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Background: Calcium channel blockers, including the recently developed cilnidipine, are widely used as first-line medications for treating newly diagnosed cases of primary essential hypertension. Cilnidipine has a unique advantage compared to amlodipine, another common calcium channel blocker. While amlodipine only targets L-type calcium channels, cilnidipine can target both L and N-type channels. This study aimed to compare the effectiveness and safety of these two medications in patients with essential hypertension. Methods: A total of n=80 cases of mild to moderate hypertension were randomly allocated to two groups. Group I n=40 received a daily dose of Amlodipine 5mg, whereas those in Group II n=40 received Cilnidipine 10mg once daily, 30 minutes after breakfast, for 8 weeks. Participants were prohibited from using any other medications during the study period. Each patient underwent three visits: a baseline visit (Visit 0) on recruitment day, visit 1 after 30 days of medication, and Visit 2 after 60 days of treatment. Systolic and diastolic blood pressures, as well as heart rate, were measured at each visit. Clinical and laboratory parameters were reassessed at the end of the 8 weeks. Results: Both medications significantly reduced Systolic and Diastolic Blood Pressure (SBP and DBP) and heart rate in both groups over 8 weeks. While Group II (Cilnidipine) consistently showed slightly lower blood pressure and heart rate, these differences were statistically insignificant, suggesting similar effectiveness between the two medications in this study. Both groups reported mild/moderate adverse events, with Group I having a consistently higher number and wider range of events compared to Group II. The most common events were fatigue and headache, with Group I experiencing additional events like headache + GI upset, vomiting, and ankle edema. Conclusion: Both the calcium channel blockers amlodipine and cilnidipine exhibit equivalent efficacy in reducing systolic and diastolic blood pressure in patients with mild to moderate essential hypertension. Cilnidipine, as a fourth-generation calcium channel blocker, offers a promising pharmacological profile. In addition to its blood pressure-lowering effects, cilnidipine demonstrates notable safety and provides additional benefits including renoprotective, cardioprotective, and neuroprotective effects. [ABSTRACT FROM AUTHOR]

Medical nutrition therapy interventions among type 2 diabetes patients administered by registered dieticians are said to be beneficial to the extent of reducing glycated hemoglobin by 1%–2%. Despite patient-centered dietary interventions, adherence continues to remain a challenge in the Indian setting due to the carbohydrate-rich dietary pattern, dietary myths coupled with lack of nutritional awareness, poor literacy, financial burden, and lack of motivation. On the contrary, the evolution of “FAD” diets through drastic dietary changes present individuals with type 2 diabetes with a possibility of reversal of the disease further increasing the nutritional dilemma. These FAD diets extend beyond being mere trends and show improvements in several biochemical processes by reducing the intake of calories either through restriction (very low-calorie diet) or fasting (intermittent fasting) or low carbohydrate diets up to one year. This article by evaluating the suitability of these promising diets to Indian adults with type 2 diabetes aimed to provide evidence that could improve diabetes-related dietary knowledge. Through this narrative review, we conclude that a single drastic dietary modification as seen in very low-calorie diets (≤ 800 kcal/day) or the low-carbohydrate diet (≤ 75 g/d) is not suitable for Indians and such dietary measures will further hamper the sustainability of prescribed diets. The future directions in diet and disease would be to develop clinical trials that will show the effectiveness of dietary regimens constituting optimal energy deficit and macronutrient balances that will contribute to the remission of disease while preventing macronutrient deficiencies and relapse in the dietary regimen.

