Non-Tuberculosis mycobacterium speciation using HPLC under Revised National TB Control Programme (RNTCP) in India.

AIMS: Non-Tuberculous Mycobacteria (NTM) are ubiquitous in nature. The data on prevalence of NTM under the RNTCP is scarce. Many NTM species have clinical significance, and hence their identification and speciation are important. METHODS AND RESULTS: It is a cross-sectional study conducted at the five RNTCP accredited culture and drug susceptibility testing (CDST) laboratory. The culture isolates from AFB positive but Immunochromatographic test negative samples were taken for identification and speciation using HPLC. Of the total 266 isolates only 164 isolates had a second sample received at the laboratory. The speciation was done using HPLC for those isolates. The type of species identified are: 26·8% (44) were Mycobacterium chelonae, 12·8% (21) were Mycobacterium fortuitum, 9% (15) were Mycobacterium gordonae, 9% (15) were Mycobacterium tuberculosis complex, 6·1% (10) were Mycobacterium kansasii, 4·9% (8) were Mycobacterium simiae, 2·4% (4) were Mycobacterium thermophile, 1·2% (2) were Mycobacterium gastri, 0·6% (1) were Mycobacterium scrofulaceum, 0·6% (1) were Mycobacterium avium and 4·9% (8) isolates had chromatogram which was un-interpretable. CONCLUSION: Identification and its speciation of NTM are not routinely done under TB control programme. Since HPLC could identify 95% of isolates belonging to 10 species, the speciation of NTM using HPLC should gain importance in the diagnosis of disease caused by NTM. SIGNIFICANCE AND IMPACT OF STUDY: NTM are emerging as important causative agents of pulmonary and extra pulmonary disease, the ability to recognize disease caused by NTM and subsequently treat such disease has become increasingly important. The identification of NTM up to its species level should gain importance in all TB reference Laboratories.

Differential expression of microRNAs in the brains of mice subjected to increasing grade of mild traumatic brain injury.

OBJECTIVE: To investigate the effect of heterogeneity in mTBI on miRNA expression in mouse brain and to identify molecular pathways targeted by the modulated miRNAs. METHODS: A weight drop device was used to induce four increasing grades of mTBI. MiRNA expression was evaluated using TaqMan rodent miRNA arrays. Bioinformatics analysis was done using the DIANA miRPath tool and Ingenuity Pathway Analysis software. Histology of brain sections was evaluated using H&E staining. RESULTS: No histologic lesions were observed in the brains of injured mice; however, significant modulation in miRNA expression profile was observed. Global miRNA profiling indicated a trend of decrease in the number of modulated miRNAs from 24 hours to day 7 post-injury, except for the most severe grade of mTBI. Canonical pathways like calcium signalling, synaptic pathways and axon guidance pathway were the major targets of the modulated miRNAs. Network correlation analyses indicated an interaction between the modulated miRNAs and putative protein biomarkers of TBI. CONCLUSIONS: The data demonstrated that varying intensities of mTBI induced a differential miRNA expression profile in the brain post-injury. Pathways such as calcium and synaptic signalling were major targets of modulated miRNAs and may play a role in the pathophysiology of mTBI.

Investigation on the emission quality, performance and combustion characteristics of the compression ignition engine fueled with environmental friendly corn oil methyl ester - Diesel blends.

This paper deals with emission quality of diesel engine based on eco toxicological studies with different methods of environmental standard toxicity tests satisfy the Bharath and European emission norms. Based on the emission norms, Corn Oil Methyl Ester (COME) with diesel is tested in a compression ignition engine and the performance and combustion characteristics are discussed. The corn oil was esterified and the property of corn oil methyl ester was within the limits specified in ASTM D 6751-03. The COME was blended together with diesel in different proportion percentages along with B20, B40, B60, B80, and B100. The emission and performance tests for various blends of COME was carried out using single cylinder, four stroke diesel engine, and compared with the performance obtained with 100% diesel (D100). The results give clear information that COME has low exhaust emissions and increase in performance compared to D100 without any modifications. It gives better performance, which is nearer to the obtained results of D100. Specific Fuel Consumption (SFC) of B100 at the full load condition is found to be 4% lower than that of (D100). The maximum Brake Thermal Efficiency (BTE) of B100 is found to be 8.5% higher than that of the D100 at full load. Also, the maximum BTE of part load for different blends is varied from 5.9% to 7.45% which is higher than D100. The exhaust gas emissions like Carbon Monoxide (CO), Carbon Dioxide (CO2), Hydro Carbon (HC) and Nitrogen Oxide (NOx) are found to be 2.3 to 18.8% lower compared to D100 for part as well as full load. The heat release rate of biodiesel and it blends are found to 16% to 35% lower as compared to D100 for part load, where as for full load it is 21% lower than D100. The results showed that the test of emissions norms are well within the limits of Bharath VI and European VI and it leads to less pollution, less effect on green eco system and potential substitute to fossil fuels.

Vertebroplasty increases trabecular microfractures in elderly female cadaver spines.

