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1.
Comp Biochem Physiol C Toxicol Pharmacol ; 283: 109970, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38944366

RESUMEN

Di-2-ethylhexyl phthalate (DEHP) is the most commonly preferred synthetic organic chemical in plastics and its products for making them ductile, flexible and durable. As DEHP is not chemically bound to the macromolecular polymer of plastics, it can be easily leached out to accumulate in food and environment. Our recent report advocated that exposure to DEHP significantly transformed the innate bottom-dwelling and scototaxis behaviour of zebrafish. Our present study aimed to understand the possible role of DEHP exposure pertaining towards the development of aggressive behaviour and its association with amplified monoamine oxidase activity and neurodegeneration in the zebrafish brain. As heightened monoamine oxidase (MAO) is linked with genesis of aggressive behaviour, our observation also coincides with DEHP-persuaded aggressive neurobehavioral transformation in zebrafish. Our preliminary findings also showed that DEHP epitomized as a prime factor in transforming native explorative behaviour and genesis of aggressive behaviour through oxidative stress induction and changes in the neuromorphology in the periventricular grey zone (PGZ) of the zebrafish brain. With the finding demarcating towards heightened chromatin condensation in the PGZ of zebrafish brain, our further observation by immunohistochemistry showed a profound augmentation in apoptotic cell death marker cleaved caspase 3 (CC3) expression following exposure to DEHP. Our further observation by immunoblotting study also demarcated a temporal augmentation in CC3 and tyrosine hydroxylase expression in the zebrafish brain. Therefore, the gross findings of the present study delineate the idea that chronic exposure to DEHP is associated with MAO-instigated aggressive neurobehavioral transformation and neurodegeneration in the zebrafish brain.

2.
Lung India ; 41(2): 98-102, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38700402

RESUMEN

INTRODUCTION: This study aimed to ascertain the accuracy of clinical examination for the determination of pleural puncture sites as compared to the use of ultrasonography in patients with pleural effusion. MATERIAL AND METHODS: A single-centre, prospective, observational study was carried out amongst 115 patients with pleural effusion in a tertiary care hospital in western India. Patients were subjected to clinical assessment for determination of pleural puncture sites and the same were confirmed with ultrasonography. All physicians were blinded to the marking of the previous physician to prevent any influence on their assessment. RESULTS: The study had 345 physician observations. The overall accuracy of the clinical examination was 94.8%. Multivariate logistic regression of the factors responsible for the accuracy of clinical examination demonstrated a significant role of higher body mass index (BMI) (OR-1.19) and lower zone pleural effusions (OR-4.99) when adjusted for age, gender, side of effusion, and experience of examining doctors. When the effusions were classified according to their location, lower zone pleural effusions and loculated pleural effusions had an error rate of 15.9% and 8.33%, respectively. CONCLUSION: An ultrasound is the standard of care to assess all pleural effusions and guide the best point for aspiration.

3.
Int Dent J ; 74(2): 335-342, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37985344

RESUMEN

BACKGROUND: Root canal re-treatment (RCR) cases are considered some of the most challenging cases in the field of endodontics, as they are mostly associated with various iatrogenic errors such as ledge formation, incomplete biomechanical preparation, file separation, and incomplete obturation. These iatrogenic errors lead to defective niches within root canals that may act as reservoirs for various viable microorganisms. Such residual microbial niches may cause postoperative pain even after thorough debridement and reshaping the canals, ultimately leading to a poor prognosis for the tooth. Nowadays, prevention of postoperative pain in re-treatment cases and prognosis are effectively managed by photobiomodulation therapy (PBMT). METHOD: Relevant studies in the English language published before November 2022 were identified using electronic databases like PubMed, SCOPUS, and EBSCO to conduct bibliographic research. This systematic review is based on 3 studies that were found eligible as per the inclusion and exclusion criteria. This systematic review is in accordance with PRISMA guidelines. RESULTS: The systematic review indicated a positive impact by significantly decreasing postoperative pain in RCR cases when treated with PBMT. The variation was statistically significant at 24 hours (P = .0002), 48 hours (P = .03), and 72 hours (P = .02). The mean difference at 24 hours was 0.65 (95% CI, 0.32-0.99), at 48 hours was 0.46 (95% CI, 0.05-0.87), and at 72 hours was 0.40 (95% CI, 0.07-0.74). There was no statistical heterogenicity at 24 hours (P > .05), but a medium heterogenicity was observed at 48 hours and 72 hours. PRACTICAL IMPLICATION: PBMT or low-level laser therapy has shown superior results as compared to the conventional pharmacologic approach in postoperative pain management in RCR cases.


