Prolonged Itraconazole Therapy as Sole Treatment for Patients with Allergic Fungal Rhinosinusitis.

BACKGROUND: Currently, the mainstay of treatment for allergic fungal rhinosinusitis (AFRS) is surgical debridement along with topical or systemic steroids. However, prolonged systemic steroid therapy comes with side effects and is also sometimes contraindicated. Systemic antifungals have been used earlier as an adjunct to steroids or in refractory cases, but they have not been used as the sole primary treatment. OBJECTIVE: To study the effectiveness of sole Itraconazole therapy in patients with AFRS by comparison of clinical, radiological, and biochemical parameters before and after treatment. METHODS: Thirty-four patients diagnosed with localized sino-nasal AFRS were recruited and started on the tablet Itraconazole 200 mg orally twice daily for 3 months with q2weekly monitoring of liver function tests. The baseline clinical, radiological, and biochemical parameters were then compared with those after completion of 3 months of Itraconazole therapy. RESULTS: There was significant difference between all the parameters-clinical: SNOT-22 score (p < 0.001) and Meltzer endoscopy score (p < 0.001), radiological: Lund-Mackay score (p = 0.004) and 20-point CT score (p = 0.002), and biochemical: serum total IgE (p < 0.001), Aspergillus-specific IgE (p < 0.001), and absolute eosinophil count (p < 0.001). The clearance of the disease was more in anterior sinuses than the posterior ones. CONCLUSION: Prolonged Itraconazole can be given as sole therapy in AFRS, especially in patients for whom steroids are contraindicated or in those who are awaiting surgery. It can result in symptomatic and radiological improvement, but surgery still remains the definitive treatment option for AFRS for complete clearance of disease. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:545-551, 2024.

Effect of surgical intervention on serum insulin-like growth factor 1 in patients with obstructive sleep apnoea.

OBJECTIVE: To evaluate the effect of surgical intervention on serum insulin-like growth factor 1 levels in patients with obstructive sleep apnoea. METHODS: A prospective study was conducted in a tertiary care hospital of adult patients with obstructive sleep apnoea for whom continuous positive airway pressure therapy failed or was refused. All patients underwent polysomnography and serum insulin-like growth factor 1 evaluation pre-operatively and at three months post-operatively. The site of surgery was determined using Müller's manoeuvre and ApneaGraph AG 200. RESULTS: Fifteen patients were included with a mean age of 38 years: 11 males and 4 females. The mean pre-operative Apnoea-Hypopnoea Index using polysomnography was 53.7 events per hour, and the mean post-operative Apnoea-Hypopnoea Index at three months was 15.3 events per hour (p = 0.0001). The mean pre-operative serum insulin-like growth factor 1 was 160.2 µg/l, while the mean post-operative value was 236.98 µg/l (p = 0.005). CONCLUSION: In adult patients with obstructive sleep apnoea for whom continuous positive airway pressure therapy fails, site-specific surgical intervention to treat the obstruction leads to an increase in serum insulin-like growth factor 1 levels.

Energy decomposition and waterswapping analysis to investigate the SNP associated DPD mediated 5-FU resistance.

5-fluorouracil is an essential component of systemic chemotherapy for colon, breast, head, and neck cancer patients. However, tumoral overexpression of the dihydropyrimidine dehydrogenase has rendered 5-FU clinically ineffective by inactivating it to 5'-6'-dihydro fluorouracil. The responses to 5-FU in terms of efficacy and toxicity greatly differ depending upon the population group, because of variability in the DPD activity levels. In the current study, key active site amino acids involved in the 5-FU inactivation were investigated by modelling the 3D structure of human DPD in a complex with 5-FU. The identified amino acids were analyzed for their possible missense mutations available in dbSNP database. Out of 12 missense SNPs, four were validated either by sequencing in the 1000 Genomes project or frequency/genotype data. The recorded validated missense SNPs were further considered to analyze the effect of their respective alterations on 5-FU binding. Overall findings suggested that population bearing the Glu611Val DPD mutation (rs762523739) is highly vulnerable to 5-FU resistance. From the docking, electrostatic complementarity, dynamics, and energy decomposition analyses it was found that the above mutation showed superior scores than the wild DPD -5FU complex. Therefore, prescribing prodrug NUC-3373 or DPD inhibitors (Gimeracil/3-Cyano-2,6-Dihydroxypyridines) as adjuvant therapy may overcome the 5-FU resistance.

