A wearable electrochemical biosensor for real-time monitoring of neurotransmitters in sweat during physical exercise is presented. The biosensor utilizes a CuMOF@InMOF architecture, enhanced with gold nanoparticles (AuNPs), to improve electron transfer, surface area, and overall stability. Thiolate nucleic acid aptamers, highly specific to dopamine, serotonin, and epinephrine, are immobilized on the biosensor surface, enabling precise and simultaneous detection of these key neurotransmitters. The flexible, multi-electrode platform is integrated into a microfluidic patch that adheres to the skin, facilitating seamless sweat collection and continuous neurochemical analysis. Structural validation confirmed the successful synthesis of the CuMOF@InMOF architecture with enhanced surface area, stability, and electron transfer properties, contributing to the biosensor's high sensitivity and selectivity. Impressively, the biosensor achieved detection limits of 0.18 nM for dopamine, 0.33 nM for serotonin, and 0.27 nM for epinephrine, with a broad dynamic range from 1 nM to 10 µM. Performance was validated through square wave voltammetry and amperometry, demonstrating exceptional sensitivity, selectivity, and stability. This innovative biosensor offers a powerful tool for non-invasive, real-time neurochemical monitoring, with significant potential in personalized healthcare.

Decreased expression of sirtuin 1 (SirT1) has been implicated in Alzheimer's disease (AD), and as we previously reported, is related to transcriptional repression by the major risk factor for sporadic AD, apolipoprotein E4 (ApoE4). Herein we describe the discovery of an orally brain-permeable small-molecule, DDL-218, that enhanced SirT1 in ApoE4-expressing neuronal cells and a murine AD model. DDL-218 increased the transcription factor NFYb resulting in upregulation of PRMT5. Mechanistic and modeling studies show that binding of ApoE4 to the SirT1 gene promoter can be displaced by PRMT5 leading to increased SirT1 transcription. DDL-218 treatment elicited improvement in memory in the AD model, suggesting that DDL-218 enhancement of neurotrophic SirT1 in the brain has potential to modulate neuronal activity that may clinically provide an improvement in cognitive function and complement the current anti-Aβ antibody monotherapy. Our findings support further development of DDL-218 as a novel ApoE4-targeted therapeutic candidate for AD.

Carbon dots (CDs) are new types of fluorescent nanomaterials with particle diameters of 1∼10 nm and have excellent photoluminescence (PL) properties, good biocompatibility, simple preparation methods and numerous raw materials; consequently, they are promising in the biomedical field. In recent years, to overcome drug resistance and toxic side effects of traditional organic drugs, the synthesis of CDs from drug molecules has become an effective strategy, which produces CDs with the same therapeutic effects as the raw drugs and even possessing new properties. At present, many CDs derived from organic drugs have been developed, which can be classified according to their sources such as antibiotics, anti-inflammatory drugs, and guanidine drugs. This article focuses on the progress of the above-mentioned drug-derived CDs compared with their drug precursors in terms of therapeutic efficacy, enhanced performance and new additional functions, with special attention to the structure-activity relationship between the drug precursors and the CD-based therapeutic agents. It demonstrates the feasibility of designing new drug-derived CDs for clinical applications, summarizes the shortcomings and research gaps of the existing work, and provides a reference for related work in the future.

Implantable cardioverter-defibrillators (ICDs) are recommended to reduce the risk of sudden cardiac death (SCD) in patients with heart failure with reduced ejection fraction (HFrEF). The landmark studies leading to the current guideline recommendations preceded the 4 pillars of guideline-directed medical therapies (GDMTs). Therefore, some have questioned the role of ICDs for primary prevention in current clinical practice. In this paper, the authors provide an overview of the current ICD recommendations, including the instrumental clinical trials, the risk of SCD as observed in clinical trials vs real-world scenarios, disparities in ICD use among different patient populations, the impact of contemporary GDMT on outcomes, and ongoing and future trials and methodologies to help identify patients who are at an increased risk of SCD and who may benefit from an ICD. The authors also propose a pragmatic guidance for clinicians when they engage in the shared decision-making discussions for primary ICD implantation.

