Safeguarding pollinators and their values to human well-being

Wild and managed pollinators provide a wide range of benefits to society in terms of contributions to food security, farmer and beekeeper livelihoods, social and cultural values, as well as the maintenance of wider biodiversity and ecosystem stability. Pollinators face numerous threats, including changes in land-use and management intensity, climate change, pesticides and genetically modified crops, pollinator management and pathogens, and invasive alien species. There are well-documented declines in some wild and managed pollinators in several regions of the world. However, many effective policy and management responses can be implemented to safeguard pollinators and sustain pollination services

Trends in HIV/AIDS morbidity and mortality in Eastern Mediterranean countries, 1990–2015: findings from the Global Burden of Disease 2015 study

OBJECTIVES: We used the results of the Global Burden of Disease 2015 study to estimate trends of HIV/AIDS burden in Eastern Mediterranean Region (EMR) countries between 1990 and 2015. METHODS: Tailored estimation methods were used to produce final estimates of mortality. Years of life lost (YLLs) were calculated by multiplying the mortality rate by population by age-specific life expectancy. Years lived with disability (YLDs) were computed as the prevalence of a sequela multiplied by its disability weight. RESULTS: In 2015, the rate of HIV/AIDS deaths in the EMR was 1.8 (1.4–2.5) per 100,000 population, a 43% increase from 1990 (0.3; 0.2–0.8). Consequently, the rate of YLLs due to HIV/AIDS increased from 15.3 (7.6–36.2) per 100,000 in 1990 to 81.9 (65.3–114.4) in 2015. The rate of YLDs increased from 1.3 (0.6–3.1) in 1990 to 4.4 (2.7–6.6) in 2015. CONCLUSIONS: HIV/AIDS morbidity and mortality increased in the EMR since 1990. To reverse this trend and achieve epidemic control, EMR countries should strengthen HIV surveillance, and scale up HIV antiretroviral therapy and comprehensive prevention services

Investigating the Links between Lower Iron Status in Pregnancy and Respiratory Disease in Offspring Using Murine Models.

Maternal iron deficiency occurs in 40-50% of all pregnancies and is associated with an increased risk of respiratory disease and asthma in children. We used murine models to examine the effects of lower iron status during pregnancy on lung function, inflammation and structure, as well as its contribution to increased severity of asthma in the offspring. A low iron diet during pregnancy impairs lung function, increases airway inflammation, and alters lung structure in the absence and presence of experimental asthma. A low iron diet during pregnancy further increases these major disease features in offspring with experimental asthma. Importantly, a low iron diet increases neutrophilic inflammation, which is indicative of more severe disease, in asthma. Together, our data demonstrate that lower dietary iron and systemic deficiency during pregnancy can lead to physiological, immunological and anatomical changes in the lungs and airways of offspring that predispose to greater susceptibility to respiratory disease. These findings suggest that correcting iron deficiency in pregnancy using iron supplements may play an important role in preventing or reducing the severity of respiratory disease in offspring. They also highlight the utility of experimental models for understanding how iron status in pregnancy affects disease outcomes in offspring and provide a means for testing the efficacy of different iron supplements for preventing disease

The PI3K p110δ regulates expression of CD38 on regulatory T cells.

The PI3K pathway has emerged as a key regulator of regulatory T cell (Treg) development and homeostasis and is required for full Treg-mediated suppression. To identify new genes involved in PI3K-dependent suppression, we compared the transcriptome of WT and p110δ(D910A) Tregs. Among the genes that were differentially expressed was the gene for the transmembrane cyclic ADP ribose hydrolase CD38. Here we show that CD38 is expressed mainly by a subset of Foxp3(+)CD25(+)CD4(+) T cells originating in the thymus and on Tregs in the spleen. CD38(high) WT Tregs showed superior suppressive activity to CD38(low) Tregs, which failed to upregulate CD73, a surface protein which is important for suppression. However, Tregs from heterozygous CD38(+/-) mice were unimpaired despite lower levels of CD38 expression. Therefore, CD38 can be used as a marker for Tregs with high suppressive activity and the impaired Treg function in p110δ(D910A) mice can in part be explained by the failure of CD38(high) cells to develop

Guidelines for diagnosis and management of the cobalamin-related remethylation disorders cblC, cblD, cblE, cblF, cblG, cblJ and MTHFR deficiency

