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Objective: To assess treatment outcomes in tuberculosis patients participating in support group meetings in five districts of Karnataka and Telangana states in southern India. Methods: Tuberculosis patients from five selected districts who began treatment in 2019 were offered regular monthly support group meetings, with a focus on patients in urban slum areas with risk factors for adverse outcomes. We tracked the patients' participation in these meetings and extracted treatment outcomes from the Nikshay national tuberculosis database for the same patients in 2021. We compared treatment outcomes based on attendance of the support groups meetings. Findings: Of 30 706 tuberculosis patients who started treatment in 2019, 3651 (11.9%) attended support groups meetings. Of patients who attended at least one support meeting, 94.1% (3426/3639) had successful treatment outcomes versus 88.2% (23 745/26 922) of patients who did not attend meetings (adjusted odds ratio, aOR: 2.44; 95% confidence interval, CI: 2.10-2.82). The odds of successful treatment outcomes were higher in meeting participants than non-participants for all variables examined including: age ≥ 60 years (aOR: 3.19; 95% CI: 2.26-4.51); female sex (aOR: 3.33; 95% CI: 2.46-4.50); diabetes comorbidity (aOR: 3.03; 95% CI: 1.91-4.81); human immunodeficiency virus infection (aOR: 3.73; 95% CI: 1.76-7.93); tuberculosis retreatment (aOR: 1.69; 1.22-2.33); and drug-resistant tuberculosis (aOR: 1.93; 95% CI: 1.21-3.09). Conclusion: Participation in support groups for tuberculosis patients was significantly associated with successful tuberculosis treatment outcomes, especially among high-risk groups. Expanding access to support groups could improve tuberculosis treatment outcomes at the population level.
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Tuberculosis , Humanos , Femenino , Persona de Mediana Edad , India/epidemiología , Tuberculosis/tratamiento farmacológico , Tuberculosis/epidemiología , Resultado del Tratamiento , Factores de Riesgo , Grupos de AutoayudaRESUMEN
BACKGROUND: Co-management of HIV-TB coinfection remains a challenge globally. Addressing TB among people living with HIV (PLHIV) is a key priority for the Government of India (GoI). In 2016, GoI implemented single-window services to prevent and manage TB in PLHIV. To strengthen HIV-TB service delivery, case-based e-learning was introduced to health care providers at Antiretroviral Therapy centres (ARTc). METHODS: We implemented a hub and spoke model to deliver biweekly, virtual, case-based e-learning at select ARTc (n = 115), from four states of India-Delhi, Uttar Pradesh, Andhra Pradesh and Tamil Nadu. We evaluated feasibility and acceptability of case-based e-learning and its impact on professional satisfaction, self-efficacy, knowledge retention using baseline and completion surveys, session feedback, pre-and post-session assessments. We reviewed routine programmatic data and patient outcomes to assess practices among participating ARTc. RESULTS: Between May 2018 and September 2020, 59 sessions were conducted with mean participation of 55 spokes and 152 participants. For 95% and 88% of sessions ≥ 80% of respondents agreed that topics were clear and relevant to practice, and duration of session was appropriate, respectively. Session participants significantly improved in perceived knowledge, skills and competencies (+ 8.6%; p = 0.025), and technical knowledge (+ 18.3%; p = 0.04) from baseline. Participating ARTc increased TB screening (+ 4.2%, p < 0.0001), TB diagnosis (+ 2.7%, p < 0.0001), ART initiation (+ 4.3%, p < 0.0001) and TB preventive treatment completion (+ 5.2%, p < 0.0001). CONCLUSION: Case-based e-learning is an acceptable and effective modus of capacity building and developing communities of practice to strengthen integrated care. E-learning could address demand for accessible and sustainable continuing professional education to manage complex diseases, and thereby enhance health equity. We recommend expansion of this initiative across the country for management of co-morbidities as well as other communicable and non-communicable diseases to augment the existing capacity building interventions by provide continued learning and routine mentorship through communities of practice.