Purpose: The use of topical corticosteroids (TCSs) has become an efficient, less-invasive treatment for phimosis. Whether any significant difference in efficacy exists between TCSs based on their potency is unclear., Methods: Electronic databases were searched up to March 2024 for randomised controlled trials (RCTs) comparing the use of any type or concentration of TCSs with placebo or no treatment in boys with any degree of physician diagnosed phimosis. A random-effects network meta-analysis (NMA) using a consistency model within a frequentist approach was employed. The primary outcome was partial or complete resolution of phimosis reported as a pooled risk ratio (RR) with 95% CI. Relative ranking was assessed with surface under the cumulative ranking curve (SUCRA) probabilities., Results: Seventeen RCTs, containing 2057 participants were identified. NMA suggested that, compared with control, the high (RR 3.19 (95% CI 1.42 to 7.16), moderate (RR 2.68 (95% CI 1.87 to 3.83) and low (RR 3.05 (95% CI 1.63 to 5.71) potency TCSs statistically significantly increased complete or partial clinical resolution of phimosis. The SUCRA plot revealed that high potency (SUCRA = 0.76) was ranked first followed by low and moderate TCSs. When we assessed comparative efficacy among TCSs based on potency, none of the classes were superior to others. The certainty of the evidence for an effect of moderate potent TCSs was that of moderate GRADE quality., Conclusion: Moderate to low potency TCSs are of comparable therapeutic effect in the treatment of phimosis to that of highly potent formulations. More high-quality RCTs are warranted., Competing Interests: Declarations. Conflict of interest: The authors have no competing interests to declare that are relevant to the content of this article. Ethical approval: Not applicable. Consent to participate: Not applicable. Consent to publish: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction: The beneficial effects of using antidepressants in improving functional dyspepsia (FD) symptoms have been reported in previous meta-analyses; however, the results have not been conclusive. The aim was to perform an updated meta-analysis coupled with trial sequential analysis (TSA) to assess the efficacy of the use of any antidepressants in the treatment of FD in adults., Methods: Electronic databases were searched up to March 2024 for randomized controlled trials (RCTs) recruiting adults with FD. Data of overall symptoms improved between the antidepressants and placebo groups was pooled to obtain risk ratio (RR) employing the random-effects model. The effect of random errors was evaluated with TSA. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence. Analyses were performed using STATA version 16.0., Results: Nine RCTs with 924 patients met the eligible criteria. The RRs of FD symptoms improving with any antidepressants, tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors were (n = 9, RR = 1.30 [95% CI, 1.02-1.67]), (n = 5, RR = 1.41 [95% CI, 1.07-1.85]) and (n = 2, RR = 0.97 [95% CI, 0.72-1.29]), respectively. TSA demonstrated conclusive evidence for the beneficial effect of TCAs. The number needed to treat (NNT) with any depressants and TCAs were 11 (95% CI, 7-36) and 6 (95% CI, 4-15), respectively. The certainty of the evidence for an effect of TCAs was that of moderate GRADE quality. The benefit, however, was limited to the western population (n = 3, RR = 1.43 [95% CI, 1.04-1.96]) and did not extend to the Asian population (n = 2, RR = 1.32 [95% CI, 0.75-2.32]). Conversely, antidepressant-using patients experienced adverse events more frequently. However, no statistically significant association was found between TCAs and any adverse events (n = 3; RR = 1.36 [95% CI, 0.91-2.04])., Conclusion: Evidence was obtained suggesting TCAs can be an effective alternative in the treatment of FD, but more evidence from high-quality large trials is required to support their use, especially in the Asian population., (© 2024. Indian Society of Gastroenterology.)

Integrating interfacial molecular nanolayers (MNL) with inorganic nanolayers is of interest for understanding processing-structure/chemistry correlations in hybrid nanolaminates. Here, we report the synthesis of Co/biphenyldithiol (BPDT)/Co nanolayer sandwiches by metal sputter-deposition and molecular sublimation. The density and surface roughness of the Co layers deposited on the native oxide are invariant with the Ar pressure p Ar during deposition. In contrast, the Co layer roughness r Co deposited on top of the BPDT MNL increases with p Ar , and correlates with a higher degree of Co oxidation. Increased roughening is attributed to MNL-accentuated self-shadowing of low mobility Co atoms at high p Ar , which consequently increases Co oxidation. These results indicating MNL-induced effects on the morphology and chemistry of the inorganic layers should be of importance for tailoring nanolayered hybrid interfaces and laminates.

