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Statins are an important but underutilized therapy to prevent cardiovascular events, particularly in high-risk patients. To increase use of statin therapy in high-risk patients, the Centers for Disease Control and Prevention funded a project led by the National Association of Community Health Centers to discover reasons for statin underuse in health centers and identify possible leverage points, particularly among vulnerable and underserved patients. The project further sought to develop training and educational materials to improve statin prescribing for and acceptance in eligible high-risk patients. As a first step, investigators implemented a questionnaire to clinical providers (n = 45) at health centers participating in the project to obtain their perspective on barriers to optimal statin use. We used the practical robust implementation and sustainability model (PRISM) domains to frame the overall project and guide the development of our questionnaire. This paper summarizes top perceived barriers to patient and health system/provider statin initiation and sustainment, as well as facilitators to prescribing, using PRISM as an organizing framework. Our questionnaire yielded important suggestions related to public awareness, education materials, health information technology (HIT)/data solutions, and clinical guidelines as key factors in optimizing statin use. It also informed the design of patient education resources and provider training tools. Future directions include using the full application of the PRISM implementation science model to assess how well our educational and training resources help overcome barriers to statin use in high-risk patients, including evaluating how key contextual factors influence successful implementation. [ABSTRACT FROM AUTHOR]

Issue: Noting high rates of burnout, depression, and suicidality among medical students, academic medical communities are trying to identify preventive and curricular measures that protect and promote student well-being. To date, the effectiveness of these efforts is unclear. In addition, evidence increasingly suggests that the major drivers of distress appear to be factors within the social, learning, and work environments. Specific to medical schools in the United States, neither the Liaison Committee on Medical Education nor the Commission on Osteopathic College Accreditation include accreditation standards regarding well-being curricula and, as such, these curricula are not well-integrated into students' medical school experience. Current accreditation standards also do not specifically require institutions to assess or address systemic factors of the learning environment that negatively affect student well-being. Evidence: This paper proposes expanding current Liaison Committee on Medical Education and Commission on Osteopathic College Accreditation standards on professionalism to incorporate well-being as a core component of professional identity formation by requiring individual and institutional-level actions. Proposed changes to accreditation standards include (1) institutional assessment of the impact of the learning environment on student well-being; (2) continuous quality improvement efforts to address structural factors associated with student well-being and modification of practices that impair student well-being; and (3) integrated curriculum with related assessment to educate students on empirically-supported strategies for well-being. Implications: Refining undergraduate medical education accreditation standards in the United States to include language specific to student well-being will facilitate long overdue changes to the learning environment. In the end, the goal is not just to improve medical student well-being, but to provide a workforce better equipped for a sustainable and meaningful career. [ABSTRACT FROM AUTHOR]

Phagocytosis is a rapid actin-dependent endocytic process used by macrophages and neutrophils to ingest and kill microorganisms . Perturbation of phagocytosis is central to the ability of some pathogenic microbes to cause disease, and we demonstrated previously that the ulcerogenic bacterium Helicobacter pylori (Hp) actively retards its uptake by macrophages and subsequently persists inside novel vacuoles called megasomes . Neither the receptor that mediates Hp binding nor the signaling pathways that regulate bacterial engulfment have been defined. Nevertheless, the fact that other phagocytic stimuli do not exhibit delayed phagocytosis suggests that Hp may be ingested by a unique mechanism. We now show that Hp transiently activated protein kinase C (PKC) in macrophages and that atypical PKCζ and novel PKC∊, but not conventional PKCα, accumulated on forming phagosomes. Pharmacologic agents, isoform-selective pseudosubstrate peptides, and antisense oligonucleotides demonstrated that PKCζ regulated local actin polymerization and bacterial engulfment, whereas other PKC isoforms did not. In contrast, opsonization of Hp with immunoglobulin G (IgG) induced rapid PKCζ-independent uptake and enhanced killing of ingested bacteria. A role for atypical PKCs in phagocytosis has not been described. We conclude that Hp defines a new phagocytic pathway in macrophages that is regulated by PKCζ. [Copyright &y& Elsevier]

Merkel cell cancer (MCC) is a rare cutaneous malignancy arising from neuroendocrine cells. This rare but lethal malignancy (mortality greater than 30%) has also tripled in incidence over the last two decades. The role of immunodeficiency in pathogenesis of this rare malignancy is well established, with elucidation of viral pathogenesis by Merkel cell polyoma virus (MCPyV), a novel polyoma virus, in a majority of patients. Viral neoantigens while playing an important role in oncogenesis can also aid in early immunologic detection of recurrent disease. Viral neoantigens can also be targets for immunotherapy. Immune checkpoint inhibitors (ICI) have established role in frontline therapy in addition to recurrence of metastatic MCC. ICI therapy is being explored in adjuvant and neoadjuvant settings as well. We would like to illustrate curative potential of early diagnosis of recurrence and prompt use of ICI in treatment of oligometastatic disease in our case presentation.

