217 research outputs found

    Migration of germline progenitor cells is directed by sphingosine-1-phosphate signalling in a basal chordate.

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    The colonial ascidian Botryllus schlosseri continuously regenerates entire bodies in an asexual budding process. The germ line of the newly developing bodies is derived from migrating germ cell precursors, but the signals governing this homing process are unknown. Here we show that germ cell precursors can be prospectively isolated based on expression of aldehyde dehydrogenase and integrin alpha-6, and that these cells express germ cell markers such as vasa, pumilio and piwi, as well as sphingosine-1-phosphate receptor. In vitro, sphingosine-1-phosphate (S1P) stimulates migration of germ cells, which depends on integrin alpha-6 activity. In vivo, S1P signalling is essential for homing of germ cells to newly developing bodies. S1P is generated by sphingosine kinase in the developing germ cell niche and degraded by lipid phosphate phosphatase in somatic tissues. These results demonstrate a previously unknown role of the S1P signalling pathway in germ cell migration in the ascidian Botryllus schlosseri

    Epidemiology of Cleft Lip and Palate

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    Orofacial cleft (OFC) anomalies are amongst the most common congenital anomalies and the most common craniofacial anomalies. Despite their poorly characterized etiologies, cases of OFC are usually grouped by epidemiological studies as cleft lip, with or without cleft palate (CL/P), and cleft palate alone (CPO). Incidence of CL/P and CPO differs according to gender and ancestry and may vary widely across studies. Cases of OFC are characterized as either “syndromic” or “nonsyndromic,” with further classification of nonsyndromic cases into isolated cases and cases that present with additional malformations. The genetic bases for many syndromic cases of OFC have been previously elucidated. Genetic associations have been described for nonsyndromic OFC as well. Importantly, etiology of OFC is known to involve interaction between genetic and environmental factors, including maternal nutrition and exposure to teratogenic agents. Furthermore, evidence points toward epigenetic as well as genetic factors influencing OFC etiology. Recent studies have begun to explore the association between CL/P and cancer. These studies report higher incidence of cancer among patients with CL/P and their family members as well as identification of common genetic markers mediating this increased risk, although much remains unknown about this link

    Prevalence of Atypical Infections in Male Patients with Chronic Pelvic Pain

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    Introduction:  Atypical infections are often considered as a potential etiology for men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). We aimed to describe the prevalence of atypical infections in this patient population to inform clinical management for male patients complaining of pelvic pain.  Methods: We retrospectively reviewed patients at a single center from January 2016 to January 2019. We included patients with CP/CPPS Type III diagnosed with pelvic or genital pain in the absence of bacterial infection. All patients underwent an atypical infection panel. The primary outcome measure was the presence of any atypical infection. Results: In total, 345 patients met the inclusion criteria. Of those, 9/345 (2.6%) had an atypical infection (5 mycoplasma and 4 ureaplasma). The mean age of patients with positive atypical infections was 34 compared to the overall study population (44 years, P=0.01). Two patients with atypical infections were also followed for infertility. Urinalysis was available for 6 of the 9 patients with positive atypical infection: 50% (3 out of 6) were normal and 50% (3 out of 6) had >5 WBC/hpf. Symptoms resolved in 66% (2 out of 3) of the patients with positive atypical infection with available follow-up data. Conclusion: Atypical infectious agents were uncommon causes of CP/CPPS. Screening for atypical microbes such as chlamydia, ureaplasma, or mycoplasma may not be necessary for male patients complaining of pelvic or genital pain

    Sustainable supply chain management trends in world regions: A data-driven analysis

