about the role of specific breast milk components in this modulation. Women with an active FUT2 gene (called secretors) secrete α1-2 fucosylated human milk oligosaccharides (HMOs), which promote Bifidobacterium in the infant’s gut and may modulate the microbiota of cesarean born infants.

To compare the microbiota composition of cesarean and vaginally born infants breastfed by secretor mothers.

Maternal secretor status was determined by the occurrence of 4 different α1-2 fucosylated HMOs in breast milk by LC-MS. The fecal microbiota composition from cesarean and vaginally born infants was analyzed by 16S rRNA gene sequencing and qPCR, stratified by the maternal secretor status, and compared.

Alpha and beta diversity were not significantly different in cesarean born, secretor-fed infants (CSe+) compared to vaginally born, secretor-fed infants (VSe+). There were no significant differences in the fecal relative abundance of Bifidobacterium between CSe+ and VSe+ infants, but the prevalence of the species B. longum was lower in CSe+. The fecal relative abundance of Bacteroides was also lower, while Akkermansia and Kluyvera were higher in CSe+ infants.

Cesarean and vaginally born infants fed with breast milk containing the α1-2 fucosylated HMOs fraction present similar amounts of Bifidobacterium in the feces, but differences are observed in other members of the microbiota.

Cesarean and vaginally born infants fed with breast milk containing the α1-2 fucosylated HMOs fraction present similar amounts of Bifidobacterium in the feces, but differences are observed in other members of the microbiota.Growth modelling is a fundamental component of fisheries assessments but is often hindered by poor quality data from biased sampling. Several methods have attempted to account for sample bias in growth analyses. However, in many cases this bias is not overcome, especially when large individuals are under-sampled. In growth models, two key parameters have a direct biological interpretation L0, which should correspond to length-at-birth and L∞, which should approximate the average length of full-grown individuals. Here, we present an approach of fitting Bayesian growth models using Markov Chain Monte Carlo (MCMC), with informative priors on these parameters to improve the biological plausibility of growth estimates. A generalised framework is provided in an R package 'BayesGrowth’, which removes the hurdle of programming an MCMC model for new users. Four case studies representing different sampling scenarios as well as three simulations with different selectivity functions were used to compare this Bayesian framework to standard frequentist growth models. The Bayesian models either outperformed or matched the results of frequentist growth models in all examples, demonstrating the broad benefits offered by this approach. This study highlights the impact that Bayesian models could provide in age and growth studies if applied more routinely rather than being limited to only complex or sophisticated applications.

Processes for transferring patients to higher acuity facilities lack a standardized approach to prognostication, increasing the risk for low value care that imposes significant burdens on patients and their families with unclear benefits. We sought to develop a rapid and feasible tool for predicting mortality using variables readily available at the time of hospital transfer.

All work was carried out at a single, large, multi-hospital integrated healthcare system. We used a retrospective cohort for model development consisting of patients aged 18 years or older transferred into the healthcare system from another hospital, hospice, skilled nursing or other healthcare facility with an admission priority of direct emergency admit. The cohort was randomly divided into training and test sets to develop first a 54-variable, and then a 14-variable gradient boosting model to predict the primary outcome of all cause in-hospital mortality. Secondary outcomes included 30-day and 90-day mortality and transition to codside nurse calculated a SafeNET score at the time of transfer, taking only 4-5 minutes per patient with discrimination consistent with the development sample for in-hospital, 30-day and 90-day mortality (c = 0.836 [95%CI 0.751-0.921], 0.815 [95% CI 0.730-0.900], and 0.794 [95% CI 0.725-0.864], respectively).

The SafeNET algorithm is feasible and valid for real-time, bedside mortality risk prediction at the time of hospital transfer. Work is ongoing to build pathways triggered by this score that direct needed resources to the patients at greatest risk of poor outcomes.

