Thrombocytopenia is the most notable phenomenon in dengue. Activation status of platelets and interaction of platelets with endothelium contribute towards dengue disease pathogenesis. Platelets are ...the major cell types known to release extracellular vesicles, especially exosomes in circulation. However, the role of platelet derived exosomes (PLT-EXOs) in endothelial dysfunction during dengue infection remains unknown.
In this study, we recruited 28 healthy subjects and 69 dengue patients categorized as WS- (n=31), WS+ (n=29) and SD (n=9). Platelets were isolated from platelet rich plasma of dengue patients and their activation was assessed by flow cytometry. PLT-EXOs were isolated by ultracentrifugation method. Western blot analyses were performed to characterize the exosomes. Exosome uptake experiment was carried out to see the internalization of exosomes inside endothelial cells (HUVECs). To observe the effect of exosomes on endothelial cells, exosomes were added on HUVECs and expression of adherens and tight junctional proteins were examined by immunofluorescence assay and western blot. Expression levels of vascular injury markers were measured in the culture supernatants of Exosome-HUVEC coculture and sera of dengue patients by MSD-multiplex assay.
As compared to healthy subjects, CD41/CD61 expression was significantly reduced (p<0.0001) and CD62p expression was significantly increased (p<0.0001) on platelets in dengue patients. PLT-EXOs isolated from the dengue patients showed higher expression of CD63 and CD9 proteins than the healthy subjects. With
immunofluorescence assays, we illustrated the internalization of PLT-EXOs by the HUVECs and observed disruption of endothelial cell monolayer integrity in the presence of PLT-EXOs from WS+ and SD patients. Furthermore, the significant reduction in the expressions of ZO-2, VE-Cadherin and CD31 in endothelial cells following exposure to PLT-EXOs from the dengue patients provide direct evidence of PLT-EXOs mediated vascular permeability. PLT-EXOs stimulated the release of inflammatory markers CRP, SAA, sVCAM-1 and sICAM-1 in the supernatants of HUVEC cells. Importantly, significantly higher levels of CRP, sVCAM-1 and sICAM-1 in the sera of severe than mild dengue patients (p<0.0001) suggest their role in disease severity.
In summary, our data suggest that PLT-EXOs promote vascular leakage via release of proinflammatory mediators and compromise vascular barrier integrity in dengue patients.
Background & objectives: The COVID-19 disease profile in Indian patients has been found to be different from the Western world. Changes in lymphocyte compartment have been correlated with disease ...course, illness severity and clinical outcome. This study was aimed to assess the peripheral lymphocyte phenotype and subset distribution in patients with COVID-19 disease from India with differential clinical manifestations.
Methods: Percentages of peripheral lymphocyte subsets were measured by flow cytometry in hospitalized asymptomatic (n=53), mild symptomatic (n=36), moderate and severe (n=30) patients with SARS-CoV-2 infection, recovered individuals (n=40) and uninfected controls (n=56) from Pune, Maharashtra, India.
Results: Percentages of CD4+Th cells were significantly high in asymptomatic, mild symptomatic, moderate and severe patients and recovered individuals compared to controls. Percentages of Th memory (CD3+CD4+CD45RO+), Tc memory (CD3+CD8+CD45RO+) and B memory (CD19+CD27+) cells were significantly higher in the recovered group compared to both asymptomatic, mild symptomatic patient and uninfected control groups. NK cell (CD56+CD3-) percentages were comparable among moderate +severe patient and uninfected control groups.