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Instrucción por Computador , Infecciones por VIH , Humanos , India/epidemiología , Aprendizaje , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , GobiernoRESUMEN
Androgenetic complete hydatidiform moles are human pregnancies with no embryos and affect 1 in every 1,400 pregnancies. They have mostly androgenetic monospermic genomes with all the chromosomes originating from a haploid sperm and no maternal chromosomes. Androgenetic complete hydatidiform moles were described in 1977, but how they occur has remained an open question. We identified bi-allelic deleterious mutations in MEI1, TOP6BL/C11orf80, and REC114, with roles in meiotic double-strand breaks formation in women with recurrent androgenetic complete hydatidiform moles. We investigated the occurrence of androgenesis in Mei1-deficient female mice and discovered that 8% of their oocytes lose all their chromosomes by extruding them with the spindles into the first polar body. We demonstrate that Mei1-/- oocytes are capable of fertilization and 5% produce androgenetic zygotes. Thus, we uncover a meiotic abnormality in mammals and a mechanism for the genesis of androgenetic zygotes that is the extrusion of all maternal chromosomes and their spindles into the first polar body.
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Andrógenos/genética , Mola Hidatiforme/genética , Mutación/genética , Alelos , Animales , Cromosomas/genética , Femenino , Humanos , Masculino , Mamíferos/genética , Ratones , Ratones Endogámicos C57BL , Oocitos/patología , Embarazo , Cigoto/patologíaRESUMEN
INTRODUCTION: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. In recent years, endoscopic procedures such as endoscopic enucleation (EN) and endoscopic full-thickness resection (EFTR) have been used to resect GISTs. This study aimed to investigate the clinical efficacy, safety, and feasibility of endoscopic resection of GISTs in a North American population. METHODS: A total of 25 patients with gastric submucosal lesions (SML) underwent endoscopic resection from December 2014 to April 2016. Data from cases with histologically proven GISTs originating from the muscularis propria layer (MP-GIST) were collected. The main outcome measures were complete resection rate, operative time, postoperative complications, length of hospital stay, narcotic analgesic requirement, and follow-up outcomes. Surveillance was performed with CT abdomen, and/or EGD along with oncology follow-up at 6- to 24-month intervals. RESULTS: Out of 25 gastric SML, there were 12 histologically proven MP-GIST. Five endophytic MP-GIST were removed by EN, and seven exophytic MP-GIST were removed by EFTR. All lesions were removed en bloc except for one hard to localize exophytic lesion which was completely removed piecemeal. The mean removal time was 79.7 min (range 17-180 min). Nine out of twelve patients required inpatient admission for observation with a mean length of stay of 2.08 days (range 1-4 days). No complications were noted and no narcotic analgesics were required. Pathology reports showed that one GIST was intermediate risk but all others were low-risk lesions. No recurrence has been noted thus far. CONCLUSION: Endoscopic removal of MP-GIST by a trained endoscopist appears to be safe and feasible in North American population. Further studies with greater sample size are necessary to compare endoscopic versus surgical resection of MP-GIST. Comparison of outcomes may support wider use of endoscopic techniques for GIST removal.
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Resección Endoscópica de la Mucosa , Tumores del Estroma Gastrointestinal/cirugía , Neoplasias Gástricas/cirugía , Anciano , Anciano de 80 o más Años , Resección Endoscópica de la Mucosa/métodos , Estudios de Factibilidad , Femenino , Tumores del Estroma Gastrointestinal/patología , Gastroscopía/métodos , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , América del Norte , Estudios Retrospectivos , Neoplasias Gástricas/patología , Resultado del TratamientoRESUMEN
In this article, we have successfully designed and demonstrated a novel continuous process for assembling targeting ligands, peptidic spacers, fluorescent tags and a chelating core for the attachment of cytotoxic molecules, radiotracers, nanomaterials in a standard Fmoc solid-phase peptide synthesis in high yield and purity. The differentially protected Fmoc-Lys-(Tfa)-OH plays a vital role in attaching fluorescent tags while growing the peptide chain in an uninterrupted manner. The methodology is versatile for solid-phase resins that are sensitive to mild and strong acidic conditions when acid-sensitive side chain amino protecting groups such as Trt (chlorotrityl), Mtt (4-methyltrityl), Mmt (4-methoxytrityl) are employed to synthesise the ligand targeted fluorescent tagged bioconjugates. Using this methodology, DUPA rhodamine B conjugate (DUPA = 2-[3-(1,3-dicarboxypropyl)ureido]pentanedioic acid), targeting prostate specific membrane antigen (PSMA) expressed on prostate, breast, bladder and brain cancers and pteroate rhodamine B, targeting folate receptor positive cancers such as ovarian, lung, endometrium as well as inflammatory diseases have been synthesized. In vitro studies using LNCaP (PSMA +ve), PC-3 (PSMA -ve, FR -ve) and CHO-ß (FR +ve) cell lines and their respective competition experiments demonstrate the specificity of the newly synthesized bioconstructs for future application in fluorescent guided intra-operative imaging.
