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Background: The development of a robust and accurate point-of-care platform for the detection of tuberculosis (TB) biomarkers is important for disease control. In the current study, the detection principle relies on the shredding of PES-modified non-specific ssDNA (Poly T) in the presence of target DNA IS6110, a reliable biomarker for TB diagnosis by the CRISPR-Cas12a mechanism. Cas protein has great potential in the detection of nucleic acids., Results: Herein, we developed a biosensing platform by utilizing the trans cleavage activity of CRISPR-Cas12a into an electrochemical biosensor. Square wave voltammetry technique is used for the analysis of the fabricated biosensing platform. In the presence of target DNA, the trans cleavage activity is observed by a nonspecific ssDNA substrate, PolyT chain. Various concentration of target DNA is tested on the constructed biosensor, the fabricated biosensor successfully detected TB target DNA by trans cleavage of PES-modified poly T. This novel biosensor was able to detect the target DNA, IS6110 with the limit of detection of 14.5 nM within 60 min by trans-cleavage activity of CRISPR-Cas12a and the results revealed the potential of Cas12a-based biosensors as a diagnostic platform., Significance: This is the first study reporting the CRISPR-Cas12a-based electrochemical sensor for TB. The developed CRISPR-Cas12a endonuclease-based electrochemical biosensor provides a potentially powerful platform for the accurate detection of Mycobacterium tuberculosis ., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Saman Taufiq reports financial support was provided by 10.13039/501100004681Higher Education Commission (HEC) Pakistan. The authors declare no other competing interests. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Background: Non-alcoholic fatty liver disease (NAFLD) is a common liver condition affecting 25%-40% of the worldwide population. NAFLD is traditionally related to obesity and metabolic disorders. NAFLD can also affect non-obese individuals, termed "lean NAFLD" (LN), who exhibit a paradoxical combination of physical leanness and metabolic obesity. Factors contributing to LN remain unclear, necessitating further research. This analysis aims to understand LN's prevalence and metabolic characteristics compared to obese NAFLD (ON) populations., Methods: This meta-analysis searched various databases until August 1, 2023. Inclusion criteria involved observational studies comparing LN with overweight/obese NAFLD. Data extraction included baseline characteristics, disease occurrence, metabolic profile, and clinical parameters-statistical analysis employed calculating risk ratios (RR) and standard mean differences., Results: Twenty-five studies were analyzed. LN is associated with lower prevalence in both NAFLD (RR 0.27, 95% confidence interval (CI) 0.14-0.52, p  = <0.0001) and total (RR 0.27, 95% CI 0.15-0.51, p  < 0.0001) population. LN had lower diabetes mellitus (RR 0.78, 95% CI 0.71-0.87, p  < 0.00001), dyslipidemia (RR 0.87, 95% CI 0.79-0.95, p  = 0.002), hypertension (RR 0.80, 95% CI 0.74-0.87, p  < 0.00001), and metabolic syndrome (RR 0.45, 95% CI 0.31-0.64, p  < 0.00001) compared to those with ON. The LN group's lipid profile, blood pressure, and other clinical parameters were favorable compared to ON., Conclusion: The prevalence of NAFLD among lean and non-lean individuals varies by region. Our analysis revealed that LN is associated with lower metabolic diseases, fasting blood sugar, blood pressure, and a more favorable lipid profile compared to ON., (© The Author(s), 2024.)

Microbubble contrast agents in ultrasound/echocardiography are used to increase the echogenicity of the target tissues, thereby raising the contrast resolution of the resultant image. Recently, the trend has shifted toward the development of phase-convertible nanodroplets as ultrasound contrast agents due to their promising theragnostic potential by switching capability at the active site. Herein, we fabricated pre-PGS- perfluoropentane phase convertible nanodroplets and checked their in vitro and in vivo enhancement and safety profile. For this, we performed experiments on 20 male Wistar rats and 2 dogs. Biochemical assays of both rats and dogs included complete blood profiles, liver function tests, and renal function tests. For rat vitals, monitoring and histopathological analysis were also performed. Converted nanodroplets showed excellent contrast enhancement, better than Sonovue upon in vitro testing, with an enhancement time of up to 14 min. In vivo, experiments showed comparable opacification of the ventricles of both rats and dogs. All biochemical assays remained within the normal range during the study period. The histopathological analysis did not show any signs of drug-induced toxicity, showing the safety of these nanodroplets. Pre-PGS-PFP nanodroplets hold great potential for use in echocardiography and abdominal imaging in both human and veterinary applications after clinical trials., (© 2024. The Author(s).)

Background: Nivolumab (Nivo) and ipilimumab (Ipi) have revolutionized cancer treatment by targeting different pathways. Their combination shows promising results in various cancers, including melanoma, but not all studies have demonstrated significant benefits. A meta-analysis was performed to assess the effectiveness and safety of Nivo-Ipi compared to Nivo alone in advanced cancer types (excluding melanoma)., Methods: Following PRISMA guidelines, we conducted a meta-analysis up to September 30, 2023, searching databases for randomized controlled trials (RCTs). We focused on advanced solid malignancies (excluding melanoma) with specific Nivo and Ipi dosing. Primary outcomes were overall survival (OS), progression-free survival (PFS), grades 3-4 adverse events (AEs), and treatment-related discontinuations. Secondary outcomes included specific adverse events. Statistical analysis in Review Manager included hazard ratio (HR) and risk ratio (RR), assessing heterogeneity (Higgins I 2 )., Results: Nine RCTs, involving 2152 patients covering various malignancies, were analyzed. The Nivo plus Ipi group exhibited a median OS of 12.3 months and a median PFS of 3.73 months, compared to monotherapy with 11.67 months and 3.98 months, respectively. OS showed no significant difference between Nivo and Ipi combination and Nivo alone (HR = 0.97, 95% CI: 0.88 to 1.08, p = 0.61). PFS had a slight improvement with combination therapy (HR = 0.91, 95% CI: 0.82 to 1.00, p = 0.04). Treatment-related cumulative grades 3-4 adverse events were higher with Nivo and Ipi (RR = 1.52, 95% CI: 1.30 to 1.78, p < 0.00001), as were treatment-related discontinuations (RR = 1.99, 95% CI: 1.46 to 2.70, p < 0.0001). Hepatotoxicity (RR = 2.42, 95% CI: 1.39 to 4.24, p = 0.002), GI toxicity (RR = 2.84, 95% CI: 1.44 to 5.59, p = 0.002), pneumonitis (RR = 2.29, 95% CI: 1.24 to 2.23, p = 0.008), dermatitis (RR = 2.96, 95% CI: 1.08 to 8.14, p = 0.04), and endocrine dysfunction (RR = 6.22, 95% CI: 2.31 to 16.71, p = 0.0003) were more frequent with Nivo and Ipi., Conclusions: Combining nivolumab and ipilimumab did not significantly improve overall survival compared to nivolumab alone in advanced cancers (except melanoma). However, it did show slightly better PFS at the cost of increased toxicity, particularly grades 3-4 adverse events. Specific AEs occurred more frequently in the combination group. Further trials are needed to fully assess this combination in treating advanced cancers., (© 2024. The Author(s).)

Competing Interests: The authors declare no potential conflicts of interest concerning the research, authorship and/or publication of this article.