UNLABELLED: This study assessed whether vertebroplasty increases trabecular bone microfractures in adjacent vertebrae of elderly female cadavers. Results indicated microfractures were almost two times greater in superior adjacent vertebrae for vertebroplasty treated spines compared to non-treated controls. This finding may aid in developing improved treatments for osteoporotic women with vertebral fractures. INTRODUCTION: Although vertebroplasty may stabilize compression fractures and reduce pain, subsequent vertebral fractures occur in approximately 25 % of patients, reducing the overall safety of this procedure. This is particularly a concern in vertebrae surrounding the treated level where bone cement may cause abnormal transfer of forces to adjacent spinal structures. Therefore, the objective of this study was to quantify the effects of vertebroplasty on local trabecular bone damage in adjacent vertebrae. METHODS: Five level motion segments (T11-L3) from osteopenic/osteoporotic female cadaver spines (T-score -2.9 ± 1.0) were assigned into either vertebroplasty or control (no vertebroplasty) groups (n = 10/group) such that T-score, trabecular microarchitecture, and age were similar between groups. Compression fractures were created in the L 1 vertebra of all specimens and PMMA bone cement was injected into the fractured vertebra of vertebroplasty specimens. All spine segments were subjected to cyclic axial compression (685-1370 N) for 115,000 cycles. Post-testing, trabecular cubes were cut from adjacent (T12 and L2) vertebral bodies and histologically processed. Trabecular microfractures were identified and normalized by bone area in each section. RESULTS: There were significantly more trabecular microfractures (p < 0.001) in superior adjacent vertebral bodies of the vertebroplasty group (0.091 ± 0.025 microfractures/mm(2)) when compared to the control group (0.049 ± 0.018 microfractures/mm(2)). However, there was no difference in trabecular microfractures (p = 0.835) between vertebroplasty (0.045 ± 0.022 microfractures/mm(2)) and control groups (0.035 ± 0.013 microfractures/mm(2)) for inferior adjacent vertebral bodies. CONCLUSIONS: Vertebroplasty specifically impacts the superior adjacent vertebrae of elderly female spines resulting in almost two times more trabecular microfractures when compared to non-treated controls.

Chikungunya Virus Infection Alters Expression of MicroRNAs Involved in Cellular Proliferation, Immune Response and Apoptosis.

OBJECTIVE(S): Chikungunya virus (CHIKV) is a reemerging virus of significant importance that has caused large-scale outbreaks in the countries with a temperate climate. CHIKV causes debilitating arthralgia which can persist for weeks and up to a year. Fibroblast cells are the main target of CHIKV infection. In this study, we analyzed microRNA (miRNA) modulation in the fibroblast cells infected with CHIKV at an early stage of infection. METHODS: 760 miRNAs were analyzed for modulation following infection with CHIKV at 6 h after infection. Bioinformatic analysis was done to identify the signaling pathway that may be targeted by the significantly modulated miRNAs. Validation of the miRNAs was done using a singleplex miRNA assay and protein target validation of modulated miRNAs was done by Western blot analysis. RESULTS: Computational analysis of the significantly modulated miRNAs indicated their involvement in signaling pathways such as Toll-like receptor, mTOR, JAK-STAT and Pi3-Akt pathways, which have been shown to play important roles during CHIKV infection. Topoisomerase IIß, a target of two of the modulated miRNAs, was downregulated upon CHIKV infection. CONCLUSION(S): We identified several miRNAs that may play important roles in early events after CHIKV infection and can be potential therapeutic targets against CHIKV infection.

Vitamin D2 from light-exposed edible mushrooms is safe, bioavailable and effectively supports bone growth in rats.

UNLABELLED: Widespread poor vitamin D status, a health risk for bone disease, increases the need for new food sources of vitamin D. Light-exposed edible mushrooms synthesize vitamin D(2). Bioavailability, safety, and efficacy of high levels of vitamin D(2) from mushrooms to support bone health was established in chronically fed growing rats. INTRODUCTION: Poor vitamin D status from reduced sun exposure is made worse by limited access to vitamin D-containing foods. Exposing white button mushrooms to ultraviolet B (UVB) light markedly increases their vitamin D(2) content, creating a new food source of vitamin D. We used a growing rat model to determine safety, bioavailability, and efficacy in support of bone growth by vitamin D(2) from UVB-exposed mushrooms. METHODS: We fed 150 weanling female rats one of five diets for 10 weeks, all formulated on AIN-93 G. Control diets contained no mushrooms either with or without vitamin D(3). Other diets contained 2.5% and 5.0% of UVB-exposed or -unexposed mushrooms. Safety of the high levels of vitamin D(2) from mushrooms was assessed by animal growth and by Von Kossa staining for soft tissue calcification. Bioavailability was determined from changes in circulating levels of 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH). Efficacy in support of bone growth was determined from measures of femur bending properties, size, mineralization, and microarchitecture. RESULTS: Diets containing 2.5% and 5.0% light-exposed mushrooms significantly raised 25(OH)D and suppressed PTH levels compared to control-fed rats or rats fed 5.0% mushroom unexposed to light. Microarchitecture and trabecular mineralization were only modestly higher in the light-treated mushroom-fed rats compared to the controls. Von Kossa staining revealed no soft tissue calcification despite very high plasma 25(OH)D. CONCLUSIONS: Vitamin D(2) from UVB-exposed mushrooms is bioavailable, safe, and functional in supporting bone growth and mineralization in a growing rat model without evidence of toxicity.

Craniosynostosis.

Craniosynostosis is a complex condition, characterized by the premature fusion of one of more of the cranial sutures. They can be seen individually or as part of multisystem syndromes. This review uses computed tomography (CT) with three-dimensional reconstructions to help describe some of the types and classifications of craniosynostosis, as well as describing some of the associations and the management of craniosynostosis.

Elevated miR-155 promotes inflammation in cystic fibrosis by driving hyperexpression of interleukin-8.

