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Opening the amino acid toolbox for peptide-based NTS2-selective ligands as promising lead compounds for pain management.

Chronic pain is one of the most critical health issues worldwide. Despite considerable efforts to find therapeutic alternatives, opioid drugs remain the gold standard for pain management. The administration of μ-opioid receptor (MOR) agonists is associated with detrimental and limiting adverse effects. Overall, these adverse effects strongly overshadow the effectiveness of opioid therapy. In this context, the development of neurotensin (NT) ligands has shown to be a promising approach for the management of chronic and acute pain. NT exerts its opioid-independent analgesic effects through the b

A rare case of sinus venosus atrial septal defect: Malpositioned right atrial pacemaker lead in the left atrium.

Incidental discovery of sinus venosus atrial septal defect (SV-ASD) in the elderly is rare. This defect allows for lead malpositioning during pacemaker placement and can lead to catastrophic cardioembolic events. Post-pacemaker implantation, chest radiography should be obtained to detect malpositioning early, and if detected, lead adjustment is recommended; if identified later, treatment with an anticoagulant is feasible. SV-ASD repair may be considered as well.

Effect of soluble phosphate and bentonite amendments on lead and cadmium bioavailability and bioaccessibility in a contaminated soil.

Effect of commonly used heavy metal immobilizing agents on risks of soil heavy metals has not been well investigated. In this work, a contaminated acidic soil (total Cd = 8.05, total Pb = 261 mg kg-1) was amended with soluble phosphate (P: 160 mg kg-1) and bentonite (3 g kg-1) and incubated for 360 d. The soil was then added to mouse feed at 1:9 soil: feed ratio (weight) and fed to mouse for 10 days, after which the liver, kidney and bone Pb and Cd concentrations were measured. The amended soils were extracted with SBRC and PBET to assay bioaccessibility, and extracted with DTPA to assess the

Cadmium exposure is associated with chronic kidney disease in a superfund site lead smelter community in Dallas, Texas.

Background: The study was conducted in a Dallas lead smelter community following an Environmental Protection Agency (EPA) Superfund Cleanup project. Lead smelters operated in the Dallas community since the mid-1930s.Aim: To test the hypothesis that cadmium (Cd) exposure is associated with chronic kidney disease (CKD) ≥ stage 3.Subjects and methods: Subjects were African American residents aged ≥19 to ≤ 89 years (n=835). CKD ≥ stage 3 was predicted by blood Cd concentration with covariates.Results: In logistic regression analysis, CKD ≥ stage 3 was predicted by age ≥ 50 years (OR = 4.41, p < 0.…

Feasibility and reliability of whintings scanwatch to record 4-lead Electrocardiogram: A comparative analysis with a standard ECG.

The recent technological advances allowed us to produce some new wearable devices, such as smartphones and smartwatches (SW). These devices provide different services to their users through different software applications installed even in the SW or smartphones. Health monitoring functionalities, among these services, are nowadays the new technological fashion. In fact, the monitoring is ensured by the sensor incorporated in the SW. The SW allows the record of only one single lead Electrocardiogram (ECG), which is sufficient to screen or diagnosis of rhythm and conduction disorders, especially…

Chronic Mild Sleep Restriction Does Not Lead to Marked Neuronal Alterations Compared With Maintained Adequate Sleep in Adults.

BACKGROUND: Sleep restriction (SR) has been shown to upregulate neuronal reward networks in response to food stimuli, but prior studies were … tion at 2-tailed voxel P < 0.001, cluster P < 0.05). CONCLUSIONS: The results suggest that mild SR leads to increased reward responsivity to foods but with low confidence given the failure to meet significance from rigorous statistical analyses. Further research is necessary to inform the mechanisms underlying the role of sleep on food intake regulati …

Lead acetate induces cartilage defects and bone loss in zebrafish embryos by disrupting the GH/IGF-1 axis.