BACKGROUND: Remethylation defects are rare inherited disorders in which impaired remethylation of homocysteine to methionine leads to accumulation of homocysteine and perturbation of numerous methylation reactions. OBJECTIVE: To summarise clinical and biochemical characteristics of these severe disorders and to provide guidelines on diagnosis and management. DATA SOURCES: Review, evaluation and discussion of the medical literature (Medline, Cochrane databases) by a panel of experts on these rare diseases following the GRADE approach. KEY RECOMMENDATIONS: We strongly recommend measuring plasma total homocysteine in any patient presenting with the combination of neurological and/or visual and/or haematological symptoms, subacute spinal cord degeneration, atypical haemolytic uraemic syndrome or unexplained vascular thrombosis. We strongly recommend to initiate treatment with parenteral hydroxocobalamin without delay in any suspected remethylation disorder; it significantly improves survival and incidence of severe complications. We strongly recommend betaine treatment in individuals with MTHFR deficiency; it improves the outcome and prevents disease when given early

Burden of cancer in the Eastern Mediterranean Region, 2005–2015: findings from the Global Burden of Disease 2015 Study

Objectives: To estimate incidence, mortality, and disability-adjusted life years (DALYs) caused by cancer in the Eastern Mediterranean Region (EMR) between 2005 and 2015. Methods: Vital registration system and cancer registry data from the EMR region were analyzed for 29 cancer groups in 22 EMR countries using the Global Burden of Disease Study 2015 methodology. Results: In 2015, cancer was responsible for 9.4% of all deaths and 5.1% of all DALYs. It accounted for 722,646 new cases, 379,093 deaths, and 11.7 million DALYs. Between 2005 and 2015, incident cases increased by 46%, deaths by 33%, and DALYs by 31%. The increase in cancer incidence was largely driven by population growth and population aging. Breast cancer, lung cancer, and leukemia were the most common cancers, while lung, breast, and stomach cancers caused most cancer deaths. Conclusions: Cancer is responsible for a substantial disease burden in the EMR, which is increasing. There is an urgent need to expand cancer prevention, screening, and awareness programs in EMR countries as well as to improve diagnosis, treatment, and palliative care services.The funding source played no role in the design of thestudy, the analysis and interpretation of data, and the writing of thepaper. GBD 2015 is funded by Bill & Melinda Gates Foundation

The therapeutic potential of regulatory T cells for the treatment of autoimmune disease

IntroductionImmune tolerance remains the holy grail of therapeutic immunology in the fields of organ and tissue transplant rejection, autoimmune diseases, and allergy and asthma. We have learned that FoxP3(+)CD4(+) regulatory T cells play a vital role in both the induction and maintenance of self-tolerance.Areas coveredIn this opinion piece, we highlight regulatory T cells (Treg) cell biology and novel immune treatments to take advantage of these cells as potent therapeutics. We discuss the potential to utilize Treg and Treg-friendly therapies to replace current general immunosuppressives and induce tolerance as a path towards a drug-free existence without associated toxicities.Expert opinionFinally, we opine on the fact that biomedicine sits on the cusp of a new revolution: the use of human cells as versatile therapeutic engines. We highlight the challenges and opportunities associated with the development of a foundational cellular engineering science that provides a systematic framework for safely and predictably regulating cellular behaviors. Although Treg therapy has become a legitimate clinical treatment, development of the therapy will require a better understanding of the underlying Treg biology, manufacturing advances to promote cost effectiveness and combinations with other drugs to alter the pathogenicity/regulatory balance

Type 1 diabetes: translating mechanistic observations into effective clinical outcomes

Type 1 diabetes remains an important health problem, particularly in Western countries where the incidence has been increasing in younger children(1). In 1986, Eisenbarth described Type 1 diabetes as a chronic autoimmune disease. Work over the past 3 ½ decades has identified many of the genetic, immunologic, and environmental factors that are involved in the disease and have led to hypotheses concerning its pathogenesis. Based on these findings, clinical trials have been conducted to test these hypotheses but have had mixed results. In this review, we discuss the findings that have led to current concepts of the disease mechanisms, how this understanding has prompted clinical studies, and the results of these studies. The findings from preclinical and clinical studies support the original proposed model for how type 1 diabetes develops, but have also suggested that this disease is more complex than originally thought and will require broader treatment approaches