Purpose: Excess body fat, insulin resistance, and abnormal lipid levels signal type 2 diabetes mellitus (DM2). Globally, 536.6 million people suffer from DM2, projected to rise to 783.2 million by 2045. Obesity fuels insulin resistance and DM2 development, with weight loss significantly improving glycemic control. Titrzepatide (TZP), a dual GIP and GLP-1 receptor agonist, proves highly effective in controlling hyperglycemia, stimulating insulin secretion, and promoting weight loss. TZP, holds promise as a treatment for DM2, surpassing insulin and GLP-1. The study aimed to meticulously assess the safety and efficacy of various doses, offering insights into optimal therapeutic strategies for managing DM2., Methods: This study aimed to comprehensively evaluate the safety and efficacy of TZP in treating DM2. The primary focus of the inclusion criteria was on trials comparing TZP with a placebo until November 23, 2023, excluding patients with certain comorbidities. Data extraction included key parameters, and outcomes were assessed for HbA1c levels, weight changes, fasting serum glucose levels, and various adverse events. Quality assessment utilized the Cochrane Collaboration's risk-of-bias tool, and a network meta-analysis explored outcomes across different TZP dosages., Results: This meta-analysis systematically reviewed ten studies on TZP for DM2. Results revealed significant reductions in HbA1c with TZP 10 mg (19%) and TZP 15 mg (31%) compared to TZP 5 mg (MD: -0.19 and MD: -0.32, respectively). Additionally, weight reduction was notable for TZP 10 mg (MD: -1.96) and TZP 15 mg (MD: -3.31). Fasting serum glucose showed improvement with TZP 15 mg (MD:-6.71). Gastrointestinal events increased with higher doses, yet without statistical significance. Death, nausea, diarrhea, vomiting, dyspepsia, decreased appetite, injection site reaction, hypoglycemia, treatment discontinuation, and serious adverse events showed no significant differences across doses., Conclusion: TZP effectively lowers HbA1c and induces weight loss across its three doses for type 2 diabetes management. The higher dose (15 mg) significantly reduces fasting serum glucose, with increased adverse events observed at higher doses. Dose-specific patterns for adverse effects emphasize the need to balance therapeutic benefits and risks. Further research is crucial for refining clinical applications and understanding TZP's role in DM2 management across doses., Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01412-8., Competing Interests: Competing interestsThe authors declare no potential conflicts of interest concerning the research, authorship, and/or publication of this article., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Hypertrophic cardiomyopathy (HCM) is a hereditary myocardial disorder, often due to sarcomere gene mutations, characterized by the left ventricular hypertrophy. Current treatments offer symptomatic relief but lack specificity. Mavacamten, an allosteric inhibitor, has shown significant improvements in HCM patients in trials, reducing the requirement for invasive treatments. This meta-analysis assesses Mavacamten's efficacy and safety as a targeted HCM intervention., Methods: This study examined four randomized controlled trials comparing Mavacamten to placebo in HCM patients. Each trial had a unique primary endpoint, and secondary outcomes included improvements in NYHA-FC, eligibility for septal reduction therapy (SRT) or undergoing it, adverse events (serious and treatment-related), atrial fibrillation, and non-sustained ventricular tachycardia. Statistical analysis involved calculating risk ratios (RRs) and assessing heterogeneity., Results: The four included studies showed minimal risk of bias and involved 503 patients with HCM (273 Mavacamten and 230 placebo). Mavacamten significantly increased the primary endpoint (RR 2.15, 95% CI 1.20-3.86, P = 0.01) and ≥ 1 NYHA-FC class (RR 2.21, 95% CI 1.48-3.3, P = 0.0001). Mavacamten group had lower rates of SRT compared to those receiving placebo (RR, 0.30, 95% CI 0.22-0.40; P < 0.00001). No significant differences existed in rates adverse events between the Mavacamten and placebo groups., Conclusions: Our study suggests that Mavacamten may have therapeutic benefits for HCM patients, as indicated by its positive impact on certain endpoints. Further research with larger samples, longer follow-up, and comprehensive analysis is needed to understand Mavacamten's safety and efficacy in HCM patients., (© 2023. The Author(s).)

According to WHO 2019, Hepatocellular carcinoma (HCC) is the fourth highest cause of cancer death worldwide. More precise diagnostic models are needed to enhance early HCC and cirrhosis quick diagnosis, treatment, and survival. Breath biomarkers known as volatile organic compounds (VOCs) in exhaled air can be used to make rapid, precise, and painless diagnoses. Gas chromatography and mass spectrometry (GCMS) are utilized to diagnose HCC and cirrhosis VOCs. In this investigation, metabolically generated VOCs in breath samples (n = 35) of HCC, (n = 35) cirrhotic, and (n = 30) controls were detected via GCMS and SPME. Moreover, this study also aims to identify diagnostic VOCs for distinction among HCC and cirrhosis liver conditions, which are most closely related, and cause misleading during diagnosis. However, using gas chromatography-mass spectrometry (GC-MS) to quantify volatile organic compounds (VOCs) is time-consuming and error-prone since it requires an expert. To verify GC-MS data analysis, we present an in-house R-based array of machine learning models that applies deep learning pattern recognition to automatically discover VOCs from raw data, without human intervention. All-machine learning diagnostic model offers 80% sensitivity, 90% specificity, and 95% accuracy, with an AUC of 0.9586. Our results demonstrated the validity and utility of GCMS-SMPE in combination with innovative ML models for early detection of HCC and cirrhosis-specific VOCs considered as potential diagnostic breath biomarkers and showed differentiation among HCC and cirrhosis. With these useful insights, we can build handheld e-nose sensors to detect HCC and cirrhosis through breath analysis and this unique approach can help in diagnosis by reducing integration time and costs without compromising accuracy or consistency., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ain Nazir et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Diabetes Mellitus (DM) is a significant global health concern, with Type 2 DM (T2DM) being highly prevalent. Glucagon-Like Peptide 1 receptor agonists (GLP-1RA), such as Danuglipron, offer potential benefits in T2DM management. This meta-analysis examines the safety and efficacy of Danuglipron, focusing on adverse outcomes and glycemic parameters., Methods: A systematic search was conducted in PubMed, Scopus, and Cochrane Library for RCTs involving Danuglipron till August 2023, following PRISMA guidelines. The Cochrane risk-of-bias tool was used for quality assessment. Adverse outcomes (diarrhea, nausea, vomiting, headache, decreased appetite, dyspepsia, dizziness) and glycemic parameters like changes in HbA1C, fasting plasma glucose (FPG), and body weight were analyzed., Results: Four RCTs published from 2021 to 2023 were included. Both doses of Danuglipron were associated with diarrhea (RR=2.66, 90% CI: 1.32 to 5.35, p=0.02), nausea (RR=5.5, 90% CI: 3.4 to 8.88, p<0.00001), and vomiting (RR=5.98, 90% CI: 2.93 to 12.23, p=0.0001). The 120mg dose showed decreased appetite (RR=3.46, 90% CI: 1.57 to 7.62, p=0.01), dyspepsia (RR=4.04, 90% CI: 1.93 to 8.43, p=0.002), and dizziness (RR=5.08, 90% CI: 1.45 to 17.82, p=0.03). Reductions in HbA1C (SMD -1.09, 90% CI -1.39 to -0.8, p < 0.00001), FPG (SMD -1.10, 90% CI -1.46 to -0.75, p < 0.00001), and body weight (SMD -1.08, 90% CI -1.42 to -0.74, p < 0.00001) were observed for both doses., Conclusion: Danuglipron demonstrates potential for glycemic control and weight reduction in T2DM. Adverse outcomes include diarrhea, nausea, vomiting, and decreased appetite, with dose-related effects. Clinicians must weigh benefits against side effects when considering Danuglipron for T2DM management., Competing Interests: The authors declare no potential conflicts of interest in this work., (© 2023 Fatima et al.)

