RESUMO
Niger is afflicted with high rates of poverty, high fertility rates, frequent environmental crises, and climate change. Recurrent droughts and floods have led to chronic food insecurity linked to poor maternal and neonatal nutrition outcomes in vulnerable regions. We analyzed maternal and neonatal nutrition trends and subnational variability between 2000 and 2021 with a focus on the implementation of policies and programs surrounding two acute climate shocks in 2005 and 2010. We used four sources of data: (a) national household surveys for maternal and newborn nutritional indicators allowing computation of trends and differences at national and regional levels; (b) document review of food security reports; (c) 30 key informant interviews and; (d) one focus group discussion. Many food security policies and nutrition programs were enacted from 2000 to 2020. Gains in maternal and neonatal nutrition indicators were more significant in targeted vulnerable regions of Maradi, Zinder, Tahoua and Tillabéri, from 2006 to 2021. However, poor access to financial resources for policy execution and suboptimal implementation of plans have hindered progress. In response to the chronic climate crisis over the last 20 years, the Nigerien government and program implementers have demonstrated their commitment to reducing food insecurity and enhancing resilience to climate shocks by adopting a deliberate multisectoral effort. However, there is more that can be achieved with a continued focus on vulnerable regions to build resilience, targeting high risk populations, and investing in infrastructure to improve health systems, food systems, agriculture systems, education systems, and social protection.
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Abastecimento de Alimentos , Estado Nutricional , Recém-Nascido , Humanos , Níger/epidemiologia , Segurança Alimentar , PolíticasRESUMO
BACKGROUND: Counseling on infant and young child feeding (IYCF) to support optimal breastfeeding and complementary feeding practices is an essential intervention, and accurate coverage data is needed to identify gaps and monitor progress. However, coverage information captured during household surveys has not yet been validated. OBJECTIVES: We examined the validity of maternal reports of IYCF counseling received during community-based contacts and factors associated with reporting accuracy. METHODS: Direct observations of home visits conducted by community workers in 40 villages in Bihar, India served as the "gold standard" to maternal reports of IYCF counseling received during 2-wk follow-up surveys (n = 444 mothers with children less than 1 y of age, interviews matched to direct observations). Individual-level validity was assessed by calculating sensitivity, specificity, and AUC. Population-level bias was measured using the inflation factor (IF). Multivariable regression models were used to examine factors associated with response accuracy. RESULTS: Prevalence of IYCF counseling during home visits was very high (90.1%). Maternal report of any IYCF counseling received in the past 2 wk was moderate (AUC: 0.60; 95% CI: 0.52, 0.67), and population bias was low (IF = 0.90). However, the recall of specific counseling messages varied. Maternal report of any breastfeeding, exclusive breastfeeding, and dietary diversity messages had moderate validity (AUC > 0.60), but other child feeding messages had low individual validity. Child age, maternal age, maternal education, mental stress, and social desirability were associated with reporting accuracy of multiple indicators. CONCLUSIONS: Validity of IYCF counseling coverage was moderate for several key indicators. IYCF counseling is an information-based intervention that may be received from various sources, and it may be challenging to achieve higher reporting accuracy over a longer recall period. We consider the modest validity results as positive and suggest that these coverage indicators may be useful for measuring coverage and tracking progress over time.
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Aleitamento Materno , Fenômenos Fisiológicos da Nutrição do Lactente , Feminino , Humanos , Lactente , Criança , Aconselhamento , Mães/psicologia , Dieta , Comportamento AlimentarRESUMO
The health sector plays an important role in the delivery of high-quality nutrition interventions to women and children in low- and middle-income countries (LMICs). However, there are no standardized approaches to defining and measuring nutrition service quality in these contexts. This study aims to systematically develop quality of care indices for direct health systems nutrition interventions using a five-step process: (1) identify recommended interventions for inclusion in indices, (2) extract service readiness, provision of care, and experience of care items from intervention-specific clinical guidelines, (3) map items to data available in global health facility surveys, (4) conduct an expert survey to prioritize interventions and items, and (5) use findings from previous steps to propose quality of care metrics. Thirty-two recommended interventions were identified, for which the guidelines review yielded 763 unique items that were reviewed by experts. The proposed nutrition quality of care indices for pregnant women reflects eight interventions and the indices for children under 5 reflects six interventions. The indices provide a standardized measure for nutrition intervention quality and can be operationalized using existing health facility assessment data, facilitating their use by LMIC decision makers for planning and resource allocation.