Asunto(s)
Terapia por Luz de Baja Intensidad , Humanos , Terapia por Luz de Baja Intensidad/métodos , Tratamiento del Conducto Radicular/métodos , Dolor Postoperatorio/etiología , Dolor Postoperatorio/prevención & control , Atención Odontológica , Enfermedad Iatrogénica
4.
J Bronchology Interv Pulmonol ; 31(2): 199-204, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38158758

RESUMEN

BACKGROUND: Flexible bronchoscopy-guided endobronchial biopsy (EBB) is routinely performed as an outpatient daycare procedure. Bleeding after EBB is a common complication, that at times disrupts the procedure and can rarely lead to a catastrophe. We aimed to compare the efficacy of prebiopsy prophylactic bronchoscopic electrocautery with adrenaline and cold saline instillation in achieving hemostasis in patients with endobronchial lesions with a higher risk of bleeding during EBB. METHODS: In this open-label, randomized controlled trial, 60 patients with endobronchial lesions were randomized to either the prophylactic electrocautery arm or the adrenaline and cold saline arm. Postbiopsy endobronchial bleed was quantified in millimeters using the Visual Analog Scale (VAS) and graded as per the British Thoracic Society grading system. Electrocautery-induced tissue damage was graded by the pathologist as "no damage," "mild," "moderate," and "severe." RESULTS: The median VAS score of bleeding was 6.14 mm (interquartile range: 8 mm) in the electrocautery arm and 10.17 mm (interquartile range: 7 mm) in the adrenaline and cold saline arm. Though the difference in the VAS score of bleeding between the two groups was statistically significant, there was no significant difference in the proportion of grade 2 or higher bleeding. CONCLUSION: No difference in postbiopsy bleed was observed between the application of electrocautery or instillation of cold saline plus adrenaline before biopsy of those endobronchial lesions which were likely to bleed more after biopsy. Although controlled prophylactic electrocautery using 15 watts did not impair the quality of EBB specimens, a higher wattage may change this observation, as well as the bleeding quantity.


Asunto(s)
Broncoscopía , Epinefrina , Humanos , Epinefrina/uso terapéutico , Biopsia/efectos adversos , Biopsia/métodos , Broncoscopía/efectos adversos , Hemorragia/etiología , Hemorragia/prevención & control , Electrocoagulación/efectos adversos
5.
Indian J Tuberc ; 70(4): 416-421, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37968047

RESUMEN

BACKGROUND: Immune checkpoint inhibitors targeting either programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1) have been established as a novel target for immunotherapy in non-small cell lung cancer (NSCLC). Prevalence of PD-L1 expression in NSCLC varies from 13% to 70%, with sparse data from the Indian subcontinent. In this study, we looked at PD-L1 expression and its association with demographic, clinical, radiologic and pathologic parameters in NSCLC patients. METHODS: This was an observational study carried over a period of 18 months in which 65 patients of NSCLC were included. Immunohistochemistry (IHC) for PD-L1 was done using an automated IHC stainer and testing was performed using PD-L1 IHC CAL10. For statistical analysis, unpaired t test, Chi square test, Fisher's exact test and binomial logistic regression were used. P < 0.05 was taken to be statistically significant. RESULTS: Mean age of the patients was 62.9 ± 9.2 years, and majority (87.3%) of them were males. Seventeen (26.2%) patients expressed PD-L1, among whom 10 had high PD-L1 expression (≥50%) and 7 had low PD-L1 expression (1-49%). PD-L1 expression was seen in 13 out of 43 cases of squamous cell carcinoma (SCC) and 4 out of 15 cases of adenocarcinoma. On applying binomial logistic regression analysis, association between smoking and PD-L1 expression was found to be insignificant. CONCLUSION: Almost a quarter of NSCLC cases were PD-L1 positive without any difference in expression between SCC and adenocarcinoma. PD-L1 status was not associated with any specific demographic, clinical or radiologic parameter including the histologic subtype.


