Exploring Mucoadhesive and Toxicological Characteristics Following Modification of Linear Polyethylenimine with Various Anhydrides.

Linear polyethylenimine (L-PEI) has numerous applications, such as in pharmaceutical formulations, gene delivery, and water treatment. However, due to the presence of secondary amine groups, L-PEI shows a relatively high toxicity and low biocompatibility. Here, various organic anhydrides were used to modify L-PEI to reduce its toxicity and enhance its functionality. We selected methacrylic anhydride, crotonic anhydride, maleic anhydride, and succinic anhydride to modify L-PEI. The structure of the resulting derivatives was characterized using 1H NMR and FTIR spectroscopies, and their behavior in aqueous solutions was studied using turbidimetric and electrophoretic mobility measurements over a broad range of pHs. A fluorescence flow through method determined the mucoadhesive properties of the polymers to the bovine palpebral conjunctiva. Methacrylated L-PEI and crotonylated L-PEI showed strong mucoadhesive properties at pH 7.4, likely due to covalent bonding with mucin thiol groups. In contrast, maleylated and succinylated L-PEI were poorly mucoadhesive as the pH was above their isoelectric point, resulting in electrostatic repulsion between the polymers and mucin. The toxicity of these polymers was evaluated using in vivo assays with planaria and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) cell viability assay in human alveolar epithelial cells. Moreover, the irritancy of polymers was assessed using a slug mucosa irritation assay. The results demonstrated that anhydride modification mitigated the adverse toxicity effects seen for parent L-PEI.

Detecting early signs of deterioration and preventing hospitalizations in skilled nursing facilities using remote respiratory monitoring.

An increase in respiratory rate (RR) can be an early indicator of clinical deterioration, yet it remains an often-neglected vital sign. The most common way of measuring RR is by manually counting chest-wall movements, a time-consuming and error-prone process. Staffing and funding shortages, particularly in post-acute and long-term care, mean these RR measurements are often infrequent, potentially leading to missed diagnoses and preventable readmissions. Here we present a case series from skilled nursing facilities, highlighting how continuous respiratory monitoring using a contactless remote patient monitoring (RPM) system can support clinicians in initiating timely interventions, potentially reducing preventable hospitalizations, mortality, and associated financial implications.

Topically Applied Therapies for the Treatment of Skin Disease: Past, Present, and Future.

The purpose of this review is to summarize essential biological, pharmaceutical, and clinical aspects in the field of topically applied medicines that may help scientists when trying to develop new topical medicines. After a brief history of topical drug delivery, a review of the structure and function of the skin and routes of drug absorption and their limitations is provided. The most prevalent diseases and current topical treatment approaches are then detailed, the organization of which reflects the key disease categories of autoimmune and inflammatory diseases, microbial infections, skin cancers, and genetic skin diseases. The complexity of topical product development through to large-scale manufacturing along with recommended risk mitigation approaches are then highlighted. As such topical treatments are applied externally, patient preferences along with the challenges they invoke are then described, and finally the future of this field of drug delivery is discussed, with an emphasis on areas that are more likely to yield significant improvements over the topical medicines in current use or would expand the range of medicines and diseases treatable by this route of administration. SIGNIFICANCE STATEMENT: This review of the key aspects of the skin and its associated diseases and current treatments along with the intricacies of topical formulation development should be helpful in making judicious decisions about the development of new or improved topical medicines. These aspects include the choices of the active ingredients, formulations, the target patient population's preferences, limitations, and the future with regard to new skin diseases and topical medicine approaches.

On the mucoadhesive properties of synthetic and natural polyampholytes.

HYPOTHESIS: The mucoadhesive characteristics of amphoteric polymers (also known as polyampholytes) can vary and are influenced by factors such as the solution's pH and its relative position against their isoelectric point (pHIEP). Whilst the literature contains numerous reports on mucoadhesive properties of either cationic or anionic polymers, very little is known about these characteristics for polyampholytes EXPERIMENTS: Here, two amphoteric polymers were synthesized by reaction of linear polyethylene imine (l-PEI) with succinic or phthalic anhydride and their mucoadhesive properties were compared to bovine serum albumin (BSA), selected as a natural polyampholyte. Interactions between these polymers and porcine gastric mucin were studied using turbidimetric titration and isothermal titration calorimetry across a wide range of pHs. Model tablets were designed, coated with these polymers and tested to evaluate their adhesion to porcine gastric mucosa at different pHs. Moreover, a retention study using fluorescein isothiocyanate (FITC)-labelled polyampholytes deposited onto mucosal surfaces was also conducted FINDINGS: All these studies indicated the importance of solution pH and its relative position against pHIEP in the mucoadhesive properties of polyampholytes. Both synthetic and natural polyampholytes exhibited strong interactions with mucin and good mucoadhesive properties at pH < pHIEP.

Association between psychosocial factors and C-reactive protein across income, race, and sex.

OBJECTIVE: A health disparity is a health difference that adversely affects disadvantaged populations, and thus could plausibly be due to social factors. Biopsychosocial processes that contribute to health disparities are not well-understood. Establishing whether candidate biomarkers are similarly associated with biologically relevant psychosocial constructs across health disparity groups is a current gap in our understanding. METHOD: This study examined associations between perceived stress, depressive symptoms, and social support with C-reactive protein (CRP) and whether associations varied by race, sex, or income in 24,395 Black and White adults aged 45 years or older from the REGARDS population-based national cohort. RESULTS: The association between depressive symptoms and CRP was slightly larger at higher (vs. lower) income levels and larger for men (vs. women) but did not vary by race. Associations between stress and CRP and social support and CRP were not moderated by income, race, or sex. An interaction between race and income, evidenced that higher income was more strongly associated with lower CRP in White participants compared to Black participants, consistent with the idea of "diminishing returns" of income for the health of Black Americans. CONCLUSIONS: Basic associations between these psychosocial factors and CRP are small and generally similar across income, race, and sex. Black and lower-income Americans likely evidence higher CRP due to greater exposure to psychosocial risk factors rather than increased biological vulnerability to these exposures. Additionally, given small associations, CRP should not be used as a proxy for the construct of psychosocial stress. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Pellagra: 4 D's and 8 Points.

Pellagra has largely been forgotten. This is unfortunate as important lessons are to be learnt for the diseases and social consequences of poverty (and of affluence) that often involve dietary nicotinamide and nicotinamide adenine dinucleotide (NAD) homeostasis. NAD disruption can occur not only from poor diet but from increased consumption of NAD from genotoxic and other stresses. High doses of nicotinamide lead to inhibition of NAD-consuming enzymes and excessive induction of nicotinamide-n-methyl transferase (NNMT) with consequent effects on the methylome giving a mechanism for a new hypervitaminosis-B3.