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1.
Immunol Rev ; 301(1): 98-121, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33955564

RESUMEN

BCG turns 100 this year and while it might not be the perfect vaccine, it has certainly contributed significantly towards eradication and prevention of spread of tuberculosis (TB). The search for newer and better vaccines for TB is an ongoing endeavor and latest results from trials of candidate TB vaccines such as M72AS01 look promising. However, recent encouraging data from BCG revaccination trials in adults combined with studies on mucosal and intravenous routes of BCG vaccination in non-human primate models have renewed interest in BCG for TB prevention. In addition, several well-demonstrated non-specific effects of BCG, for example, prevention of viral and respiratory infections, give BCG an added advantage. Also, BCG vaccination is currently being widely tested in human clinical trials to determine whether it protects against SARS-CoV-2 infection and/or death with detailed analyses and outcomes from several ongoing trials across the world awaited. Through this review, we attempt to bring together information on various aspects of the BCG-induced immune response, its efficacy in TB control, comparison with other candidate TB vaccines and strategies to improve its efficiency including revaccination and alternate routes of administration. Finally, we discuss the future relevance of BCG use especially in light of its several heterologous benefits.


Asunto(s)
Vacuna BCG/inmunología , Mycobacterium tuberculosis/inmunología , Tuberculosis/inmunología , Tuberculosis/prevención & control , Vacunación , Inmunidad Adaptativa , Vacuna BCG/administración & dosificación , Humanos , Inmunidad Heteróloga , Inmunidad Innata , Inmunogenicidad Vacunal , Memoria Inmunológica
2.
Clin Exp Immunol ; 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38695079

RESUMEN

Neonate responses to pathogen-associated molecular patterns (PAMPS) differ from adults; such understanding is poor in Indian neonates, despite recognised significant infectious risk. Immune profiling analysis was undertaken of ten secreted mediators contextualised with cellular source induced by six PAMPs in umbilical cord (CB; n=21) and adult-blood (PBMC, n=14) from a tertiary care hospital in South India. Differential cytokine expression analysis (minimum log2-fold difference; adj p-value<0.05) identified bacterial PAMPs induced higher concentrations of IL-1ß, IL-10, TNF-α in adults versus IL-8, GM-CSF, IFN-γ and IL-2 in CB. CB responded to poly I:C and SARS-CoV-2 lysate with a dominant IL-8 response, whereas, in PBMC, CXCL-10 dominated poly I:C, but not SARS-CoV-2, responses, highlighting potential IL-8 importance, in absence of Type I Interferons, in antiviral CB immunity. Candida albicans was the only PAMP to uniformly induce higher secretion of effectors in CB. The predominant source of IL-8/IL-6/TNF-α/IL-1ß in both CB and PBMC was polyfunctional monocytes and IFN-γ /IL-2/IL-17 from innate lymphocytes. Correlation matrix analyses revealed IL-8 to be the most differentially regulated, correlating positively in CB versus negatively in PBMC with IL-6, GM-CSF, IFN-γ, IL-2, consistent with more negatively regulated cytokine modules in adults, potentially linked to higher anti-inflammatory IL-10. Cord and adult blood from India respond robustly to PAMPs with unique effector combinations. These data provide a strong foundation to monitor, explore, mechanisms that regulate such immunity during the life course, an area of significant global health importance given infection-related infant mortality incidence.

3.
J Pediatr ; 266: 113863, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38096975

RESUMEN

OBJECTIVE: To quantify site-specific costs and their association with survival without major morbidity (SWMM) in Canada for neonates <28 weeks of gestation admitted to large tertiary neonatal intensive care units. METHODS: We conducted a retrospective analysis of infants born at <28 weeks of gestation and admitted to Canadian Neonatal Network sites from 2010 through 2021. Sites that cared for at least 50 eligible infants by gestational age in weeks over the study period were included. Using a validated costing algorithm that assessed physician, nursing, respiratory therapy, diagnostic imaging, transfusions, procedural, medication, and certain indirect costs, we calculated site and resource-specific costs in 2017 Canadian dollars (CAD) and evaluated their relationship with SWMM. RESULTS: Seven sites with 8180 (range 841-1605) eligible neonates with a mean (SD) gestation of 25.4 [1.3] weeks were included. Survival to discharge or transfer was 85.3% with a mean (SD) length of stay of 75 (46) days. The mean (SD) total and daily costs per neonate varied between $94 992 ($60 283) and $174 438 ($130 501) CAD and $1833 ($916) to $2307 ($1281) CAD, respectively. Between sites, there was no relationship between costs and SWMM. CONCLUSIONS: There was marked variation in costs and SWMM between sites in Canada with universal health care. The lack of concordance between both outcomes and costs among sites may provide possibilities for outcomes improvement and cost containment.