Asunto(s)
Adenocarcinoma , Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Apoptosis , Antígeno B7-H1/análisis , Antígeno B7-H1/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Ligandos , Neoplasias Pulmonares/patología , Atención Terciaria de Salud
6.
Cell Rep ; 42(11): 113275, 2023 11 28.
Artículo en Inglés | MEDLINE | ID: mdl-37874678

RESUMEN

Type I interferon (IFN-I) response is the first line of host defense against invading viruses. In the absence of definite mouse models, the role of IFN-I in SARS-CoV-2 infection remains perplexing. Here, we develop two mouse models, one with constitutively high IFN-I response (hACE2; Irgm1-/-) and the other with dampened IFN-I response (hACE2; Ifnar1-/-), to comprehend the role of IFN-I response. We report that hACE2; Irgm1-/- mice are resistant to lethal SARS-CoV-2 infection. In contrast, a severe SARS-CoV-2 infection along with immune cell infiltration, cytokine storm, and enhanced pathology is observed in the lungs and brain of hACE2; Ifnar1-/- mice. The hACE2; Irgm1-/-Ifnar1-/- double-knockout mice display loss of the protective phenotype observed in hACE2; Irgm1-/- mice, suggesting that heightened IFN-I response accounts for the observed immunity. Taking the results together, we demonstrate that IFN-I protects from lethal SARS-CoV-2 infection, and Irgm1 (IRGM) could be an excellent therapeutic target against SARS-CoV-2.


Asunto(s)
COVID-19 , Interferón Tipo I , Ratones , Animales , Ratones Transgénicos , SARS-CoV-2 , Ratones Noqueados , Anticuerpos , Modelos Animales de Enfermedad , Pulmón
7.
Cureus ; 15(7): e42162, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37602059

RESUMEN

Introduction It is hypothesized that bronchoalveolar lavage (BAL) neutrophilia, Krebs von den Lungen-6 (KL-6), and C-reactive protein (CRP) predict the severity of chronic fibrosing interstitial lung diseases (CF-ILDs). Methods This cross-sectional study enrolled 30 CF-ILD patients. Using Pearson's correlation analysis, BAL neutrophils, KL-6, and CRP were correlated with forced vital capacity (FVC), diffusing lung capacity for carbon monoxide (DLCO), six-minute walk distance (6MWD), partial pressure of oxygen (PaO2), computed tomography fibrosis score (CTFS), and pulmonary artery systolic pressure (PASP). Using the receiver operator characteristic (ROC) curve, BAL KL-6 and CRP were evaluated against FVC% and DLCO% in isolation and combination with BAL neutrophilia for predicting the severity of CF-ILDs. Results BAL neutrophilia significantly correlated only with FVC% (r = -0.38, P = 0.04) and DLCO% (r = -0.43, P = 0.03). BAL KL-6 showed a good correlation with FVC% (r = -0.44, P < 0.05) and DLCO% (r = -0.50, P = 0.02), while BAL CRP poorly correlated with all parameters (r = 0.0-0.2). Subset analysis of BAL CRP in patients with CTFS ≤ 15 showed a better association with FVC% (r = -0.28, P = 0.05) and DLCO% (r = -0.36, P = 0.04). BAL KL-6 cut-off ≥ 72.32 U/ml and BAL CRP ≥ 14.55 mg/L predicted severe disease with area under the curve (AUC) values of 0.77 and 0.71, respectively. The combination of BAL neutrophilia, KL-6, and CRP predicted severity with an AUC value of 0.89. Conclusion The combination of BAL neutrophilia, KL-6, and CRP facilitates the severity stratification of CF-ILDs complementing existing severity parameters.

8.
Brain Sci ; 13(7)2023 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-37508978

RESUMEN

Alzheimer's disease (AD) is a progressive chronic illness that leads to cognitive decline and dementia. Neuroimaging technologies, such as functional magnetic resonance imaging (fMRI), and deep learning approaches offer promising avenues for AD classification. In this study, we investigate the use of fMRI-based functional connectivity (FC) measures, including the Pearson correlation coefficient (PCC), maximal information coefficient (MIC), and extended maximal information coefficient (eMIC), combined with extreme learning machines (ELM) for AD classification. Our findings demonstrate that employing non-linear techniques, such as MIC and eMIC, as features for classification yields accurate results. Specifically, eMIC-based features achieve a high accuracy of 94% for classifying cognitively normal (CN) and mild cognitive impairment (MCI) individuals, outperforming PCC (81%) and MIC (85%). For MCI and AD classification, MIC achieves higher accuracy (81%) compared to PCC (58%) and eMIC (78%). In CN and AD classification, eMIC exhibits the best accuracy of 95% compared to MIC (90%) and PCC (87%). These results underscore the effectiveness of fMRI-based features derived from non-linear techniques in accurately differentiating AD and MCI individuals from CN individuals, emphasizing the potential of neuroimaging and machine learning methods for improving AD diagnosis and classification.