Cystic Fibrosis (CF) is characterized by a massive proinflammatory phenotype in the lung arising from profound expression of inflammatory genes, including interleukin-8 (IL-8). We have previously reported that IL-8 mRNA is stabilized in CF lung epithelial cells, resulting in concomitant hyperexpression of IL-8 protein. However, the mechanistic link between mutations in CFTR and acquisition of the proinflammatory phenotype in the CF airway has remained elusive. We hypothesized that specific microRNAs (miRNAs) might mediate this linkage. To identify the potential link, we screened an miRNA library for differential expression in ΔF508-CFTR and wild type CFTR lung epithelial cell lines. Of 22 differentially and significantly expressed miRNAs, we found that expression of miR-155 was more than 5-fold elevated in CF IB3-1 lung epithelial cells in culture, compared with control IB3-1/S9 cells. Clinically, miR-155 was also highly expressed in CF lung epithelial cells and circulating CF neutrophils biopsied from CF patients. We report here that high levels of miR-155 specifically reduced levels of SHIP1, thereby promoting PI3K/Akt activation. However, overexpressing SHIP1 or inhibition of PI3K in CF cells suppressed IL-8 expression. Finally, we found that phospho-Akt levels were elevated in CF lung epithelial cells and were specifically lowered by either antagomir-155 or elevated expression of SHIP1. We therefore suggest that elevated miR-155 contributes to the proinflammatory expression of IL-8 in CF lung epithelial cells by lowering SHIP1 expression and thereby activating the PI3K/Akt signaling pathway. These data suggest that miR-155 may play an important role in the activation of IL-8-dependent inflammation in CF.

Prevalence of methicillin-resistant Staphylococcus aureus in a tertiary hospital in Nepal.

SETTING: Patan Hospital, Lalitpur, Nepal. OBJECTIVES: To describe 1) the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and its antibiotic sensitivity pattern; 2) the demographic and clinical characteristics associated with MRSA infections; and 3) the treatment outcomes of in-patients with MRSA infection among patients with S. aureus infection between January 2018 and December 2020. DESIGN: This was a cross-sectional study using electronic and paper-based hospital records of patients with S. aureus infection. RESULTS: Of the 1,804 patients with S. aureus infection, 1,027 patients (57%, 95% CI 55-59) had MRSA. The MRSA were susceptible to vancomycin (100%), linezolid (96%), doxycycline (96%), chloramphenicol (86%) and cotrimoxazole (70%), and resistant to erythromycin (68%), clindamycin (56%), gentamycin (58%), ciprofloxacin (92%) and ofloxacin (91%). The prevalence of MRSA was higher in 2019, among out-patients, and in respiratory samples, and lower in blood samples. Of the 142 in-patients with MRSA, 93% had a successful clinical outcome (cured/improved). CONCLUSION: More than 50% of patients with S. aureus infection had MRSA that were resistant to commonly available antibiotics. This calls for strengthening surveil-lance and good infection control practices in this hospital.

LIEU: Hôpital de Patan, Lalitpur, Népal. OBJECTIFS: Décrire 1) la prévalence de Staphylococcus aureus résistant à la méticilline (MRSA) et son profil de sensibilité aux antibiotiques ; 2) les caractéristiques démographiques et cliniques associées aux infections à MRSA ; et 3) les résultats thérapeutiques des patients hospitalisés atteints d'infection à MRSA parmi ceux atteints d'infection à S. aureus de janvier 2018 à décembre 2020. MÉTHODE: Il s'agissait d'une étude transversale réalisée en utilisant les dossiers hospitaliers électroniques et papiers des patients atteints d'infection à S. aureus. RÉSULTATS: Sur les 1 804 patients atteints d'infection à S. aureus, 1 027 patients (57%, IC 95% 55-59) avaient un MRSA. Les MRSA étaient susceptibles à la vancomycine (100%), au linézolide (96%), à la doxycycline (96%), au chloramphénicol (86%) et au co-trimoxazole (70%), et résistants à l'érythromycine (68%), la clindamycine (56%), la gentamycine (58%), la ciprofloxacine (92%) et l'ofloxacine (91%). La prévalence des MRSA était plus élevée en 2019, parmi les patients ambulatoires, ainsi que dans les échantillons respiratoires. Elle était plus faible dans les échantillons sanguins. Sur les 142 patients hospitalisés avec MRSA, 93% ont connu un résultat clinique favorable (guérison/amélioration de l'état). CONCLUSION: Plus de 50% des patients atteints d'infection à S. aureus avaient un MRSA résistant aux antibiotiques habituellement disponibles. La surveillance et les pratiques de contrôle des infections doivent donc être renforcées dans cet hôpital.

MicroRNAs in Basolateral Amygdala Associated with Stress and Fear Memories Regulate Rapid Eye Movement Sleep in Rats.

Stress-related sleep disturbances are distressing clinical symptoms in posttraumatic stress disorder patients. Intensely stressful events and their memories change rapid eye movement (REM) sleep in animal models. REM sleep varies with individual differences of stress resilience or vulnerability. The basolateral amygdala (BLA) is a primary mediator of the effects of stress and fear memories on sleep. However, the molecular mechanisms in BLA regulating the effects of fear conditioning, shock training (ST) and context re-exposure (CTX) on REM sleep are not well known. MicroRNAs (miRNAs) are small, non-coding RNAs and posttranscriptional gene regulators of diverse biological processes. The aim of this study is to investigate ST- and CTX-altered miRNAs in the BLA of resilience and vulnerable animals and on REM sleep regulation. MiRNAs expression profiles in BLA were generated following ST and CTX using the Taqman Low Density rodent microRNA array. The altered BLA miRNAs expression and REM sleep reduction observed in ST and CTX vulnerable animals. AntagomiR-221 microinjection into BLA for one of the upregulated miRNAs, miR-221 in BLA, attenuated the REM sleep reduction. This study suggests that miRNAs in the BLA may play a significant role in mediating the effects of stress and fear memories on REM sleep.

Discrepancy in reporting among specialist registrars and the role of a paediatric neuroradiologist in reporting paediatric CT head examinations.