Skeletal system toxicity due to lead exposure has attracted extensive attention in recent years, but few studies focus on the skeletal toxicity of lead in the early life stages of zebrafish. The endocrine system, especially the GH/IGF-1 axis, plays an important role in bone development and bone health of zebrafish in the early life. In the present study, we investigated whether lead acetate (PbAc) affected the GH/IGF-1 axis, thereby causing skeletal toxicity in zebrafish embryos. Zebrafish embryos were exposed to lead PbAc between 2 and 120 h post fertilization (hpf). At 120 hpf, we measured d…

Performance of interferon-gamma levels may lead to earlier diagnosing macrophage activation syndrome complicating systemic juvenile idiopathic arthritis.

Macrophage activation syndrome (MAS) is a severe, potentially fatal complication of rheumatic diseases, predominantly in systemic juvenile idiopathic arthritis (SJIA), and is considered as an autoinflammatory disease. Specific cytokine profiles could play a pivotal role in this inflammatory response. Gram-negative bacteremia, bacterial pneumonia, Kawasaki disease, and active SJIA exhibited similar cytokine profiles with elevated interleukin-6 (IL-6) and/or IL-10, further suggesting a correlation between them. Only when JIA is complicated by MAS can increased interferon-γ (IFN-γ) levels be obse

Predictors of implantation failure in left bundle branch area pacing using a lumenless lead in patients with bradycardia.

BACKGROUND: Left bundle branch area pacing (LBBAP) is a novel conduction system pacing technique. In this multicenter study, we aimed to eva … % of the population. The primary reasons for procedural failure were the inability of the pacemaker lead to penetrate deep into the septum (76.3%) and failure to achieve shortening of stimulus to left ventricular (LV) activation time in lead V6 (18.4%). Thickened interventricular septum (odds ratio [OR], 2.48; 95% confidence interval [CI], 1.15-5.35), …

Single-lead arrhythmia detection through machine learning: cross-sectional evaluation of a novel algorithm using real-world data.

BACKGROUND: Computer-assisted interpretation of single-lead ECG is the preliminary method for clinicians to flag and further evaluate an arrhythmia of clinical importance for acutely ill patients. Critical scrutiny of novel detection algorithms is lacking, particularly in external real-world data sets. This study's objective was to evaluate a hybrid machine learning model's ability to classify eight arrhythmias from a single-lead ECG signal from acutely ill patients. METHODS: This cross-sectional external retrospective evaluation of a previously trained hybrid machine learning model against a…

Quercetin as a Dietary Supplementary Flavonoid Alleviates the Oxidative Stress Induced by Lead Toxicity in Male Wistar Rats.

Quercetin is a naturally existing plant pigment belonging to the flavonoid group; it is contained in a wide range of vegetables and fruits. The accumulated evidence points to the potential uses of quercetin in protection of some disease conditions. Lead is one of the highly toxicant heavy metals that are widely spread in the environment and implicated in a wide spectrum of industries. No previous study has been reported to evaluate the effect of quercetin on lead toxicity. Therefore, the present study was conducted to elucidate some aspects of quercetin bioactivities in regard to its ability t…

Glutamine Is a Superior Protector Against Lead-Induced Hepatotoxicity in Rats via Antioxidant, Anti-inflammatory, and Chelating Properties.

Lead acetate-motivated oxidative stress can affect all organ systems, particularly the liver. Glutamine (Gln) has both antioxidant and chelating properties. Therefore, we investigated for the first time the effect of Gln on the biochemical and histopathological alternations in a rat model of lead toxicity. Thirty-two rats were divided into four groups (eight rats in each): untreated normal, lead poisoning, and two similar groups receiving Gln (0.1% in drinking water for 4 weeks). To induce lead poisoning, rats received 50 mg/L lead acetate in drinking water for 4 weeks. Oxidative stress indice…

Dynamics lead-lag relationship of jumps among Chinese stock index and futures market during the Covid-19 epidemic.

This paper introduces thermal optimal path method to investigate the dynamics lead-lag relationship of jumps among Chinese stock index and futures market under the background of the Covid-19 epidemic. Based on three representative stock indexes and their index futures in China, we find the lead-lag structure changes significantly before and after the outbreak of COVID-19. Before the epidemic, there is mutual effect between different markets jumps. However, CSI 300 futures and SSE 50 futures significantly lead other markets for the after-epidemic period. For the volatility forecasting based on …

Case report: Biallelic variants in POLR3B gene lead to 4H leukodystrophy from the study of brother and sister.