9.
Clin Oral Investig ; 27(9): 5617-5625, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37522992

RESUMEN

OBJECTIVE: The objective of this study is to investigate the effect of endodontic treatment on flow-mediated dilatation (FMD) and carotid intima-media thickness (c-IMT) in patients with apical periodontitis (AP). MATERIAL AND METHOD: The study includes 32 young men having AP with a mean age of 25.78 years free from cardiovascular disease (CVD) and its risk factors, including periodontitis. All subjects underwent complete physical and dental examination, echocardiography, and ultrasound assessment of FMD on the brachial artery and c-IMT on the carotid artery at baseline and 12 months after the endodontic treatment. Data were analyzed using paired Student's t-test and Pearson's correlation coefficient (r) test using SPSS 26 version. RESULTS: Endodontic treatment leads to the improvement of FMD significantly from a pooled baseline value of 4.84 ± 1.55% to 7.68 ± 2.08% (p < 0.05). The study also depicts a statistically significant difference between c-IMT (mean = 0.62 ± 0.11 mm) before treatment as compared to 12 months after treatment (mean = 0.59 ± 0.11 mm) (p < 0.05). CONCLUSION: Endodontic treatment leads to improved FMD and decreased c-IMT suggesting that treating AP can be help revert the early stages of CVD. CLINICAL RELEVANCE: AP could be a potential etiological factor of future CVD and should be treated as soon as diagnosed.


Asunto(s)
Aterosclerosis , Enfermedades Cardiovasculares , Masculino , Humanos , Adulto , Grosor Intima-Media Carotídeo , Estudios Prospectivos , Vasodilatación , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/terapia , Aterosclerosis/complicaciones , Factores de Riesgo , Ultrasonografía , Endotelio Vascular/diagnóstico por imagen
10.
Fish Physiol Biochem ; 49(3): 501-514, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37131059

RESUMEN

The contamination of life-sustaining environments with synthetic pollutants such as plastic-derived compounds has increased at an alarming rate in recent decades. Among such contaminants, di-2-ethylhexyl phthalate (DEHP) is an extensively used compound in plastics and plastic products to make them flexible. DEHP causes several adverse effects such as reproductive toxicity leading to infertility, miscarriage and litter size reduction, disruption of the thyroid endocrine system, oxidative stress, neurodevelopmental defect and cognitive impairment. An aquatic environment is a fragile site, where the accumulation of DEHP poses a significant threat to living organisms. In this context, the present study focused on whether the neurobehavioural transformation following exposure to DEHP is an outcome of augmented oxidative stress and neuromorphological alteration in the zebrafish brain. Our preliminary findings advocate that DEHP acts as a typical neurotoxicant in inducing neurobehavioural transformation in zebrafish. Furthermore, our study also supports the idea that DEHP itself acts as a potent neurotoxicant by altering the glutathione biosynthetic pathway through the induction of oxidative stress in the zebrafish brain. Similarly, our findings also link the abovementioned neurobehavioural transformation and oxidative stress with augmented neuronal pyknosis and chromatin condensation in the periventricular grey zone of the zebrafish brain following chronic exposure to DEHP. Therefore, the overall conclusion of the present study advocates the potential role of DEHP in inducing neuropathological manifestation in the zebrafish brain. Future research directed towards elucidating the neuroprotective efficacy of natural compounds against DEHP-induced neurotoxicity may provide a new line of intervention.


Asunto(s)
Dietilhexil Ftalato , Pez Cebra , Animales , Pez Cebra/fisiología , Dietilhexil Ftalato/toxicidad , Estrés Oxidativo , Encéfalo , Plásticos/farmacología , Glutatión
12.
Environ Toxicol Pharmacol ; 97: 104027, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36462733