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Instalações de Saúde , Gestantes , Criança , Países em Desenvolvimento , Feminino , Programas Governamentais , Humanos , Estado Nutricional , Pobreza , GravidezRESUMO
BACKGROUND: Therapeutic vaccines against cervical cancer remain ineffective. Previously, we demonstrated that blocking the signalling of a cytokine, interleukin 10, at the time of immunisation elicited significantly higher numbers of antigen specific T cells and inhibited tumour growth in mice. RESULTS: In the current paper, we demonstrate, in a HPV16 E6/E7 transformed TC-1 tumour mouse model, that despite increased antigen specific T cell numbers, blocking IL-10 signalling at the time of immunisation does not increase the survival time of the TC-1 tumour bearing mice compared to mice receiving the same immunisation with no IL-10 signalling blockade. Moreover, the function of tumour infiltrating T cells isolated 3 weeks post TC-1 transplantation is more suppressed than those isolated 2 weeks after tumour inoculation. We demonstrate that synthesized caerin peptides, derived from amphibian skin secretions, 1) were able to inhibit TC-1 tumour growth both in vitro and in vivo; 2) are environmentally stable; and 3) promote the secretion of pro-inflammatory interlukine-6 by TC-1 cells. Notably caerin peptides were able to increase the survival time of TC-1 tumour bearing mice after therapeutic vaccination with a HPV16E7 peptide-based vaccine containing IL-10 inhibitor, via recruiting increased levels of T cells to the tumour site. CONCLUSION: Caerin peptides increase the efficacy of a therapeutic vaccine by recruiting more T cells to the tumour site.
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Proteínas de Anfíbios/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Vacinas Anticâncer/uso terapêutico , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Proteínas de Anfíbios/uso terapêutico , Animais , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Vacinas Anticâncer/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Células HeLa , Humanos , Interleucina-10/antagonistas & inibidores , Interleucina-6/metabolismo , Linfócitos do Interstício Tumoral/metabolismo , Camundongos Endogâmicos C57BL , Transplante de Neoplasias , Neoplasias Experimentais/tratamento farmacológico , Linfócitos T/metabolismoRESUMO
Moxidectin is under consideration for development as a treatment for human scabies. As some arthropods show decreased sensitivity to moxidectin relative to ivermectin, it was important to assess this for Sarcoptes scabieiIn vitro assays showed that the concentration of moxidectin required to kill 50% of mites was lower than that of ivermectin (0.5 µM versus 1.8 µM at 24 h; P < 0.0001). This finding provides further support for moxidectin as a candidate for the treatment of human scabies.
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Acaricidas/uso terapêutico , Ivermectina/uso terapêutico , Macrolídeos/uso terapêutico , Sarcoptes scabiei/efeitos dos fármacos , Escabiose/tratamento farmacológico , Animais , Feminino , Humanos , Masculino , Análise de SobrevidaRESUMO
Realistic planning for a nutrition intervention is a critical component of implementation, yet effective approaches have been poorly documented. Under the auspices of "The Micronutrient Powders Consultation: Lessons Learned for Operational Guidance," 3 working groups were formed to summarize experiences and lessons across countries regarding micronutrient powders (MNP) interventions for young children. This paper focuses on programmatic experiences in the planning stages of an MNP intervention, encompassing assessment, enabling environment and adaptation, as well as considerations for supply. Methods included a review of published and grey literature, key informant interviews, and deliberations throughout the consultation process. We found that assessments helped justify adopting an MNP intervention, but these assessments were often limited by their narrow scope and inadequate data. Establishing coordinating bodies and integrating MNP into existing policies and programmes have helped foster an enabling environment and support programme stability. Formative research and pilots have been used to adapt MNP interventions to specific contexts, but they have been insufficient to inform scale-up. In terms of supply, most countries have opted to procure MNP through international suppliers, but this still requires understanding and navigating the local regulatory environment at the earliest stages of an intervention. Overall, these findings indicate that although some key planning and supply activities are generally undertaken, improvements are needed to plan for effective scale-up. Much still needs to be learned on MNP planning, and we propose a set of research questions that require further investigation.