AIM: To evaluate the discrepancy rate among specialist registrars (SPR) to assess whether seniority had a bearing on the discrepancy rate. To investigate which were the commonly missed abnormalities and the consequences for teaching purposes. To investigate the role of a specialist consultant neuroradiologist in reporting paediatric head computed tomography examinations. MATERIALS AND METHODS: The study was carried out over a 9-month period at the regional paediatric hospital during which time 270 CT head examinations were reported. Reporting in the department is carried out by one of the five general paediatric radiologists (GR) and also a specialist paediatric neuroradiologist (NR). The NR was considered the reference standard, who corroborated in areas of discrepancy with a second senior NR for this study. Of the 270 examinations, 260 were reported by the paediatric NR, 160 were reported by the SPR, GR, and NR, and 51 were reported by an SPR and the NR. In addition, four were reported by the GR and the NR, 45 by the NR only, seven by the GR only, and three cases were reported by the GR and an SPR. The discrepancy rates were calculated for GR versus NR, and SPR versus NR. All the discrepancies were re-evaluated by a second senior NR and confirmed in all cases. The reports of the SPR were further scrutinized. The trainees of training years 1-3 were considered junior and 4-5 were considered senior. RESULTS: There was a discrepancy in 26/164 cases (15.9%) reported by the GR and NR. There was a discrepancy in 59/211 cases (28%) reported by an SPR and NR. The chi-squared test (two-sided) showed a significant difference (p=0.005) between the two groups. There was a discrepancy in 36/118 cases (30.5%) reported by the junior SPR and NR. There was a discrepancy in 23/93 cases (24.7%) reported by a senior SPR and NR. The chi-squared test (two-sided) showed a non-significant difference (p=0.353) between the two groups. CONCLUSION: The performance of the SPR was considered to be significantly different than the GR in this study. The year of training did not have a statistically significant bearing on the discrepancy rates. This study has been useful in guiding SPR with regards to paediatric CT head examination reporting. The NR played an important role, particularly in picking up subtle fractures and congenital abnormalities, which were missed by both the SPR and GR.

Using mHealth to enhance TB referrals in a tribal district of India.

Background: A mobile health (mHealth) technology based application was developed to help rural health care providers (RHCPs) identify and refer presumptive tuberculosis (TB) patients to the nearest microscopy centre for sputum examination using mobile applications on their smart phones. Objective: To determine the feasibility and yield of presumptive TB case referrals by RHCPs using mHealth technology. Methods: The project was implemented in the tribal population of Khunti District, Jharkhand State, India, from April 2012 to February 2015. 'ComCare', a mobile application designed as an aid for health care providers, was introduced and RHCPs were trained in its use. Results: Of 171 RHCPs who were formally trained to identify and refer presumptive TB patients, 30 were trained in the use of the mobile application. There were 35 referrals of presumptive TB patients per RHCP using the mobile application, and four each by RHCPs who were not using the application. Of the 194 TB cases diagnosed, RHCPs using the application contributed 127 (i.e., 4 TB cases per RHCP), while other RHCPs contributed 67 (0.5 TB case per RHCP). Conclusion: mHealth technology was highly effective, and increased both public and private health care provider accountability to patients.

Contexte: Un modèle de soins de santé via une application mobile (mHealth) a été élaboré afin de donner davantage d'autonomie aux prestataires de soins ruraux (RHCP) pour identifier et référer les patients présumés atteints de tuberculose (TB) au centre de microscopie le plus proche pour un test basé sur une application mobile.Objectif: Déterminer la faisabilité et le rendement de la référence des cas de TB présumés par les RHCP en utilisant mHealth.Méthodes: Le projet a été mis en œuvre dans la population tribale du district de Khunti, dans l'état de Jharkhand, Inde, d'avril 2012 à février 2015. L'application mobile, appelée « ComCare ¼, qui permet d'intégrer les prestataires de soins de santé, a été introduite et les prestataires de soins ont été formés à son utilisation.Résultats: Ont bénéficié 171 RHCP d'une formation officielle afin d'identifier et de référer les patients présumés TB ; 30 d'entre eux ont été formés à l'utilisation de l'application mobile (mRHCP). Il y a eu 35 références pour TBP des cas présumés par les mRHCP (c'est-à-dire les utilisateurs de l'application mobile) et 4 références pour TBP par les RHCP parmi les oRHCP (ceux n'utilisant pas l'application mobile). Au total, 194 cas de TB ont été diagnostiqués : la contribution des mRHCP a été de 127 (soit 4 cas de TB par RHCP), tandis que les références des oRHCP ont été de 67 (soit 0,5 cas de TB par RHCP). Le nombre de patients TB diagnostiqués et mis sous traitement dans la journée suivant le diagnostic a été plus élevé parmi les patients référés par les mRHCP comparés aux oRHCP.Conclusion: L'utilisation de la mHealth pour les RHCP est très efficace et elle augmente la responsabilité des prestataires de soins de santé à la fois publics et privés vis-à-vis des patients.

Marco de referencia: Se elaboró un modelo de atención de salud utilizando una aplicación para teléfonos portátiles (mHealth), que faculta a los trabajadores de salud en medio rural (RHCP) a detectar a los pacientes con presunción clínica de tuberculosis (TB) y remitirlos al centro de microscopia más cercano, a fin de practicar las pruebas diagnósticas.Objetivo: Determinar la viabilidad y el rendimiento de la remisión de casos con presunción de TB por parte de los RHCP mediante la utilización de una aplicación mHealth.Métodos: El proyecto se ejecutó en la población tribal del distrito de Khunti, en el estado de Jharkhand de la India, de abril del 2012 a febrero del 2015. Se introdujo una aplicación para teléfonos portátiles denominada 'ComCare' que comporta una función de integración de los prestadores de atención de salud y se ofreció capacitación sobre su funcionamiento a estos usuarios.Resultados: Se impartió la capacitación formal sobre la detección y la remisión de los pacientes con presunción de TB a 171 RHCP y 30 de ellos se capacitaron en la utilización de la aplicación para teléfonos portátiles (mRHCP). Los profesionales que utilizaban la aplicación remitieron 35 pacientes por RHCP con presunción de TB y los demás profesionales que no la utilizaban (oRHCP) remitieron cuatro pacientes por RHCP. Se diagnosticaron 194 casos de TB, de los cuales 127 por conducto del programa de telefonía móvil (4 casos por mRHCP) y 67 fueron remitidos por los RHCP que no utilizaban la aplicación (0,5 casos por oRHCP).Conclusión: La utilización de aplicaciones sanitarias mHealth por parte de los RHCP es de gran eficiencia y fomenta la responsabilización de los trabajadores del sector público y el sector privado frente a los pacientes.

