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The present study was designed to check the serum levels of protease-activated receptor (PAR-1) in patients during different phases of dengue severity. Moreover, a correlation between serum PAR-1 levels and hematological parameters, inflammatory cytokine levels, and liver functional changes was also determined. Based on the World Health Organization criteria, the study population was divided into: nonsevere dengue fever (DF; n = 30), severe dengue hemorrhagic fever (DHF; n = 19), and severe dengue shock syndrome (DSS; n = 11). The platelet count (PLT) and hematocrit (HCT) were analyzed using an automated hematology analyzer and liver function enzymes aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphate (ALP), bilirubin were checked by auto-analyzer using diagnostic kits. Moreover, the levels of inflammatory mediators C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-17 (IL-17), and PAR-1 were determined using respective ELISA kits. The HCT levels were elevated and platelet count decreased significantly during dengue complications (DHF and DSS) compared to the DF patients, while the levels of liver functional biomarkers AST, ALT, ALP, and bilirubin remained elevated in DHF and DSS groups than in the corresponding DF group. Similarly, the inflammatory cytokine levels of CRP, TNF-α, IL-6, and IL-17 in DHF and DSS subjects were markedly increased when observed against DF subjects. Notably, the PAR-1 levels were significantly elevated in DHF and DSS groups than in the DF group and positively correlated with changes in HCT levels, inflammatory biomarkers, and liver enzymes. Our findings conclude that PAR-1 levels persistently increased with the severity of the dengue infection and are strongly associated with various clinical manifestations. Thus, PAR-1 levels can be used as a diagnostic marker for assessing dengue severity.
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Dengue , Dengue Grave , Humanos , Interleucina-17 , Fator de Necrose Tumoral alfa , Interleucina-6 , Citocinas , Biomarcadores , Bilirrubina , Alanina Transaminase , Aspartato Aminotransferases , Proteína C-Reativa , InflamaçãoRESUMO
OBJECTIVE: To compare the efficacy and safety of avanafil as compared with sildenafil in the management of patients with erectile dysfunction. METHODS: It was a prospective, randomized, double-blind, two-arm, active-controlled, parallel, multicenter, non-inferiority clinical study carried out in patients with erectile dysfunction for at least 3 months and International Index of Erectile Function - Erectile Function domain score of <26 at enrolment. RESULTS: A total of 220 patients were randomized to receive either avanafil tablets 100 mg or sildenafil tablets 50 mg in 1:1 ratio. After 4 weeks of treatment, 40.0% of patients in the avanafil group and 45.6% of patients in the sildenafil group required dose escalation to a high dose (avanafil 200 mg/sildenafil 100 mg). The difference in the mean change of International Index of Erectile Function - Erectile Function score from baseline in the two groups increased from week 4 (1.1, 95% confidence interval -0.2 to 2.5) to week 8 (1.4, 95% confidence interval 0.1-2.7) and week 12 (2.1, 95% confidence interval 0.8-3.5), showing non-inferiority at week 4, and superiority at week 8 and week 12. Avanafil showed a faster onset of action as shown by a significantly better response to modified Sexual Encounter Profile 1 in the avanafil group (84.8%) as compared with that in the sildenafil group (28.2%; P < 0.001). Both avanafil and sildenafil were well tolerated by all the patients in the study; the most common adverse event reported during the study was headache in both the groups. CONCLUSION: Avanafil is superior to sildenafil in improving the International Index of Erectile Function - Erectile Function domain score at the end of 12 weeks of treatment with the added advantage of faster onset of action.
