Treatment algorithm for infants diagnosed with spinal muscular atrophy through newborn screening

Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by the degeneration of alpha motor neurons in the spinal cord, leading to muscular atrophy. SMA is caused by deletions or mutations in the survival motor neuron 1 gene (SMN1). In humans, a nearly identical copy gene, SMN2, is present. Because SMN2 has been shown to decrease disease severity in a dose-dependent manner, SMN2 copy number is predictive of disease severity. To develop a treatment algorithm for SMA-positive infants identified through newborn screening based upon SMN2 copy number. A working group comprised of 15 SMA experts participated in a modified Delphi process, moderated by a neutral third-party expert, to develop treatment guidelines. The overarching recommendation is that all infants with two or three copies of SMN2 should receive immediate treatment (n = 13). For those infants in which immediate treatment is not recommended, guidelines were developed that outline the timing and appropriate screens and tests to be used to determine the timing of treatment initiation. The identification SMA affected infants via newborn screening presents an unprecedented opportunity for achievement of maximal therapeutic benefit through the administration of treatment pre-symptomatically. The recommendations provided here are intended to help formulate treatment guidelines for infants who test positive during the newborn screening process

Increased MDSC Accumulation and Th2 Biased Response to Influenza A Virus Infection in the Absence of TLR7 in Mice

Toll-like receptors (TLRs) play an important role in the induction of innate and adaptive immune response against influenza A virus (IAV) infection; however, the role of Toll-like receptor 7 (TLR7) during the innate immune response to IAV infection and the cell types affected by the absence of TLR7 are not clearly understood. In this study, we show that myeloid derived suppressor cells (MDSC) accumulate in the lungs of TLR7 deficient mice more so than in wild-type C57Bl/6 mice, and display increased cytokine expression. Furthermore, there is an increase in production of Th2 cytokines by TLR7-/- compared with wildtype CD4+ T-cells in vivo, leading to a Th2 polarized humoral response. Our findings indicate that TLR7 modulates the accumulation of MDSCs during an IAV infection in mice, and that lack of TLR7 signaling leads to a Th2-biased response

COVID-19 impacts and adaptations in Asia and Africa's aquatic food value chains

The COVID-19 pandemic is a shock affecting all areas of the global food system. We tracked the impacts of COVID-19 and associated policy responses on the availability and price of aquatic foods and production inputs during 2020, using a high frequency longitudinal survey of 768 respondents in Bangladesh, Egypt, India, Myanmar, Nigeria. We found the following: (1) Aquatic food value chains were severely disrupted but most effects on the availability and accessibility of aquatic foods and production inputs were short-lived. (2) Impacts on demand for aquatic foods, production inputs, and labor have been longer lasting than impacts on their supply. (3) Retail prices of aquatic foods spiked briefly during March-May 2020 but trended down thereafter, whereas prices of production inputs rose. These trends suggest a deepening ‘squeeze’ on the financial viability of producers and other value chain actors. (4) Survey respondents adapted to the challenges of COVID-19 by reducing production costs, sourcing alternative inputs, diversifying business activities, leveraging social capital, borrowing, seeking alternative employment, and reducing food consumption. Many of these coping strategies are likely to undermine well-being and longer-term resilience, but we also find some evidence of proactive strategies with potential to strengthen business performance. Global production of aquatic food likely contracted significantly in 2020. The importance of aquatic food value chains in supporting livelihoods and food and nutrition security in Asia and Africa makes their revitalization essential in the context of COVID-19 recovery efforts. We outline immediate and longer-term policies and interventions to support this goal.Additional co-authors: Arun Padiyar, Suresh Rajendran, A B C Mohan, Ravi Babu, Michael Joseph Akester, Ei Ei Phyo, Khin Maung Soe, Ajibola Olaniyi, Sunil N Siriwardena, Michael Phillips, Shakuntala H Thilste