Stroke, a prevalent medical emergency, comprises ischemic and hemorrhagic subtypes, with acute ischemic stroke (AIS) being a predominant type. The application of computed tomography perfusion (CTP) imaging has gained prominence due to its rapidity and accessibility in stroke evaluation. This study systematically reviews and conducts a meta-analysis of existing literature to assess the diagnostic accuracy of CTP in detecting AIS and predicting hemorrhagic transformation (HT). Employing Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, an extensive search was conducted across electronic databases and relevant radiology journals. Studies conducted between 2007 and 2023 that fulfilled predetermined inclusion criteria underwent quality assessment using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS 2) tool. Cochrane diagnostic accuracy tools were used for data extraction. Thirteen studies involving a total of 1014 patients were included in the analysis. The diagnostic performance of CTP in predicting HT demonstrated high sensitivity (86.7%) and moderate specificity (77.8%), resulting in an overall accuracy of 79.1%. The negative predictive value (NPV) was notably high (92.9%), signifying its efficacy in excluding patients at risk of HT. The positive predictive value (PPV) was comparatively lower (60.3%), highlighting the need for clinical context when making thrombolysis decisions. The false positive rate was 16.2%, while the false negative rate was minimal (9.8%). Subgroup analysis underscored consistent sensitivity and specificity across diverse imaging metrics. The findings of this study emphasize the promising diagnostic accuracy of CTP imaging in predicting HT subsequent to AIS. This non-invasive technique can aid treatment decisions and patient management strategies. By effectively assessing perfusion status and offering predictive insights, CTP imaging improves stroke intervention choices, especially in identifying patients with a lower risk of HT., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Mubarak et al.)

Cadmium (Cd) is a heavy metal with various human exposure sources. It accumulates in the liver, forming a complex with metallothionein protein and progresses to other organs. As a heavy metal, cadmium can replace calcium and other divalent ions and disturb their cascades, ultimately affecting the vital organs. Since cadmium acetate (CA) is considered more lethal than other Cd compounds, the current study examines the effect of different concentrations of CA doses in drinking water for different exposure times in murine models (Mus musculus). After the exposure period, the murine models were then examined histopathologically and biochemically. The histopathological examination of the heart, liver, and kidneys of the experimental group showed extensive degenerative effects. Atomic absorption spectroscopy was used to determine the quantity of cadmium in serum, kidney, and hepatic tissues. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of hepatic proteins, especially metallothionein, directly related to Cd administration. The biochemical parameters, including creatine kinase, alanine aminotransferase, aspartate aminotransferase, total proteins, glucose, urea, uric acid, and creatinine, were also analyzed. After thorough histochemical and biochemical analysis, it was concluded that even low dose exposure of CA is hazardous to murine models with damaging effects., (© 2023 Wiley Periodicals LLC.)

Due to lack of robust, sensitive and low cost detection strategies, Tuberculosis (TB) remains a significant global health issue. WHO reports 1.5 million deaths per year, ∼80 % cases occur in low- to middle-income countries, where resource limitations complicate the diagnosis. Robust detection of TB infection is important to contain the spread and treat disease. We developed a label-free DNA biosensor based on commercially available screen printed electrodes (SPEs) (DropSens and Zensors) that can detect TB robustly, sensitively, and specifically via DNA hybridization with its IS6110 gene marker, in purified DNA and raw sputum samples. The fabricated biosensor was morphologically characterized by scanning electron microscopy coupled with energy dispersive X-ray spectroscopy. Cyclic voltammetry and Differential Pulse Voltammetry was used for electrochemical analysis of the modified electrode. The fabricated biosensor demonstrated satisfactory selectivity for Mycobacterium tuberculosis (MTB) against Salmonella typhimurium and Escherichia coli and was able to detect MTB; the limit of detection (LOD) of 1.90 nM with R 2  = 0.993, when analyzed over a range of concentrations of DNA (0.5-10 nM). It is being exploited to detect target MTB from clinical samples, without DNA purification. The approach is robust, sensitive, and specific, requires low sample volume and can be extended towards portable point of care diagnosis of TB., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Background: According to WHO, Hepatocellular cancer (HCC) was the second leading cause of death in 2019 and is gradually increasing. The lipid peroxidation mechanism in cancer cells causes the emission of VOCs in the breath. Volatile organic compounds (VOCs) in breath are becoming favorable biomarkers, especially for cancers, for their sample retrieval and specific association with early metabolic changes. Since both diagnosis and prognosis of the disease depend on the quantity and kind of circulatory biomarkers to be detected, sensitive and selective biosensors with the possibility for portability are constantly in demand., Results: In this study, breath samples of HCC patients were screened for identification of VOCs via GCMS and later verified by applying unsupervised machine learning models. Phenol 2,2 methylene bis [6-(1,1-dimethyl ethyl)-4-methyl] (MBMBP) was found to be significant VOC in the breath of HCC patients, with a minimum concentration of 2100 ppm. Thiol-modified AuNPs were synthesized, as we reported earlier, and immobilized on the working electrode surface to electrochemically sense MBMBP in purified form and later from clinical breath samples. During the electrochemical experiment of AuNPs with MPMBP, the analyte gets electro-oxidized, whereas the Au (III) ions get reduced to the phenoxy radical's species. The electrochemical analysis of MBMBP detection using hexane thiol AuNPs showed a LOD of 0.005 molL 1 . The thiolated AuNPs-based biosensor for HCC diagnosis via VOC detection confirmed MPMBP in lab standards and raw clinical breath samples of HCC patients., Significance: This study reveals that GCE modified with hexanethiol AuNPs for the adsorption of significant breath biomarker, is a potential platform for the development of e-nose sensor for the detection of HCC at early stage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Tuberculosis (TB) remains a leading cause of death globally, especially in underdeveloped nations. The main impediment to TB eradication is a lack of efficient diagnostic tools for disease diagnosis. In this work, label free and ultrasensitive electrochemical DNA biosensor for detecting Mycobacterium tuberculosis has been developed based on the electrodeposition of gold nanoparticles on the surface of carbon screen-printed carbon electrode (Zensors) for signal amplification. Particularly, screen-printed electrodes were modified by electrochemical deposition of Au to enhance the conductivity and facilitate the immobilization of ssDNA probes via Au-S bonds. The electrochemically modified SPEs were characterized using Scanning electron microscopy/Energy Dispersive X-Ray Analysis (SEM/EDX) and X-Ray Diffraction (XRD). Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) techniques were used to investigate the DNA hybridization between single-stranded (ssDNA) probe and target DNA (tDNA). Under the ideal conditions, DPV exhibited a correlation coefficient R2 = 0.97, when analyzed with different tDNA concentrations. The proposed DNA biosensor exhibits a good detection range from 2 to 10 nm with a low detection limit of 1.91 nm, as well as high selectivity that, under ideal conditions, distinguishes non-complementary DNA from perfectly matched tDNA. By eliminating the need for DNA purification, this work paves the path for creating disposable biosensors capable of detecting DNA from raw sputum samples., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sharif, Taufiq, Sohail and Abbas.)