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Disfunção Erétil , Método Duplo-Cego , Disfunção Erétil/tratamento farmacológico , Humanos , Masculino , Estudos Prospectivos , Pirimidinas , Citrato de Sildenafila/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Inflammation is a prominent clinical manifestation in type 2 diabetes mellitus (T2DM) patients, often associated with insulin resistance, metabolic dysregulation, and other complications. AIM OF THE STUDY: The present study has been designed to check the serum levels of PAR-1 and correlate with various clinical manifestations and inflammatory cytokines levels in type 2 diabetic subjects. MATERIAL AND METHODS: The study population was divided into two groups, healthy volunteers (n = 15): normal glycated hemoglobin (HbA1c) (4.26 ± 0.55) and type 2 diabetic subjects (n = 30): HbA1c levels (7.80 ± 2.41). The serum levels of PAR-1 (ELISA method) were studied in both groups and correlated with demographic parameters age, weight, body mass index (BMI), and conventional inflammation biomarkers like C-reactive protein (CRP), interleukin 6 (IL-6), interleukin 8 (IL-8), and tumour necrosis factor-alpha (TNF-α). RESULTS: The demographic variables including the body weight (77.38 ± 10.00 vs. controls 55.26 ± 6.99), BMI (29.39 ± 3.61 vs. controls 25.25 ± 4.01), glycemic index HbA1c (7.80 ± 2.41 vs. controls 4.26 ± 0.55) were found to be statistically increased in T2DM subjects than the healthy control group. The levels of various inflammatory biomarkers and PAR-1 were significantly elevated in T2DM groups in comparison to healthy volunteers. The univariate and multivariate regression analysis revealed that elevated PAR-1 levels positively correlated with increased body weight, BMI, HbA1c, and inflammatory cytokines. CONCLUSION: Our findings indicate that the elevated serum PAR-1 levels serve as an independent predictor of inflammation in T2DM subjects and might have prognostic value for determining T2DM progression.
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Diabetes Mellitus Tipo 2 , Receptor PAR-1 , Fator de Necrose Tumoral alfa , Biomarcadores , Glicemia/metabolismo , Peso Corporal , Proteína C-Reativa/análise , Citocinas , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Humanos , Inflamação/complicações , Inflamação/diagnóstico , Interleucina-6 , Interleucina-8 , Receptor PAR-1/sangueRESUMO
INTRODUCTION: Cataract represents one of the most frequent eye complications in type 1 DM and type 2 DM patients; contrarily, acute cataract in young diabetic patients occurs very rarely. Only few cases with acute bilateral cataract - all relatively shortly after the diagnosis of type 1 DM have been reported. It can affect visual acuity from slight visual impairment to complete blindness. Although usually associated with chronic hyperglycaemia, it may also occur on rapid restoration of euglycaemia.1 Early detection of diabetes and adequate glycaemic control, particularly in female adolescents, may prevent this debilitating complication of diabetes.
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Catarata/complicações , Complicações do Diabetes/diagnóstico , Diabetes Mellitus Tipo 1/complicações , Adolescente , Cegueira , Glicemia , Feminino , Humanos , PrevalênciaRESUMO
INTRODUCTION: Traditional percutaneous nephrolithotomy (PCNL) training involved subjective award of cases to the trainee. We restructured this according to the Guy's stone score (GSS) such that each trainee stepwise completed 25 cases of each grade before progressing. This study compares the outcomes of training with traditional versus stepwise approach. METHODS: Four hundred consecutive cases equally distributed for two trainees in each group were compared in terms of complications (Clavien-Dindo), stone free rate (SFR), operative and fluoroscopy time. External comparison was also done against a benchmark surgeon. Multivariable regression model was created to compare SFR and complications while adjusting for comorbidity, Amplatz size, access tract location, number of punctures, body mass index, stone complexity, and training approach. RESULTS: The distribution of cases in terms of calculus complexity was similar. Overall, in comparison to traditional training, stepwise training had significantly shorter median operative time (100 vs. 120 min, P < 0.05), fluoroscopy time (136 vs. 150 min, P < 0.05) and fewer overall (29.5% vs. 43.5%, P < 0.005) as well as major complications (3% vs. 8.5%, P - 0.029), though initial SFR was higher but not statistically significant (77% vs. 71.5%). On multivariable analyses, stepwise training was independently associated with lower complications (odds ratio 0.46 [0.20-0.74], P - 0.0013) along with GSS grade, number of punctures, and Amplatz size. Stepwise training had similar fluoroscopy time, major complications and final clearance rate compared to expert surgeon. CONCLUSIONS: PCNL has a learning curve specific for each grade of calculus complexity and stepwise training protocol improves outcomes.