Intracellular cytokine expression in invasive fungal sinusitis and its impact on patient outcome.

BACKGROUND: Cell-mediated immunity plays an important role in host defence against fungal pathogens, regulated by differentiation of lymphocytes towards T-helper 1 or 2 cells. This study reports intracellular cytokine variation in terms of invasive fungal sinusitis type and outcome. METHODS: The mononuclear leukocytes of 15 patients with invasive fungal sinusitis (mucormycosis in 8, aspergillus in 7) were stained with antibodies against intracellular cytokines, after fungal antigen stimulation and culture, and immunophenotyped. Patients were followed up for six months, with clinical course categorised as improvement, worsening or death. RESULTS: The mean percentages of mononuclear cells producing interleukins 4, 5, 10 and 12, and interferon-γ, in the mucormycosis group were 0.575, 0.284, 8.661, 4.460 and 1.134, respectively, while percentages in the aspergillosis group were 0.233, 0.492, 4.196, 4.466 and 1.533. Cells producing interleukin 4 and 10 were higher in the mucormycosis group, while those producing interleukin-12 and interferon-γ were lower. Cells producing interleukins 4 and 12 were higher in patients with a poor outcome (p-values of 0.0662 and 0.0373, respectively), while those producing interferon-γ were lower (p = 0.0864). CONCLUSION: Adaptive cell-mediated immunity is expressed differently in two categories of invasive fungal sinusitis, and the cytokine expression pattern is related to prognosis.

Facial neuritis in coronavirus disease 2019 associated mucormycosis: study on clinico-radiological correlates.

OBJECTIVE: To elucidate the aetiopathogenesis of facial neuritis in coronavirus disease 2019 associated mucormycosis. METHODS: A retrospective review was conducted of coronavirus disease 2019 associated mucormycosis patients who presented with peripheral facial nerve palsy from January 2021 to July 2021. The clinico-radiological details of four patients were assessed to examine the potential mechanism of facial nerve involvement. RESULTS: Serial radiological evaluation with contrast-enhanced computed tomography and contrast-enhanced magnetic resonance imaging revealed infratemporal fossa involvement in all cases, with the inflammation extending along fascial planes to reach the stylomastoid foramen. Ascending neuritis with an enhancement of the facial nerve was demonstrated in all cases. CONCLUSION: The likely explanation for facial palsy in patients with coronavirus disease 2019 associated mucormycosis, backed by radiology, is the disease abutting the facial nerve at the stylomastoid foramen and causing ascending neuritis of the facial nerve.

Indications and advantages of endoscopic trans-sphenoid approach for petrous apex lesions: two case reports.

BACKGROUND: The choice of surgical approach for a petrous apex lesion depends on its relationship with the internal carotid artery, degree of medial expansion and pathology. The correct identification of patients who will benefit from this approach is necessary. CASE REPORTS: Two adult patients presented with a lesion in the left petrous apex. Computed tomography showed a homogeneous mass extending anteromedially, and abutting the internal carotid artery and the sphenoid sinus in both patients. Using magnetic resonance imaging, a third recurrence of cholesterol granuloma in case one and cholesteatoma in case two were diagnosed. Both patients underwent trans-sphenoid excision, as the sphenoid sinus was well pneumatised and the lesion was medial to the internal carotid artery. CONCLUSION: Nasal endoscopic access to the petrous apex via the trans-sphenoid corridor should be preferred for benign lesions extending anteromedially in cases where lateral access is impeded by the internal carotid artery, the labyrinth and the facial nerve, and anterior trans-sphenoidal access offers a low-morbidity alternative.

Serum otolin-1 as a biomarker for benign paroxysmal positional vertigo: a case-control study.

OBJECTIVES: This study aimed to evaluate serum otolin-1 levels in patients with benign paroxysmal positional vertigo and to compare these levels with healthy individuals. METHOD: This was a case-control study. After obtaining institutional ethical committee clearance, the serum level of otolin-1 was calculated in adult individuals (18-75 years old) who were divided into group 1 (patients presenting with benign paroxysmal positional vertigo) and group 2 (healthy patients without benign paroxysmal positional vertigo as the control group). Data analysis was carried out to compare the serum levels in the cases and controls. A p-value less than 0.05 was considered significant. RESULTS: A total of 70 age-matched individuals (cases, n = 40; controls, n = 30) were included in the study. The mean serum level of otolin-1 was 636.8 pg/ml (range, 259-981 pg/ml) in the group of patients with benign paroxysmal positional vertigo and 236.2 pg/ml (range, 189-370 pg/ml) in the control group. The difference was statistically significant (p = 0.0000). CONCLUSION: The serum levels of otolin-1 in patients with benign paroxysmal positional vertigo are significantly higher compared with individuals without benign paroxysmal positional vertigo.

