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Objective: To evaluate the efficacy of intravenous (IV) amino acids in preventing acute kidney injury (AKI) in patients undergoing cardiac surgery., Methods: PubMed, EMBASE, and Cochrane Library databases were systematically searched for all relevant randomised controlled trials (RCTs) published from inception to July 25, 2024. A random effects model was used to pool the risk ratios (RR) for dichotomous outcomes, and the combined data was visually represented using forest plots., Results: 3 studies involving 3646 patients were included in the meta-analysis. IV amino acids did not significantly lower the overall AKI incidence compared with control measures. However, they significantly reduced the risk of Stage 1 AKI and Stage 3 AKI. No differences were observed between intervention and control for Stage 2 AKI or need for kidney replacement therapy., Conclusion: IV amino acids may offer protective benefits against severe AKI stages in cardiac surgery patients. Further studies are warranted to validate our findings., Competing Interests: Declaration of conflicting interestThe authors declare there are no conflicts of interest.

Background and Objective: Primary hyperoxaluria (PH), a rare autosomal recessive disorder, results in defective metabolism of oxalate, leading to increased oxalate levels. Oxalobacter formigenes (O. formigenes) is a nonpathological anaerobic bacterium that uses oxalate for its survival and thus decreases the plasma oxalate levels. We aimed to use randomized controlled trials (RCTs) to evaluate the efficacy of O. formigenes in treating PH., Methods: A literature review was conducted for synthesizing the evidence from RCTs on Scopus, Web of Science, Embase, PubMed, and CENTRAL until January 2023. The outcomes were pooled using mean difference (MD) for continuous data and odds ratios (OR) for dichotomous data along with confidence interval (CI). The systematic review is registered with Prospero ID CRD42023404421., Results: We included five RCTs with 208 patients. The pooled analysis did not favor O. formigenes over placebo in reducing the plasma oxalate levels (MD: -0.00 mmol/day; 95% CI: [ - 0.01-0.00]; P = 0.06). Similar results were observed for urinary oxalate levels (MD: -0.01 mmol/day; 95% CI: [ - 0.12-0.10]; P = 0.86). There were no significant adverse events (OR: 0.44; 95% CI: [0.14-1.39]; P = 0.16) or serious adverse events (OR: 0.80; 95% CI: [0.29-2.25]; P = 0.67)., Conclusion: O. formigenes was ineffective in reducing the serum and urine oxalate levels in patients with PH but has an acceptable safety profile. As PH is a relatively rare disease and few patients consent for the trials, stringent protocols are required in the future to achieve data accuracy pertinent for making conclusive recommendations on the efficacy of O. formigenes in patients with PH., Competing Interests: There are no conflicts of interest., (Copyright: © 2025 Indian Journal of Urology.)

Elevated serine peptidase inhibitor, Kazal type 1 (SPINK1) levels in ∼10%-25% of prostate cancer (PCa) patients associate with aggressive phenotype, for which there are limited treatment choices and dismal clinical outcomes. Using an integrative proteomics approach involving label-free phosphoproteome and proteome profiling, we delineated the downstream signaling pathways involved in SPINK1-mediated tumorigenesis and identified tyrosine kinase KIT as highly enriched. Furthermore, high to moderate levels of KIT expression were detected in ∼85% of SPINK1-positive PCa specimens. We show KIT signaling orchestrates SPINK1-mediated oncogenesis, and treatment with KIT inhibitor reduces tumor growth and metastases in preclinical mice models. Mechanistically, KIT signaling modulates WNT/β-catenin pathway and confers stemness-related features in PCa. Notably, inhibiting KIT signaling led to restoration of AR/REST levels, forming a feedback loop enabling SPINK1 repression. Overall, we uncover the role of KIT signaling downstream of SPINK1 in maintaining lineage plasticity and provide distinct treatment modalities for advanced-stage SPINK1-positive patients., Competing Interests: N.P. is a consultant to Astrazeneca., (© 2024 The Authors.)