The SafeNET algorithm is feasible and valid for real-time, bedside mortality risk prediction at the time of hospital transfer. Work is ongoing to build pathways triggered by this score that direct needed resources to the patients at greatest risk of poor outcomes.In 2006 and 2007, sheep and cattle farms in the Netherlands were affected by an epidemic of bluetongue virus serotype 8 (BTV-8). In order to obtain insight into the within-farm spread of the virus, five affected cattle and five affected sheep farms were longitudinally monitored between early 2007 and mid or late 2008. The farms were visited between four and seven times to collect blood samples. During each visit, all animals present in the flock or herd were sampled. The samples were analysed for the presence of BTV-8 antibodies (ELISA) and BTV-8 antigen (rRT-PCR). The observed patterns of RT-PCR positives indicate a rapid within-farm virus spread during the vector season. During vector-free periods we observed a complete rRT-PCR positivity decline within a few months. During the vector season a lower bound estimate of the basic reproduction number (R0) ranges from 2.9-6.9 in the cattle herds (one herd not analysed), and from 1.3-3.2 in the sheep flocks in this study.Osteosarcoma is a rare disease in children but is one of the most common cancers in adult large breed dogs. The mutational landscape of both the primary and pulmonary metastatic tumor in two dogs with appendicular osteosarcoma (OSA) was comprehensively evaluated using an automated whole genome sequencing, exome and RNA-seq pipeline that was adapted for this study for use in dogs. Chromosomal lesions were the most common type of mutation. The mutational landscape varied substantially between dogs but the lesions within the same patient were similar. Copy number neutral loss of heterozygosity in mutant TP53 was the most significant driver mutation and involved a large region in the middle of chromosome 5. Canine and human OSA is characterized by loss of cell cycle checkpoint integrity and DNA damage response pathways. Mutational profiling of individual patients with canine OSA would be recommended prior to targeted therapy, given the heterogeneity seen in our study and previous studies.Compared with root-associated habitats, little is known about the role of microbiota inside other rice organs, especially the rhizome of perennial wild rice, and this information may be of importance for agriculture. Oryza longistaminata is perennial wild rice with various agronomically valuable traits, including large biomass on poor soils, high nitrogen use efficiency, and resistance to insect pests and disease. Here, we compared the endophytic bacterial and archaeal communities and network structures of the rhizome to other compartments of O. longistaminata using 16S rRNA gene sequencing. Diverse microbiota and significant variation in community structure were identified among different compartments of O. longistaminata. The rhizome microbial community showed low taxonomic and phylogenetic diversity as well as the lowest network complexity among four compartments. Rhizomes exhibited less phylogenetic clustering than roots and leaves, but similar phylogenetic clustering with stems. Streptococcus, Bacillus, and Methylobacteriaceae were the major genera in the rhizome. ASVs belonging to the Enhydrobacter, YS2, and Roseburia are specifically present in the rhizome. The relative abundance of Methylobacteriaceae in the rhizome and stem was significantly higher than that in leaf and root. Noteworthy type II methanotrophs were observed across all compartments, including the dominant Methylobacteriaceae, which potentially benefits the host by facilitating CH4-dependent N2 fixation under nitrogen nutrient-poor conditions. Our data offers a robust knowledge of host and microbiome interactions across various compartments and lends guidelines to the investigation of adaptation mechanisms of O. longistaminata in nutrient-poor environments for biofertilizer development in agriculture.Despite significant modern medicine progress, having an infectious disease is a major risk factor for humans. Mucosal vaccination is now widely considered as the most promising strategy to defeat infectious diseases; however, only live-attenuated and inactivated mucosal vaccines are used in the clinical field. To date, no subunit mucosal vaccine was approved mainly because of the lack of safe and effective methodologies to either activate or initiate host mucosal immune responses. We have recently elucidated that intranasal administration of enzymatically polymerised caffeic acid potentiates antigen-specific mucosal and systemic antibody responses in mice. However, our earlier study has not confirmed whether these effects are specific to the polymer synthesised from caffeic acid. Here, we show that enzymatically polymerised polyphenols (EPPs) from various phenolic compounds possess mucosal adjuvant activities when administered nasally with an antigen to mice. Potentiation of antigen-specific immune responses by all EPPs tested in this study showed no clear difference among the precursors used. We found that intranasal administration of ovalbumin as the antigen, in combination with all enzymatically polymerised polyphenols used in this study, induced ovalbumin-specific mucosal IgA in the nasal cavity, bronchoalveolar lavage fluid, vaginal fluids, and systemic IgG, especially IgG1, in sera. Our results demonstrate that the mucosal adjuvant activities of polyphenols are not limited to polymerised caffeic acid but are broadly observable across the studied polyphenols. These properties of polyphenols may be advantageous for the development of safe and effective nasal vaccine systems to prevent and/or treat various infectious diseases.

