The Importance of Continued Compliance with Completing Advance Directives in an Outpatient Setting

Despite continued efforts with conversation, guidelines, and even law, studies still show that the compliance with completing advance directives amongst a global patient population remains around 3 in 100. Those in compliance are more often chronically ill, over 65, or in an acute or terminal care setting. The COVID-19 pandemic is evidence that anything can happen and that helping patients adhere to medical wishes should be a top priority for primary care providers and their patients of all ages and health. Because previous studies have proven to be effective in increasing AD compliance when highlighted, this project aims to reignite the successful workflow of incorporating advance care planning into non-acute outpatient visits.https://scholarworks.uvm.edu/fmclerk/1913/thumbnail.jp

Duplicated Palmaris Longus Muscle With Insertion Onto The Transverse Carpal Ligament: A Case Report

The palmaris longus muscle is one of the most anatomically variable muscles in the human body, with incidence ranging from 0-63.9%.  While these anatomical variations are typically benign, they are of clinical importance as they can contribute to neurovascular and biomechanical dysfunction.  We report here a duplicated palmaris longus muscle with an insertion onto the transverse carpal ligament found during cadaveric dissection in a graduate anatomy course for physical and occupational therapy students.&nbsp

Ames hypopituitary dwarf mice demonstrate imbalanced myelopoiesis between bone marrow and spleen

Ames hypopituitary dwarf mice are deficient in growth hormone, thyroid-stimulating hormone, and prolactin. The phenotype of these mice demonstrates irregularities in the immune system with skewing of the normal cytokine milieu towards a more anti-inflammatory environment. However, the hematopoietic stem and progenitor cell composition of the bone marrow (BM) and spleen in Ames dwarf mice has not been well characterized. We found that there was a significant decrease in overall cell count when comparing the BM and spleen of 4-5 month old dwarf mice to their littermate controls. Upon adjusting counts to differences in body weight between the dwarf and control mice, the number of granulocyte-macrophage progenitors, confirmed by immunophenotyping and colony-formation assay was increased in the BM. In contrast, the numbers of all myeloid progenitor populations in the spleen were greatly reduced, as confirmed by colony-formation assays. This suggests that there is a shift of myelopoiesis from the spleen to the BM of Ames dwarf mice; however, this shift does not appear to involve erythropoiesis. The reasons for this unusual shift in spleen to marrow hematopoiesis in Ames dwarf mice are yet to be determined but may relate to the decreased hormone levels in these mice

Essential role of syntaxin-binding protein-1 in the regulation of glucagon-like peptide-1 secretion

Circadian secretion of the incretin, glucagon-like peptide-1 (GLP-1), correlates with expression of the core clock gene, Bmal1, in the intestinal L-cell. Several SNARE proteins known to be circadian in pancreatic α- and β-cells are also necessary for GLP-1 secretion. However, the role of the accessory SNARE, Syntaxin binding protein-1 (Stxbp1; also known as Munc18-1) in the L-cell is unknown. The aim of this study was to determine whether Stxbp1 is under circadian regulation in the L-cell and its role in the control of GLP-1 secretion. Stxbp1 was highly-enriched in L-cells, and STXBP1 was expressed in a subpopulation of L-cells in mouse and human intestinal sections. Stxbp1 transcripts and protein displayed circadian patterns in mGLUTag L-cells line, while chromatin-immunoprecipitation revealed increased interaction between BMAL1 and Stxbp1 at the peak time-point of the circadian pattern. STXBP1 recruitment to the cytosol and plasma membrane within 30 minutes of L-cell stimulation was also observed at this time-point. Loss of Stxbp1 in vitro and in vivo led to reduced stimulated GLP-1 secretion at the peak time-point of circadian release, and impaired GLP-1 secretion ex vivo. In conclusion, Stxbp1 is a circadian regulated exocytotic protein in the intestinal L-cell that is an essential regulatory component of GLP-1 secretion.Wellcome Trust MR

Genetics as a novel tool in mining impact assessment and biomonitoring of critically endangered western chimpanzees in the Nimba Mountains, Guinea