In silico guided design of non-covalent inhibitors of DprE1: synthesis and biological evaluation.

DprE1 is a potential target of resistant tuberculosis (TB), especially multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB. 2-benzoxazolinone is a closely related bioisostere of some scaffolds such as benzoxazoles, benzimidazole, benzothiazolinone, and benzothiazoles that have been previously explored against DprE1. Thus, a ligand-based quantitative pharmacophore model (AHRR.8) of DprE1 was developed and this pharmacophore model was utilized in activity profiling of some 2-benzoxazolinones from an in-house database using virtual screening. Obtained hits were subject to molecular docking, molecular dynamics (MD), and MM/GBSA calculations, which resulted in benzoyl-substituted derivatives of 2-benzoxazolinone showing strong interactions with the key amino acid residues in the active site of DprE1. Based on in silico results, the top five hits were duly synthesized and evaluated against the XDR-TB strain. This study is an initial effort to explore 2-benzoxazolinones against XDR-TB, which can be submitted further to lead optimization for refining the results.

Trehalose limits opportunistic mycobacterial survival during HIV co-infection by reversing HIV-mediated autophagy block.

Opportunistic bacterial infections amongst HIV-infected individuals contribute significantly to HIV-associated mortality. The role of HIV-mediated modulation of innate mechanisms like autophagy in promoting opportunistic infections, however, remains obscure. Here we show, HIV reactivation in or infection of macrophages inhibits autophagy and helps the survival of pathogenic Mycobacterium tuberculosis (Mtb) and nonpathogenic non-tuberculous mycobacterial strains (NTMs). The HIV-mediated impairment of xenophagy flux facilitated bacterial survival. Activation of autophagy by trehalose could induce xenophagy flux and kill intracellular Mtb or NTMs either during single or co-infections. Trehalose, we delineate, activates PIKFYVE leading to TFEB nuclear translocation in MCOLN1-dependent manner to induce autophagy. Remarkably, trehalose significantly reduced HIV-p24 levels in ex-vivo-infected PBMCs or PBMCs from treatment-naive HIV patients and also controlled mycobacterial survival within Mtb-infected animals. To conclude, we report leveraging of HIV-mediated perturbed host innate-immunity by opportunistic bacterial pathogens and show an attractive therapeutic strategy for HIV and associated co-morbidities.Abbreviations: AIDS: acquired immune deficiency syndrome; AMPK: AMP-activated protein kinase; ATG5: autophagy related 5; BafA1: bafilomycin A1; CFU: colony forming unit; CTSD: cathepsin D; CD63: CD63 molecule; EGFP: enhanced green fluorescent protein; FRET: Förster resonance energy transfer; GABARAP: gamma-aminobutyric acid receptor-associated protein; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; GLUT: glucose transporter; HIV: human immunodeficiency virus; hMDMs: human monocyte derived macrophages; IL2: interleukin 2; LAMP1: lysosomal-associated membrane protein 1; LC3B-II: lipidated microtubule-associated proteins 1A/1B light chain 3B; Mtb: Mycobacterium tuberculosis; MTOR: mechanistic target of rapamycin; mRFP: monomeric red fluorescent protein; M6PR: mannose-6-phosphate receptor; NAC: N- acetyl- L -cysteine; NTM's: non-tuberculous mycobacteria; PBMC: Peripheral Blood Mononuclear cells; PIKFYVE: phosphoinositide kinase; FYVE-Type Zinc Finger; PHA: phytohemagglutinin; PMA: phorbol 12-myristate 13-acetate; PtdIns(3,5)P2: Phosphatidylinositol 3,5-bisphosphate; ptfLC3: pEGFP-mRFP-LC3; ROS: reactive oxygen species; SQSTM1: sequestosome1; TFEB: transcription factor EB; MCOLN1/TRPML1: mucolipin 1; PIP4P1/TMEM55B: Human trans-membrane Protein 55B; UVRAG: UV Radiation Resistance Associate; VPS35: vacuolar protein sorting associated protein 35; WDR45: WD repeat domain 45; YCAM: Yellow Chameleon.

