Childhood Lead Exposure in the Palestinian Authority, Israel, and Jordan: Results from the Middle Eastern Regional Cooperation Project, 1996–2000

In the Middle East, the major sources of lead exposure have been leaded gasoline, lead-contaminated flour from traditional stone mills, focal exposures from small battery plants and smelters, and kohl (blue color) in cosmetics. In 1998–2000, we measured blood lead (PbB) levels in children 2–6 years of age in Israel, Jordan, and the Palestinian Authority (n = 1478), using a fingerstick method. Mean (peak; percentage > 10 μg/dL) PbB levels in Israel (n = 317), the West Bank (n = 344), Jordan (n = 382), and Gaza (n = 435) were 3.2 μg/dL (18.2; 2.2%), 4.2 μg/dL (25.7; 5.2%), 3.2 μg/dL (39.3; < 1%), and 8.6 μg/dL (> 80.0; 17.2%), respectively. High levels in Gaza were all among children living near a battery factory. The findings, taken together with data on time trends in lead emissions and in PbB in children in previous years, indicate the benefits from phasing out of leaded gasoline but state the case for further reductions and investigation of hot spots. The project demonstrated the benefits of regional cooperation in planning and carrying out a jointly designed project

Mapping subnational HIV mortality in six Latin American countries with incomplete vital registration systems

BackgroundHuman immunodeficiency virus (HIV) remains a public health priority in Latin America. While the burden of HIV is historically concentrated in urban areas and high-risk groups, subnational estimates that cover multiple countries and years are missing. This paucity is partially due to incomplete vital registration (VR) systems and statistical challenges related to estimating mortality rates in areas with low numbers of HIV deaths. In this analysis, we address this gap and provide novel estimates of the HIV mortality rate and the number of HIV deaths by age group, sex, and municipality in Brazil, Colombia, Costa Rica, Ecuador, Guatemala, and Mexico.MethodsWe performed an ecological study using VR data ranging from 2000 to 2017, dependent on individual country data availability. We modeled HIV mortality using a Bayesian spatially explicit mixed-effects regression model that incorporates prior information on VR completeness. We calibrated our results to the Global Burden of Disease Study 2017.ResultsAll countries displayed over a 40-fold difference in HIV mortality between municipalities with the highest and lowest age-standardized HIV mortality rate in the last year of study for men, and over a 20-fold difference for women. Despite decreases in national HIV mortality in all countries-apart from Ecuador-across the period of study, we found broad variation in relative changes in HIV mortality at the municipality level and increasing relative inequality over time in all countries. In all six countries included in this analysis, 50% or more HIV deaths were concentrated in fewer than 10% of municipalities in the latest year of study. In addition, national age patterns reflected shifts in mortality to older age groups-the median age group among decedents ranged from 30 to 45years of age at the municipality level in Brazil, Colombia, and Mexico in 2017.ConclusionsOur subnational estimates of HIV mortality revealed significant spatial variation and diverging local trends in HIV mortality over time and by age. This analysis provides a framework for incorporating data and uncertainty from incomplete VR systems and can help guide more geographically precise public health intervention to support HIV-related care and reduce HIV-related deaths.Peer reviewe

Mapping subnational HIV mortality in six Latin American countries with incomplete vital registration systems

