26 research outputs found

    Female Entrepreneurs in Windsor-Essex County A General Profile with Significant Differences of Opinion as a Function of Industry-Type and Age of Firk Categorizations

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    Female entrepreneurship is a relatively new phenomenon in North America due to two distinct yet interrelated sociological issues - increased labour force involvement and higher level of education attainment. Historically women did not work outside the home, or if they did, they were in traditionally female-oriented jobs such as nursing or secretarial. Forerunners of entrepreneurial businesses such as in-home private babysitting, private housekeeping services and hobby related activities, although they generated income, were rarely claimed for tax purposes and therefore went unrecognized in proprietorship statistics

    Comparison of routine health management information system versus enhanced inpatient malaria surveillance for estimating the burden of malaria among children admitted to four hospitals in Uganda.

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    The primary source of malaria surveillance data in Uganda is the Health Management Information System (HMIS), which does not require laboratory confirmation of reported malaria cases. To improve data quality, an enhanced inpatient malaria surveillance system (EIMSS) was implemented with emphasis on malaria testing of all children admitted in select hospitals. Data were compared between the HMIS and the EIMSS at four hospitals over a period of 12 months. After the implementation of the EIMSS, over 96% of admitted children under 5 years of age underwent laboratory testing for malaria. The HMIS significantly overreported the proportion of children under 5 years of age admitted with malaria (average absolute difference = 19%, range = 8-27% across the four hospitals) compared with the EIMSS. To improve the quality of the HMIS data for malaria surveillance, the National Malaria Control Program should, in addition to increasing malaria testing rates, focus on linking laboratory test results to reported malaria cases

    Leptin: A Metabolic Signal for the Differentiation of Pituitary Cells

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    Pituitary cell function is impacted by metabolic states and therefore must receive signals that inform them about nutritional status or adiposity. A primary signal from adipocytes is leptin, which recent studies have shown regulates most pituitary cell types. Subsets of all pituitary cell types express leptin receptors and leptin has been shown to exert transcriptional control through classical JAK/STAT pathways. Recent studies show that leptin also signals through post-transcriptional pathways that involve the translational regulatory protein Musashi. Mechanistically, post-transcriptional control would permit rapid cellular regulation of critical pre-existing pituitary transcripts as energy states change. The chapter will review evidence for transcriptional and/or post-transcriptional regulation of leptin targets (including Gnrhr, activin, Fshb, Gh, Ghrhr, and Pou11f1) and the consequences of the loss of leptin signaling to gonadotrope and somatotrope functions

    Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

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    Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

    Malaria Trends in Six Outpatient Sites in Uganda, 2008 - 2011

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    With the intensification of malaria efforts in Uganda, accurate and timely data are needed to monitor impact and guide control program planning. We present trends in malaria burden from six health facilities; Aduku (community received IRS), Nagongera and Kamwezi (ITNs distributed), Walukuba, Kasambya and Kihihi (no major intervention). Between 2008 and 2011, the proportion of th

    Malaria Trends in Six Outpatient Sites in Uganda, 2008 - 2011

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    OBJECTIVE: To estimate trends in malaria morbidity at six sentinel sites in Uganda. INTRODUCTION: Over the past five years, efforts to control malaria have been intensified in Uganda (1). With the intensification of these efforts, accurate and timely data are needed to monitor impact of the interventions and guide malaria control program planning (2, 3). We present data on trends in malaria burden over four years from six out-patient health facilities located in regions of varying malaria endemicity in Uganda. METHODS: The study utilized data from the on-going malaria sentinel surveillance program involving six level IV outpatient health facilities: Aduku, Nagongera, Walukuba, Kasambya, Kihihi and Kamwezi. Major malaria control interventions between 2008 and 2010 in sub-counties where these sites are located included Indoor residual spraying (IRS) conducted in Aduku; insecticide-treated nets (ITNs) distributed in Nagongera and Kamwezi. There has been no major control intervention(s) in sub-counties where Walukuba, Kasambya and Kihihi are located. Treatment with artemisinin-combination therapies have however been deployed nationally. Patient information; demographics, malaria test results and diagnosis are recorded on a standardized patient record. The test positivity rate (TPR) defined as the number of persons testing positive for malaria divided by the total number of persons tested was calculated by year from 2008 to 2011 for two age categories (< 5 years and > 5 years). RESULTS: A total of 560,586 patients were seen, of which 25% were <5 years. Over 325,500 patients were suspected to have malaria, with the proportion of these having a confirmatory test done increasing from 62% in 2008 to 98% in 2011. Between 2008 and 2011, the proportion of the <5 years testing positive for malaria significantly decreased from 66% to 34% in Aduku, from 61% to 41% in Nagongera, and from 54% to 24% in Kamwezi. However, significant increases were seen in Kasambya and Kihihi from 41% to 51% and from 28% to 44% respectively. The TPR at Walukuba remained stable (41% to 45%). Similar trends were seen in the > 5 years. CONCLUSIONS: Sentinel site surveillance has been a reliable and timely method/tool for monitoring trends in malaria morbidity thereby informing and guiding the Uganda malaria control program