INTRODUCTION: 4H leukodystrophy, one of POLR3-related leukodystrophy, is a rare hereditary brain white matter disease caused by the pathogenic biallelic variations in POLR3A, POLR3B, or POLR1C. Hypomyelination, hypodontia, and hypogonadotropic hypogonadism is mainly presented in patients with 4H leukodystrophy. PATIENT CONCERNS: Here, we reported the brother and the sister with new compound heterozygous (c.1615G>T and c.165-167del) with various degrees of phenotypes including dysbasia, myopia, dental abnormal, and hypogonadotropic hypogonadism. DIAGNOSIS: The brother and sister were diagnose

Non-invasive estimation of QLV from the standard 12-lead ECG in patients with left bundle branch block.

Background: Cardiac resynchronization therapy (CRT) is a treatment for patients with heart failure and electrical dyssynchrony, i.e., left bundle branch block (LBBB) ECG pattern. CRT resynchronizes ventricular contraction with a right ventricle (RV) and a left ventricle (LV) pacemaker lead. Positioning the LV lead in the latest electrically activated region (measured from Q wave onset in the ECG to LV sensing by the left pacemaker electrode [QLV]) is associated with favorable outcome. However, optimal LV lead placement is limited by coronary venous anatomy and the inability to measure QLV non-…

Permanent His bundle pacing using a Biotronik stylet-driven Lead: feasibility and early outcomes from a single centre.

His bundle pacing (HBP) has been shown to be a good alternative to conventional cardiac resynchronisation therapy (CRT) and may theoretically provide an additional benefit where CRT has a response deficit of at least 30%. HBP requires mapping and identification of the His bundle, and to this purpose the lead delivery is challenging. This first-reported case series from Africa shares early experience with different pacing indications (complete heart block and pre-existing right ventricular pacing; heart failure with left bundle branch block) for using a standard 5.6F, Solia S 60, IS-1, ProMRI b…

Lysocin E Targeting Menaquinone in the Membrane of Mycobacterium tuberculosis Is a Promising Lead Compound for Antituberculosis Drugs.

Tuberculosis remains a public health crisis and a health security threat. There is an urgent need to develop new antituberculosis drugs with … ice was still superior to that of streptomycin. Our findings indicate that lysocin E is a promising lead compound for the development of a new tuberculosis drug that cures drug-resistant and latent tuberculosis in a shorter period.

Cancer mortality and chemical exposure in a retrospective zinc and lead smelter cohort: A 48-year follow-up.

INTRODUCTION: Very few studies to date have investigated cancer mortality in non-ferrous metal smelters. Existing studies mainly focus on lead exposure and have reported inconsistent results. The aim of this study was to investigate the risk of excess cancer mortality in the employees of a lead and zinc smelter located in the north of France by 1) comparing mortality in this cohort of employees with that of the regional population; 2) studying the associations between occupational exposure and cancer deaths. METHODS: The study cohort was composed of male workers, born in France, who had been …

Response-The Road Less Travelled: Why did Miles Little Turn to Qualitative Research and Where Did This Lead?

Miles Little is an Australian surgeon, poet, and philosopher whose published work spans diverse topics in surgery, medicine, philosophy, and bioethics. In 1974 he co-authored a survey that included an analysis of interviews conducted with amputees. This was his first foray into qualitative research. Twenty years later he established a research centre at the University of Sydney that initiated a programme of qualitative research in cancer medicine. For twenty years after that, the centre acted as a hub for research that applied qualitative methods from the social sciences to study the experienc

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… Two Paths Not Taken Two years before the publication of Little’s ( 1974 ) survey of amputees, a Scottish epidemiologist authored an influential report (Cochrane 1972 ) that would, in time, lead to his anointment as the founding figure of evidence-based medicine (EBM). … According to a leading advocate, “most clinicians ignored or dismissed these attempts to communicate” (Chase 1999 , 452). Relations between ISNA and the medical profession improved as critics inside and outside the profession, including bioethicists, gave the complaints due attention. …