microRNA-33 controls hunger signaling in hypothalamic AgRP neurons.

AgRP neurons drive hunger, and excessive nutrient intake is the primary driver of obesity and associated metabolic disorders. While many factors impacting central regulation of feeding behavior have been established, the role of microRNAs in this process is poorly understood. Utilizing unique mouse models, we demonstrate that miR-33 plays a critical role in the regulation of AgRP neurons, and that loss of miR-33 leads to increased feeding, obesity, and metabolic dysfunction in mice. These effects include the regulation of multiple miR-33 target genes involved in mitochondrial biogenesis and fatty acid metabolism. Our findings elucidate a key regulatory pathway regulated by a non-coding RNA that impacts hunger by controlling multiple bioenergetic processes associated with the activation of AgRP neurons, providing alternative therapeutic approaches to modulate feeding behavior and associated metabolic diseases.

Predictors of Depression and Anxiety among Medical Students.

BACKGROUND: Medical undergraduates are more prone to emotional distress in comparison to the general population and non-medical undergraduates. This study aimed to identify the prevalence and factors associated with depression and anxiety symptoms among undergraduate medical students. METHODS: A cross-sectional study was conducted among 204 medical students in a medical institute in Kathmandu. Depression, Anxiety and Stress Scale-42 was used to identify the prevalence of depression and anxiety symptoms. The data were analyzed using multivariable logistic regression models. RESULTS: The prevalence of depression and anxiety symptoms was 30.9% and 38.7% respectively. Depression symptoms were more likely to be prevalent among fourth and fifth-year students, with an adjusted odds ratio (aOR 1.96, 95% CI: 1.03-3.75) compared to second and third-year students, and those who failed in the last academic examination (aOR 2.55, 95% CI: 1.28-5.09). Anxiety symptoms were more prevalent among male students (aOR 2.11, 95% CI: 1.04-4.27), those who were from the relatively less advantaged ethnic group (aOR 2.08, 95% CI: 1.04-4.16) and those who stayed outside the dormitory (aOR 2.90, 95% CI: 1.46-5.78). CONCLUSIONS: The prevalence of depression and anxiety symptoms among medical students was high. Psychological support is needed to ensure the mental well-being of medical students.

The taste of vitamin C in Drosophila.

Vitamins are essential micronutrients, but the mechanisms of vitamin chemoreception in animals are poorly understood. Here, we provide evidence that vitamin C doubles starvation resistance and induces egg laying in Drosophila melanogaster. Our behavioral analyses of genetically engineered and anatomically ablated flies show that fruit flies sense vitamin C via sweet-sensing gustatory receptor neurons (GRNs) in the labellum. Using a behavioral screen and in vivo electrophysiological analyses of ionotropic receptors (IRs) and sweet-sensing gustatory receptors (GRs), we find that two broadly tuned IRs (i.e., IR25a and IR76b) and five GRs (i.e., GR5a, GR61a, GR64b, GR64c, and GR64e) are essential for vitamin C detection. Thus, vitamin C is directly detected by the fly labellum and requires at least two distinct receptor types. Next, we expand our electrophysiological study to test attractive tastants such as sugars, carboxylic acids, and glycerol. Our analysis elucidates the molecular basis of chemoreception in sweet-sensing GRNs.

The age of bone marrow dictates the clonality of smooth muscle-derived cells in atherosclerotic plaques.

Aging is the predominant risk factor for atherosclerosis, the leading cause of death. Rare smooth muscle cell (SMC) progenitors clonally expand giving rise to up to ~70% of atherosclerotic plaque cells; however, the effect of age on SMC clonality is not known. Our results indicate that aged bone marrow (BM)-derived cells non-cell autonomously induce SMC polyclonality and worsen atherosclerosis. Indeed, in myeloid cells from aged mice and humans, TET2 levels are reduced which epigenetically silences integrin ß3 resulting in increased tumor necrosis factor [TNF]-α signaling. TNFα signals through TNF receptor 1 on SMCs to promote proliferation and induces recruitment and expansion of multiple SMC progenitors into the atherosclerotic plaque. Notably, integrin ß3 overexpression in aged BM preserves dominance of the lineage of a single SMC progenitor and attenuates plaque burden. Our results demonstrate a molecular mechanism of aged macrophage-induced SMC polyclonality and atherogenesis and suggest novel therapeutic strategies.

Factors Associated with Acute Malnutrition among Pregnant Women in Flood Affected Region.