Background: Human immunodeficiency virus (HIV) remains a public health priority in Latin America. While the burden of HIV is historically concentrated in urban areas and high-risk groups, subnational estimates that cover multiple countries and years are missing. This paucity is partially due to incomplete vital registration (VR) systems and statistical challenges related to estimating mortality rates in areas with low numbers of HIV deaths. In this analysis, we address this gap and provide novel estimates of the HIV mortality rate and the number of HIV deaths by age group, sex, and municipality in Brazil, Colombia, Costa Rica, Ecuador, Guatemala, and Mexico. Methods: We performed an ecological study using VR data ranging from 2000 to 2017, dependent on individual country data availability. We modeled HIV mortality using a Bayesian spatially explicit mixed-effects regression model that incorporates prior information on VR completeness. We calibrated our results to the Global Burden of Disease Study 2017. Results: All countries displayed over a 40-fold difference in HIV mortality between municipalities with the highest and lowest age-standardized HIV mortality rate in the last year of study for men, and over a 20-fold difference for women. Despite decreases in national HIV mortality in all countries—apart from Ecuador—across the period of study, we found broad variation in relative changes in HIV mortality at the municipality level and increasing relative inequality over time in all countries. In all six countries included in this analysis, 50% or more HIV deaths were concentrated in fewer than 10% of municipalities in the latest year of study. In addition, national age patterns reflected shifts in mortality to older age groups—the median age group among decedents ranged from 30 to 45 years of age at the municipality level in Brazil, Colombia, and Mexico in 2017. Conclusions: Our subnational estimates of HIV mortality revealed significant spatial variation and diverging local trends in HIV mortality over time and by age. This analysis provides a framework for incorporating data and uncertainty from incomplete VR systems and can help guide more geographically precise public health intervention to support HIV-related care and reduce HIV-related deaths

Mapping subnational HIV mortality in six Latin American countries with incomplete vital registration systems

Background: Human immunodeficiency virus (HIV) remains a public health priority in Latin America. While the burden of HIV is historically concentrated in urban areas and high-risk groups, subnational estimates that cover multiple countries and years are missing. This paucity is partially due to incomplete vital registration (VR) systems and statistical challenges related to estimating mortality rates in areas with low numbers of HIV deaths. In this analysis, we address this gap and provide novel estimates of the HIV mortality rate and the number of HIV deaths by age group, sex, and municipality in Brazil, Colombia, Costa Rica, Ecuador, Guatemala, and Mexico. Methods: We performed an ecological study using VR data ranging from 2000 to 2017, dependent on individual country data availability. We modeled HIV mortality using a Bayesian spatially explicit mixed-effects regression model that incorporates prior information on VR completeness. We calibrated our results to the Global Burden of Disease Study 2017. Results: All countries displayed over a 40-fold difference in HIV mortality between municipalities with the highest and lowest age-standardized HIV mortality rate in the last year of study for men, and over a 20-fold difference for women. Despite decreases in national HIV mortality in all countries�apart from Ecuador�across the period of study, we found broad variation in relative changes in HIV mortality at the municipality level and increasing relative inequality over time in all countries. In all six countries included in this analysis, 50 or more HIV deaths were concentrated in fewer than 10 of municipalities in the latest year of study. In addition, national age patterns reflected shifts in mortality to older age groups�the median age group among decedents ranged from 30 to 45 years of age at the municipality level in Brazil, Colombia, and Mexico in 2017. Conclusions: Our subnational estimates of HIV mortality revealed significant spatial variation and diverging local trends in HIV mortality over time and by age. This analysis provides a framework for incorporating data and uncertainty from incomplete VR systems and can help guide more geographically precise public health intervention to support HIV-related care and reduce HIV-related deaths

Mapping subnational HIV mortality in six Latin American countries with incomplete vital registration systems

Background Human immunodeficiency virus (HIV) remains a public health priority in Latin America. While the burden of HIV is historically concentrated in urban areas and high-risk groups, subnational estimates that cover multiple countries and years are missing. This paucity is partially due to incomplete vital registration (VR) systems and statistical challenges related to estimating mortality rates in areas with low numbers of HIV deaths. In this analysis, we address this gap and provide novel estimates of the HIV mortality rate and the number of HIV deaths by age group, sex, and municipality in Brazil, Colombia, Costa Rica, Ecuador, Guatemala, and Mexico. Methods We performed an ecological study using VR data ranging from 2000 to 2017, dependent on individual country data availability. We modeled HIV mortality using a Bayesian spatially explicit mixed-effects regression model that incorporates prior information on VR completeness. We calibrated our results to the Global Burden of Disease Study 2017. Results All countries displayed over a 40-fold difference in HIV mortality between municipalities with the highest and lowest age-standardized HIV mortality rate in the last year of study for men, and over a 20-fold difference for women. Despite decreases in national HIV mortality in all countries—apart from Ecuador—across the period of study, we found broad variation in relative changes in HIV mortality at the municipality level and increasing relative inequality over time in all countries. In all six countries included in this analysis, 50% or more HIV deaths were concentrated in fewer than 10% of municipalities in the latest year of study. In addition, national age patterns reflected shifts in mortality to older age groups—the median age group among decedents ranged from 30 to 45 years of age at the municipality level in Brazil, Colombia, and Mexico in 2017. Conclusions Our subnational estimates of HIV mortality revealed significant spatial variation and diverging local trends in HIV mortality over time and by age. This analysis provides a framework for incorporating data and uncertainty from incomplete VR systems and can help guide more geographically precise public health intervention to support HIV-related care and reduce HIV-related deaths