Western chimpanzees (Pan troglodytes verus) are Critically Endangered and Guinea is a key stronghold for this subspecies. However, Guinea is also rich in minerals with some of the highest‐grade iron‐ore deposits in the world. Specifically, the Nimba Mountains, home to western chimpanzees, is one of the sites under consideration for mining activities. To assess the impact of mining activities in the area, we used non‐invasive genetic sampling to estimate chimpanzee population size, sex ratio, community composition, and range boundaries on the western flank of the massif. The level of genetic diversity and affinity between communities was estimated and recommendations for future genetic censusing provided. Between 2003 and 2018, we collected 999 fecal samples of which 663 were analyzed using a panel of 26 microsatellites. We identified a minimum of 136 chimpanzees in four communities, with evidence of migratory events, a high level of shared ancestry and genetic diversity. We assessed sampling intensities and capture rates for each community. Saturation was reached in two communities with sampling between 3.2 and 4.3 times the estimated number of chimpanzees. Our findings highlight the utility of genetic censusing for temporal monitoring of ape abundance, as well as capturing migratory events and gauging genetic diversity and population viability over time. We recommend genetic sampling, combined with camera trapping, for use in future Environmental and Social Impact Assessments, as these methods can yield robust baselines for implementing the mitigation hierarchy, future biomonitoring and conservation management

Effectiveness of live health professional-led group eHealth interventions for adult mental health: systematic review of randomized controlled trials

Open access article. Creative Commons Attribution 4.0 License (CC BY 4.0) appliesBackground: The COVID-19 pandemic has had adverse impacts on mental health and substance use worldwide. Systematic reviews suggest eHealth interventions can be effective at addressing these problems. However, strong positive eHealth outcomes are often tied to the intensity of web-based therapist guidance, which has time and cost implications that can make the population scale-up of more effective interventions difficult. A way to offset cost while maintaining the intensity of therapist guidance is to offer eHealth programs to groups rather than more standard one-on-one formats. Objective: This systematic review aims to assess experimental evidence for the effectiveness of live health professional–led group eHealth interventions on mental health, substance use, or bereavement among community-dwelling adults. Within the articles selected for our primary aim, we also seek to examine the impact of interventions that encourage physical activity compared with those that do not. Methods: Overall, 4 databases (MEDLINE, CINAHL, PsycINFO, and the Cochrane Library) were searched in July 2020. Eligible studies were randomized controlled trials (RCTs) of eHealth interventions led by health professionals and delivered entirely to adult groups by videoconference, teleconference, or webchat. Eligible studies reported mental health, substance use, or bereavement as primary outcomes. The results were examined by outcome, eHealth platform, and intervention length. Postintervention data were used to calculate effect size by study. The findings were summarized using the Synthesis Without Meta-Analysis guidelines. Risk of bias was assessed using the Cochrane Collaboration Tool. Results: Of the 4099 identified studies, 21 (0.51%) RCTs representing 20 interventions met the inclusion criteria. These studies examined mental health outcomes among 2438 participants (sample size range: 47-361 participants per study) across 7 countries. When effect sizes were pooled, live health professional–led group eHealth interventions had a medium effect on reducing anxiety compared with inactive (Cohen d=0.57) or active control (Cohen d=0.48), a medium to small effect on reducing depression compared with inactive (Cohen d=0.61) or active control (Cohen d=0.21), and mixed effects on mental distress and coping. Interventions led by videoconference, and those that provided 8-12 hours of live health professional–led group contact had more robust effects on adult mental health. Risk of bias was high in 91% (19/21) of the studies. Heterogeneity across interventions was significant, resulting in low to very low quality of evidence. No eligible RCT was found that examined substance use, bereavement, or physical activity. Conclusions: Live eHealth group interventions led by health professionals can foster moderate improvements in anxiety and moderate to small improvements in depression among community-based adults, particularly those delivered by videoconference and those providing 8-12 hours of synchronous engagement.Ye

Effects of Eupalinilide E and UM171, Alone and in Combination on Cytokine Stimulated Ex-Vivo Expansion of Human Cord Blood Hematopoietic Stem Cells

