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Sea star wasting syndrome (SSWS) can cause widespread mortality in starfish populations as well as long-lasting changes to benthic community structure and dynamics. SSWS symptoms have been documented in numerous species and locations around the world, but to date there is only one record of SSWS from the Antarctic and this outbreak was associated with volcanically-driven high temperature anomalies. Here we report outbreaks of SSWS-like symptoms that affected ~30% of individuals of Odontaster validus at two different sites in McMurdo Sound, Antarctica in 2019 and 2022. Unlike many SSWS events in other parts of the world, these outbreaks were not associated with anomalously warm temperatures. Instead, we suggest they may have been triggered by high nutrient input events on a local scale. Although the exact cause of these outbreaks is not known, these findings are of great concern because of the keystone role of O. validus and the slow recovery rate of Antarctic benthic ecosystems to environmental stressors. [ABSTRACT FROM AUTHOR]

Long-term datasets can reveal otherwise undetectable ecological trends, illuminating the historical context of contemporary ecosystem states. We used two decades (1997–2019) of scientific trawling data from a subtidal, benthic site in Puget Sound, Washington, USA to test for gradual trends and sudden shifts in total sea star abundance across 11 species. We specifically assessed whether this community responded to the sea star wasting disease (SSWD) epizootic, which began in 2013. We sampled at depths of 10, 25, 50 and 70 m near Port Madison, WA, and obtained long-term water temperature data. To account for species-level differences in SSWD susceptibility, we divided our sea star abundance data into two categories, depending on the extent to which the species is susceptible to SSWD, then conducted parallel analyses for high-susceptibility and moderate-susceptibility species. The abundance of high-susceptibility sea stars declined in 2014 across depths. In contrast, the abundance of moderate-susceptibility species trended downward throughout the years at the deepest depths– 50 and 70 m–and suddenly declined in 2006 across depths. Water temperature was positively correlated with the abundance of moderate-susceptibility species, and uncorrelated with high-susceptibility sea star abundance. The reported emergence of SSWD in Washington State in the summer of 2014 provides a plausible explanation for the subsequent decline in abundance of high-susceptibility species. However, no long-term stressors or mortality events affecting sea stars were reported in Washington State prior to these years, leaving the declines we observed in moderate-susceptibility species preceding the 2013–2015 SSWD epizootic unexplained. These results suggest that the subtidal sea star community in Port Madison is dynamic, and emphasizes the value of long-term datasets for evaluating patterns of change. [ABSTRACT FROM AUTHOR]

Pre-clinical murine models are critical for translating drug candidates from the bench to the bedside. There is interest in better understanding how anti-human CD3 therapy works based on recent longitudinal studies of short-term administration. Although several models have been created in this pursuit, each have their own advantages and disadvantages in Type-1 diabetes. In this study, we report a murine genetic knock-in model which expresses both a murine and a humanized-CD3ε-exon, rendering it sensitive to manipulation with anti-human CD3. These huCD3εHET mice are viable and display no gross abnormalities. Specifically, thymocyte development and T cell peripheral homeostasis is unaffected. We tested immune functionality of these mice by immunizing them with T cell-dependent antigens and no differences in antibody titers compared to wild type mice were recorded. Finally, we performed a graft-vs-host disease model that is driven by effector T cell responses and observed a wasting disease upon transfer of huCD3εHET T cells. Our results show a viable humanized CD3 murine model that develops normally, is functionally engaged by anti-human CD3 and can instruct on pre-clinical tests of anti-human CD3 antibodies. [ABSTRACT FROM AUTHOR]

Animal African trypanosomiasis (AAT) is a severe, wasting disease of domestic livestock and diverse wildlife species. The disease in cattle kills millions of animals each year and inflicts a major economic cost on agriculture in sub-Saharan Africa. Cattle AAT is caused predominantly by the protozoan parasites Trypanosoma congolense and T. vivax, but laboratory research on the pathogenic stages of these organisms is severely inhibited by difficulties in making even minor genetic modifications. As a result, many of the important basic questions about the biology of these parasites cannot be addressed. Here we demonstrate that an in vitro culture of the T. congolense genomic reference strain can be modified directly in the bloodstream form reliably and at high efficiency. We describe a parental single marker line that expresses T. congolense-optimized T7 RNA polymerase and Tet repressor and show that minichromosome loci can be used as sites for stable, regulatable transgene expression with low background in non-induced cells. Using these tools, we describe organism-specific constructs for inducible RNA-interference (RNAi) and demonstrate knockdown of multiple essential and non-essential genes. We also show that a minichromosomal site can be exploited to create a stable bloodstream-form line that robustly provides >40,000 independent stable clones per transfection–enabling the production of high-complexity libraries of genome-scale. Finally, we show that modified forms of T. congolense are still infectious, create stable high-bioluminescence lines that can be used in models of AAT, and follow the course of infections in mice by in vivo imaging. These experiments establish a base set of tools to change T. congolense from a technically challenging organism to a routine model for functional genetics and allow us to begin to address some of the fundamental questions about the biology of this important parasite. Author summary: The parasites Trypanosoma congolense and T. vivax are the most significant causative agents of Animal African trypanosomiasis (AAT). AAT kills an estimated 3 million cattle each year and represents a huge financial burden on food production in sub-Saharan Africa. A critical tool for understanding pathogen biology is the ability to make genetic modifications, especially creating specific mutants of target genes that can be used to investigate the locations of gene products, the effects of changes in expression, or consequence of complete gene removal. However, work on AAT is severely limited by difficulties in making even small genetic modifications and lack of tools for many functional genetics applications. Here, we design, test and validate a set of tools for T. congolense that brings for the first time: routine high-efficiency gene tagging and knockout, regulatable transgene expression from silent loci, a species-specific system for inducible gene knockdown, bioluminescent lines for in vivo disease models, and a means to generate highly complex libraries of mutants that will enable genome-scale work. These data and the tools around them will greatly aid research into AAT and T. congolense biology. [ABSTRACT FROM AUTHOR]