BACKGROUND: Adequate nutrition before and during pregnancy is necessary to maintain women's reproductive health and to ensure healthy foetal outcome. Pregnant women are at high risk of acute malnutrition specifically during humanitarian crisis leading to adverse effects in foetal outcomes and women's health. This study aimed to assess the factors associated with acute malnutrition among pregnant women visiting Antenatal Clinics in two hospitals and a Primary Health Care Centre of Siraha district in the south-eastern plains of Nepal immediately after 2017 flash flood. METHODS: A health-institution based cross-sectional study was conducted among 444 pregnant women of reproductive age (15-49 years) in second and third trimester in three health institutions. Data collection was done in the aftermath of 2017 flash floods through face to face interview. Multiple logistic regression analysis was used to identify the factors associated with acute malnutrition defined as Mid Upper Arm Circumference less than or equals to 21 centimetres. RESULTS: Out of 444 participants, 9.9% were found to be acutely malnourished. Participant's education (AOR[Adjusted Odds Ratio]: 3.09, 95% CI[Confidence Interval]: 1.43-6.70), occupation (AOR: 3.16, 95% CI: 1.08-9.22), husband's occupation (AOR: 6.61, 95% CI: 2.17-20.12), household food security (AOR: 3.39, 95% CI: 1.36-8.49) and participant's dietary diversity (AOR:10.06, 95% CI: 3.35-30.27) were found to be statistically significant factors associated with acute malnutrition among pregnant women. CONCLUSIONS: Participants' silliteracy, unemployment, husband not employed for cash, household food insecurity and low dietary diversity were found to be statistically significant predictors of acute malnutrition among pregnant women during flash floods.

Protocol for binary food choice assays using Drosophila melanogaster.

Food preference is a fundamental behavior for animals to choose nutritious foods while rejecting foods containing toxins. Here, we describe binary food choice assays using Drosophila melanogaster, which are straightforward approaches for the characterization of two-way choice tastants. We detail the preparation of flies and dye-containing food, followed by the binary-choice feeding assays and the determination of the preference index (PI). This protocol is simple, sensitive, and reproducible in qualitatively detecting attractive or aversive characteristics toward any two-way choice tastants. For complete details on the use and execution of this protocol, please refer to Aryal et al. (2022).

Histamine avoidance through three gustatory receptors in Drosophila melanogaster.

Histamine is a fermented food product that exerts adverse health effects on animals when consumed in high amounts. This biogenic amine is fermented by microorganisms from histidine through the activity of histidine decarboxylase. Drosophila melanogaster can discriminate histidine and histamine using GR22e and IR76b in bitter-sensing gustatory receptor neurons (GRNs). In this study, RNA interference screens were conducted to examine 28 uncharacterized gustatory receptor genes using electrophysiology and behavioral experiments, including the binary food choice and proboscis extension response assays. GR9a and GR98a were first identified as specific histamine receptors by evaluating newly generated null mutants and recovery experiments by expressing their wild-type cDNA in the bitter-sensing GRNs. We further determined that histamine sensation was mainly mediated by the labellum but not by the legs, as demonstrated by the proboscis extension response assay. Our findings indicated that toxic histamine directly activates bitter-sensing GRNs in S-type sensilla, and this response is mediated by the GR9a, GR22e, and GR98a gustatory receptors.

Molecular and neuronal mechanisms for amino acid taste perception in the Drosophila labellum.

Amino acids are essential nutrients that act as building blocks for protein synthesis. Recent studies in Drosophila have demonstrated that glycine, phenylalanine, and threonine elicit attraction, whereas tryptophan elicits aversion at ecologically relevant concentrations. Here, we demonstrated that eight amino acids, including arginine, glycine, alanine, serine, phenylalanine, threonine, cysteine, and proline, differentially stimulate feeding behavior by activating sweet-sensing gustatory receptor neurons (GRNs) in L-type and S-type sensilla. In turn, this process is mediated by three GRs (GR5a, GR61a, and GR64f), as well as two broadly required ionotropic receptors (IRs), IR25a and IR76b. However, GR5a, GR61a, and GR64f are only required for sensing amino acids in the sweet-sensing GRNs of L-type sensilla. This suggests that amino acid sensing in different type sensilla occurs through dual mechanisms. Furthermore, our findings indicated that ecologically relevant high concentrations of arginine, lysine, proline, valine, tryptophan, isoleucine, and leucine elicit aversive responses via bitter-sensing GRNs, which are mediated by three IRs (IR25a, IR51b, and IR76b). More importantly, our results demonstrate that arginine, lysine, and proline induce biphasic responses in a concentration-dependent manner. Therefore, amino acid detection in Drosophila occurs through two classes of receptors that activate two sets of sensory neurons in physiologically distinct pathways, which ultimately mediates attraction or aversion behaviors.

