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1.
Crit Rev Microbiol ; : 1-20, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38470107

RESUMO

Autophagy is a crucial immune defense mechanism that controls the survival and pathogenesis of M. tb by maintaining cell physiology during stress and pathogen attack. The E3-Ub ligases (PRKN, SMURF1, and NEDD4) and autophagy receptors (SQSTM1, TAX1BP1, CALCOCO2, OPTN, and NBR1) play key roles in this process. Galectins (LGALSs), which bind to sugars and are involved in identifying damaged cell membranes caused by intracellular pathogens such as M. tb, are essential. These include LGALS3, LGALS8, and LGALS9, which respond to endomembrane damage and regulate endomembrane damage caused by toxic chemicals, protein aggregates, and intracellular pathogens, including M. tb. They also activate selective autophagy and de novo endolysosome biogenesis. LGALS3, LGALS9, and LGALS8 interact with various components to activate autophagy and repair damage, while CGAS-STING1 plays a critical role in providing immunity against M. tb by activating selective autophagy and producing type I IFNs with antimycobacterial functions. STING1 activates cGAMP-dependent autophagy which provides immunity against various pathogens. Additionally, cytoplasmic surveillance pathways activated by ds-DNA, such as inflammasomes mediated by NLRP3 and AIM2 complexes, control M. tb. Modulation of E3-Ub ligases with small regulatory molecules of LGALSs and TRIM proteins could be a novel host-based therapeutic approach for controlling TB.

2.
Int J Med Microbiol ; 312(1): 151544, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34922100

RESUMO

Mycobacterium tuberculosis (M. tuberculosis) encodes an essential enzyme acetyl ornithine aminotransferase ArgD (Rv1655) of arginine biosynthetic pathway which plays crucial role in M. tuberculosis growth and survival. ArgD catalyzes the reversible conversion of N-acetylornithine and 2 oxoglutarate into glutamate-5-semialdehyde and L-glutamate. It also possesses succinyl diaminopimelate aminotransferase activity and can thus carry out the corresponding step in lysine biosynthesis. These essential roles played by ArgD in amino acid biosynthetic pathways highlight it as an important metabolic chokepoint thus an important drug target. We showed that M. tuberculosis ArgD rescues the growth of ΔargD E. coli grown in minimal media validating its functional importance. Phylogenetic analysis of M. tuberculosis ArgD showed homology with proteins in gram positive bacteria, pathogenic and non-pathogenic mycobacteria suggesting the essentiality of this protein. ArgD is a secretory protein that could be utilized by M. tuberculosis to modulate host innate immunity as its moonlighting function. In-silico analysis predicted it to be a highly antigenic protein. The recombinant ArgD protein when exposed to macrophage cells induced enhanced production of pro-inflammatory cytokines TNF, IL6 and IL12 in a dose dependent manner. ArgD also induced the increased production of innate immune effector molecule NOS2 and NO in macrophages. We also demonstrated ArgD mediated activation of the canonical NFkB pathway. Notably, we also show that ArgD is a specific TLR4 agonist involved in the activation of pro-inflammatory signaling for sustained production of effector cytokines. Intriguingly, ArgD protein treatment activated macrophages to acquire the M1 phenotype through the increased surface expression of MHCII and costimulatory molecules CD80 and CD86. ArgD induced robust B-cell response in immunized mice, validating its antigenicity potential as predicted by the in-silico analysis. These properties of M. tuberculosis ArgD signify its functional plasticity that could be exploited as a possible drug target to combat tuberculosis.


Assuntos
Mycobacterium tuberculosis , Animais , Proteínas de Bactérias/genética , Escherichia coli , Camundongos , Filogenia , Transaminases/genética
3.
Pituitary ; 25(1): 92-99, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34328604

