Periscapular Strength Profile Changes in Collegiate Baseball Pitchers Over the Course of a Season.

Background: Repetitive application of high forces to the shoulder and scapular musculature during the pitching motion over the course of a collegiate baseball season may lead to changes in strength and increased fatigue, potentially predisposing pitching athletes to injury. The purpose of this study was to investigate periscapular strength profiles of Division I collegiate baseball players over the course of a season. Methods: This study was a retrospective data analysis of 18 Division I baseball pitchers. Isometric scapular plane abduction (scaption), external rotator, internal rotator, middle trapezius, and lower trapezius isometric strength was measured on throwing arm of each subject using a MicroFET 2 handheld dynamometer. Data were collected in a single session at the preseason, midseason, and postseason of the college baseball season, which spanned a five-month period. A repeated measures ANOVA was utilized to determine if there was a significant change in periscapular strength across the baseball season. Results: Over the three time-points, all strength values decreased for each muscle group, with decreases ranging from 3-14%. Changes in scaption strength values were statistically significant (p=0.018, partial eta squared =0.284) with an 8% reduction over the entire season, specifically with a 5% decline from mid-season to post-season. While external rotator, internal rotator, middle trapezius, and lower trapezius strength values all decreased over the course of the season (range 0.02kg to 1.8kg), these differences were not statistically significant. However, the middle trapezius strength value change (1.3kg loss) exceeded the minimal detectible change. Conclusion: Periscapular muscles in baseball pitchers diminish in strength over the course of a collegiate baseball season. Understanding strength changes over the course of a season may influence training and therapeutic interventions. Level of Evidence: 3b.

Morphological characterisation of pediatric Turner syndrome aortae: Insights from a small cohort study.

Cardiovascular disease is widespread in girls and women living with Turner syndrome (TS). Despite this prevalence, cardiovascular risk evaluation using the current guidelines has seen life-threatening aortic events occurring at dimensions classified within the normal threshold. In this study, we characterized the three-dimensional aortic geometries of Turner syndrome children and their age-matched healthy counterparts to evaluate various morphological parameters. Turner syndrome girls had overall greater values in ten out of fifteen parameters examined (p > 0.05), when compared to healthy children: the aortic arch height and width; the ascending aorta, aortic arch (2 locations), and descending aorta diameters; the ratio of the ascending to descending aorta diameter; average curvature; average torsion; and average curvature-torsion score. Additionally, significant associations were found in the TS group: body surface area and both arch height (p = 0.03) and arch height to width ratio (p = 0.05), and aortic arch diameter and both body surface area (p = 0.04) and weight (p = 0.04). The new information resulting from this small cohort study contributes to an improved understanding of the morphological parameters affecting the hemodynamic environment in TS, and the clinical assessment of the increased cardiovascular risk in this population.

Safety and effectiveness of nano-pulse stimulation™ technology to treat acne vulgaris of the back.

BACKGROUND AND OBJECTIVES: This feasibility study describes the effects of Nano-pulse stimulation™ (NPS™) technology using the CellFX™ System on acne vulgaris of the back with the objectives of demonstrating safety and effectiveness. The CellFX System applies nanosecond pulses of electrical energy to induce highly localized regulated cell death (RCD) in the cellular structures of the targeted zone with no thermal effect on the tissue and negligible effects on surrounding non-cellular components. STUDY DESIGN/MATERIALS AND METHODS: Seventeen subjects were enrolled at two sites with thirteen subjects completing treatment. Three 7 X 7 cm regions containing at least five bacne lesions each were identified, one region treated with the CellFX across three treatment sessions, the second region treated as a sham using microneedle tip placement without delivering energy, and the third as an untreated control. RESULTS: CellFX-treated areas showed an average reduction of acne lesions of 82% by 90 days post-last procedure. Acne improvement was observed in 100% of CellFX-treated regions compared to 39% improvement in Sham regions and 31% improvement in the control regions. The most common skin effects were erythema and hyperpigmentation observed in 23% and 92% of the subjects, respectively, at the last timepoint. No serious adverse events were reported. CONCLUSIONS: CellFX is a safe and effective procedure for clearing back acne.

Should adding pain, oxygen saturation and physical assessment to vital signs become the new standard of care for detecting blood transfusion reactions?