Astrocytic lipid metabolism determines susceptibility to diet-induced obesity.

Hypothalamic astrocytes play pivotal roles in both nutrient sensing and the modulation of synaptic plasticity of hypothalamic neuronal circuits in control of feeding and systemic glucose and energy metabolism. Here, we show the relevance of astrocytic fatty acid (FA) homeostasis under the opposing control of angiopoietin-like 4 (ANGPTL-4) and peroxisome proliferator­activated receptor gamma (PPARγ) in the cellular adaptations of hypothalamic astrocytes and neurons to the changing metabolic milieu. We observed that increased availability of FA in astrocytes induced by cell- and time-selective knockdown of Angptl4 protected against diet-induced obesity, while cell- and time-selective knockdown of Angptl4-regulated Pparγ lead to elevated susceptibility to obesity. Overall, our results unravel a previously unidentified role for astrocytic FA metabolism in central control of body weight and glucose homeostasis.

Ionotropic receptors mediate nitrogenous waste avoidance in Drosophila melanogaster.

Ammonia and its amine-containing derivatives are widely found in natural decomposition byproducts. Here, we conducted biased chemoreceptor screening to investigate the mechanisms by which different concentrations of ammonium salt, urea, and putrescine in rotten fruits affect feeding and oviposition behavior. We identified three ionotropic receptors, including the two broadly required IR25a and IR76b receptors, as well as the narrowly tuned IR51b receptor. These three IRs were fundamental in eliciting avoidance against nitrogenous waste products, which is mediated by bitter-sensing gustatory receptor neurons (GRNs). The aversion of nitrogenous wastes was evaluated by the cellular requirement by expressing Kir2.1 and behavioral recoveries of the mutants in bitter-sensing GRNs. Furthermore, by conducting electrophysiology assays, we confirmed that ammonia compounds are aversive in taste as they directly activated bitter-sensing GRNs. Therefore, our findings provide insights into the ecological roles of IRs as a means to detect and avoid toxic nitrogenous waste products in nature.

Desmosterol suppresses macrophage inflammasome activation and protects against vascular inflammation and atherosclerosis.

Cholesterol biosynthetic intermediates, such as lanosterol and desmosterol, are emergent immune regulators of macrophages in response to inflammatory stimuli or lipid overloading, respectively. However, the participation of these sterols in regulating macrophage functions in the physiological context of atherosclerosis, an inflammatory disease driven by the accumulation of cholesterol-laden macrophages in the artery wall, has remained elusive. Here, we report that desmosterol, the most abundant cholesterol biosynthetic intermediate in human coronary artery lesions, plays an essential role during atherogenesis, serving as a key molecule integrating cholesterol homeostasis and immune responses in macrophages. Depletion of desmosterol in myeloid cells by overexpression of 3ß-hydroxysterol Δ24-reductase (DHCR24), the enzyme that catalyzes conversion of desmosterol to cholesterol, promotes the progression of atherosclerosis. Single-cell transcriptomics in isolated CD45+CD11b+ cells from atherosclerotic plaques demonstrate that depletion of desmosterol increases interferon responses and attenuates the expression of antiinflammatory macrophage markers. Lipidomic and transcriptomic analysis of in vivo macrophage foam cells demonstrate that desmosterol is a major endogenous liver X receptor (LXR) ligand involved in LXR/retinoid X receptor (RXR) activation and thus macrophage foam cell formation. Decreased desmosterol accumulation in mitochondria promotes macrophage mitochondrial reactive oxygen species production and NLR family pyrin domain containing 3 (NLRP3)-dependent inflammasome activation. Deficiency of NLRP3 or apoptosis-associated speck-like protein containing a CARD (ASC) rescues the increased inflammasome activity and atherogenesis observed in desmosterol-depleted macrophages. Altogether, these findings underscore the critical function of desmosterol in the atherosclerotic plaque to dampen inflammation by integrating with macrophage cholesterol metabolism and inflammatory activation and protecting from disease progression.

Effect of an Educational Intervention on Dietary Diversity Practices among Public School Students.

