TNFα and IFNγ cooperate for efficient pro- to anti-inflammatory transition of macrophages during muscle regeneration.

IFNγ is traditionally known as a proinflammatory cytokine with diverse roles in antimicrobial and antitumor immunity. Yet, findings regarding its sources and functions during the regeneration process following a sterile injury are conflicting. Here, we show that natural killer (NK) cells are the main source of IFNγ in regenerating muscle. Beyond this cell population, IFNγ production is limited to a small population of T cells. We further show that NK cells do not play a major role in muscle regeneration following an acute injury or in dystrophic mice. Surprisingly, the absence of IFNγ per se also has no effect on muscle regeneration following an acute injury. However, the role of IFNγ is partially unmasked when TNFα is also neutralized, suggesting a compensatory mechanism. Using transgenic mice, we showed that conditional inhibition of IFNGR1 signaling in muscle stem cells or fibro-adipogenic progenitors does not play a major role in muscle regeneration. In contrast to common belief, we found that IFNγ is not present in the early inflammatory phase of the regeneration process but rather peaks when macrophages are acquiring an anti-inflammatory phenotype. Further transcriptomic analysis suggests that IFNγ cooperates with TNFα to regulate the transition of macrophages from pro- to anti-inflammatory states. The absence of the cooperative effect of these cytokines on macrophages, however, does not result in significant regeneration impairment likely due to the presence of other compensatory mechanisms. Our findings support the arising view of IFNγ as a pleiotropic inflammatory regulator rather than an inducer of the inflammatory response.

Is size in the eye of the beholder? Visual estimation of penis size among transgender and cisgender people and implications for genital gender-affirming surgery and sexual medicine.

BACKGROUND: Transgender men (TM) seeking gender-affirming phalloplasty and transgender women (TW) seeking vaginoplasty and desiring insertive intercourse must consider penis size. Evidence has shown that, at least among cisgender men (CM), penile dimensions tend to be poorly estimated. In transgender patients desiring gender-affirming surgery, inaccuracy in estimation of penis dimensions may lead to unnecessary morbidity: for TW, trauma to the neovagina; for TM with excess girth, an inability to insert. Studies on the accuracy with which transgender and cisgender patients estimate penis size are limited. AIM: To assess the degree of accuracy with which CM and CW, as well as TM and TW, visually estimate the size of the human penis, including length, width, and girth. METHODS: There were 142 participants included (25 TM, 47 TW, 30 CM, and 40 CW; net mean ± SD age, 36.6 ± 11.2 years). Participants were shown these models and asked to estimate length, width, and midshaft girth by visual inspection of 6 realistic models of a penis and scrotum of varying lengths and widths. We evaluated the accuracy of the visual measurements by comparing mean perceived dimensions with the actual dimensions of each model. OUTCOMES: We used a multivariate model of all 3 bias dimensions to test for differences in average bias among gender groups (CM, CW, TM, and TW). RESULTS: TM significantly overestimated length across the longest models. TW significantly overestimated length in the longer 3 models. All groups except for TM significantly underestimated girth in at least 1 model. No groups significantly underestimated width. CM, CW, and TM significantly overestimated width in all 6 models. CLINICAL IMPLICATIONS: When transgender patients use numbers to express penis size (either in neophallus or vaginal depth based on perceived partner size), the result is likely to be larger than expected. Use of realistic penis models as a decision-making tool may help manage patient expectations and surgery decision making preoperatively and improve postoperative patient satisfaction and safety. STRENGTHS AND LIMITATIONS: To our knowledge, this is the first study to assess visual estimation in penis size in TM and CM, as well as TW and CW. The penile models in our study were shown side by side and in the flaccid state despite having dimensions more consistent with an erect penis, which may have influenced estimations across all dimensions. CONCLUSION: Men and women (cisgender and transgender) tend to significantly overestimate penis length and width.