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Anemia Ferropriva/prevenção & controle , Anemia/prevenção & controle , Planejamento em Saúde , Micronutrientes/administração & dosagem , Avaliação de Programas e Projetos de Saúde , Suplementos Nutricionais , Assistência Alimentar/organização & administração , Assistência Alimentar/estatística & dados numéricos , Alimentos Fortificados , Implementação de Plano de Saúde , Planejamento em Saúde/métodos , Promoção da Saúde , Humanos , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente , Micronutrientes/deficiência , Micronutrientes/provisão & distribuição , Pobreza , Pós , Estados Unidos , United States Agency for International DevelopmentRESUMO
Corn Soy Blend (CSB) porridge is commonly prepared with oil for treatment of moderate acute malnutrition (MAM). A recent review recommended that 30 g of oil be used with 100 g of CSB to increase energy density and micronutrient absorption. This study assessed the effectiveness and cost-effectiveness of program changes aimed at achieving that target oil:CSB ratio in prepared porridge. Caregivers of children in MAM supplementary feeding programs were assigned to three groups: a control group received monthly rations of 1 L oil, 8 kg CSB in bulk, and social and behavior change communication (SBCC); intervention groups received 2.6 L oil, 8 kg CSB provided either in bulk (Group 1) or four 2-kg packages with printed messages (Group 2), and enhanced SBCC emphasizing the target oil:CSB ratio. Compared to the control, both intervention groups had higher mean added oil per 100 g CSB (18 g, p < 0.01, and 13 g, p= 0.04, higher in groups 1 and 2, respectively), and greater odds of meeting or exceeding the target ratio (28.4, p< 0.01, and 12.7, p= 0.02, in groups 1 and 2, respectively). Cost per caregiver reaching the target ratio was most favorable in Group 1 ($391 in Group 1, $527 in Group 2, and $1,666 in the control). Enhanced SBCC combined with increased oil ration resulted in increased use of oil in CSB porridge in a supplementary feeding program. Modified packaging did not improve effectiveness. However, both interventions were more cost-effective than standard programming.
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Análise Custo-Benefício , Alimentos Fortificados , Glycine max , Desnutrição/dietoterapia , Óleos de Plantas/administração & dosagem , Zea mays , Doença Aguda , Adulto , Pré-Escolar , Estudos Transversais , Dieta/economia , Humanos , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente , Malaui/epidemiologia , Desnutrição/economia , Micronutrientes/administração & dosagem , Micronutrientes/análise , Óleos de Plantas/química , Tamanho da Amostra , Fatores Socioeconômicos , Adulto JovemRESUMO
Interleukin 10 is a cytokine with the ability to reduce or terminate inflammation. Chronic viral infection, such as infection of chronic hepatitis B, hepatitis C and HIV, has increased levels of interleukin 10 in peripheral blood. Serum IL-10 levels are also high in certain cancers. Blocking IL-10 signalling at the time of immunisation clears chronic viral infection and prevents tumour growth in animal models. We review recent advances in this area, with the emphasis on potential use of this novel strategy to treat chronic viral infection and cancer in human.