RESUMEN

As bisphenol A (BPA) effortlessly crosses the blood-brain barrier, its serious impacts on the neuronal microenvironment towards precocious induction of oxidative stress and neuromorphological alteration can't be ignored. Incidentally, a symmetric study establishing the possible link of transformed neurobehavior with heightened monoamine oxidase (MAO) activity and neuromorphological alteration in zebrafish brain subsequent to BPA-exposure is limiting in the literature. The study was conducted to delineate the role of BPA towards the genesis of aggressive behaviour in zebrafish and its correlation with brain MAO activity. Mirror biting test and open field test were conducted to evaluate the aggressive and explorative behaviour respectively. Biochemical studies were performed to delineate the modulation of the antioxidant defence system. Cresyl violet staining and Hoechst staining in the periventricular grey zone of the zebrafish brain were conducted to evaluate neuronal pyknosis and chromatin condensation. Our study showed that BPA exposure is associated with the genesis of aggressive neurobehavioral response. Moreover, the brain MAO activity, oxidative stress and chromatin condensation were increased with increase in exposure duration. The results of the present study gave conclusive evidence that BPA act as a potent neurotoxicant in transforming the native neurobehavioral response of zebrafish through heightened oxidative stress, MAO activity and altered neuromorphology.


Asunto(s)
Encéfalo , Pez Cebra , Animales , Pez Cebra/metabolismo , Encéfalo/metabolismo , Antioxidantes , Compuestos de Bencidrilo/toxicidad , Monoaminooxidasa/metabolismo
13.
J Basic Clin Physiol Pharmacol ; 34(1): 83-89, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36239667

RESUMEN

OBJECTIVES: Disease progression of tuberculosis (TB) depends on the balance between the microorganism's virulence and the host defense systems (mainly T cell-mediated immune response). Interleukin-22 (IL-22) helps in cell proliferation and regeneration and provides protection against microbial diseases. The IL-22-producing T cells can migrate into the granulomas during TB infection. However, disparity exists in literature regarding its role. The present study aims to compare serum IL-22 levels and its' expression in TB patients and healthy controls. METHODS: 87 TB patients and 85 healthy subjects were enrolled in the study. Under aseptic conditions, venous blood was withdrawn. Serum IL-22 levels were estimated using enzyme-linked immunosorbent assay, and its gene expression was assessed using SYBR green-based quantitative PCR technology. A statistical analysis was performed using SPSS. RESULTS: The median (interquartile range) of serum IL-22 levels was significantly lower in TB patients (18.55 (5.08) pg/mL) when compared to controls (49.38 (162.88) pg/mL) (p<0.0001). The IL-22 expression was significantly upregulated with a fold change value of 29.44 in TB patients. CONCLUSIONS: The IL-22 levels were found to be significantly decreased in patients, contradictory to its expression, which is upregulated. It plays a crucial role for the modulation of tissues in response to TB infection.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis , Humanos , Mycobacterium tuberculosis/genética , Tuberculosis/prevención & control , Interleucinas , Ensayo de Inmunoadsorción Enzimática , Interleucina-22
14.
Neurochem Res ; 48(1): 82-95, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36001190

RESUMEN

Neuropsychiatric upshots following chronic exposure to unpredictable adverse stressors have been well documented in the literature. Considering the significant impact of chronic unpredictable stress (CUS), the literature is elusive regarding the neuroprotective efficacy of taurine against CUS-induced oxidative stress and chromatin condensation in the zebrafish brain. In this study, to ameliorate CUS-persuaded neurological outcomes, waterborne treatment of taurine as a prophylactic intervention was undertaken. Further, our approach also focused on the gross neurobehavioral response of zebrafish, oxidative stress indices and neuromorphology of the zebrafish brain following CUS exposure with taurine treatment. Because taurine provides significant neuroprotection against oxidative insult, the cytosolic level of monoamine oxidase (MAO) in the zebrafish brain following CUS exposure is worth investigating. Further, as heightened MAO activity is associated with augmented oxidative and chromatin condensation, the focus of this study was on whether taurine provides neuroprotection by downregulating MAO levels in the brain. Our findings show that CUS-persuaded altered neurobehavioral response was significantly rescued by taurine. Moreover, our findings firmly support the hypothesis that taurine acts as a radical neuroprotector by restoring glutathione biosynthesis in the zebrafish brain subsequent to CUS exposure. Additionally, the rising level of brain MAO following chronic exposure to CUS is ameliorated by taurine treatment. These findings strongly advocate the role of taurine as a natural MAO inhibitor through the neuroprotection it provides against CUS-instigated oxidative stress in zebrafish. However, the fundamental neuroprotective mechanism of such natural compounds needs to be elucidated to determine their neuroprotective efficacy against stress regimens.