Interpretation & conclusions: The observed lower CD4+Th cells in moderate+severe group requiring oxygen support compared to asymptomatic+mild symptomatic group not requiring oxygen support could be indicative of poor prognosis. Higher Th memory, Tc memory and B memory cells in the recovered group compared to mild symptomatic patient groups might be markers of recovery from mild infection; however, it remains to be established if the persistence of any of these cells could be considered as a correlate of protection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The cellular immune cell subsets affecting COVID-19 disease severity are being studied by researchers from many countries. The current study was carried out to investigate the alteration of ...peripheral blood mononuclear cells (PBMCs) and their subsets in hospitalized COVID-19 patients in a tertiary care center in Pune, India. The PBMCs were isolated from enrolled study participants, and flow cytometry analysis was done to assess peripheral white blood cell alterations. The lymphocyte subsets of naive, effector, central memory, and effector memory CD4+ or CD8+ T cells were then evaluated in COVID-19 patients with different disease categories and compared to healthy controls. The immunophenotypic characterization of the immune cell subset was done for 139 COVID-19 patients and 21 healthy controls. These data were evaluated based on the disease severity. A total of 139 COVID-19 patients were classified as mild (
= 30), moderate (
= 57), or severe (
= 52) cases. The decreased percentages of total lymphocytes, CD3+ T cells, CD4+ T cells, naive T cells, central memory T cells, and Natural Killer (NK) cytotoxic cells were found, and there was increase in effector T (TEf) cells and effector memory T cells in patients with severe COVID-19 compared to healthy controls. The severity of SARS-CoV-2 infection has an effect on lymphocyte subsets, resulting in reduced T memory cells and NK cells but increased TEf cells in severe cases. Clinical Trial Registration: CTRI ID-CTRI/2021/03/032028.
ABSTRACT
Context:
Corrosive compounds are either acids or alkalis, and their ingestion can cause esophageal strictures which may be tortuous and multiple.
Aims:
The aim of study was to assess ...therapeutic efficacy and safety of dilatation using Savary‑Gilliard dilators in these patients without the use of fluoroscopy.
Settings and Design:
A cross‑sectional observational study, conducted for 18 months in a tertiary care teaching hospital in Western India.
Subjects and Methods:
Ten dysphagic patients who had a history of corrosive ingestion 2 months or more before presentation, who had documented esophageal strictures on endoscopy were included. Barium swallow and endoscopy confirmed the site, length, and number of strictures. Dilatation with Savary‑Gilliard dilators was done without the use of fluoroscopy with the help of guide wire in “rule of threes.” Patients were followed up immediately and for 12 months. Descriptive statistics, mean, and SD were applied in EPI info version 7 software.
Results:
The mean age of 29 + 6.5 years and 70% were females. About 80% had dysphagia Grades III and IV. On endoscopy, 40% had strictures at multiple sites and 60% of patients had strictures more than 5 cm in length. 50% strictures were very tight. Number of patients in whom there was the passage of one dilator more than the stricture in the first session were 80%. A mean of 8.28 sessions of dilatation were required. Adequate dysphagia relief was achieved in 8 (80%) patients, while there were 2 failures. A total of 180 dilatations were performed on these 10 patients of corrosive strictures over a period of 12 months. One minor perforation occurred in this study.
Conclusions:
In resource‑limited settings such as India, dilatation without fluoroscopy can be considered as effective and safe initial management for corrosive strictures.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The risk for occupational exposure to HIV has been well characterized in the developed world, but limited information is available about this transmission risk in resource-constrained settings facing ...the largest burden of HIV infection. In addition, the feasibility and utilization of post-exposure prophylaxis (PEP) programs in these settings are unclear. Therefore, we examined the rate and characteristics of occupational exposure to HIV and the utilization of PEP among health care workers (HCW) in a large, urban government teaching hospital in Pune, India.
Demographic and clinical data on occupational exposures and their management were prospectively collected from January 2003-December 2005. US Centers for Diseases Control guidelines were utilized to define risk exposures, for which PEP was recommended. Incidence rates of reported exposures and trends in PEP utilization were examined using logistic regression.
Of 1955 HCW, 557 exposures were reported by 484 HCW with an incidence of 9.5 exposures per 100 person-years (PY). Housestaff, particularly interns, reported the greatest number of exposures with an annual incidence of 47.0 per 100 PY. Personal protective equipment (PPE) was used in only 55.1% of these exposures. The incidence of high-risk exposures was 6.8/100 PY (n = 339); 49.1% occurred during a procedure or disposing of equipment and 265 (80.0%) received a stat dose of PEP. After excluding cases in which the source tested HIV negative, 48.4% of high-risk cases began an extended PEP regimen, of whom only 49.5% completed it. There were no HIV or Hepatitis B seroconversions identified. Extended PEP was continued unnecessarily in 7 (35%) of 20 cases who were confirmed to be HIV-negative. Over time, there was a significant reduction in proportion of percutaneous exposures and high-risk exposures (p < 0.01) and an increase in PEP utilization for high risk exposures (44% in 2003 to 100% in 2005, p = 0.002).