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Infecções por HIV/imunologia , Hepatite B Crônica/imunologia , Hepatite C Crônica/imunologia , Interleucina-10/imunologia , Transdução de Sinais/imunologia , Linfócitos T/imunologia , Animais , Infecções por HIV/terapia , Hepatite B Crônica/terapia , Hepatite C Crônica/terapia , Humanos , Imunoterapia , Linfócitos T/virologiaRESUMO
BACKGROUND: Scabies is an ancient disease (documented as far back as 2500 years ago). It affects about 300 million people annually worldwide, and the prevalence is as high as about 60% in Indigenous and Torres Strait Islander children in Australia. This is more than six times the rate seen in the rest of the developed world. Scabies is frequently complicated by bacterial infection leading to the development of skin sores and other more serious consequences such as septicaemia and chronic heart and kidney diseases. This causes a substantial social and economic burden especially in resource poor communities around the world. DISCUSSION: Very few treatment options are currently available for the management of scabies infection. In this manuscript we briefly discuss the clinical consequences of scabies and the problems found (studies conducted in Australia) with the currently used topical and oral treatments. Current scabies treatment options are fairly ineffective in preventing treatment relapse, inflammatory skin reactions and associated bacterial skin infections. None have ovicidal, antibacterial, anti-inflammatory and/or anti-pruritic properties. Treatments which are currently available for scabies can be problematic with adverse effects and perhaps of greater concern the risk of treatment failure. The development of new chemical entities is doubtful in the near future. Though there may be potential for immunological control, the development of a vaccine or other immunotherapy modalities may be decades away. The emergence of resistance among scabies mites to classical scabicides and ineffectiveness of current treatments (in reducing inflammatory skin reactions and secondary bacterial infections associated with scabies), raise serious concerns regarding current therapy. Treatment adherence difficulties, and safety and efficacy uncertainties in the young and elderly, all signal the need to identify new treatments for scabies.
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Escabiose/terapia , Austrália/epidemiologia , Criança , Humanos , Imunoterapia , Prevalência , Escabiose/epidemiologiaRESUMO
Scabies is an infectious disease that is endemic in poorly resourced communities, and also common in industrialized countries. Although the disease, which is caused by infestation of Sarcoptes scabiei, is generally mild, the need for a vaccine against S. scabiei is proposed. The immunological mechanisms that control S. scabiei infection are discussed and the current status of scabies vaccine development reviewed. Future directions for scabies vaccine development are also addressed.
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Sarcoptes scabiei/imunologia , Escabiose/imunologia , Vacinas/imunologia , Animais , Humanos , Escabiose/prevenção & controleRESUMO
INTRODUCTION: Recent modelled estimates suggest that Niger made progress in maternal mortality since 2000. However, neonatal mortality has not declined since 2012 and maternal mortality estimates were based on limited data. We researched the drivers of progress and challenges. METHODS: We reviewed two decades of health policies, analysed mortality trends from United Nations data and six national household surveys between 1998 and 2021 and assessed coverage and inequalities of maternal and newborn health indicators. Quality of care was evaluated from health facility surveys in 2015 and 2019 and emergency obstetric assessments in 2011 and 2017. We determined the impact of intervention coverage on maternal and neonatal lives saved between 2000 and 2020. We interviewed 31 key informants to understand the factors underpinning policy implementation. RESULTS: Empirical maternal mortality ratio declined from 709 to 520 per 100 000 live births during 2000-2011, while neonatal mortality rate declined from 46 to 23 per 1000 live births during 2000-2012 then increased to 43 in 2018. Inequalities in neonatal mortality were reduced across socioeconomic and demographic strata. Key maternal and newborn health indicators improved over 2000-2012, except for caesarean sections, although the overall levels were low. Interventions delivered during childbirth saved most maternal and newborn lives. Progress came from health centre expansion, emergency care and the 2006 fee exemptions policy. During the past decade, challenges included expansion of emergency care, continued high fertility, security issues, financing and health workforce. Social determinants saw minimal change. CONCLUSIONS: Niger reduced maternal and neonatal mortality during 2000-2012, but progress has stalled. Further reductions require strategies targeting comprehensive care, referrals, quality of care, fertility reduction, social determinants and improved security nationwide.