Current thrombolytic therapies for deep venous thrombosis are limited due to the wide side effect profile. Contrast mediated sonothrombolysis is a promising approach for thrombus treatment. The current study examines the effectiveness of in vitro streptokinase (SK) loaded phase-change nanodroplet (PCND) mediated sonothrombolysis at 7 MHz for the diagnosis of deep venous thrombosis. Lecithin shell and perfluorohexane core nanodroplets were prepared via the thin-film hydration method and morphologically characterized. Sonothrombolysis was performed at 7 MHz at different mechanical indexes of samples i.e. , only sonothrombolysis, PCND mediated sonothrombolysis, sonothrombolysis with SK and SK loaded PCND mediated sonothrombolysis. Thrombolysis efficacy was assessed by measuring clot weight changes during 30 min US exposure, recording the mean gray intensity from the US images of the clot by computer software ImageJ, and spectrophotometric quantification of the hemoglobin in the clot lysate. In 15 minutes of sonothrombolysis performed at high mechanical index (0.9 and 1.2), SK loaded PCNDs showed a 48.61% and 74.29% reduction of mean gray intensity. At 0.9 and 1.2 MI, 86% and 92% weight loss was noted for SK-loaded PCNDs in confidence with spectrophotometric results. A significant difference ( P < 0.05) was noted for SK-loaded PCND mediated sonothrombolysis compared to other groups. Loading of SK inside the PCNDs enhanced the efficacy of sonothrombolysis. An increase in MI and time also increased the efficacy of sonothrombolysis. This in vitro study showed the potential use of SK-loaded perfluorohexane core PCNDs as sonothrombolytic agents for deep venous thrombosis., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Recently, dual-mode imaging systems merging magnetic resonance imaging (MRI) and ultrasound (US) have been developed. Designing a dual-mode contrast agent is complex due to different mechanisms of enhancement. Herein, we describe novel phase change nanodroplets (PCNDs) with perfluoropentane encapsulated in a pre-polyglycerol sebacate (pre-PGS) shell loaded with polyethylene glycol (PEG)-coated iron oxide nanoparticles as having a dual-mode contrast agent effect. Iron oxide nanoparticles were prepared via the chemical co-precipitation method and PCNDs were prepared via the solvent displacement technique. PCNDs showed excellent enhancement in the in vitro US much more than Sonovue ® microbubbles. Furthermore, they caused a susceptibility effect resulting in a reduction of signal intensity on MRI. An increase in the concentration of nanoparticles caused an increase in the MR contrast effect but a reduction in US intensity. The concentration of nanoparticles in a shell of PCNDs was optimized to obtain a dual-mode contrast effect. Biocompatibility, hemocompatibility, and immunogenicity assays showed that PCNDs were safe and non-immunogenic. Another finding was the dual-mode potential of unloaded PCNDs as T1 MR and US contrast agents. Results suggest the excellent potential of these PCNDs for use as dual-mode contrast agents for both MRI and US.

Diagnosis of fluid overload (FO) in early stage is essential to manage fluid balance of patients with chronic kidney disease (CKD) and to prevent cardiovascular disease (CVD). However, the identification of fluid status in patients with CKD is largely dependent on the physician's clinical acumen. The ratio of fluid overload to extracellular volume (FO/ECV) has been used as a reference to assess fluid status. The primary aim of this study was to compare FO/ECV with other bioimpedance methods and clinical assessments in patients with CKD. Whole body ECV, intracellular volume (ICV), total body water (TBW), and calf normalized resistivity (CNR) were measured (Hydra 4200). Thresholds of FO utilizing CNR and ECV/TBW were derived by receiver operator characteristic (ROC) analysis based on data from pooled patients with CKD and healthy subjects (HSs). Clinical assessments of FO in patients with CKD were performed by nephrologists. Patients with CKD (stage 3 and stage 4) ( n = 50) and HSs ( n = 189) were studied. The thresholds of FO were ≤14.3 (10 -2 Ωm 3 /kg) for females and ≤13.1 (10 -2 Ωm 3 /kg) for males using CNR and ≥0.445 in females and ≥0.434 in males using ECV/TBW. FO was diagnosed in 78%, 62%, and 52% of patients with CKD by CNR, FO/ECV, and ECV/TBW, respectively, whereas only 24% of patients with CKD were diagnosed to be FO by clinical assessment. The proportion of FO in patients with nondialysis CKD was largely underestimated by clinical assessment compared with FO/ECV, CNR, and ECV/TBW. CNR and FO/ECV methods were more sensitive than ECV/TBW in identifying fluid overload in these patients with CKD. NEW & NOTEWORTHY We found that fluid overload (FO) in patients with nondialysis CKD was largely underestimated by clinical assessment compared with bioimpedance methods, which was majorly due to lack of appropriate techniques to assess FO. In addition, although degree of FO by bioimpedance markers positively correlated with the age in healthy subjects (HSs), no difference was observed in the three hydration markers between groups of 50 ≤ age <70 yr and age ≥70 yr in the patients with CKD.

Multimodal imaging is a recent idea of combining two or more imaging methods synergistically to overcome the weakness of individual imaging modalities and utilizing complementary benefits. Ultrasound (US) and magnetic resonance imaging (MRI) are widely used imaging techniques in healthcare and to fully utilize the potential of fusion imaging, dual-modal contrast agents are necessary to improve disease diagnosis by enhancing contrast resolution and reducing health risks associated with the dual dosage of contrast agents. In this study, magnetic microbubbles were synthesized by incorporating oleic acid stabilized superparamagnetic iron oxide nanoparticles (OA-SPIONs) into lecithin microbubbles, encapsulating the perfluoropentane (PFP) core. The magnetic microbubbles were characterized by FTIR, SEM, MFM, zeta potential, in vitro MRI, and ultrasound. Upon in vitro MRI, magnetic microbubbles showed a negative contrast effect by producing darker T2 weighted images. Magnetic microbubbles showed concentration-dependent response with a decrease in signal intensity with an increase in the concentration of OA-IONP in microbubbles. However, a decrease in acoustic enhancement was also observed with an increase in OA-IONP concentration, therefore concentration was optimized to achieve the best effect on both modalities. The magnetic lecithin microbubble with 10 mg SPIONs provided the best contrast on both US and MR imaging. The hemocompatibility testing resulted in hemolysis less than 7% with plasma recalcification time and thrombin time of 240 s and 6 s corresponding to excellent hemocompatibility. Thus the magnetic microbubbles with a phase convertible PFP core encapsulated by a lecithin shell loaded with OA-SPIONs can serve as a potential bimodal contrast agent for both US and MRI imaging., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

By applying the in-silico method, resveratrol was docked on those proteins which are responsible for bone loss. The Molecular docking data between the resveratrol and Receptor activator of nuclear factor-kappa-Β ligand [RANKL] receptors proved that resveratrol binds tightly to the receptors, showed the highest binding affinities of -6.9, -7.6, -7.1, -6.9, -6.7, and -7.1 kcal/mol. According to in-vitro data, Resveratrol reduced the osteoclasts after treating Marrow-Derived Macrophages [BMM] with Macrophage colony-stimulating factor [MCSF] 20ng / ml and RANKL 50ng / ml, with different concentrations of resveratrol (2.5, 10 μg / ml) For 7 days, the cells were treated with MCSF (20 ng / ml) and RANKL (40 ng / ml) together with concentrated trimethyl ether and resveratrol (2.5, 10 μg / ml) within 12 hours. Which, not affect cell survival. After fixing osteoclast cells with formaldehyde fixative on glass coverslip followed by incubation with 0.1% Triton X-100 in PBS for 5 min and after that stain with rhodamine phalloidin staining for actin and Hoechst for nuclei. Fluorescence microscopy was performed to see the distribution of filaments actin [F.actin]. Finally, resveratrol reduced the actin ring formation. Resveratrol is the best bioactive compound for drug preparation against bone loss.