RESUMO

PURPOSE: Sheehan's Syndrome (SS) is one of the most important causes of hypopituitarism in developing countries with patients having varying degrees and severity of anterior pituitary hormone deficiency including growth hormone deficiency (GHD). SS is characterized by increased clustering of metabolic and proinflammatory risk factors predisposing them to increased cardiovascular morbidity and mortality. Coronary calcium deposits (CCD), a marker for significant coronary atherosclerosis, is used for evaluation in asymptomatic individuals of global cardiac risk to develop events related to coronary heart disease (CHD). This study therefore aimed to evaluate the prevalence of coronary artery disease in patients with SS appropriately replaced for pituitary hormone deficiencies but untreated for GHD. METHODS: Thirty patients previously diagnosed with SS and stable on a conventional replacement treatment for at least 6 months before the study and thirty age and Body Mass Index (BMI) matched controls were enrolled in this observational study. The subjects underwent detailed clinical, biochemical, and hormone analysis. Coronary multidetector computed tomography was performed in 19 SS patients and 19 healthy participants by a 16-row multislice scanner. Non contrast acquisitions were performed to detect coronary calcifications. Calcium was quantified by the Agatston score (AS) in all subjects. AS > 10 indicates increased CHD risk. RESULTS: The mean (± SD) age was 38.30 ± 10.73 years and the diagnostic delay was 11.35 ± 4.74 years. Patients with SS had significantly higher mean triglyceride, total cholesterol, and low density lipoprotein (LDL) cholesterol and lower HDL cholesterol concentrations on conventional replacement therapy. The prevalence of CCD was significantly higher in patients of SS compared to controls (42.1% vs. 5.3%; P = 0.023). The presence of CCD and AS > 10 were detected in 42.1% and 31.6% of patients respectively. The presence of significant calcification (Agatston score > 10) was documented in 75% of patients (6/8) of the SS patients with CCD compared to none in the control group (P = 0.019). (Left anteriordescending, 1; left circumflex, 2; right coronary artery, 2 and posterior descending, 1) CONCLUSION: Since coronary artery calcium is an independent predictor of CHD events, the presence of significant prevalence of CCD in patients with SS compared to healthy matched controls, undermines the importance of early risk stratification of SS individuals with plethora of conventional cardiovascular risk factors that are at relatively high risk to avoid the adverse vascular consequences.


Assuntos
Hormônio do Crescimento Humano , Hipopituitarismo , Adulto , Cálcio , Diagnóstico Tardio , Humanos , Hipopituitarismo/epidemiologia , Pessoa de Meia-Idade , Prevalência , Fatores de Risco
4.
Environ Monit Assess ; 194(4): 281, 2022 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-35294659

RESUMO

Trees outside forests (TOFs) have assumed importance in view of its potential to mitigate CO2 under different carbon pools with soil as the prominent pool. The ability of any TOF practice to fix soil organic carbon (SOC) efficiently depends on its SOC build up and soil quality that varies across different strata within TOFs. Soil physico-chemical properties under six TOF practices (boundary plantation, roadside plantation, riverside plantation, horticulture, scattered patches with clumpy plantation (SPCP), and woodlot) in central region of Kashmir valley were investigated to assess SOC content and soil quality. Additive soil quality index (ASQI) approach was used to assess soil quality using "lower or higher is better" criteria. Correlation analysis between soil variables was carried out to assess the relationships. The results showed that TOF soils in the region were sandy clay loam in texture with slightly acidic to alkaline pH and electrical conductivity within normal limits. Lowest bulk density (0.94 g cm-3) was found in SPCP and highest (1.38 g cm-3) in roadside plantation. Highest SOC %, available nitrogen (N), and available phosphorus (P) values were observed in SPCP and lowest in boundary plantation. Average available potassium (K) was observed highest in SPCP (333.04 kg ha-1) and lowest in riverside plantation (244.58 kg ha-1). Soil pH showed significant but negative correlations with SOC and other nutrients (N and P). A significant but perfect positive correlation was observed between SOC and available N. SOC content was found highest in SPCP (60.16 t ha-1) and lowest in boundary plantation (34.56 t ha-1). The hypothesis that all soils under different TOF strata have similar quality and same SOC build up rate was observed otherwise with SPCP exhibiting highest CSQI. SPCP was observed to be more qualitative and dynamic growing system among all strata with an enhanced capacity to fix and conserve SOC to help mitigate climate change. Present study demands plantation of more trees outside the forest areas especially in the pattern of SPCP for enrichment of soil and enhancement of carbon sequestration.