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Background and Aims: Multiple sources of medical oxygen, namely liquid medical oxygen (LMO) tanks, pressure swing adsorption (PSA) plants, concentrators, and gaseous cylinders, are available at different healthcare facilities. These sources of oxygen have varying installation and operational costs. In low-resource settings, it is imperative to utilise these assets optimally. This study investigated the operational costs of multiple oxygen sources available at a healthcare facility. Methods: A Microsoft (MS) Excel-based model was developed to analyse and compare the oxygen manufacturing costs (in â¹/m3) using PSA plants and procurement costs (in â¹/m3) of LMO and third-party vendor-refilled cylinders. Results: The oxygen manufacturing costs for PSA plants of different capacities and running times on electricity and diesel generators (DGs) as a power source were calculated. This study highlights the cost-benefit of using PSA plants over LMO and third-party vendor-refilled cylinders as a source of oxygen. PSA plants are most economical when they are of higher capacity and used to their maximum capacity on electricity as the power source. On the contrary, they are most expensive when used on a DG set as a power source. Furthermore, this study provides evidence of PSA plants being more cost-effective for refilling cylinders using a booster compressor unit when compared to third-party vendor-cylinder refilling. Conclusion: Given their cost-effectiveness and low third-party dependence, they should be utilised to their maximum capacity as medical oxygen sources at healthcare facilities.
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INTRODUCTION: The primary goal of periodontal therapy is to arrest the inï¬ammatory disease process which is done by non-surgical and surgical therapies in order to reduce the microorganisms. The outcome of periodontal therapy may not reveal the desired results owing to inaccessible areas for instrumentation, pathogenicity, resistance of the microorganisms, or even due to compromised host response to the treatment. Thus, adjunctive laser therapy has been proposed as a novel treatment modality in the treatment of periodontal disease. Aim: The aim of this study was to clinically evaluate the effect of a 980 nm diode laser (DEN10B; Wuhan Gigaa Optronics Technology Co., Ltd., Wuhan, China) therapy as an adjunct to scaling and root planing in patients with chronic periodontitis and type II diabetes. METHODS: Twenty patients were divided into two groups in a split-mouth study design. Group I (Control) comprised mechanical debridement alone and Group II (test) comprised mechanical debridement followed by adjunctive laser therapy. The clinical parameters were recorded at baseline, six weeks, and three months, and the results were analyzed. RESULTS: There was a significant improvement in gingival and plaque index in the test group. Though there was no significant improvement in probing pocket depth and clinical attachment, the results in the test group were superior relative to the control group. CONCLUSION: Non-surgical periodontal therapy with adjunctive use of diode laser is effective in the management of generalized chronic periodontitis in patients with type II diabetes which led to a significant reduction in plaque score, gingival index score, probing pocket depth, and gain in clinical attachment level.
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Background: Dengue fever is a highly endemic tropical infectious disease that is quickly spreading over the world. Diabetes Mellitus has been linked to chronic inflammation. This present study was designed to compare the severity of dengue infection among diabetic and non-diabetic populations. Methods: A prospective observational study was conducted on 40 patients (20 diabetic and 20 non-diabetic) who suffered from dengue infection. The study involved the collection of data of the dengue patients includes patient's demographic details, medical condition as well as biochemical investigations. Results: Dengue-infected individuals with diabetes showed greater CRP, Endocan levels, IL-8 and Perfusion Index than those without diabetes (CRP; 35.308 ± 1.32 vs. 18.6365 ± 0.64) mg/dl (p≤ 0.001) (Endocan 42.316 ± 1.46vs. 32.839 ± 0.33), ng/dl (p≤ 0.001), (142.98 ± 1.05 vs 103.69 ± 0.64) (p ≤ 0.001) and (3.695 ± 0.18 vs. 1.98 ± 0.08) (p ≤ 0.001) respectively. Conclusion: In conclusion the results indicate that prognosis of DHF grade II with diabetes mellitus tends to be more prone to bleeding disorder and can result into morbidity and mortality considering by triggering of the various inflammatory cascade resulting in hyperglycaemia and poor glycemic control.
