Consensus guidelines on pediatric acute rheumatic fever and rheumatic heart disease

JUSTIFICATION: Acute rheumatic fever and rheumatic chronic valvular heart disease is an important preventable cause of morbidity and mortality in suburban and rural India. Its diagnosis is based on clinical criteria. These criteria need verification and revision in the Indian context. Furthermore, there are glaring differences in management protocols available in literature. These facts prompted Indian Academy of Pediatrics to review the management of rheumatic fever. PROCESS: Management of Rheumatic fever was reviewed and recommendation was formulated at national consultative meeting on 20th May 2007 at New Delhi. OBJECTIVES: To formulate uniform guidelines on management of acute rheumatic fever and rheumatic heart disease in the Indian context. Guidelines were formulated for the management of streptococcal pharyngitis, acute rheumatic fever and its cardiac complication as well as secondary prophylaxis for recurrent episodes. RECOMMENDATIONS: (1) Streptococcal eradication with appropriate antibiotics (Benzathine penicillin single dose or penicillin V oral or azithromycin). (2) Diagnosis of rheumatic fever based on Jones criteria. (3) Control inflammatory process with aspirin with or without steroids (total duration of treatment of 12 weeks). (4) Treatment of chorea according to severity (therapy to continue for 2-3 weeks after clinical improvement). (5) Protocol for managing cardiac complication like valvular heart disease, congestive heart failure and atrial fibrillation. (6) Secondary prophylaxis with benzathine penicillin and management of anaphylaxis.     

Distinct histopathological phenotypes of severe alcoholic hepatitis suggest different mechanisms driving liver injury and failure

Intrahepatic neutrophil infiltration has been implicated in severe alcoholic hepatitis (SAH) pathogenesis; however, the mechanism underlying neutrophil-induced injury in SAH remains obscure. This translational study aims to describe the patterns of intrahepatic neutrophil infiltration and its involvement in SAH pathogenesis. Immunohistochemistry analyses of explanted livers identified two SAH phenotypes despite a similar clinical presentation, one with high intrahepatic neutrophils (Neu^hi), but low levels of CD8⁺ T cells, and vice versa. RNA-Seq analyses demonstrated that neutrophil cytosolic factor 1 (NCF1), a key factor in controlling neutrophilic ROS production, was upregulated and correlated with hepatic inflammation and disease progression. To study specifically the mechanisms related to Neu^hi in AH patients and liver injury, we used the mouse model of chronic-plus-binge ethanol feeding and found that myeloid-specific deletion of the Ncf1 gene abolished ethanol-induced hepatic inflammation and steatosis. RNA-Seq analysis and the data from experimental models revealed that neutrophilic NCF1-dependent ROS promoted alcoholic hepatitis (AH) by inhibiting AMP-activated protein kinase (a key regulator of lipid metabolism) and microRNA-223 (a key antiinflammatory and antifibrotic microRNA). In conclusion, two distinct histopathological phenotypes based on liver immune phenotyping are observed in SAH patients, suggesting a separate mechanism driving liver injury and/or failure in these patients.     

Genetic evidence for a potential causal relationship between insomnia symptoms and suicidal behavior: a Mendelian randomization study

Insomnia and restless leg syndrome (RLS) are associated with increased risk for suicidal behavior (SB), which is often comorbid with mood or thought disorders; however, it is unclear whether these relationships are causal. We performed a two-sample Mendelian randomization study using summary-level genetic associations with insomnia symptoms and RLS against the outcomes of risk of major depressive disorder (MDD), bipolar disorder (BP), schizophrenia (SCZ), and SB. The inverse-variance weighted method was used in the main analysis. We performed replication and sensitivity analyses to examine the robustness of the results. We identified outcome cohorts for MDD (n = 170,756 cases/329,443 controls), BP (n = 20,352/31,358), SCZ (n = 69,369/236,642), SB-Cohort-2019 (n = 6569/14,996 all with MDD, BP or SCZ; and SB within individual disease categories), and SB-Cohort-2020 (n = 29,782/519,961). Genetically proxied liability to insomnia symptoms significantly associated with increased risk of MDD (odds ratio (OR) = 1.23, 95% confidence interval (CI) = 1.2–1.26, P = 1.37 × 10^–61), BP (OR = 1.15, 95% CI = 1.07–1.23, P = 5.11 × 10^–5), SB-Cohort-2019 (OR = 1.17, 95% CI = 1.07–1.27, P = 2.30 × 10^–4), SB-Cohort-2019 in depressed patients (OR = 1.34, 95% CI = 1.16–1.54, P = 5.97 × 10^–5), and SB-Cohort-2020 (OR = 1.24, 95% CI = 1.18–1.3, P = 1.47 × 10^–18). Genetically proxied liability to RLS did not significantly influence the risk of any of the outcomes (all corrected P > 0.05). Results were replicated for insomnia with MDD and SB in Mass General Brigham Biobank and were consistent in multiple lines of sensitivity analyses. In conclusion, human genetic evidence supports for the first time a potentially independent and causal effect of insomnia on SB and encourages further clinical investigation of treatment of insomnia for prevention or treatment of SB.Subject terms: Genetic markers, Risk factors, Psychiatric disorders     