Groebke Blackburn Bienaymé-mediated multi-component synthesis of selective HDAC6 inhibitors with anti-inflammatory properties.

Histone deacetylases (HDACs) are a class of enzymes that cleave acyl groups from lysine residues of histone and non-histone proteins. There are 18 human HDAC isoforms with different cellular targets and functions. Among them, HDAC6 was found to be overexpressed in different types of cancer. However, when used in monotherapy, HDAC6 inhibition by selective inhibitors fails to show pronounced anti-cancer effects. The HDAC6 enzyme also addresses non-histone proteins like α-tubulin and cortactin, making it important for cell migration and angiogenesis. Recently, the NLRP3 inflammasome was identified as an important regulator of inflammation and immune responses and, importantly, HDAC6 is critically involved the activation of the inflammasome. We herein report the design, synthesis and biological evaluation of a library of selective HDAC6 inhibitors. Starting from the previously published crystal structure of MAIP-032 in complex with CD2 of zHDAC6, we performed docking studies to evaluate additional possible interactions of the cap group with the L1-loop pocket. Based on the results we synthesized 13 novel HDAC6 inhibitors via the Groebke-Blackburn-Bienaymé three component reaction as the key step. Compounds 8k (HDAC1 IC50: 5.87 µM; HDAC6 IC50: 0.024 µM; selectivity factor (SF1/6): 245) and 8m (HDAC1 IC50: 3.07 µM; HDAC6 IC50: 0.026 µM; SF1/6: 118) emerged as the most potent and selective inhibitors of HDAC6 and outperformed the lead structure MAIP-032 (HDAC1 IC50: 2.20 µM; HDAC6 IC50: 0.058 µM; SF1/6: 38) both in terms of inhibitory potency and selectivity. Subsequent immunoblot analysis confirmed the high selectivity of 8k and 8m for HDAC6 in a cellular environment. While neither 8k and 8m nor the selectivity HDAC6 inhibitor tubastatin A showed antiproliferative effects in the U-87 MG glioblastoma cell line, compound 8m attenuated cell migration significantly in wound healing assays in U-87 MG cells. Moreover, in macrophages compounds 8k and 8m demonstrated significant inhibition of LPS-induced IL1B mRNA expression and TNF release. These findings suggest that our imidazo[1,2-a]pyridine-capped HDAC6 inhibitors may serve as promising candidates for the development of drugs to effectively treat NLRP3 inflammasome-driven inflammatory diseases.

Squaric esters as peptide stapling reagents.

We report that squaric esters can serve as bifunctional reagents for selective peptide stapling reactions. Formation of the squaric amide staple occurs under mild conditions with amine-containing side chains. We show that short resin-bound peptides are readily stapled on solid phase and that stapling can occur at various relative positions along the peptide and with various amine tether lengths (e.g. Lysine, ornithine, etc). The squaric amide staples are stable to strong acid conditions used to cleave the stapled peptide from the resin and the stapled peptides show an increase in helicity as analyzed through circular dichroism.

Insights into the Clinical, Biological and Therapeutic Impact of Copy Number Alteration in Cancer.

Copy number alterations (CNAs), resulting from the gain or loss of genetic material from as little as 50 base pairs or as big as entire chromosome(s), have been associated with many congenital diseases, de novo syndromes and cancer. It is established that CNAs disturb the dosage of genomic regions including enhancers/promoters, long non-coding RNA and gene(s) among others, ultimately leading to an altered balance of key cellular functions. In cancer, CNAs have been associated with almost all steps of the disease: predisposition, initiation, development, maintenance, response to treatment, resistance, and relapse. Therefore, understanding how specific CNAs contribute to tumourigenesis may provide prognostic insight and ultimately lead to the development of new therapeutic approaches to improve patient outcomes. In this review, we provide a snapshot of what is currently known about CNAs and cancer, incorporating topics regarding their detection, clinical impact, origin, and nature, and discuss the integration of innovative genetic engineering strategies, to highlight the potential for targeting CNAs using novel, dosage-sensitive and less toxic therapies for CNA-driven cancer.