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Mortalidade Infantil , Mortalidade Materna , Humanos , Níger , Mortalidade Materna/tendências , Recém-Nascido , Feminino , Mortalidade Infantil/tendências , Gravidez , Lactente , Serviços de Saúde Materna/normas , Política de Saúde , Qualidade da Assistência à Saúde , AdultoRESUMO
PURPOSE OF REVIEW: We propose that a major gap in the control, prevention, diagnosis and treatment of scabies exists because of lack of key translational understandings related to the immunopathology of scabies and the associated severe form of the disease, crusted scabies. Understanding the complex network of innate and adaptive immune responses, including the long lag period from infection to clinical symptoms, is fundamental to developing early interventions and decreasing transmission. Such interventions must be driven by clinical need and include user-friendly translational outcomes for improved control in endemic and resource-poor settings. RECENT FINDINGS: In the last few years, we have seen an increase in the molecular characterization of scabies mite proteins. However, owing to limited capacity in scabies immunology-related research, little is still known regarding the immunological effects of the mite or mite products on disease progression or protection. SUMMARY: Detailing the skin immunopathogenesis in relation to scabies, including the role of macrophages, mast cells and eosinophils, as well as the immunomodulatory effects of parasite evasion mechanisms are essential for the rational design of future therapeutic, diagnostic and preventative tools. Resolving this knowledge gap could ultimately lead to significant improvements in clinical and public health interventions. This article proposes a conceptual model for capacity building to inform future research activities in the field.
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Imunidade Adaptativa , Imunidade Inata , Escabiose/imunologia , Citocinas/imunologia , Interações Hospedeiro-Parasita/imunologia , Humanos , Evasão da Resposta Imune/imunologia , Pele/imunologia , Linfócitos T/imunologia , Vacinas/imunologiaRESUMO
Scabies, a human skin infestation caused by the ectoparasitic mite Sarcoptes scabiei var. hominis, affects more than 200 million people globally. The prevailing knowledge of the disease process and host immune response mechanisms is limited. A better understanding of the host-parasite relationship is essential for the identification of novel vaccine and drug targets. Here we aimed to interrogate the transcriptomic profiles of mite-infested human skin biopsies with clinical manifestations of ordinary scabies subjects ("OS"; n = 05) and subjects naive to scabies ("control"; n = 03) using RNASeq data analysis. A combined clustering, network, and pathway mapping approach enabled us to identify key signaling events in the host immune and pro-inflammatory responses to S. scabiei infestation. The clustering patterns showed various differentially expressed genes including inflammatory responses and innate immunity genes (DEFB4A, IL-19, CXCL8, CSF3, SERPINB4, S100A7A, HRNR) and notably upregulation of the JAK-STAT pathway in scabies-infested samples. Mite-infested human skin biopsies (GSE178563) were compared with an ex-vivo porcine infested model (E-MTAB-6433) and human skin equivalents (GSE48459). Marked enrichment of immune response pathways (JAK-STAT signaling, IL-4 and IL-13 pathway, and Toll receptor cascade), chemokine ligands and receptors (CCL17, CCL18, CCL3L1, CCL3L3, CCR7), and cytokines (IL-13 and IL-20) were observed. Additionally, genes known for their role in psoriasis and atopic dermatitis were upregulated, e.g., IL-19. The detailed transcriptomic profile has provided an insight into molecular functions, biological processes, and immunological responses and increased our understanding about transcriptomic regulation of scabies in human.