Sodium Hypochlorite Treatment and Nitinol Performance for Medical Devices.

Processing of nitinol medical devices has evolved over the years as manufacturers have identified methods of reducing surface defects such as inclusions. One recent method proposes to soak nitinol medical devices in a 6% sodium hypochlorite (NaClO) solution as a means of identifying surface inclusions. Devices with surface inclusions could in theory then be removed from production because inclusions would interact with NaClO to form a visible black material on the nitinol surface. To understand the effects of an NaClO soak on performance, we compared as-received and NaClO-soaked nitinol wires with two different surface finishes (black oxide and electropolished). Pitting corrosion susceptibility was equivalent between the as-received and NaClO-soaked groups for both surface finishes. Nickel ion release increased in the NaClO-soaked group for black oxide nitinol, but was equivalent for electropolished nitinol. Fatigue testing revealed a lower fatigue life for NaClO-soaked black oxide nitinol at all alternating strains. With the exception of 0.83% alternating strain, NaClO-soaked and as-received electropolished nitinol had similar average fatigue life, but the NaClO-soaked group showed higher variability. NaClO-soaked electropolished nitinol had specimens with the lowest number of cycles to fracture for all alternating strains tested with the exception of the highest alternating strain 1.2%. The NaClO treatment identified only one specimen with surface inclusions and caused readily identifiable surface damage to the black oxide nitinol. Damage from the NaClO soak to electropolished nitinol surface also appears to have occurred and is likely the cause of the increased variability of the fatigue results. Overall, the NaClO soak appears to not lead to an improvement in nitinol performance and seems to be damaging to the nitinol surface in ways that may not be detectable with a simple visual inspection for black material on the nitinol surface.

Unfavourable outcomes among patients with MDR-TB on the standard 24-month regimen in Maharashtra, India.

Setting: Patients with multidrug-resistant tuberculosis (MDR-TB) registered for treatment (2011-2012 cohort) using the standard 24-month regimen, under the Revised National TB Control Programme's programmatic management of drug-resistant TB (PMDT), Maharashtra, India. Objectives: To assess the treatment outcomes and the timing and risk factors for unfavourable treatment outcomes, with a focus on death and loss to follow-up (LTFU). Method: This was a retrospective cohort study involving a review of PMDT records. Treatment outcomes were reported on 31 December 2014. Results: Of 4024 patients, treatment success was recorded in 1168 (29%). Unfavourable outcomes occurred in 2242 (56%), of whom 857 (21%) died and 768 (19%) were lost to follow-up. Treatment outcomes were missing on record review for 375 (9%) patients, and 239 (6%) were still undergoing treatment. Half of LTFU occurred within 3 months, and more than four fifths of deaths occurred after 6 months of treatment. Human immunodeficiency virus infection, being underweight, age ⩾ 15 years, male sex and pulmonary TB were the main risk factors for death, LTFU or other unfavourable treatment outcomes. Conclusion: The study found poor treatment outcomes in patients with MDR-TB registered for treatment in Maharashtra, India. Interventions are required to address the high rates of LTFU and death.

Contexte: Les patients atteints d'une tuberculose multi-résistante (TB-MDR) enregistrés en vue d'un traitement (cohorte de décembre 2011) recourant au protocole standard de 24 mois de la prise en charge programmatique de la TB pharmacorésistante (PMDT) sous l'égide du Programme national révisé de lutte contre la TB, à Maharashtra, Inde.Objectifs: Evaluer les résultats du traitement, et le timing et les facteurs de risque de résultats défavorables du traitement en particulier, le décès et les pertes de vue.Méthode: Etude rétrospective de cohorte impliquant la revue des dossiers du PMDT. Les résultats du traitement ont été rapportés au 31 décembre 2014.Résultats: Sur 4024 patients, 1168 (29%) patients ont connu un succès, tandis que 2242 (56%) ont eu un résultat défavorable : 857 (21%) sont décédés et 768 (19%) ont été perdus de vue. Les résultats du traitement ont été manquants lors de la revue des dossiers pour 375 (9%) patients et 239 (6%) patients étaient toujours sous traitement. La moitié des pertes de vue est survenue dans les 3 mois et plus de quatre décès sur cinq sont survenus après 6 mois de traitement. Le virus de l'immunodéficience humaine, la maigreur, l'âge ⩾ 15 ans, le sexe masculin et la TB pulmonaire ont été des facteurs de risque de décès ou de perte de vue ou de résultat défavorable du traitement.Conclusion: Cette étude a découvert des résultats médiocres du traitement chez des patients atteints de TB-MDR enregistrés pour traitement à Maharashtra, Inde. Des interventions sont requises pour combattre ce taux élevé de pertes de vue et de décès.

