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BackgroundMalaria is one of the leading causes of morbidity in the world. It is a significant health concern in most developing countries, including Ghana. Even though there are several orthodox medications used for decades in treating malaria effectively, a substantial number of individuals in developing countries are resorting to the use of herbs in the treatment of malaria. The study aim at exploring the practices of herbal management of malaria among trading mothers in Shai Osudoku District, Accra.MethodsA qualitative approach with an exploratory, descriptive design was adopted in analyzing the research problem. Purposive sampling technique was used to select twenty (20) participants to partake in a face-face interview, guided by a semi-structured interview guide. The data were transcribed verbatim and analysed by adopting content analysis.ResultsTwo significant themes and seven subthemes were generated following the analysis of this study. The main themes were; preferences for herbal malaria treatment and the practices and effectiveness of herbal medicine used for malaria treatment. It was worth noting that the women's cultural beliefs did not influence their preference for herbal malaria treatment. The main challenge associated with the herbal malaria treatment was inappropriate dosage specification.ConclusionThis study discovered that several factors influenced participants' preferences for malaria treatment. Participants further listed some traditional ways of treating malaria which implies that there is herbal malaria practice. However, literature in this area is inadequate, and most herbs lack specifications for use. It is therefore recommended that future research focus on scientific herbal malaria treatment. Also, regulating bodies should ensure that quality herbal drugs are sold for consumption.

Quantitative MRI (qMRI) has been shown to be clinically useful for numerous applications in the brain and body. The development of rapid, accurate, and reproducible qMRI techniques offers access to new multiparametric data, which can provide a comprehensive view of tissue pathology. This work introduces a multiparametric qMRI protocol along with full postprocessing pipelines, optimized for brain imaging at 3 Tesla and using state-of-the-art qMRI tools. The total scan time is under 50 minutes and includes eight pulse-sequences, which produce range of quantitative maps including T1, T2, and T2* relaxation times, magnetic susceptibility, water and macromolecular tissue fractions, mean diffusivity and fractional anisotropy, magnetization transfer ratio (MTR), and inhomogeneous MTR. Practical tips and limitations of using the protocol are also provided and discussed. Application of the protocol is presented on a cohort of 28 healthy volunteers and 12 brain regions-of-interest (ROIs). Quantitative values agreed with previously reported values. Statistical analysis revealed low variability of qMRI parameters across subjects, which, compared to intra-ROI variability, was x4.1 ± 0.9 times higher on average. Significant and positive linear relationship was found between right and left hemispheres' values for all parameters and ROIs with Pearson correlation coefficients of r>0.89 (P

Background A host-protein score (BV score) that combines the circulating levels of TNF-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein 10 (IP-10) and C-reactive protein (CRP) was developed for distinguishing bacterial from viral infection. This study assessed the potential of the BV score to impact decision making and antibiotic stewardship at the emergency department (ED), by comparing BV score’s performance to physician’s etiological suspicion at patient presentation. Methods Rosetta study participants, aged 3 months to 18 years with febrile respiratory tract infection or fever without source, were prospectively recruited in a tertiary care pediatric ED. 465 patients were recruited, 298 met eligibility criteria and 287 were enrolled. ED physician’s etiological suspicion was recorded in a questionnaire. BV score was measured retrospectively with results interpreted as viral, bacterial or equivocal and compared to reference standard etiology, which was adjudicated by three independent experts based on all available data. Experts were blinded to BV scores. Results Median age was 1.3 years (interquartile range 1.7), 39.7% females. 196 cases were reference standard viral and 18 cases were reference standard bacterial. BV score attained sensitivity of 88.9% (95% confidence interval: 74.4–100), specificity 92.1% (88.1–96.0), positive predictive value 53.3% (35.5–71.2) and negative predictive value 98.8% (97.1–100). Positive likelihood ratio was 11.18 (6.59–18.97) and negative likelihood ratio was 0.12 (0.03–0.45). The rate of BV equivocal scores was 9.4%. Comparing physician’s suspicion to BV score and to the reference standard, and assuming full adoption, BV score could potentially correct the physician’s diagnosis and reduce error ~2-fold, from 15.9% to 8.2%. Conclusions BV score has potential to aid the diagnostic process. Future studies are warranted to assess the impact of real-time BV results on ED practice.

Fibromyalgia is a chronic pain syndrome with unsatisfactory response to current treatments. Physical trauma, including traumatic brain Injury (TBI) is among the etiological triggers. Hyperbaric Oxygen therapy (HBOT) is an intervention that combines 100% oxygen with elevated atmospheric pressure. HBOT has been applied as a neuro-modulatory treatment in central nervous system-related conditions. The current study investigated the utility of HBOT for TBI-related fibromyalgia. Fibromyalgia patients with a history of TBI were randomized to either HBOT or pharmacological intervention. HBOT protocol comprised 60 daily sessions, breathing 100% oxygen by mask at 2 absolute atmospheres (ATA) for 90 minutes. Pharmacological treatment included Pregabalin or Duloxetine. The primary outcome was subjective pain intensity on visual analogue scale (VAS); Secondary endpoints included questionnaires assessing fibromyalgia symptoms as well as Tc-99m-ECD SPECT brain imaging. Pain threshold and conditioned pain modulation (CPM) were also assessed. Results demonstrated a significant group-by-time interaction in pain intensity post-HBOT compared to the medication group (p = 0.001), with a large net effect size (d = -0.95) in pain intensity reduction following HBOT compared to medications. Fibromyalgia related symptoms and pain questionnaires demonstrated significant improvements induced by HBOT as well as improvements in quality of life and increase in pain thresholds and CPM. SPECT demonstrated significant group-by-time interactions between HBOT and medication groups in the left frontal and the right temporal cortex. In conclusion, HBOT can improve pain symptoms, quality of life, emotional and social function of patients suffering from FMS triggered by TBI. The beneficial clinical effect is correlated with increased brain activity in frontal and parietal regions, associated with executive function and emotional processing.