The effect of the period before a mother’s death on child survival has been assessed in only a few studies. We conducted a comparative investigation of the effect of the timing of a mother’s death on child survival up to age five years in rural South Africa.

We used discrete time survival analysis on data from two HIV-endemic population surveillance sites (2000-2015) to estimate a child’s risk of dying before and after their mother’s death. We tested if this relationship varied between sites and by availability of antiretroviral therapy (ART). We assessed if related adults in the household altered the effect of a mother’s death on child survival.

3,618 children died from 2000-2015. The probability of a child dying began to increase in the 7-11 months prior to the mother’s death and increased markedly in the 3 months before (2000-2003 relative risk = 22.2, 95% CI = 14.2-34.6) and 3 months following her death (2000-2003 RR = 20.1; CI = 10.3-39.4). This increased risk pattern was evident at both sites. There and abrupt breastfeeding cessation might be crucial risk factors. Formative research is needed to understand the circumstances for children when a mother is very ill or dies, and behavioral and other risk factors that increase both the mother and child’s risk of dying. Identifying families when a mother is very ill and implementing training and support strategies for other members of the household are urgently needed to reduce preventable child mortality.COVID-19 has had a substantial impact on clinical care and lifestyles globally. The State of Michigan reports over 80,000 positive COVID-19 tests between March 1, 2020 and July 29, 2020. We surveyed 8,041 Michigan Medicine biorepository participants in late June 2020. We found that 55% of COVID-19 cases reported no known exposure to family members or to someone outside the house diagnosed with COVID-19. A significantly higher rate of COVID-19 cases were employed as essential workers (45% vs 19%, p = 9×10-12). COVID-19 cases reporting a fever were more likely to require hospitalization (categorized as severe; OR = 4.4 [95% CI 1.6-12.5, p = 0.005]) whereas respondents reporting rhinorrhea was less likely to require hospitalization (categorized as mild-to-moderate; OR = 0.16 [95% CI 0.04-0.73, p = 0.018]). African-Americans reported higher rates of being diagnosed with COVID-19 (OR = 4.0 [95% CI 2.2-7.2, p = 5×10-6]), as well as higher rates of exposure to family or someone outside the household diagnosed with COVID-19, an annual household income less then $40,000, living in rental housing, and chronic diseases. During the Executive Order in Michigan, African Americans, women, and the lowest income group reported worsening health behaviors and higher overall concern for the potential detrimental effects of the pandemic. The higher risk of contracting COVID-19 observed among African Americans may be due to the increased rates of working as essential employees, lower socioeconomic status, and exposure to known positive cases. Continued efforts should focus on COVID-19 prevention and mitigation strategies, as well as address the inequality gaps that result in higher risks for both short-term and long-term health outcomes.The C-type lectin-like receptor NKG2D contributes to the immunosurveillance of virally infected and malignant cells by cytotoxic lymphocytes. A peculiar and puzzling feature of the NKG2D-based immunorecognition system is the high number of ligands for this single immunoreceptor. In humans, there are a total of eight NKG2D ligands (NKG2DL) comprising two members of the MIC (MICA, MICB) and six members of the ULBP family of glycoproteins (ULBP1 to ULBP6). While MICA has been extensively studied with regard to its biochemistry, cellular expression and function, very little is known about the NKG2DL ULBP4. This is, at least in part, due to its rather restricted expression by very few cell lines and tissues. Recently, constitutive ULBP4 expression by human monocytes was reported, questioning the view of tissue-restricted ULBP4 expression. Here, we scrutinized ULBP4 expression by human peripheral blood mononuclear cells and monocytes by analyzing ULBP4 transcripts and ULBP4 surface expression. In contrast to MICA, there was no ULBP4 expression detectable, neither by freshly isolated monocytes nor by PAMP-activated monocytes. However, a commercial antibody erroneously indicated surface ULBP4 on monocytes due to a non-ULBP4-specific binding activity, emphasizing the critical importance of validated reagents for life sciences. Collectively, our data show that ULBP4 is not expressed by monocytes, and likely also not by