Protein energy wasting (PEW) including muscle atrophy is a common complication in chronic hemodialysis patients. The ubiquitin proteasome system (UPS) is the main proteolytic system causing muscle atrophy in chronic kidney disease and proteasome 20S is the catalytic component of the UPS. Circulating proteasome 20S (c20S proteasome) is present in the blood and its level is related to disease severity and prognosis in several disorders. We hypothesized that c20S proteasome could be related with muscle mass, other PEW criteria and their evolution in hemodialysis patients. Stable hemodialysis patients treated at our center for more than 3 months were followed over 2 years. C20S proteasome assay was performed at baseline. Biological and clinical data were collected, muscle mass was assessed by multi-frequency bio-impedancemetry, and nutritional scores were calculated at baseline, 1 year and 2 years. Hospitalizations and mortality data were collected over the 2 years. Forty-nine patients were included. At baseline, the c20S proteasome level was 0.40[0.26–0.55] μg/ml. Low muscle mass as defined by a lean tissue index (LTI) < 10th in accordance with the International Society of Renal Nutrition and Metabolism guidelines was observed in 36% and PEW in 62%. Increased c20S proteasome levels were related with LTI at baseline (R = 0.43, p = 0.004) and with its 2 year-variation (R = -0.56, p = 0.003). Two-year survival rate was not different between higher and lower c20S proteasome values (78.9 vs 78.4%, p = 0.98 log-rank test). C20S proteasome is not a good marker for assessing nutritional status in hemodialysis patients and predicting patient outcomes. [ABSTRACT FROM AUTHOR]

Marmoset wasting syndrome (MWS) is clinically characterized by progressive weight loss. Although morbidity and mortality of MWS are relatively high in captive marmosets, its causes remain unknown. Lipid mediators are bioactive metabolites which are produced from polyunsaturated fatty acids, such as arachidonic acid (AA) and eicosapentaenoic acid. These lipid metabolites regulate a wide range of inflammatory responses and they are excreted into the urine. As urinary lipid profiles reflect systemic inflammatory conditions, we comprehensively measured the levels of 141 types of lipid metabolites in the urines obtained from healthy common marmoset (Callithrix jacchus) (N = 7) or marmosets with MWS (N = 7). We found that 41 types of metabolites were detected in all urine samples of both groups. Among them, AA-derived metabolites accounted for 63% (26/41 types) of all detected metabolites. Notably, the levels of AA-derived prostaglandin (PG) E2, PGF2α, thromboxane (TX) B2 and F2-isoprostanes significantly increased in the urine samples of marmosets with MWS. In this study, we found some urinary lipid metabolites which may be involved in the development of MWS. Although the cause of MWS remains unclear, our findings may provide some insight into understanding the mechanisms of development of MWS. [ABSTRACT FROM AUTHOR]

Signal transducers and activators of transcription (STAT) 1 is critical for cellular responses to type I interferons (IFN-Is), with the capacity to determine the outcome of viral infection. We previously showed that while wildtype (WT) mice develop mild disease and survive infection with lymphocytic choriomeningitis virus (LCMV), LCMV infection of STAT1-deficient mice results in a lethal wasting disease that is dependent on IFN-I and CD4+ cells. IFN-Is are considered to act as a bridge between innate and adaptive immunity. Here, we determined the relative contribution of STAT1 on innate and adaptive immunity during LCMV infection. We show that STAT1 deficiency results in a biphasic disease following LCMV infection. The initial, innate immunity-driven phase of disease was characterized by rapid weight loss, thrombocytopenia, systemic cytokine and chemokine responses and leukocyte infiltration of infected organs. In the absence of an adaptive immune response, this first phase of disease largely resolved resulting in survival of the infected host. However, in the presence of adaptive immunity, the disease progressed into a second phase with continued cytokine and chemokine production, persistent leukocyte extravasation into infected tissues and ultimately, host death. Overall, our findings demonstrate the key contribution of STAT1 in modulating innate and adaptive immunity during type I interferon-mediated lethal virus infection. Author summary: The mammalian immune system is divided into innate and adaptive immunity. In response to harmful agents, innate immunity acts first, followed by late-acting, specialized, adaptive immunity. Type I interferons (IFN-Is) are important means of communication between innate and adaptive immunity. IFN-Is mediate their effects via a number of signaling molecules, principally including signal transducers and activators of transcription 1 (STAT1). The importance of STAT1 to the immune response is evident from our previous finding that mice deficient in STAT1 develop a lethal, host immunity-mediated disease following infection with the otherwise harmless lymphocytic choriomeningitis virus (LCMV). In the present study, we characterized the role of STAT1 in protecting against harmful host immune responses against LCMV. We report that STAT1 plays a significant role in lessening both the early, inflammatory responses of innate immunity and the sustained, destructive actions of adaptive immunity. These findings exemplify the extent of STAT1's role as a key immune response modulating factor. [ABSTRACT FROM AUTHOR]

Recent trends suggest that marine disease outbreaks caused by opportunistic pathogens are increasing in frequency and severity. One such malady is seagrass wasting disease, caused by pathogens in the genus Labyrinthula. It is suspected that pathogenicity is intimately linked to the ability of the host to initiate defense responses; however, supportive evidence is lacking. To address this, we developed two techniques, including 1) a new qPCR-based pathogen detection method, and 2) an immune profiling panel via four host-biomarker assays (measuring peroxidase, exochitinase, polyphenol oxidase, and lysozyme activities). These techniques were then used to experimentally investigate the impact of environmental stressors (namely, elevated temperature and salinity) on host immunity and how immune status might affect susceptibility to Labyrinthula infection. In the first experiment, we subjected individual turtlegrass (Thalassia testudinum) shoots to short-term (7 d) abiotic stressors alone. In a second experiment, the same abiotic stressor conditions were followed by pathogen exposure (7 additional d), simulating a scenario where we attempt to isolate the impact of environmental stressors on the host seagrass species by removing the stressor as the pathogen is introduced. The qPCR assay successfully quantified the abundance of Labyrinthula spp. cells from both pure cultures and seagrass tissues across a broad range of predominately pathogenic strains, with high sensitivity. Immune enzyme assays revealed that all four biomarkers were constitutively active in turtlegrass individuals, but specific activities were largely unaffected by the chosen abiotic stressor conditions. We also identified positive correlations between pathogen load and two biomarkers (peroxidase, exochitinase), regardless of abiotic stress treatment, further demonstrating the potential utility of these biomarkers in future applications. [ABSTRACT FROM AUTHOR]