Quantitative MRI (qMRI) has been shown to be clinically useful for numerous applications in the brain and body. The development of rapid, accurate, and reproducible qMRI techniques offers access to new multiparametric data, which can provide a comprehensive view of tissue pathology. This work introduces a multiparametric qMRI protocol along with full postprocessing pipelines, optimized for brain imaging at 3 Tesla and using state-of-the-art qMRI tools. The total scan time is under 50 minutes and includes eight pulse-sequences, which produce range of quantitative maps including T1, T2, and T2* relaxation times, magnetic susceptibility, water and macromolecular tissue fractions, mean diffusivity and fractional anisotropy, magnetization transfer ratio (MTR), and inhomogeneous MTR. Practical tips and limitations of using the protocol are also provided and discussed. Application of the protocol is presented on a cohort of 28 healthy volunteers and 12 brain regions-of-interest (ROIs). Quantitative values agreed with previously reported values. Statistical analysis revealed low variability of qMRI parameters across subjects, which, compared to intra-ROI variability, was x4.1 ± 0.9 times higher on average. Significant and positive linear relationship was found between right and left hemispheres' values for all parameters and ROIs with Pearson correlation coefficients of r>0.89 (P<0.001), and mean slope of 0.95 ± 0.04. Finally, scan-rescan stability demonstrated high reproducibility of the measured parameters across ROIs and volunteers, with close-to-zero mean difference and without correlation between the mean and difference values (across map types, mean P value was 0.48 ± 0.27). The entire quantitative data and postprocessing scripts described in the manuscript are publicly available under dedicated GitHub and Figshare repositories. The quantitative maps produced by the presented protocol can promote longitudinal and multi-center studies, and improve the biological interpretability of qMRI by integrating multiple metrics that can reveal information, which is not apparent when examined using only a single contrast mechanism. [ABSTRACT FROM AUTHOR]

IntroductionPost-traumatic stress disorder (PTSD) is characterized by changes in both brain activity and microstructural integrity. Cumulative evidence demonstrates that hyperbaric oxygen therapy (HBOT) induces neuroplasticity and case-series studies indicate its potentially positive effects on PTSD. The aim of the study was to evaluate HBOT's effect in veterans with treatment resistant PTSD.MethodsVeterans with treatment resistant PTSD were 1:1 randomized to HBOT or control groups. All other brain pathologies served as exclusion criteria. Outcome measures included clinician-administered PTSD scale-V (CAPS-V) questionnaires, brief symptom inventory (BSI), BECK depression inventory (BDI), brain microstructural integrity evaluated by MRI diffuse tensor imaging sequence (DTI), and brain function was evaluated by an n-back task using functional MRI (fMRI). The treatment group underwent sixty daily hyperbaric sessions. No interventions were performed in the control group.ResultsThirty-five veterans were randomized to HBOT (N = 18) or control (n = 17) and 29 completed the protocol. Following HBOT, there was a significant improvement in CAPS-V scores and no change in the control (F = 30.57, PConclusionsHBOT improved symptoms, brain microstructure and functionality in veterans with treatment resistant PTSD.

Spaghetti meat (SM), woody breast (WB), and white striping (WS) are myopathies that affect the pectoral muscle of fast-growing broiler chickens. The prevalence and possible risk factors of these myopathies have been reported in other countries, but not yet in Canada. Thus, the objective of this study was to assess the prevalence and risk factors associated with these myopathies in a representative population of Canadian broilers. From May 2019 to March 2020, 250 random breast fillets from each of 37 flocks (total, 9,250) were obtained from two processing plants and assessed for the presence and severity of myopathies. Demographic data (e.g., sex and average live weight), environmental conditions during the grow-out period (e.g., temperature), and husbandry parameters (e.g., vaccination) were collected for each flock. Associations between these factors and the myopathies were tested using logistic regression analyses. The prevalence of SM, severe WB, and mild or moderate WS was 36.3% (95% CI: 35.3-37.3), 11.8% (95% CI: 11.2-12.5), and 96.0% (95% CI: 95.6-96.4), respectively. Most (85.1%) of the fillets showed multiple myopathies. Regression analyses showed that the odds of SM increased with live weight (OR = 1.30, 95% CI 1.01-1.69) and higher environmental temperature during the grow-out period (OR = 1.75, 95% CI 1.31-2.34). The odds of WB increased with live weight (OR = 1.23, 95% CI 1.03-1.47) and when flocks were not vaccinated against coccidia (OR = 1.86, 95% CI 1.51-2.29). This study documents for the first time a high prevalence of myopathies in Ontario broilers, and suggests that these lesions may have a significant economic impact on the Canadian poultry industry. Our results indicate that environmental conditions and husbandry are associated with the development of breast myopathies, in agreement with the current literature. Future studies are needed to determine how risk factors can promote the occurrence of these conditions, in order to implement possible mitigating strategies.

The identification of SARS-CoV-2 variants across the globe and their implications on the outspread of the pandemic, infection potential and resistance to vaccination, requires modification of the current diagnostic methods to map out viral mutations rapidly and reliably. Here, we demonstrate that integrating DNA barcoding technology, sample pooling and Next Generation Sequencing (NGS) provide an applicable solution for large-population viral screening combined with specific variant analysis. Our solution allows high throughput testing by barcoding each sample, followed by pooling of test samples using a multi-step procedure. First, patient-specific barcodes are added to the primers used in a one-step RT-PCR reaction, amplifying three different viral genes and one human housekeeping gene (as internal control). Then, samples are pooled, purified and finally, the generated sequences are read using an Illumina NGS system to identify the positive samples with a sensitivity of 82.5% and a specificity of 97.3%. Using this solution, we were able to identify six known and one unknown SARS-CoV-2 variants in a screen of 960 samples out of which 258 (27%) were positive for the virus. Thus, our diagnostic solution integrates the benefits of large population and epidemiological screening together with sensitive and specific identification of positive samples including variant analysis at a single nucleotide resolution.

Although there has been extensive research on pharmaceutical industry payments to healthcare professionals, healthcare organisations with key roles in health systems have received little attention. We seek to contribute to addressing this gap in research by examining drug company payments to General Practices in England in 2015. We combine a publicly available payments database managed by the pharmaceutical industry with datasets covering key practice characteristics. We find that practices were an important target of company payments, receiving £2,726,018, equivalent to 6.5% of the value of payments to all healthcare organisations in England. Payments to practices were highly concentrated and specific companies were also highly dominant. The top 10 donors and the top 10 recipients amassed 87.9% and 13.6% of the value of payments, respectively. Practices with more patients, a greater proportion of elderly patients, and those in more affluent areas received significantly more payments on average. However, the patterns of payments were similar across England’s regions. We also found that company networks–established by making payments to the same practices–were largely dominated by a single company, which was also by far the biggest donor. Greater policy attention is required to the risk of financial dependency and conflicts of interests that might arise from payments to practices and to organisational conflicts of interests more broadly. Our research also demonstrates that the comprehensiveness and quality of payment data disclosed via industry self-regulatory arrangements needs improvement. More interconnectivity between payment data and other datasets is needed to capture company marketing strategies systematically.