Background and Objectives: Current productivity assessment models lack the ability to measure the quality of pharmacy services through workload validation. The goal of our efforts was to create a model to more accurately assess workload at multiple outpatient infusion centers., Method: Current procedural terminology codes were identified as representative of the key drivers of pharmacy workload. Fourteen current procedural terminology codes representing medication orders were selected and categorized into eight distinctive groups associated with varying amounts of pharmacy workload. A three-month average of current procedural terminology volumes were calculated and used to create a workload baseline., Results: Our study found a usable productivity assessment and coefficient to compare relevant clinical workload across outpatient oncology sites. The current procedural terminology codes were readily retrievable from our system electronic medical record. By assigning activities, e.g. clinical review, verification, barcoding, batch preparation, we were able to compute a workload and then adjust staffing to achieve a median coefficient across sites., Discussion: This study evaluated the use of administration current procedural terminology codes for an outpatient oncology productivity model. Based upon our analysis, it can be successfully used to determine workload for pharmacists and technicians across variable locations. We believe it is the first study to demonstrate a productivity model for this setting.

We evaluated a preliminary method for examining the antecedent and consequent contributions to noncompliance exhibited by two children with disabilities. In Phase 1, we assessed whether noncompliance was a result of a skill deficit. For one participant, we then conducted a functional analysis to determine the variables maintaining noncompliance in Phase 2. In Phase 3, we conducted a treatment evaluation to increase compliance for each participant. We identified the antecedent and consequent variables responsible for noncompliance and developed an effective intervention for both participants., (© 2016 Society for the Experimental Analysis of Behavior.)

JOURNAL/nrgr/04.03/01300535-202504000-00033/figure1/v/2024-07-06T104127Z/r/image-tiff Behavioral recovery using (viable) peripheral nerve allografts to repair ablation-type (segmental-loss) peripheral nerve injuries is delayed or poor due to slow and inaccurate axonal regeneration. Furthermore, such peripheral nerve allografts undergo immunological rejection by the host immune system. In contrast, peripheral nerve injuries repaired by polyethylene glycol fusion of peripheral nerve allografts exhibit excellent behavioral recovery within weeks, reduced immune responses, and many axons do not undergo Wallerian degeneration. The relative contribution of neurorrhaphy and polyethylene glycol-fusion of axons versus the effects of polyethylene glycol per se was unknown prior to this study. We hypothesized that polyethylene glycol might have some immune-protective effects, but polyethylene glycol-fusion was necessary to prevent Wallerian degeneration and functional/behavioral recovery. We examined how polyethylene glycol solutions per se affect functional and behavioral recovery and peripheral nerve allograft morphological and immunological responses in the absence of polyethylene glycol-induced axonal fusion. Ablation-type sciatic nerve injuries in outbred Sprague-Dawley rats were repaired according to a modified protocol using the same solutions as polyethylene glycol-fused peripheral nerve allografts, but peripheral nerve allografts were loose-sutured (loose-sutured polyethylene glycol) with an intentional gap of 1-2 mm to prevent fusion by polyethylene glycol of peripheral nerve allograft axons with host axons. Similar to negative control peripheral nerve allografts not treated by polyethylene glycol and in contrast to polyethylene glycol-fused peripheral nerve allografts, animals with loose-sutured polyethylene glycol peripheral nerve allografts exhibited Wallerian degeneration for all axons and myelin degeneration by 7 days postoperatively and did not recover sciatic-mediated behavioral functions by 42 days postoperatively. Other morphological signs of rejection, such as collapsed Schwann cell basal lamina tubes, were absent in polyethylene glycol-fused peripheral nerve allografts but commonly observed in negative control and loose-sutured polyethylene glycol peripheral nerve allografts at 21 days postoperatively. Loose-sutured polyethylene glycol peripheral nerve allografts had more pro-inflammatory and less anti-inflammatory macrophages than negative control peripheral nerve allografts. While T cell counts were similarly high in loose-sutured-polyethylene glycol and negative control peripheral nerve allografts, loose-sutured polyethylene glycol peripheral nerve allografts expressed some cytokines/chemokines important for T cell activation at much lower levels at 14 days postoperatively. MHCI expression was elevated in loose-sutured polyethylene glycol peripheral nerve allografts, but MHCII expression was modestly lower compared to negative control at 21 days postoperatively. We conclude that, while polyethylene glycol per se reduces some immune responses of peripheral nerve allografts, successful polyethylene glycol-fusion repair of some axons is necessary to prevent Wallerian degeneration of those axons and immune rejection of peripheral nerve allografts, and produce recovery of sensory/motor functions and voluntary behaviors. Translation of polyethylene glycol-fusion technologies would produce a paradigm shift from the current clinical practice of waiting days to months to repair ablation peripheral nerve injuries., (Copyright © 2025 Copyright: © 2025 Neural Regeneration Research.)