Sea star wasting disease (SSWD) describes a suite of disease signs believed to have led to catastrophic die-offs in many asteroid species, beginning in 2013. While most studies have focused on large, easily visible sea stars with widely-dispersing larvae, less information is available on the effect of this disease outbreak on smaller sea star species, such as the six-armed sea star Leptasterias spp. Unlike many larger sea stars, Leptasterias brood non-feeding young instead of broadcast-spawning planktonic larvae. Limited dispersal and thus limited gene flow may make these sea stars more vulnerable to local selective pressures, such as disease outbreaks. Here, we examined Leptasterias populations at sites along the California coast and documented abundance changes coincident with recent Pacific coast SSWD in 2014. Detection of Leptasterias in central California declined, and Leptasterias were not detected at multiple sites clustered around the San Francisco Bay outflow in the most recent surveys. Additionally, we categorized disease signs in Leptasterias in the field and laboratory, which mirrored those seen in larger sea stars in both settings. Finally, we found that magnesium chloride (MgCl2) slowed the progression of physical deterioration related to SSWD when applied to sea stars in the laboratory, suggesting that MgCl2 may prolong the survival of diseased individuals. [ABSTRACT FROM AUTHOR]

South Asia continues to carry the greatest share and number of wasted children worldwide. Understanding the determinants of wasting is important as policymakers renew efforts to tackle this persistent public health and development problem. Using data from national surveys in Bangladesh, India, the Maldives, Nepal, Pakistan and Afghanistan, this analysis explores factors associated with wasting among children aged 0 to 59 months (n = 252,797). We conducted multivariate mixed logistic regression and backwards stepwise methods to identify parsimonious models for each country separately (all p values <0.05). Younger children (0 to 5 months), and those whose mothers had a low body mass index (<18.5 kg/m2) had greater odds of being wasted in all countries. Later birth order, being male, maternal illiteracy, short maternal stature, lack of improved water source, and household poverty were also associated with wasting in various countries, but not systematically in all. Seasonality was also not consistently associated with wasting in the final models. These findings suggest that pre-conception (adolescence), pregnancy and early postpartum, represent windows of opportunity for tackling child wasting, not only stunting. Our analysis suggests that the underlying determinants of wasting and stunting in South Asia are similar, but not universal across geographies. Cost-effective interventions to prevent both stunting and wasting, and to treat severe wasting, need to be scaled up urgently. Separating these two manifestations of child undernutrition in conceptual and programmatic terms may unnecessarily impair progress to reach the Sustainable Development Goals targets aimed at addressing both child stunting and wasting. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the molecular pathways involved in muscle wasting in an animal model of osteoarthritis (OA) induced by anterior cruciate ligament transection (ACLT) in rats. Reduction of protein syntheses, increased proteolysis and impaired muscle regeneration are important pathways related to muscle wasting, and myogenin, MyoD, myostatin and MuRF-1 are some of their markers. Female Wistar rats were allocated into two groups: OA (submitted to the ACLT) and SHAM (submitted to surgery without ACLT). Nociception, spontaneous exploratory locomotion and body weight of animals were evaluated weekly. Twelve weeks after the disease induction, animals were euthanized, and the right knee joints were collected. Gastrocnemius muscle of the right hind paw were dissected and weighed. Gastrocnemius was used for evaluation of muscle atrophy and expression of IL-1β, TNF-α, Pax7, myogenin, MyoD, myostatin and MuRF-1. Histopathology of the knee confirmed the development of the disease in animals of OA group. Gastrocnemius of OA animals showed a reduction of about 10% in area and an increased IL-1β expression compared to animals of SHAM group. Expression of myostatin was increased in OA group, while myogenin expression was decreased. TNF-α, Pax7, MuRF-1 and MyoD expression was similar in both OA and SHAM groups. Nociception was significantly elevated in OA animals in the last two weeks of experimental period. Spontaneous exploratory locomotion, body weight and weight of gastrocnemius showed no difference between OA and SHAM groups. Gastrocnemius atrophy in OA induced by ACLT involves elevated expression of IL-1β within the muscle, as well as increased expression of myostatin and decreased expression of myogenin. Therefore, muscle wasting may be linked to impaired muscle regeneration. [ABSTRACT FROM AUTHOR]

Disease outbreaks can have substantial impacts on wild populations, but the often patchy or anecdotal evidence of these impacts impedes our ability to understand outbreak dynamics. Recently however, a severe disease outbreak occurred in a group of very well-studied organisms–sea stars along the west coast of North America. We analyzed nearly two decades of data from a coordinated monitoring effort at 88 sites ranging from southern British Columbia to San Diego, California along with 2 sites near Sitka, Alaska to better understand the effects of sea star wasting disease (SSWD) on the keystone intertidal predator, Pisaster ochraceus. Quantitative surveys revealed unprecedented declines of P. ochraceus in 2014 and 2015 across nearly the entire geographic range of the species. The intensity of the impact of SSWD was not uniform across the affected area, with proportionally greater population declines in the southern regions relative to the north. The degree of population decline was unrelated to pre-outbreak P. ochraceus density, although these factors have been linked in other well-documented disease events. While elevated seawater temperatures were not broadly linked to the initial emergence of SSWD, anomalously high seawater temperatures in 2014 and 2015 might have exacerbated the disease’s impact. Both before and after the onset of the SSWD outbreak, we documented higher recruitment of P. ochraceus in the north than in the south, and while some juveniles are surviving (as evidenced by transition of recruitment pulses to larger size classes), post-SSWD survivorship is lower than during pre-SSWD periods. In hindsight, our data suggest that the SSWD event defied prediction based on two factors found to be important in other marine disease events, sea water temperature and population density, and illustrate the importance of surveillance of natural populations as one element of an integrated approach to marine disease ecology. Low levels of SSWD-symptomatic sea stars are still present throughout the impacted range, thus the outlook for population recovery is uncertain. [ABSTRACT FROM AUTHOR]