The prevalence of morbid obesity in today's population around the world is alarming. Morbid obesity involves substantial changes in body composition and function, which can affect the pharmacodynamics and pharmacokinetics of many drugs. This paper aims to discuss the application of muscle relaxants and their reversing agents in patients with morbid obesity. This work is based both on the available literature and the author's personal experience. Dosage recommendations for muscle relaxants in morbidly obese patients are as follows: non-depolarizing relaxants like rocuronium, vecuronium, atracurium, and cisatracurium should be based on ideal body weight. Succinylcholine dosage should be adjusted to total body weight with a 200 mg maximum, while mivacurium should also be based on total body weight. Pancuronium is not used due to its long duration. Neostigmine dosing remains uncertain, but some suggest using total body weight. When it comes to Sugammadex opinions of the authors are divided, some indicate that it should be dosed based on ideal body weight, but more recent studies show that it should be based on 40% of corrected body weight.

Kidney disease is a critical and potentially life-threatening degenerative condition that poses a significant global public health challenge due to its elevated rates of morbidity and mortality. It manifests primarily in two distinct clinical forms: acute kidney injury (AKI) and chronic kidney disease (CKD). The development of these conditions hinges on a multitude of factors, including the etiological agents and the presence of coexisting medical conditions. Despite disparities in their underlying pathogenic mechanisms, both AKI and CKD can progress to end-stage kidney disease (ESKD). This advanced stage is characterized by organ failure and its associated complications, greatly increasing the risk of mortality. There is an urgent need to delve into the pathogenic mechanisms underlying these diseases and to identify novel biomarkers that can facilitate earlier diagnosis. Such early detection is crucial for enhancing the efficacy of therapy and impeding disease progression. In this context, proteomic approaches have emerged as invaluable tools for uncovering potential new markers of different pathological conditions, including kidney diseases. In this chapter, we overview the recent discoveries achieved through diverse proteomic techniques aimed at identifying novel molecules that may play a pivotal role in kidney diseases such as diabetic kidney disease (DKD), IgA nephropathy (IgAN), CKD of unknown origin (CKDu), autosomal dominant polycystic kidney disease (ADPKD), lupus nephritis (LN), hypertensive nephropathy (HN), and COVID-19-associated acute kidney injury (COVID-AKI).

Observational findings achieved during the past two decades suggest that the intestinal microbiota may contribute to the metabolic health of the human host and, when aberrant, to the pathogenesis of various common metabolic disorders including obesity, type 2 diabetes, non-alcoholic liver disease, cardio-metabolic diseases and malnutrition. However, to gain a mechanistic understanding of how the gut microbiota affects host metabolism, research is moving from descriptive microbiota census analyses to cause-and-effect studies. Joint analyses of high-throughput human multi-omics data, including metagenomics and metabolomics data, together with measures of host physiology and mechanistic experiments in humans, animals and cells hold potential as initial steps in the identification of potential molecular mechanisms behind reported associations. In this Review, we discuss the current knowledge on how gut microbiota and derived microbial compounds may link to metabolism of the healthy host or to the pathogenesis of common metabolic diseases. We highlight examples of microbiota-targeted interventions aiming to optimize metabolic health, and we provide perspectives for future basic and translational investigations within the nascent and promising research field.

Functional capacity is an important component of risk assessment for major surgery. Doctors' clinical subjective assessment of patients' functional capacity has uncertain accuracy. We did a study to compare preoperative subjective assessment with alternative markers of fitness (cardiopulmonary exercise testing [CPET], scores on the Duke Activity Status Index [DASI] questionnaire, and serum N-terminal pro-B-type natriuretic peptide [NT pro-BNP] concentrations) for predicting death or complications after major elective non-cardiac surgery.

Stigma is one of the greatest obstacles to care and impedes recovery. The Stigma Scale for Receiving Professional Psychological Help (SSRPH), a measure of public stigma, has been used in young adults and has limited psychometric data in adolescents. This article reports the reliability and validity of the SSRPH in adolescent girls (N = 156, age = 13-17). Discriminant validity was supported, but concurrent validity was not. The confirmatory factor analysis revealed excellent model fit and serves as beginning evidence for construct validity. Cronbach's alpha for the SSRPH was .65. The SSRPH was stable over 8 weeks. Findings suggest that the SSRPH can serve as a foundation for further instrument development. Future studies may explore enhancing the reliability and validity of the SSRPH and use advanced analytic techniques to examine the overall global construct of stigma, the latent constructs of public and private stigma, and associations of individual items to these constructs.