Assuntos
Solo , Árvores , Carbono/análise , Monitoramento Ambiental , Florestas , Solo/química
5.
BMC Public Health ; 21(1): 21, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33402145

RESUMO

BACKGROUND: The Novel Coronavirus Disease (COVID-19) has created havoc globally as countries worldwide struggle to combat this pandemic. Since prevention and social isolation are known to be the only ways to prevent the spread of COVID-19, this has created challenges among the lower-middle income countries (LMIC) including Pakistan, as it battles between an under-resourced healthcare, an economic shutdown, and widespread myths and misconceptions. Therefore, a study was conducted to evaluate the knowledge, attitude and perceptions regarding COVID-19 as public understanding is vital to help facilitate the control of this outbreak. METHODS: A pre-validated online questionnaire was distributed among the general population of Pakistan from 1st to 12th June 2020. Descriptive statistics were analyzed using SPSS v25. Adequate knowledge was assigned as a score of > 4 (range: 0-8) and good perception as a score of > 3 (range: 0-5). Chi-square test was used to determine the significance of difference in knowledge and perception of COVID-19 with socio-demographic characteristics. Logistic regression analysis was run to identify factors associated with adequate knowledge and perception. P < 0.05 was considered as significant. RESULTS: A total of 1200 respondents participated in this study with a wide range of age groups and education. Majority of the respondents had adequate knowledge (93.3%) with a mean score of 6.59 ± 1.35, and good perception (85.6%) with a mean score of 4.29 ± 0.82. Significant differences in knowledge and perception were observed among genders, age groups, education and between students and employees in the healthcare and non-healthcare department. A multivariate analysis revealed a higher educational status and female gender to be significant predictors of adequate knowledge and perception. CONCLUSIONS: Albeit the surge of COVID-19 cases in Pakistan, the participants demonstrated an overall adequate knowledge and good perception towards COVID-19. There is a need to follow the preventive protocols and dissemination of correct information through conducting educational interventions that target safe health practices and provide appropriate information on this infection.


Assuntos
COVID-19/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Adolescente , Adulto , COVID-19/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paquistão/epidemiologia , Inquéritos e Questionários , Adulto Jovem
7.
BMC Public Health ; 19(1): 360, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30935404

RESUMO

BACKGROUND: The incidence of cancer is rising but data available regarding prevalence of cancer and patient perception of the disease in Pakistan is limited. It is difficult to deal with Cancer if the main causes are negligence towards risk factors and bizarre myths. This study was aimed to investigate common cancer presentations at a government sector hospital and to gain insight into patient knowledge of the disease. METHODS: This was a cross-sectional study conducted on cancer patients from Jinnah Postgraduate Medical Centre. A self-made questionnaire was used to assess the norms related to cancer prevalence in our society, associated myths, and the most common risk factors per them. RESULTS: A total of 402 participants consented to participate in the study (mean age 42.3 ± 15.07 years), 204(50.7%) were females and 190(47.3%) were illiterate. Biomass exposure was found in 147(37%), drug abuse in 132(33%) and smoking in 63(16%). We found 103(25.6%) had positive family histories of cancer. The most common primary tumor site was breast for females 98(48%) and Head and neck 66(33.3%) for males. Patients considered fate 328(82%), gutka 284(71%) and injuries 282(70%) as the most common causes for cancer; while 222(55.5%) considered black magic and 236(58.75%) considered evil eye as a risk factor for cancer. Cancer treatment caused significant financial stress in 376(93.5%) patients. CONCLUSION: Breast and head and neck cancers were found to be prevalent among patients. It was noted that patients are negligent in daily life regarding the consumption of substances that commonly cause cancer. Individuals had diminished knowledge and majority linked cancer to unrelated causes and myths like black magic and fate. Almost all the patients complained of severe financial stress imposed by the disease.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Neoplasias , Adulto , Idoso , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Estudos Transversais , Feminino , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/etiologia , Gastos em Saúde , Humanos , Incidência , Magia , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/etiologia , Paquistão/epidemiologia , Percepção , Prevalência , Fatores de Risco , Inquéritos e Questionários , Centros de Atenção Terciária , Tabaco sem Fumaça
8.
Sensors (Basel) ; 19(8)2019 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-31010081