Introduction: Given the high prevalence of malnutrition in a malaria-endemic setting, improving nutritional status could serve as a tool to prevent malaria. However, the relationship between the two conditions remains unclear. Therefore, this study assessed the association between under-nutrition and malaria among a cohort of children aged 6 to 59 months old. Methods: Two cohorts of children were followed for 89 weeks in a rural Rift Valley area of Ethiopia. In the first approach (malaria-malnutrition), a cohort of 2,330 non-stunted and 4,204 non-wasted children were included to assess under-nutrition (outcome) based on their previous malaria status (exposure). In the second approach (malnutrition–malaria), a cohort of 4,468 children were followed-up to measure malaria (outcome), taking under-nutrition as an exposure. A weekly home visit was carried out to identify malaria cases. Four anthropometry surveys were conducted, and generalized estimating equation (GEE) method was used to measure the association between undernutrition and malaria. Results: The prevalence of stunting was 44.9% in December 2014, 51.5% in August 2015, 50.7% in December 2015 and 48.1% in August 2016. We observed 103 cases with 118 episodes of malaria, 684 new stunting and 239 new wasting cases. The incidence rate per 10,000 weeks of observation was 3.8 for malaria, 50.4 for stunting and 8.2 for wasting. Children with malaria infection, [Adjusted Odds Ratio (AOR) = 1.9; 95% Confidence Interval (CI), 1.2–2.9)] and younger age (AOR = 1.3; 95% CI, 1.1–1.5) were more likely to be stunted. Furthermore, children with malaria infection (AOR = 8.5; 95% CI, 5.0–14.5) and young age group (AOR = 1.6; 95% CI, 1.2–2.1) were more likely to be wasted. However, stunting and wasting were not risk factors of subsequent malaria illness. Conclusions: Malaria infection was a risk factor for stunting and wasting, but stunting or wasting was not associated with subsequent malaria illness. As our study shows that malaria is a risk factor for stunting and wasting, a close follow-up of the nutritional status of such children may be needed. Trial registration: PACT R2014 11000 882128 (8 September 2014). [ABSTRACT FROM AUTHOR]

Severe burns are typically followed by hypermetabolism characterized by significant muscle wasting, which causes considerable morbidity and mortality. The aim of the present study was to explore the underlying mechanisms of skeletal muscle damage/wasting post-burn. Rats were randomized to the sham, sham+4-phenylbutyrate (4-PBA, a pharmacological chaperone promoting endoplasmic reticulum (ER) folding/trafficking, commonly considered as an inhibitor of ER), burn (30% total body surface area), and burn+4-PBA groups; and sacrificed at 1, 4, 7, 14 days after the burn injury. Tibial anterior muscle was harvested for transmission electron microscopy, calcium imaging, gene expression and protein analysis of ER stress / ubiquitin-proteasome system / autophagy, and calpain activity measurement. The results showed that ER stress markers were increased in the burn group compared with the sham group, especially at post-burn days 4 and 7, which might consequently elevate cytoplasmic calcium concentration, promote calpain production as well as activation, and cause skeletal muscle damage/wasting of TA muscle after severe burn injury. Interestingly, treatment with 4-PBA prevented burn-induced ER swelling and altered protein expression of ER stress markers and calcium release, attenuating calpain activation and skeletal muscle damage/wasting after severe burn injury. Atrogin-1 and LC3-II/LC3-I ratio were also increased in the burn group compared with the sham group, while MuRF-1 remained unchanged; 4-PBA decreased atrogin-1 in the burn group. Taken together, these findings suggested that severe burn injury induces ER stress, which in turns causes calpain activation. ER stress and subsequent activated calpain play a critical role in skeletal muscle damage/wasting in burned rats. [ABSTRACT FROM AUTHOR]