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Perfilação da Expressão Gênica , Interações Hospedeiro-Parasita , Inflamação/etiologia , Escabiose/imunologia , Adolescente , Adulto , Animais , Criança , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , RNA-Seq , Sarcoptes scabiei/imunologia , Escabiose/genética , Pele/metabolismo , Suínos , Adulto JovemRESUMO
Examining the role of environmental enteric dysfunction (EED) in child growth requires noninvasive, field-appropriate biomarkers. Alternatives to the traditionally used lactulose:mannitol (L:M) test have been explored, but few studies have compared the L:M test to host fecal mRNA transcripts. The objectives of this study were to examine whether 1) host fecal mRNA transcripts could predict presence and severity of EED, measured using the L:M test, and 2) EED modifies the effect of specialized nutritious foods (SNFs) on recovery from moderate acute malnutrition (MAM). This substudy was nested within a cluster randomized trial comparing four SNFs in the treatment of MAM among children 6 to 59 months in Sierra Leone. EED was assessed at enrollment using the L:M test and 15 host fecal mRNA transcripts on 522 children. Recovery from MAM was defined as achieving mid-upper arm circumference ≥ 12.5 cm within 12 weeks of supplementation. Random forest classification models were used to examine prediction of presence and severity of EED by host fecal mRNA transcripts. Logistic regression was used to test for effect modification by L:M test variables including % lactulose excreted (%L). Eight host fecal mRNA transcripts (AQP9, REG3A, IFI30, DECR1, BIRC3, SELL, PIK3AP1, DEFA6) identified EED (%L ≥ 0.2) and severe EED (%L ≥ 0.45) with high sensitivity and specificity. The L:M test variables did not modify the effect of SNFs on recovery from MAM. In this study, we found host fecal mRNA transcripts that could be biomarkers of EED but did not find EED to modify the effect of SNFs on MAM treatment.
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Biomarcadores/análise , Testes Diagnósticos de Rotina/normas , Fezes/química , Desnutrição/diagnóstico , Guias de Prática Clínica como Assunto , RNA Mensageiro/análise , Pré-Escolar , Feminino , Previsões , Humanos , Lactente , Masculino , Valor Preditivo dos Testes , Serra LeoaRESUMO
BACKGROUND: Moderate acute malnutrition (MAM) affects 33 million children annually. Investments in formulations of corn-soy blended flours and lipid-based nutrient supplements have effectively improved MAM recovery rates. Information costs and cost-effectiveness differences are still needed. OBJECTIVES: We assessed recovery and sustained recovery rates of MAM children receiving a supplementary food: ready-to-use supplementary food (RUSF), corn soy whey blend with fortified vegetable oil (CSWB w/oil), or Super Cereal Plus with amylase (SC + A) compared to Corn Soy Blend Plus with fortified vegetable oil (CSB+ w/oil). We also estimated differences in costs and cost effectiveness of each supplement. METHODS: In Sierra Leone, we randomly assigned 29 health centers to provide a supplement containing 550 kcal/d for â¼12 wk to 2691 children with MAM aged 6-59 mo. We calculated cost per enrollee, cost per child who recovered, and cost per child who sustained recovery each from 2 perspectives: program perspective and caregiver perspective, combined. RESULTS: Of 2653 MAM children (98.6%) with complete data, 1676 children (63%) recovered. There were no significant differences in the odds of recovery compared to CSB+ w/oil [0.83 (95% CI: 0.64-1.08) for CSWB w/oil, 1.01 (95% CI: 0.78-1.3) for SC + A, 1.05 (95% CI: 0.82-1.34) for RUSF]. The odds of sustaining recovery were significantly lower for RUSF (0.7; 95% CI 0.49-0.99) but not CSWB w/oil or SC + A [1.08 (95% CI: 0.73-1.6) and 0.96 (95% CI: 0.67-1.4), respectively] when compared to CSB+ w/oil. Costs per enrollee [US dollars (USD)/child] ranged from $105/child in RUSF to $112/child in SC + A and costs per recovered child (USD/child) ranged from $163/child in RUSF to $179/child in CSWB w/oil, with overlapping uncertainty ranges. Costs were highest per sustained recovery (USD/child), ranging from $214/child with the CSB+ w/oil to $226/child with the SC + A, with overlapping uncertainty ranges. CONCLUSIONS: The 4 supplements performed similarly across recovery (but not sustained recovery) and costed measures. Analyses of posttreatment outcomes are necessary to estimate the full cost of MAM treatment. This trial was registered at clinicaltrials.gov as NCT03146897.