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AIM: To investigate the correlation between the status of interstitial cells of Cajal (ICC) in ureteropelvic junction (UPJ) and the resected ureteric margin and the postoperative outcome of Anderson-Hynes pyeloplasty in UPJ obstruction (UPJO) and to compare the ICC in the UPJ and the resected margin of the normal ureter. MATERIALS AND METHODS: An observational study was conducted over a period of 2 years at the Department of Pediatric Surgery at Niloufer Institute of Women and Child Health. Children with intrinsic UPJO who underwent Anderson-Hynes dismembered pyeloplasty were included in the study. Six months postoperatively, the patients were divided into two groups based on diuretic isotopic renogram using technetium-99m-labeled diethylene triaminepentaacetic acid. Group 1 comprised patients with good surgical outcome. Group 2 comprised patients with a poor outcome. The histologic specimens were evaluated for ICC, and the immunohistochemical findings were correlated with the outcome. RESULTS: Twenty-five patients were included in this study (19 male and 6 female). Seventy-six percent of patients were under the age of 1 year. Group 1 had 23 cases and Group 2 had 2 cases. Out of the two patients with a poor outcome, one had negative grading at the UPJ and one had positive grading. Both these patients had a negative grading at the lower resected margins. More number of patients (24%) had +++ grading at the lower resected margin when compared to the UPJ (8%). CONCLUSION: This is the first study which correlates the status of ICC in UPJ with the outcome of pyeloplasty in pediatric patients. Both the cases with bad outcome had no ICC at the lower margin of the resected specimen and one case had no ICC at the UPJ. There is a statistically significant difference (P = 0.001) in the number of ICC at the UPJ and the resected margin.
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BACKGROUND: Hydatidiform mole (HM) is a human pregnancy with excessive trophoblastic proliferation and abnormal embryonic development that may be sporadic or recurrent. In the sporadic form, the HM phenotype is driven by an abnormal ratio of paternal to maternal genomes, whereas in the recurrent form, the HM phenotype is caused by maternal-recessive mutations, mostly in NLRP7, despite the diploid biparental origin of the HM tissues. In this study, we characterised the expression of the imprinted, maternally expressed gene, CDKN1C (p57(KIP2)), the genotype, and the histopathology of 36 products of conception (POC) from patients with two defective alleles in NLRP7 and looked for potential correlations between the nature of the mutations in the patients and the various HM features. METHODS/RESULTS: We found that all the 36 POCs are diploid biparental and have the same parental contribution to their genomes. However, some of them expressed variable levels of p57(KIP2) and this expression was strongly associated with the presence of embryonic tissues of inner cell mass origin and mild trophoblastic proliferation, which are features of triploid partial HMs, and were associated with missense mutations. Negative p57(KIP2) expression was associated with the absence of embryonic tissues and excessive trophoblastic proliferation, which are features of androgenetic complete HMs and were associated with protein-truncating mutations. CONCLUSIONS: Our data suggest that NLRP7, depending on the severity of its mutations, regulates the imprinted expression of p57(KIP2) and consequently the balance between tissue differentiation and proliferation during early human development. This role is novel and could not have been revealed by any other approach on somatic cells.