BackgroundCorporal punishment (CP) is still a common practice in schools globally. Although illegal, studies in South Africa report its continued use, but only a few have explored factors associated with school CP. Moreover, extant studies have not shown the interrelationships between explanatory factors. This study aimed to determine the prevalence and factors associated with learners' experiences, and to examine pathways to the learners' experiences of CP at school.Method3743 grade 8 learners (2118 girls and 1625 boys) from 24 selected public schools in Tshwane, South Africa, enrolled in a cluster randomised controlled trial evaluating a multi-component school-based intervention to prevent intimate partner violence, and completed self-administered questionnaires. We carried out descriptive analysis, simple linear and structural equation modelling to examine factors and pathways to the learners' experience of CP at school.ResultsAbout 52% of learners had experienced CP at school in the last 6 months. It was higher among boys compared to girls. Experience of CP at school amongst learners was associated with learner behavior, home environment, and school environment. Learners from households with low-socio economic status (SES) had an increased risk of CP experience at school. Amongst boys, low family SES status was associated with a negative home environment and had a direct negative impact on a learner's mental health, directly associated with misbehavior.ConclusionCP in public schools in South Africa continues despite legislation prohibiting its use. While addressing learner behaviour is critical, evidence-based interventions addressing home and school environment are needed to change the culture among teachers of using corporal punishment to discipline adolescents and inculcate one that promotes positive discipline.

ObjectivesWe examined how caregivers who had cared for a relative at end of life (EoL) wished to be cared for in the event that they experienced advanced dementia or physical disability in the future, and what factors influenced their preferences for EoL care.MethodsIn this mixed-methods study, 83 participants, recruited from multiple sources in Israel, were interviewed concerning socio-demographic factors, health status, past experience with EoL, preference for extension of life vs. quality of life (QoL), willingness to be dependent on others, and preferences for EoL care.ResultsIn case of advanced dementia, 58% preferred euthanasia or suicide; around a third chose those for physical disability. Care by family members was the least desired form of care in the advanced dementia scenario, although more desirable than institutional care in the physical disability scenario. QoL was rated as the highest factor impacting preferences for EoL care. Men demonstrated a higher preference than women for extension of life over QoL.ConclusionOur study points to the need for society to consider solutions to the request of participants to reject the type of EoL experienced by their relatives. Those solutions include investing in improving the quality of life at the end of life, and offering alternatives such as euthanasia, which a large proportion of our participants found ethically and medically appropriate within the current system of care in the event of severe physical disability, and more so in the event of advanced dementia.

OBJECTIVE:The American College of Gynecology (ACOG) recommendation does not limit air travel during pregnancy, yet the evidence for air travel effect on adverse pregnancy outcomes is limited and debatable. Study objectives were to examine the association between air travel during pregnancy and preterm birth together with decreased birth weight. STUDY DESIGN:A retrospective cohort study. METHODS:The study evaluated 628,292 women who gave birth to singleton infants from 9/2000 to 9/2016 and classified them into "air travel during pregnancy" or not, based on flight insurance as proxy. Multiple linear regression models were utilized to examine the relationship between air travel during pregnancy and newborn's gestational age and birth weight, while accounting for socioeconomic status, diabetes, high-risk pregnancies, and smoking. RESULTS:A total of 41,677 (6.6%) births of women who air traveled during pregnancy was included, and 586,615 (93.4%) births of women who did not. Air travel during pregnancy was associated with a statistically significant (p

In this paper we present a new method for automatic transliteration and segmentation of Unicode cuneiform glyphs using Natural Language Processing (NLP) techniques. Cuneiform is one of the earliest known writing system in the world, which documents millennia of human civilizations in the ancient Near East. Hundreds of thousands of cuneiform texts were found in the nineteenth and twentieth centuries CE, most of which are written in Akkadian. However, there are still tens of thousands of texts to be published. We use models based on machine learning algorithms such as recurrent neural networks (RNN) with an accuracy reaching up to 97% for automatically transliterating and segmenting standard Unicode cuneiform glyphs into words. Therefore, our method and results form a major step towards creating a human-machine interface for creating digitized editions. Our code, Akkademia, is made publicly available for use via a web application, a python package, and a github repository.

BACKGROUND:We developed, and pilot tested a family focused intervention Sammanit Jeevan "Living with Dignity" to reduce gender-based violence by husbands, change harmful social and gender norms and improve the economic conditions of women through young married women-led income generating activities (IGAs). METHODS:We conducted a modified interrupted time series study and qualitative research to evaluate the intervention in two migrant communities in Baglung district, Nepal. We enrolled young married women, their husbands and in-laws from 100 families. 200 women and 157 men completed questionnaires before the programme, and 6, 12 and 18 months afterwards. 18 in-depth interviews were conducted before the programme and 6 and 12 months later. We analysed the data for trends. RESULTS:The intervention positively impacted young married women's economic conditions, exposure to violence and changed inequitable gender attitudes. Some positive outcomes were observed among older women and men. Young women's past month earnings (35.0% - 81.3%, β = 0.11, p-value

BackgroundMany patient organisations collaborate with drug companies, resulting in concerns about commercial agendas influencing patient advocacy. We contribute to an international body of knowledge on patient organisation-industry relations by considering payments reported in the industry's centralised 'collaboration database' in Sweden. We also investigate possible commercial motives behind the funding by assessing its association with drug commercialisation.MethodsOur primary data source were 1,337 payment reports from 2014-2018. After extraction and coding, we analysed the data descriptively, calculating the number, value and distribution of payments for various units of analysis, e.g. individual companies, diseases and payment goals. The association between drug commercialisation and patient organisation funding was assessed by, first, the concordance between leading companies marketing drugs in specific diseases and their funding of corresponding patient organisations and, second, the correlation between new drugs in broader condition areas and payments to corresponding patient organisations.Results46 companies reported paying €6,449.224 (median €2,411; IQR €1,024-4,569) to 77 patient organisations, but ten companies provided 67% of the funding. Small payments dominated, many of which covered costs of events organised by patient organisations. An association existed between drug commercialisation and industry funding. Companies supported patient organisations in diseases linked to their drug portfolios, with the top 3 condition areas in terms of funding-cancer; endocrine, nutritional and metabolic disorders; and infectious and parasitic disorders-accounting for 63% of new drugs and 56% of the funding.ConclusionThis study reveals close and widespread ties between patient organisations and drug companies. A relatively few number of companies dominated the funding landscape by supporting patient organisations in disease areas linked to their drug portfolios. This commercially motivated funding may contribute to inequalities in resource and influence between patient organisations. The association between drug commercialisation and industry funding is also worrying because of the therapeutic uncertainty of many new drugs. Our analysis benefited from the existence of a centralised database of payments-which should be adopted by other countries too-but databases should be downloadable in an analysable format to permit efficient and independent analysis.