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Transtornos da Nutrição Infantil/dietoterapia , Análise Custo-Benefício , Suplementos Nutricionais , Alimentos Formulados/análise , Alimentos Formulados/economia , Transtornos da Nutrição Infantil/epidemiologia , Pré-Escolar , Análise por Conglomerados , Feminino , Humanos , Lactente , Masculino , Serra Leoa/epidemiologiaRESUMO
Sarcoptes scabiei is a causative organism for scabies that affects an estimated global population of 300 million and remains a disease of significant concern. Recently, a number of potential drug targets were identified for scabies, including hydrolytic enzymes, inactivated paralogues of hydrolytic enzymes, inhibitors of host proteolytic enzymes and other proteins of interest. These discoveries remain confined to academic laboratories and institutions, failing to attract interest from researchers in commercial drug development. Here, we summarize the latest developments in the scabies mite biology and the drug targets that were subsequently identified, and we propose several peptide and nonpeptide ligands targeting the hot spots for protein-protein interactions. We also identify gaps in the development of ligands as inhibitors or modulators of these macromolecules.
Assuntos
Preparações Farmacêuticas/química , Sarcoptes scabiei/efeitos dos fármacos , Escabiose/tratamento farmacológico , Animais , Química Farmacêutica , Humanos , Ligantes , Estrutura MolecularRESUMO
Interleukin 10 (IL-10) belongs to IL-10 family cytokines that are critical for maintaining the integrity of epithelial tissues, protecting pathogenic infection, and preventing excessive immune responses to damage self. Temporal IL-10 signaling blockade enhances vaccine-induced tumor regression by CD8 + T cells. IL-10, especially pegylated IL-10, mediates tumor regression by expanding tumor-infiltrating CD8 + T cells. Moreover, targeting IL-10 enhances immune checkpoint inhibitor mediated tumor regression. In the current paper, we will review recent advances in this area and discuss the complexity of IL-10 manipulation for cancer therapy.
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Interleucina-10 , Neoplasias , Linfócitos T CD8-Positivos , Citocinas , Humanos , Imunoterapia , Interleucina-15 , Interleucina-2 , Neoplasias/terapiaRESUMO
Scabies is a neglected tropical disease of global significance. Our understanding of host-parasite interactions has been limited, particularly in crusted scabies (CS), a severe clinical manifestation involving hyper-infestation of Sarcoptes scabiei mites. Susceptibility to CS may be associated with immunosuppressive conditions but CS has also been seen in cases with no identifiable risk factor or immune deficit. Due to ethical and logistical difficulties with undertaking research on clinical patients with CS, we adopted a porcine model which parallels human clinical manifestations. Transcriptomic analysis using microarrays was used to explore scabies pathogenesis, and to identify early events differentiating pigs with ordinary (OS) and crusted scabies. Pigs with OS (n = 4), CS (n = 4) and non-infested controls (n = 4) were compared at pre-infestation, weeks 1, 2, 4 and 8 post-infestation. In CS relative to OS, there were numerous differentially expressed genes including pro-inflammatory cytokines (IL17A, IL8, IL19, IL20 and OSM) and chemokines involved in immune cell activation and recruitment (CCL20, CCL27 and CXCL6). The influence of genes associated with immune regulation (CD274/PD-L1 and IL27), immune signalling (TLR2, TLR8) and antigen presentation (RFX5, HLA-5 and HLA-DOB) were highlighted in the early host response to CS. We observed similarities with gene expression profiles associated with psoriasis and atopic dermatitis and confirmed previous observations of Th2/17 pronounced responses in CS. This is the first comprehensive study describing transcriptional changes associated with the development of CS and significantly, the distinction between OS and CS. This provides a basis for clinical follow-up studies, potentially identifying new control strategies for this severely debilitating disease.
