Estrogen treatment decreases matrix metalloproteinase (MMP)-9 in autoimmune demyelinating disease through estrogen receptor alpha (ERalpha).

Matrix metalloproteinases (MMPs) have a crucial function in migration of inflammatory cells into the central nervous system (CNS). Levels of MMP-9 are elevated in multiple sclerosis (MS) and predict the occurrence of new active lesions on magnetic resonance imaging (MRI). This translational study aims to determine whether in vivo treatment with the pregnancy hormone estriol affects MMP-9 levels from immune cells in patients with MS and mice with experimental autoimmune encephalomyelitis (EAE). Peripheral blood mononuclear cells (PBMCs) collected from three female MS patients treated with estriol and splenocytes from EAE mice treated with estriol, estrogen receptor (ER) alpha ligand, ERbeta ligand or vehicle were stimulated ex vivo and analyzed for levels of MMP-9. Markers of CNS infiltration were assessed using MRI in patients and immunohistochemistry in mice. Supernatants from PBMCs obtained during estriol treatment in female MS patients showed significantly decreased MMP-9 compared with pretreatment. Decreases in MMP-9 coincided with a decrease in enhancing lesion volume on MRI. Estriol treatment of mice with EAE reduced MMP-9 in supernatants from autoantigen-stimulated splenocytes, coinciding with decreased CNS infiltration by T cells and monocytes. Experiments with selective ER ligands showed that this effect was mediated through ERalpha. In conclusion, estriol acting through ERalpha to reduce MMP-9 from immune cells is one mechanism potentially underlying the estriol-mediated reduction in enhancing lesions in MS and inflammatory lesions in EAE

Urinary Retention due to Imperforate Hymen - A Case Series

Urinary retention due to imperforate hymen in young girls in ZambiaFour cases are reported, of young girls in their early teens with urinary retention due to imperforate hymen. The girls presented to the University Teaching Hospital Lusaka Zambia with history of recurrent episodes of urinary retention during their menses. Upon examinations they were found to have hematocolpos and thickened hymen, which ranged from complete to partially imperforate. Ultrasound studies showed evidence of non homogenous echogenic masses suggestive of blood in the uterus. These patients were referred to the obstetrics department where the diagnosis was confirmed and subsequent excision of hymen with uterine evacuations was done. No subsequent episodes of urinary retention were observed. Urinary retention is the commonest cause of emergency admission in urology at the university Teaching Hospital Lusaka. It is more common in men than women. It is even uncommon in young teenage women. These case reports highlight the importance of high index of suspicion, careful examination and reproductive health education for young women especially in the African context.Office of Global AIDS/US Department of State

Mechanisms of Oncogene Activation

The main modifications that characterize cancer are represented by alterations in oncogenes, tumor-suppressor genes, and non-coding RNA genes. Most of these alterations are somatic and the process is a multistep one. Tumors often arise from an initial transformed cell, and after subsequent genetic alterations different cytogenetically clones lead to tumor heterogeneity

Mapping 123 million neonatal, infant and child deaths between 2000 and 2017

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations

EARTH QUAKE PROGNOSTICATION USING DATA MINING AND CURVE FITTING TECHNIQUES

The title “EARTHQUAKE PROGNOSTICATION” is a Global Earthquake prediction, that is used to predict that an earthquake of a specific magnitude will occur in a particular place at a particular time, we however cannot tell the exact time and date the earthquake is going to occur but we can well predict that an earthquake will affect a given location over a certain number of years. The “Gutenberg Richter power-law distribution of earthquake sizes” implies that the largest events are surrounded by a large number of small events, with this statement we collected the data sets of all the EARTHQUAKES of magnitude ranging from small to big since 1900 to 2010 all over the world. After collecting this data we performed clustering techniques to the datasets available with latitude, longitude and time as parameters, which helped to find similarities between them and discovered patterns using non-linear regression functions that helped to forecast earthquakes. This prediction is based on both the historical seismic catalogue and the structural zoning

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk outcome pairs, and new data on risk exposure levels and risk outcome associations. Methods: We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings: In 2017,34.1 million (95% uncertainty interval [UI] 33.3-35.0) deaths and 121 billion (144-1.28) DALYs were attributable to GBD risk factors. Globally, 61.0% (59.6-62.4) of deaths and 48.3% (46.3-50.2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10.4 million (9.39-11.5) deaths and 218 million (198-237) DALYs, followed by smoking (7.10 million [6.83-7.37] deaths and 182 million [173-193] DALYs), high fasting plasma glucose (6.53 million [5.23-8.23] deaths and 171 million [144-201] DALYs), high body-mass index (BMI; 4.72 million [2.99-6.70] deaths and 148 million [98.6-202] DALYs), and short gestation for birthweight (1.43 million [1.36-1.51] deaths and 139 million [131-147] DALYs). In total, risk-attributable DALYs declined by 4.9% (3.3-6.5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23.5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18.6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation: By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning

Effect of a Primary Care-Based Psychological Intervention on Symptoms of Common Mental Disorders in Zimbabwe:A Randomized Clinical Trial

Depression and anxiety are common mental disorders globally but are rarely recognized or treated in low-income settings. Task-shifting of mental health care to lay health workers (LHWs) might decrease the treatment gap. : To evaluate the effectiveness of a culturally adapted psychological intervention for common mental disorders delivered by LHWs in primary care. : Cluster randomized clinical trial with 6 months' follow-up conducted from September 1, 2014, to May 25, 2015, in Harare, Zimbabwe. Twenty-four clinics were randomized 1:1 to the intervention or enhanced usual care (control). Participants were clinic attenders 18 years or older who screened positive for common mental disorders on the locally validated Shona Symptom Questionnaire (SSQ-14). : The Friendship Bench intervention comprised 6 sessions of individual problem-solving therapy delivered by trained, supervised LHWs plus an optional 6-session peer support program. The control group received standard care plus information, education, and support on common mental disorders. : Primary outcome was common mental disorder measured at 6 months as a continuous variable via the SSQ-14 score, with a range of 0 (best) to 14 and a cutpoint of 9. The secondary outcome was depression symptoms measured as a binary variable via the 9-item Patient Health Questionnaire, with a range of 0 (best) to 27 and a cutpoint of 11. Outcomes were analyzed by modified intention-to-treat. : Among 573 randomized patients (286 in the intervention group and 287 in the control group), 495 (86.4 were women, median age was 33 years (interquartile range, 27-41 years), 238 (41.7 were human immunodeficiency virus positive, and 521 (90.9 completed follow-up at 6 months. Intervention group participants had fewer symptoms than control group participants on the SSQ-14 (3.81; 95% CI, 3.28 to 4.34 vs 8.90; 95% CI, 8.33 to 9.47; adjusted mean difference, -4.86; 95% CI, -5.63 to -4.10; P lt; .001; adjusted risk ratio [ARR], 0.21; 95% CI, 0.15 to 0.29; P lt; .001). Intervention group participants also had lower risk of symptoms of depression (13.7% vs 49.9 ARR, 0.28; 95% CI, 0.22 to 0.34; P lt; .001). : Among individuals screening positive for common mental disorders in Zimbabwe, LHW-administered, primary care-based problem-solving therapy with education and support compared with standard care plus education and support resulted in improved symptoms at 6 months. Scaled-up primary care integration of this intervention should be evaluated. : pactr.org Identifier: PACTR201410000876178.<br/