Asunto(s)
Recien Nacido Extremadamente Prematuro , Unidades de Cuidado Intensivo Neonatal , Recién Nacido , Lactante , Humanos , Estudios Retrospectivos , Canadá , Edad Gestacional
4.
BMC Endocr Disord ; 24(1): 41, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38509509

RESUMEN

INTRODUCTION: The prevalence of hyperthyroidism in Pakistan is 2.9%, which is two times higher than in the United States. Most high-quality hyperthyroidism clinical practice guidelines (CPGs) used internationally originate from high-income countries in the West. Local CPGs in Pakistan are not backed by transparent methodologies. We aimed to produce comprehensive, high-quality CPGs for the management of hyperthyroidism in Pakistan. METHODS: We employed the GRADE-ADOLOPMENT approach utilizing the 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis as the source CPG. Recommendations from the source guideline were either adopted as is, excluded, or adapted according to our local context. RESULTS: The source guideline included a total of 124 recommendations, out of which 71 were adopted and 49 were excluded. 4 recommendations were carried forward for adaptation via the ETD process, with modifications being made to 2 of these. The first addressed the need for liver function tests (LFTs) amongst patients experiencing symptoms of hepatotoxicity while being treated with anti-thyroid drugs (ATDs). The second pertained to thyroid status testing post-treatment by radioactive iodine (RAI) therapy for Graves' Disease (GD). Both adaptations centered around the judicious use of laboratory investigations to reduce costs of hyperthyroidism management. CONCLUSION: Our newly developed hyperthyroidism CPGs for Pakistan contain two context-specific modifications that prioritize patients' finances during the course of hyperthyroidism management and to limit the overuse of laboratory testing in a resource-constrained setting. Future research must investigate the cost-effectiveness and risk-benefit ratio of these modified recommendations.


Asunto(s)
Enfermedad de Graves , Hipertiroidismo , Neoplasias de la Tiroides , Humanos , Pakistán/epidemiología , Radioisótopos de Yodo/uso terapéutico , Neoplasias de la Tiroides/tratamiento farmacológico , Hipertiroidismo/diagnóstico , Hipertiroidismo/epidemiología , Hipertiroidismo/terapia , Enfermedad de Graves/diagnóstico , Enfermedad de Graves/epidemiología , Enfermedad de Graves/terapia
5.
Epidemiology ; 34(2): 247-258, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36722807

RESUMEN

BACKGROUND: Evidence on the effects of in utero exposure to maternal diabetes on cerebral palsy (CP) in offspring is limited. We aimed to examine the effects of pregestational (PGDM) and gestational diabetes (GDM) separately on CP risk and the mediating role of increased fetal size. METHODS: In a population-based study, we included all live births in Ontario, Canada, between 2002 and 2017 followed up through 2018 (n = 2,110,177). Using administrative health data, we estimated crude and adjusted associations between PGDM or GDM and CP using Cox proportional hazards models to account for unequal follow-up in children. For the mediation analysis, we used marginal structural models to estimate the controlled direct effect of PGDM (and GDM) on the risk of CP not mediated by large-for-gestational age (LGA). RESULTS: During the study period, 5,317 children were diagnosed with CP (187 exposed to PGDM and 171 exposed to GDM). Children of mothers with PGDM showed an increased risk (hazard ratio [HR]: 1.84 [95% confidence interval (CI): 1.59, 2.14]) after adjusting for maternal sociodemographic and clinical factors. We found no associations between GDM and CP (adjusted HR: 0.91 [0.77, 1.06]). Our mediation analysis estimated that LGA explained 14% of the PDGM-CP association. CONCLUSIONS: In this population-based birth cohort study, maternal pregestational diabetes was associated with increased risk of CP, and the increased risk was not substantially mediated by the increased fetal size.