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Proteínas Adaptadoras Transductoras de Señales/genética , Diferenciación Celular/fisiología , Proliferación Celular/fisiología , Inhibidor p57 de las Quinasas Dependientes de la Ciclina/metabolismo , Regulación del Desarrollo de la Expresión Génica/genética , Mola Hidatiforme/genética , Trofoblastos/fisiología , Diferenciación Celular/genética , Proliferación Celular/genética , Inhibidor p57 de las Quinasas Dependientes de la Ciclina/genética , Análisis Mutacional de ADN , Femenino , Citometría de Flujo , Impresión Genómica/genética , Genotipo , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Repeticiones de Microsatélite/genética , Mutación Missense/genética , EmbarazoRESUMEN
Recurrent hydatidiform moles is an uncommon occurrence. Over the past decade, genetic studies of women with multiple recurrent molar pregnancies have revealed that maternal mutations in two different genes, NLRP7 and C6orf221, result in recurrent moles. We report a 23 year old woman, born of unrelated parents, who has experienced three molar pregnancies in succession. Whilst the first pregnancy was classified as a complete hydatidiform mole, the second and third moles defied classification as complete or partial mole using conventional histology, p57 nuclear staining pattern and ploidy studies. Molecular and cytogenetic studies proved that all three molar pregnancies were diploid and biparental in origin. Gene sequencing analysis showed that the patient is homozygous for a previously described mutation in NLRP7. A SNP microarray ruled out the presence of deletion of the NLRP7 locus. This case draws attention to the fact that recurrent molar pregnancies may be the result of specific, identifiable gene mutations, even in patients from non-consanguineous backgrounds. When pathologists encounter patients with molar pregnancies that are diploid and p57 negative and yet have fetal elements such as nucleated red blood cells or immature fetal tissues, it should heighten their suspicion of a possible genetic basis and appropriate molecular genetic workup performed with counseling offered.
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Proteínas Adaptadoras Transductoras de Señales/genética , Biomarcadores de Tumor/genética , Inhibidor p57 de las Quinasas Dependientes de la Ciclina/genética , Mola Hidatiforme/genética , Complicaciones del Embarazo , Neoplasias Uterinas/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adulto , Alelos , Biomarcadores de Tumor/metabolismo , Inhibidor p57 de las Quinasas Dependientes de la Ciclina/metabolismo , Femenino , Perfilación de la Expresión Génica , Técnicas de Genotipaje , Humanos , Mola Hidatiforme/clasificación , Mola Hidatiforme/patología , Hibridación Fluorescente in Situ , Mutación , Recurrencia Local de Neoplasia , Análisis de Secuencia por Matrices de Oligonucleótidos , Ploidias , Embarazo , Análisis de Secuencia de ADN , Neoplasias Uterinas/clasificación , Neoplasias Uterinas/patología , Adulto JovenRESUMEN
Background: India's National TB Elimination Program emphasizes patient-centered care to improve TB treatment outcomes. We describe the lessons learned from the implementation of a differentiated care model for TB care among individuals diagnosed with active TB. Design and methods: Used mixed methods to pilot the Differentiated Care Model. Community health workers (CHWs) conducted a risk and needs assessment among individuals who were recently began TB treatment. Individuals identified with specific factors that are associated with poor treatment adherence were provided education, counseling, and linked to treatment and support services. Examined changes in TB treatment outcomes between the two cohorts of individuals on TB treatment before and after the intervention. We used qualitative research methods to explore the experiences of patients, family members, and front-line TB workers with the implementation of the DCM pilot. Results: The CHWs were adept at the identification of individuals with risks to non-adherence. However, only a few provided differentiated care, as envisioned. There was no significant change in the TB treatment outcomes between the two cohorts of patients examined. CHWs' ability to provide differentiated care on a scale was limited by the short duration of implementation, their inadequate skills to manage co-morbidities, and the suboptimal support at the field level. Conclusions: It is feasible for a cadre of well-trained front-line workers, mentored and supported by counselors and doctors, to provide differentiated care to those at risk for unfavorable TB treatment outcomes. However, differentiated care must be implemented on a scale for a duration that allows a change from the conventional practice of front-line workers, in order to influence the outcomes of population-level TB treatment.