Background: Children with moderate acute malnutrition (MAM) are treated with lipid-based nutrient supplement (LNS) or corn-soy blend (CSB). We assessed the effectiveness of (a) matrix, i.e., LNS or CSB, (b) soy quality, i.e., soy isolate (SI) or dehulled soy (DS), and (c) percentage of total protein from dry skimmed milk, i.e., 0%, 20%, or 50%, in increasing fat-free tissue accretion.Methods and Findings: Between September 9, 2013, and August 29, 2014, a randomised 2 × 2 × 3 factorial trial recruited 6- to 23-month-old children with MAM in Burkina Faso. The intervention comprised 12 weeks of food supplementation providing 500 kcal/day as LNS or CSB, each containing SI or DS, and 0%, 20%, or 50% of protein from milk. Fat-free mass (FFM) was assessed by deuterium dilution technique. By dividing FFM by length squared, the primary outcome was expressed independent of length as FFM index (FFMI) accretion over 12 weeks. Other outcomes comprised recovery rate and additional anthropometric measures. Of 1,609 children, 4 died, 61 were lost to follow-up, and 119 were transferred out due to supplementation being switched to non-experimental products. No children developed allergic reaction. At inclusion, 95% were breastfed, mean (SD) weight was 6.91 kg (0.93), with 83.5% (5.5) FFM. In the whole cohort, weight increased 0.90 kg (95% CI 0.88, 0.93; p < 0.01) comprising 93.5% (95% CI 89.5, 97.3) FFM. As compared to children who received CSB, FFMI accretion was increased by 0.083 kg/m2 (95% CI 0.003, 0.163; p = 0.042) in those who received LNS. In contrast, SI did not increase FFMI compared to DS (mean difference 0.038 kg/m2; 95% CI -0.041, 0.118; p = 0.35), irrespective of matrix. Having 20% milk protein was associated with 0.097 kg/m2 (95% CI -0.002, 0.196) greater FFMI accretion than having 0% milk protein, although this difference was not significant (p = 0.055), and there was no effect of 50% milk protein (0.049 kg/m2; 95% CI -0.047, 0.146; p = 0.32). There was no effect modification by season, admission criteria, or baseline FFMI, stunting, inflammation, or breastfeeding (p > 0.05). LNS compared to CSB resulted in 128 g (95% CI 67, 190; p < 0.01) greater weight gain if both contained SI, but there was no difference between LNS and CSB if both contained DS (mean difference 22 g; 95% CI -40, 84; p = 0.49) (interaction p = 0.017). Accordingly, SI compared to DS increased weight by 89 g (95% CI 27, 150; p = 0.005) when combined with LNS, but not when combined with CSB. A limitation of this and other food supplementation trials is that it is not possible to collect reliable data on individual adherence.Conclusions: Based on this study, children with MAM mainly gain fat-free tissue when rehabilitated. Nevertheless, LNS yields more fat-free tissue and higher recovery rates than CSB. Moreover, current LNSs with DS may be improved by shifting to SI. The role of milk relative to soy merits further research.Trial Registration: ISRCTN registry ISRCTN42569496. [ABSTRACT FROM AUTHOR]

Childhood wasting is a global problem and is significantly more pronounced in low and middle income countries like Bangladesh. Socio Economic Status (SES) and Water, Sanitation and Hygiene (WASH) practices may be significantly associated with wasting. Most previous research is consistent about the role of SES, but the significance of WASH in the context of wasting remains ambiguous. The effect of SES and WASH on weight for length (WHZ) is examined using a Structural Equation Model (SEM) to explicitly describe the direct and indirect role of WASH in the context of SES.A nationally representative survey of 10,478 Bangladeshi children under 5 were examined. An expert defined SEM was used to construct latent variables for SES and WASH. The SEM included a direct pathway from SES to WHZ and an indirect pathway from SES to WHZ via WASH along with regression of relevant covariates on the outcome WHZ and the latent variables. Both SES (p<0.01) and WASH (p<0.05) significantly affect WHZ. SES (p<0.01) also significantly affects WASH. Other structural components showed that child’s age (p<0.01) affects WHZ and types of residence (p<0.01) affects SES. WASH practices at least partially mediate the association between SES and wasting status. WASH and SES are both significantly associated with WHZ. [ABSTRACT FROM AUTHOR]

Sea star wasting disease devastated intertidal sea star populations from Mexico to Alaska between 2013–15, but little detail is known about its impacts to subtidal species. We assessed the impacts of sea star wasting disease in the Salish Sea, a Canadian / United States transboundary marine ecosystem, and world-wide hotspot for temperate asteroid species diversity with a high degree of endemism. We analyzed roving diver survey data for the three most common subtidal sea star species collected by trained volunteer scuba divers between 2006–15 in 5 basins and on the outer coast of Washington, as well as scientific strip transect data for 11 common subtidal asteroid taxa collected by scientific divers in the San Juan Islands during the spring/summer of 2014 and 2015. Our findings highlight differential susceptibility and impact of sea star wasting disease among asteroid species populations and lack of differences between basins or on Washington’s outer coast. Specifically, severe depletion of sunflower sea stars (Pycnopodia helianthoides) in the Salish Sea support reports of major declines in this species from California to Alaska, raising concern for the conservation of this ecologically important subtidal predator. [ABSTRACT FROM AUTHOR]

Porcine circovirus type 2 (PCV2), an economically important pathogen, causes postweaning multisystemic wasting syndrome (PMWS) and other syndrome diseases collectively known as porcine circovirus-associated disease (PCVAD). Previous studies revealed breed-dependent differences in porcine susceptibility to PCV2; however, the genetic mechanism underlying different resistance to PCV2 infection remains largely unknown. In this study, we found that Yorkshire × Landrace (YL) pigs exhibited serious clinical features typifying PCV2 disease, while the Laiwu (a Chinese indigenous pig breed, LW) pigs showed little clinical symptoms of the disease during PCV2 infection. At 35 days post infection (dpi), the PCV2 DNA copy in YL pigs was significantly higher than that in LW pigs (P < 0.05). The serum level of IL-4, IL-6, IL-8, IL-12 and TGF-β1 in LW pigs and TNF-α in YL pigs increased significantly at the early infected stages, respectively; while that of IL-10 and IFN-γ in YL pigs was greatly increased at 35 dpi. RNA-seq analysis revealed that, at 35 dpi, 83 genes were up-regulated and 86 genes were down-regulated in the lung tissues of LW pigs, while in YL pigs, the numbers were 187 and 18, respectively. In LW pigs, the differentially expressed genes (DEGs) were mainly involved in complement and coagulation cascades, metabolism of xenobiotics by cytochrome P450, RIG-I-like receptor signaling and B cell receptor signaling pathways. Four up-regulated genes (TFPI, SERPNC1, SERPNA1, and SERPNA5) that are enriched in complement and coagulation cascades pathway were identified in the PCV2-infected LW pigs, among which the mRNA expression of SERPNA1, as well as three genes including TGF-β1, TGF-β2 and VEGF that are regulated by SERPNA1 was significantly increased (P < 0.05). We speculate that higher expression of SERPNA1 may effectively suppress excessive inflammation reaction and reduce the pathological degree of lung tissue in PCV2-infected pigs. Collectively, our findings indicate that the susceptibility to PCV2 infection depends on a genetic difference between LW and YL pigs, and SERPNA1 likely plays an important role in the resistance of LW pigs to PCV2 infection. [ABSTRACT FROM AUTHOR]