Determination of Optimum Machining Parameters for Face Milling Process of Ti6A14V Metal Matrix Composite

This paper shows the novel approach of Taguchi-Based Grey Relational Analysis of Ti6Al4V Machining parameter. Ti6Al4V metal matrix composite has been fabricated using the powder metallurgy route. Here, all the components of TI6Al4V machining forces, including longitudinal force (F_x), radial force (F_y), tangential force (F_z), surface roughness and material removal rate (MRR) are measured during the facing operation. The effect of three process parameters, cutting speed, tool feed and cutting depth, is being studied on the matching responses. Orthogonal design of experiment (Taguchi L9) has been adopted to execute the process parameters in each level. To validate the process output parameters, the Grey Relational Analysis (GRA) optimization approach was applied. The percentage contribution of machining parameters to the parameter of response performance was interpreted through variance analysis (ANOVA). Through the GRA process, the emphasis was on the fact that for TI6Al4V metal matrix composite among all machining parameters, tool feed serves as the highest contribution to the output responses accompanied by the cutting depth with the cutting speed in addition. From optimal testing, it is found that for minimization of machining forces, maximization of MRR and minimization of Ra, the best combinations of input parameters are the 2nd stage of cutting speed (175 m/min), the 3rd stage of feed (0.25 mm/edge) as well as the 2nd stage of cutting depth (1.2 mm). It is also found that hardness of Ti6Al4V MMC is 59.4 HRA and composition of that material remain the same after milling operation.     

Epidemiology of breast cancer in Indian women

Breast cancer has ranked number one cancer among Indian females with age adjusted rate as high as 25.8 per 100,000 women and mortality 12.7 per 100,000 women. Data reports from various latest national cancer registries were compared for incidence, mortality rates. The age adjusted incidence rate of carcinoma of the breast was found as high as 41 per 100,000 women for Delhi, followed by Chennai (37.9), Bangalore (34.4) and Thiruvananthapuram District (33.7). A statistically significant increase in age adjusted rate over time (1982–2014) in all the PBCRs namely Bangalore (annual percentage change: 2.84%), Barshi (1.87%), Bhopal (2.00%), Chennai (2.44%), Delhi (1.44%) and Mumbai (1.42%) was observed. Mortality‐to‐incidence ratio was found to be as high as 66 in rural registries whereas as low as 8 in urban registries. Besides this young age has been found as a major risk factor for breast cancer in Indian women. Breast cancer projection for India during time periods 2020 suggests the number to go as high as 1797900. Better health awareness and availability of breast cancer screening programmes and treatment facilities would cause a favorable and positive clinical picture in the country.     

Optimization of Selective Laser Melting Parameter for Invar Material by Using JAYA Algorithm: Comparison with TLBO,GA and JAYA

In this study, the hardness and surface roughness of selective laser-melted parts have been evaluated by considering a wide variety of input parameters. The Invar-36 has been considered a workpiece material that is mainly used in the aerospace industry for making parts as well as widely used in bimetallic thermostats. It is the mechanical properties and metallurgical properties of parts that drive the final product’s quality in today’s competitive marketplace. The study aims to examine how laser power, scanning speed, and orientation influence fabricated specimens. Using ANOVA, the established models were tested and the parameters were evaluated for their significance in predicting response. In the next step, the fuzzy-based JAYA algorithm has been implemented to determine which parameter is optimal in the proposed study. In addition, the optimal parametric combination obtained by the JAYA algorithm was compared with the optimal parametric combination obtained by TLBO and genetic algorithm (GA) to establish the effectiveness of the JAYA algorithm. Based on the results, an orientation of 90°, 136 KW of laser power, and 650 mm/s scanning speed were found to be the best combination of process parameters for generating the desired hardness and roughness for the Invar-36 material.     