    A real-time neurophysiologic stress test for the aging brain: novel perioperative and ICU applications of EEG in older surgical patients

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    As of 2022, individuals age 65 and older represent approximately 10% of the global population [1], and older adults make up more than one third of anesthesia and surgical cases in developed countries [2, 3]. With approximately &gt; 234 million major surgical procedures performed annually worldwide [4], this suggests that &gt; 70 million surgeries are performed on older adults across the globe each year. The most common postoperative complications seen in these older surgical patients are perioperative neurocognitive disorders including postoperative delirium, which are associated with an increased risk for mortality [5], greater economic burden [6, 7], and greater risk for developing long-term cognitive decline [8] such as Alzheimer's disease and/or related dementias (ADRD). Thus, anesthesia, surgery, and postoperative hospitalization have been viewed as a biological "stress test" for the aging brain, in which postoperative delirium indicates a failed stress test and consequent risk for later cognitive decline ( see Fig. 3). Further, it has been hypothesized that interventions that prevent postoperative delirium might reduce the risk of long-term cognitive decline. Recent advances suggest that rather than waiting for the development of postoperative delirium to indicate whether a patient "passed" or "failed" this stress test, the status of the brain can be monitored in real-time via electroencephalography (EEG) in the perioperative period. Beyond the traditional intraoperative use of EEG monitoring for anesthetic titration, perioperative EEG may be a viable tool for identifying waveforms indicative of reduced brain integrity and potential risk for postoperative delirium and long-term cognitive decline. In principle, research incorporating routine perioperative EEG monitoring may provide insight into neuronal patterns of dysfunction associated with risk of postoperative delirium, long-term cognitive decline, or even specific types of aging-related neurodegenerative disease pathology. This research would accelerate our understanding of which waveforms or neuronal patterns necessitate diagnostic workup and intervention in the perioperative period, which could potentially reduce postoperative delirium and/ or dementia risk. Thus, here we present recommendations for the use of perioperative EEG as a "predictor" of delirium and perioperative cognitive decline in older surgical patients

    A CRISPR Activation Screen Identifies an Atypical Rho GTPase That Enhances Zika Viral Entry

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    Zika virus (ZIKV) is a re-emerging flavivirus that has caused large-scale epidemics. Infection during pregnancy can lead to neurologic developmental abnormalities in children. There is no approved vaccine or therapy for ZIKV. To uncover cellular pathways required for ZIKV that can be therapeutically targeted, we transcriptionally upregulated all known human coding genes with an engineered CRISPR–Cas9 activation complex in human fibroblasts deficient in interferon (IFN) signaling. We identified Ras homolog family member V (RhoV) and WW domain-containing transcription regulator 1 (WWTR1) as proviral factors, and found them to play important roles during early ZIKV infection in A549 cells. We then focused on RhoV, a Rho GTPase with atypical terminal sequences and membrane association, and validated its proviral effects on ZIKV infection and virion production in SNB-19 cells. We found that RhoV promotes infection of some flaviviruses and acts at the step of viral entry. Furthermore, RhoV proviral effects depend on the complete GTPase cycle. By depleting Rho GTPases and related proteins, we identified RhoB and Pak1 as additional proviral factors. Taken together, these results highlight the positive role of RhoV in ZIKV infection and confirm CRISPR activation as a relevant method to identify novel host–pathogen interactions

    A CRISPR Activation Screen Identifies an Atypical Rho GTPase That Enhances Zika Viral Entry

    No full text
    Zika virus (ZIKV) is a re-emerging flavivirus that has caused large-scale epidemics. Infection during pregnancy can lead to neurologic developmental abnormalities in children. There is no approved vaccine or therapy for ZIKV. To uncover cellular pathways required for ZIKV that can be therapeutically targeted, we transcriptionally upregulated all known human coding genes with an engineered CRISPR–Cas9 activation complex in human fibroblasts deficient in interferon (IFN) signaling. We identified Ras homolog family member V (RhoV) and WW domain-containing transcription regulator 1 (WWTR1) as proviral factors, and found them to play important roles during early ZIKV infection in A549 cells. We then focused on RhoV, a Rho GTPase with atypical terminal sequences and membrane association, and validated its proviral effects on ZIKV infection and virion production in SNB-19 cells. We found that RhoV promotes infection of some flaviviruses and acts at the step of viral entry. Furthermore, RhoV proviral effects depend on the complete GTPase cycle. By depleting Rho GTPases and related proteins, we identified RhoB and Pak1 as additional proviral factors. Taken together, these results highlight the positive role of RhoV in ZIKV infection and confirm CRISPR activation as a relevant method to identify novel host–pathogen interactions
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