Elevated miR-499 Levels Blunt the Cardiac Stress Response

The heart responds to myriad stresses by well-described transcriptional responses that involve long-term changes in gene expression as well as more immediate, transient adaptations. MicroRNAs quantitatively regulate mRNAs and thus may affect the cardiac transcriptional output and cardiac function. Here we investigate miR-499, a microRNA embedded within a ventricular-specific myosin heavy chain gene, which is expressed in heart and skeletal muscle.We assessed miR-499 expression in human tissue to confirm its potential relevance to human cardiac gene regulation. Using a transgenic mouse model, we found that elevated miR-499 levels caused cellular hypertrophy and cardiac dysfunction in a dose-dependent manner. Global gene expression profiling revealed altered levels of the immediate early stress response genes (Egr1, Egr2 and Fos), ß-myosin heavy chain (Myh7), and skeletal muscle actin (Acta1). We verified the effect of miR-499 on the immediate early response genes by miR-499 gain- and loss-of-function in vitro. Consistent with a role for miR-499 in blunting the response to cardiac stress, asymptomatic miR-499-expressing mice had an impaired response to pressure overload and accentuated cardiac dysfunction.Elevated miR-499 levels affect cardiac gene expression and predispose to cardiac stress-induced dysfunction. miR-499 may titrate the cardiac response to stress in part by regulating the immediate early gene response

Food insecurity and low access to high-quality food for preconception women in Nepal: the importance of household relationships.

OBJECTIVE:Women in South Asia, including Nepal, have some of the poorest nutritional indicators globally, leading to poor maternal and child health outcomes. Nepal also suffers from high levels of household food insecurity, and newly married women are at high risk. Intra-household relationships may mediate the relationship between food insecurity and women's nutrition in Nepal for newly married women. Our aim is to understand how newly married, preconception, women's food consumption changes when she enters her husband's home, compared with her natal home. We also explore whether relationship quality with husbands and mothers-in-law mediates the association between food insecurity and eating less high-quality food, using structural equation modelling. DESIGN:Cross-sectional survey data. SETTING:Rural Nepal in 2018. PARTICIPANTS:Data were collected from 200 newly married, preconception women. RESULTS:Women had poor diet quality, and most ate fewer high-quality foods important for pregnancy in their marital, compared with natal, home. Higher quality relationships with mothers-in-laws mediated the association between food insecurity and a woman eating fewer high-quality foods in her marital, compared with natal, home. Relationship quality with husbands was not associated with changes in food consumption. CONCLUSIONS:Preconception, newly married women in Nepal are eating less high-quality foods important for women's health during the preconception period - a key period for avoiding adverse maternal and infant health outcomes. Relationships with mothers-in-law are key to women's access to high-quality food, suggesting that interventions aiming to improve maternal and child nutrition should target all household members

Elevated miR-499 levels blunt the cardiac stress response.

BackgroundThe heart responds to myriad stresses by well-described transcriptional responses that involve long-term changes in gene expression as well as more immediate, transient adaptations. MicroRNAs quantitatively regulate mRNAs and thus may affect the cardiac transcriptional output and cardiac function. Here we investigate miR-499, a microRNA embedded within a ventricular-specific myosin heavy chain gene, which is expressed in heart and skeletal muscle.Methodology/principal findingsWe assessed miR-499 expression in human tissue to confirm its potential relevance to human cardiac gene regulation. Using a transgenic mouse model, we found that elevated miR-499 levels caused cellular hypertrophy and cardiac dysfunction in a dose-dependent manner. Global gene expression profiling revealed altered levels of the immediate early stress response genes (Egr1, Egr2 and Fos), ß-myosin heavy chain (Myh7), and skeletal muscle actin (Acta1). We verified the effect of miR-499 on the immediate early response genes by miR-499 gain- and loss-of-function in vitro. Consistent with a role for miR-499 in blunting the response to cardiac stress, asymptomatic miR-499-expressing mice had an impaired response to pressure overload and accentuated cardiac dysfunction.ConclusionsElevated miR-499 levels affect cardiac gene expression and predispose to cardiac stress-induced dysfunction. miR-499 may titrate the cardiac response to stress in part by regulating the immediate early gene response

Elevated miR-499 levels blunt the cardiac stress response. PLoS ONE 2011; 6: e19481

Abstract Background: The heart responds to myriad stresses by well-described transcriptional responses that involve long-term changes in gene expression as well as more immediate, transient adaptations. MicroRNAs quantitatively regulate mRNAs and thus may affect the cardiac transcriptional output and cardiac function. Here we investigate miR-499, a microRNA embedded within a ventricular-specific myosin heavy chain gene, which is expressed in heart and skeletal muscle