Investigation on Carbonation and Permeability of Concrete with Rice Hush Ash and Shop Solution Addition

The goal of this study was to determine the coefficient of permeability as well as the rate of carbonation of concrete constructed with rice husk ash (RHA) as a partial replacement for cement (i.e., 5%, 10%, and 15%) and two different concentrations of soap solutions (i.e., 1 percent and 2 percent). The microstructural studies of RHA, and carbonated samples have been conducted by using Scanning Electron Microscope (SEM) and X-Ray Diffraction (XRD) analysis. According to this study, the carbonation depth of concrete made with 1% and 2% soap solution concentration and without rice husk ash decreased by 11.89% and 46.55%, respectively. From the results, it may also be observed that the carbonation depth of concrete made with up to 10% replacement of cement by rice husk ash led to maximum carbonation resistance, while more than 10% replacement of cement showed higher carbonation depth. It is also observed that the coefficient of permeability of concrete with 2% soap solution significantly decreased as compared to the 1% soap solution and control mix. It may be observed from the SEM images that 0% soap solution (M1) concrete has a very rough concrete surface which may indicate more voids. However, 2% soap solution concrete has a much smoother surface, which indicates a smaller number of voids. Furthermore, the SEM images showed that the soap solution helps in filling the voids of concrete which ultimately helps in reduction in permeability. Energy Dispersive X-Ray Analysis (EDX) of concrete with 0% (M1) and 2% (M6) soap solution disclosed that the concrete with 2% soap solution (M6) exhibited more silica element formation than the concrete with no soap solution (M1).     

Enzobiotics—A Novel Therapy for the Elimination of Uremic Toxins in Patients with CKD (EETOX Study): A Multicenter Double-Blind Randomized Controlled Trial

Design, participants, setting, and measurements: Predialysis adult participants with chronic kidney disease (CKD) and mean estimated glomerular filtration rate (eGFR) <45 mL/min per 1.73 m²) were recruited in 2019 to a multicentric double-blinded randomized controlled trial of enzobiotic therapy (synbiotics and proteolytic enzymes) conducted over 12 weeks. The primary objective was to evaluate the efficacy and safety of enzobiotics in reducing the generation of p-cresol sulfate (PCS) and indoxyl sulfate (IS), stabilizing renal function, and improving quality of life (QoL), while the secondary objective was to evaluate the feasibility of the diagnostic prediction of IS and PCS from CKD parameters. Results: Of the 85 patients randomized (age 48.76 years, mean eGFR 23.24 mL/min per 1.73 m² in the placebo group; age 54.03 years, eGFR 28.93 mL/min per 1.73 m² in the enzobiotic group), 50 completed the study. The absolute mean value of PCS increased by 12% from 19 µg/mL (Day 0) to 21 µg/mL (Day90) for the placebo group, whereas it decreased by 31% from 23 µg/mL (Day 0) to 16 µg/mL (Day 90) for the enzobiotic group. For IS, the enzobiotic group showed a decrease (6.7%) from 11,668 to 10,888 ng/mL, whereas the placebo group showed an increase (8.8%) from 11,462 to 12,466 ng/mL (Day 90). Each patient improvement ratio for Day 90/Day 0 analysis showed that enzobiotics reduced PCS by 23% (0.77, p = 0.01). IS levels remained unchanged. In the placebo group, PCS increased by 27% (1.27, p = 0.14) and IS increased by 20% (1.20, p = 0.14). The proportion of individuals beyond the risk threshold for PCS (>20 µg/mL) was 53% for the placebo group and 32% for the enzobiotic group. The corresponding levels for IS risk (threshold >20,000 ng/mL) were 35% and 24% for the placebo and enzobiotic groups, respectively. In the placebo group, eGFR decreased by 7% (Day 90) but remained stable (1.00) in the enzobiotic group. QoL as assessed by the adversity ratio decreased significantly (p = 0.00), highlighting an improvement in the enzobiotic group compared to the placebo group. The predictive equations were as follows: PCS (Day 0 = −5.97 + 0.0453 PC + 2.987 UA − 1.310 Creat; IS (Day 0) = 756 + 1143 Creat + 436.0 Creat². Conclusion: Enzobiotics significantly reduced the PCS and IS, as well as improved the QoL.