RESUMO

Over the past two decades, automatic facial emotion recognition has received enormous attention. This is due to the increase in the need for behavioral biometric systems and human-machine interaction where the facial emotion recognition and the intensity of emotion play vital roles. The existing works usually do not encode the intensity of the observed facial emotion and even less involve modeling the multi-class facial behavior data jointly. Our work involves recognizing the emotion along with the respective intensities of those emotions. The algorithms used in this comparative study are Gabor filters, a Histogram of Oriented Gradients (HOG), and Local Binary Pattern (LBP) for feature extraction. For classification, we have used Support Vector Machine (SVM), Random Forest (RF), and Nearest Neighbor Algorithm (kNN). This attains emotion recognition and intensity estimation of each recognized emotion. This is a comparative study of classifiers used for facial emotion recognition along with the intensity estimation of those emotions for databases. The results verified that the comparative study could be further used in real-time behavioral facial emotion and intensity of emotion recognition.


Assuntos
Emoções/fisiologia , Face/fisiologia , Expressão Facial , Reconhecimento Automatizado de Padrão/métodos , Algoritmos , Biometria/métodos , Bases de Dados Factuais , Feminino , Humanos , Aprendizado de Máquina , Masculino , Máquina de Vetores de Suporte
10.
Gynecol Endocrinol ; 34(11): 965-969, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29734859

RESUMO

Polycystic ovary syndrome (PCOS), a major endocrinopathy is associated with barrage of metabolic aberrations. Reports in literature on association of PCOS and autoimmunity are conflicting. We aim to evaluate serum levels of anti-nuclear antibody (ANA) among Indian women with PCOS. In this hospital-based single center cross-sectional study, women qualifying a diagnosis of PCOS by Rotterdam criteria 2003 were recruited. Eighty-nine eligible women who consented were enrolled. All these women along with 87 age-matched, healthy controls underwent, clinical (menstrual history, anthropometry, hirsutism scoring), biochemical, hormonal assessment and serum ANA estimation. OGTT after overnight (8-12 h) fast with 75 g oral glucose load was done for 1 h, 2 h glucose and insulin measurements. The mean age of cases and controls was comparable (22.67 ± 5.53 vs. 22.84 ± 3.64 years). The prevalence of ANA positivity was significantly higher among women with PCOS (18.4% vs. 2.29%; p < .001). Though significant correlation was observed between ANA positivity and clinical signs of hyperandrogenism and plasma glucose, no significant correlation was noted between ANA status and other hormonal parameters. Higher prevalence of ANA positivity among women with PCOS, being a marker of autoimmunity, suggests a possible role of autoimmunity in causation of PCOS and needs further elucidation.


Assuntos
Anticorpos Antinucleares/sangue , Síndrome do Ovário Policístico/imunologia , Adolescente , Adulto , Autoimunidade , Índice de Massa Corporal , Estudos Transversais , Feminino , Teste de Tolerância a Glucose , Hospitais , Humanos , Hiperandrogenismo , Índia , Insulina/sangue , Ciclo Menstrual , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/diagnóstico , Adulto Jovem
11.
Sensors (Basel) ; 18(2)2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29389845

RESUMO

Extensive possibilities of applications have made emotion recognition ineluctable and challenging in the field of computer science. The use of non-verbal cues such as gestures, body movement, and facial expressions convey the feeling and the feedback to the user. This discipline of Human-Computer Interaction places reliance on the algorithmic robustness and the sensitivity of the sensor to ameliorate the recognition. Sensors play a significant role in accurate detection by providing a very high-quality input, hence increasing the efficiency and the reliability of the system. Automatic recognition of human emotions would help in teaching social intelligence in the machines. This paper presents a brief study of the various approaches and the techniques of emotion recognition. The survey covers a succinct review of the databases that are considered as data sets for algorithms detecting the emotions by facial expressions. Later, mixed reality device Microsoft HoloLens (MHL) is introduced for observing emotion recognition in Augmented Reality (AR). A brief introduction of its sensors, their application in emotion recognition and some preliminary results of emotion recognition using MHL are presented. The paper then concludes by comparing results of emotion recognition by the MHL and a regular webcam.