Purpose: Self-assessment of a physician's performance in both procedure and non-procedural activities can be used to identify their deficiencies to allow for appropriate corrective measures. Physicians are inaccurate in their self-assessments, which may compromise opportunities for self- development. To improve this accuracy, video-based interventions of physicians watching their own performance, an experts' performance or both, have been proposed to inform their self-assessment. We conducted a systematic review of the effectiveness of video-based interventions targeting improved self-assessment accuracy among physicians. Materials and methods: The authors performed a systematic search of MEDLINE, Embase, EBM reviews, and Scopus databases from inception to August 23, 2022, using combinations of terms for "self-assessment", "video-recording", and "physician". Eligible studies were empirical investigations assessing the effect of video-based interventions on physicians' self-assessment accuracy with a comparison of self-assessment accuracy pre- and post- video intervention. We defined self-assessment accuracy as a "direct comparison between an external evaluator and self-assessment that was quantified using formal statistical analysis". Two reviewers independently screened records, extracted data, assessed risk of bias, and evaluated quality of evidence. A narrative synthesis was conducted, as variable outcomes precluded a meta-analysis. Results: A total of 2,376 papers were initially retrieved. Of these, 22 papers were selected for full-text review; a final 9 studies met inclusion criteria for data extraction. Across studies, 240 participants from 5 specialties were represented. Video-based interventions included self-video review (8/9), benchmark video review (3/9), and/or a combination of both types (1/9). Five out of nine studies reported that participants had inaccurate self-assessment at baseline. After the intervention, 5 of 9 studies found a statistically significant improvement in self-assessment accuracy. Conclusions: Overall, current data suggests video-based interventions can improve self-assessment accuracy. Benchmark video review may enable physicians to improve self-assessment accuracy, especially for those with limited experience performing a particular clinical skill. In contrast, self-video review may be able to provide improvement in self-assessment accuracy for more experience physicians. Future research should use standardized methods of comparison for self-assessment accuracy, such as the Bland-Altman analysis, to facilitate meta-analytic summation. [ABSTRACT FROM AUTHOR]

BACKGROUND:Chronic obstructive pulmonary disease (COPD) is an inflammatory disease characterized by a progressive and irreversible deterioration of lung function. Exacerbations of COPD have prolonged negative effects on pulmonary function and a major impact on health status and outcomes. NLRP3 inflammasome is a cardinal component of the inflammatory response, with marked evidence in stable and exacerbations of COPD. The aim of our study was to evaluate the NLRP3 inflammasome activity during COPD exacerbation by using an in vitro model. METHODS:A549 cells were stimulated with different concentrations (10%, 4%, 2%) of cigarette smoke extract (CSE) with or without LPS (0.1μg/ml) for 24 hours. Cell viability was assessed by using XTT test. Levels of inflammatory cytokines (IL-8, MCP-1, and IL-1β) were measured by ELISA and the activity level of NLRP-3 was evaluated by flow cytometry. RESULTS:Cells exposed to CSE present an increase in inflammatory cytokines (IL-8 and MCP-1) production in a dose-dependent manner. Incubation with LPS to these cells results in higher levels of IL-8 and MCP-1 compared to stimulation of CSE alone. NLRP3 inflammasome activity and IL-1β levels were significantly increased in cells exposed to both CSE and LPS compared to CSE alone. CONCLUSIONS:NLRP3 inflammasome is upregulated in an in-vitro model of COPD and COPD exacerbation. Our findings provide novel biomarkers for COPD exacerbation and may present new targets for future research.

This paper aims to describe the prevalent forms of intimate partner violence (IPV), and the factors associated with IPV among women and men living in the two migrant communities of Baglung district, Nepal. 357 adult women and men were enrolled following a family model, interviewing young married women with daughter-in-law status in the home, their husbands, and mothers-in-law and fathers-in-laws using an electronic questionnaire. Random effects regression modelling compared men and women, as well as young married women with daughter-in-law status and older women with mothers-in-law with status. 28.6% of women had ever experienced physical and/or sexual violence by an intimate partner compared to 18.2% of men ever perpetrated these forms of violence against their wives. Being older, male controlling behaviour and poor relations with husband increased women's IPV in their lifetime while perceptions that the mother-in-law is kind were protective. Being ashamed of being unemployed and childhood trauma were associated with men perpetrating IPV in their lifetime. Borrowing money or food increased young married women's lifetime IPV risk while mother-in-law cruelty and male control increased older married women's lifetime IPV exposure. Factors associated with IPV in the past year among men were being younger, job seeking, experiences of childhood trauma and depression exposure among men while difficulty accessing money for emergencies, holding inequitable gender attitudes, and depression was associated with women's increased IPV exposure. Unemployment stress, holding inequitable gender attitudes and mother-in-law kindness were associated with young women's increased IPV risk and hunger, mother-in-law cruelty and depression with older women's IPV risk. There is a need to critically challenge harmful social and gender norms by using approaches that are sensitive to young married women's position and unequal gender relations in the family. IPV prevention interventions need to employ a holistic approach that combines changing social and gender norms and improving socioeconomic conditions of women living in migrant communities.

IntroductionThe primary rational for using mesenchymal stromal cells (MSCs) to rejuvenate damaged tissue is mostly based on their capacity to trans-differentiate and repair injured organs. However, previous studies have demonstrated that MSCs are beneficial even at very early stages, before differentiation and proliferation can be expected. The aim of the current study was to investigate the multifaceted immunological effects of systemically administrating MSCs in the setting of acute kidney injury (AKI) induced by ischemic-reperfusion (I/R).MethodsA rat model of I/R induced AKI was used. The rats underwent a unilateral nephrectomy with simultaneously clamping the contralateral kidney for 60 minutes. Four treatment groups received intravenously, increasing doses of human MSCs and after 48 hours, the rats were sacrificed. Blood was taken to evaluate renal functions and to measure systemic inflammatory markers. Kidneys were taken for histopathologic examinations and evaluations of intra-renal complement activation and inflammatory mediators.ResultsRenal functions improved in U shaped dose dependent manner. Mean serum creatinine levels were 4.5, 2.9, 2.6, 1.7 and 4.1 mg/dL in I/R + placebo, I/R + 150x103 cells, I/R + 250x103 cells, I/R + 500x103 cells and I/R + 1,000x103 cells respectfully (p-valuesConclusionsThe early beneficial effect of MSCs in the setting of AKI may be attributed to their immunomodulatory effects. Safe treatment with MSCs can block the deleterious activation of the complement cascade and alleviate the hazardous inflammatory mediator-related cascade.

Music making, in the form of free improvisations, is a common technique in music therapy, used to express one's feelings or ideas in the non-verbal language of music. In the broader sense, arts therapies, and music therapy in particular, are used to induce therapeutic and psychosocial effects, and to help mitigate symptoms in serious and chronic diseases. They are also used to empower the wellbeing and quality of life for both healthy individuals and patients. However, much research is still required to understand how music-based and arts-based approaches work, and to eventually enhance their effectivity. The clinical setting employing the arts constitutes a rich dynamic environment of occurrences that is difficult to capture, being driven by complex, simultaneous, and interwoven behavioral processes. Our computational paradigm is designed to allow substantial barriers in the arts-based fields to be overcome by enabling the rigorous and quantitative tracking, analyzing and documenting of the underlying dynamic processes. Here we expand the method for the music modality and apply it in a proof of principle experimentation to study expressive behavioral effects of diverse musical improvisation tasks on individuals and collectives. We have obtained statistically significant results that include empirical expressive patterns of feelings, as well as proficiency, gender and age behavioral differences, which point to variation factors of these categorized collectives in music making. Our results also suggest that males are more exploratory than females (e.g., they exhibit a larger range of octaves and intensity) and that the older people express musical characterized negativity more than younger ones (e.g., exhibiting larger note clusters and more chromatic transitions). We discuss implications of these findings to music therapy, such as behavioral diversity causality in treatment, as well as future scientific and clinical applications of the methodology.