Rationale: Conventional electromagnetic navigation bronchoscopy and other guided bronchoscopic modalities have a very desirable safety profile, but their diagnostic yield is only 60-70% for pulmonary lesions. Recently, robotic-assisted bronchoscopy (RAB) platforms have been introduced to improve the diagnostic performance of bronchoscopic modalities. Objectives: To determine the diagnostic performance and safety profile of RAB (using shape-sensing and electromagnetic navigation-based platforms) by performing a systematic review and meta-analysis. Methods: The PubMed, Embase, and Google Scholar databases were searched to find studies that reported on the diagnostic performance and/or the safety profile of one of the RAB systems. The quality of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Meta-analysis was performed using MedCalc version 20.118. Pooled diagnostic yield was calculated using a Freeman-Tukey transformation. We planned to use a random-effects model if the I 2 index was >40%. Results: Twenty-five studies were included: 20 including diagnostic and safety analyses and 5 including only safety analyses. The pooled diagnostic yield of RAB (20 studies, 1,779 lesions) was 84.3% (95% confidence interval, 81.1-87.2%). The I 2 index was 65.6%. On the basis of our subgroup analyses, the heterogeneity was likely driven by differences in study designs (prospective vs. retrospective) and procedural protocols (such as different RAB systems). Lesion size > 2 cm, the presence of a computed tomography bronchus sign, and concentric radial endobronchial ultrasound view were associated with a statistically significant increase in the odds of diagnosis with RAB. The overall rates of pneumothorax, need for tube thoracostomy, and significant hemorrhage were 2.3%, 1.2%, and 0.5%, respectively. Conclusions: RAB systems have significantly increased the diagnostic yield of navigational bronchoscopy compared with conventional systems such as electromagnetic navigation bronchoscopy, but well-designed prospective studies are needed to better understand the impact of various factors, such as the use of three-dimensional imaging modalities, cryobiopsy, and specific ventilatory protocols, on the diagnostic yield of RAB.

Rationale: Transbronchial lung biopsies (TBLBs) are commonly performed by pulmonologists. Most providers consider pulmonary hypertension to be at least a relative contraindication to TBLB. This practice is based primarily on expert opinion, as there are very few patient outcomes data backing it. Objectives: We performed a systematic review and meta-analysis of previously published studies to determine the safety of TBLB in patients with pulmonary hypertension. Methods: The MEDLINE, Embase, Scopus, and Google Scholar databases were searched for pertinent studies. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. Meta-analysis was performed using MedCalc version 20.118 to calculate the weighted pooled relative risk of complications in patients with pulmonary hypertension. Results: Nine studies with a total of 1,699 patients were included in the meta-analysis. On the basis of the Newcastle-Ottawa Scale, the risk of bias was low in the included studies. The overall weighted relative risk of bleeding with TBLB in patients with pulmonary hypertension was 1.01 (95% confidence interval, 0.71-1.45) compared with patients without pulmonary hypertension. Heterogeneity was low; therefore, the fixed-effects model was used. In a subgroup analysis of three studies, the overall weighted relative risk of significant hypoxia in patients with pulmonary hypertension was 2.06 (95% confidence interval, 1.12-3.76). Conclusions: Our results show that the patients with pulmonary hypertension do not have a significantly elevated risk of bleeding with TBLB compared with control subjects. We hypothesize that significant postbiopsy bleeding might be preferentially originating from bronchial artery circulation as opposed to pulmonary artery circulation, much like episodes of massive spontaneous hemoptysis. This hypothesis can explain our results, as in this scenario, elevated pulmonary arterial pressure would not be expected to have a bearing on the risk of post-TBLB bleeding. Most of the studies in our analysis included patients with mild to moderate pulmonary hypertension and it is not clear if our results can be extrapolated to patients with severe pulmonary hypertension. We noted that the patients with pulmonary hypertension were at a higher risk of developing hypoxia and needing a longer duration of mechanical ventilation with TBLB compared with control subjects. Further studies are needed to better understand the origin and pathophysiology of post-TBLB bleeding.