Rosetta's Predictive Ability for Low-Affinity Ligand Binding in Fragment-Based Drug Discovery.

Fragment-based drug discovery begins with the identification of small molecules with a molecular weight of usually less than 250 Da which weakly bind to the protein of interest. This technique is challenging for computational docking methods as binding is determined by only a few specific interactions. Inaccuracies in the energy function or slight deviations in the docking pose can lead to the prediction of incorrect binding or difficulties in ranking fragments in in silico screening. Here, we test RosettaLigand by docking a series of fragments to a cysteine-depleted variant of the TIM-barrel protein, HisF (UniProtKB Q9X0C6). We compare the computational results with experimental NMR spectroscopy screens. NMR spectroscopy gives details on binding affinities of individual ligands, which allows assessment of the ligand-ranking ability using RosettaLigand and also provides feedback on the location of the binding pocket, which serves as a reliable test of RosettaLigand's ability to identify plausible binding poses. From a library screen of 3456 fragments, we identified a set of 31 ligands with intrinsic affinities to HisF with dissociation constants as low as 400 µM. The same library of fragments was blindly screened in silico. RosettaLigand was able to rank binders before non-binders with an area under the curve of the receiver operating characteristics of 0.74. The docking poses observed for binders agreed with the binding pocket identified by NMR chemical shift perturbations for all fragments. Taken together, these results provide a baseline performance of RosettaLigand in a fragment-based drug discovery setting.

Shallow-depth vaginoplasty: preoperative goals, postoperative satisfaction, and why shallow-depth vaginoplasty should be offered as a standard feminizing genital gender-affirming surgery option.

BACKGROUND: Shallow-depth vaginoplasty (SDV), also referred to as vaginoplasty without creation of a vaginal canal, is an understudied alternative to full-depth vaginoplasty (FDV), or vaginoplasty with creation of a vaginal canal. SDV is associated with fewer short- and long-term risks and shorter recovery, and does not require a lifelong commitment to vaginal dilation and douching. AIM: To describe a surgical technique for SDV that creates a dimpled introitus, together with clinical outcomes, decision-making prioritization, and satisfaction data. We hypothesize that SDV patients prioritize comparable appearance and sexual function to FDV over shorter-term risk factors, and experience high satisfaction. METHODS: We describe (1) a surgical technique for SDV; (2) the proportion of patients who underwent SDV vs. FDV, with SDV complication rates; and (3) the results of an anonymous, electronic questionnaire administered via Qualtrics that assessed SDV patient demographics, terminology preferences, prioritization of decision-guiding factors for choosing SDV over FDV, and postoperative satisfaction across various domains. OUTCOMES: A total of 110 patients underwent primary feminizing genital gender-affirming surgery at a single institution between April 2017 and July 2022: 35 (32%) of 110 underwent SDV and 75 (68%) underwent FDV. The 35 SDV patients were invited to answer the study questionnaire, of which 29 (83%) completed it (mean age 51.9 ± 16.7 years, mean body mass index 27.3 ± 5.3 kg/m2). RESULTS: All but one survey respondent met one or more of the following characteristics: (1) ≥40 years of age, (2) exclusively feminine-identifying sexual partners, and/or (3) significant aversion to performing long-term vaginal dilation and douching. Ranking of 8 decision-guiding factors revealed prioritization of long-term over short-term outcomes. Postoperatively, patients reported high satisfaction across all 3 domains. When asked if they had to choose between SDV and FDV over again, 86% reported that they would choose SDV. While 14% would choose FDV, all but one reported new interest in receptive vaginal intercourse due to finding masculine-identifying partners post-SDV surgery. A total of 27% of SDV patients experienced complications that required additional surgeries; 82% of complications were related to urinary spraying. CLINICAL IMPLICATIONS: SDV is a lower-risk alternative to FDV and is associated with reduced postoperative maintenance and high postoperative satisfaction. STRENGTHS AND LIMITATIONS: This study describes the clinical outcomes of the largest documented cohort of patients to undergo SDV to date. Limitations include recall bias due to the retrospective survey and use of nonvalidated questions attributed to the paucity of validated gender-affirming surgery questionnaires. CONCLUSION: SDV's appeal to a large subset of patients (32% in this study), low complication rate, high satisfaction, and low decisional regret suggests that this surgical option should be offered to all patients seeking feminizing genital gender-affirming surgery.