The Sirt1 Activators SRT2183 and SRT3025 Inhibit RANKL-Induced Osteoclastogenesis in Bone Marrow-Derived Macrophages and Down-Regulate Sirt3 in Sirt1 Null Cells.

Increased osteoclast-mediated bone resorption is characteristic of osteoporosis, malignant bone disease and inflammatory arthritis. Targeted deletion of Sirtuin1 (Sirt1), a key player in aging and metabolism, in osteoclasts results in increased osteoclast-mediated bone resorption in vivo, making it a potential novel therapeutic target to block bone resorption. Sirt1 activating compounds (STACs) were generated and were investigated in animal disease models and in humans however their mechanism of action was a source of controversy. We studied the effect of SRT2183 and SRT3025 on osteoclastogenesis in bone-marrow derived macrophages (BMMs) in vitro, and discovered that these STACs inhibit RANKL-induced osteoclast differentiation, fusion and resorptive capacity without affecting osteoclast survival. SRT2183 and SRT3025 activated AMPK, increased Sirt1 expression and decreased RelA/p65 lysine310 acetylation, critical for NF-κB activation, and an established Sirt1 target. However, inhibition of osteoclastogenesis by these STACs was also observed in BMMs derived from sirt1 knock out (sirt1-/-) mice lacking the Sirt1 protein, in which neither AMPK nor RelA/p65 lysine 310 acetylation was affected, confirming that these effects require Sirt1, but suggesting that Sirt1 is not essential for inhibition of osteoclastogenesis by these STACs under these conditions. In sirt1 null osteoclasts treated with SRT2183 or SRT3025 Sirt3 was found to be down-regulated. Our findings suggest that SRT2183 and SRT3025 activate Sirt1 and inhibit RANKL-induced osteoclastogenesis in vitro however under conditions of Sirt1 deficiency can affect Sirt3. As aging is associated with reduced Sirt1 level and activity, the influence of STACs on Sirt3 needs to be investigated in vivo in animal and human disease models of aging and osteoporosis

Sirt1 Promotes a Thermogenic Gene Program in Bone Marrow Adipocytes: From Mice to (Wo)Men

Bone marrow adipose tissue (MAT) is influenced by nutritional cues, and participates in whole body energy metabolism. To investigate the role of Sirtuin1 (Sirt1), a key player in metabolism, in MAT, marrow adiposity was evaluated in inbred 5-month-old 129/Sv Sirt1 haplo-insufficient (Sirt1Δ/+) and wild type (WT) mice. Decreased expression of the thermogenic genes: Prdm16, Pgc1α, Foxc2, Dio2, and β3AR was detected in whole tibiae derived from Sirt1Δ/+ compared to WT female mice. Similarly, decreased expression of Prdm16 and Pgc1α was observed in primary bone marrow mesenchymal stem cell (BM-MSC) cultures obtained from Sirt1Δ/+ compared to WT female mice, suggesting a cell autonomous effect of Sirt1 in BM-MSCs. In vitro, Sirt1 over-expression in the mesenchymal embryonic fibroblast stem cell line C3HT101/2 increased Pgc1α and Prdm16 protein level. Similarly, pharmacologic activation of Sirt1 by SRT3025 increased Foxc2, Pgc1α, Dio2, Tfam, and Cyc1 expression while inhibition of Sirt1 by EX527 down-regulated UCP1 in C3HT101/2 cells. Importantly, in human femoral BM-MSCs obtained from female patients undergoing hip operations for fracture or osteoarthritis, Sirt1 activation by SRT3025 increased PGC1α mRNA and protein level. Blocking sclerostin, an inhibitor of the WNT pathway and a Sirt1 target, by the monoclonal humanized antibody (Sc-AbII), stimulated β3AR, PRDM16, and UCP1 gene expression, and increased PGC1α protein level. These results show that Sirt1 stimulates a thermogenic gene program in marrow adipocytes in mice and humans via PGC1α activation and sclerostin inhibition. The implications of these findings to bone health, hematopoiesis and whole body energy metabolism remain to be investigated.ISSN:1664-239