High-altitude cerebral edema is a rare type of acute mountain illness characterized by consciousness disruption and truncal ataxia. Here we discuss a 40-year-old nondiabetic, nonsmoker male who went on a tour to Nanga Parbat. On returning home, the patient developed symptoms of headache, nausea, and vomiting. His symptoms worsened with time and he developed lower limb weakness and shortness of breath. Later, he underwent a computerized tomography chest scan. On the basis of CT scan findings, the doctors decided that the patient was suffering from COVID-19 Pneumonia despite having negative COVID-19 PCR tests multiple times. Later, the patient presented to our hospital with similar complaints. MRI of the brain revealed T2/fluid-attenuated inversion recovery hyperintense and T1 hypointense signals in the bilateral semioval centrum, posterior periventricular white matter, and corpus callosum genu, body, and splenium. These abnormal signals were discovered to be more evident in the corpus callosum's splenium. Moreover, susceptibility-weighted imaging revealed micro hemorrhages in the corpus callosum. This verified the diagnosis that the patient is suffering from high-altitude cerebral edema. Within 5 days, his symptoms resolved and he was discharged with full recovery., (© 2023 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Transcription factors (TFs) represent the most commonly deregulated DNA-binding class of proteins associated with multiple human cancers. They can act as transcriptional activators or repressors that rewire the cistrome, resulting in cellular reprogramming during cancer progression. Deregulation of TFs is associated with the onset and maintenance of various cancer types including prostate cancer. An emerging subset of TFs has been implicated in the regulation of multiple cancer hallmarks during tumorigenesis. Here, we discuss the role of key TFs which modulate transcriptional cicuitries involved in the development and progression of prostate cancer. We further highlight the role of TFs associated with key cancer hallmarks, including, chromatin remodeling, genome instability, DNA repair, invasion, and metastasis. We also discuss the pluripotent function of TFs in conferring lineage plasticity, that aids in disease progression to neuroendocrine prostate cancer. At the end, we summarize the current understanding and approaches employed for the therapeutic targeting of TFs and their cofactors in the clinical setups to prevent disease progression., Competing Interests: Conflict of interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

We theoretically demonstrated a class of plasmonic coupled elliptical nanostructure for achieving a spaser or a nanolaser with high intensity. The plasmonic ellipse is made up of gold film substrate. The proposed structure is then trialed for various light polarizations, moreover, a simple elliptical nanostructure has been chosen primarily from which different cases have been formed by geometry alteration. The structure supports strong coupled resonance mode i.e. localized surface plasmon (LSP). The localized surface plasmon resonance (LSPR) of the investigated system is numerically examined using the finite-element method (FEM). The calculations showed that the LSPR peaks and the local field intensity or near field enhancement (NFE) of the active nanosystem can be amplified to higher values by introducing symmetry-breaking techniques in the proposed ellipse and its variants. The coupled nanostructure having different stages of wavelengths can be excited with different plasmonic resonance modes by the selection of suitable gain media. In addition, a small-sized nanolaser with high tunability range can be developed using this nanostructure. The spaser phenomena are achieved at several wavelengths by changing light polarization and structure alteration methods. Giant localized field enhancement and high LSPR values enable the proposed model to be highly appealing for sensing applications, surface-enhanced Raman spectroscopy, and much more., Competing Interests: The authors have declared that no competing interests exist.

Neurodegenerative diseases are a group of debilitating maladies involving protein aggregation. To this day, all advances in neurodegenerative disease therapeutics have helped symptomatically but have not prevented the root cause of the disease, i.e., the aggregation of involved proteins. Antibiotics are becoming increasingly obsolete due to the rising multidrug resistance strains of bacteria. Thus, antibiotics, if put to different use as therapeutics against other diseases, could pave a new direction to the world of antibiotics. Hence, we studied the antibiotic levofloxacin for its potential anti-amyloidogenic behavior using human lysozyme, a protein involved in non-systemic amyloidosis, as a model system. At the sub-stoichiometric level, levofloxacin was able to inhibit amyloid formation in human lysozyme as observed by various spectroscopic and microscopic methods, with IC 50 values as low as 8.8 ± 0.1 μM. Levofloxacin also displayed a retarding effect on seeding phenomena by elongating the lag-phase (from 0 to 88 h) at lower concentration, and arresting lysozyme fibrillation at the lag stage in sub-stoichiometric concentrations. Structural and computational analyses provided mechanistic insight showing that levofloxacin stabilizes the lysozyme in the native state by binding to the aggregation-prone residues, and thereby inhibiting amyloid fibrillation. Levofloxacin also showed the property of disrupting amyloid fibrils into a smaller polymeric form of proteins which were less cytotoxic as confirmed by hemolytic assay. Therefore, we throw new light on levofloxacin as an amyloid inhibitor and disruptor which could pave way to utilization of levofloxacin as a potential therapeutic against non-systemic amyloidosis and neurodegenerative diseases., (Copyright © 2021. Published by Elsevier Inc.)