Unlocking Population-Specific Treatments to Render Equitable Approaches and Management in Cardiovascular Disease: Development of a Situation-Specific Theory for African American Emerging Adults.

BACKGROUND: Emerging adulthood (18-25 years old) is a distinct developmental period in which multiple life transitions pose barriers to engaging in healthy lifestyle behaviors that reduce cardiovascular disease risk. There is limited theory-based research on African American emerging adults. OBJECTIVE: This article introduces a synthesized empirically testable situation-specific theory for cardiovascular disease prevention in African American emerging adults. METHODOLOGY: Im and Meleis' integrative approach was used to develop the situation-specific theory. RESULTS: Unlocking Population-Specific Treatments to Render Equitable Approach and Management in Cardiovascular Disease is a situation-specific theory developed based on theoretical and empirical evidence and theorists' research and clinical practice experiences. DISCUSSION: African American emerging adults have multifaceted factors that influence health behaviors and healthcare needs. Unlocking Population-Specific Treatments to Render Equitable Approaches and Management in Cardiovascular Disease has the potential to inform theory-guided clinical practice and nursing research. Recommendations for integration in nursing practice, research, and policy advocacy are presented. Further critique and testing of the theory are required.

Osteoregenerative Potential of 3D-Printed Poly ε-Caprolactone Tissue Scaffolds In Vitro Using Minimally Manipulative Expansion of Primary Human Bone Marrow Stem Cells.

The repair of orthopedic and maxillofacial defects in modern medicine currently relies heavily on the use of autograft, allograft, void fillers, or other structural material composites. This study examines the in vitro osteo regenerative potential of polycaprolactone (PCL) tissue scaffolding, fabricated via a three-dimensional (3D) additive manufacturing technology, i.e., a pneumatic micro extrusion (PME) process. The objectives of this study were: (i) To examine the innate osteoinductive and osteoconductive potential of 3D-printed PCL tissue scaffolding and (ii) To perform a direct in vitro comparison of 3D-printed PCL scaffolding with allograft Allowash® cancellous bone cubes with regards to cell-scaffold interactions and biocompatibility with three primary human bone marrow (hBM) stem cell lines. This study specifically examined cell survival, cell integration, intra-scaffold cell proliferation, and differentiation of progenitor cells to investigate the potential of 3D-printed PCL scaffolds as an alternative to allograft bone material for the repair of orthopedic injuries. We found that mechanically robust PCL bone scaffolds can be fabricated via the PME process and the resulting material did not elicit detectable cytotoxicity. When the widely used osteogenic model SAOS-2 was cultured in PCL extract medium, no detectable effect was observed on cell viability or proliferation with multiple test groups showing viability ranges of 92.2% to 100% relative to a control group with a standard deviation of ±10%. In addition, we found that the honeycomb infill pattern of the 3D-printed PCL scaffold allowed for superior mesenchymal stem-cell integration, proliferation, and biomass increase. When healthy and active primary hBM cell lines, having documented in vitro growth rates with doubling times of 23.9, 24.67, and 30.94 h, were cultured directly into 3D-printed PCL scaffolds, impressive biomass increase values were observed. It was found that the PCL scaffolding material allowed for biomass increase values of 17.17%, 17.14%, and 18.18%, compared to values of 4.29% for allograph material cultured under identical parameters. It was also found that the honeycomb scaffold infill pattern was superior to the cubic and rectangular matrix structures, and provided a superior microenvironment for osteogenic and hematopoietic progenitor cell activity and auto-differentiation of primary hBM stem cells. Histological and immunohistochemical studies performed in this work confirmed the regenerative potential of PCL matrices in the orthopedic setting by displaying the integration, self-organization, and auto-differentiation of hBM progenitor cells within the matrix. Differentiation products including mineralization, self-organizing "proto-osteon" structures, and in vitro erythropoiesis were observed in conjunction with the documented expression of expected bone marrow differentiative markers including CD-99 (>70%), CD-71 (>60%), and CD-61 (>5%). All of the studies were conducted without the addition of any exogenous chemical or hormonal stimulation and exclusively utilized the abiotic and inert material polycaprolactone; setting this work apart from the vast majority of contemporary investigations into synthetic bone scaffold fabrication In summary, this study demonstrates the unique clinical potential of 3D-printed PCL scaffolds for stem cell expansion and incorporation into advanced microstructures created via PME manufacturing to generate a physiologically inert temporary bony defect graft with significant autograft features for enhanced end-stage healing.