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    This study proposes a data-driven analysis that describes the overall situation and reveals the factors hindering improvement in the sustainable supply chain management field. The literature has presented a summary of the evolution of sustainable supply chain management across attributes. Prior studies have evaluated different parts of the supply chain as independent entities. An integrated systematic assessment is absent in the extant literature and makes it necessary to identify potential opportunities for research direction. A hybrid of data-driven analysis, the fuzzy Delphi method, the entropy weight method and fuzzy decision-making trial and evaluation laboratory is adopted to address uncertainty and complexity. This study contributes to locating the boundary of fundamental knowledge to advance future research and support practical execution. Valuable direction is provided by reviewing the existing literature to identify the critical indicators that need further examination. The results show that big data, closed-loop supply chains, industry 4.0, policy, remanufacturing, and supply chain network design are the most important indicators of future trends and disputes. The challenges and gaps among different geographical regions is offered that provides both a local viewpoint and a state-of-the-art advanced sustainable supply chain management assessment

    Human resources for health in Peru: recent trends (2007-2013) in the labour market for physicians, nurses and midwives.

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    BACKGROUND: Most analyses of gaps in human resources for health (HRH) do not consider training and the transition of graduates into the labour market. This study aims to explore the labour market for Peru's recent medical, nursing, and midwifery graduates as well as their transition into employment in the Ministry of Health's (MOH) system. METHODS: Data from four different datasets, covering 2007-2013, was used to characterize the patterns of recently trained physicians, nurses, midwives, and postgraduate-trained physicians that enter employment in the MOH system, and scenario analyses were used to describe how this rate of entry needs to adapt in order to fill current HRH shortages. RESULTS: HRH graduates have been increasing from 2007 to 2011, but the proportions that enter employment in the MOH system 2 years later range from 8 to 45% and less than 10% of newly trained medical specialists. Scenario analyses indicate that the gap for physicians and nurses will be met in 2027 and 2024, respectively, while midwives in 2017. However, if the number of HRH graduates entering the MOH system doubles, these gaps could be filled as early as 2020 for physicians and 2019 for nurses. In this latter scenario, the MOH system would still only utilize 56% of newly qualified physicians, 74% of nurses, and 66% of midwives available in the labour market. CONCLUSION: At 2013 training rates, Peru has the number of physicians, nurses, and midwives it needs to address HRH shortages and meet estimated HRH gaps in the national MOH system during the next decade. However, a significant number of newly qualified health professionals do not work for the MOH system within 2 years of graduation. These analyses highlight the importance of building adequate incentive structures to improve the entry and retention of HRH into the public sector

    Circular economy needs the resilient systems in COVID-19 pandemic

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    This note reveals the gaps from circular economy (CE) and resilience in the literature during COVID-19 pandemic. The disruptive event affects the circularity in the supply chain due to numerous single-use-products in food, health, plastic industries. The unsustainable production and consumption is harmful for social, ecological, and economic systems. The industrial practices need a highly resilient network to have better visibility and agility to shift sourcing. Prior studies reveal the gap that CE needs the resilient systems. Still, there is a need to conceptualize and models resilience in CE studies using quantitative and qualitative approaches

    Unexpected phenotypic and molecular changes of combined glucocerebrosidase and acid sphingomyelinase deficiency

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    Heterozygous variants in GBA1 encoding glucocerebrosidase (GCase) are the most common genetic risk factor for Parkinson's disease (PD). Moreover, sporadic PD patients also have a substantial reduction of GCase activity. Genetic variants in SMPD1 are also overrepresented in PD cohorts, whilst a reduction of its encoded enzyme (ASM) activity is linked to an earlier age of PD onset. Despite both converging on the ceramide pathway, how combined deficiencies of both enzymes may interact to modulate PD has yet to be explored. Therefore, we created a double knock out (DKO) zebrafish line for both gba1 and smpd1 to test for an interaction in vivo, hypothesising an exacerbation of phenotypes in the DKO compared to single mutants. Unexpectedly, DKOs maintained conventional swimming behaviour and had normalised neuronal gene expression signatures when compared to single mutants. We further identified rescue of mitochondrial Complexes I and IV in DKOs. Despite having an unexpected rescue effect, our results confirm ASM as a modifier of GBA1 deficiency in vivo. Our study highlights the need for validating how genetic variants and enzymatic deficiencies may interact in vivo
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