In petroleum refineries, naphtha reforming units produce reformate streams and as a by-product, hydrogen (H 2 ). Naphtha reforming units traditionally deployed are designed as packed bed reactors (PBR). However, they are restrained by a high-pressure drop, diffusion limitations in the catalyst, and radial and axial gradients of temperature and concentration. A new design using the fluidized bed reactor (FBR) surpasses the issues of the PBR, whereby the incorporation of the membrane can improve the yield of products by selectively removing hydrogen from the reaction side. In this work, a sequential modular simulation (SMS) approach is adopted to simulate the hydrodynamics of a fluidized bed membrane reactor (FBMR) for catalytic reforming of naphtha in Aspen Plus. The reformer reactor is divided into five sections of plug flow reactors and a continuous stirrer tank reactor with the membrane module to simulate the overall FBMR. Similarly, a fluidized bed reactor (FBR), without membrane permeation phenomenon, is also modelled in the Aspen Plus environment for a comparative study with FBMR. In FBMR, the continuous elimination of permeated hydrogen enhanced the production of aromatics compound in the reformate stream. Moreover, the exergy and economic analyses were carried out for both FBR and FBMR.

Objective: The main objective of the study was to evaluate the health of University of Karachi students (aged 19 to 21) by observing the correlation of haemoglobin level with underweight BMI., Methods: In this study 151 students were enrolled from the Department of Biotechnology, University of Karachi, Sindh Pakistan. Blood samples were collected and Haemoglobin estimation was performed by Sahli's Haemoglobinometer. BMI of each student was calculated as per WHO criteria for South Asian., Results: Out of 151 students, 60 (39.7%) students had anaemia, among which 41(27.1%) were showing grade 1 anaemia and 19(12.5%) were showing grade 2 anaemia. BMI results showed that 50 (33.1%) students were underweight whereas, 19(12.5%) students were overweight and 12( 7.9%) students were obese. Correlation showed that 34 (22.5%) students had anaemia with underweight BMI., Conclusions: This study concluded that anaemia with underweight BMI is more prevalent among females especially adolescent girls. This could be as they followed poor dietary habits and had some infections. This data evaluated the health status of University students on a small scale.

Background: Liver disease is a risk factor for development of atrial fibrillation (AF). We aim to study inpatient mortality and resource utilization of end-stage liver disease (ESLD) patients with AF from a nationally representative United States population sample., Methods: For the purpose of our study, we utilized data from National Inpatient Sample for calendar years 2005-2015. Patients with ESLD and AF were identified using relevant International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Key outcomes of inpatient mortality and resource utilization were assessed. We also constructed a multiple logistic regression model to determine predictors of mortality in ESLD patients. Propensity matching was also done to balance confounding variables., Results: A total of 309,959 ESLD patients were included in final analysis. Out of these, about 32,858 (10.6%) patients have concomitant AF. ESLD patients with AF were older and had higher burden of key co-morbidities such as heart failure, diabetes and hypertension. Mortality was significantly higher in both unmatched (12.3% vs. 9.2%, p < 0.01) and matched cohorts (12.2% vs. 10.8%, p < 0.01). Additionally, ESLD patients with AF have longer length of stay, increased facility discharge and cost of hospitalization compared to ESLD patients with out AF. In multivariate analysis, AF is an independent predictor of mortality in ESLD patients., Conclusions: AF portends worse outcomes in patients with ESLD. Strong index of suspicion is warranted to timely identify AF in this patient population.