Acute myelitis encompasses syndromes associated with inflammation of the spinal cord. In cases of inflammatory lesions that only involve a unilateral portion of the axial plane of the cord, Brown-Séquard syndrome may occur, resulting in potential ipsilateral corticospinal, dorsal spinocerebellar, or dorsal column dysfunction or contralateral spinothalamic dysfunction below the level of the lesion. We report a case of an adult male who presented with Brown-Séquard syndrome and with a positive SARS-CoV-2 nasopharyngeal swab PCR test. Neurological symptoms rapidly resolved after initiation of high-dose methylprednisolone. The findings reported not only contribute to documenting a new presentation of neurological complications associated with SARS-CoV-2 infection but also non-exclusively supports the body of literature suggesting the immune-mediated response to this infection as a mechanism of neuropathogenesis. In this case, COVID-19-related acute myelitis responded to treatment with a short regimen of high-dose glucocorticoids., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

We describe a patient with concurrent ocular and pulmonary tuberculosis (TB) in whom the diagnosis of extensively drug-resistant TB was made through phenotypic drug-sensitivity testing of an ocular fluid sample after sputum testing yielded incomplete results. Our results are remarkable, because culture-based diagnosis of TB in ocular fluid is unusual. We not only overcame this limitation, but also were able to create a complete drug-sensitivity testing profile from ocular samples, which led to effecting appropriate therapy for the patient.

Introduction: Lower respiratory tract infections (LRTIs) among renal transplant recipients (RTRs) are a significant cause of morbidity and mortality. This study aimed to analyse the aetiology, outcome, and risk factors associated with mortality., Methods: We analysed baseline transplant characteristics, symptoms, hospital course, laboratory, serological and microbial results, and their association with the outcome of all RTRs between January 2011 and December 2019., Results: A total of 206 LRTI patients out of 1051 RTRs were analysed. The incidence proportion was nearly 22 episodes per 1000 patients per year. The mean age was 39.3 years, with male predominance. Bacterial was the most common aetiology (53%), and staphylococcus was the most common species. Among the fungal causes (14%), 68% had aspergillus infection. More than one-third RTRs died during the hospital course mainly because of bacterial causes (42.6%). The aspergillus infection was the most common fungus associated with 50% mortality. On multi-variate analysis, sepsis, septic shock, and the need for mechanical ventilation independently predicted mortality., Conclusion: Bacterial aetiology was the most common cause; though the fungal aetiology was seen less, it was associated with higher mortality. Mortality in RTR with LRTI was associated with sepsis, septic shock, and the need for mechanical ventilation., Competing Interests: None

Introduction: BKV nephropathy (BKVN) is one of the major causes of graft loss with the advent of potent immunosuppressive drugs. The literature on the co-existence of acute rejection (AR) and BKVN is scarce., Materials and Methods: This is a single-center retrospective analysis, where the allograft biopsies of patients transplanted between 2011 and 2021 were reviewed. The biopsies, which showed evidence of coexistent AR and BKVN, were included. In addition, demographic profiles, clinical presentation, treatment details, response to therapy, and follow-up were analyzed., Results: Out of 1175 live transplants done between January 2011 and March 2021, 49 had BKVN representing 4.17%. Only seven patients (0.59%) had coexistent BKVN with AR. The mean serum creatinine at presentation was 2.3 mg/dl. The mean duration to diagnosis from transplant was seven months (range 3-22 months). All had significant viremia at presentation (17450-4,750,000 copies/ml). All biopsies showed type 1 inclusion bodies with SV40 positivity except one. Coexistent acute T cell-mediated rejection (TCMR) was found in five and acute ABMR in two patients. Three patients received pulse IV methylprednisolone, five received 2 g/kg IVIG, two received plasma exchange as upfront therapies. Maintenance immunosuppression reduction was made in all. Viremia clearance was noted at a mean duration of 3.5 months. However, three patients lost their grafts on follow-up. Four had stable graft function with a mean serum creatinine of 1.54 mg/dl., Conclusion: Intensifying immunosuppression to treat AR followed by a reduction in maintenance immunosuppression and IVIG and antiviral therapies seems better strategy and showed good long-term graft survival in patients with coexistent BKVN and AR., (Copyright © 2022 Elsevier B.V. All rights reserved.)