Asunto(s)
Neuroprotección , Pez Cebra , Animales , Taurina/farmacología , Encéfalo , Monoaminooxidasa
15.
Cureus ; 14(10): e30608, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36426311

RESUMEN

INTRODUCTION: SARS -CoV-2 was first reported in Wuhan and declared a pandemic in March 2020. Co-infections during other pandemics have been associated with severe outcomes, but data are scarce regarding co-infections in COVID-19 patients. Our study evaluated co-infections prevalence and its impact on morbidity and mortality in hospitalized COVID -19 patients. METHODS: This prospective observational study included 100 patients admitted to a high-dependency unit at a tertiary care hospital in India. Prevalence of co-infections and clinical outcome-related data were analyzed in COVID-19 patients satisfying the inclusion criteria. RESULTS: 14% of patients had co-infections, out of which urinary tract infection was found in 9%. Patients with co-infections had a higher mortality rate (p<0.0004). Urinary co-infection emerged as an independent risk factor for mortality (p <0.001). CONCLUSION: Co-infections associated with COVID-19 infections are an essential risk factor for morbidity and mortality. Early identification and timely treatment of co-infections may help in improving clinical outcomes.

16.
Monaldi Arch Chest Dis ; 93(3)2022 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-36426897

RESUMEN

Mucormycosis is an opportunistic infection seen in immunocompromised patients or in surgical and trauma settings with Mucorales wound contamination. In immunocompetent people, disseminated mucormycosis is uncommon. To ensure survival, patients with mucormycosis require early diagnosis and aggressive treatment using a multi-modality approach. We present a case of disseminated mucormycosis in an immunocompetent patient who also had pulmonary embolism and gastrointestinal bleeding. A recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, identified retrospectively by a positive IgM against SARS-CoV-2, was the only risk factor present. This report emphasizes the increased risk of mucormycosis and thromboembolic complications following a recent SARS-CoV-2 infection, as well as its successful treatment with medical therapy alone.


Asunto(s)
COVID-19 , Mucormicosis , Embolia Pulmonar , Humanos , Mucormicosis/complicaciones , Mucormicosis/diagnóstico , Estudios Retrospectivos , COVID-19/complicaciones , SARS-CoV-2 , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/terapia , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/terapia
17.
EMBO J ; 41(23): e111289, 2022 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-36221902

RESUMEN

The NOD1/2-RIPK2 is a key cytosolic signaling complex that activates NF-κB pro-inflammatory response against invading pathogens. However, uncontrolled NF-κB signaling can cause tissue damage leading to chronic diseases. The mechanisms by which the NODs-RIPK2-NF-κB innate immune axis is activated and resolved remain poorly understood. Here, we demonstrate that bacterial infection induces the formation of endogenous RIPK2 oligomers (RIPosomes) that are self-assembling entities that coat the bacteria to induce NF-κB response. Next, we show that autophagy proteins IRGM and p62/SQSTM1 physically interact with NOD1/2, RIPK2 and RIPosomes to promote their selective autophagy and limit NF-κB activation. IRGM suppresses RIPK2-dependent pro-inflammatory programs induced by Shigella and Salmonella. Consistently, the therapeutic inhibition of RIPK2 ameliorates Shigella infection- and DSS-induced gut inflammation in Irgm1 KO mice. This study identifies a unique mechanism where the innate immune proteins and autophagy machinery are recruited together to the bacteria for defense as well as for maintaining immune homeostasis.


Asunto(s)
Infecciones Bacterianas , FN-kappa B , Ratones , Animales , FN-kappa B/metabolismo , Ratones Endogámicos NOD , Autofagia , Inmunidad Innata , Homeostasis
18.
Cureus ; 14(8): e27759, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36106257

RESUMEN

Background The data on the impact of coronavirus disease 2019 (COVID-19) on interstitial lung disease (ILD) is still limited. To the best of our knowledge, there has been no study from India to date to assess the impact of COVID-19 in patients with preexisting ILD. We undertook this study to assess the clinical outcome of ILD patients admitted to our hospital with COVID-19. Methods In this retrospective observational study, records of reverse transcription polymerase chain reaction (RT-PCR)-confirmed COVID-19 patients with preexisting ILD who were admitted to the hospital in the period from May 1, 2020, to April 30, 2021, were obtained from the hospital database. The clinical outcomes of the patients were recorded. Univariate analysis was performed to find relation between various predetermined risk factors for mortality and those with significant p values (p<0.05) were subjected to multiple logistic regression to determine independent risk factors. Results In our study of 28 patients, the overall mortality was 35.7%. On comparing the parameters associated with increased mortality, there was no effect of age, gender, comorbidities, type of ILD, CT thorax findings on diagnosis, use of corticosteroids and antifibrotics in the past, spirometric findings on mortality. On multivariate analysis, the significant parameters were interleukin 6 (IL-6), p=0.02, OR=1.020 (1.006-1.043) and D-dimer, p=0.04, OR=2.14 (5.55-1.14). Conclusion COVID-19 in patients with pre-existing ILD has a comparatively higher mortality. D-dimer and IL-6 are significant predictors of mortality in ILD patients infected with COVID-19.

