Elements of Weight Management Among Pre-Kidney Transplant Candidates: The Patient Perspective.

Obesity and related comorbidities heighten risks for complications in kidney transplant settings. While pre-transplant patients often have access to nutrition counseling and health support, literature is limited on patients' perceptions of weight and motivation to lose weight prior to transplantation. We conducted a survey among ≥18-year-old patients on the kidney transplant waitlist at a single center. Questions addressed weight perception, motivation for weight loss, available resources, and engagement in physical activity. Medical records provided demographic and clinical data. Statistical tests analyzed quantitative data, while free-text responses were thematically grouped and described. Of 1055 patients, 291 responded and were matched with demographic data. Perceived weight changes correlated with actual changes in body mass index (BMI) (<24.9) were more receptive to weight center resources (<30 kg/m2) are most interested in weight loss resources and demonstrate motivation. Furthermore, pre-transplant nutrition counseling correlates with healthier behaviors. Integrating patients' perspectives enhances pre-transplant protocols by encouraging active involvement in health decisions.

Emerging Approaches to Functionalizing Cell Membrane-Coated Nanoparticles.

There has been significant interest in developing cell membrane-coated nanoparticles due to their unique abilities of biomimicry and biointerfacing. As the technology progresses, it becomes clear that the application of these nanoparticles can be drastically broadened if additional functions beyond those derived from the natural cell membranes can be integrated. Herein, we summarize the most recent advances in the functionalization of cell membrane-coated nanoparticles. In particular, we focus on emerging methods, including (1) lipid insertion, (2) membrane hybridization, (3) metabolic engineering, and (4) genetic modification. These approaches contribute diverse functions in a nondisruptive fashion while preserving the natural function of the cell membranes. They also improve on the multifunctional and multitasking ability of cell membrane-coated nanoparticles, making them more adaptive to the complexity of biological systems. We hope that these approaches will serve as inspiration for more strategies and innovations to advance cell membrane coating technology.

Catalytic Effects of Ammonium and Sulfonium Salts and External Electric Fields on Aza-Diels-Alder Reactions.

The mechanism of the aza-Diels-Alder reaction catalyzed by tetraalkylammonium or trialkylsulfonium salts is explored with density functional theory. Favorable electrostatic interactions between the dienophile and the charged catalyst stabilize the highly polar transition state, leading to lower free energy barriers and higher dipole moments. Endo selectivity is predicted for both uncatalyzed and catalyzed systems. We also computationally evaluate the effects of oriented external electric fields (EEFs) on the same aza-Diels-Alder reaction, demonstrating that very strong EEFs would be needed to achieve the catalytic strength of these cationic catalysts.

Inkjet-Printed Molybdenum Disulfide and Nitrogen-Doped Graphene Active Layer High On/Off Ratio Transistors.

Fully inkjet-printed device fabrication is a crucial goal to enable large-area printed electronics. The limited number of two-dimensional (2D) material inks, the bottom-gated structures, and the low current on/off ratio of thin-film transistors (TFTs) has impeded the practical applications of the printed 2D material TFTs. In the search for TFTs with high current ratios, we introduce a stable and efficient method of nitrogen-doped graphene (NDG) ink preparation for inkjet printing by liquid-phase exfoliation. The NDG thin film is print-stacked with molybdenum disulfide (MoS2) by multiple printing passes to construct a MoS2-NDG stack. We demonstrate top-gated fully inkjet-printed MoS2-NDG transistors with silver drain, source, and gate electrodes, and a barium titanate (BaTiO3) dielectric. A 100% inkjet-printed MoS2-NDG vertical 2D active heterostructure layer transistor with a current on/off ratio of 1200 is exhibited. The results may lead towards the development of all-printed 2D material-based transistor switches.

Mechanism and Regioselectivity of an Unsymmetrical Hexadehydro-Diels-Alder (HDDA) Reaction.

Hoye reported intramolecular hexadehydro-Diels-Alder (HDDA) reactions to generate arynes that functionalize natural product phenols and amines. In their studies, Hoye found that unsymmetrical tetraynes selectively form a single aryne. We report density functional theory (DFT) calculations that reveal the factors controlling the regioselectivity.

Evaluation of statistical methods for safety signal detection: a simulation study.

Proactive evaluation of drug safety with systematic screening and detection is critical to protect patients' safety and important in regulatory approval of new drug indications and postmarketing communications and label renewals. In recent years, quite a few statistical methodologies have been developed to better evaluate drug safety through the life cycle of the product development. The statistical methods for flagging safety signals have been developed in two major areas - one for data collected from spontaneous reporting system, mostly in the postmarketing area, and the other for data from clinical trials. To our knowledge, the methods developed for one area have not been applied to the other one so far. In this article, we propose to utilize all such methods for flagging safety signals in both areas regardless of which specific area they were originally developed for. Therefore, we selected eight typical methods, that is, proportional reporting ratios, reporting odds ratios, the maximum likelihood ratio test, Bayesian confidence propagation neural network method, chi-square test for rates comparison, Benjamini and Hochberg procedure, new double false discovery rate control procedure, and Bayesian hierarchical mixture model for systematic comparison through simulations. The Benjamini and Hochberg procedure and new double false discovery rate control procedure perform best overall in terms of sensitivity and false discovery rate. The likelihood ratio test also performs well when the sample sizes are large.