In this research, we study a new metaheuristic algorithm called Moth-Flame Optimization (MFO) for hyperspectral band selection. With the hundreds of highly correlated narrow spectral bands, the number of training samples required to train a statistical classifier is high. Thus, the problem is to select a subset of bands without compromising the classification accuracy. One of the ways to solve this problem is to model an objective function that measures class separability and utilize it to arrive at a subset of bands. In this research, we studied MFO to select optimal spectral bands for classification. MFO is inspired by the behavior of moths with respect to flames, which is the navigation method of moths in nature called transverse orientation. In MFO, a moth navigates the search space through a process called transverse orientation by keeping a constant angle with the Moon, which is a compelling strategy for traveling long distances in a straight line, considering that the Moon's distance from the moth is considerably long. Our research tested MFO on three benchmark hyperspectral datasets-Indian Pines, University of Pavia, and Salinas. MFO produced an Overall Accuracy (OA) of 88.98%, 94.85%, and 97.17%, respectively, on the three datasets. Our experimental results indicate that MFO produces better OA and Kappa when compared to state-of-the-art band selection algorithms such as particle swarm optimization, grey wolf, cuckoo search, and genetic algorithms. The analysis results prove that the proposed approach effectively addresses the spectral band selection problem and provides a high classification accuracy.