There are hundreds of rare orphan lung diseases. We have highlighted five of them, one from each of the five major categories of pulmonary disorders: pleuroparenchymal fibroelastosis (a rare diffuse parenchymal lung disease), pulmonary alveolar proteinosis (a rare autoimmune and diffuse parenchymal lung disease), lymphangioleiomyomatosis (a rare cystic lung disease), yellow nail syndrome (a rare pleural disease), and Mounier-Kuhn syndrome (a rare airway disorder). The pathogenesis, clinical presentation, diagnostic criteria, treatment options, and prognosis of each disorder is discussed. This review is by no means exhaustive and further research is needed to improve our understanding of these disorders., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To determine the association of Lady Health Worker's role with immunization of children in Pakistan., Methods: Secondary analysis was conducted on data obtained from Pakistan's Demographic and Health Survey. Children who did not receive all doses of vaccines were considered incompletely immunized or vice versa. The association between determinants was assessed by simple and multivariable binary logistic regression., Results: The mothers and fathers had a mean age of 32.7 (SD+8.6) years and 37.9 (SD +10.1) years, respectively. Age of mother greater than 35 (OR=0.93; 95% CI:0.70-1.25); born in Baluchistan (OR=3.47,95% CI:2.21-5.49); rural area dwellers (OR=2.04; 95% CI:1.65-2.51); female gender (OR=1.06; 95% CI:0.87-1.29); birth order (of last born child) greater than 7 (OR=2.21, 95% CI:1.60-3.06); delivered at home (OR=2.20, 95% CI:1.76-2.74); long distance to health care facility (OR=2.66, 95% CI:2.16-3.28); and no LHW visit in last 12 months (OR=1.91, CI:1.48-2.47) were significantly associated with incomplete immunization in bivariate analysis. In final model of multinomial regression analysis the absence of visit by LHW in last 12 months was the most significant factor when all risk factors were analyzed in last model., Conclusions: This study has concluded that visit of LHW in last 12 months was significantly associated with immunization.

TRPA1 channels are non-selective cation channels that could be activated by plant-derived pungent products, including gingerol, a main active constituent of ginger. Ginger could improve the digestive function; however whether ginger improves the digestive function through activating TRPA1 receptor in gastrointestinal tract has not been investigated. In the present study, gingerol was used to stimulate cell lines (RIN14B or STC-1) while depletion of extracellular calcium. TRPA1 inhibitor (rethenium red) and TRPA1 gene silencing via TRPA1-specific siRNA were also used for mechanistic studies. The intracellular calcium and secretion of serotonin or cholecystokinin were measured by fura-2/AM and ELISA. Stimulation of those cells with gingerol increased intracellular calcium levels and the serotonin or cholecystokinin secretion. The gingerol-induced intracellular calcium increase and secretion (serotonin or cholecystokinin) release were completely blocked by ruthenium red, EGTA, and TRPA1-specific siRNA. In summary, our results suggested that gingerol derived from ginger might improve the digestive function through secretion releasing from endocrine cells of the gut by inducing TRPA1-mediated calcium influx., (Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Since 1982, we have treated 79 pemphigus patients with an arbitrarily designed regimen of 100 mg dexamethasone dissolved in 5% glucose given by an intravenous infusion over 1 h, daily on 3 consecutive days and in addition, 500 mg cyclophosphamide on day 1 only. The intermittent high doses (IHD) of dexamethasone are repeated every 2-4 weeks, and the patient continues to take 50 mg/day oral cyclophosphamide. This treatment is divided into four phases. During Phase I, the patient continues to develop relapses of pemphigus a variable number of days after IHD, but the lesions heal up quickly after IHD. These relapses become progressively milder and stop after a few months, but the IHD are continued once a month for 6-9 months (Phase II). In the next phase (Phase III), the monthly IHD are stopped, and the patient continues to take 50 mg/day cyclophosphamide orally. After approximately 1 year this maintenance treatment is withdrawn and the patient is observed for any relapses (Phase IV). Of the 79 patients treated, 10 patients have been lost to follow-up and two have died, one due to leukopaenia caused by inadvertent additional administration of methotrexate, and the other of an unknown cause. Of the remaining 67 patients, 25 are off treatment (Phase IV), 25 are taking only 50 mg cyclophosphamide daily (Phase III), ten are also in remission, but still receiving intermittent high doses of dexamethasone-cyclophosphamide (Phase II), and seven still have active disease (Phase I).(ABSTRACT TRUNCATED AT 250 WORDS)