BACKGROUND: Poor dietary diversity leading to malnutrition among children and adolescents is a serious public health problem in Nepal. Though nutrition education intervention has been effective in changing the dietary intake habits of individuals in school settings, the contextual educational intervention has not been tested in our study area. This study is aimed at assessing the effect of dietary diversity education based on the Health Belief Model among secondary level students in selected schools of Siddhicharan Municipality, Okhaldhunga. METHODS: Quasi-experimental study design was employed during the intervention study. Our study was conducted in 3 phases: Phase I, Baseline Study; Phase II, Education Package Development; and Phase III- Intervention Study (Implementation and evaluation of the package). The data was collected for getting baseline that was used to develop package, pre-intervention assessment and after intervention assessment, using a self-administered structured questionnaire based on constructs of Health Belief Model (HBM). Study participants were students from grade 7 and 8. The collected data was analyzed using SPSS version 21. RESULTS: After the education intervention, dietary diversity knowledge and practice in the intervention group increased from 16.4% to 54.2% and 32.8% to 48.6% respectively. Significant association (P<0.001) was noted between knowledge of dietary diversity with intervention in post-test. Similarly, the mean score of the Health Belief Model construct was significantly improved and showed an association (P<0.001) with nutrition education after the intervention. CONCLUSIONS: Nutrition education based on the Health Belief Model showed a positive impact on knowledge and practice of dietary diversity among school students. Hence, such education intervention should be promoted by educational institutions, the Ministry of Education, Ministry of Health and Population, NGOs and INGOs.

Hepatocyte-specific suppression of ANGPTL4 improves obesity-associated diabetes and mitigates atherosclerosis in mice.

Hepatic uptake and biosynthesis of fatty acids (FA), as well as the partitioning of FA into oxidative, storage, and secretory pathways are tightly regulated processes. Dysregulation of one or more of these processes can promote excess hepatic lipid accumulation, ultimately leading to systemic metabolic dysfunction. Angiopoietin-like-4 (ANGPTL4) is a secretory protein that inhibits lipoprotein lipase (LPL) and modulates triacylglycerol (TAG) homeostasis. To understand the role of ANGPTL4 in liver lipid metabolism under normal and high-fat fed conditions, we generated hepatocyte specific Angptl4 mutant mice (Hmut). Using metabolic turnover studies, we demonstrate that hepatic Angptl4 deficiency facilitates catabolism of TAG-rich lipoprotein (TRL) remnants in the liver via increased hepatic lipase (HL) activity, which results in a significant reduction in circulating TAG and cholesterol levels. Consequently, depletion of hepatocyte Angptl4 protects against diet-induce obesity, glucose intolerance, liver steatosis, and atherogenesis. Mechanistically, we demonstrate that loss of Angptl4 in hepatocytes promotes FA uptake which results in increased FA oxidation, ROS production, and AMPK activation. Finally, we demonstrate the utility of a targeted pharmacologic therapy that specifically inhibits Angptl4 gene expression in the liver and protects against diet-induced obesity, dyslipidemia, glucose intolerance, and liver damage, which likely occurs via increased HL activity. Notably, this novel inhibition strategy does not cause any of the deleterious effects previously observed with neutralizing antibodies.

Histamine gustatory aversion in Drosophila melanogaster.

Many foods and drinks contain histamine; however, the mechanisms that drive histamine taste perception have not yet been investigated. Here, we use a simple model organism, Drosophila melanogaster, to dissect the molecular sensors required to taste histamine. We first investigated histidine and histamine taste perception by performing a binary food choice assay and electrophysiology to identify essential sensilla for histamine sensing in the labellum. Histamine was found to activate S-type sensilla, which harbor bitter-sensing gustatory receptor neurons. Moreover, unbiased genetic screening for chemoreceptors revealed that a gustatory receptor, GR22e and an ionotropic receptor, IR76b are required for histamine sensing. Ectopic expression of GR22e was sufficient to induce a response in I-type sensilla, which normally do not respond to histamine. Taken together, our findings provide new insights into the mechanisms by which insects discriminate between the toxic histamine and beneficial histidine via their taste receptors.

Deficiency of histone lysine methyltransferase SETDB2 in hematopoietic cells promotes vascular inflammation and accelerates atherosclerosis.