Asunto(s)
Parálisis Cerebral , Diabetes Gestacional , Niño , Femenino , Embarazo , Humanos , Parálisis Cerebral/epidemiología , Parálisis Cerebral/etiología , Estudios de Cohortes , Diabetes Gestacional/epidemiología , Cohorte de Nacimiento , Ontario/epidemiología , Aumento de Peso
6.
Diabetes Metab Res Rev ; 39(3): e3604, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36547366

RESUMEN

BACKGROUND: Fasting during the holy month of Ramadan is one of the five pillars of Islam. Fasting is not meant to create excessive hardship on the Muslim individual according to religious tenets. It is important that health professionals are aware of potential risks associated with fasting during the month of Ramadan (mainly hypoglycemia and hyperglycemia). AIMS: To explore the impact of applying the principles of our 2020 recommendations for the management of type 2 diabetes (T2D) during the month of Ramadan. METHODS: A multinational randomized controlled trial (RCT) was conducted in five Muslim majority countries. Six hundred and sixty participants were deemed eligible for the study; however, 23% declined to participate later for various reasons. In total, 506 participants were enroled and were equally randomized to the intervention or the control group. At the end of the study, data from 231 participants in the intervention group and 221 participants from the control group were collected after 12.6% and 8.7% were, respectively, lost to follow-up. Participants were randomized to receive a Ramadan-focussed education with treatment for diabetes adjusted as per our 2020 recommendation update compared with the local usual care (control group). Results are presented using mean, standard deviation, odds ratio (OR), and percentages. RESULTS: At the end of the study, the number of hypoglycemic episodes in the intervention group was less than in participants who received usual care. The intervention group had significantly lower severe hypoglycemia compared to the control group with an OR of 0.2 [0.1-0.8]. Compared to baseline, both groups had a significant reduction in glycated haemoglobin (HbA1c), but the improvements were significantly greater in the intervention group. Whilst body weight reduced and high-density lipoprotein cholesterol increased with the intervention, these changes were not significantly different from usual care. CONCLUSIONS: A pre-Ramadan assessment of people with T2D coupled with pre-Ramadan education and an adjustment of glucose-lowering treatment as per our updated 2020 recommendations can prevent acute complications and allow a safer fast for people with T2D. We have shown that such an approach reduces the risk of developing severe hypoglycemia and improves the metabolic outcomes in people with T2D.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hipoglucemia , Humanos , Hipoglucemiantes/efectos adversos , Consenso , Ayuno/efectos adversos , Diabetes Mellitus Tipo 2/terapia , Hipoglucemia/etiología , Hipoglucemia/prevención & control , Islamismo , Glucemia/metabolismo
7.
Dev Med Child Neurol ; 65(2): 243-253, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-35771681

RESUMEN

AIM: To examine the prevalence and temporal trends of cerebral palsy (CP) overall and by population characteristics. METHOD: We identified 2 110 177 live births born in the province of Ontario, Canada, between 2002 and 2017 using administrative health data and estimated CP prevalence in children aged 0 to 16 years overall and by specific population characteristics. We also examined temporal trends in CP rates - overall and by characteristics - in young children (0-4 years) by their year of birth between 2002 and 2013 (n=1 587 087 live births) to allow for an equal follow-up time (4 years and 364 days) for all children. RESULTS: Overall CP prevalence among children aged 0 to 16 years was 2.52 (95% confidence interval 2.45-2.59) per 1000 live births. CP rates in ages 0 to 4 years peaked at 2.86 in 2007 births, but steadily declined afterwards to 1.94 per 1000 live births in 2013. CP rates were higher in children born preterm, small for gestational age, males, multiples, children with congenital malformations, and in children of young (<20 years), old (≥40 years), primiparous, or grand multiparous (≥4) mothers; differences by these characteristics decreased over time. We observed socioeconomic disparities in CP rates that persisted over time. INTERPRETATION: Despite the decreasing trend of CP rates overall, CP rates varied by the child and maternal characteristics over time. WHAT THIS PAPER ADDS: Overall cerebral palsy (CP) prevalence was 2.5 per 1000 live births among children born from 2002 to 2017. CP prevalence peaked in children born in 2007 then steadily decreased between 2007 and 2013. Changes in CP rates varied over time by child and maternal characteristics. Socioeconomic inequalities in CP persisted and remained stable over the study period.


Asunto(s)
Parálisis Cerebral , Recién Nacido , Masculino , Femenino , Humanos , Niño , Preescolar , Adulto Joven , Adulto , Estudios de Cohortes , Ontario/epidemiología , Parálisis Cerebral/epidemiología , Prevalencia , Edad Gestacional , Madres
8.
Aesthetic Plast Surg ; 46(Suppl 1): 94-95, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34231024

RESUMEN

This is a letter to the editor about a meta-analysis titled "The efficacy of cell-assisted lipotransfer versus conventional lipotransfer in breast augmentation: a systematic review and meta-analysis" by Li and Chen published in the year 2021. The most frequently performed aesthetic procedure is breast augmentation surgery. In breast augmentation, cell-assisted lipotransfer (CAL) has received high recognition due to its positive outcomes. There are controversies in the medical literature on the use of CAL for breast augmentation. This meta-analysis by Li and Chen has concluded that CAL using ASC was superior to other methods as it improved fat survival rate in breast augmentation. We have written this letter to the editor of the Aesthetic Plastic Surgery journal about this meta-analysis because of its impactful information provided by this study to the medical literature for breast augmentation surgery using cell-assisted lipotransfer. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.