19.
Int J Infect Dis ; 122: 693-702, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35843496

RESUMEN

OBJECTIVES: India introduced BBV152/Covaxin and AZD1222/Covishield vaccines in January 2021. We estimated the effectiveness of these vaccines against severe COVID-19 among individuals aged ≥45 years. METHODS: We did a multi-centric, hospital-based, case-control study between May and July 2021. Cases were severe COVID-19 patients, and controls were COVID-19 negative individuals from 11 hospitals. Vaccine effectiveness (VE) was estimated for complete (2 doses ≥ 14 days) and partial (1 dose ≥ 21 days) vaccination; interval between two vaccine doses and vaccination against the Delta variant. We used the random effects logistic regression model to calculate the adjusted odds ratios (aOR) with a 95% confidence interval (CI) after adjusting for relevant known confounders. RESULTS: We enrolled 1143 cases and 2541 control patients. The VE of complete vaccination was 85% (95% CI: 79-89%) with AZD1222/Covishield and 71% (95% CI: 57-81%) with BBV152/Covaxin. The VE was highest for 6-8 weeks between two doses of AZD1222/Covishield (94%, 95% CI: 86-97%) and BBV152/Covaxin (93%, 95% CI: 34-99%). The VE estimates were similar against the Delta strain and sub-lineages. CONCLUSION: BBV152/Covaxin and AZD1222/Covishield were effective against severe COVID-19 among the Indian population during the period of dominance of the highly transmissible Delta variant in the second wave of the pandemic. An escalation of two-dose coverage with COVID-19 vaccines is critical to reduce severe COVID-19 and further mitigate the pandemic in the country.


Asunto(s)
COVID-19 , Vacunas contra la Influenza , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19 , Estudios de Casos y Controles , ChAdOx1 nCoV-19 , Hospitales , Humanos , SARS-CoV-2
20.
Lung India ; 39(3): 220-229, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35488678

RESUMEN

Context: Lung cancer is the leading cause of cancer-related deaths in the world. Computed tomography perfusion (CTP) parameters can be used to evaluate the vascular flow dynamics of lung tumours. We set out to evaluate the CTP parameters in lung cancer and correlate them with histopathological subtype and other characteristics of patients with Lung Cancer. Settings and Design: This prospective study was conducted at a tertiary care referral hospital in western India. Methods: Between January 2019 and July 2020, CTP was performed in 46 patients of lung cancer with histopathological confirmation. The CTP parameters were evaluated in detail and correlated with histopathological subtypes, staging and immunohistochemistry (IHC) markers. Analysis of variance (ANOVA) test, receiver operator characteristic (ROC) curve, Box and whiskers plot graph and Pearson correlation tests were used for statistical analysis. Results: The most common subtype was adenocarcinoma (AC) in 21 patients, followed by squamous cell carcinoma (SCC) in 15 patients and others in 10 patients. Statistically significant difference in blood flow (BF) (f = 5.563, P = 0.007), blood volume (BV) (f = 3.548, P = 0.038) and permeability/flow extraction (FE) (f = 3.617, P = 0.036) were seen in different histopathological subtypes of lung cancer. BF is the main perfusion parameter for differentiation of AC from SCC. P63 positive lesions showed statistically significant lower BF, BV and FE parameters compared to P63 negative lesions (P = 0.013, 0.016 and 0.014, respectively). Different T stages showed statistically significant differences in BF (f = 3.573, P = 0.037), BV (f = 5.145, P = 0.010) and in FE (f = 4.849, P = 0.013). Conclusion: CTP is a non-invasive imaging method to assess the vascular flow dynamics of the tumours that may predict the histopathological subtypes in lung cancer. It can be used to target large-sized lesions during biopsy and to predict the chemotherapy response.

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