Hemangiopericytoma of meningo-fronto-naso-orbito-maxillary complex.

Hemangiopericytoma (HPC) is a rare vascular tumour and difficult to diagnose clinically. Incidence is reported in fourth to fifth decade of life.With female predominance, 3%-5% cases affect the oral cavity, sinus lining and meninges. The patient presented with 8×6 cm swelling on her face, evaluation reported it to be HPC. Bilateral maxillary artery embolisation, wide local excision of the lesion, preserving the left eye and its function, was done. No recurrence is reported at 1-year follow-up. Response of such lesions to radiotherapy is questionable; with no lymphadenopathy and adequate encapsulation, embolisation of feeder vessel followed by a wide local excision of the lesion seems to be a fairly good option of treatment.

Hepatitis E outbreak in Jaipur due to Genotype IA.

Purpose: Suddenly, many cases of fever with jaundice were reported from Sodala area at Jaipur. This outbreak of acute hepatitis at Jaipur Rajasthan was investigated for aetiology and subsequent phylogenetic analysis. Methods: Blood samples were collected from 106 symptomatic patients of acute hepatitis and 39 pregnant females (with or without symptoms of hepatitis) during an outbreak at Jaipur. The samples were tested for hepatitis A virus (HAV) and hepatitis E virus (HEV) by serological and molecular methods (polymerase chain reaction [PCR]). Sequencing of nested PCR product was done for phylogenetic analysis. Hepatitis B surface antigen (HBs antigen), anti-hepatitis C virus (HCV), anti-Leptospira and anti-scrub typhus IgM enzyme-linked immunosorbent assay (ELISA) was done for patients negative for HEV and HAV. Results: Among 106 symptomatic patients, HEV IgM was positive in 84/106 (79.2%) patients and HEV RNA in 72/106 (67.9%) patients. Among pregnant women, 6/39 (15.4%) were HEV IgM positive and 5/39 (12.8%) for HEV RNA. One (2.5%) pregnant woman died due to hepatitis. All the isolates belonged to genotype 1A of HEV. All HAV, HEV-negative samples were negative for HBs antigen, HCV antibody, Leptospira and scrub typhus IgM ELISA. Conclusion: The outbreak was due to HEV genotype 1A. The municipal water supply was contaminated and sanitary conditions and waste disposal were poor in the area. Boiling of drinking water, fixing the water supply pipes and frequent hand washing helped in controlling the outbreak.

Variability Assessment for Root and Drought Tolerance Traits and Genetic Diversity Analysis of Rice Germplasm using SSR Markers.

The studies on genetic variation, diversity and population structure of rice germplasm of North East India could be an important step for improvements of abiotic and biotic stress tolerance in rice. Genetic diversity and genetic relatedness among 114 rice genotypes of North East India were assessed using genotypic data of 65 SSR markers and phenotypic data. The phenotypic diversity analysis showed the considerable variation across genotypes for root, shoot and drought tolerance traits. The principal component analysis (PCA) revealed the fresh shoot weight, root volume, dry shoot weight, fresh root weight and drought score as a major contributor to diversity. Genotyping of 114 rice genotypes using 65 SSR markers detected 147 alleles with the average polymorphic information content (PIC) value of 0.51. Population structure analysis using the Bayesian clustering model approach, distance-based neighbor-joining cluster and principal coordinate analysis using genotypic data grouped the accession into three sub-populations. Population structure analysis revealed that rice accession was moderately structured based on FST value estimates. Analysis of molecular variance (AMOVA) and pairwise FST values showed significant differentiation among all the pairs of sub-population ranging from 0.152 to 0.222 suggesting that all the three subpopulations were significantly different from each other. AMOVA revealed that most of the variation in rice accession mainly occurred among individuals. The present study suggests that diverse germplasm of NE India could be used for the improvement of root and drought tolerance in rice breeding programmes.

Temporal bone meningoencephaloceles and cerebrospinal fluid leaks: experience in a tertiary care hospital.

