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PURPOSE OF REVIEW: Crohn's Disease (CD) is a chronic inflammatory disease that can lead to progressive damage to the gastrointestinal tract and significant disability. Early, "top-down" biologic therapy is recommended in moderate-to-severe CD to induce remission and to prevent hospitalization and complications. However, an estimated 20-30% of patients with CD have a mild disease course and may not garner sufficient benefit from expensive, immunosuppressing agents to justify their risks. Herein, we review characteristics of patients with mild CD, the available options for disease treatment and monitoring, and future directions of research. RECENT FINDINGS: For ambulatory outpatients with low-risk, mild, ileal or ileocolonic CD, induction of remission with budesonide is recommended. For colonic CD, sulfasalazine is a reasonable choice, although other aminosalicylates have no role in the treatment of CD. No large, randomized trial has supported the use of antibiotics or antimycobacterials in the treatment of CD. Partial Enteral Nutrition and Crohn's Disease Exclusion Diets may be appropriate for inducing remission in some adult patients, with trials ongoing. Select patients with mild-to-moderate CD may benefit from maintenance therapy with azathioprines or gut specific biologics, such as vedolizumab. The role of complementary and alternative medicine is not well defined. The identification, risk stratification, and monitoring of patients with mild CD can be a challenging clinical scenario. Some patients with low risk of disease progression may be appropriate for initial induction of remission with budesonide or sulfasalazine, followed by close clinical monitoring. Future research should focus on pre-clinical biomarkers to stratify disease, novel therapies with minimal systemic immune suppression, and validation of rigorous clinical monitoring algorithms.
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Enfermedad de Crohn , Humanos , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/tratamiento farmacológico , Sulfasalazina/uso terapéutico , Budesonida/uso terapéutico , Antibacterianos/uso terapéutico , Nutrición Enteral , Inducción de RemisiónRESUMEN
Objectives: With the introduction of antiretroviral treatment (ART), opportunistic infections (OIs) reduced a lot and most HIV-associated OIs are preventable and treatable with safe cost-effective interventions. But however, in order to prevent and early diagnosis, we need to have baseline estimation of OIs among HIV positive children and other factors associated, especially nutritional deficiencies. Methodology: A cross-sectional study was carried out in pediatric outpatient department (OPD) of a large multicentric hospital among 106 children. Data were collected by means of pretested predesigned semi-structed questionnaire prepared on consultation with experts in the subjects and clinical assessment was done in day light to detect signs of nutritional disorders. Institutional ethical clearance was taken, and strict confidentiality was maintained. Results: Majority (39.6%) of the children belong to 5-9 years. Children were equitably distributed between orphanage and family care giver. Bitot's spots, cheilosis, and gum bleeding were found to be more than twice as common in subjects living with family, as compared to those living in orphanage while aphthous ulcer, knock knee, bow leg were found to be more than twice as common in female subjects as compared males. The prevalence of Pneumonia, Mumps, Herpes zoster, Pulmonary Tuberculosis, Oral candidiasis, and recurrent upper respiratory tract infections (URTI) was found to be about twice as common in subjects living with family, as compared to those living in orphanage while males had more Chicken pox, Herpes zoster, Pulmonary Tuberculosis, Oral candidiasis, and Recurrent URTI as compared to those in females. Conclusion: Vitamin deficiencies and opportunistic infections were higher than the prevalence reported by the various studies done on normal children. All efforts to be made to improve adequate nutrition to HIV positive children and ensure protection against opportunistic infections especially for children in home-based care.
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Pharmacological and genetic studies over the past decade have established the follicle-stimulating hormone (FSH) as an actionable target for diseases affecting millions, namely osteoporosis, obesity, and Alzheimer's disease. Blocking FSH action prevents bone loss, fat gain, and neurodegeneration in mice. We recently developed a first-in-class, humanized, epitope-specific FSH-blocking antibody, MS-Hu6, with a KD of 7.52 nM. Using a Good Laboratory Practice (GLP)-compliant platform, we now report the efficacy of MS-Hu6 in preventing and treating osteoporosis in mice and parameters of acute safety in monkeys. Biodistribution studies using 89Zr-labeled, biotinylated or unconjugated MS-Hu6 in mice and monkeys showed localization to bone and bone marrow. The MS-Hu6 displayed a ß phase t½ of 7.5 days (180 hr) in humanized Tg32 mice. We tested 217 variations of excipients using the protein thermal shift assay to generate a final formulation that rendered MS-Hu6 stable in solution upon freeze-thaw and at different temperatures, with minimal aggregation, and without self-, cross-, or hydrophobic interactions or appreciable binding to relevant human antigens. The MS-Hu6 showed the same level of "humanness" as human IgG1 in silico and was non-immunogenic in ELISpot assays for IL-2 and IFN-γ in human peripheral blood mononuclear cell cultures. We conclude that MS-Hu6 is efficacious, durable, and manufacturable, and is therefore poised for future human testing.
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Hormona Folículo Estimulante , Osteoporosis , Animales , Epítopos/metabolismo , Excipientes , Hormona Folículo Estimulante/metabolismo , Humanos , Inmunoglobulina G/metabolismo , Interleucina-2/metabolismo , Leucocitos Mononucleares/metabolismo , Ratones , Osteoporosis/tratamiento farmacológico , Distribución TisularRESUMEN
Diabetes is one of the leading causes of death globally. India is home to the second-largest population suffering from diabetes. This underscores the need to build capacity of primary care physicians (PCPs) for better disease management. This narrative review article aims to describe the emergence of diabetes education and capacity-building programs for PCPs and its current situation in India. The review highlighted that major emphasis on diabetes was given only when the WHO estimated that morbidity and mortality due to diabetes would increase to 35% in India. As a result, National Diabetes Control Program was launched in 1987. Yet, very little attention was paid to diabetology in under-graduation. In the last decade, few public and private institutions have developed diabetes related capacity-building programs for PCPs independently or in collaborations. These programs include 16 fellowships, 4 diplomas, 12 certificate programs, and 6 other diabetes training programs, which have their own pros and cons. As medical science is changing rapidly, PCPs need to upgrade their skills and knowledge regularly to manage NCDs such as diabetes more effectively and efficiently. This can be possible only if scientific, evidence-based, and quality-oriented capacity-building programs are provided to the healthcare workforce.