BACKGROUND: The 13q-deletion syndrome causes human congenital birth defects due to the loss of regions of one long arm of human chromosome 13. A distal critical region for severe genitourinary and anorectal birth defects in the region of 13q32.2-34 has been suggested; we sought to narrow this critical region. METHODS: From patients with karyotypes revealing haploinsufficiency for distal chromosome 13q and their parents, peripheral blood was obtained and lymphocytes were immortalized for DNA isolation. Genetic and molecular cytogenetic methods were used to map deletions. Patient and parental samples were genotyped with a panel of 20 microsatellite markers spanning 13q31.3 qter and deletions identified by loss of heterozygosity. Deletions were also mapped using a panel of 35 BAC clones from the same region as probes for fluorescence in-situ hybridization on patient lymphoblastoid metaphase preparations. The data were synthesized and a deletion map defining the critical region was generated. RESULTS: Eight patients with known deletions around 13q32qter and their parents were analyzed, and categorized into three groups: three patients with anorectal and genitourinary anomalies (hypospadias, penoscrotal transposition), four male patients without anorectal and genitourinary anomalies, and one XY patient with ambiguous genitalia without anorectal anomalies. We mapped the critical region for anorectal and genitourinary anomalies to a approximately 9.5-Mb interval of 13q33.3-q34 delineated by markers D13S280-D13S285; this spans approximately 8% of the chromosome and contains 20 annotated genes CONCLUSION: The critical region of chromosome 13q mediating genitourinary/anorectal anomalies has been mapped, and will be narrowed by additional patients and further mapping. Identification of the gene(s) mediating these syndromic genitourinary defects should further our knowledge of molecular mediators of non-syndromic hypospadias, penoscrotal transposition and anorectal malformations.

Medicinal plants may carry residuals of environmentally persistent pesticides or assimilate heavy metals in varying degrees. Several factors may influence contaminant accumulation, including species, level and duration of contaminant exposure, and topography. As part of a program for assessment of the quality of herbal medicines, we have analyzed 21 over-the-counter ginseng (Panax ginseng) products in various dosage forms. Chromium, mercury, and arsenic were undetectable above their limits of detection in both liquid and solid samples; while cadmium, lead, and nickel were present in the majority of samples. The chlorinated pesticide levels varied widely. In most samples, the total concentration of pesticides was below 100 ppb; while in 5 samples the total concentration exceeded 100 ppb.

Sediments and/or fish were collected from Sardis, Enid and Grenada Lakes, which are located in three different watersheds in North Mississippi, in order to assess mercury contamination. The mean total mercury concentration in sediments from Enid Lake in 1997 was 0.154 mg Hg/kg, while 1998 sediment concentrations in Sardis, Enid and Grenada Lakes were 0.112, 0.088 and 0.133 mg Hg/kg, respectively. Sediment mercury concentrations in 1999 were similar in all three lakes but, generally lower than 1998. Mean total mercury concentrations in edible fillets of fish collected from Enid Lake in 1998 were above the human health FDA action level (> 1.0 mg Hg/kg) for bass (1.40), crappie (1.69) and gar (1.89); however, tissue concentrations were less than 1.0 mg Hg/kg in carp (0.63) and catfish (0.82). Human hazard indexes for each species was > or = 1 for both adults and children, indicating that there is a potential for toxic effects to occur. In addition, calculated consumption limits indicate that adults may consume 4-12 oz. of fish per month, depending on the species consumed. For children, 2 oz. per month may be consumed. Further studies are needed to determine the exact environmental consequences and human health impacts associated with mercury contamination in North Mississippi and the Southeastern United States.