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Calcineurin is an important signal transduction mediator in T cells, neurons, the heart, and kidneys. Recent evidence points to unique actions of the two main isoforms of the catalytic subunit. Although the ß isoform is required for T-cell development, α is important in the brain and kidney. In addition, mice lacking α but not ß suffer from failure to thrive and early mortality. The purpose of this study was to identify the cause of postnatal death of calcineurin α null (CnAα(-/-)) mice and to determine the mechanism of α activity that contributes to the phenotype. CnAα(-/-) mice and wild-type littermate controls were fed a modified diet and then salivary gland function and histology were examined. In vitro studies were performed to identify the mechanism of α action. Data show that calcineurin is required for normal submandibular gland function and secretion of digestive enzymes. Loss of α does not impair nuclear factor of activated T-cell activity or expression but results in impaired protein trafficking downstream of the inositol trisphosphate receptor. These findings show a novel function of calcineurin in digestion and protein trafficking. Significantly, these data also provide a mechanism to rescue to adulthood a valuable animal model of calcineurin inhibitor-mediated neuronal and renal toxicities.
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Calcineurina/genética , Calcineurina/fisiología , Glándulas Salivales/metabolismo , Animales , Encéfalo/metabolismo , Calcineurina/metabolismo , Femenino , Inmunohistoquímica/métodos , Riñón/metabolismo , Luciferasas/metabolismo , Masculino , Ratones , Ratones Transgénicos , Neuronas/metabolismo , Isoformas de Proteínas , Transporte de Proteínas , Transducción de Señal , Fracciones Subcelulares/metabolismoRESUMEN
A rare case of thoracic fetus in fetu is reported. Complete excision was curative.
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Due to the coronavirus disease (COVID-19) pandemic and its associated response, TB deaths increased for the first time in a decade. In any potentially fatal illness, an assessment of severity is essential. This is not systematically done for adults with TB, mostly due to a lack of policy and/or limited availability of diagnostic and clinical capacity. We developed a screening tool using simple and easily measurable indicators that can be used by paramedical TB program staff to quickly identify people with severe illness. During October-November 2020 in Karnataka, India, the paramedical program staff from 16 districts screened people with TB (aged ≥15 years) notified by public facilities for "high risk of severe illness," which was defined as the presence of any of the following indicators: (1) body mass index (BMI) ≤14.0 kg/m2; (2) BMI ≤16.0 kg/m2 with bilateral leg swelling; (3) respiratory rate >24/minute; (4) oxygen saturation <94%; (5) inability to stand without support. In this cohort study, we determined the incidence of program-recorded early deaths (within 2 months) and its association with high risk of severe illness. Of 3,010 people with TB, 1,529 (50.8%) were screened at diagnosis/notification, of whom 537 (35.1%) had a high risk of severe illness. There were 195 (6.5%, 95% CI=5.7, 7.4) early deaths: 59 (30.2%) within a week and 100 (51.3%) within 2 weeks of treatment initiation. The incidence of early deaths was significantly higher among those with high risk of severe illness (8.9%) at diagnosis compared to those without (3.8%) [adjusted relative risk: 2.36 (95% confidence interval=1.57, 3.55)]. To conclude, early deaths were especially high during the first 2 weeks and strongly associated with a high risk of severe illness at diagnosis/notification. Screening for severe illness should be explored as a potential strategy to end TB deaths.