other peripheral blood immune cells, and therefore exhibits an expression pattern rather distinct from other human NKG2DL.The settlement of Iceland in the Viking Age has been the focus of much research, but the composition of the founding population remains the subject of debate. Some lines of evidence suggest that almost all the founding population were Scandinavian, while others indicate a mix of Scandinavians and people of Scottish and Irish ancestry. To explore this issue further, we used three-dimensional techniques to compare the basicrania of skeletons from archaeological sites in Iceland, Scandinavia, and the British Isles. Our analyses yielded two main results. One was that the founding population likely consisted of roughly equal numbers of Scandinavians and people from the British Isles. The other was that the immigrants who originated from the British Isles included individuals of southern British ancestry as well as individuals of Scottish and Irish ancestry. The first of these findings is consistent with the results of recent analyses of modern and ancient DNA, while the second is novel. Our study, therefore, strengthens the idea that the founding population was a mix of Scandinavians and people from the British Isles, but also raises a new possibility regarding the regions from which the settlers originated.Coxsackievirus B3 (CVB3) belongs to the genus Enterovirus of the family Picornaviridae and can cause acute acinar pancreatitis in adults. However, the molecular mechanisms of pathogenesis underlying CVB3-induced acute pancreatitis have remained unclear. In this study, we discovered that CVB3 capsid protein VP1 inhibited pancreatic cell proliferation and exerted strong cytopathic effects on HPAC cells. Through yeast two-hybrid, co-immunoprecipitation, and confocal microscopy, we show that Menage a trois 1 (MAT1), a subunit of the Cdk-Activating Kinase (CAK) complex involved in cell proliferation and transcription, is a novel interaction protein with CVB3 VP1. Moreover, CVB3 VP1 inhibited MAT1 accumulation and localization, thus interfering with its interaction with CDK7. Furthermore, CVB3 VP1 could suppress CAK complex enzymic phosphorylation activity towards RNA Pol II and CDK4/6, direct substrates of CAK. VP1 also suppresses phosphorylation of retinoblastoma protein (pRb), an indirect CAK substrate, especially at phospho-pRb Ser780 and phospho-pRb Ser807/811 residues, which are associated with cell proliferation. Finally, we present evidence using deletion mutants that the C-terminal domain (VP1-D8, 768-859aa) is the minimal VP1 region required for its interaction with MAT1, and furthermore, VP1-D8 alone was sufficient to arrest cells in G1/S phase as observed during CVB3 infection. Taken together, we demonstrate that CVB3 VP1 can inhibit CAK complex assembly and activity through direct interaction with MAT1, to block MAT1-mediated CAK-CDK4/6-Rb signaling, and ultimately suppress cell proliferation in pancreatic cells. These findings substantially extend our basic understanding of CVB3-mediated pancreatitis, providing strong candidates for strategic therapeutic targeting.Vesicular trafficking defects, particularly those in the autophagolysosomal system, have been strongly implicated in the pathogenesis of Parkinson’s disease and related α-synucleinopathies. However, mechanisms mediating dysfunction of membrane trafficking remain incompletely understood. Using a Drosophila model of α-synuclein neurotoxicity with widespread and robust pathology, we find that human α-synuclein expression impairs autophagic flux in aging adult neurons. Genetic destabilization of the actin cytoskeleton rescues F-actin accumulation, promotes autophagosome clearance, normalizes the autophagolysosomal system, and rescues neurotoxicity in α-synuclein transgenic animals through an Arp2/3 dependent mechanism. Similarly, mitophagosomes accumulate in human α-synuclein-expressing neurons, and reversal of excessive actin stabilization promotes both clearance of these abnormal mitochondria-containing organelles and rescue of mitochondrial dysfunction. These results suggest that Arp2/3 dependent actin cytoskeleton stabilization mediates autophagic and mitophagic dysfunction and implicate failure of autophagosome maturation as a pathological mechanism in Parkinson’s disease and related α-synucleinopathies.This study aims to understand tourists’ willingness to pay a price premium for a local green hotel certification, and is one of only a few in the literature for small-island tourism destinations in emerging economies with their unique and pressing sustainability challenges. In a survey of 