المهددات التي تواجه البيئة البحرية والصيد السمكي في قطاع غزة: دراسة ميدانية ومرجعية

The importance of marine resources in the Gaza Strip stems from the fact that it represents a significant source of animal protein to the Palestinians and as a source of income to the fishery sector which covers more than 2500 fishermen. Due to the small fishing area available to the Palestinians, the fishermen usually exert intensive fishing efforts using all available means to achieve abundant catches with no respect to the impacts of their activities on the marine environment and fisheries resources. The current study aims at identifying the threats facing the marine environment and fisheries resources in the Gaza Strip and at suggesting possible recommendations dealing with their progress. The factors threatening the marine environment and fishing in the Gaza Strip included untreated wastewater disposal from various sources including Wadi Gaza, multi-source solid waste disposal and alteration of the landscape of the marine coast through rock removal, shanty constructions and coastal sand dunes depletion. The weakness of fishermen infrastructure, overfishing using inappropriate means including bottom trawling and small-meshed nets, fishing using chemical pesticides, catch of threatened marine turtles and lack of efficient fishing harbors are also major threats to marine life and environment. Besides, the Israeli military aggressions and restrictions by controlling fishing areas, sea closure, poaching and arresting of fishermen and intentional destruction of fishing gear are actual threats to marine fishing and fishermen saftey. Finally, the study suggests the necessity of stopping pollution sources, improving the infrastructure of fishing sector and fishermen and improving the cooperation level among different parties to ensure better management and sustainability of the coastal and marine environment. The role of official and non-official media and educational institutions in enhancing research, respect and awareness to all stakeholders and public towards marine environment should be encouraged, elevated and put into action.تكمن أهمية الثروة السمكية في قطاع غزة في كونها تمثل أحد مصادر البروتين الحيواني الذي يحتاج إليه الفلسطينيون لتلبية احتياجاتهم الغذائية و مصدر دخل مستمر لقطاع الصيادين الذين يفوق تعدادهم الـ 2500 صياد. ونظرا لضيق المساحة البحرية المتاحة للصيد السمكي في قطـاع غزة يلجأ الصيادون إلي تكثيف جهد الصيد بكافة السبل و الوسائل للحصول على إنتاج سمكي وفير دون الاكتراث بالنواحي البيئية لهذا النشــاط على الموارد السمكية و البيئة البحرية. تهدف هذه الدراسة المسحية إلى تحديد المهددات التي تواجه البيئة البحرية و الصيد السمكي في قطاع غزة و إلى وضع مقترحات ممكنة في سبيل النهوض بهما. أظهرت الدراسة العديد من العوامل التي تعترض البيئة البحرية والصيد السمكي في قطاع غزة متمثلة بإلقاء المياه العادمة غير المعالجة من مصادر متعددة تشمل مجرى وادي غزة و بؤر التفريغ المنتشرة على طول الساحل، طرح النفايات الصلبة متعددة المصادر، تغيير تركيبة و ملامح الساحل الفلسطيني باقتلاع الصخور و بناء المنشآت العشوائية و استنزاف رمال البحر و الكثبان الرملية الساحلية مما يثبط من الوظيفة البيئية لها، ضعف البنية التحتية للصيادين، الصيد الجائر باستخدام معدات و وسائل صيد غير ملائمة مثل شباك الجر القاعي و الشباك ذات العيون الصغيرة، استعمال السموم الكيماوية في صيد الأسماك، صيد السلاحف البحرية المهددة بالاختفاء عالميا، افتقار قطاع غزة لموانئ صيد عالية الكفاءة مما يحدو بالصيادين لاستخدام رمال الشاطئ لإنزال مراكبهم في البحر و إخراجها منه مما يؤثر على العمر الإنتاجي لها. تضاف إلى ذلك كله القيود و الانتهاكات العسكرية الإسرائيلية المتمثلة بالتحكم بمناطق الصيد السمكي و إغلاق البحر أمام الصيادين و المطاردات الزورقية و الاعتقالات للصيادين و تدمير معدات الصيد و إتلافها. و في الختام، اقترحت الدراسة ضرورة وقف مصادر التلوث البحري و التعديات، و ضرورة تحسين البنية التحتية لقطاع الصيد و الصيادين، و تحسين مستوى التعاون بين المؤسسات المختلفة بما يكفل إدارة و تنمية البيئة البحرية و الساحلية بشكل مستدام، كما و تؤكد الدراسة على ضرورة تناول وسائل الإعلام الرسمي و غير الرسمي لقضايا البيئة البحرية الفلسطينية و على دور المؤسسات التعليمية في زيادة النشاط العلمي و التثقيفي و التوعوي لكافة شرائح المجتمع الفلسطيني و ضرورة افتتاح أقسام و مراكز بحوث للعلوم البحرية