Preoccupation in bulimia nervosa, binge-eating disorder, anorexia nervosa, and higher weight.

OBJECTIVE: Preoccupation (excessive and constant thoughts) about shape/weight and food/eating is thought to be prominent in individuals with eating disorders but has received much less research than overt behavioral features. This study examined the significance and distinctiveness of different foci of preoccupation in individuals categorized with different forms of eating disorders and in individuals with higher weight. METHOD: Participants (N = 1,363) completed a web-based survey with established measures of eating-disorder psychopathology and depression. The current study compared preoccupation among individuals with core features of bulimia nervosa (BN; n = 144), binge-eating disorder (BED; n = 576), anorexia nervosa (AN; n = 48), and higher body weight (body mass index [BMI] ≥ 25) without eating-disorder features (higher weight [HW]; n = 595). Associations of each type of preoccupation with other eating-disorder psychopathology and depression were examined both between and within study groups. RESULTS: Preoccupation with shape/weight and with food/eating showed a graded pattern of statistically significant differences: AN and BN had higher preoccupation than BED, which was higher than HW. Within BN, BED, and AN study groups, correlation magnitudes of shape/weight and food/eating preoccupation with eating-disorder psychopathology and depression did not differ significantly. Within the HW group, shape/weight preoccupation was significantly more strongly correlated than food/eating preoccupation with overvaluation, body dissatisfaction, and depression. DISCUSSION: The preoccupation cognitive style, as well as focus, appears associated with other facets of eating-disorder psychopathology and depression. If results are confirmed among individuals with formal diagnoses, clinicians addressing maladaptive cognitions in cognitive-behavioral therapy should consider the role of preoccupation. Future research should investigate whether preoccupation predicts or moderates eating disorder treatment outcomes.

Modeling Immunity with Rosetta: Methods for Antibody and Antigen Design.

Structure-based antibody and antigen design has advanced greatly in recent years, due not only to the increasing availability of experimentally determined structures but also to improved computational methods for both prediction and design. Constant improvements in performance within the Rosetta software suite for biomolecular modeling have given rise to a greater breadth of structure prediction, including docking and design application cases for antibody and antigen modeling. Here, we present an overview of current protocols for antibody and antigen modeling using Rosetta and exemplify those by detailed tutorials originally developed for a Rosetta workshop at Vanderbilt University. These tutorials cover antibody structure prediction, docking, and design and antigen design strategies, including the addition of glycans in Rosetta. We expect that these materials will allow novice users to apply Rosetta in their own projects for modeling antibodies and antigens.

Frailty as predictor of complications in patients undergoing percutaneous nephrolithotomy (PCNL).