Background: Renal graft cortical necrosis (GCN) is a catastrophic cause of graft failure. We evaluated the incidence, causes, management, and outcome of GCN across two decades from our center., Methods: This is a retrospective analysis of transplant patients who had biopsy-proven GCN transplanted between 2000 and 2020. The clinical details, immunological workup, induction, maintenance regimen, causes of cortical necrosis, and the outcomes were compared between the first period 2000-2012, and the second period 2013-2020, when Flow cytometric and Luminex based crossmatch were included in the workup plan., Results: Among 2333 live ABO-compatible renal transplants, 37 (0.015%) patients (36 patients between 2000 and 2012 and 1 between 2013 and 2020) developed GCN (60% had diffuse and 40% patchy GCN) at a median of 8 days after transplantation.Twenty-six (60%) received ATG, 4 received plasmapheresis and ATG (10.8%) as antirejection therapy. The cyclosporine-based regimen was associated with a higher risk of GCN (RR 2.54; 95% CI 1.26 to 5.12, p = 0.009), whereas tacrolimus-based therapy had a lower risk (RR 0.39; 95% CI 0.19 to 0.79, p = 0.009). The introduction of flow cytometry and DSA assay has significantly decreased the incidence of acute rejection and GCN. Only one patient had GCN during the 2013-2020 period because of graft's mucormycosis. Twenty-five (67.56%) patients had no recovery, and 12 (32.43%) had partial recovery of graft function., Conclusion: GCN is mainly associated with rejection, and cyclosporin-based maintenance regimen had a higher incidence. The remarkable decrease in GCN after 2012 onwards could be attributed to the use of Flowcytometry, Luminex-based DSA assays, and tacrolimus-based regimens., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Despite the exalted status of sputum mycobacterial load for gauging pulmonary tuberculosis treatment and progress, Chest X-rays supplement valuable information for taking instantaneous therapeutic decisions, especially during the COVID-19 pandemic. Even though literature on individual parameters is overwhelming, few studies have explored the interaction between radiographic parameters denoting severity with mycobacterial burden signifying infectivity. By using a sophisticated approach of integrating Chest X-ray parameters with sputum mycobacterial characteristics, evaluated at all the three crucial time points of TB treatment namely pre-treatment, end of intensive phase and completion of treatment, utilizing the interactive Cox Proportional Hazards model, we aimed to precisely deduce predictors of unfavorable response to TB treatment., Materials and Method: We extracted de-identified data from well characterized clinical trial cohorts that recruited rifampicin-sensitive Pulmonary TB patients without any comorbidities, taking their first spell of anti-tuberculosis therapy under supervision and meticulous follow up for 24 months post treatment completion, to accurately predict TB outcomes. Radiographic data independently obtained, interpreted by two experienced pulmonologists was collated with demographic details and, sputum smear and culture grades of participants by an independent statistician and analyzed using the Cox Proportional Hazards model, to not only adjust for confounding factors including treatment effect, but also explore the interaction between radiological and bacteriological parameters for better therapeutic application., Results: Of 667 TB patients with data available, cavitation, extent of involvement, lower zone involvement, smear and culture grade at baseline were significant parameters predisposing to an unfavorable TB treatment outcome in the univariate analysis. Reduction in radiological lesions in Chest X-ray by at least 50% at 2 months and 75% at the end of treatment helped in averting unfavorable responses. Smear and Culture conversion at the end of 2 months was highly significant as a predictor (p<0.001). In the multivariate analysis, the adjusted hazards ratios (HR) for an unfavorable response to TB therapy for extent of involvement, baseline cavitation and persistence (post treatment) were 1.21 (95% CI: 1.01-1.44), 1.73 (95% CI: 1.05-2.84) and 2.68 (95% CI: 1.4-5.12) respectively. A 3+ smear had an HR of 1.94 (95% CI: 0.81-4.64). Further probing into the interaction, among patients with 3+ and 2+ smears, HRs for cavitation were 3.26 (95% CI: 1.33-8.00) and 1.92 (95% CI: 0.80-4.60) while for >2 zones, were 3.05 (95% CI: 1.12-8.23) and 1.92 (95% CI: 0.72-5.08) respectively. Patients without cavitation, zonal involvement <2, and a smear grade less than 2+ had a better prognosis and constituted minimal disease., Conclusion: Baseline Cavitation, Opacities occupying >2 zones and 3+ smear grade individually and independently forecasted a poorer TB outcome. The interaction model revealed that Zonal involvement confined to 2 zones, without a cavity and smear grade up to 2+, constituting "minimal disease", had a better prognosis. Radiological clearance >50% along with smear conversion at the end of intensive phase of treatment, observed to be a reasonable alternative to culture conversion in predicting a successful outcome. These parameters may potentially take up key positions as stratification factors for future trials contemplating on shorter TB regimens., Competing Interests: The authors have declared that no competing interests exist.

Objectives: N,N-Diethyl-3-methylbenzamide (DEET) is a broad-spectrum insect repellent that can easily permeate through the skin and can cause undesirable effects, especially in children and pregnant women. The objective of this research was to formulate and evaluate DEET-encapsulated microparticles containing a hydrogel designed to reduce skin permeation and prolong drug release., Materials and Methods: The formulation design was based on the independent formulation variables of the concentration of chitosan and sodium tripolyphosphate using a simple factorial design experiment. DEET-loaded microparticles were developed and incorporated into a hydrogel. The size of the microparticles was analyzed using the Zetasizer Nano ® particle size analyzer, and the surface morphology, using field emission scanning electron microscopy. Drug release from the microparticles was determined by the dialysis bag method. A rheological evaluation of the formulated gel was performed using a Thermo Haake Rheometer. The in vitro permeation of the formulation was performed using a synthetic Strat-M ® membrane., Results: The size of the microparticles ranged from 0.45 to 8.3 μm, and the encapsulation efficiencies were >50% for all the formulations. The drug-release curves showed no initial burst release from the microparticle formulation. Instead, a slow and controlled drug release was observed over 24 hours that followed Higuchi kinetics. The cumulative amount of DEET permeated (over 24 h) from the DEET solution (control), and the formulation was 211.6±19.5 μg/cm 2 and 4.07±0.08 μg/cm 2 , respectively., Conclusion: A significantly low DEET permeation from the microparticle formulations indicated minimal absorption of the drug into the body and thus, reduced systemic toxicity. Thixotropic evaluation of the hydrogel formulation demonstrated a hysteresis loop that fitted closely to the Herschel-Bulkley rheological model, ensuring an effortless application and prolonged retention on the skin. Hence, it can be concluded that the developed formulation is an effective delivery approach for controlled insect repellent activity with reduced skin absorption.