Most papers on the physical condition of birds during spring migration focused on food availability preceding migratory take-off. Only a few studies examined the effect of climate conditions at the wintering grounds upon autumn arrival on bird physical condition later on. Here, we hypothesized that environmental conditions upon arrival at the wintering grounds, and not necessarily upon departure, have a crucial carry-over effect on bird spring migration. Using 29,000 observations of the lesser whitethroat, Sylvia curruca, and the eastern Bonelli's warbler, Phylloscopus orientalis, we found temperatures upon arrival at the African wintering grounds to be the only climatic variable correlated with birds' body state upon spring stopover in Israel, six months later. Two different mechanisms could explain these results. One possibility is that high temperatures create favorable conditions for insect activity, which allows rapid recovery from autumn migration and hence successful winter survival and maintenance. Another possible scenario is that harsh conditions, due to the heat and dry environment, cause high mortality, permitting survival of larger individuals which, then, enjoy reduced inter- and intra-specific competition. Whatever the mechanism is, our findings suggest that conditions upon autumn arrival, and not necessarily at the end of winter as traditionally thought, may have a major impact on migrating birds.

Kin-biased behavior (that is responding differentially to kin and non-kin) is thought to be adaptive in many social interactions. One example of this kin bias is behaving less aggressively toward a relative than a non-relative, a behavior which yields inclusive fitness benefits. However, data are lacking about the ability of animals to weigh their preference for kinship and the density of conspecifics simultaneously and to respond accordingly. Fire salamanders (Salamandra infraimmaculata) larviposit in high densities in ponds. Thus, larvae of different females confront competition and predation by other larvae. We studied whether larvae prefer their kin over particular density or vice versa. We experimentally used a transparent glass aquarium with inner chambers to test the responses of a focal larva toward its siblings and non-siblings. Specifically, we quantified the time a focal larva spent near its siblings or non-siblings, presented in varying densities, and the aggression level it demonstrated. We found that focal larvae spent more time near non-siblings if non-sibling and sibling groups were of equal density. The focal larvae were also more aggressive toward non-siblings. The results may be explained by the cannibalistic nature of these larvae: high density may provide more opportunities for food, especially when non-siblings are present. Further explanations for these findings may include other advantages of staying in a larger group and/or the stronger olfactory and visual stimulation offered by groups compared to a single individual. These findings suggest that larvae make differential responses toward conspecifics depending simultaneously on the level of relatedness and the density of the group. Such responses have important implications for social-aggregation decisions and may especially affect the fitness of cannibalistic species.

Treated wastewater (TWW) constitutes a sustainable water resource and has been used for fish culture in some countries around the world, although there are no comprehensive data on the effect of TWW on fish growth and health in the context of aquaculture production. Our objectives were to examine how fish culture in TWW affected fish growth and fitness, as well as compliance with the international standards for safe consumption. Guppy (Poecilia reticulata) fingerlings were reared in 0%, 50% and 100% tertiary TWW (TTWW), from the age of five days, for a period of four months. In water analyses, 33 out of 67 tested organic micropollutants (OMPs) were detected in the TTWW samples at least once, at concentrations that are typically reported in domestic TTWW. Fish survival ranged between 77-80% and did not differ between treatment groups. Fish growth and mortality following challenge infection with Tetrahymena sp. (which ranged between 64-68%), were similar among treatment groups. Of tested immunological parameters, lysozyme and anti-protease was similar among treatments while complement activity was highest in the 50% TTWW-reared fish. No abnormalities were observed in the histopathological analysis. Levels of heavy metals, polychlorinated-biphenyls (PCBs) and organochlorines (OCs) in fish were below the detection limit and below the Food and Agriculture Organization of the United Nations (FAO) and the European Union EU maximal permitted levels in food fish. Results suggest that the yield of fish grown in TTWW is potentially similar to that in freshwater, and the produced fish comply with the standards of consumer safety. The results are in line with previous studies that examined the feasibility of TWW-fed aquaculture.

TRIAL REGISTRATION:ClinicalTrials.gov NCT02349321.

Introduction: The prevalence of epilepsy in sub-Saharan Africa varies considerably, and the exact estimate for Ghana remains unclear, particularly in peri-urban areas where data are scarce. More community-based studies are required to understand better the actual burden of epilepsy in these areas and the difficulties in accessing healthcare. Objective: To adapt and validate a household survey epilepsy-screening instrument in Shai-Osudoku and Ningo-Prampram District of Greater Accra Region, Ghana. Methods: We developed a 17-item epilepsy screening instrument by modifying previously validated English language questionnaires. We included questions that could identify convulsive and non-convulsive seizures. Language experts forward- and back-translated the questionnaires into the two languages: Asante Twi and Dangme. Cases were people with confirmed epilepsy attending healthcare facilities where these languages are used. Controls were unaffected relatives of cases or people attending the same healthcare facilities for other medical conditions. We matched cases and controls for geographical location and ethnicity. An affirmative response to one of the seventeen questions by a participant was deemed a positive screen. The questionnaires were divided into two stages. The first stage consisted of broader, more general questions aimed at identifying potential cases of epilepsy. The second stage involved a more detailed and focused set of questions administered to those who screened positive in the first stage. Results: One hundred and forty Dangme speakers (70 cases and 70 controls) and 100 Asante Twi speakers (50 cases and 50 controls) were recruited. The sensitivity and specificity for Dangme were: Stage 1, 100% and 80%, and Stage 2, 98.6% and 85.7%. The Dangme version reliably identified epilepsy with positive predictive values of 83.3% and 87.3% at stages 1 and 2. The questionnaire excluded epilepsy with 100% and 98.4% negative predictive values. For the Asante Twi version, the sensitivity and specificity were 98% and 92% (95% at Stage 1, and for Stage 2, 96% and 94%. The Asante Twi questionnaire reliably specified epilepsy with positive predictive values of 92.5% and 94.1% at stages 1 and 2. It excluded epilepsy with negative predictive values of 97.9% and 95.9% for the two stages Conclusions: Our questionnaire is valid for the two languages and usable for community-based epilepsy surveys in Ghana. It can also be adapted for other resource-poor settings, although translation and iterative in-country testing will be needed to ensure its validity. [ABSTRACT FROM AUTHOR]

Analysis of a sacrificed and interred domestic donkey from an Early Bronze Age (EB) IIIB (c. 2800-2600 BCE) domestic residential neighborhood at Tell eṣ-Ṣâfi/Gath, Israel, indicate the presence of bit wear on the Lower Premolar 2 (LPM2). This is the earliest evidence for the use of a bit among early domestic equids, and in particular donkeys, in the Near East. The mesial enamel surfaces on both the right and left LPM2 of the particular donkey in question are slightly worn in a fashion that suggests that a dental bit (metal, bone, wood, etc.) was used to control the animal. Given the secure chronological context of the burial (beneath the floor of an EB IIIB house), it is suggested that this animal provides the earliest evidence for the use of a bit on an early domestic equid from the Near East.