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COVID-19 , Tuberculosis , Adulto , COVID-19/diagnóstico , COVID-19/prevención & control , Prueba de COVID-19 , Estudios de Cohortes , Humanos , India/epidemiología , Tamizaje Masivo , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Tuberculosis/prevención & controlRESUMEN
Calcineurin is an important signalling protein that regulates a number of molecular and cellular processes. Previously, we found that inhibition of calcineurin with cyclosporine reduced renal hypertrophy and blocked glomerular matrix expansion in the diabetic kidney. Isoforms of the catalytic subunit of calcineurin are reported to have tissue specific expression and functions. In particular, the ß isoform has been implicated in cardiac and skeletal muscle hypertrophy. Therefore, we examined the role of calcineurin ß in diabetic renal hypertrophy and glomerular matrix expansion. Type I diabetes was induced in wild-type and ß(-/-) mice and then renal function, extracellular matrix expansion and hypertrophy were evaluated. The absence of ß produced a significant decrease in total calcineurin activity in the inner medulla (IM) and reduced nuclear factor of activated T-cells (NFATc) activity. Loss of ß did not alter diabetic renal dysfunction assessed by glomerular filtration rate, urine albumin excretion and blood urea nitrogen. Similarly, matrix expansion in the whole kidney and glomerulus was not different between diabetic wild-type and ß(-/-) mice. In contrast, whole kidney and glomerular hypertrophy were significantly reduced in diabetic ß(-/-) mice. Moreover, ß(-/-) renal fibroblasts demonstrated impaired phosphorylation of Erk1/Erk2, c-Jun N-terminal kinases (JNK) and mammalian target of rapamycin (mTOR) following stimulation with transforming growth factor-ß and did not undergo hypertrophy with 48 hrs culture in high glucose. In conclusion, loss of the ß isoform of calcineurin is sufficient to reproduce beneficial aspects of cyclosporine on diabetic renal hypertrophy but not matrix expansion. Therefore, while multiple signals appear to regulate matrix, calcineurin ß appears to be a central mechanism involved in organ hypertrophy.
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Calcineurina/metabolismo , Diabetes Mellitus Experimental/metabolismo , Matriz Extracelular/metabolismo , Riñón/metabolismo , Riñón/patología , Factores de Transcripción NFATC/metabolismo , Albúminas , Animales , Nitrógeno de la Urea Sanguínea , Ciclosporina/farmacología , Diabetes Mellitus Experimental/patología , Tasa de Filtración Glomerular , Glucosa/farmacología , Hipertrofia , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patología , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Sistema de Señalización de MAP Quinasas , Ratones , Ratones Noqueados , Factores de Transcripción NFATC/biosíntesis , Serina-Treonina Quinasas TOR/metabolismo , Factor de Crecimiento Transformador beta/farmacologíaRESUMEN
PGC-1alpha is a transcriptional coactivator that controls energy homeostasis through regulation of glucose and oxidative metabolism. Both PGC-1alpha expression and oxidative capacity are decreased in skeletal muscle of patients and animals undergoing atrophy, suggesting that PGC-1alpha participates in the regulation of muscle mass. PGC-1alpha gene expression is controlled by calcium- and cAMP-sensitive pathways. However, the mechanism regulating PGC-1alpha in skeletal muscle during atrophy remains unclear. Therefore, we examined the mechanism responsible for decreased PGC-1alpha expression using a rodent streptozotocin (STZ) model of chronic diabetes and atrophy. After 21days, the levels of PGC-1alpha protein and mRNA were decreased. We examined the activation state of CREB, a potent activator of PGC-1alpha transcription, and found that phospho-CREB was paradoxically high in muscle of STZ-rats, suggesting that the cAMP pathway was not involved in PGC-1alpha regulation. In contrast, expression of calcineurin (Cn), a calcium-dependent phosphatase, was suppressed in the same muscles. PGC-1alpha expression is regulated by two Cn substrates, MEF2 and NFATc. Therefore, we examined MEF2 and NFATc activity in muscles from STZ-rats. Target genes MRF4 and MCIP1.4 mRNAs were both significantly reduced, consistent with reduced Cn signaling. Moreover, levels of MRF4, MCIP1.4, and PGC-1alpha were also decreased in muscles of CnAalpha-/- and CnAbeta-/- mice without diabetes indicating that decreased Cn signaling, rather than changes in other calcium- or cAMP-sensitive pathways, were responsible for decreased PGC-1alpha expression. These findings demonstrate that Cn activity is a major determinant of PGC-1alpha expression in skeletal muscle during diabetes and possibly other conditions associated with loss of muscle mass.