Asunto(s)
Mamoplastia , Estética , Humanos , Mamoplastia/métodos
9.
J Environ Manage ; 324: 116363, 2022 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-36208511

RESUMEN

Biological removal of nitrogen and phosphorous from wastewater conventionally involves multiple processing steps to satisfy the differing oxygen requirements of the microbial species involved. In this work, simultaneous nitrification, denitrification, and phosphorous removal from synthetic wastewater were achieved by the fungus Neurospora discreta in a single-step, biofilm-based, aerobic process. The concentrations of carbon, nitrogen, and phosphorous in the synthetic wastewater were systematically varied to investigate their effects on nutrient removal rates and biofilm properties. Biofilm growth was significantly (p < 0.05) affected by carbon and nitrogen, but not by phosphorous concentration. Scanning electron microscopy revealed the effects of nutrients on biofilm microstructure, which in turn correlated with nutrient removal efficiencies. The carbohydrate and protein content in the biofilm matrix decreased with increasing carbon and nitrogen concentrations but increased with increasing phosphorous concentration in the wastewater. High removal efficiencies of carbon (96%), ammonium (86%), nitrate (100%), and phosphorus (82%) were achieved under varying nutrient conditions. Interestingly, decreasing the phosphorus concentration increased the nitrification and denitrification rates, and decreasing the nitrogen concentration increased the phosphorus removal rates significantly (p < 0.05). Correlations between biofilm properties and nutrient removal rates were also evaluated in this study.


Asunto(s)
Nitrificación , Aguas Residuales , Desnitrificación , Eliminación de Residuos Líquidos , Reactores Biológicos/microbiología , Fósforo/metabolismo , Nitrógeno , Biopelículas , Carbono
10.
PLoS Pathog ; 14(9): e1007289, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30231065

RESUMEN

Chronic T cell activation is a hallmark of pulmonary tuberculosis (PTB). The mechanisms underpinning this important phenomenon are however, poorly elucidated, though known to rely on control of T effector cells (Teff) by regulatory T cells (Treg). Our studies show that circulating natural Treg cells in adults with PTB preserve their suppressive potential but Teff cells from such subjects are resistant to Treg-mediated suppression. We found this to be due to expansion of an activated Teff subset identified by Human Leukocyte Antigen (HLA)-DR expression. Sensitivity to suppression was restored to control levels by depletion of this subset. Comparative transcriptome analysis of Teff cells that contain HLA-DR+ cells versus the fraction depleted of this population identified putative resistance mechanisms linked to IFNG, IL17A, IL22, PD-L1 and ß-chemokines CCL3L3, CCL4 expression. Antibody blocking experiments confirmed HLA-DR+ Teff cells, but not the fraction depleted of HLA-DR+ effectors, to be resistant to Treg suppression mediated via CCR5 and PD-L1 associated pathways. In the presence of HLA-DR+ Teff cells, activation of NFκB downstream of CCR5 and PD-L1 was perturbed. In addition, HLA-DR+ Teff cells expressed significantly higher levels of Th1/Th17 cytokines that may regulate Treg function through a reciprocal counter-balancing relationship. Taken together, our study provides novel insight on how activated HLA-DR+CD4+ T cells may contribute to disease associated inflammation by compromising Treg-mediated suppression in PTB.


Asunto(s)
Antígeno B7-H1/metabolismo , Linfocitos T CD4-Positivos/inmunología , Receptores CCR5/metabolismo , Linfocitos T Reguladores/inmunología , Tuberculosis Pulmonar/inmunología , Adulto , Antígeno B7-H1/antagonistas & inhibidores , Linfocitos T CD4-Positivos/microbiología , Citocinas/genética , Citocinas/metabolismo , Femenino , Antígenos HLA-DR/metabolismo , Interacciones Huésped-Patógeno/inmunología , Humanos , Tolerancia Inmunológica , Memoria Inmunológica , Tuberculosis Latente/inmunología , Tuberculosis Latente/microbiología , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/inmunología , Mycobacterium tuberculosis/patogenicidad , Linfocitos T Reguladores/microbiología , Tuberculosis Pulmonar/genética , Tuberculosis Pulmonar/microbiología , Regulación hacia Arriba
11.
IUBMB Life ; 72(8): 1799-1806, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32472977