Background: Wasting and stunting are global public health problems that frequently co-exist. However, they are usually separated in terms of policy, guidance, programming and financing. Though both wasting and stunting are manifestations of undernutrition caused by disease and poor diet, there are critical gaps in our understanding of the physiological relationship between them, and how interventions for one may affect the other. The aim of this exercise was to establish research priorities in the relationships between wasting and stunting to guide future research investments. Methods and Findings: We used the CHNRI (Child Health and Nutrition Research Initiative) methodology for setting research priorities in health. We utilised a group of experts in nutrition, growth and child health to prioritise 30 research questions against three criteria (answerability, usefulness and impact) using an online survey. Eighteen of 25 (72%) experts took part and prioritised research directly related to programming, particularly at the public health level. The highest-rated questions were: “Can interventions outside of the 1000 days, e.g. pre-school, school age and adolescence, lead to catch-up in height and in other developmental markers?”; “What timely interventions work to mitigate seasonal peaks in both wasting and stunting?”; and “What is the optimal formulation of ready-to-use foods to promote optimal ponderal growth and also support linear growth during and after recovery from severe acute malnutrition?” There was a high level of agreement between experts, particularly for the highest ranking questions. Conclusions: Increased commitment to rigorous evaluations of treatment and prevention interventions at the public health level, addressing questions of the timing of intervention, and the extent to which impacts for both wasting and stunting can be achieved, is needed to inform global efforts to tackle undernutrition and its consequences. [ABSTRACT FROM AUTHOR]

Sea star wasting disease (SSWD) first appeared in Oregon in April 2014, and by June had spread to most of the coast. Although delayed compared to areas to the north and south, SSWD was initially most intense in north and central Oregon and spread southward. Up to 90% of individuals showed signs of disease from June-August 2014. In rocky intertidal habitats, populations of the dominant sea star Pisaster ochraceus were rapidly depleted, with magnitudes of decline in density among sites ranging from -2x to -9x (59 to 84%) and of biomass from -2.6x to -15.8x (60 to 90%) by September 2014. The frequency of symptomatic individuals declined over winter and persisted at a low rate through the spring and summer 2015 (~5–15%, at most sites) and into fall 2015. Disease expression included six symptoms: initially with twisting arms, then deflation and/or lesions, lost arms, losing grip on substrate, and final disintegration. SSWD was disproportionally higher in orange individuals, and higher in tidepools. Although historically P. ochraceus recruitment has been low, from fall 2014 to spring 2015 an unprecedented surge of sea star recruitment occurred at all sites, ranging from ~7x to 300x greater than in 2014. The loss of adult and juvenile individuals in 2014 led to a dramatic decline in predation rate on mussels compared to the previous two decades. A proximate cause of wasting was likely the “Sea Star associated Densovirus” (SSaDV), but the ultimate factors triggering the epidemic, if any, remain unclear. Although warm temperature has been proposed as a possible trigger, SSWD in Oregon populations increased with cool temperatures. Since P. ochraceus is a keystone predator that can strongly influence the biodiversity and community structure of the intertidal community, major community-level responses to the disease are expected. However, predicting the specific impacts and time course of change across west coast meta-communities is difficult, suggesting the need for detailed coast-wide investigation of the effects of this outbreak. [ABSTRACT FROM AUTHOR]

An extensive 2013 mass mortality event along the West Coast of North America due to Sea Star Wasting Disease (SSWD) has affected at least 20 species of sea stars. Among environmental factors potentially contributing to the timing of the current outbreak, increased coastal water temperatures are hypothesized to have contributed to previous and current outbreaks of SSWD. With a laboratory experiment, we tested whether cooler temperatures, similar to average winter temperatures, compared to average summer temperatures could slow the progression of morbidity or prevent SSWD mortality entirely in Pisaster ochraceus. Sea stars housed in cooler water progressed through SSWD states more slowly than sea stars housed at summer temperatures. However, the cooler temperature did not prevent SSWD mortality, and all stars died of the disease. Our data are consistent with experimental studies and field observations during previous and current outbreaks, and support the hypothesis that changes in coastal water temperatures have influenced one of the largest disease related mass mortality events in our oceans. [ABSTRACT FROM AUTHOR]

We consider the problem of estimating the basic reproduction number R0 from data on prevalence dynamics at the beginning of a disease outbreak. We derive discrete and continuous time models, some coefficients of which are to be fitted from data. We show that prevalence of the disease is sufficient to determine R0. We apply this method to chronic wasting disease spread in Alberta determining a range of possible R0 and their sensitivity to the probability of deer annual survival. [ABSTRACT FROM AUTHOR]

Sea star wasting disease (SSWD) describes a suite of symptoms reported in asteroids of the North American Pacific Coast. We performed a metatranscriptomic survey of asymptomatic and symptomatic sunflower star (Pycnopodia helianthoides) body wall tissues to understand holobiont gene expression in tissues affected by SSWD. Metatranscriptomes were highly variable between replicate libraries, and most differentially expressed genes represented either transcripts of associated microorganisms (particularly Pseudomonas and Vibrio relatives) or low-level echinoderm transcripts of unknown function. However, the pattern of annotated host functional genes reflects enhanced apoptotic and tissue degradation processes and decreased energy metabolism, while signalling of death-related proteins was greater in asymptomatic and symptomatic tissues. Our results suggest that the body wall tissues of SSWD-affected asteroids may undergo structural changes during disease progression, and that they are stimulated to undergo autocatalytic cell death processes. [ABSTRACT FROM AUTHOR]