Assuntos
Interações Hospedeiro-Parasita/imunologia , Sarcoptes scabiei/imunologia , Escabiose/veterinária , Sus scrofa/imunologia , Sus scrofa/parasitologia , Animais , Citocinas/genética , Citocinas/imunologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/genética , Imunomodulação/imunologia , Escabiose/imunologia , Escabiose/patologia , Pele/imunologia , Pele/parasitologia , Pele/patologia , Suínos , Doenças dos Suínos/imunologia , Doenças dos Suínos/parasitologia , Células Th17/imunologia , Células Th2/imunologia , Transcriptoma/genéticaRESUMO
Host defense caerin 1.1 and 1.9 peptides, isolated from the glandular secretion of Australian tree frogs, the genus Litoria, have been previously shown to have multiple biological activities, including the inhibition of human papillomavirus (HPV) 16 early protein E7 transformed murine as well as human cancerous cell proliferation both in vitro and in vivo. However, the mechanism underlying their anti-proliferative activities against HPV18+ cervical cancer HeLa cells remains unknown. This study comparatively investigated the anti-proliferation on HeLa cells by caerin 1.1, 1.9, and their mixture, followed by confocal microscopy examination to assess the cellular intake of the peptides. Tandem mass tag labeling proteomics was employed to reveal the proteins that were significantly regulated by the peptide treatment in cells and cell growth environment, to elucidate the signaling pathways that were modulated. Western blot was performed to confirm the modulation of the pathways. Both caerin 1.1 and 1.9 highly inhibited HeLa cell proliferation with a significant additive effect compared to untreated and control peptide. They entered the cells with different magnitudes. Intensive protein-protein interaction was detected among significantly upregulated proteins. Translation, folding and localization of proteins and RNA processing, apoptosis process was significantly enriched post the treatments. The apoptotic signaling was suggested as a result of tumor necrosis factor-α (TNF-α) pathway activation, indicated by the dose-dependent elevated levels of caspase 3 and caspase 9. The epidermal growth factor receptor and androgen receptor pathways appeared inhibited by the peptides. Moreover, the activation of T-cell receptor derived from the quantitation results further implies the likelihood of recruiting more T cells to the cell growth environment post the treatment and more sensitive to T cell mediated killing of HeLa cells. Our results indicate that caerin 1.1 and 1.9 mediate apoptotic signals of HeLa cells and may subsequently enhances adaptive T cell immune responses.
RESUMO
BACKGROUND: A trial in Burkina Faso compared the cost-effectiveness of 4 specialized nutritious foods (SNFs) used to prevent stunting and wasting in children aged 6-23 mo. OBJECTIVES: This article explores differences in SNF use that may have influenced effectiveness, specifically in relation to consumption by the recipient child and by any other person (i.e., sharing), other diversion from the recipient child, preparation, storage, and hygiene. METHODS: Subsamples from a geographically clustered, longitudinal trial with random assignment to Corn Soy Blend Plus with oil (CSB+ w/oil), Corn Soy Whey Blend with oil (CSWB w/oil), Super Cereal Plus (SC+), or ready-to-use supplementary food (RUSF) were selected for in-depth interviews, in-home observations, and focus group discussions. RESULTS: Sharing was common in all arms, with the highest reported in SC+ (73%) and highest observed in CSWB w/oil (36%). Some reported giving the ration away (highest in SC+ at 17%) or using it for other purposes (highest in CSWB w/oil at 17%). The recipient child was observed consuming the ration in 49% of households on average (38-60% by arm in CSB+ w/oil and RUSF, respectively). Qualitative reports of bitterness and spoilage emerged in the CSWB w/oil arm. Most observed households (excluding RUSF) did not prepare porridge daily as instructed (35-46% by arm). Household water samples showed either high-risk or unsafe contamination with Escherichia coli (72-78% by arm). Low percentages were observed handwashing (both child and server) before consuming the porridge. CONCLUSIONS: The SNFs were not prepared or served as intended and diversion from the recipient was common. Storage conditions may have resulted in spoilage of the ration containing whey before reaching recipients. This article provides context about factors that may have influenced the effectiveness of these SNFs. Programming and household use of SNFs are as important as their nutrient composition. This trial was registered at clinicaltrials.gov as NCT02071563.