Epigenetic modifications of the genome, including DNA methylation, histone methylation/acetylation, and noncoding RNAs, have been reported to play a fundamental role in regulating immune response during the progression of atherosclerosis. SETDB2 is a member of the KMT1 family of lysine methyltransferases, and members of this family typically methylate histone H3 Lys9 (H3K9), an epigenetic mark associated with gene silencing. Previous studies have shown that SETDB2 is involved in innate and adaptive immunity, the proinflammatory response, and hepatic lipid metabolism. Here, we report that expression of SETDB2 is markedly upregulated in human and murine atherosclerotic lesions. Upregulation of SETDB2 was observed in proinflammatory M1 but not antiinflammatory M2 macrophages. Notably, we found that genetic deletion of SETDB2 in hematopoietic cells promoted vascular inflammation and enhanced the progression of atherosclerosis in BM transfer studies in Ldlr-knockout mice. Single-cell RNA-Seq analysis in isolated CD45+ cells from atherosclerotic plaques from mice transplanted with SETDB2-deficient BM revealed a significant increase in monocyte population and enhanced expression of genes involved in inflammation and myeloid cell recruitment. Additionally, we found that loss of SETDB2 in hematopoietic cells was associated with macrophage accumulation in atherosclerotic lesions and attenuated efferocytosis. Overall, these studies identify SETDB2 as an important inflammatory cell regulator that controls macrophage activation in atherosclerotic plaques.

American Society of Clinical Oncology (ASCO) Cervical Cancer Prevention Program: A Hands-On Training Course in Nepal.

Cervical cancer is the leading cause of death among women in Nepal. The American Society of Clinical Oncology (ASCO) and The University of Texas MD Anderson Cancer Center collaborated with international and local experts to hold a cervical cancer prevention course in Nepal in November 2019. The course included didactic lectures and a hands-on workshop. The didactic lectures included the epidemiology of cervical cancer globally and locally, cervical cancer screening guidelines, human papillomavirus vaccination, colposcopy and visual inspection with acetic acid (VIA), cervical dysplasia, and cervical cancer treatment. The hands-on workshop consisted of four stations: (1) VIA; (2) colposcopy, cervical biopsy, and endocervical curettage; (3) thermal ablation; and (4) loop electrosurgical excision procedure (LEEP). A train-the-trainer model short course was held by the international faculty to assist six local faculty to become familiar with the instruments, procedures, and models used in the hands-on training stations. Forty-two people (84% gynecologist, 8% radiation oncologist, and 8% other) attended the course. Following the course, the international faculty visited the regional hospitals for additional educational activities. Increased knowledge in cervical cancer screening guidelines and ability in performing VIA, colposcopy and cervical biopsy, thermal ablation, and LEEP were reported by 89%, 84%, 84%, 87%, and 84% of participants, respectively, from the postcourse on-site evaluations. From the 6-month follow-up survey, all respondents reported that they had made practice changes based on what they learned in the course and had implemented or tried to implement the cervical cancer screening guidelines presented at the course. In conclusion, the course evaluations suggested an improvement in participants' ability to perform cervical cancer screening and diagnostic procedures and reported the changes in practices after training.

Loss of hepatic miR-33 improves metabolic homeostasis and liver function without altering body weight or atherosclerosis.

miR-33 is an intronic microRNA within the gene encoding the SREBP2 transcription factor. Like its host gene, miR-33 has been shown to be an important regulator of lipid metabolism. Inhibition of miR-33 has been shown to promote cholesterol efflux in macrophages by targeting the cholesterol transporter ABCA1, thus reducing atherosclerotic plaque burden. Inhibition of miR-33 has also been shown to improve high-density lipoprotein (HDL) biogenesis in the liver and increase circulating HDL-C levels in both rodents and nonhuman primates. However, evaluating the extent to which these changes in HDL metabolism contribute to atherogenesis has been hindered by the obesity and metabolic dysfunction observed in whole-body miR-33-knockout mice. To determine the impact of hepatic miR-33 deficiency on obesity, metabolic function, and atherosclerosis, we have generated a conditional knockout mouse model that lacks miR-33 only in the liver. Characterization of this model demonstrates that loss of miR-33 in the liver does not lead to increased body weight or adiposity. Hepatic miR-33 deficiency actually improves regulation of glucose homeostasis and impedes the development of fibrosis and inflammation. We further demonstrate that hepatic miR-33 deficiency increases circulating HDL-C levels and reverse cholesterol transport capacity in mice fed a chow diet, but these changes are not sufficient to reduce atherosclerotic plaque size under hyperlipidemic conditions. By elucidating the role of miR-33 in the liver and the impact of hepatic miR-33 deficiency on obesity and atherosclerosis, this work will help inform ongoing efforts to develop novel targeted therapies against cardiometabolic diseases.