Housestaff are a vulnerable population at high risk for bloodborne exposures in teaching hospital settings in India. With implementation of a hospital-wide PEP program, there was an encouraging decrease of high-risk exposures over time and appropriate use of PEP. However, overall use of PPE was low, suggesting further measures are needed to prevent occupational exposures in India.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background. In contrast with many other countries, isoniazid preventative therapy is not recommended in clinical care guidelines for human immunodeficiency virus (HIV)—infected persons with latent ...tuberculosis (TB) in India. Methods. Seven hundred fifteen HIV-infected mothers and their infants were prospectively followed up for 1 year after delivery at a public hospital in Pune, India. Women were evaluated for active TB during regular clinic visits, and tuberculin skin tests were performed. World Health Organization definitions for confirmed, probable, and presumed TB were used. Poisson regression was performed to determine correlates of incident TB, and adjusted probabilities of mortality were calculated. Results. Twenty-four of 715 HIV-infected women who were followed up for 480 postpartum person-years developed TB, yielding a TB incidence of 5.0 cases per 100 person-years (95% confidence interval CI, 3.2–7.4 cases per 100 person-years). Predictors of incident TB included a baseline CD4 cell count <200 cells/mm3 (adjusted incident rate ratio IRR, 7.58; 95% CI, 3.07–18.71), an HIV load <50,000 copies/mL (adjusted IRR, 3.92; 95% CI, 1.69–9.11), and a positive tuberculin skin test result (adjusted IRR, 3.08; 95% CI, 1.27–7.47). Three (12.5%) of 24 women with TB died, compared with 7 (1.0%) of 691 women without TB (IRR, 12.2; 95% CI, 2.03–53.33). Among 23 viable infants with mothers with TB, 2 received a diagnosis of TB. Four infants with mothers with TB died, compared with 28 infants with mothers without TB (IRR, 4.71; 95% CI, 1.19–13.57). Women with incident TB and their infants had a 2.2- and 3.4-fold increased probability of death, respectively, compared with women without active TB and their infants, controlling for factors independently associated with mortality (adjusted IRR, 2.2 95% CI, 0.6–3.8 and 3.4 95% CI, 1.22–10.59, respectively). Conclusions. Among Indian HIV-infected women, we found a high incidence of postpartum TB and associated postpartum maternal and infant death. Active screening and targeted use of isoniazid preventative therapy among HIV-infected women in India should be considered to prevent postpartum maternal TB and associated mother-to-child morbidity and mortality.
Background: Non-alcoholic fatty liver disease (NAFLD) is one of the commonest liver pathologies and is increasing due to increasing obesity. Non-alcoholic fatty liver disease-liver fat score is a ...non-invasive diagnostic tool with a sensitivity and specificity of 95%. Methods: This was a cross-sectional observational study on 50 overweight and obese individuals with a body mass index (BMI) of more than or equal to 25 kg/m2 and fatty liver on ultrasonography (USG). Alcoholics (≥30 g/day for men and ≥20 g/day for women), other etiologies like drugs and patients who had bowel resection surgeries for obesity were excluded from the study. Non-alcoholic fatty liver disease-liver fat score of more than -0.64 ruled in NAFLD. Data were entered into Microsoft Excel and analyzed using the SPSS (Statistical Package for Social Sciences) Software 20. Results: About 33/50 patients had a score of more than -0.64. Metabolic syndrome was present in 29 (58%), dyslipidemia in 38 (76%), and diabetes mellitus (46%) was the commonest comorbidity. There was a statistically significant difference in the mean age, weight, BMI, blood pressure, liver enzymes, fasting lipid profile, serum albumin, glycosylated Hemoglobin A1C (HBA1C), international normalised ratio (INR), and fasting blood sugars between the two groups with scores >-0.64 and ≤-0.64. There was a negative correlation of high-density lipoprotein and a positive correlation of liver enzymes, triglycerides, low-density lipoprotein, total cholesterol, fasting blood sugar level, and HBA1c with a score of >-0.64. Conclusion: Higher BMI, metabolic syndrome, diabetes mellitus, and dyslipidemia were significantly associated with a score of >-0.64. This score confirmed the ultrasonographically diagnosed fatty liver.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Purpose of Review: Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease globally. Hyperglycemia, hypertension, and family history are the traditional risk factors for the ...initiation and progression of DKD. Glycemic variability (GV) has also been considered as a risk factor for diabetes complications. Studies have already shown that GV increases the risk of macrovascular complications. The purpose of this review is to study the association of GV with DKD. Journal articles related to this topic were reviewed to get the data for this article. Summary In the setting of DKD, a higher GV has been observed. However, evidence to suggest GV as a risk factor for the development and progression of DKD is not sufficient. The data seem to suggest that the link between GV and diabetic microvascular complications has remained a hypothetical one, yet to be proven or disproven by appropriate studies. Randomized controlled trials using continuous glucose monitoring data will clarify the impact of GV and its management in DKD.