Background: Mycobacterium tuberculosis' rapid detection is still a formidable challenge to have control over the lethal disease. New diagnostic methods such as LED fluorescence microscopy, Genexpert, Interferon Gamma Release Assay (IGRA) are limited on efficacy spectrum owing to their high cost, time-intensive and laborious nature, in addition their low sensitivity hinders their robustness and portability. Electroanalytical methods are now being considered as an excellent alternative, being currently employed for efficient detection of the analytes with the potential of being portable. This report suggests label-free electrochemical detection of Mycobacterium tuberculosis (Mtb) via its marker, insertion sequence (IS6110)., Methods: In this pursuit, graphene oxide-chitosan nanocomposite (GO-CHI), a biocompatible matrix, having a large electroactive area with an overall positively charged surface, is fabricated and characterized. The obtained GO-CHI nanocomposite is then immobilized on the ITO surface to form a positively functionalized electrochemical sensor for the detection of Mtb. DNA probe, specific for the IS6110, was electrostatically anchored on a positively charged electrode surface and the resistance of charge transfer was investigated for the sensitive and specific (complementary vs non-complementary) detection of Mtb by cyclic voltammetry and differential pulse voltammetry techniques., Results: The cyclic voltammetry was found to be diffusion controlled facilitating the absorption of analyte on the electrode surface. The label-free "genosensor" was found to detect a hybridization efficiency with a limit of detection of 3.4 pM, and correlation coefficient R 2 =0.99 when analysed over a range of concentrations of DNA from 7.86 pM to 94.3pM. The genosensor was also able to detect target DNA from raw sputum samples of clinical isolates without DNA purification., Conclusion: This electrochemical genosensor provides high sensitivity and specificity; thus offering a promising platform for clinical diagnosis of TB and other infectious diseases in general., Competing Interests: Dr Shah Rukh Abbas reports a Utility Patent Application No. 175/2019 pending; not licensed yet. The authors declare no other potential conflicts of interest for this work., (© 2021 Javed et al.)

The present study was aimed to evaluate the antioxidant potential and inhibitory effect ofCannabis sativa and Morus nigra against lipid peroxidation in goat brain and liver homogenates. The formation of free radicals, highly reactive oxygen species (ROS) and reactive nitrogen species (RNS) is a normal metabolic process for cellular signaling and countering the antigens. However, they may cause serious damage if they produced at amplified tolls. In addition, metabolic disorders also serve as sources of these reactive species. Although the issue can be addressed through supplements and other phytochemicals. In this study, two plant species were evaluated for their biological potential by employing a spectrum of antioxidant assays. The antioxidant activity was performed by lipid peroxidation assay. The water extract prepared from leaves of Cannabis sativa and Morus nigra showed significant (P<0.05) inhibition as compared to control i.e., 522.6±0.06 and 659.97±0.03 µg/mL against iron-induced lipid peroxidation in goat brain homogenate while the inhibitions were 273.54±0.04 and 309.18±0.05 µg/mL against nitroprusside induced lipid peroxidation of the brain. The iron and nitroprusside induced lipid peroxidation was also significantly inhibited by leaf extracts of Cannabis sativa and Morus nigra in liver homogenates such as 230.63±0.52 and 326.91±0.01 µg/mL (iron-induced) while 300.47±0.07 and 300.47±0.07 µg/mL (nitroprusside induced), respectively. The extracts of Cannabis sativa extract showed promising activity (96.04±0.060%) against DPPH radicals while Morus nigra showed a moderate activity (34.11±0.120%). The results suggest that different accessions ofCannabis sativa and Morus nigra are a potential source of antioxidants and have a therapeutic effect against disease induced by oxidative stress and hence can be used for novel drug discovery and development.

Berberis lycium Royle has a long history of medicinal uses to treat different diseases. It naturally grows on the mountains of Indian subcontinent. Its ethnobotanical and biochemical study from the state of Azad Jammu and Kashmir (AJ&K) was not previously explored. So, the objective of the current study was to explore the ethnobotanical and biochemical properties of the B. lycium Royle population of AJ&K. For this purpose, samples of B. lycium Royle were randomly collected from five districts of Azad Jammu and Kashmir, including thirty-five locations. Demographic features of informants such as plant part used, methods of preparation, modes of administration, conservation status, and ethnomedicinal uses were documented. It was used for treating different diseases such as diabetes, arthritis, joint pain, and stomach ulcer. This plant is very famous for providing medicinal roots, leaves, and fruits which are extensively used in many parts of the world. The biochemical analysis was conducted for total phenolic contents (TPC), chlorophyll contents, and antioxidant activity. The highest level of TPC found was 88.66 ± 1.07  µ g/g of gallic acid equivalent phenolic (GAE) from leaves collected from Patikka (Chanjhal), Muzaffarabad District, AJ&K. The highest total chlorophyll contents (3.75 ± 0.53  µ g/ml) were found in samples collected from Sathrian, Neelum District. The highest antioxidant activity with lowest IC50 value (33.26  µ g/ml) was obtained from the root of sample collected from Bakreyali, Muzaffarabad District, as compared with other districts. The concentration of berberine was found to be 4.76 percent in the root bark of B. lycium Royle, estimated by high-performance liquid chromatography (HPLC). In syrup composition, 0.95 mg/5 ml of berberine was used. Hence, it is concluded that amongst the five districts, the plant parts (stem, fruits, and root) collected from Muzaffarabad District, AJ&K, showed the highest medicinal potential due to its unique climatic conditions., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Syeda Maria Fiaz Bukhari et al.)

Curcuma longa is an important dietary plant which possess several pharmacological activities, including antioxidant, antimicrobial, anti-inflamatory, anticancer and anti clotting etc. The aim of the present study was to determine the phenolic profile of Curcuma longa and in vitro antioxidant and antidiabetic activities. In HPLC chromatogram of Curcuma longa rhizome extract 15 phenolic compounds were identified namely Digalloyl-hexoside, Caffeic acid hexoside, Curdione, Coumaric, Caffeic acid, Sinapic acid, Qurecetin-3-D-galactoside, Casuarinin, Bisdemethoxycurcumin, Curcuminol, Demethoxycurcumin, and Isorhamnetin, Valoneic acid bilactone, Curcumin, Curcumin-O-glucuronide respectively. The ethanolic extract displayed an IC50 value of 37.1±0.3 µg/ml against alpha glucosidase. The IC50 value of DPPH radical scavenging activity was 27.2 ± 1.1 μg/mL. It is concluded that ethanolic extract of Curcuma long is rich source of curcumin and contain several important phenolics. The in vitro antioxidant and alpha glucosidase inhibitory effect of the plant justifies its popular use in traditional medicine.

Nanoparticles are known bio elicitors in plant biotechnology. Different concentrations of ZnO, CuO and CoO nanoparticles were used for the enhanced accumulation of secondary metabolites and antioxidant activities in the callus derived from root, shoot and leaf of Artemisia annua L. Biomass of callus was somehow affected on high concentrations of Nps. Phenolic content was observed maximum (60µg) in shoot callus at 0.1mg/l of CuONps. Total antioxidant activity was observed maximum (33µg) in root callus at 0.1mg/l of ZnOnps. Total reducing power maximum (33µg) was observed in root callus at concentration of 0.05 mg/l of CoONps. Maximum radical scavenging activity was observed in shoot callus at 0.05mg/l of ZnONps. Rutin gallic acid and caffic acid were also determined in most of the samples by HPLC. The study concludes that different Nps have positive effect on the induction of secondary metabolites in A.annua plant.