SRT2183 inhibits RANKL-induced osteoclastogenesis and pit formation in s<i>irt1</i>^<i>-/-</i> BMMs.

<p>(A) Sirt1 expression in WT- and in <i>Sirt1</i>^<i>-/-</i>-derived osteoclasts. PCR amplification of exons 1–9 of the s<i>irt1</i> gene (left panel) and Western blot analysis with Sirt1 antibody (right panel) demonstrates complete loss of Sirt1 protein in osteoclasts obtained from <i>Sirt1</i>^<i>Δ/Δ</i> (<i>Sirt1</i>^<i>-/-</i>) mice. (B) The effect of SRT2183 on osteoclast differentiation in <i>Sirt1</i>^<i>-/-</i>-derived BMMs. BMMs were inducted to osteoclastogenesis with RANKL in the presence or absence of SRT2183. TRAP staining performed 4 days post induction. (C) The effect of SRT2183 on pit formation in <i>Sirt1</i>^<i>-/-</i>-derived BMMs stimulated with RANKL. An eroded area (left panel) and pit formation assay (right) are shown. (D) The effect of SRT2183 on p65 acetylation (Lys310). Western blot analysis of p65K310 ac and p65 in SRT2183- and vehicle-treated osteoclasts 4 days post RANKL stimulation. (E) The effect of SRT2183 on AMPKα phosphorylation (Thr172). Western blot analysis of pAMPKα and AMPKα in SRT2183- and vehicle-treated osteoclasts 4 days post RANKL stimulation. (F) The effect of SRT2183 on IκBα protein level. Western blot analysis of IκBα and GAPDH in SRT2183- and vehicle-treated BMMs 24 hours post RANKL stimulation. (G-H) The effect of SRT2183 on Sirt3 protein (G) and gene expression (H). Western blot analysis of Sirt3 and GAPDH in SRT2183- and vehicle-treated osteoclasts 4 days post RANKL stimulation (G). Gene expression analysis by quantitative Real-Time PCR 4 days post RANKL stimulation is shown. Results are relative to <i>Polr2a</i> (H). (I) The effect of SRT2183 on superoxide dismutase 2 (Sod2) Lys68 acetylation. Western blot analysis of acetylated (ac) Sod2K68 and Sod2 in SRT2183- and vehicle-treated osteoclasts 4 days post RANKL stimulation. Data are Mean ± SEM (n = 3 independent experiments), analyzed by paired Student's <i>t</i>-test paired (C) or one-sample Student's <i>t</i>-test (H-I); ***<i>P</i><0.001, ****<i>P</i><0.0001, versus vehicle-treated BMMs. Magnification X40; scale bar 1mm.</p