Fish and fish-based products for nutrition and health in the first 1000 days: a systematic review of the evidence from low and middle-income countries

Fish provide essential nutrients for the critical window of growth and development in the first 1000 d of life and are thus an attractive option for inclusion in nutrition-sensitive and nutrition-specific programming. We conducted a systematic review of the evidence for fish and fish-based products for nutrition and health outcomes during the first 1000 d of life in low- and middle-income countries, searching the peer-reviewed and gray literature from 1999 to 2020. Databases included PubMed, Web of Science, Embase, ProQuest, and the Clinical Trials repository. Our search returned 1135 articles, 39 of which met the inclusion criteria. All studies were dual evaluated for risk of bias. Of the included studies, 18 measured maternal health and nutrition outcomes and 24 measured infant/child outcomes (3 measured both). Our search uncovered 10 impact evaluations, all of which measured consumption of fish or fish-based complementary food products in children aged 6-24 mo. We did not find strong evidence for fish consumption in children improving child growth from the impact evaluations; however, the studies were highly heterogeneous in their design and likely underpowered to detect an effect. Results from observational studies were mixed but provided evidence that adding fish to maternal and child diets is associated with improved nutrition outcomes, such as reducing the risk of anemia and improving vitamin D status. Given the nutrient richness of fish and the fact that production is often more environmentally friendly as compared with other animal source foods, more robust evidence is needed on the role of fish consumption in nutrition interventions to inform policy and programming recommendations in low- and middle-income countries

Exploring the role of social capital in managing food insecurity among older women in the United States

Food insecurity, which affects 37 million individuals in the United States (U.S.) and disproportionately burdens women, minorities and older adults, is a well-established determinant of poor health. Previous studies suggest social capital, defined as the material and social benefits arising from relationships among individuals within and between groups, may be protective against food insecurity. Drawing on this evidence, calls have been made for interventions and policies to promote social capital to address food insecurity. However, limited research has explored in-depth how social capital shapes the lived experience of food insecurity in the U.S. We explored how older women from three settings in the U.S. used forms of social capital to navigate their food environments. Between November 2017-July 2018, we conducted 38 semi-structured interviews with food-insecure women aged 50 years or older enrolled in the Northern California, Georgia, and North Carolina sites of the Women's Interagency HIV study, an ongoing cohort study of women living with and at risk of HIV. Interviews were analyzed using an inductive-deductive approach. Women from the three sites explained how they drew upon different forms of capital to access food. Women in Georgia and North Carolina depended on support from members within their social group (bonding social capital) to address food insecurity but described limited opportunities to build relationships with members from other social groups (bridging social capital) or representatives of institutions (linking social capital). In contrast, women from Northern California frequently used bridging and linking social capital to access food but described limited bonding social capital. Findings show how the role of social capital in protecting against food insecurity is diverse, complex, and structurally determined. Intervention implications are discussed

Pathogenesis of Avian Influenza A (H5N1) Viruses in Ferrets

Highly pathogenic avian influenza A H5N1 viruses caused outbreaks of disease in domestic poultry and humans in Hong Kong in 1997. Direct transmission of the H5N1 viruses from birds to humans resulted in 18 documented cases of respiratory illness, including six deaths. Here we evaluated two of the avian H5N1 viruses isolated from humans for their ability to replicate and cause disease in outbred ferrets. A/Hong Kong/483/97 virus was isolated from a fatal case and was highly pathogenic in the BALB/c mouse model, whereas A/Hong Kong/486/97 virus was isolated from a case with mild illness and exhibited a low-pathogenicity phenotype in mice. Ferrets infected intranasally with 10(7) 50% egg infectious doses (EID(50)) of either H5N1 virus exhibited severe lethargy, fever, weight loss, transient lymphopenia, and replication in the upper and lower respiratory tract, as well as multiple systemic organs, including the brain. Gastrointestinal symptoms were seen in some animals. In contrast, weight loss and severe lethargy were not noted in ferrets infected with 10(7) EID(50) of two recent human H3N2 viruses, although these viruses were also isolated from the brains, but not other extrapulmonary organs, of infected animals. The results demonstrate that both H5N1 viruses were highly virulent in the outbred ferret model, unlike the differential pathogenicity documented in inbred BALB/c mice. We propose the ferret as an alternative model system for the study of these highly pathogenic avian viruses