RESUMEN

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common monogenic disease that has an adverse impact on the patients' health and quality of life. ADPKD is usually known as "adult-type disease," but rare cases have been reported in pediatric patients. We present here a 2-year-old Tunisian girl with renal cyst formation and her mother with adult onset ADPKD. Disease-causing mutation has been searched in PKD1 and PKD2 using Long-Range and PCR followed by sequencing. Molecular sequencing displayed us to identify a novel likely pathogenic mutation (c.696 T > G; p.C232W, exon 5) in PKD1. The identified PKD1 mutation is inherited and unreported variant, which can alter the formation of intramolecular disulfide bonds essential for polycystin-1 function. We report here the first mutational study in pediatric patient with ADPKD in Tunisia.


Asunto(s)
Predisposición Genética a la Enfermedad , Riñón Poliquístico Autosómico Dominante/genética , Canales Catiónicos TRPP/genética , Preescolar , Exones/genética , Femenino , Humanos , Mutación/genética , Riñón Poliquístico Autosómico Dominante/epidemiología , Riñón Poliquístico Autosómico Dominante/patología , Túnez/epidemiología
12.
J Immunol ; 200(10): 3587-3598, 2018 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-29669785

RESUMEN

Mycobacterium tuberculosis PPE18 is a member of the PPE family. Previous studies have shown that recombinant PPE18 (rPPE18) protein binds to TLR2 and triggers a signaling cascade which reduces levels of TNF-α and IL-12, and increases IL-10 in macrophages. Because TNF-α is a major mediator of the pathophysiology of sepsis and blocking inflammation is a possible line of therapy in such circumstances, we tested the efficacy of rPPE18 in reducing symptoms of sepsis in a mouse model of Escherichia coli-induced septic peritonitis. rPPE18 significantly decreased levels of serum TNF-α, IL-1ß, IL-6, and IL-12 and reduced organ damage in mice injected i.p. with high doses of E. coli Peritoneal cells isolated from rPPE18-treated mice had characteristics of M2 macrophages which are protective in excessive inflammation. Additionally, rPPE18 inhibited disseminated intravascular coagulation, which can cause organ damage resulting in death. rPPE18 was able to reduce sepsis-induced mortality when given prophylactically or therapeutically. Additionally, in a mouse model of cecal ligation and puncture-induced sepsis, rPPE18 reduced TNF-α, alanine transaminase, and creatinine, attenuated organ damage, prevented depletion of monocytes and lymphocytes, and improved survival. Our studies show that rPPE18 has potent anti-inflammatory properties and can serve as a novel therapeutic to control sepsis.


Asunto(s)
Antígenos Bacterianos/metabolismo , Proteínas Bacterianas/metabolismo , Inflamación/microbiología , Mycobacterium tuberculosis/metabolismo , Sepsis/microbiología , Animales , Ciego/metabolismo , Ciego/microbiología , Línea Celular , Citocinas/metabolismo , Modelos Animales de Enfermedad , Escherichia coli/metabolismo , Inflamación/metabolismo , Macrófagos/metabolismo , Macrófagos/microbiología , Masculino , Ratones , Ratones Endogámicos BALB C , Monocitos/metabolismo , Monocitos/microbiología , Proteínas Recombinantes/metabolismo , Sepsis/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
13.
Int J Environ Health Res ; 30(6): 643-652, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31094221

RESUMEN

The aim of this study was to investigate the antimicrobial phenotypes, major virulence factors, and the molecular typing of 66 P. aeruginosa isolates collected from various sources: human patients and hospital environment, raw milk, poultry meat, chicken/sheep fecal samples, wastewater, thermal water, and seawater. All isolates, except one, were susceptible to all tested antibiotics. exoA, lasB, rhlR, and lasR genes were harbored by 60 isolates. Forty-six, 18, and 2 isolates amplified exoS, exoU, and exoS+exoU genes, respectively. Twenty-one isolates showed high elastase and pigment production. The PFGE typing identified 26 pulsotypes. Some pulsotypes included isolates from different environmental niches and areas. Twelve selected isolates were typed by MLST and eight different STs were found, three of them were new. Our results highlighted the dissemination of some clones amongst different settings and the occurrence of antibiotic susceptible 'high-risk clones' that might be very harmful when acquiring genes encoding antibiotic resistance.