Marco de referencia: Los pacientes con diagnóstico de tuberculosis multidrogorresistente (TB-MDR) registrados para tratamiento (cohorte de 2011 y 2012) con el régimen normalizado de 24 meses del tratamiento programático de la TB farmacorresistente (PMDT, por su equivalente en inglés) en el marco del Programa Nacional Revisado contra la TB en Maharashtra, en la India.Objetivos: Evaluar los desenlaces terapéuticos, la evolución cronológica y los factores de riesgo de alcanzar un desenlace desfavorable, en especial la muerte y la pérdida durante el seguimiento.Método: Un estudio retrospectivo de cohortes con análisis de los registros del PMDT. Los desenlaces terapéuticos se notificaron el 31 de diciembre del 2014.Resultados: De los 4024 pacientes tratados, 1168 alcanzaron el éxito terapéutico (29%). Se observaron desenlaces desfavorables en 2242 pacientes (56%), así: 857 fallecieron (21%) y 768 se perdieron durante el seguimiento (19%). En el examen de los registros, faltaba el desenlace terapéutico de 375 pacientes (9%) y 239 estaban aun recibiendo tratamiento (6%). La mitad de las pérdidas durante el seguimiento ocurrió durante los primeros 3 meses y más de cuatro quintos de las muertes ocurrieron después de 6 meses de tratamiento. Los factores que se asociaron con la muerte, la pérdida durante el seguimiento u otros desenlaces desfavorables fueron la infección por el virus de la inmunodeficiencia humana, el peso insuficiente, la edad ⩾ 15 años, el sexo masculino y la TB de localización pulmonar.Conclusión: En el presente estudio se observaron desenlaces terapéuticos deficientes en los pacientes registrados en tratamiento por TB-MDR en Maharashtra, en la India. Es necesario introducir intervenciones que aborden la alta tasa de pérdida durante el seguimiento y de muertes.

Hemorrhage enhances cytokine, complement component 3, and caspase-3, and regulates microRNAs associated with intestinal damage after whole-body gamma-irradiation in combined injury.

Hemorrhage following whole-body γ-irradiation in a combined injury (CI) model increases mortality compared to whole-body γ-irradiation alone (RI). The decreased survival in CI is accompanied by increased bone marrow injury, decreased hematocrit, and alterations of miRNA in the kidney. In this study, our aim was to examine cytokine homeostasis, susceptibility to systemic bacterial infection, and intestinal injury. More specifically, we evaluated the interleukin-6 (IL-6)-induced stress proteins including C-reactive protein (CRP), complement 3 (C3), Flt-3 ligand, and corticosterone. CD2F1 male mice received 8.75 Gy 60Co gamma photons (0.6 Gy/min, bilateral) which was followed by a hemorrhage of 20% of the blood volume. In serum, RI caused an increase of IL-1, IL-2, IL-3, IL-5, IL-6, IL-12, IL-13, IL-15, IL-17A, IL-18, G-CSF, CM-CSF, eotaxin, IFN-γ, MCP-1, MIP, RANTES, and TNF-α, which were all increased by hemorrhage alone, except IL-9, IL-17A, and MCP-1. Nevertheless, CI further elevated RI-induced increases of these cytokines except for G-CSF, IFN- γ and RANTES in serum. In the ileum, hemorrhage in the CI model significantly enhanced RI-induced IL-1ß, IL-3, IL-6, IL-10, IL-12p70, IL-13, IL-18, and TNF-α concentrations. In addition, Proteus mirabilis Gram(-) was found in only 1 of 6 surviving RI mice on Day 15, whereas Streptococcus sanguinis Gram(+) and Sphingomonas paucimobilis Gram(-) were detected in 2 of 3 surviving CI mice (with 3 CI mice diseased due to inflammation and infection before day 15) at the same time point. Hemorrhage in the CI model enhanced the RI-induced increases in C3 and decreases in CRP concentrations. However, hemorrhage alone did not alter the basal levels, but hemorrhage in the CI model displayed similar increases in Flt-3 ligand levels as RI did. Hemorrhage alone altered the basal levels of corticosterone early after injury, which then returned to the baseline, but in RI mice and CI mice the increased corticosterone concentration remained elevated throughout the 15 day study. CI increased 8 miRNAs and decreased 10 miRNAs in serum, and increased 16 miRNA and decreased 6 miRNAs in ileum tissue. Among the altered miRNAs, CI increased miR-34 in the serum and ileum which targeted an increased phosphorylation of ERK, p38, and increased NF-κB, thereby leading to increased iNOS expression and activation of caspase-3 in the ileum. Further, let-7g/miR-98 targeted the increased phosphorylation of STAT3 in the ileum, which is known to bind to the iNOS gene. These changes may correlate with cell death in the ileum of CI mice. The histopathology displayed blunted villi and villus edema in RI and CI mice. Based on the in silico analysis, miR-15, miR-99, and miR-100 were predicted to regulate IL-6 and TNF. These results suggest that CI-induced alterations of cytokines/chemokines, CRP, and C3 cause a homeostatic imbalance and may contribute to the pathophysiology of the gastrointestinal injury. Inhibitory intervention in these responses may prove therapeutic for CI and improve recovery of the ileal morphologic damage.

Perspectives towards predictive testing in Huntington disease.

OBJECTIVE: Genetic counseling for individuals undergoing presymptomatic testing is lacking in India although testing is easily available. This has an impact on family members of Huntington's disease (HD), an autosomal dominant disease, wherein the age at onset of symptoms varies. AIM: We examine if attitudes differ towards presymptomatic testing for HD amongst HD family members, physicians and laypersons. MATERIALS AND METHODS: A modified questionnaire enquiring about opinions on various personal, family, social and future health care with regards to presymptomatic testing of HD was designed. A physician explained briefly about HD and presymptomatic testing of HD and recorded responses of unaffected family members of HD (n=25) and laypersons (n=50). Medical doctors (n=50) answered the questionnaire based on their knowledge of HD. RESULTS: HD family members, Medical doctors and laypersons were similar in their opinion to undergo the testing. Majority (60%) of HD family members did not wish to communicate test results with their friends when compared to the other two groups. Medical doctors and HD family members were more concerned about certainty of developing disease when the test results are positive. Majority (80%) of Medical doctors and less than half in the other groups felt that their decision to have a child would strongly depend on test results. Large proportion (80%) of HD family members did not wish to report their test results to their employers. CONCLUSIONS: Individuals with knowledge about HD and the test differ in their decision of sharing test results and reproductive choices.