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Calcineurina/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Atrofia Muscular , Proteínas de Unión al ARN/metabolismo , Transducción de Señal/fisiología , Transactivadores/metabolismo , Factores de Transcripción/metabolismo , Animales , Calcineurina/genética , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Complicaciones de la Diabetes/metabolismo , Complicaciones de la Diabetes/patología , Diabetes Mellitus Experimental/genética , Humanos , Masculino , Ratones , Músculo Esquelético/citología , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Atrofia Muscular/etiología , Atrofia Muscular/metabolismo , Atrofia Muscular/patología , Factores Reguladores Miogénicos/genética , Factores Reguladores Miogénicos/metabolismo , Factores de Transcripción NFATC/genética , Factores de Transcripción NFATC/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Proteínas de Unión al ARN/genética , Ratas , Ratas Sprague-Dawley , Transactivadores/genética , Factores de Transcripción/genética , Transcripción GenéticaRESUMEN
BACKGROUND: Tuberculosis Health Action Learning Initiative (THALI) funded by USAID is a person-centered initiative, supporting vulnerable urban populations to gain access to TB services. THALI trained and placed 112 Community health workers (CHWs) to detect and support individuals with TB symptoms or disease within urban slums in two cities, Hyderabad and Bengaluru, covering a population of about 3 million. METHODS: CHWs visited the slums once in a fortnight. They conducted TB awareness activities. They referred individuals with TB symptoms for sputum testing to nearest public sector laboratories. They visited those testing TB positive, once a fortnight in the intensive phase, and once a month thereafter. They supported TB patients and families with counselling, contact screening and social scheme linkages. They complemented the shortfall in urban TB government field staff numbers and their capacity to engage with TB patients. Data on CHWs' patient referral for TB diagnosis and treatment support activities was entered into a database and analyzed to examine CHWs' role in the cascade of TB care. We compared achievements of six monthly referral cohorts from September 2016 to February 2019. RESULTS: Overall, 31 617 (approximately 1%) of slum population were identified as TB symptomatic and referred for diagnosis. Among the referred persons, 23 976 (76%) underwent testing of which 3841 (16%) were TB positive. Overall, 3812 (99%) were initiated on treatment and 2760 (72%) agreed for regular follow up by the CHWs. Fifty-seven percent of 2952 referred were tested in the first cohort, against 86% of 8315 in the last cohort. The annualized case detection rate through CHW referrals in Bengaluru increased from 5.5 to 52.0 per 100 000 during the period, while in Hyderabad it was 35.4 initially and increased up to 118.9 per 100 000 persons. The treatment success rate was 87.1% among 193 in the first cohort vs 91.3% among 677 in the last cohort. CONCLUSIONS: CHWs in urban slums augment TB detection to care cascade. Their performance and TB treatment outcomes improve over time. It would be important to examine the cost per TB case detected and successfully treated.
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Agentes Comunitarios de Salud , Áreas de Pobreza , Servicios de Salud Rural , Tuberculosis , Adolescente , Adulto , Ciudades , Femenino , Humanos , India , Masculino , Persona de Mediana Edad , Servicios de Salud Rural/organización & administración , Tuberculosis/diagnóstico , Tuberculosis/terapia , Adulto JovenRESUMEN
Due to limited availability of diagnostics and capacity, people with tuberculosis do not always undergo systematic assessment for severe illness (requiring inpatient care). In Karnataka (south India), para-medical programme staff used a screening tool to identify people at 'high risk of severe illness', defined using indicators of very severe undernutrition, abnormal vital signs and poor performance status (any one): (i) body mass index (BMI) ≤ 14.0 kg/m2 (ii) BMI ≤ 16.0 kg/m2 with bilateral leg swelling (iii) respiratory rate > 24/min (iv) oxygen saturation < 94% (v) inability to stand without support. Of 3020 adults notified from public facilities (15 October to 30 November 2020) in 16 districts, 1531 (51%) were screened (district-wise range: 13-90%) and of them, 538 (35%) were classified as 'high risk of severe illness'. Short median delays in screening from notification (five days), and all five indicators being collected for 88% of patients, suggests the feasibility of using this tool in programme settings. However, districts with poor screening coverage require further attention. To end tuberculosis deaths, screening should be followed by referral to higher facilities for comprehensive clinical evaluation, to assess the need for inpatient care. Future studies should assess the validity (especially sensitivity in picking severely ill patients) of this screening tool.