Eupalinilide E was assessed for ex-vivo expansion activity on hematopoietic stem cells (HSCs) from human cord blood (CB) CD34+ cells in serum-free, SCF, TPO and FL stimulated 7 day cultures. Eupalinilide E ex-vivo enhanced phenotyped (p) HSCs and glycolysis of CD34+ cells isolated 7 days after culture as measured by extracellular acidification rate, but did not alone show enhanced NSG engrafting capability of HSCs as determined by chimerism and numbers of SCID Repopulating cells, a quantitative measure of functional human HSCs. This is another example of pHSCs not necessarily recapitulating functional activity of these cells. Lack of effect on engrafting HSCs may be due to a number of possibilities, including down regulation of CXCR4 or of the homing capacity of these treated cells. However, Eupalinilide did act in an additive to synergistic fashion with UM171 to enhance ex vivo expansion of both pHSCs, and functionally engrafting HSCs. While reasons for the disconnect between pHSC and function of HSCs with Eupalinilide E alone cultured CB CD34+ cells is yet to be determined, the data suggest possible future use of Eupalinilide and UM171 together to enhance ex vivo production of CB HSCs for clinical hematopoietic cell transplantation

NADPH Oxidase Limits Innate Immune Responses in the Lungs in Mice

Background: Chronic granulomatous disease (CGD), an inherited disorder of the NADPH oxidase in which phagocytes are defective in generating superoxide anion and downstream reactive oxidant intermediates (ROIs), is characterized by recurrent bacterial and fungal infections and by excessive inflammation (e.g., inflammatory bowel disease). The mechanisms by which NADPH oxidase regulates inflammation are not well understood. Methodology/Principal Findings: We found that NADPH oxidase restrains inflammation by modulating redox-sensitive innate immune pathways. When challenged with either intratracheal zymosan or LPS, NADPH oxidase-deficient p47phox-/- mice and gp91phox-deficient mice developed exaggerated and progressive lung inflammation, augmented NF-kB activation, and elevated downstream pro-inflammatory cytokines (TNF-α, IL-17, and G-CSF) compared to wildtype mice. Replacement of functional NADPH oxidase in bone marrow-derived cells restored the normal lung inflammatory response. Studies in vivo and in isolated macrophages demonstrated that in the absence of functional NADPH oxidase, zymosan failed to activate Nrf2, a key redox-sensitive anti-inflammatory regulator. The triterpenoid, CDDO-Im, activated Nrf2 independently of NADPH oxidase and reduced zymosan-induced lung inflammation in CGD mice. Consistent with these findings, zymosan-treated peripheral blood mononuclear cells from X-linked CGD patients showed impaired Nrf2 activity and increased NF-kB activation. Conclusions/Significance: These studies support a model in which NADPH oxidase-dependent, redox-mediated signaling is critical for termination of lung inflammation and suggest new potential therapeutic targets for CGD

The HMGB1-RAGE axis mediates traumatic brain injury-induced pulmonary dysfunction in lung transplantation

Traumatic brain injury (TBI) results in systemic inflammatory responses that affect the lung. This is especially critical in the setting of lung transplantation, where more than half of donor allografts are obtained postmortem from individuals with TBI. The mechanism by which TBI causes pulmonary dysfunction remains unclear but may involve the interaction of high-mobility group box-1 (HMGB1) protein with the receptor for advanced glycation end products (RAGE). To investigate the role of HMGB1 and RAGE in TBI-induced lung dysfunction, RAGE-sufficient (wild-type) or RAGE-deficient (RAGE(-/-)) C57BL/6 mice were subjected to TBI through controlled cortical impact and studied for cardiopulmonary injury. Compared to control animals, TBI induced systemic hypoxia, acute lung injury, pulmonary neutrophilia, and decreased compliance (a measure of the lungs' ability to expand), all of which were attenuated in RAGE(-/-) mice. Neutralizing systemic HMGB1 induced by TBI reversed hypoxia and improved lung compliance. Compared to wild-type donors, lungs from RAGE(-/-) TBI donors did not develop acute lung injury after transplantation. In a study of clinical transplantation, elevated systemic HMGB1 in donors correlated with impaired systemic oxygenation of the donor lung before transplantation and predicted impaired oxygenation after transplantation. These data suggest that the HMGB1-RAGE axis plays a role in the mechanism by which TBI induces lung dysfunction and that targeting this pathway before transplant may improve recipient outcomes after lung transplantation

Le FORUM, Vol. 39 No. 1

https://digitalcommons.library.umaine.edu/francoamericain_forum/1044/thumbnail.jp