OBJECTIVE: To recount experience with cerebrospinal fluid otorrhoea and temporal bone meningoencephalocele repair in a tertiary care hospital. METHOD: A retrospective review was conducted of 16 cerebrospinal fluid otorrhoea and meningoencephalic herniation patients managed surgically from 1991 to 2016. RESULTS: Aetiology was: congenital (n = 3), post-traumatic (n = 2), spontaneous (n = 1) or post-mastoidectomy (n = 10). Surgical repair was undertaken by combined middle cranial fossa and transmastoid approach in 3 patients, transmastoid approach in 2, oval window plugging in 1, and subtotal petrosectomy with middle-ear obliteration in 10. All patients had successful long-term outcomes, except one, who experienced recurrence after primary stage oval window plugging, but has been recurrence-free after second-stage subtotal petrosectomy with middle-ear obliteration. CONCLUSION: Dural injury or exposure in mastoidectomy may lead to cerebrospinal fluid otorrhoea or meningoencephalic herniation years later. Congenital, spontaneous and traumatic temporal bone defects may present similarly. Middle cranial fossa dural repair, transmastoid multilayer closure and subtotal petrosectomy with middle-ear obliteration were successful procedures. Subtotal petrosectomy with middle-ear obliteration offers advantages over middle cranial fossa dural repair alone; soft tissue closure is more robust and is preferred in situations where hearing preservation is not a priority.

Redox-dependent condensation of the mycobacterial nucleoid by WhiB4.

Oxidative stress response in bacteria is mediated through coordination between the regulators of oxidant-remediation systems (e.g. OxyR, SoxR) and nucleoid condensation (e.g. Dps, Fis). However, these genetic factors are either absent or rendered non-functional in the human pathogen Mycobacterium tuberculosis (Mtb). Therefore, how Mtb organizes genome architecture and regulates gene expression to counterbalance oxidative imbalance is unknown. Here, we report that an intracellular redox-sensor, WhiB4, dynamically links genome condensation and oxidative stress response in Mtb. Disruption of WhiB4 affects the expression of genes involved in maintaining redox homeostasis, central metabolism, and respiration under oxidative stress. Notably, disulfide-linked oligomerization of WhiB4 in response to oxidative stress activates the protein's ability to condense DNA. Further, overexpression of WhiB4 led to hypercondensation of nucleoids, redox imbalance and increased susceptibility to oxidative stress, whereas WhiB4 disruption reversed this effect. In accordance with the findings in vitro, ChIP-Seq data demonstrated non-specific binding of WhiB4 to GC-rich regions of the Mtb genome. Lastly, data indicate that WhiB4 deletion affected the expression of ~ 30% of genes preferentially bound by the protein, suggesting both direct and indirect effects on gene expression. We propose that WhiB4 structurally couples Mtb's response to oxidative stress with genome organization and transcription.

Molecular characterization of hepatitis A virus from children hospitalized at a tertiary care centre in northwest India.

Background & objectives: Hepatitis A virus (HAV) infection is a major cause of childhood hepatitis, prevalent worldwide. HAV is classified into seven genotypes I-VII; genotypes III and I are the most common among humans. The present work was carried out to identify the genotypes prevalent in children suspected to have acute viral hepatitis (AVH), hospitalized at a tertiary care centre in northwest India. Methods: A total of 1269 blood samples from children (0-15 yr of age) clinically suspected of viral hepatitis were screened for anti-HAV IgM. Acute phase serum was processed for RNA extraction and amplified by nested polymerase chain reaction (PCR) followed by sequencing of representative samples. Results: Among the 1269 samples tested, 642 (50.59%) were positive for anti-HAV IgM; among the positive samples, 171 patients having a history of less than seven days were tested by PCR, of whom 141 (82.45%) were found to be PCR positive. Nucleotide sequencing of a representative 44 samples showed high homology; all the samples were found to be of genotype IIIA. Interpretation & conclusions: Hepatitis A was prevalent during July to September and in predominantly children less than five years age. Only genotype IIIA was detected in all the samples.

Co-circulation of Chikungunya and Dengue viruses in Dengue endemic region of New Delhi, India during 2016.