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Background: In India, challenges in pediatric TB contact screening and chemoprophylaxis initiation are still underexplored. Elucidating these challenges will help in better implementation of the programme at the grass-roots level thereby helping in early detection of pediatric cases and timely initiation of preventive therapy. This study aimed at exploring the challenges faced by the health care provider in contact screening and chemoprophylaxis initiation implementation of the pediatric household contacts. Methods: A qualitative study was conducted in the districts of Bengaluru and Udupi and in-depth interviews of key participants were adopted to explore the challenges. Qualitative data analysis was done after developing transcripts by generating themes and codes. Results: The key challenges were identified as stigma towards the disease, migrant patients with changing address, difficulty in sample collection, anxiety among parents due to long duration of the prophylactic treatment and adherence to IPT is not well documented, inadequate transportation from rural areas, and the ongoing COVID-19 pandemic. Conclusions: It is important for the National TB programme to address these challenges efficiently and effectively. Innovative solutions, feasible engagements, and massive efforts are to be taken by the programme to improve contact screening and isoniazid chemoprophylaxis implementation.
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Hot water epilepsy (HWE) is a form of reflex or sensory epilepsy wherein seizures are precipitated by an unusual stimulus, the contact of hot water over the head and body. Genome-wide linkage analysis of a large family with ten affected members, provided evidence of linkage (Z (max) = 3.17 at theta = 0 for D10S412) to chromosome 10q21. Analysis of five additional HWE families, for markers on chromosome 10, further strengthened the evidence of linkage to the same chromosomal region with three out of five families showing concordance for the disease haplotype and providing a two-point LOD score of 4.86 at theta = 0 and 60% penetrance for D10S412. The centromere-proximal and -distal boundaries of the critical genetic interval of about 15 Mb at 10q21.3-q22.3 were defined by D10S581 and D10S201, respectively. Sequence analysis of a group of functional candidate genes, the ion channels KCNMA1, VDAC2 and solute carriers SLC25A16, SLC29A3 revealed no potentially pathogenic mutation. We propose to carry out further analysis of positional candidate genes from this region to identify the gene responsible for this unusual neurobehavioral phenotype.
Asunto(s)
Mapeo Cromosómico , Cromosomas Humanos Par 10/genética , Epilepsia Refleja/genética , Genes Dominantes , Análisis Mutacional de ADN , Epilepsia Refleja/epidemiología , Femenino , Marcadores Genéticos , Haplotipos , Humanos , India/epidemiología , Escala de Lod , Masculino , Repeticiones de Microsatélite , LinajeRESUMEN
OBJECTIVE: To identify the disease locus in a three-generation south Indian family having several of its members affected with idiopathic epilepsy. METHODS: Genome-wide parametric linkage analysis was performed with 382 autosomal markers. Mutational analysis of the positional candidate genes in linked interval was performed by direct sequencing of genomic DNA from the proband in the family. Expression analysis in human adult brain was performed by Western blotting. RESULTS: A novel epilepsy genetic locus on chromosome 3q13.3-q21 was identified by linkage analysis. This locus comprises about 12 megabases of the genomic interval, with its proximal and distal genetic boundaries defined by microsatellite markers, D3S3675 and D3S1551, respectively. In this interval, we found a novel, patient-specific, missense variant, Arg898Gln, at the extracellular calcium sensing receptor (CASR), a gene belonging to the G-protein-coupled receptor family. CASR expression was detected in the temporal lobe, frontal lobe, parietal lobe, cerebellum, and hippocampus. Four additional, potentially pathogenic, missense CASR variants, Glu354Ala, Ile686Val, Ala988Val, and Ala988Gly, were observed in five individuals affected with idiopathic generalized epilepsy. INTERPRETATION: A novel idiopathic epilepsy locus has been mapped on chromosome 3q13.3-q21, as evident by presence of significant genetic linkage. Identification of novel, rare missense CASR variants at evolutionary-conserved residues in epilepsy patients and CASR expression in various subregions of human brain raises an interesting possibility of involvement of CASR in pathophysiology of epileptic disorders.