Prions enter the environment from infected hosts, bind to a wide range of soil and soil minerals, and remain highly infectious. Environmental sources of prions almost certainly contribute to the transmission of chronic wasting disease in cervids and scrapie in sheep and goats. While much is known about the introduction of prions into the environment and their interaction with soil, relatively little is known about prion degradation and inactivation by natural environmental processes. In this study, we examined the effect of repeated cycles of drying and wetting on prion fitness and determined that 10 cycles of repeated drying and wetting could reduce PrPSc abundance, PMCA amplification efficiency and extend the incubation period of disease. Importantly, prions bound to soil were more susceptible to inactivation by repeated cycles of drying and wetting compared to unbound prions, a result which may be due to conformational changes in soil-bound PrPSc or consolidation of the bonding between PrPSc and soil. This novel finding demonstrates that naturally-occurring environmental process can degrade prions. [ABSTRACT FROM AUTHOR]

Loss of muscle mass related to anti-cancer therapy is a major concern in cancer patients, being associated with important clinical endpoints including survival, treatment toxicity and patient-related outcomes. We investigated effects of voluntary exercise during cisplatin treatment on body weight, food intake as well as muscle mass, strength and signalling. Mice were treated weekly with 4 mg/kg cisplatin or saline for 6 weeks, and randomized to voluntary wheel running or not. Cisplatin treatment induced loss of body weight (29.8%, P<0.001), lean body mass (20.6%, P = 0.001), as well as anorexia, impaired muscle strength (22.5% decrease, P<0.001) and decreased glucose tolerance. In addition, cisplatin impaired Akt-signalling, induced genes related to protein degradation and inflammation, and reduced muscle glycogen content. Voluntary wheel running during treatment attenuated body weight loss by 50% (P<0.001), maintained lean body mass (P<0.001) and muscle strength (P<0.001), reversed anorexia and impairments in Akt and protein degradation signalling. Cisplatin-induced muscular inflammation was not prevented by voluntary wheel running, nor was glucose tolerance improved. Exercise training may preserve muscle mass in cancer patients receiving cisplatin treatment, potentially improving physical capacity, quality of life and overall survival. [ABSTRACT FROM AUTHOR]

Seagrass beds are the foundation species of functionally important coastal ecosystems worldwide. The world’s largest losses of the widespread seagrass Zostera marina (eelgrass) have been reported as a consequence of wasting disease, an infection with the endophytic protist Labyrinthula zosterae. During one of the most extended epidemics in the marine realm, ∼90% of East and Western Atlantic eelgrass beds died-off between 1932 and 1934. Today, small outbreaks continue to be reported, but the current extent of L. zosterae in European meadows is completely unknown. In this study we quantify the abundance and prevalence of the wasting disease pathogen among 19 Z. marina populations in northern European coastal waters, using quantitative PCR (QPCR) with primers targeting a species specific portion of the internally transcribed spacer (ITS1) of L. zosterae. Spatially, we found marked variation among sites with abundances varying between 0 and 126 cells mg−1Z. marina dry weight (mean: 5.7 L. zosterae cells mg−1Z. marina dry weight ±1.9 SE) and prevalences ranged from 0–88.9%. Temporarily, abundances varied between 0 and 271 cells mg−1Z. marina dry weight (mean: 8.5±2.6 SE), while prevalences ranged from zero in winter and early spring to 96% in summer. Field concentrations accessed via bulk DNA extraction and subsequent QPCR correlated well with prevalence data estimated via isolation and cultivation from live plant tissue. L. zosterae was not only detectable in black lesions, a sign of Labyrinthula-induced necrosis, but also occurred in green, apparently healthy tissue. We conclude that L. zosterae infection is common (84% infected populations) in (northern) European eelgrass populations with highest abundances during the summer months. In the light of global climate change and increasing rate of marine diseases our data provide a baseline for further studies on the causes of pathogenic outbreaks of L. zosterae. [ABSTRACT FROM AUTHOR]

The purpose of this study was to analyze whether nutritional status and body composition varies according to the environment of residence (urban or rural) of children in the Brandsen district (Argentina). Weight, height, arm circumference and tricipital and subscapular skinfolds were performed in 1368 schoolchildren aged 3 to 14. NHANES III reference was used to estimate nutritional status -underweight, stunting, wasting, overweight, and obesity- and to evaluate body composition - deficit and excess of adipose (DA, EA) and muscular (DM, EM) tissues of the arm-. Central fat distribution (CFD) was estimated using the subscapular-tricipital index. A structured questionnaire was implemented to evaluate socio-environmental characteristics. Nutritional categories based on body size and body composition were compared between urban and rural areas of residence using Chi-squared tests (χ2). The results indicated for the total sample: 1.1% underweight, 6.9% stunting, 0.4% wasting, 12.1% overweight, 9.7% obesity, 22.0% DM, 2.5% EM, 0.1% DA, 17.6% EA, and 8.5% CFD. Significant differences between urban and rural areas were found only for CFD. The socio-environmental analysis showed that while access to public services and housing quality was significantly better in the urban area, a considerable number of city households lived under deficient conditions, lacked health insurance and had low socioeconomic level. Fifty-three percent of the undernourished children had DM without urban-rural significant differences, and none of them showed DA. In the overweight plus obesity group, 62.8% presented EA, 6.4% EM, 4.7% DM, and 22.8% CFD. The highest percentages of DM and CFD were recorded in rural areas (p = 0.00). We conclude that the child population shows the "double burden" of malnutrition. The environment of residence does not promote any differentiation in the nutritional status. Nevertheless, the increment of central adiposity and, in some cases of muscle deficit in rural children, suggests a consumption of unbalanced diet. [ABSTRACT FROM AUTHOR]