INTRODUCTION & OBJECTIVE: Surgical complications are difficult to predict, despite existing tools. Frailty phenotype has shown promise estimating postoperative risk among the elderly. We evaluate the use of frailty as a predictive tool on patients undergoing percutaneous renal surgery. METHODS: Frailty was prospectively analyzed using the Hopkins Frailty Index, consisting of 5 components yielding an additive score: patients categorized not frail, intermediate, or severely frail. Primary outcomes were complications during admission and 30-day complication rate. Secondary outcomes included overall hospital length of stay (LOS) and discharge location. RESULTS: A total of 100 patients recruited, of whom five excluded as they did not need the procedure. A total of 95 patients analyzed; 69, 10, and 16 patients were not frail, intermediate, and severely frail, respectively. There were no differences in blood loss, number of dilations, presence of a staghorn calculus, laterality, or location of dilation. Severely frail patients were likely to be older and have a higher American Society of Anesthesiologists score and Charlson comorbidity index. Patients of intermediate or severe frailty were more likely to exhibit postoperative fevers, bacteremia, sepsis, and require ICU admissions (P < 0.05). Frail patients had a longer LOS (P < 0.001) and tended to require skilled assistance when discharge (p < 0.0001). CONCLUSIONS: Frailty assessment appears useful stratifying those at risk of extended hospitalization, septic complications, and need for assistance following percutaneous renal surgery. Risks of sepsis, bacteremia, and post-operative hemorrhage may be higher in frail individuals. Preoperative assessment of frailty phenotype may give insight into treatment decisions and represent a modifiable marker allowing future trials exploring the concept of "prehabilitation".

Blood Dehydroepiandrosterone and Dehydroepiandrosterone Sulfate as Pathophysiological Correlates of Chronic Pain: Analyses Using a National Sample of Midlife Adults in the United States.

OBJECTIVE: Identifying biomarkers is a priority in translational chronic pain research. Dehydroepiandrosterone (DHEA) and its sulfated form, DHEA-S, are adrenocortical steroids in the blood with neuroprotective properties that also produce sex hormones. They may capture key sex-specific neuroendocrine mechanisms of chronic pain. DESIGN: Cross-sectional study. METHODS: Using data from 1,216 community-dwelling adults aged 34-84 from the Midlife in the United States (MIDUS) cohort, we examined blood DHEA and DHEA-S levels in association with chronic pain in men and women, adjusting for demographics, chronic diseases, medications including opioids, and psychosocial factors. If an association was found, we further explored dose-response relationships by the number of pain locations and the degree of pain interference. RESULTS: In women, chronic pain was associated with 0.072 lower (95% confidence interval [CI], -0.127 to -0.017) log10 DHEA-S µg/dL, with pain in one to two locations associated with 0.068 lower (95% CI, -0.131 to -0.006) and in three or more locations 0.071 lower (95% CI, -0.148 to 0.007) log10 DHEA-S (P for trend = 0.074). Furthermore for women, low-interference pain was associated with 0.062 lower (95% CI, -0.125 to -0.000), whereas high-interference pain was associated with 0.138 lower (95% CI, -0.233 to -0.043) log10 DHEA-S (P for trend = 0.004). Chronic pain was not associated with DHEA or DHEA-S levels in men or DHEA levels in women. CONCLUSIONS: Chronic pain and its functional interference correspond to lower blood DHEA-S levels in women.

Association between dysmenorrhea and chronic pain: a systematic review and meta-analysis of population-based studies.