535 tourists visiting Gili Trawangan, Indonesia, facing numerous waste management and coral reef conservation issues, the willingness to pay extra for sustainable hotel services was elicited. There were five discrete pricing levels across the surveys that ranged from $0.75 USD to $7.50 USD extra per night. We examined the relationship of the respondents’ payment choice to their socio-demographic attributes and attitudes regarding environmental issues such as climate change. The main findings and practical implications of the study are (1) to demonstrate the broad willingness to pay for sustainable hotel services. Findings indicate at all price levels (between $0.75 USD and $7.50 USD), more than 50% of tourists are willing to pay. (2) To estimate a lower bound mean willingness to pay per night for a local green hotel certificate of $1.55USD and 1.34€ EUR, and (3) To identify individual attributes that influence willingness to pay. Findings indicate environmental knowledge and preferences play a role. These results can be used generally to incorporate evidence-based practices into the development of a green hotel marketing strategy, and to help define the target market for small-scale green hotel certification. Additionally, we propose a finance strategy for funding local and sustainable initiatives that support the hotel industry and the island’s infrastructure through the premiums collected from the 'Gili Green Award’ certificate.In this study, based on the regional land-use risk space division (regional ecological risk source/receptor space identification) using production-living-ecology analysis, three spatial function indexes, i.e., production, living, and ecology function indexes, were proposed for regional ecological risk assessment (RERA) with respect to human disturbance. The first two indexes can be regarded as regional ecological risk source indexes, whereas the final index can be regarded as a regional ecological risk receptor index. Using an artificial assignment method based on the land-use types and Defense Meteorological Program Operational Line-Scan System (DMSP/OLS) nighttime light intensity data, these three spatial function indexes were effectively manifested. By incorporating these indexes with eco-environmental vulnerability proxies, an RERA framework was established and applied in the Poyang Lake Eco-economic Zone (PLEZ), which is an ecological-protection and economic-development coordination-oriented region in Cht results can provide a scientific basis for regional ecological risk management within the PLEZ.Anopheles stephensi with three different biotypes is a major vector of malaria in Asia. It breeds in a wide range of habitats. Therefore, safer and more sustainable methods are needed to control its immature stages rather than chemical pesticides. The larvicidal and antibacterial properties of the Pelargonium roseum essential oil (PREO) formulations were investigated against mysorensis and intermediate forms of An. stephensi in laboratory conditions. A series of nanoemulsions containing different amounts of PREO, equivalent to the calculated LC50 values for each An. stephensi form, and various quantities of surfactants and co-surfactants were developed. The physical and morphological properties of the most lethal formulations were also determined. PREO and its major components, i.e. citronellol (21.34%), L-menthone (6.41%), linalool (4.214%), and geraniol (2.19%), showed potent larvicidal activity against the studied mosquitoes. The LC50/90 values for mysorensis and intermediate forms were computed as 11.44/4. stephensi.Winter turnip rape (Brassica rapa L.) is an important overwintering oil crop that is widely planted in northwestern China. It considered to be a good genetic resource for cold-tolerant research because its roots can survive harsh winter conditions. Here, we performed comparative transcriptomics analysis of the roots of two winter turnip rape varieties, Longyou7 (L7, strong cold tolerance) and Tianyou2 (T2, low cold tolerance), under normal condition (CK) and cold stress (CT) condition. A total of 8,366 differentially expressed genes (DEGs) were detected between the two L7 root groups (L7CK_VS_L7CT), and 8,106 DEGs were detected for T2CK_VS_T2CT. Among the DEGs, two ω-3 fatty acid desaturase (FAD3), two delta-9 acyl-lipid desaturase 2 (ADS2), one diacylglycerol kinase (DGK), and one 3-ketoacyl-CoA synthase 2 (KCS2) were differentially expressed in the two varieties and identified to be related to fatty acid synthesis. Four glutamine synthetase cytosolic isozymes (GLN), serine acetyltransferase 1 (SAT1), and ses during cold treatment.