Value of information methods for assessing a new diagnostic test.

Value-of-information methods are applied to assess the evidence in support of a new diagnostic test and, where the evidence is insufficient for decision making, to determine the optimal sample size for future studies. Net benefit formulations are derived under various diagnostic and treatment scenarios. The expressions for the expected opportunity loss of adopting strategies that include the new test are given. Expressions for the expected value of information from future studies are derived. One-sample and two-sample designs, with or without known prevalence, are considered. An example is given.

Effectiveness of quality improvement strategies for coordination of care to reduce use of health care services: a systematic review and meta-analysis.

BACKGROUND: Frequent users of health care services are a relatively small group of patients who account for a disproportionately large amount of health care utilization. We conducted a meta-analysis of the effectiveness of interventions to improve the coordination of care to reduce health care utilization in this patient group. METHODS: We searched MEDLINE, Embase and the Cochrane Library from inception until May 2014 for randomized clinical trials (RCTs) assessing quality improvement strategies for the coordination of care of frequent users of the health care system. Articles were screened, and data abstracted and appraised for quality by 2 reviewers, independently. Random effects meta-analyses were conducted. RESULTS: We identified 36 RCTs and 14 companion reports (total 7494 patients). Significantly fewer patients in the intervention group than in the control group were admitted to hospital (relative risk [RR] 0.81, 95% confidence interval [CI] 0.72-0.91). In subgroup analyses, a similar effect was observed among patients with chronic medical conditions other than mental illness, but not among patients with mental illness. In addition, significantly fewer patients 65 years and older in the intervention group than in the control group visited emergency departments (RR 0.69, 95% CI 0.54-0.89). INTERPRETATION: We found that quality improvement strategies for coordination of care reduced hospital admissions among patients with chronic conditions other than mental illness and reduced emergency department visits among older patients. Our results may help clinicians and policy-makers reduce utilization through the use of strategies that target the system (team changes, case management) and the patient (promotion of self-management).

Photodynamic Therapy in Treating a Subset of Basal Cell Carcinoma: Strengths, Shortcomings, Comparisons with Surgical Modalities, and Potential Role as Adjunctive Therapy.

Basal cell carcinoma (BCC) is the most common skin cancer, for which there are multiple treatment options, including the gold standard Mohs micrographic surgery (MMS), surgical excision, electrodesiccation and curettage, radiation therapy, cryosurgery, and photodynamic therapy (PDT). While PDT is currently approved for treating actinic keratosis, it has been used off-label to treat BCC patients who may not tolerate surgery or other treatment modalities. We present a review of the efficacy of these modalities and describe important considerations that affect the usage of PDT and MMS. ALA-PDT and MAL-PDT are both efficacious treatment options for lower-risk BCC that can serve as non-invasive alternatives to surgical excision with favorable cosmetic outcomes in patients unsuitable to undergo surgery. In particular, PDT may be considered an adjuvant for the prevention and treatment of BCC lesions in patients with some genetic syndromes such as Gorlin syndrome, and in combination with surgical excision in lesions presenting in certain locations. Limitations to PDT include lack of margin control to prevent recurrence, pain, and cost of certain photosensitizers. Future studies should investigate the role of PDT as adjunctive therapy, standardization of protocols, and causes and ways to address recurrence following PDT treatment.

Ethics of artificial intelligence in dermatology.

The integration of artificial intelligence (AI) in dermatology holds promise for enhancing clinical accuracy, enabling earlier detection of skin malignancies, suggesting potential management of skin lesions and eruptions, and promoting improved continuity of care. AI implementation in dermatology, however, raises several ethical concerns. This review explores the current benefits and challenges associated with AI integration, underscoring ethical considerations related to autonomy, informed consent, and privacy. We also examine the ways in which beneficence, nonmaleficence, and distributive justice may be impacted. Clarifying the role of AI, striking a balance between security and transparency, fostering open dialogue with our patients, collaborating with developers of AI, implementing educational initiatives for dermatologists and their patients, and participating in the establishment of regulatory guidelines are essential to navigating ethical and responsible AI incorporation into dermatology.

Fillable Magnetic Microrobots for Drug Delivery to Cardiac Tissues In Vitro.