OBJECTIVE: The objective of the study was to synthesize the epidemiological findings for the associations between dysmenorrhea, including primary dysmenorrhea and endometriosis-associated dysmenorrhea and any chronic pain conditions, including chronic pelvic pain, and chronic nonpelvic pain. DATA SOURCES: The data sources included PubMed, Embase, and CINAHL from inception to December 2019. STUDY ELIGIBILITY CRITERIA: The study criteria included observational population-based studies in which the relationship between dysmenorrhea and the presence or severity of chronic pain was examined. STUDY APPRAISAL AND SYNTHESIS METHODS: Each study was double coded and evaluated for bias based on the modified Newcastle and Ottawa Scale. Random-effect meta-analyses were conducted to quantify the associations between dysmenorrhea and the presence of chronic pelvic and nonpelvic pain. RESULTS: Out of 9452 records, 32 studies were included, with 14 reporting associations between dysmenorrhea and chronic pelvic pain, and 20 for dysmenorrhea and chronic nonpelvic pain. Primary dysmenorrhea and endometriosis-associated dysmenorrhea were examined in 7 studies, respectively. More than 30% of the studies were categorized as poor quality, 56% as moderate, and 12.5% as high. Dysmenorrhea was positively associated with both the presence and severity of chronic pelvic and nonpelvic pain conditions. Based on 6689 women from 8 studies, those with chronic pelvic pain had 2.43 (95% confidence interval, 1.98-2.99, I2, 42%) times the odds of having dysmenorrhea compared with those without. Based on 3750 women from 11 studies, those with chronic nonpelvic pain had 2.62 (95% confidence interval, 1.84-3.72, I2, 72%) times the odds of having dysmenorrhea compared with those without. Overall, dysmenorrhea was associated with 2.50 (95% confidence interval, 2.02-3.10) times the odds of chronic pain, which did not differ by chronic pelvic vs chronic nonpelvic pain, community vs clinical populations, or different geographical regions. CONCLUSIONS: Dysmenorrhea may be a general risk factor for chronic pain, although whether primary dysmenorrhea increases the risk for chronic pain is unclear. Given that adolescence is a sensitive period for neurodevelopment, elucidating the role of primary dysmenorrhea in pain chronicity in future longitudinal studies is important for preventing both chronic pelvic and nonpelvic pain.

Evaluation of the Impact of the Wound Treatment Associate (WTA) Education Program on Practice and Quality Patient Outcomes.

PURPOSE: The Wound Treatment Associate (WTA) program is an education offering of the WOCN Society. This evidence-based continuing education program prepares nurses to serve as a unit-based resource for nursing staff. The WTA program is approved by the American Nurses Credentialing Association (ANCC) for 32.25 contact hours and aimed at licensed health care personnel. This article focuses on the impact of this education program, in particular a reduction in hospital-acquired pressure injury (HAPI) in acute care and decrease in visits per episode (VPE) and supply costs in home health. METHODS: Surveys were sent to all course participants to date to fulfill the summative evaluation requirement for ANCC approval to determine the perception of improvement in knowledge, skills, and practice. An additional survey was developed and reviewed by members to send to WTA program course coordinators. RESULTS: Participants (n = 153) reported an increase in confidence in knowledge and skills about wound care and use in nursing practice. The number of respondents to the course coordinator survey was lower (n = 48). Coordinators did report a reduction in pressure injuries in acute care. Home health respondents noted a decrease in VPE and reduction in the cost of supplies. Data reported on abstracts and posters suggested positive impacts of pressure injury prevention programs in acute and home health care. CONCLUSIONS: Although there are limitations to the aforementioned reporting, incorporating the WTA program into pressure injury prevention programs and wound treatment programs showed a reduction in HAPIs in acute care and decreased VPE and supply costs in home health.

Bone marrow transplantation for adolescents and young adults with sickle cell disease: Results of a prospective multicenter pilot study.