Background: Like human immunodeficiency virus (HIV), ovine lentivirus (OvLV) is macrophage-tropic and causes lifelong infection. OvLV infects one quarter of U.S. sheep and induces pneumonia and body condition wasting. There is no vaccine to prevent OvLV infection and no cost-effective treatment for infected animals. However, breed differences in prevalence and proviral concentration have indicated a genetic basis for susceptibility to OvLV. A recent study identified TMEM154 variants in OvLV susceptibility. The objective here was to identify additional loci associated with odds and/or control of OvLV infection. Methodology/Principal Findings: This genome-wide association study (GWAS) included 964 sheep from Rambouillet, Polypay, and Columbia breeds with serological status and proviral concentration phenotypes. Analytic models accounted for breed and age, as well as genotype. This approach identified TMEM154 (nominal P = 9.2 x 10-7; empirical P = 0.13), provided 12 additional genomic regions associated with odds of infection, and provided 13 regions associated with control of infection (all nominal P<1 x 10-5). Rapid decline of linkage disequilibrium with distance suggested many regions included few genes each. Genes in regions associated with odds of infection included DPPA2/DPPA4 (empirical P = 0.006), and SYTL3 (P = 0.051). Genes in regions associated with control of infection included a zinc finger cluster (ZNF192, ZSCAN16, ZNF389, and ZNF165; P = 0.001), C19orf42/TMEM38A (P = 0.047), and DLGAP1 (P = 0.092). Conclusions/Significance: These associations provide targets for mutation discovery in sheep susceptibility to OvLV. Aside from TMEM154, these genes have not been associated previously with lentiviral infection in any species, to our knowledge. Further, data from other species suggest functional hypotheses for future testing of these genes in OvLV and other lentiviral infections. Specifically, SYTL3 binds and may regulate RAB27A, which is required for enveloped virus assembly of human cytomegalovirus. Zinc finger transcription factors have been associated with positive selection for repression of retroviral replication. DLGAP1 binds and may regulate DLG1, a known regulator of HIV infectivity. [ABSTRACT FROM AUTHOR]

Translation elongation factor isoform eEF1A2 is expressed in muscle and neurons. Deletion of eEF1A2 in mice gives rise to the neurodegenerative phenotype ''wasted'' (wst). Mice homozygous for the wasted mutation die of muscle wasting and neurodegeneration at four weeks post-natal. Although the mutation is said to be recessive, aged heterozygous mice have never been examined in detail; a number of other mouse models of motor neuron degeneration have recently been shown to have similar, albeit less severe, phenotypic abnormalities in the heterozygous state. We therefore examined the effects of ageing on a cohort of heterozygous +/wst mice and control mice, in order to establish whether a presumed 50% reduction in eEF1A2 expression was compatible with normal function. We evaluated the grip strength assay as a way of distinguishing between wasted and wild-type mice at 3-4 weeks, and then performed the same assay in older +/wst and wild-type mice. We also used rotarod performance and immunohistochemistry of spinal cord sections to evaluate the phenotype of aged heterozygous mice. Heterozygous mutant mice showed no deficit in neuromuscular function or signs of spinal cord pathology, in spite of the low levels of eEF1A2. [ABSTRACT FROM AUTHOR]

Background: Despite remarkable progress in reducing under five mortalities in Malawi, a relative proportion of under nutrition among children still exist., Objectives: The study examines dietary consumption factors and their effect on under nutrition outcomes among children under five years' children in rural Malawi., Methods: Using the 2015-16 Malawi Demographic and Health Survey, in which 4,150 children were reported of under nutrition statuses, the study used nested logistic regression models to estimate factors influencing the prevalence of under nutrition among children., Results: Based on the results, exclusive breast feeding among children under five years, after controlling for parental socioeconomic factors, was found to reduce the levels of wasting (ODDS RATIO [OR] = 0.763; p < 0.05), underweight (OR = 0.548; p < 0.001) and stunting (OR = 0.709; p < 0.005). Furthermore, it was found that despite the perceived adequacy among women in accessing fruits and vegetables, carbohydrates and micro-nutrient supplements, their children under five years, still experiences public health challenges and suffers from wasting, underweight and stunting., Conclusion: There is need to implement extensive pro-rural under five nutritional and health educational advocacy using community-based approaches, targeting parents, emphasizing the significance of exclusive breast feeding and consistencies in giving dietary foods, if and only if the persistent public health challenges due to under nutrition among children under five years, is to be sustainably dealt with, in Malawi., Competing Interests: The authors have declared that no competing interest exists.

Inflammation is a key pathological characteristic of dystrophic muscle lesion formation, limiting muscle regeneration and resulting in fibrotic and fatty tissue replacement of muscle, which exacerbates the wasting process in dystrophic muscles. Limiting immune response is thus one of the therapeutic options to improve healing, as well as to improve the efficacy of gene- or cell-mediated strategies to restore dystrophin expression. Protein kinase C θ (PKCθ) is a member of the PKCs family highly expressed in both immune cells and skeletal muscle; given its crucial role in adaptive, but also innate, immunity, it is being proposed as a valuable pharmacological target for immune disorders. In our study we asked whether targeting PKCθ could represent a valuable approach to efficiently prevent inflammatory response and disease progression in a mouse model of muscular dystrophy. We generated the bi-genetic mouse model mdx/θ(-/-), where PKCθ expression is lacking in mdx mice, the mouse model of Duchenne muscular dystrophy. We found that muscle wasting in mdx/θ(-/-) mice was greatly prevented, while muscle regeneration, maintenance and performance was significantly improved, as compared to mdx mice. This phenotype was associated to reduction in inflammatory infiltrate, pro-inflammatory gene expression and pro-fibrotic markers activity, as compared to mdx mice. Moreover, BM transplantation experiments demonstrated that the phenotype observed was primarily dependent on lack of PKCθ expression in hematopoietic cells.These results demonstrate a hitherto unrecognized role of immune-cell intrinsic PKCθ activity in the development of DMD. Although the immune cell population(s) involved remain unidentified, our findings reveal that PKCθ can be proposed as a new pharmacological target to counteract the disease, as well as to improve the efficacy of gene- or cell- therapy approaches.