Asunto(s)
Farmacorresistencia Bacteriana , Microbiología Ambiental , Carne/microbiología , Leche/microbiología , Pseudomonas aeruginosa/efectos de los fármacos , Factores de Virulencia/aislamiento & purificación , Animales , Antiinfecciosos/farmacología , Pollos/microbiología , Heces/microbiología , Microbiología de Alimentos , Hospitales , Manantiales de Aguas Termales/microbiología , Humanos , Tipificación Molecular , Fenotipo , Aves de Corral , Pseudomonas aeruginosa/aislamiento & purificación , Pseudomonas aeruginosa/fisiología , Agua de Mar/microbiología , Ovinos/microbiología , Túnez , Aguas Residuales/microbiología , Microbiología del Agua
14.
Genes Immun ; 20(7): 566-576, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-30686824

RESUMEN

Inflammatory bowel disease (IBD), such as Crohn's disease and ulcerative colitis are devastating chronic immunopathologies of the intestinal mucosa, which are frequently treated by immunosuppressive glucocorticoids. Endogenous glucocorticoids are not only produced by the adrenal glands, but also by the intestinal epithelium. Local glucocorticoid synthesis critically contributes to the immune homeostasis of the intestinal mucosa. As defective intestinal glucocorticoid synthesis has been associated with the development of IBD, we investigated the expression of steroidogenic enzymes and the key transcriptional regulator Liver Receptor Homolog-1 (LRH-1/NR5A2) in ileal and colonic biopsies human pediatric IBD and control patients. Furthermore, the induction of steroidogenic enzymes and their transcriptional regulation by LRH-1 was investigated in a mouse model of experimental colitis. These analyses revealed that colitis-induced expression of steroidogenic enzymes in the murine colon is dependent on the presence of LRH-1, as intestinal deletion of LRH-1 strongly reduced their colitis-induced expression. Similarly, a strong correlation between the expression of LRH-1 and different steroidogenic enzymes was seen in intestinal biopsies of human pediatric patients. Importantly, reduced expression of hydroxysteroid dehydrogenase 11B1 (HSD11B1) was observed in IBD patients compared to control patients, suggesting that defective local reactivation of glucocorticoids could contribute to the pathogenesis of IBD.


Asunto(s)
Glucocorticoides/biosíntesis , Enfermedades Inflamatorias del Intestino/enzimología , Receptores Citoplasmáticos y Nucleares/metabolismo , Adolescente , Animales , Niño , Preescolar , Colitis Ulcerosa/metabolismo , Enfermedad de Crohn/metabolismo , Modelos Animales de Enfermedad , Femenino , Regulación de la Expresión Génica/genética , Humanos , Hidroxiesteroide Deshidrogenasas , Enfermedades Inflamatorias del Intestino/metabolismo , Mucosa Intestinal/enzimología , Mucosa Intestinal/metabolismo , Intestinos/enzimología , Masculino , Ratones , Ratones Endogámicos C57BL , Receptores Citoplasmáticos y Nucleares/genética
15.
Eur Phys J E Soft Matter ; 42(10): 134, 2019 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-31643003

RESUMEN

Biofilms are self-assembling structures consisting of rigid microbial cells embedded in a soft biopolymeric extracellular matrix (ECM), and have been commonly viewed as being detrimental to health and equipment. In this work, we show that biofilms formed by a non-pathogenic fungus Neurospora discreta, are fungal bio-composites (FBCs) that can be directed to self-organize through active stresses to achieve specific properties. We induced active stresses by systematically varying the agitation rate during the growth of FBCs. By growing FBCs that are strong enough to be conventionally tensile loaded, we find that as agitation rate increases, the elongation strain at which the FBCs break, increases linearly, and their elastic modulus correspondingly decreases. Using results from microstructural imaging and thermogravimetry, we rationalize that agitation increases the production of ECM, which concomitantly increases the water content of agitated FBCs up to 250% more than un-agitated FBCs. Water held in the nanopores of the ECM acts a plasticizer and controls the ductility of FBCs in close analogy with polyelectrolyte complexes. This paradigm shift in viewing biofilms as bio-composites opens up the possibility for their use as sustainable, biodegradable, low-modulus structural materials.


Asunto(s)
Biopelículas , Módulo de Elasticidad , Interacciones Hidrofóbicas e Hidrofílicas , Neurospora/fisiología , Biopolímeros/química , Matriz Extracelular/química , Matriz Extracelular/ultraestructura , Nanoporos , Neurospora/química , Neurospora/ultraestructura , Polielectrolitos/química , Resistencia a la Tracción
16.
BMC Pregnancy Childbirth ; 19(1): 26, 2019 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-30642277