To determine if the presence of microorganisms in follicular fluid of women undergoing in vitro fertilization-embryo transfer (IVF-ET) adversely affects the outcome of the treatment cycles.

Follicular fluid was collected from 86 women enrolled for IVF-ET at the National Hospital, Abuja from June 1, 2018 to December 1, 2018. Microscopy imaging and cultures were performed to identify bacteria and fungi in the follicular fluid and the vagina. Women with follicular fluid microorganisms were the test group while the controls were those without follicular fluid microorganisms. Fertilization and pregnancy rates were subsequently determined and their association with the presence of follicular fluid microorganisms was assessed using univariable and multivariable logistic regression modelling.

The mean age and mean Body Mass Index (BMI) of the participants were 35(± 3.5) years and 28(± 4.9) kg/m2 respectively. Bacteria and fungi were isolated in 17% of the follicular fluid samples collected (n = 15/86). Most common isolates were Streptococcus spp. (n = 4/15), Staphylococcus aureus (n = 7/15), Enterococcus spp. (n = 4/15), Lactobacillus species (n = 2/15) and Candida albicans (n = 2/15). There was no statistically significant difference in the fertilization rates (adjusted odds ratio [AdjOR] 0.55, 95% confidence interval [CI] 0.04-7.34; P = 0.10) and pregnancy rates (AdjOR 4.02, 95% CI 0.56-28.92; P = 0.19) between the group of women with positive follicular fluid bacterial /fungal colonization as compared against those with negative follicular fluid colonization.

Isolation of microorganisms from follicular fluid did not adversely affect fertilization and pregnancy rates following IVF-ET treatment cycles at the fertility centre of National Hospital, Abuja.

Isolation of microorganisms from follicular fluid did not adversely affect fertilization and pregnancy rates following IVF-ET treatment cycles at the fertility centre of National Hospital, Abuja.

To assess the feasibility of radiologic measurements and find out whether hearing outcome could be predicted based on computer tomography (CT) scan evaluation in patients with temporal bone fractures and suspected ossicular joint dislocation.

We assessed 4002 temporal bone CT scans and identified 34 patients with reported ossicular joint dislocation due to trauma. We excluded those with no proven traumatic ossicular dislocation in CT scan and patients with bilateral temporal bone fractures. We measured four parameters such as malleus-incus axis distance, malleus-incus angle at midpoints, malleus- incus axis angle and ossicular joint space. The contralateral healthy side served as its own control. Hearing outcome 1-3 months after the index visit was analyzed. We assessed diagnostic accuracy and performed a logistic regression using radiologic measurement parameters for outcome prediction of conductive hearing loss (defined as >20dB air-bone gap).

We found excellent inter-rater agreement on the measures and the malleus were strongly predictive for poor hearing outcome in terms of air conduction 1-3 months after trauma. We propose a 3-level classification system for hearing outcome prediction based on radiologic measures.Tick-borne encephalitis (TBE) is a widespread viral infection of the central nervous system with increasing incidence in Europe and northern Asia. Post-infectious sequelae are frequent, and patients with TBE commonly experience long-term fatigue and subjective sleep disturbances. Obstructive sleep apnea (OSA) may be a contributing factor, and objective sleep studies with polysomnography (PSG) are lacking. Forty-two adults, 22 TBE patients (cases), diagnosed in Region Västra Götaland, Sweden, between 2012 and 2015, and 20 controls without a known TBE history, underwent an overnight PSG, respectively. All participants responded to questionnaires. The cases and controls were similar regarding age, sex, obesity, concomitant diseases, smoking, and alcohol habits. Despite similar PSG characteristics such as total sleep time and OSA severity indices, the TBE cases reported statistically more sleep-related functional impairment on the Functional Outcome of Sleep Questionnaire (FOSQ) compared with the controls (median scores 18.1 vs. 19.9; p less then 0.05). In a multivariate analysis, TBE correlated significantly with the lower FOSQ scores (unstandardized β -1.80 [%95 confidence interval -3.02 – -0.58]; p = 0.005) independent of age, sex, total sleep time and apnea-hypopnea-index. TBE cases with OSA reported the lowest scores on the FOSQ compared with the other subgroups with TBE or OSA alone, and the ones with neither TBE nor OSA. TBE is associated with impaired functional outcomes, in which concomitant OSA may worsen the subjective symptoms. Further studies are warranted to determine the effect of treatment of concomitant OSA on functional outcomes with regard to optimal rehabilitation of TBE.