Childhood traumas, in the form of physical, sexual, and emotional abuse and neglect, are globally widespread and highly prevalent, and associated with a range of subsequent poor health outcomes. This study sought to understand the relationship between physical, sexual and emotional childhood abuse and subsequent HIV-risk behaviours amongst young people (18-30) living in urban informal settlements in Durban, South Africa. Data came from self-completed questionnaires amongst 680 women and 677 men comprising the baseline of the Stepping Stones and Creating Futures intervention trial. Men and women were analysed separately. Logistic regression models assessed the relationship between six HIV-risk behaviours and four measures of trauma: the form of trauma, the severity of each trauma, the range of traumas, and overall severity of childhood trauma. Childhood traumas were incredibly prevalent in this population. All childhood traumas were associated with a range of HIV-risk behaviours. This was for the ever/never trauma, as well as the severity of each type of trauma, the range of trauma, and overall severity of childhood trauma. Despite the wider harsh contexts of urban informal settlements, childhood traumas still play a significant role in shaping subsequent HIV-risk behaviours amongst young people. Interventions to reduce childhood traumas for populations in informal settlements need to be developed. In addition, trauma focused therapies need to be considered as part of wider HIV-prevention interventions for young adults.ClinicalTrials.gov NCT03022370.

[This corrects the article DOI: 10.1371/journal.pone.0196335.].

The Caenorhabditis elegans cell lineage is nearly invariant. Whether this stereotyped cell-division pattern promotes reproducibility in cell shapes/positions is not generally known, as manual spatiotemporal cell-shape/position alignments are labor-intensive, and fully-automated methods are not described. Here, we report automated algorithms for spatiotemporal alignments of C. elegans embryos from pre-morphogenesis to motor-activity initiation. We use sparsely-labeled green-fluorescent nuclei and a pan-nuclear red-fluorescent reporter to register consecutive imaging time points and compare embryos. Using our method, we monitor early assembly of the nerve-ring (NR) brain neuropil. While NR pioneer neurons exhibit reproducible growth kinetics and axon positions, cell-body placements are variable. Thus, pioneer-neuron axon locations, but not cell-body positions, are under selection. We also show that anterior NR displacement in cam-1/ROR Wnt-receptor mutants is not an early NR assembly defect. Our results demonstrate the utility of automated spatiotemporal alignments of C. elegans embryos, and uncover key principles guiding nervous-system development in this animal.

Developing interventions that address psychosocial wellbeing of people living with HIV is critical to ensure strong linkages to and retention in HIV care. This paper describes the development of Sondela, an HIV adjustment and coping intervention for heterosexual men and women living with HIV, and its relevance and feasibility in the South African context. Sondela is a six three-hour, small group-based, participatory workshop series. We followed an iterative, multi-phased process of curriculum development that involved research, theoretical frameworks and piloting. A systematic review highlighted the absence of psychosocial interventions targeting heterosexual HIV positive populations living in high HIV prevalence and resource-poor settings. Formative studies demonstrated risk and social factors associated with adjustment and coping with HIV, emphasising the need for interventions that acknowledge gendered experiences. Our pilot of Sondela demonstrated high levels of relevance and feasibility. Men appreciated the workshop "space" to openly talk about their HIV positive status and what is means for their role as partners and fathers and friends. Women valued the skills and approaches because they were relevant to "real life" situations and not just about HIV. Sondela promises to be valuable in supporting health system initiatives and psychosocial support to strengthen linkages to and retention in HIV care, and this suggests a need for rigorous evaluation of Sondela to establish evidence for its effectiveness in a general population.

Violence against women is often exacerbated by war, but most civilian research has investigated short term impact. We describe the conflict experiences of men and women from the general population of Bougainville Papua New Guinea, perceptions of the enduring impact of conflict, and the associations between these and the major health and development problems on the islands: mental ill-health and violence against women.Fourteen years after the end of the decade long civil war, we conducted a household survey with a random sample of adult (n = 864) men and (n = 879) women living in Bougainville. The interviews were mostly conducted face-to-face, with very sensitive questions self-completed.Mental ill-health was highly prevalent, 37.8% of women and 32% of men had high levels of depressive symptomatology, 34.4% of men abused alcohol and 15.1% of women and 24.6% of men had high levels of PTSD symptoms. Among women, 23.3% had been raped in the year prior to the interview and 33.3% had experience physical or sexual partner violence. The prevalence of exposure to trauma during the civil war was very high and many of the men and women experienced lingering impact of conflict. Multiple logistic regression models showed that war trauma was associated with PTSD symptoms in women and PTSD symptoms, alcohol abuse and depressive symptoms in men. The perceived enduring impact of conflict was associated with depressive symptoms in men and women, problem drinking and suicidal thoughts in women and drug use in men. The perceived enduring conflict impact was associated with perpetration of past year rape and physical and/or sexual partner violence.The Bougainville civil war had a devastating impact on the population's lives. Reversing this legacy is essential but requires addressing what is perceived as the enduring social, economic and psychological impact of the conflict and a major focus on prevention of violence against women.