RESUMEN

BACKGROUND: Maternal depression and anxiety have distinct constellations of symptom trajectories, which are associated with factors that may vary between different groups of women. The aim of this study was to identify subgroups of women who exhibit unique longitudinal trajectory patterns of depressive and anxiety symptoms from pregnancy to 5 years postpartum and the antenatal predictors associated with these maternal groups. METHODS: The study used a longitudinal data collected from 615 women in Saskatchewan from pregnancy to 5 years postpartum. Semiparametric group-based models were used to identify latent maternal depressive and anxiety trajectory groups. Multinomial logit models were then used to assess the association between maternal characteristics and the identified latent trajectory groups. RESULTS: We identified four trajectory groups of maternal depressive symptoms: low-stable (35%); moderate-stable (54%); moderate-increasing (5%); and high-decreasing (6%), and three trajectory groups of maternal anxiety symptoms: very low-stable (13%); low-stable (58%); and moderate-stable (29%). We also identified several risk factors, most notably history of depression and stress, that were significantly associated with these trajectories. CONCLUSION: History of depression and increased stress are significant risk factors that can be identified during regular perinatal visits; therefore, clinicians should inquire about these risk factors to identify women at high risk of ongoing depression or anxiety.


Asunto(s)
Trastornos de Ansiedad/psicología , Ansiedad/psicología , Depresión Posparto/psicología , Depresión/psicología , Madres/psicología , Complicaciones del Embarazo/psicología , Adulto , Trastorno Depresivo/psicología , Progresión de la Enfermedad , Femenino , Humanos , Estudios Longitudinales , Periodo Posparto/psicología , Embarazo , Factores de Riesgo , Saskatchewan , Estrés Psicológico/psicología , Adulto Joven
17.
J Pak Med Assoc ; 69(6): 899-901, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31201401

RESUMEN

Treatment of Cushing syndrome depends on diagnosis of etiology responsible for hypercortisolism in the body, which sometimes presents with a challenge. Inferior petrosal sinus sampling for ACTH levels, followed by peripheral venous sampling is a proven tool to be a gold standard for differentiating between peripheral and central cause of ACTH dependent Cushing syndrome. This case report is of an elderly female who presented as an outpatient in the endocrinology clinic of Aga Khan university hospital on 22/6/2017 with clinical features of hypercortisolism. After workup she was found to have cushing syndrome secondary to ACTH secreting bronchial carcinoid tumour.


Asunto(s)
Hormona Adrenocorticotrópica/metabolismo , Neoplasias de los Bronquios/diagnóstico por imagen , Tumor Carcinoide/diagnóstico por imagen , Síndrome de Cushing/diagnóstico , Anciano , Neoplasias de los Bronquios/complicaciones , Neoplasias de los Bronquios/metabolismo , Tumor Carcinoide/complicaciones , Tumor Carcinoide/metabolismo , Síndrome de Cushing/etiología , Síndrome de Cushing/metabolismo , Femenino , Humanos , Hidrocortisona/orina , Tomografía Computarizada por Rayos X
18.
Arch Womens Ment Health ; 21(6): 689-698, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-29654413

RESUMEN

The aim of this study is to identify subgroups of women who exhibit distinct trajectory patterns of depressive and anxiety disorders from pregnancy to early postpartum and the risk factors associated with the latent trajectory group memberships. Women (n = 615) from the Feelings in Pregnancy and Motherhood (FIP) longitudinal study were followed from early pregnancy to early postpartum for a 7-month period in 2006-2007. The semi-parametric group-based trajectory modeling approach was used to identify the latent trajectory groups. Multinomial logit models were then used to explore the association between latent trajectory group membership and antenatal characteristics. We identified four latent trajectory groups of perinatal depressive symptoms: "low-stable" (49.6%), "moderate-stable" (42.3%), "postpartum" (3.6%), and "antepartum" (4.6%). Significant risk factors associated with these trajectory group memberships were past depression, stress level, ethnicity, the mother's age, and relationship satisfaction. Three latent trajectory groups of perinatal anxiety symptoms were identified: "very low-stable" (8.9%); "low-stable" (60.7%); and "moderate-stable" (30.4%). Significant risk factor associated with these trajectories were past depression, stress level, and income level. Latent trajectory groups of perinatal depressive and anxiety symptoms were identified to uncover potential heterogeneity in populations. Our findings support the need for multiple assessments starting from early pregnancy to the postpartum, which can give some important insights on the characteristics of the women at high symptom burden trajectories for early interventions that may alter the progress of their mental symptoms.


