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11.
The antigenic heterogeneity of Orientia in India is still unknown in many disease endemic areas. The present study aims to characterize the strains of O. tsutsugamushi circulating in Nagaland, Northeast India. Two patients clinically diagnosed with ST and hospitalized in Mon district hospital, Nagaland were identified from whom eschar tissues were collected. Both patients demonstrated antibodies against O. tsutsugamushi along with positive PCR amplification for 56 ?kDa gene. The prototype strain TA763 shared 90.4% homology with the sequences. Both the sequences formed a distinctive cluster demonstrating 100% similarity with strains identified from Thailand, Vietnam, China and southern parts of India.  相似文献   
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Objective

To assay peripheral inter-ictal cytokine serum levels and possible relations with non-invasive vagus nerve stimulation (nVNS) responsiveness in migraineurs.

Methods

This double-blinded, sham-controlled study enrolled 48 subjects and measured headache severity, frequency [headache days/month, number of total and mild/moderate/severe classified attacks/month], functional state [sleep, mood, body weight, migraine-associated disability] and serum levels of inflammatory markers [inter-ictal] using enzyme-linked immunoassays at baseline and after 2 months of adjunctive nVNS compared to sham stimulation and suitably matched controls.

Results

No significant differences were observed at baseline and after 2 months for headache severity, total attacks/month, headache days/month and functional outcome [sleep, mood, disability] between verum and sham nVNS. However, the number of severe attacks/month significantly decreased in the verum nVNS group and circulating pro-inflammatory IL-1β was elevated significantly in the sham group compared to nVNS. Levels of anti-inflammatory IL-10 were significantly higher at baseline in both groups compared to healthy controls, but not at 2 months follow-up [p?<?0.05]. Concentrations of high-mobility group box-1 (HMGB-1), IL-6, tumor-necrosis factor-α (TNF-α), leptin, adiponectin, ghrelin remained unchanged [p?>?0.05]. No severe device-/stimulation-related adverse events occurred.

Conclusion

2 months of adjunctive cervical nVNS significantly declined the number of severe attacks/month. Pro-inflammatory IL-1β plasma levels [inter-ictal] were higher in sham-treated migraine patients compared to verum nVNS. However, pro- [IL-6, HMGB-1, TNF-α, leptin] and anti-inflammatory [IL-10, adiponectin, ghrelin] mediators did not differ statistically. Profiling of neuroinflammatory circuits in migraine to predict nVNS responsiveness remains an experimental approach, which may be biased by pre-analytic variables warranting large-scale biobank-based systematic investigations [omics].  相似文献   
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Hepatitis C is a global public health problem, and Pakistan is the second largest country in the globe with highest prevalence rate of hepatitis C virus (HCV). Until 2014, pegylated interferon (PEG-IFN) plus ribavirin (RBV) has been the standard therapy for HCV, however, owing to its adverse side effects and very low sustained virologic response (SVR) rates therapeutics trend is shifted toward direct-acting antivirals. Tripartite motif containing 22 (TRIM22) is a dynamic antiviral protein that can inhibit multiple viruses in vivo. Expression of TRIM22 mRNA has been linked to outcome of PEG-IFN and ribavirin therapy, where its higher expression leads to rapid virus clearance. However, in terms of therapy with direct-acting antiviral (DAA) or double DAA, impact of TRIM22 expression is largely unknown. These new drugs show more than 90% of SVR rates and lesser side effects and have proven to be better than IFN therapy. Endogenous IFN system suppresses various pathogens through the induction of antiviral effectors termed as interferon-stimulating genes (ISGs). We have studied the expression levels of one of these antiviral effectors, TRIM22 in response to sofosbuvir (SOF) and daclatasvir (DAC) in combination with RBV, using quantitative PCR in the peripheral blood mononuclear cells (PBMCs) of HCV-infected patients. We have observed sustained virus clearance in more than 90% of patients treated with DAA and double DAA and have seen the expression of TRIM22 to be higher in patients who attained SVR as compared to the untreated patients. We have also observed downregulation of TRIM22 in patients who failed to attain rapid virus clearance, and upregulation in those who achieved rapid clearance of virus. Genetic factors that determine the lower TRIM22 expression in these patients are needed to be explored that may also play a role in lower response to anti-HCV therapy. Endogenous IFN system and effects of antiviral proteins in response to DAA therapy is needed to be studied in order to better understand the host response toward these drugs to make them more effective.  相似文献   
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Arsenic (As) and cadmium (Cd) have recently emerged as major health concerns owing to their strong association with diabetes mellitus (DM). We aimed to investigate the heavy metals exposure towards incidence of DM at various enzymatic and hormonal levels. Additionally, association of As and Cd with Zinc (Zn, essential metal) was also evaluated. Spot urine samples were collected to assess As, Cd and Zn through ICP-OES. Serum was analyzed by assay method for fasting blood glucose, liver and renal function biomarkers. ELISA was performed to investigate the impact of heavy metals on HbA1c, α-amylase, DPP-IV, IGF-1, leptin, GSH, MDA, SOD, HDL, FFA, TG and interleukin (IL)-6. Association of heavy metals with DM was measured by odds ratio (OR) and level of significance was assessed by Chi-squared test. Unpaired student's t-test was used to compare DM-associated risk factors in heavy metals-exposed and unexposed participants. As and Cd were detectable in 75.4% and 83% participants with mean concentration of 75.5 ppb and 54.5 ppb, respectively. For As exposure, OR in the third quartile was maximum ie 1.34 (95% CI, 0.80 to 2.23), however the result was not statistically significant (P > .05). For Cd exposure, OR in the fourth quartile was considerably high, 1.62 (95% CI, 1.00 to 2.61), with a significant probability value (P < .05). Urinary Cd was negatively associated with Zn. As and Cd exposure increases the incidence of DM in the general population. Impaired hormonal and enzymatic levels in diabetic and non-diabetic exposed participants reflect the multiple organ damage by heavy metal exposure.  相似文献   
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ObjectivesSevere acute kidney injury (AKI) is a known risk factor for infection and mortality. However, whether stage 1 AKI is a risk factor for infection has not been evaluated in adults. We hypothesized that stage 1 AKI following cardiac surgery would independently associate with infection and mortality.MethodsIn this retrospective propensity score–matched study, we evaluated 1620 adult patients who underwent nonemergent cardiac surgery at the University of Colorado Hospital from 2011 to 2017. Patients who developed stage 1 AKI by Kidney Disease Improving Global Outcomes creatinine criteria within 72 hours of surgery were matched to patients who did not develop AKI. The primary outcome was an infection, defined as a new surgical-site infection, positive blood or urine culture, or development of pneumonia. Secondary outcomes included in-hospital mortality, stroke, and intensive care unit (ICU) and hospital length of stay (LOS).ResultsStage 1 AKI occurred in 293 patients (18.3%). Infection occurred in 20.9% of patients with stage 1 AKI compared with 8.1% in the no-AKI group (P < .001). In propensity-score matched analysis, stage 1 AKI independently associated with increased infection (odds ratio [OR]; 2.24, 95% confidence interval [CI], 1.37-3.17), ICU LOS (OR, 2.38; 95% CI, 1.71–3.31), and hospital LOS (OR, 1.30; 95% CI, 1.17-1.45).ConclusionsStage 1 AKI is independently associated with postoperative infection, ICU LOS, and hospital LOS. Treatment strategies focused on prevention, early recognition, and optimal medical management of AKI may decrease significant postoperative morbidity.  相似文献   
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