Amygdalin, despite possessing anticancerous properties, has been viewed as a controversial choice due to the presence of the cyanide group. Here, we synthesise and investigate the potential of alginate-chitosan nanoparticles (ACNPs) as drug delivery agents for amygdalin encapsulation and its delivery to cancer cells. Amygdalin loaded ACNPs were made with both anionic and cationic outer layer to further investigate charge dependency on drug delivery and cytotoxicity. ACNPs encapsulating amygdalin were monodisperse, colloidally stable with ~90% drug encapsulation efficiency and were entirely made from natural materials. The nanoparticles exhibited sustained drug release for a duration of 10 h and significant swelling rates in neutral and slightly acidic environments. The ACNPs successfully adhered to porcine mucin type II when assessed for its mucoadhesion and shown to transmigrate with an average velocity of 1.68 μm/s in uncoated channels, under biomimicked flow conditions. To investigate charge dependency on drug delivery and cytotoxicity, amygdalin loaded ACNPs were made with both anionic and cationic outer layer and assessed. ACNPs demonstrated greater yet sustained anti-cancerous effect on H1299 cell lines in a dose-dependent manner than free amygdalin suggesting greater cellular uptake of the former. In conclusion, biocompatible and biodegradable alginate-chitosan nanoparticles can be used as an effective drug delivery system for sustained and controlled amygdalin release with its improved cytotoxic effect on cancerous cells while protecting normal cells and tissues., Competing Interests: Declaration of competing interest The authors declare that they have no known conflict or competing financial interests that could have appeared to influence the work which is reported., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Reports on vitamin C in HD patients have shown effects of vitamin C deficiency in association with scurvy symptoms. Dialyzability of water soluble vitamins is high, and substantial losses in those who are dialyzed more frequently were hypothesized. The randomized FHN Daily Trial compared the effects of in-center HD six versus three times per week. We studied baseline correlations between vitamin C and potentially associated parameters, and the effect of more frequent HD on circulating vitamin C concentrations., Methods: We studied vitamin C levels at baseline and months, 3, 5 and 11. Patients enrolled between 2007 and 2009 into the randomized FHN Daily trial in the East Coast consortium were approached for participation. Predialysis plasma samples were processed with metaphosphoric acid and frozen at - 70 °C for measurement with HPLC. Regression models between baseline log-transformed vitamin C and hemoglobin, CRP, eKt/V, ePCR and PTH, and a linear mixed-effects model to estimate the effect size of more frequent HD on plasma vitamin C, were constructed., Results: We studied 44 subjects enrolled in the FHN Daily trial (50 ± 12 years, 36% female, 29% Hispanics and 64% blacks, 60% anuric). Vitamin C correlated significantly with predialysis hemoglobin (r = 0.3; P = 0.03) and PTH (r = - 0.3, P = 0.04), respectively. Vitamin C did not significantly differ at baseline (6×/week, 25.8 ± 25.9 versus 3×/week, 32.6 ± 39.4 μmol/L) and no significant treatment effect on plasma vitamin C concentrations was found [- 26.2 (95%CI -57.5 to 5.1) μmol/L at Month 4 and - 2.5 (95%CI -15.6 to 10.6) μmol/L at Month 12., Conclusions: Based on data from this large randomized-controlled trial no significant effect of the intervention on circulating plasma vitamin C concentrations was found, allaying the concerns that more frequent HD would affect the concentrations of water-soluble vitamins and adversely affect patient's well-being. Correlations between vitamin C and hemoglobin and PTH support the importance of vitamin C for normal bone and mineral metabolism, and anemia management.

Background: Ultrafiltration failure and fluid overload are common in peritoneal dialysis (PD) patients. Knowledge of intraperitoneal volume (IPV) and time to peak IPV during a dwell would permit improved PD prescription. This study aimed to utilize trunk segmental bioimpedance analysis (SBIA) to quasi-continuously monitor IPV (IPVSBIA) during the peritoneal dwell., Methods: IPVSBIA was measured every minute using lower-trunk SBIA (Hydra 4200; Xitron Technologies Inc., CA, USA) in 10 PD patients during a standard 240-min peritoneal equilibration test (PET). The known dialysate volume (2 L) rendered IPVSBIA calibration and calculation of instantaneous ultrafiltration volume (UFVSBIA) possible. UFVSBIA was defined as IPVSBIA - 2 L., Results: Based on dialysate-to-plasma creatinine ratio, 2 patients were high, 7 high-average, and 1 low-average transporters. Technically sound IPVSBIA measurements were obtained in 9 patients (age 59.0 ± 8.8 years, 7 females, 5 African Americans). Drained ultrafiltration volume (UFVdrain) was 0.47 ± 0.21 L and correlated (r = 0.74; p < 0.05) with end-dwell UFVSBIA (0.55 ± 0.17 L). Peak UFVSBIA was 1.04 ± 0.32 L, it was reached 177 ± 61 min into the dwell and exceeded end-dwell UFVSBIA by 0.49 ± 0.28 L (95% CI: 0.27-0.7) and UFVdrain by 0.52 ± 0.31 L (95% CI: 0.29-0.76), respectively., Conclusion: This pilot study demonstrates the feasibility of trunk segmental bioimpedance to quasi-continuously monitor IPVSBIA and identify the time to peak UFVSBIA during a standard PET. Such new insights into the dynamics of intraperitoneal fluid volume during the dwell may advance our understanding of the underlying transport physiology and eventually assist in improving PD treatment prescriptions., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

The presence of P-glycoprotein in the human intestine represents a significant barrier to effective drug therapy. These proteins form a multidrug-resistant barrier to most drugs, especially those administered orally. Thus, strategies are needed to prepare molecules to combat these resistant proteins and enable an increase in drug efficacy. We developed a novel tin-Schiff base complex using an ultrasonic bath, a new technique in small molecule synthesis. New bond formation was confirmed using ultraviolet and Fourier transform spectroscopies. A computational study was carried out using Absorption, Distribution, Metabolism, Excretion and Toxicity software. The novel tin-entecavir (ETV)-piperonal Schiff base acts as a potent P-glycoprotein inhibitor, which overcomes the multidrug resistance to all drugs that are substrates for P-glycoprotein. Further study showed that the novel tin complex is less toxic than the parent compound at the same dose. The development of this tin-piperonal-ETV Schiff base complex is a major breakthrough for overcoming multidrug resistance barriers and can be applied to other drug molecules.

Objective: This prospective study uses calf bioimpedance spectroscopy (cBIS) to guide the attainment of dry weight (DW cBIS ) in chronic hemodialysis (HD) patients. The primary aim of this study was to evaluate whether body composition is altered when fluid status is reduced to DW cBIS ., Methods: Target post-HD weight was gradually reduced from baseline (BL) until DW cBIS was achieved. DW cBIS was defined as the presence of both flattening of the curve of extracellular resistance and the attainment calf normalized resistivity in the normal range during the dialysis treatment. Extracellular volume (ECV), intracellular volume, and total body water (TBW) were measured using whole body BIS (Hydra 4200). Fluid overload, lean body mass, and fat mass were calculated according to a body composition model., Results: Seventy-three patients enrolled and 60 completed the study (55 ± 13 years, 49% male). Twenty-eight patients (25% diabetes) achieved DW cBIS , whereas 32 patients (47% diabetes) did not. Number of treatment measurements were 16 ± 10 and 12 ± 13 studies per patient in the DW cBIS and non-DW cBIS groups, respectively. Although significant decreases in body weight and ECV were observed, lean body mass and FM did not differ significantly in both groups from BL to the end of study. ECV, ECV/TBW, and fluid overload were higher in the non-DW cBIS than in the DW cBIS group both at BL and at the end of study. Ratios of intradialytic changes in calf normalized resistivity, ECV, and ECV/TBW to ultrafiltration volume were significantly lower in diabetic than in non-diabetic patients., Conclusions: This study shows that decreasing fluid status by gradual reduction of post-HD weight in both DW cBIS and Non-DW cBIS groups did not affect body composition significantly over a period of about 4 weeks., (Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background It has been seen that despite the increasing incidence of benign testicular disorders (BTDs), little work has been done towards its awareness among the male populace. Also, the trend of not seeking help in this regard is concerning. In this study, we aim to better perceive the level of understanding and common practices regarding BTDs among educated young men. Methods A cross-sectional study was carried out among two groups of ages 14-20 and 21-28 years. The inclusion criterion was that of educated males in an urban setting. Data were collected through a standardized questionnaire using cluster sampling by independent interviewers. The questionnaire consisted of four parts dealing with demographics, knowledge, attitudes and practices. Chi-square and Mann-Whitney U test were used as the primary statistical tests. Results The sample population consisted of an equal number of participants between the ages of 14 and 20, and between 21 and 28 years (n = 200, 50%). About half the participants (n = 215, 53.8%) were not familiar with the term BTDs. The majority (n = 324, 78.8%) of participants were not aware of symptoms of BTDs. Three-fourth of the participants believed that the subject is considered taboo in Pakistan (n = 307, 73.6%) while a majority of participants (n = 340, 85%) believed media coverage can help spread awareness of BTDs. A huge number (n = 268, 67%) thought that BTDs can cause fertility problems while one-third of them would not perform testicular self-examination (TSE) in case of pain or swelling in the scrotal region (n = 119, 29.8). The level of education and age were significantly associated with the knowledge regarding symptoms and types of BTDs. Conclusion Knowledge of BTDs and practices of TSE in the young educated men of Karachi are alarmingly poor. Therefore, there is an urgent need to create awareness at all levels using different strategies and platforms., Competing Interests: The authors have declared that no competing interests exist.