Assuntos
Identificação Biométrica/normas , Emoções , Expressão Facial , Algoritmos , Bases de Dados Factuais , Inteligência Emocional , Humanos , Aprendizado de Máquina , Reprodutibilidade dos Testes , Inquéritos e Questionários
13.
J Pak Med Assoc ; 67(11): 1787-1790, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29171591

RESUMO

OBJECTIVE: To determine knowledge and misconceptions about asthma among the local population.. METHODS: This cross-sectional study was conducted at four tertiary care hospitals; Aga Khan University Hospital, Civil Hospital Karachi, Jinnah Postgraduate Medical Centre and Ojha Institute of Chest Diseases, Karachi, from October to November 2016, and comprised hospital attendants. The questionnaire used in the study comprised 26 questions answered with a true, false or not sure answer.SPSS 20 was used for data analysis. RESULTS: There were 400 participants. The overall mean age was 41.2±14.2 years, and 214(53.5%) of the participants were males. Moreover, 75(19%) participants thought that asthma was a psychological disorder while 181(45%) considered it an infectious disease. Nearly 174(43.5%) believed that inhaled medications had significant side effects. Besides, 264(66%) participants considered steam inhalation to be an effective treatment for asthma, 269(67%) thought that patients with asthma should avoid rice in their diet and 167(42%) considered milk as a common trigger. CONCLUSIONS: Participants' knowledge about asthma was poor and misconceptions were common about the condition.


Assuntos
Asma/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paquistão/epidemiologia , Inquéritos e Questionários , Adulto Jovem
14.
Clin Endocrinol (Oxf) ; 80(1): 141-7, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23679109

RESUMO

BACKGROUND: An extensive survey on schoolchildren in Kashmir Valley in 1995 showed a high prevalence of goitre, making it imperative to have a relook at our iodine status, 15 years postiodization. OBJECTIVE: To study the total prevalence of goitre and urinary iodine excretion (UIE) in Kashmiri schoolchildren, 15 years postiodization. DESIGN: A cross-sectional survey, covering 9576 schoolchildren, aged 5-15 years (5988 in 6-12 year age group) was conducted. Goitres were graded as per WHO/UNICEF/ICCIDD. UIE was measured by the arsenic acid reduction in ceric ions method and was estimated in 208 subsampled children. Results were compared with that of 1995 survey. RESULTS: The overall prevalence of goitre in the present study was 3·8% (95% CI: 3·4-4·2) and 3·7% (95% CI: 3·2-4·2) in those aged 6-12 years. No significant difference in prevalence of goitre was observed between boys and girls overall (3·6% vs 4·1%. P > 0·2), nor in the 6-12 year age group (3·3% vs 4·0%, P > 0·1). There was a significant trend of increasing prevalence of goitre with age (P < 0·005). UIE ranged from 12 to 397 µg/g.creatinine (median, 104); 11% subjects had UIE of <50 µg/g.creatinine. Overall, prevalence of goitre was significantly lower (3·8% vs 45·2%, P < 0·001), and mean UIE was significantly higher (123·6 ± 5·3 vs 49·60 ± 3·55 µg/g.creatinine, P < 0·001), compared to that in the 1995 survey. CONCLUSION: The marked improvement in overall iodine nutrition in Kashmir Valley- one and a half decades after implementation of salt iodization should encourage healthcare providers to make tangible efforts for implementation of iodization programmes in areas with iodine deficiency.


Assuntos
Bócio Endêmico/epidemiologia , Bócio Endêmico/urina , Iodo/urina , Criança , Estudos Transversais , Feminino , Humanos , Índia/epidemiologia , Masculino , Prevalência
15.
Korean Circ J ; 54(4): 165-171, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38654562

RESUMO

Beta blockers are one of the commonest prescription drugs in medicine and they have been thought to revolutionize the treatment of heart failure (HF) with reduced ejection fraction (HFrEF) in the last century. In addition to HFrEF, they are prescribed for a variety of diseases in cardiology from hypertension to HF, angina, and stable coronary artery disease (CAD). The increased prescription of beta blockers in conditions like HF with preserved ejection fraction (HFpEF), and stable CAD may be doing more harm than good as per the data we have so far. The available data shows that beta blockers are associated with increased stroke risk and atrial fibrillation (AF) in hypertension and in patients with HFpEF, they have been associated with decreased exercise capacity. In patients with stable CAD and patients with myocardial infarction with normal systolic functions, beta blockers don't offer any mortality benefit. In this article, we critically review the common indications and the uses of beta blockers in patients with HFpEF, CAD, hypertension and AF and we propose that beta blockers are over-prescribed under the shadow of their beneficial effects in patients with HFrEF.