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Biologic-based medicines are used to treat a variety of diseases and account for around one-quarter of the worldwide pharmaceutical market. The use of biologic medications among cancer patients has resulted in substantial advancements in cancer treatment and supportive care. Biosimilar medications (or biosimilars) are very similar to the reference biologic drugs, although they are not identical. As patent protection for some of the most extensively used biologics begins to expire, biosimilars have the potential to enhance access and provide lower-cost options for cancer treatment. Initially, regulatory guidelines were set up in Europe in 2003, and the first biosimilar was approved in 2006 in Europe. Many countries, including the United States of America (USA), Canada, and Japan, have adopted Europe's worldwide regulatory framework. The use of numerous biosimilars in the treatment and supportive care of cancer has been approved and, indeed, the count is set to climb in the future around the world. However, there are many challenges associated with biosimilars, such as cost, immunogenicity, lack of awareness, extrapolation of indications, and interchangeability. The purpose of this review is to provide an insight into biosimilars, which include various options available for oncology, and the associated adverse events. We compare the regulatory guidelines for biosimilars across the world, and also present the latest trends and challenges in medical oncology both now and in the future, which will assist healthcare professionals, payers, and patients in making informed decisions, increasing the acceptance of biosimilars in clinical practice, increasing accessibility, and speeding up the health and economic benefits associated with biosimilars.
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Major depressive disorder (MDD) is a heterogeneous disease which is why there are currently no specific methods to accurately test the severity, endophenotype or therapy response. This lack of progress is partly attributed to the com-plexity and variability of depression, in association with analytical variability of clinical literature and the wide number of theoretically complex biomarkers. The literature accessible, indicates that markers involved in inflammatory, neuro-trophic and metabolic processes and components of neurotransmitters and neuroendocrine systems are rather strong indicators to be considered clinically and can be measured through genetic and epigenetic, transcriptomic and proteomic, metabolomics and neuroimaging assessments. Promising biologic systems/markers found were i.e., growth biomarkers, endocrine markers, oxidant stress markers, proteomic and chronic inflammatory markers, are discussed in this review. Several lines of evidence suggest that a portion of MDD is a dopamine agonist-responsive subtype. This review analyzes concise reports on the pathophysiological biomarkers of MDD and therapeutic reactions via peripheral developmental factors, inflammative cytokines, endocrine factors and metabolic markers. Various literatures also support that endocrine and metabolism changes are associated with MDD. Accumulating evidence suggests that at least a portion of MDD patients show characteristics pathological changes regarding different clinical pathological biomarkers. By this review we sum up all the different biomarkers playing an important role in the detection or treatment of the different patients suffering from MDD. The review also gives an overview of different biomarker's playing a potential role in modulating effect of MDD.
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A 65-year-old woman from a rural area presented to the surgical service with a very large abdominal lump that the patient had first noticed 8 years previously. The lump had steadily increased in size over time, and the patient had dysuria, weakness and dyspnoea on exertion. On examination she was grossly anaemic with a large retroperitoneal lump that occupied the whole right side of abdomen; the lump was soft to firm in consistency and non-tender. She had no lymphoedema or other palpable lymph nodes. Ultrasound revealed a large retroperitoneal tumour with fatty elements, arising from the right kidney. There was no involvement of the intestines. Findings of the computed tomography scan were typical for renal angiomyolipoma. The patient underwent surgery and the tumour was excised. Four units of blood were transfused preoperatively and in addition two units were given postoperatively. The patient was given thromboprophylaxis perioperatively and in the postoperative period because she was bedridden and could not ambulate. She made an uneventful recovery.