Normal fluid status (dry weight) can be identified by hydration markers established in the healthy population. The general population average could be influenced by age with its accompanying physiological changes and/or illness. The aims of this study were (1) to evaluate the effect of age and systolic blood pressure (SBP) on these markers; (2) to compare mean values of hydration markers as assessed by different bioimpedance techniques. Subjects from the general population (n  =  212, males 105, 57.1% White, 31.6% Black, and 11.3% others) were studied. Body weight, height and SBP were measured. Whole body and calf bioimpedance (Hydra 4200) methods were utilized with subjects in the supine position. Calf normalized resistivity (CNR), fluid overload (FO), extracellular (ECV) and intracellular (ICV) volume measurements ECV/total body water (TBW) were calculated. Subjects were stratified by age; young (Group1): 18-35 years; middle (Group2): 36-60 years, senior (Group3): 61-80 years. Body mass index (BMI), CNR, and ECV/TBW differed significantly between age groups, and genders. ECV and FO increased with age in males. Decreased CNR (indicating relative increased fluid load) (p  <  0.001) and increased SBP (p  <  0.001) were associated with age in all three groups. CNR in Group1 was the same as in 36.0% of subjects in Group2 and 12.5% of subjects in Group3. In those subjects in Group2 and Group3, with CNR levels comparable to Group1 subjects, SBP was lower than in their peers in each respective age group. In conclusion average CNR in Group1 represents the range of healthy subjects. Since CNR is correlated with age, subjects in Group2 and Group3 are more likely to have fluid overload. Although about a third of subjects in Group2 and Group3 were in the range of Group1, the age and associated factors should be considered when CNR is used to identify fluid status in senior patients.

Background and Objectives: Patients with chronic kidney disease (CKD) are often volume expanded and hypertensive. Few controlled studies have assessed the effects of a sodium-restricted diet (SRD) in CKD., Design, Setting, Participants, & Measurements: We conducted a randomized crossover trial to evaluate the effect of SRD (target <2 g sodium per day) versus usual diet on hydration status (by bioelectrical impedance spectroscopy) and blood pressure (BP) between May of 2009 and May of 2013. A total of 58 adults with stage 3-4 CKD were enrolled from two academic sites: University of Michigan ( n =37) and University of North Carolina at Chapel Hill ( n =21); 60% were men, 43% were diabetic, 93% were hypertensive, and mean age was 61 years. Participants followed SRD or usual diet for 4 weeks, followed by a 2-week washout period and a 4-week crossover phase. During the SRD, dieticians provided counseling every 2 weeks, using motivational interviewing techniques., Results: Whole-body extracellular volume and calf intracellular volume decreased by 1.02 L (95% confidence interval [95% CI], -1.48 to -0.56; P <0.001) and -0.06 L (95% CI, -0.12 to -0.01; P =0.02), respectively, implying decreased fluid content on the SRD compared with usual diet. Significant reductions in urinary sodium (-57.3 mEq/24 h; 95% CI, -81.8 to -32.9), weight (-2.3 kg; 95% CI, -3.2 to -1.5), and 24-hour systolic BP (-10.8 mmHg; 95% CI, -17.0 to -4.6) were also observed (all P <0.01). Albumin-to-creatinine ratio did not change significantly and mean serum creatinine increased slightly (0.1 mg/dl; 95% CI, -0.01 to 0.2; P =0.06). No period or carryover effects were observed. Results were similar when analyzed from phase 1 only before crossover, although P values were modestly larger because of the loss of power., Conclusions: In this randomized crossover trial, implementation of SRD in patients with CKD stage 3-4 resulted in clinically and statistically significant improvement in BP and hydration status. This simple dietary intervention merits a larger trial in CKD to evaluate effects on major clinical outcomes., (Copyright © 2017 by the American Society of Nephrology.)

Bioimpedance (BI) techniques for measuring normal hydration status (NHS) can be generally classified as (1) by frequency as single frequency at 50 kHz, BI analysis, and multifrequency BI spectroscopy and (2) by method as whole body (wrist to ankle) measurement and calf BI spectroscopy. The aim of this article was to review current BI methods for clinical practice in patients with end-stage of kidney disease. BI vector analysis using whole-body single-frequency BI at 50 kHz may be useful for population studies to indicate a range of degree of fluid loading and of nutritional status. Whole body multifrequency BI spectroscopy is used to estimate extracellular (ECV), intracellular fluid volume, and total body water in dialysis patients. The whole-body BI model is used in the body composition monitor (BCM). The whole-body BI model is established with ECV, intracellular fluid volume, and body weight based on parameters from regression analysis in healthy subjects to calculate fluid overload in dialysis patients. Calf BI methods have been developed to measure NHS by 2 ways: (1) continuous measurement of the intradialytic resistance curve until flattening occurs; (2) calf normalized resistivity in the range of healthy subjects (18.5 × 10(-2) Ω m(3)/kg in male and 19.1 × 10(-2) Ω m(3)/kg in female). In general, for population studies, BI vector analysis or ECV/total body water may be useful; BCM is a commercially available device that can certainly guide volume reduction safely over time. For more exact measure of fluid overload, calf BI methods appear to be most accurate, but these are at present research tools. BI techniques are not only useful in assessing NHS but also in the study of nutrition and body composition., (Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: In this study our aim was to evaluate the relationship between degree of fluid status and arterial stiffness measured by pulse wave velocity (PWV) in peritoneal dialysis (PD) patients. Fluid status was determined by different methods including fluid overload measured by bioimpedance (Body Composition Monitor, BCM), calf normalized resistivity (CNR), plasma N-terminal fragment of B-type natriuretic peptide (NT-proBNP) and extracellular to intracellular water ratio (ECW/ICW)., Methods: Sixty PD patients were evaluated. They were stratified into normo- and hypervolemic groups according to their fluid overload (FO). CNR was calculated from resistance at 5 kHz using calf bioimpedance spectroscopy. Arterial stiffness was assessed by PWV. Additionally, all patients underwent transthoracic echocardiography and had levels of NT-proBNP measured., Results: PWV was higher in the hypervolemic compared to normovolemic patients (9.99 ± 2.4 m/sec vs 7.48 ± 2.3 m/sec, p < 0.001). Hypervolemic patients had higher NT-proBNP levels (3065 ± 981 pg/mL vs 1095 ± 502 pg/mL, p < 0.001), a higher ratio of ECW/ICW; (0.93 ± 0.11 vs 0.81 ± 0.08, p < 0.001) and lower CNR (13.7 ± 2.4 vs 16.0 ± 3.3 W m(3)/kg(*)10(-2), p = 0.005). NT-pro BNP level, ECW/ICW ratio, relative FO, and left ventricular (LV) mass index were positively and CNR negatively correlated with PWV. Relative FO and CNR independently predicted PWV in multivariate analysis adjusted for age, duration of PD, body mass index and mean arterial pressure., Conclusions: Arterial stiffness is increased in fluid-overloaded PD patients. Our results indicated that fluid status is an independent predictor of PWV., (Copyright © 2014 International Society for Peritoneal Dialysis.)