Intramyocellular triacylglycerol (IMTG) is utilized as metabolic fuel during exercise and is linked to insulin resistance, but the long-term effect of weight loss strategies on IMTG among participants with abdominal fat, remain unclear.In an 18-month trial, sedentary participants with abdominal fat/dyslipidemia were randomized to either a low-fat (LF) or Mediterranean/low-carbohydrate (MED/LC) diet (including 28g·day-1 of walnuts). After 6-months, the participants were re-randomized to moderate intense physical activity (PA+) or non-physical activity (PA-). Magnetic resonance imaging (MRI) was used to quantify changes of IMTG, abdominal sub-depots, hepatic and intermuscular fats.Across the 277 participants [86% men, age = 48 years, body-mass-index (BMI) = 31kg/m2, visceral fat = 33%] 86% completed the 18-m trial. At baseline, women had higher IMTG than men (3.4% vs. 2.3%, p

Anhedonia is defined as a diminished ability to obtain pleasure from otherwise positive stimuli. Anxiety and mood disorders have been previously associated with dysregulation of the reward system, with anhedonia as a core element of major depressive disorder (MDD). The aim of the present study was to investigate whether stress-induced anhedonia could be prevented by treatments with escitalopram or novel herbal treatment (NHT) in an animal model of depression. Unpredictable chronic mild stress (UCMS) was administered for 4 weeks on ICR outbred mice. Following stress exposure, animals were randomly assigned to pharmacological treatment groups (i.e., saline, escitalopram or NHT). Treatments were delivered for 3 weeks. Hedonic tone was examined via ethanol and sucrose preferences. Biological indices pertinent to MDD and anhedonia were assessed: namely, hippocampal brain-derived neurotrophic factor (BDNF) and striatal dopamine receptor D2 (Drd2) mRNA expression levels. The results indicate that the UCMS-induced reductions in ethanol or sucrose preferences were normalized by escitalopram or NHT. This implies a resemblance between sucrose and ethanol in their hedonic-eliciting property. On a neurobiological aspect, UCMS-induced reduction in hippocampal BDNF levels was normalized by escitalopram or NHT, while UCMS-induced reduction in striatal Drd2 mRNA levels was normalized solely by NHT. The results accentuate the association of stress and anhedonia, and pinpoint a distinct effect for NHT on striatal Drd2 expression.

Background: Diabetes mellitus is a growing public health emergency with prevalence in sub-Sahara Africa expected to experience the highest increase by 2045. Glycemic control is central to diabetes management, but it is influenced by various factors. This study determines the level of glycemic control and the associated individual factors among type 2 diabetes mellitus (T2DM) patients. Methods: A cross-sectional descriptive study was conducted at the Shai-Osudoku District Hospital from 9th November to 15th December 2022. A structured questionnaire was used to collect data on socio-demographic characteristics, lifestyle modifications, co-morbidities, adherence to medication and diet regimens and duration of diabetes. Anthropometric and glycated hemoglobin (HbA1c) measurements were taken. Chi-squared and multivariate logistic regression analyses were carried out to determine factors associated with glycemic control at 95% confidence levels. Results: A total of 227 patients participated in this study. The majority of the participants were females (77.97%) and the mean (+SD) age was 60.76 + 12.12 years. Good glycemic control (HbA1c < 7%) among the participants was 38.77% (n = 88) and the median HbA1c was 7.5% (IQR: 6.5% to 9.4%). Significant factors associated with good glycemic control were eating healthy meals (AOR: 4.78, 95% CI: 1.65, 13.88: p = 0.004), oral hypoglycemic agents alone (AOR: 15.71, 95% CI: 1.90, 129.44: p = 0.010) and those with previously good glycemic control (AOR: 4.27, 95% CI: 2.16, 8.43: <0.001). Conclusion: This study showed low levels of good glycemic control among T2DM patients at the primary care level in Ghana. Healthy eating, oral hypoglycemic agents and those with previously normal HbA1c were associated with glycemic control. [ABSTRACT FROM AUTHOR]

BACKGROUND:Interventions to prevent rape perpetration must be designed to address its drivers. This paper seeks to extend understanding of drivers of single and multiple perpetrator rape (referred to here as SPR and MPR respectively) and the relationships between socio-economic status, childhood trauma, peer pressure, other masculine behaviours and rape. METHOD:1370 young men aged 15 to 26 were interviewed as part of the randomised controlled trial evaluation of Stepping Stones in the rural Eastern Cape. We used multinomial to compare the characteristics of men who reported rape perpetration at baseline. We used structural equation modelling (SEM) to examine pathways to rape perpetration. RESULTS:76.1% of young men had never raped, 10.0% had perpetrated SPR and 13.9% MPR. The factors associated with both MPR and SPR (compared to never having raped) were indicators of socio-economic status (SES), childhood trauma, sexual coercion by a woman, drug and alcohol use, peer pressure susceptibility, having had transactional sex, multiple sexual partners and being physically violent towards a partner. The SEM showed the relationship between SES and rape perpetration to be mediated by gender inequitable masculinity. It was complex as there was a direct path indicating that SES correlated with the masculinity variable directly such that men of higher SES had more gender inequitable masculinities, and indirect path mediated by peer pressure resistance indicated that the former pertained so long as men lacked peer pressure resistance. Having a higher SES conveyed greater resistance for some men. There was also a path mediated through childhood trauma, such that men of lower SES were more likely to have a higher childhood trauma exposure and this correlated with a higher likelihood of having the gender inequitable masculinity (with or without the mediating effect of peer pressure resistance). DISCUSSION:Both higher and lower socio-economic status were associated with raping. Prevention of rape perpetration must focus on changing men's gender ideals, entitlements and inequitable practices. Reducing poverty and adverse childhood experiences should also be of benefit.

BACKGROUND:Regulation of hepatic glucose production has been a target for antidiabetic drug development, due to its major contribution to glucose homeostasis. Previous pre-clinical study demonstrated that peripheral electrical stimulation (PES) may stimulate glucose utilization and improve hepatic insulin sensitivity. The aim of the present study was to evaluate safety, tolerability, and the glucose-lowering effect of this approach in patients with type 2 diabetes (T2DM). METHODS:Twelve patients with T2DM were recruited for an open label, interventional, randomized trial. Eleven patients underwent, in a crossover design, an active, and a no-intervention control periods, separated with a two-week washout phase. During the active period, the patients received a daily lower extremity PES treatment (1.33Hz/16Hz burst mode), for 14 days. Study endpoints included changes in glucose levels, number of hypoglycemic episodes, and other potential side effects. Endpoints were analyzed based on continuous glucose meter readings, and laboratory evaluation. RESULTS:We found that during the active period, the most significant effect was on nocturnal glucose control (P < 0.0004), as well as on pre-meal mean glucose levels (P < 0.02). The mean daily glucose levels were also decreased although it did not reach clinical significance (P = 0.07). A reduction in serum cortisol (P < 0.01) but not in insulin was also detected after 2 weeks of treatment. No adverse events were recorded. CONCLUSIONS:These results indicate that repeated PES treatment, even for a very short duration, can improve blood glucose control, possibly by suppressing hepatic glucose production. This effect may be mediated via hypothalamic-pituitary-adrenal axis modulation. TRIAL REGISTRATION:ClinicalTrials.gov NCT02727790.