We conducted a multicenter pilot investigation of the safety and feasibility of bone marrow transplantation (BMT) in adults with severe sickle cell disease (SCD) (NCT 01565616) using a reduced toxicity preparative regimen of busulfan (13.2 mg/kg), fludarabine (175 mg/m2 ) and thymoglobulin (6 mg/kg) and cyclosporine or tacrolimus and methotrexate for graft-vs-host disease (GVHD) prophylaxis. Twenty-two patients (median age 22 years; range 17-36) were enrolled at eight centers. Seventeen patients received marrow from an HLA-identical sibling donor and five patients received marrow from an 8/8 HLA-allele matched unrelated donor. Before BMT, patients had stroke, acute chest syndrome, recurrent pain events, were receiving regular red blood cell transfusions, or had an elevated tricuspid regurgitant jet (TRJ) velocity, which fulfilled eligibility criteria. Four patients developed grades II-III acute GVHD (18%) and six developed chronic GVHD (27%) that was moderate in two and severe in one patient. One patient died of intracranial hemorrhage and one of GVHD. Nineteen patients had stable donor chimerism, 1-year post-transplant. One patient who developed secondary graft failure survives disease-free after a second BMT. The one-year overall survival and event-free survival (EFS) are 91% (95% CI 68%-98%) and 86% (95% CI, 63%-95%), respectively, and 3-year EFS is 82%. Statistically significant improvements in the pain interference and physical function domains of health-related quality of life were observed. The study satisfied the primary endpoint of 1-year EFS ≥70%. This regimen is being studied in a prospective clinical trial comparing HLA-matched donor BMT with standard of care in adults with severe SCD (NCT02766465).

Factors associated with using alternative sources of primary care: a cross-sectional study.

BACKGROUND: Mobile (MHCs), Community (CHCs), and School-based health clinics (SBHCs) are understudied alternative sources of health care delivery used to provide more accessible primary care to disenfranchised populations. However, providing access does not guarantee utilization. This study explored the utilization of these alternative sources of health care and assessed factors associated with residential segregation that may influence their utilization. METHODS: A cross-sectional study design assessed the associations between travel distance, perceived quality of care, satisfaction-adjusted distance (SAD) and patient utilization of alternative health care clinics. Adults (n = 165), child caregivers (n = 124), and adult caregivers (n = 7) residing in New Orleans, Louisiana between 2014 and 2015 were conveniently sampled. Data were obtained via face-to face interviews using standardized questionnaires and geospatial data geocoded using GIS mapping tools. Multivariate regression models were used to predict alternative care utilization. RESULTS: Overall 49.4% of respondents reported ever using a MCH, CHC, or SBHC. Travel distance was not significantly associated with using either MCH, CHC, or SBHC (OR = 0.91, 0.74-1.11 p > .05). Controlling for covariates, higher perceived quality of care (OR = 1.02, 1.01-1.04 p < .01) and lower SAD (OR = 0.81, 0.73-0.91 p < .01) were significantly associated with utilization. CONCLUSIONS: Provision of primary care via alternative health clinics may overcome some barriers to care but have yet to be fully integrated as regular sources of care. Perceived quality and mixed-methods measures are useful indicators of access to care. Future health delivery research is needed to understand the multiple mechanisms by which residential segregation influences health-seeking behavior.

Rapid detection of human blood in triatomines (kissing bugs) utilizing a lateral flow immunochromatographic assay - A pilot study.

OBJECTIVES: We tested a rapid and specific immunochromatographic assay (that detects human blood in forensic samples) to determine if human blood was present in triatomines and their fecal excreta. METHODS: We fed Triatoma rubida human blood (positive control) or mouse blood (negative control) and performed the assay on the abdominal contents and fecal excreta. Triatomine field specimens collected in and around human habitations and excreta were also tested. FINDINGS: The assay was positive in triatomines fed human blood (N = 5/5) and fecal excreta from bugs known to have ingested human blood (N = 5/5). Bugs feeding on mice (N = 15/15) and their fecal excreta (N = 8/8) were negative for human blood. Human blood was detected in 47% (N = 23/49) triatomines, representing six different species, collected in the field. MAIN CONCLUSIONS: The pilot study shows that this rapid and specific test may have applications in triatomine research. Further study is needed to determine the sensitivity of this assay compared to other well-established techniques, such as DNA- and proteomics-based methodologies and the assay's application in the field.