Metal halide lights (MHLs) emit ultraviolet radiation (UVR) and should be used with enclosed fixtures. We investigated a cluster of blurred vision in a locality in South India reported among light music event attendees to identify risk factors., Methods: We searched for attendees with any eye-related symptoms by door-to-door. We described cases by time, place, and person and inspected the environment to generate a hypothesis. We followed-up the cohort of the attendees to examine the hypothesis of exposure to MHL as the cause of the outbreak. We computed relative risk (RR) and 95% confidence interval (CI) by comparing attack rates among attendees by seating location and duration of exposure., Results: Of the total 500 attendees, we could interview 319 (64%) and 89% (284/319) attendees developed bilateral photokeratitis (median age = 24 years [range: 2-80 years]). Attack rate was higher among female (92% [172/189]) than male (85% [110/130]). Attack rate among those seated within 12 meters from dais was higher (95% [241/253]) than the rest (65% [43/66]; RR = 1.5; 95% CI = 1.2, 1.7) and attack rate was higher among those continuously exposed to MHL (97% [268/277]) than others (38% [16/42]; RR = 2.5; 95% CI = 1.7, 3.7). The duration of exposure was associated with increased risk of bilateral photokeratitis (χ 2 test for linear trend = 74; P < 0.00001). During the environmental inspection, we identified the use of MHL with a broken outer envelope., Conclusions: Photokeratitis was associated with exposure to UVR from MHL with a broken outer envelope. We recommended the usage of MHL along with enclosed fixtures., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report., (Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of Environmental Epidemiology. All rights reserved.)

Background: In the past few years, the artificial pancreas-the commonly accepted term for closed-loop control (CLC) of blood glucose in diabetes-has become a hot topic in research and technology development. In the summer of 2014, we initiated a 6-month trial evaluating the safety of 24/7 CLC during free-living conditions., Research Design and Methods: Following an initial 1-month Phase 1, 14 individuals (10 males/4 females) with type 1 diabetes at three clinical centers in the United States and one in Italy continued with a 5-month Phase 2, which included 24/7 CLC using the wireless portable Diabetes Assistant (DiAs) developed at the University of Virginia Center for Diabetes Technology. Median subject characteristics were age 45 years, duration of diabetes 27 years, total daily insulin 0.53 U/kg/day, and baseline HbA1c 7.2% (55 mmol/mol)., Results: Compared with the baseline observation period, the frequency of hypoglycemia below 3.9 mmol/L during the last 3 months of CLC was lower: 4.1% versus 1.3%, P < 0.001. This was accompanied by a downward trend in HbA1c from 7.2% (55 mmol/mol) to 7.0% (53 mmol/mol) at 6 months. HbA1c improvement was correlated with system use (Spearman r = 0.55). The user experience was favorable with identified benefit particularly at night and overall trust in the system. There were no serious adverse events, severe hypoglycemia, or diabetic ketoacidosis., Conclusion: We conclude that CLC technology has matured and is safe for prolonged use in patients' natural environment. Based on these promising results, a large randomized trial is warranted to assess long-term CLC efficacy and safety.