A Panel of Serum MiRNA Biomarkers for the Diagnosis of Severe to Mild Traumatic Brain Injury in Humans.

MicroRNAs (MiRNAs) are small endogenous RNA molecules and have emerged as novel serum diagnostic biomarkers for several diseases due to their stability and detection at minute quantities. In this study, we have identified a serum miRNA signature in human serum samples of mild to severe TBI, which can be used for diagnosis of mild and moderate TBI (MMTBI). Human serum samples of MMTBI, severe TBI (STBI), orthopedic injury and healthy controls were used and miRNA profiling was done using taqman real time PCR. The real time PCR data for the MMTBI, STBI and orthopedic injury was normalized to the control samples which showed upregulation of 39, 37 and 33 miRNAs in MMTBI, STBI and orthopedic injury groups respectively. TBI groups were compared to orthopedic injury group and an up-regulation of 18 and 20 miRNAs in MMTBI and STBI groups was observed. Among these, a signature of 10 miRNAs was found to be present in both MMTBI and STBI groups. These 10 miRNAs were validated in cerebrospinal fluid (CSF) from STBI and four miRNAs were found to be upregulated in CSF. In conclusion, we identified a subset of 10 unique miRNAs which can be used for diagnosis of MMTBI and STBI.

Differential compaction of transcriptionally competent and repressed chromatin reconstituted with histone H1 subtypes.

Chromatin fragments stripped of H1 histones regain the ability to form higher order structures and aggregates in 0.15 M NaCl following reconstitution with histone H1. However, transcriptionally competent chromatin fragments are resistant to chicken erythrocyte H1/H5 histone-induced 0.15 M NaCl aggregation/precipitation. In this study, we investigated the ability of stripped chromatin fragments reconstituted with one of four histone H1 subtypes (chicken erythrocyte H1, H5, trout liver H1a, H1b) at various stoichiometries to form salt precipitable higher order structures. Our results provide evidence that chicken erythrocyte histone H1 was more effective than histone H5 and trout liver histone H1b better than H1a in forming higher order structures. None of the histone H1 subtypes could render transcriptionally competent chromatin fragments insoluble in 0.15 M NaCl. These results are consistent with the ideas that the histone H1 subtypes differ in their capacities to compact chromatin fiber, and that the alterations in the structure of transcriptionally competent nucleosomes interfere with the capacity of all H1 subtypes to form higher order structures.

Follow-up examinations: are multidrug-resistant tuberculosis patients in Uttar Pradesh, India, on track?

SETTING: All multidrug-resistant tuberculosis (MDR-TB) patients who had completed 6 months of treatment under the Revised National Tuberculosis Control Programme (RNTCP) in Uttar Pradesh, the largest state in northern India. OBJECTIVE: To determine the proportion of MDR-TB patients with regular follow-up examinations, and underlying provider and patient perspectives of follow-up services. METHODS: A retrospective cohort study was undertaken involving record reviews of 64 eligible MDR-TB patients registered during April-June 2013 in 11 districts of the state. Patients and programme personnel from the selected districts were interviewed using a semi-structured questionnaire. RESULTS: A total of 34 (53.1%) patients underwent follow-up sputum culture at month 3, 43 (67.2%) at month 4, 36 (56.3%) at month 5 and 37 (57.8%) at month 6. Themes associated with irregular follow-up that emerged from the interviews were multiple visits, long travel distances, shortages of equipment at the facility and lack of knowledge among patients regarding the follow-up schedule. CONCLUSION: The majority of the MDR-TB patients had irregular follow-up visits. Provider-related factors outweigh patient-related factors on the poor follow-up examinations. The programme should focus on the decentralisation of follow-up services and ensure logistics and patient-centred counselling to improve the regularisation of follow up.

Contexte : Tous les patients atteints de tuberculose multirésistante (TB-MDR) qui avaient achevé 6 mois de traitement dans le cadre du Programme National Révisé de Lutte contre la Tuberculose (RNTCP) dans l'Uttar Pradesh, le plus grand état dans le nord de l'Inde.Objectif : Déterminer la proportion de patients TB-MDR bénéficiant d'examens de suivi régulier et la vision des prestataires et des patients sur ces services de suivi.Méthodes : Une étude rétrospective de cohorte a été réalisée grâce à la revue des dossiers de 64 patients TB-MDR éligibles enregistrés entre avril et juin 2013 dans 11 districts de l'état. Les patients et le personnel du RNTCP des districts sélectionnés ont également été interviewés grâce à un questionnaire semi-structuré.Résultats : Au total, 34 (53,1%) patients ont bénéficié d'examens de culture de crachats au 3e mois, 43 (67,2%) au 4e mois, 36 (56,3%) au 5e mois et 37 (57,8%) au 6e mois. Les principaux facteurs associés à un suivi irrégulier émanant des entretiens étaient le nombre élevé de consultations, la distance à parcourir, les ruptures de stock dans les structures et le manque de connaissances des patients vis-à-vis du programme de suivi.Conclusion : La majorité des patients TB-MDR ont eu un suivi irrégulier. Les facteurs liés aux prestataires dépassent ceux liés aux patients en matière d'examens de suivi médiocres. Le RNTCP devrait se concentrer sur la décentralisation des services de suivi, assurer la logistique et le conseil centré sur le patient afin d'accroitre la régularité du suivi.