16.
Mol Inform ; 43(3): e202300284, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38123523

RESUMO

Tuberculosis (TB) is the second leading cause of mortality after COVID-19, with a global death toll of 1.6 million in 2021. The escalating situation of drug-resistant forms of TB has threatened the current TB management strategies. New therapeutics with novel mechanisms of action are urgently required to address the current global TB crisis. The essential mycobacterial primase DnaG with no structural homology to homo sapiens presents itself as a good candidate for drug targeting. In the present study, Mitoxantrone and Vapreotide, two FDA-approved drugs, were identified as potential anti-mycobacterial agents. Both Mitoxantrone and Vapreotide exhibit a strong Minimum Inhibitory Concentration (MIC) of ≤25µg/ml against both the virulent (M.tb-H37Rv) and avirulent (M.tb-H37Ra) strains of M.tb. Extending the validations further revealed the inhibitory potential drugs in ex vivo conditions. Leveraging the computational high-throughput multi-level docking procedures from the pool of ~2700 FDA-approved compounds, Mitoxantrone and Vapreotide were screened out as potential inhibitors of DnaG. Extensive 200 ns long all-atoms molecular dynamic simulation of DnaGDrugs complexes revealed that both drugs bind strongly and stabilize the DnaG during simulations. Reduced solvent exposure and confined motions of the active centre of DnaG upon complexation with drugs indicated that both drugs led to the closure of the active site of DnaG. From this study's findings, we propose Mitoxantrone and Vapreotide as potential anti-mycobacterial agents, with their novel mechanism of action against mycobacterial DnaG.


Assuntos
Mycobacterium tuberculosis , Somatostatina/análogos & derivados , Humanos , Antituberculosos/farmacologia , DNA Primase/química , DNA Primase/metabolismo , Mitoxantrona/farmacologia
17.
Front Microbiol ; 15: 1344857, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38803374

RESUMO

Mycobacterium tuberculosis (M. tb) genome encompasses 4,173 genes, about a quarter of which remain uncharacterized and hypothetical. Considering the current limitations associated with the diagnosis and treatment of tuberculosis, it is imperative to comprehend the pathomechanism of the disease and host-pathogen interactions to identify new drug targets for intervention strategies. Using in-silico comparative genome analysis, we identified one of the M. tb genes, Rv1509, as a signature protein exclusively present in M. tb. To explore the role of Rv1509, a likely methyl transferase, we constructed a knock-in Mycobacterium smegmatis (M. smegmatis) constitutively expressing Rv1509 (Ms_Rv1509). The Ms_Rv1509 led to differential expression of many transcriptional regulator genes as assessed by RNA-seq analysis. Further, in-vitro and in-vivo studies demonstrated an enhanced survival of Ms_Rv1509 inside the host macrophages. Ms_Rv1509 also promoted phagolysosomal escape inside macrophages to boost bacterial replication and dissemination. In-vivo infection studies revealed that Ms_Rv1509 survives better than BCG and causes pathological manifestations in the pancreas after intraperitoneal infection. Long-time survival of Ms_Rv1509 resulted in lymphocyte migration, increased T regulatory cells, giant cell formation, and likely granuloma formation in the pancreas, pointing toward the role of Rv1509 in M. tb pathogenesis.