Many cardiac diseases, such as arrhythmia or cardiogenic shock, cause irregular beating patterns that must be regulated to prevent disease progression toward heart failure. Treatments can include invasive surgery or high systemic drug dosages, which lack precision, localization, and control. Drug delivery systems (DDSs) that can deliver cargo to the cardiac injury site could address these unmet clinical challenges. Here, a microrobotic DDS that can be mobilized to specific sites via magnetic control is presented. This DDS incorporates an internal chamber that can protect drug cargo. Furthermore, the DDS contains a tunable thermosensitive sealing layer that gradually degrades upon exposure to body temperature, enabling prolonged drug release. Once loaded with the small molecule drug norepinephrine, this microrobotic DDS modulated beating frequency in induced pluripotent stem-cell derived cardiomyocytes (iPSC-CMs) in a dose-dependent manner, thus simulating drug delivery to cardiac cells in vitro. The DDS also navigates several maze-like structures seeded with cardiomyocytes to demonstrate precise locomotion under a rotating low-intensity magnetic field and on-site drug delivery. This work demonstrates the utility of a magnetically actuating DDS for precise, localized, and controlled drug delivery which is of interest for a myriad of future opportunities such as in treating cardiac diseases.

Comparing influenza vaccine efficacy against mismatched and matched strains: a systematic review and meta-analysis.

BACKGROUND: Influenza vaccines are most effective when the antigens in the vaccine match those of circulating strains. However, antigens contained in the vaccines do not always match circulating strains. In the present work we aimed to examine the vaccine efficacy (VE) afforded by influenza vaccines when they are not well matched to circulating strains. METHODS: We identified randomized clinical trials (RCTs) through MEDLINE, EMBASE, the Cochrane Library, and references of included RCTs. RCTs reporting laboratory-confirmed influenza among healthy participants vaccinated with antigens of matching and non-matching influenza strains were included. Two independent reviewers screened citations/full-text articles, abstracted data, and appraised risk of bias. Conflicts were resolved by discussion. A random effects meta-analysis was conducted. VE was calculated using the following formula: (1 - relative risk × 100%). RESULTS: We included 34 RCTs, providing data on 47 influenza seasons and 94,821 participants. The live-attenuated influenza vaccine (LAIV) showed significant protection against mismatched (six RCTs, VE 54%, 95% confidence interval (CI) 28% to 71%) and matched (seven RCTs, VE 83%, 95% CI 75% to 88%) influenza strains among children aged 6 to 36 months. Differences were observed between the point estimates for mismatched influenza A (five RCTs, VE 75%, 95% CI 41% to 90%) and mismatched influenza B (five RCTs, VE 42%, 95% CI 22% to 56%) estimates among children aged 6 to 36 months. The trivalent inactivated vaccine (TIV) also afforded significant protection against mismatched (nine RCTs, VE 52%, 95% CI 37% to 63%) and matched (eight RCTs, VE 65%, 95% CI 54% to 73%) influenza strains among adults. Numerical differences were observed between the point estimates for mismatched influenza A (five RCTs, VE 64%, 95% CI 23% to 82%) and mismatched influenza B (eight RCTs, VE 52%, 95% CI 19% to 72%) estimates among adults. Statistical heterogeneity was low (I2 <50%) across all meta-analyses, except for the LAIV meta-analyses among children (I2 = 79%). CONCLUSIONS: The TIV and LAIV vaccines can provide cross protection against non-matching circulating strains. The point estimates for VE were different for matching versus non-matching strains, with overlapping CIs.

Efficacy and safety of cognitive enhancers for patients with mild cognitive impairment: a systematic review and meta-analysis.

BACKGROUND: Cognitive enhancers, including cholinesterase inhibitors and memantine, are used to treat dementia, but their effectiveness for mild cognitive impairment is unclear. We conducted a systematic review to examine the efficacy and safety of cognitive enhancers for mild cognitive impairment. METHODS: Our eligibility criteria were studies of the effects of donepezil, rivastigmine, galantamine or memantine on mild cognitive impairment reporting cognition, function, behaviour, global status, and mortality or harms. We identified relevant material by searching electronic databases (e.g., MEDLINE, Embase), the references of included studies, trial registries and conference proceedings, and by contacting experts. Two reviewers independently screened the results of the literature search, abstracted data and appraised risk of bias using the Cochrane risk-of-bias tool. RESULTS: We screened 15,554 titles and abstracts and 1384 full-text articles. Eight randomized clinical trials and 3 companion reports met our inclusion criteria. We found no significant effects of cognitive enhancers on cognition (Mini-Mental State Examination: 3 randomized clinical trials [RCTs], mean difference [MD] 0.14, 95% confidence interval [CI] -0.22 to 0.50; Alzheimer's Disease Assessment Scale - cognition subscale: 3 RCTs, standardized MD -0.07, 95% CI-0.16 to 0.01]) or function (Alzheimer's Disease Cooperative Study activities of daily living inventory: 2 RCTs, MD 0.30, 95% CI -0.26 to 0.86). Cognitive enhancers were associated with higher risks of nausea, diarrhea and vomiting than placebo. INTERPRETATION: Cognitive enhancers did not improve cognition or function among patients with mild cognitive impairment and were associated with a greater risk of gastrointestinal harms. Our findings do not support the use of cognitive enhancers for mild cognitive impairment.