Asunto(s)
Trastornos de Ansiedad , Depresión Posparto , Trastorno Depresivo , Complicaciones del Embarazo , Estrés Psicológico , Adulto , Trastornos de Ansiedad/diagnóstico , Trastornos de Ansiedad/psicología , Canadá/epidemiología , Depresión Posparto/diagnóstico , Depresión Posparto/epidemiología , Depresión Posparto/psicología , Trastorno Depresivo/diagnóstico , Trastorno Depresivo/epidemiología , Trastorno Depresivo/psicología , Femenino , Humanos , Estudios Longitudinales , Madres/psicología , Periodo Posparto/psicología , Embarazo , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/psicología , Mujeres Embarazadas/psicología , Pronóstico , Escalas de Valoración Psiquiátrica , Medición de Riesgo/métodos , Factores de Riesgo , Estrés Psicológico/diagnóstico , Estrés Psicológico/epidemiología , Estrés Psicológico/etiología , Estrés Psicológico/psicología
19.
BMC Endocr Disord ; 17(1): 30, 2017 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-28583113

RESUMEN

BACKGROUND: Diabetes registry enables practitioners to measure the characteristics and patterns of diabetes across their patient population. They also provide insight into practice patterns which can be very effective in improving care and preventing complications. The aim of this study was to assess the patterns, control levels and complications at the baseline of the patients attending clinic at the large tertiary care hospital in Karachi, Pakistan with the help of the registry. This can be used as a reference to monitor the control and also for a comparison between peer groups. METHODS: This was a cross sectional study with the data obtained from diabetes registry collected with the help of pre-designed questionnaire. HbA1c was used as a central diabetes measure and other related factors and complications were assessed with it. RESULTS: Only 16.6% of the participants had optimal HbA1c ≤ 7.0%. 52.9% of the patients were classified as having poor control defined by HbA1c of >8%. Three fourth of the study population were obese according to Asian specific BMI cutoffs and majority had type 2 diabetes with duration of diabetes ranging from less than one to about 35 years, mean(SD) duration being 7.6 years (7.1). Overall only 4% of the patients were on combine target of HbA1c, LDL and BP. Results of multivariable logistic regression showed that the odds of having optimal glycemic control increased by 3% with every one year increase in age. In addition, having longer duration of diabetes was associated with 56% lower odds of having good glycemic control. Moreover, having higher triglyceride levels was associated with 1% lower odds of having good glycemic control. CONCLUSION: This highlights the large burden of sub optimally controlled people with diabetes in Pakistani population, a low income country with huge diabetes prevalence and ineffective primary health care system creating enormous health and economic burden.


Asunto(s)
Complicaciones de la Diabetes/epidemiología , Diabetes Mellitus/epidemiología , Hemoglobina Glucada/metabolismo , Sistema de Registros , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pakistán , Pobreza , Triglicéridos/sangre
20.
BMC Pregnancy Childbirth ; 17(1): 240, 2017 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-28738869

RESUMEN

BACKGROUND: Refugee women are almost five times more likely to develop postpartum depression than Canadian-born women. This can be attributed to various difficulties they faced before coming to Canada as well as during resettlement. Moreover, refugee women usually face many obstacles when accessing health services, including language and cultural barriers, as well as unique help-seeking behaviors that are influenced by various cultural and practical factors. There has been a recent, rapid influx of Syrian refugees to Canada, and many of them are childbearing women. However, little is known about the experiences that these women have encountered pre- and post-resettlement, and their perceptions of mental health issues. Thus, there is an urgent need to understand refugee women's experiences of having a baby in Canada from a mental health perspective. METHODS: A mixed methods research design included 12 Syrian refugee women who migrated to Saskatoon in 2015-16 and who were either pregnant or 1 year postpartum. The data were collected during a single focus group discussion and a structured questionnaire. RESULTS: Our results showed that more than half of participants have depressive symptoms, half of them have anxiety symptoms, and one sixth have PTSD symptoms. Three major themes emerged from the qualitative data: 1) Understanding of maternal depression; 2) Protective factors for mental health; and 3) Barriers to mental health services. CONCLUSIONS: Maternal depression is an important feature in Syrian refugee women recently resettled in Canada. Reuniting these women with their families and engaging them in culturally appropriate support programs may improve their mental health outcomes.


Asunto(s)
Depresión/etnología , Aceptación de la Atención de Salud/etnología , Complicaciones del Embarazo/etnología , Refugiados/psicología , Adulto , Ansiedad/epidemiología , Ansiedad/etnología , Canadá/epidemiología , Depresión/epidemiología , Femenino , Grupos Focales , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Humanos , Aceptación de la Atención de Salud/psicología , Periodo Posparto/etnología , Periodo Posparto/psicología , Embarazo , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/psicología , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/etnología , Encuestas y Cuestionarios , Siria/etnología
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