Cav-1 (Caveolin-1) Deficiency Increases Autophagy in the Endothelium and Attenuates Vascular Inflammation and Atherosclerosis.

OBJECTIVE: Endothelial Cav-1 (caveolin-1) expression plays a relevant role during atherogenesis by controlling NO production, vascular inflammation, LDL (low-density lipoprotein) transcytosis, and extracellular matrix remodeling. Additional studies have identified cholesterol-rich membrane domains as important regulators of autophagy by recruiting ATGs (autophagy-related proteins) to the plasma membrane. Here, we investigate how the expression of Cav-1 in the aortic endothelium influences autophagy and whether enhanced autophagy contributes to the atheroprotective phenotype observed in Cav-1-deficient mice. Approach and Results: To analyze the impact of Cav-1 deficiency on regulation of autophagy in the aortic endothelium during the progression of atherosclerosis, we fed Ldlr-/- and Cav-1-/-Ldlr-/- mice a Western diet and assessed autophagy in the vasculature. We observe that the absence of Cav-1 promotes autophagy activation in athero-prone areas of the aortic endothelium by enhancing autophagic flux. Mechanistically, we found that Cav-1 interacts with the ATG5-ATG12 complex and influences the cellular localization of autophagosome components in lipid rafts, which controls the autophagosome formation and autophagic flux. Pharmacological inhibition of autophagy attenuates the atheroprotection observed in Cav-1-/- mice by increasing endothelial inflammation and macrophage recruitment, identifying a novel molecular mechanism by which Cav-1 deficiency protects against the progression of atherosclerosis. CONCLUSIONS: These results identify Cav-1 as a relevant regulator of autophagy in the aortic endothelium and demonstrate that pharmacological suppression of autophagic flux in Cav-1-deficient mice attenuates the atheroprotection observed in Cav-1-/- mice. Additionally, these findings suggest that activation of endothelial autophagy by blocking Cav-1 might provide a potential therapeutic strategy for cardiovascular diseases including atherosclerosis.

Severe acute malnutrition and its associated factors among children under-five years: a facility-based cross-sectional study.

BACKGROUND: Despite consistent efforts to enhance child nutrition, poor nutritional status of children continues to be a major public health problem in Nepal. This study identified the predictors of severe acute malnutrition (SAM) among children aged 6 to 59 months in the two districts of Nepal. METHODS: We used data from a cross-sectional study conducted among 6 to 59 months children admitted to the Outpatient Therapeutic Care Centers (OTCC). The nutritional status of children was assessed using mid-upper arm circumference (MUAC) measurement. To determine which variables predict the occurrence of SAM, adjusted odds ratio was computed using multivariate logistic regression and p-value < 0.05 was considered as significant. RESULTS: Out of 398 children, 5.8% were severely malnourished and the higher percentage of female children were malnourished. Multivariate analysis showed that severe acute malnutrition was significantly associated with family size (five or more members) (Adjusted Odds Ratio [AOR]: 3.96; 95% Confidence Interval [CI]: 1.23-12.71). Children from severely food insecure households (AOR: 4.04; 95% CI: 1.88-10.53) were four times more likely to be severely malnourished. Higher odds of SAM were found among younger age-group (AOR: 12.10; 95% CI: 2.06-71.09) children (0-12 vs. 24-59 months). CONCLUSIONS: The findings of this study indicated that household size, household food access, and the child's age were the major predictors of severe acute malnutrition. Engaging poor families in kitchen gardening to ensure household food access and nutritious diet to the children, along with health education and promotion to the mothers of young children are therefore recommended to reduce child undernutrition.

Endothelial TGF-ß signalling drives vascular inflammation and atherosclerosis.

Atherosclerosis is a progressive vascular disease triggered by interplay between abnormal shear stress and endothelial lipid retention. A combination of these and, potentially, other factors leads to a chronic inflammatory response in the vessel wall, which is thought to be responsible for disease progression characterized by a buildup of atherosclerotic plaques. Yet molecular events responsible for maintenance of plaque inflammation and plaque growth have not been fully defined. Here we show that endothelial TGFß signaling is one of the primary drivers of atherosclerosis-associated vascular inflammation. Inhibition of endothelial TGFß signaling in hyperlipidemic mice reduces vessel wall inflammation and vascular permeability and leads to arrest of disease progression and regression of established lesions. These pro-inflammatory effects of endothelial TGFß signaling are in stark contrast with its effects in other cell types and identify it as an important driver of atherosclerotic plaque growth and show the potential of cell-type specific therapeutic intervention aimed at control of this disease.