18.
BMC Pulm Med ; 13: 20, 2013 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-23537391

RESUMO

BACKGROUND: Leukotriene receptor antagonists (LTRAs) are well established in the management of outpatient asthma. However, there is very little information as to their role in acute asthma exacerbations. We hypothesized that LTRAs may accelerate lung function recovery when given in an acute exacerbation. METHODS: A randomized, double blind, placebo-controlled trial was conducted at the Aga Khan University Hospital to assess the efficacy of oral montelukast on patients of 16 years of age and above who were hospitalized with acute asthma exacerbation. The patients were given either montelukast or placebo along with standard therapy throughout the hospital stay for acute asthma. Improvements in lung function and duration of hospital stay were monitored. RESULTS: 100 patients were randomized; their mean age was 52 years (SD +/- 18.50). The majority were females (79%) and non-smokers (89%). The mean hospital stay was 3.70 ± 1.93 days with 80% of patients discharged in 3 days. There was no significant difference in clinical symptoms, PEF over the course of hospital stay (p = 0.20 at day 2 and p = 0.47 at day 3) and discharge (p = 0.15), FEV1 at discharge (p = 0.29) or length of hospital stay (p = 0.90) between the two groups. No serious adverse effects were noted during the course of the study. CONCLUSION: Our study suggests that there is no benefit of addition of oral montelukast over conventional treatment in the management of acute asthma attack. TRIAL REGISTRATION NUMBER: 375-Med/ERC-04.


Assuntos
Acetatos/administração & dosagem , Asma/tratamento farmacológico , Asma/imunologia , Antagonistas de Leucotrienos/administração & dosagem , Pulmão/efeitos dos fármacos , Quinolinas/administração & dosagem , Doença Aguda , Administração Oral , Adulto , Idoso , Ciclopropanos , Método Duplo-Cego , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Pulmão/imunologia , Pulmão/fisiologia , Masculino , Pessoa de Meia-Idade , Pico do Fluxo Expiratório/efeitos dos fármacos , Placebos , Recuperação de Função Fisiológica/efeitos dos fármacos , Sulfetos , Resultado do Tratamento
19.
Environ Sci Pollut Res Int ; 30(17): 51191-51205, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36808034

RESUMO

The rapidly growing urbanization and the consequent land use/land cover (LULC) changes have resulted in unsustainable growth of cities in Indian subcontinent especially in Himalayan region which are highly sensitivity to condition like climate change. Using multi-temporal and multi-spectral satellite datasets, this study analyzes the impact of LULC changes on land surface temperature (LST) in the Himalayan city of Srinagar from 1992 to 2020. For LULC classification, the maximum likelihood classifier technique was utilized, and to extract LST from Landsat 5 (TM) and Landsat 8 (TM) (OLI), spectral radiance was employed. The results show that, among various LULC classes, built-up area has seen a maximum increase of 14% while agriculture has decreased by about 21%. On the whole, Srinagar city has witnessed an increase in LST by 4.5 °C with maximum increase of 5.35 °C especially over marshes and a minimum increase of 4 °C on agriculture landscape. Other LULC categories of built-up, water bodies, and plantation saw an increase in LST by 4.19 °C, 4.47 °C, and 5.07 °C, respectively. The transformation of marshes into built-up saw a maximum increase in LST by 7.18 °C followed by water body to built-up (6.96 °C) and water body to agriculture (6.18 °C) while minimum increase was seen in the conversion of agriculture to marshes by about 2.42 °C followed by agriculture to plantation (3.84 °C) and plantation to marshes (3.86 °C). The findings may be useful to urban planners and policymakers in terms of land use planning and city thermal environment control.


Assuntos
Monitoramento Ambiental , Urbanização , Temperatura , Monitoramento Ambiental/métodos , Cidades , Água
20.
Disaster Med Public Health Prep ; 17: e484, 2023 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-37694304

RESUMO

This article presents a reflective analysis of the role of public leadership within the context of crises, advocating for increased involvement of public health experts in crisis management. The study delves into the intricate dynamics that executives and board members exhibit when faced with crises. A primary focus of this research is the essential aspects that illuminate the engagement of public officials in the ongoing crisis, notably rapid decision-making and innovative thinking. The article underscores the paramount importance of leaders emphasizing values and mission while employing clear, meaningful, and empathetic communication. A comprehensive comprehension of public leadership emerges as a pivotal factor in crisis management, particularly when devising policy remedies for public health emergencies. The criticality of nurturing a new generation of healthcare CEOs and elevating the visibility of public health roles is underscored as an imperative for adeptly addressing the array of crises confronting us. This article broadens our insights into the multifaceted responsibilities of human resource management in both crisis response and recovery. Consequently, this endeavor facilitates the identification of evolving leadership roles essential for efficacious crisis management, fostering preparedness for prospective public health challenges.


Assuntos
COVID-19 , Liderança , Humanos , COVID-19/epidemiologia , Pandemias , Estudos Prospectivos , Comunicação
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