Co-circulation of Chikungunya and Dengue viral infections (CHIKV and DENV) have been reported mainly due to transmission by common Aedes vector. The purpose of the study was to identify and characterise the circulating strains of CHIKV and DENV in DENV endemic region of New Delhi during 2016. CHIKV and DENV were identified in the blood samples (n = 130) collected from suspected patients by RT-PCR. CHIKV was identified in 26 of 65 samples (40%). Similarly, DENV was detected in 48 of 120 samples (40%). Co-infection with both the viruses was identified in five (9%) of the samples. Interestingly, concurrent infection with DENV, CHIKV and Plasmodium vivax was detected in two samples. CHIKV strains (n = 11) belonged to the ECSA genotype whereas DENV-3 sequences (n = eight) clustered in Genotype III by phylogenetic analysis. Selection pressure of E1 protein of CHIKV and CprM protein of DENV-3 revealed purifying selection with four and two positive sites, respectively. Four amino acids of the CHIKV were positively selected and had high entropy suggesting probable variations. Co-circulation of both viruses in DENV endemic regions warrants effective monitoring of these emerging pathogens via comprehensive surveillance for implementation of effective control measures.

Integration of tobacco cessation and tuberculosis management by NGOs in urban India: a mixed-methods study.

Setting and objectives: Tobacco use compromises tuberculosis (TB) treatment outcomes. Tobacco cessation is beneficial to TB patients at the individual level and from the perspective of a larger spectrum of non-communicable diseases associated with tobacco use. We assessed feasibility, effectiveness and provider perceptions on integrating brief tobacco cessation advice into routine TB care by DOTS providers from 27 TB treatment centres run by three non-governmental organisations (NGOs) in urban India. Design: A mixed-methods study (triangulation design) involving analysis of programme data and semi-structured interviews (quantitative) and thematic analysis of focus group discussions of TB treatment providers (qualitative) regarding brief advice and cessation support provided to self-reported tobacco users from August 2015 to July 2017. Results: All 27 centres initiated tobacco cessation. Of 2132 registered TB patients, 377 (18%) were tobacco users, 333 (88%) of whom used smokeless tobacco. There was a progressive drop in documentation of tobacco status at each visit, reaching respectively 36% and 30% at the end of treatment for new and retreatment TB patients. Seven-day point prevalence abstinence at 6 months was 32% among new and 15% among retreatment cases. Enablers for integration included NGO collaboration, supervision and capacity building. Challenges included providers spending 15-45 min per patient (10 min recommended), multiple addictions, documentation load, self-reporting and social normalisation of tobacco. Conclusions: Integration of tobacco cessation into routine TB care in an urban NGO setting was feasible, although without continued support, rigour in documentation declined. This should be scaled up with special attention paid to tackling smokeless tobacco and related operational challenges.

Contexte : La consommation de tabac compromet les résultats du traitement de la tuberculose (TB). L'arrêt du tabac est bénéfique aux patients TB au niveau individuel et dans la perspective plus large des maladies non transmissibles associées à la consommation de tabac.Objectif : Evaluer la faisabilité, l'efficacité et les perceptions des prestataires de soins concernant l'intégration d'un bref conseil relatif à l'arrêt du tabac dans la prise en charge de routine de la TB par les prestataires de DOTS de 27 centres de traitement de la TB gérés par trois organisations non gouvernementales (ONG) dans des zones urbaines d'Inde.Schéma : Une étude à méthodes mixtes (schéma de triangulation) impliquant l'analyse de données de programme et des entretiens semi structurés (quantitatifs) et une analyse thématique des discussions en groupe focal de prestataires de traitement de TB (qualitatifs) relatifs à un conseil bref et à un soutien à l'arrêt du tabac offert aux fumeurs auto déclarés d'août 2015 à juillet 2017.Résultats : Les 27 centres ont mis en route l'arrêt du tabac. Sur 2132 patients TB enregistrés, 377 (18%) étaient des fumeurs, dont 333 (88%) recouraient à du tabac sans fumée. Il y a eu une diminution progressive de la documentation de la consommation de tabac lors de chaque consultation, atteignant 36% et 30% en fin de traitement pour les patients nouveaux et ceux en retraitement, respectivement. La prévalence ponctuelle de 7 jours d'abstinence à 6 mois a été de 32% parmi les nouveaux patients et de 15% parmi les cas en retraitement. Les facteurs favorables à cette intégration ont inclus la collaboration, la supervision et le renforcement des capacités des ONG. Les défis ont inclus les 15­45 min passées par les prestataires de soins auprès de chaque patient (10 min étaient recommandées), les addictions multiples, la charge administrative, l'auto déclaration et la normalisation sociale du tabac.Conclusion : L'intégration de l'arrêt du tabac dans la prise en charge de routine de la TB dans un contexte d'ONG urbaine s'est avérée faisable, mais sans un soutien continu, la rigueur de la documentation a diminué. Cette stratégie devrait être étendue en portant une attention particulière vis-à-vis du tabac sans fumée et des défis opérationnels.