This study explored divergence (error) between ultrafiltration volumes (UFV) and intradialytic changes in extracellular volume (ΔECV) in hemodialysis (HD) patients measured by whole body (wBIS) and sum of segmental bioimpedance spectroscopy (sBIS). The primary aim of the study was to evaluate the effect of different ultrafiltration rates (UFR) on error of estimation of ΔECV by changes in their distribution in body segments (arm, trunk, and leg). Forty-four HD patients (26 men, age 63.5 ± 14.3 yr) were studied twice in the same week following high and low UFR treatments. ΔECV and distributions (segmental ΔECV/Σsegmental ΔECV, %) in arm, trunk, and leg were measured. ΔECV by wBIS underestimated UFV (0.58 ± 0.43 in high vs. 0.36 ± 0.5 liters at low UFR; P < 0.001, respectively); however, using sBIS no significant difference between UFV and ΔECV was present. Divergence using wBIS but not sBIS correlated positively with UFR. ΔECV distribution in trunk and leg at high UFR (44.1 ± 8.3, 47.2 ± 8.5, %) differed significantly (P < 0.01) from low UFR (36 ± 15.7, 53.8 ± 14.7) respectively, but in arm did not differ between UFR. Primary sources of whole body resistance are arms and legs. Due to different cross-sectional areas between trunk and limbs, wBIS is insensitive to detection of changes in trunk volume. At higher UFR, plasma water was rapidly and largely removed from the trunk but with only a small change in whole body resistance. As a result, accuracy of estimation of ECV by wBIS is further decreased by high UFR, while sBIS remains accurate using separate measurements of segmental volumes., (Copyright © 2014 the American Physiological Society.)

The present study investigated the antioxidant and phenolic composition of sugarcane. The leaves and juices of thirteen varieties of sugarcane were studied for their antioxidant activity and protective effect on DNA damage. 2,2-Diphenyl-1-picrylhydrazyl radical (DPPH) assay was used to determine the radical scavenging activities in leaves and juices. Different varieties of sugarcane showed good antioxidant properties, IC50 values ranged from 20.82 to 27.47 μg/ml for leaves and from 63.95 to higher than 200 μg/ml for juice. The leaves and juice possess strong ability to protect against DNA damage induced by hydroxyl radical generated in Fenton reaction. The major phenolic acids, some flavonoid aglycone and glycosides were identified in leaves by high performance liquid chromatography. Ferulic acid (14.63 ± 0.03 mg/g), cumaric acid (11.65 ± 0.03 mg/g), quercetrin (10.96 ± 0.02 mg/g), caffeic acid (9.16 ± 0.01 mg/g) and ellagic acid (9.03 ± 0.02 mg/g) were prédominant in infusion of sugarcane., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Bioimpedance analysis (BIA) is well established to assess body composition. Agreements between single- and multi-frequency bioimpedance (SF-BIA, MF-BIS) measurements in subjects undergoing 6 or 3 times/week hemodialysis (HD) were analyzed., Methods: Total body water (TBW) and intra- and extracellular fluid (ICF, ECF) of subjects enrolled in the Frequent Hemodialysis Network (FHN) Daily Trial (www.clinicaltrials.gov No. NCT00264758) were measured with a Hydra 4200 at baseline (BL) and at 5 months (M5). Volumes were computed using SF (at 50 kHz) and MF approaches. Agreement was assessed by means of linear regression and Bland-Altman analysis and treatment effects by t test., Results: 35 subjects (17 on the more frequent regimen, 26 males, 20 African-American, 48 ± 9 years, pre-HD weight 84 ± 19 kg) were studied. Assessments with SF-BIA and MF-BIS correlated significantly at BL and M5 in both arms. No proportional errors, but systematic biases over the entire range of values were found at BL and M5. Agreement did not differ between subjects randomized to either HD treatment arm at both time points. MF-BIS appears to have better precision than SF-BIA allowing the observation of a significant treatment effect by the intervention [-1.5 (95% CI -2.5 to -0.5) l] on ECF, not found for ECF SF-BIA. Precision also affected the statistical power of the SF-BIA data in the current analysis., Conclusion: Both methods showed agreement without significant proportional errors regardless of HD frequency and can be used for longitudinal analyses. SF-BIA has lower precision which needs thorough consideration in the design of future trials with similar outcomes., (© 2014 S. Karger AG, Basel.)

Unlabelled: Bioimpedance (BI) is maturing as a clinical technique for assessing fluid volume status. The aim of this study was to compare the sensitivity of four BI methods to detect changes in fluid status in hemodialysis patients., Methods: Forty-five patients were studied twice in the same week, i.e. once after the long and short interdialytic intervals, respectively. The four BI methods used were: (a) calf normalized resistivity (CNR) at a 5-kHz frequency, (b) whole-body multifrequency BI spectroscopy (MF-BIS) to estimate the normal hydration weight (NHWWBM), (c) whole-body MF-BIS to estimate the ratio of extracellular volume to total body water (wECV/wTBW), and (d) whole-body single-frequency (50 kHz) BI analysis to compute the ratio of ECV (sfECV) to TBW (sfTBW)., Results: The relationship (slope of the regressive line) between relative changes (%) in the above mentioned four BI parameters and differences in weight (kg) was most pronounced with CNR (5.2 ± 1.6%/kg), followed by wECV/wTBW (1.7 ± 0.7%/kg) and NHWWBM (0.73 ± 0.2%/kg). Changes in sfECV/sfTBW and differences in weight were not correlated., Conclusions: CNR is more sensitive than whole-body BIS for detecting differences in fluid status., (© 2014 S. Karger AG, Basel.)

Background: In incident hemodialysis (HD) patients, the relationship between early systolic blood pressure (SBP) dynamics and mortality is unknown., Methods: Baseline SBP levels were stratified into 5 categories ranging from <120 and ≥180 mm Hg. Early pre-HD SBP change was defined as the slope of pre-HD SBP from week 1 to 12 and categorized in quartiles (Q1, lowest slope). SBP slopes were computed for each patient by simple linear regression., Results: In 3,446 incident HD patients (42% females, 44% black, age 62 ± 15 years), the median pre-HD SBP slope was -1.7 (Q1) to +2.3 (Q4) mm Hg/week. In an adjusted multivariate Cox regression analysis, patients with declining SBP (slope Q1) had higher mortality compared to patients with increasing pre-HD SBP (slope Q4) at 12 months (hazard ratio 2.01, 95% confidence interval 1.35-3.01). In addition, patients with baseline pre-HD SBP <120 mm Hg showed higher mortality compared to the reference group (SBP ≥180 mm Hg) at 12 months (hazard ratio 1.89, 95% confidence interval 1.03-3.45)., Conclusion: Baseline pre-HD SBP and early SBP dynamics are associated with mortality in the first year of dialysis. Patients who had low (pre-HD SBP <120 mm Hg) or declining SBP had the highest mortality rates. Particular attention is warranted in incident HD patients with low or declining SBP., (Copyright © 2012 S. Karger AG, Basel.)