Summary The human stomach is colonized by diverse bacterial species. The presence of non- Helicobacter pylori bacteria in urease-positive biopsies of individuals has been reported. Bacteria belonging ...to the Ochrobactrum genus have been documented in the human gastric niche. The co-occurrence of Ochrobactrum spp. with H. pylori was previously reported in an antral biopsy of a non-ulcer dyspeptic (NUD) subject from Northern India. There is no information on the genetic diversity of Ochrobactrum spp. isolated from the gastric niche in the stomach. We aimed to study the species distribution and diversity of Ochrobactrum spp. with and without H. pylori in urease-positive biopsies across three different geographical regions in India. Sixty-two Ochrobactrum isolates recovered from patients with an upper gastric disorder ( n = 218) were subjected to molecular identification and multilocus sequence typing. H. pylori DNA was found in the majority of biopsies, which had a variable degree of Ochrobactrum spp present. Interestingly, some of the urease-positive biopsies only had Ochrobactrum without any H. pylori DNA. Based on phylogenetic analysis, the Ochrobactrum isolates were distributed into the O. intermedium , O. anthropi and O. oryzae groups. This indicates there are multiple species in the gastric niche irrespective of the presence or absence of H. pylori . Antibiotyping based on colistin and polymyxin B could differentiate between O. intermedium and O. anthropi without revealing the resistance-driven diversity. Considering the prevalence of multiple Ochrobactrum spp. in the human gastric niche, it is important to evaluate the commensal and/or pathogenic nature of non- H. pylori bacteria with respect to their geographical distribution, lifestyle and nutrition needs.
ABSTRACT
Introduction:
Multisystem involvement is a norm in Type 2 diabetes mellitus (T2DM). Dyspepsia is a common gastrointestinal (GI) tract symptom in people with diabetes. We aimed to study the ...esophageal, gastric, and duodenal mucosal changes; presence of Helicobacter pylori (HP) infection; and its significance in dyspeptic diabetes patients.
Materials and Methods:
A prospective observational study done on 287 patients (147 patient with diabetes and 140 nondiabetic controls) with dyspepsia of more than 6 months duration. All patients underwent upper GI endoscopy and evaluation for HP infection. Gross and histopathological examination (HPE) features of biopsies from the esophagus, stomach (fundus, body, and antrum), and duodenum were analyzed and rapid urease test as well as HPE was done for HP detection. Statistical analysis was done and results were expressed as mean ± standard deviation. P < 0.05 was considered to be statistically significant.
Results:
Average age for dyspeptic T2DM patients was 56.0 ± 8.44 years. Total 67.35% diabetes patients were addicted to tobacco. Epigastric pain and heartburn were the most common symptoms. Antral gastritis was the most common gross (75.08%) and HPE (70.38%) finding in patients with diabetes. In all, 44.21% patients with diabetes tested positive for HP infection, and there was a statistically significant association of HP with T2DM when compared with nondiabetics (P < 0.00001). However, HP infection did not correlate significantly with either glycosylated hemoglobin (HbA1c) or duration of T2DM.
Conclusion:
Antral gastritis was a common finding in dyspeptic diabetic patients. HP infection although associated with T2DM dyspeptic patients, was not associated with either uncontrolled sugar levels or duration of diabetes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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