Marco de referencia y objetivos: El consumo de tabaco pone en peligro el desenlace del tratamiento de la tuberculosis (TB). El abandono del tabaco es útil para los pacientes con TB desde el punto de vista individual y desde la perspectiva más amplia de las enfermedades no transmisibles que se asocian con el tabaquismo. En el presente estudio se evaluó la factibilidad, la eficacia y las percepciones de los proveedores de atención de salud con respecto a la integración de un asesoramiento breve sobre el abandono del tabaco en la atención corriente de la TB, practicado por quienes proveen el DOTS en 27 centros de tratamiento de la tuberculosis de tres organizaciones no gubernamentales (ONG) en una zona urbana de la India.Métodos: Fue este un estudio de métodos mixtos (técnica de triangulación) que comportó un análisis de los datos del programa y entrevistas semiestructuradas (evaluación cuantitativa) y análisis temáticos en sesiones de grupos de opinión con los proveedores de tratamiento antituberculoso (evaluación cualitativa), sobre el asesoramiento breve y el apoyo al abandono del tabaquismo dirigidos a los pacientes que comunicaban su consumo de tabaco; el estudio tuvo lugar de agosto del 2015 a julio del 2017.Resultados: Los 27 centros iniciaron el apoyo al abandono del tabaquismo. De los 2132 pacientes con TB registrados, 377 (18%) eran consumidores de tabaco y de ellos 333 (88%) utilizaban el tabaco sin humo. Se observó una disminución progresiva de la verificación del tabaquismo en cada consulta y al final del tratamiento, solo se practicaba en un 36% de los casos nuevos y un 30% de los pacientes en retratamiento. La prevalencia puntual de abstinencia durante 7 días a los 6 meses fue 32% en los casos nuevos y 15% en los casos de retratamiento. Entre los factores mencionados como facilitadores de la integración se destacaron la colaboración con una ONG, la supervisión y el mejoramiento de la capacidad. Las dificultades a la integración consistieron en que cada proveedor debe utilizar 15­45 min por paciente (10 min recomendados), las adicciones múltiples, la carga que representa verificar el tabaquismo, la validación del abandono autonotificado y la normalización social del consumo de tabaco.Conclusiones: Se demostró que es factible integrar el apoyo al abandono del tabaco en la atención corriente de la TB en un centro urbano administrado por una ONG; no obstante, sin un apoyo continuo disminuye el rigor en la documentación del consumo. Se recomienda ampliar la escala de aplicación de estas iniciativas, con una atención especial en el tabaco sin humo y las dificultades operativas.

CYP1A1 expression and organochlorine pesticides level in the etiology of bladder cancer in North Indian population.

Urinary bladder cancer (UBC) is one of the most common malignancies worldwide. The etiology of UBC is multifactorial and includes both exogenous and endogenous factors. Exogenous risk factors include exposure to heavy metals, aromatic amines, and environmental pollutants including pesticides such as organochlorine pesticides (OCPs). Environmental factors alone are incapable of directly producing DNA damage and may require activation by phase I metabolizing enzymes like cytochrome P450 in order to become active carcinogen. The present study is designed to study CYP1A1 gene expression, OCP level in cases of UBC, as well as to explore the plausible role of gene-environment interaction in the etiology of UBC among North Indian population. A total of 60 cases with equal number of controls were enrolled under this study, the OCP levels were estimated using gas chromatography, CYP1A1 mRNA expression was quantified by real-time quantitative polymerase chain reaction, and fold change was calculated using the ΔΔCt method. In the present study, the levels of OCP were found to be significantly higher with the upregulation of CYP1A1 mRNA expression among UBC cases as compared to controls. While putting multiple linear regression, it has been observed that there is a significant interaction between the levels of OCPs and ΔCt value of CYP1A1 gene taken into account hematuria episodes as dependent variable. The study concludes that when there is predisposition of OCPs and upregulation of CYP1A1 gene, then the result will be an increment in hematuria episodes which indicates that gene-environment interaction plays a significant role in the causation of UBC among North Indian population.