Programmed cell death is a ubiquitous process in metazoan development. Apoptosis, one cell death form, has been studied extensively. However, mutations inactivating key mammalian apoptosis regulators do not block most developmental cell culling, suggesting that other cell death pathways are likely important. Recent work in the nematode Caenorhabditis elegans identified a non-apoptotic cell death form mediating the demise of the male-specific linker cell. This cell death process (LCD, linker cell-type death) is morphologically conserved, and its molecular effectors also mediate axon degeneration in mammals and Drosophila. To develop reagents to manipulate LCD, we established a simple high-throughput screening protocol for interrogating the effects of small molecules on C. elegans linker cell death in vivo. From 23,797 compounds assayed, 11 reproducibly block linker cell death onset. Of these, five induce animal lethality, and six promote a reversible developmental delay. These results provide proof-of principle validation of our screening protocol, demonstrate that developmental progression is required for linker cell death, and suggest that larger scale screens may identify LCD-specific small-molecule regulators that target the LCD execution machinery.

The development of antibacterial drugs to overcome various pathogenic species, which inhabit the oral cavity, faces several challenges, such as salivary flow and enzymatic activity that restrict dosage retention. Owing to their amphipathic nature, antimicrobial peptides (AMPs) serve as the first line of defense of the innate immune system. The ability to synthesize different types of AMPs enables exploitation of their advantages as alternatives to antibiotics. Sustained release of AMPs incorporated in biodegradable polymers can be advantageous in maintaining high levels of the peptides. In this study, four potent ultra-short lipopeptides, conjugated to an aliphatic acid chain (16C) were incorporated in two different biodegradable polymers: poly (lactic acid co castor oil) (PLACO) and ricinoleic acid-based poly (ester-anhydride) (P(SA-RA)) for sustained release. The lipopeptide and polymer formulations were tested for antibacterial activity during one week, by turbidometric measurements of bacterial outgrowth, anti-biofilm activity by live/dead staining, biocompatibility by hemolysis and XTT colorimetric assays, mode of action by fluorescence-activated cell sorting (FACS) and release profile by a fluorometric assay. The results show that an antibacterial and anti-biofilm effect, as well as membrane disruption, can be achieved by the use of a formulation of lipopeptide incorporated in biodegradable polymer.

Visceral adipose tissue foam cells are increased in human obesity, and were implicated in adipose dysfunction and increased cardio-metabolic risk. In the circulation, non-classical monocytes (NCM) are elevated in obesity and associate with atherosclerosis and type 2 diabetes. We hypothesized that circulating NCM correlate and/or are functionally linked to visceral adipose tissue foam cells in obesity, potentially providing an approach to estimate visceral adipose tissue status in the non-surgical obese patient.We preformed ex-vivo functional studies utilizing sorted monocyte subclasses from healthy donors. Moreover, we assessed circulating blood monocyte subclasses and visceral fat adipose tissue macrophage (ATM) lipid content by flow-cytometry in paired blood and omental-fat samples collected from patients (n = 65) undergoing elective abdominal surgery.Ex-vivo, NCM and NCM-derived macrophages exhibited lower lipid accumulation capacity compared to classical or intermediate monocytes/-derived macrophages. Moreover, of the three subclasses, NCM exhibited the lowest migration towards adipose tissue conditioned-media. In a cohort of n = 65, increased %NCM associated with higher BMI (r = 0.250,p

Organophosphates (OPs) are potentially able to affect serine proteases by reacting with their active site. The potential effects of OPs on coagulation factors such as thrombin and on coagulation tests have been only partially characterized and potential interactions with OPs antidotes such as oximes and muscarinic blockers have not been addressed. In the current study, we investigated the in vitro interactions between coagulation, thrombin, the OP paraoxon, and its antidotes obidoxime and atropine. The effects of these substances on thrombin activity were measured in a fluorescent substrate and on coagulation by standard tests. Both paraoxon and obidoxime but not atropine significantly inhibited thrombin activity, and prolonged prothrombin time, thrombin time, and partial thromboplastin time. When paraoxon and obidoxime were combined, a significant synergistic effect was found on both thrombin activity and coagulation tests. In conclusion, paraoxon and obidoxime affect thrombin activity and consequently alter the function of the coagulation system. Similar interactions may be clinically relevant for coagulation pathways in the blood and possibly in the brain.

Transferring Saccharomyces cerevisiae cells to water is known to extend their lifespan. However, it is unclear whether this lifespan extension is due to slowing the aging process or merely keeping old yeast alive. Here we show that in water-transferred yeast, the toxicity of polyQ proteins is decreased and the aging biomarker 47Q aggregates at a reduced rate and to a lesser extent. These beneficial effects of water-transfer could not be reproduced by diluting the growth medium and depended on de novo protein synthesis and proteasomes levels. Interestingly, we found that upon water-transfer 27 proteins are downregulated, 4 proteins are upregulated and 81 proteins change their intracellular localization, hinting at an active genetic program enabling the lifespan extension. Furthermore, the aging-related deterioration of the heat shock response (HSR), the unfolded protein response (UPR) and the endoplasmic reticulum-associated protein degradation (ERAD), was largely prevented in water-transferred yeast, as the activities of these proteostatic network pathways remained nearly as robust as in young yeast. The characteristics of young yeast that are actively maintained upon water-transfer indicate that the extended lifespan is the outcome of slowing the rate of the aging process.

Isotope data from a sacrificial ass and several ovicaprines (sheep/goat) from Early Bronze Age household deposits at Tell es-Safi/Gath, Israel provide direct evidence for the movement of domestic draught/draft and husbandry animals between Old Kingdom Egypt (during the time of the Pyramids) and Early Bronze Age III Canaan (ca. 2900-2500 BCE). Vacillating, bi-directional connections between Egypt and Canaan are known throughout the Early Bronze Age, but here we provide the first concrete evidence of early trade in animals from Egypt to Canaan.

The ε-amino group of lysine residues may be mono-, di- or tri-methylated by protein lysine methyltransferases. In the past few years it has been highly considered that methylation of both histone and non-histone proteins has fundamental role in development and progression of various human diseases. Thus, the establishment of tools to study lysine methylation that will distinguish between the different states of methylation is required to elucidate their cellular functions. The 3X malignant brain tumor domain (3XMBT) repeats of the Lethal(3)malignant brain tumor-like protein 1 (L3MBTL1) have been utilized in the past as an affinity reagent for the identification of mono- and di-methylated lysine residues on individual proteins and on a proteomic scale. Here, we have utilized the 3XMBT domain to develop an enzyme-linked immunosorbent assay (ELISA) that allows the high-throughput detection of 3XMBT binding to methylated lysines. We demonstrated that this system allows the detection of methylated peptides, methylated proteins and PKMT activity on both peptides and proteins. We also optimized the assay to detect 3XMBT binding in crude E. coli lysates which facilitated the high throughput screening of 3XMBT mutant libraries. We have utilized protein engineering tools and generated a double site saturation 3XMBT library of residues 361 and 411 that were shown before to be important for binding mono and di-methylated substrates and identified variants that can exclusively recognize only di-methylated peptides. Together, our results demonstrate a powerful new approach that will contribute to deeper understanding of lysine methylation biology and that can be utilized for the engineering of domains for specific binders of other post-translational modifications.