Marco de referencia: Todos los pacientes con diagnóstico de tuberculosis multidrogorresistente (TB-MDR) después de haber completado los 6 meses de tratamiento en el contexto del Programa Nacional de Control de la Tuberculosis (RNTCP) en Uttar Pradesh, la provincia más grande del norte de la India.Objetivo: Determinar la proporción de pacientes con TB-MDR en quienes se practicaron exámenes periódicos de seguimiento y conocer las opiniones de los profesionales y de los pacientes sobre los servicios de seguimiento.Métodos: Se llevó a cabo un estudio de cohortes retrospectivo a partir del examen de las historias clínicas de 64 pacientes con diagnóstico de TB-MDR, que cumplían con los requisitos de inclusión, registrados entre abril y junio del 2013 en 11 distritos del estado. Se realizaron además entrevistas a los pacientes y al personal del RNTCP de algunos distritos mediante un cuestionario semi-estructurado.Resultados: En 34 pacientes se practicó el seguimiento del cultivo de esputo al tercer mes (53,1%), en 43 casos al cuarto mes (67,2%), en 36 al quinto mes (56,3%) y en 37 pacientes al sexto mes de tratamiento (57,8%). Los principales factores asociados con la irregularidad del seguimiento que revelaron las entrevistas fueron la multiplicidad de las citas, la larga distancia de los desplazamientos, la carencia de insumos en los centros y el desconocimiento del calendario del seguimiento por parte de los pacientes.Conclusión: El seguimiento de la mayoría de los pacientes con diagnóstico de TB-MDR fue irregular. En las causas de la deficiencia del seguimiento predominaron los factores dependientes de los profesionales en comparación con los factores propios a los pacientes. El RNTCP debe considerar seriamente la descentralización de los servicios de seguimiento, suministrarlos materiales necesarios y proveer una orientación centrada en los pacientes con el objeto de mejorar la regularidad de los seguimientos.

Compliance with infection control practices in sputum microscopy centres: a study from Kerala, India.

BACKGROUND: One of the strategies of the Revised National Tuberculosis Control Programme in India to achieve tuberculosis control is by increasing case detection through a nationwide network of designated microscopy centres (DMC). Practice of standard precautions for infection control in these DMCs is very important to prevent transmission of infection not only to the laboratory personnel, but also to the general population. However, in India this has not been evaluated by an external agency. METHOD: A cross-sectional study was carried out to assess knowledge, facilities and compliance regarding infection control practices (ICP) in all 38 DMCs in Kannur district, Kerala, India, in 2015. Using observations and interviews, the investigators collected data in a structured format. RESULTS: Overall knowledge about infection control was found to be satisfactory among 29% of laboratory technicians. Overall facilities for infection control were satisfactory in 61% of the DMCs, while adherence to ICP was satisfactory in 45% of the DMCs. Knowledge regarding ICP was better in government DMCs, whereas facilities for ICP and adherence to biomedical waste management guidelines were better in private DMCs. CONCLUSION: Given the higher risk of infection among laboratory technicians, there is an urgent need to address the shortcomings in infection control practices.

Contexte : Une des stratégies du Programme national révisé de lutte contre la tuberculose (RNTCP) en Inde consiste à lutter contre la tuberculose en augmentant la détection des cas à travers un réseau national de Centres de Diagnostic par Microscopie (DMC). La mise en oeuvre des précautions standard de lutte contre les infections dans ces DMC est très importante pour prévenir la transmission des infections, non seulement vis-à-vis du personnel de laboratoire, mais également vis-à-vis de la population générale. Cependant, en Inde, ceci n'a pas été évalué par une agence externe.Méthode : Une étude transversale a été réalisée pour évaluer les connaissances, la structure et l'adhésion aux pratiques de lutte contre l'infection (ICP) dans les 38 DMC du district de Kannur, état du Kerala, Inde en 2015. Grâce à des observations et à des entretiens, les investigateurs ont recueilli des données dans un format structuré.Résultats : Les connaissances d'ensemble relatives à la lutte contre l'infection ont été jugées satisfaisantes pour 29% des techniciens de laboratoire. Le niveau d'ensemble des centres en matière de lutte contre l'infection a été satisfaisant dans 61% des DMC. L'adhésion aux pratiques de lutte contre l'infection a été satisfaisante dans 45% des DMC. Les connaissances relatives aux pratiques d'ICP ont été meilleures dans les DMC du gouvernement tandis que les installations et l'adhésion aux directives de gestion des déchets biomédicaux ont été meilleures dans les DMC privés.Conclusion : Connaissant le risque très élevé d'infection parmi les techniciens de laboratoire, il y a un besoin urgent de corriger les déficiences des pratiques de lutte contre l'infection.

Marco de referencia: Una de las estrategias del Programa Nacional Revisado contra la Tuberculosis de la India consiste en controlar la enfermedad al aumentar la detección de casos por conducto de una red nacional de centros de microscopia diagnóstica (DMC). La práctica de las precauciones corrientes de control de las infecciones en estos centros es muy importante con el fin de evitar la transmisión no solo al personal de laboratorio, sino también a la población general. Sin embargo, ningún organismo externo ha evaluado estas prácticas en el país.Método: Se llevó a cabo un estudio transversal con el fin de evaluar los conocimientos, la adecuación de los establecimientos y el cumplimiento de las prácticas en materia de control de las infecciones (ICP) en 38 DMC del distrito de Kannur en el estado de Kerala en la India en 2015. Los investigadores recogieron datos mediante observaciones y entrevistas estructuradas.Resultados: En general, el 29% del personal auxiliar de laboratorio poseía un grado satisfactorio de conocimientos sobre el control de las infecciones; el 61% de los DMC contaba con dispositivos adecuados de ICP y en el 45% se observó el cumplimiento de las normas. El conocimiento de las ICP fue mayor en los DMC del sector público, pero los dispositivos de los establecimientos y el cumplimiento de las directrices de eliminación de los desechos biológicos fueron de mejor calidad en los DMC del sector privado.Conclusión: Teniendo en cuenta el mayor riesgo de exposición a las infecciones que presenta el personal auxiliar de laboratorio, existe una necesidad urgente de abordar las deficiencias observadas en las prácticas de control de las infecciones.