BACKGROUND AND OBJECTIVES: Clinicians sought to ascertain what frequency of vital signs best detects blood transfusion reactions. This review discusses early and delayed blood product transfusion reaction detection through the lens of scientific literature. METHODS: A comprehensive appraisal of published literature was conducted using Integrative Research Review methodology through June 2022 not limited to English or research in Cumulative Index to Nursing and Allied Health Literature, Cochrane Library of Systematic Reviews, Medline and PubMed. RESULTS: Full-text articles in the final sample included four articles discussing vital signs detecting blood transfusion reactions and four articles reporting the importance of adding physical assessments for early reaction detection. None of the studies provided evidence regarding how often vital signs should be monitored to detect transfusion reactions. No studies included identical screening components for detecting blood product transfusion reactions. Main themes emerged including variations in what was included in vital signs, importance of respiratory assessment, inclusion of physical assessment, nurse documentation and reporting compliance, and patient and family inclusion in transfusion reaction recognition. CONCLUSION: Vital sign components varied across reviewed studies. Respiratory rate and pain were not always included in 'vital signs' to identify transfusion reactions. Only low-level data and no clinical trials loosely informing frequency of vital sign monitoring to transfusion reaction detection were found. Respiratory (to include oxygen saturation, lung sounds and respiratory rate) and pain assessment emerged as crucial to acute and delayed transfusion reaction recognition. The disconnect between 'vital signs' and the varied vital sign components reported to detect transfusion reactions in scientific literature requires further exploration.

Multicenter, prospective feasibility study of Nano-Pulse Stimulation™ technology for the treatment of both nodular and superficial low-risk basal cell carcinoma.

Background: Nano-Pulse Stimulation™ (NPS™) therapy is a new, non-thermal bioelectric modality that applies ultrashort pulses of electric energy to trigger regulated cell death (RCD) in treated tissues. Instead of initiating necrosis by heating or freezing, NPS therapy permeabilizes intracellular organelles to activate the cell's own self-destruct pathway of programmed or regulated cell death. Unlike cryotherapeutic procedures that can both damage structural tissues and diffuse into the periphery beyond the margins of the lesion, NPS therapy only affects cells within the treated zone leaving surrounding tissue and acellular components unaffected. Methods: In this study we treated 37 basal cell carcinoma lesions on 30 subjects (NCT04918381). The treated lesions were photographed on 3-, 7-, 14-, 30- and 60-days after treatment. All subjects then underwent surgical excision for histological examination of the treated tissue. Results: 92% of the BCC lesions (34 of 37) showed complete histological clearance of BCC. Histologic analysis of the 3 cases where residual BCC was noted indicated that full energy coverage was not achieved, which could be remedied with an improved treatment guide to standardize and optimize the CellFX® procedure based on NPS technology. Conclusion: The CellFX procedure was shown to be safe and effective for the treatment of low-risk nodular and superficial BCC lesions.

Uveal melanoma patient attitudes towards prognostic testing using gene expression profiling.

Aim: This study explored uveal melanoma patient experiences and regret following molecular prognostic testing using a 15-gene expression profile (GEP) test. Materials & methods: A retrospective, cross-sectional survey study was conducted through an online questionnaire capturing patient-reported experiences with prognostic biopsy/molecular testing. Results: Of 177 respondents, 159 (90%) wanted prognostic information at diagnosis. Most 15-GEP-tested patients who shared their results (99%) reported gaining value from testing, as did patients tested with other methods. Patients who received prognostic testing experienced lower decision regret than those who opted out. Decision regret did not differ based on GEP class. Conclusion: Most uveal melanoma patients desire prognostic testing and gain value from the GEP, independent of a high- or low-risk result.

Uveal melanoma is a rare but aggressive eye cancer, resulting in distant metastasis in nearly 50% of patients. Molecular prognostic testing is often employed to determine who is at high or low risk of developing metastatic disease. A prognostic 15-gene expression profiling (GEP) test is commonly used throughout the USA and parts of Canada. The goal of this survey was to assess patient experiences with the 15-GEP and other prognostic methods. Of the 177 patients who participated in the survey, the majority reported that they wanted prognostic information at the time of diagnosis. Of patients who underwent 15-GEP testing, nearly all reported gaining value from their test result, regardless of their individual risk profile. This study supports prior findings using other prognostic methods that patients prefer information about their risk of metastasis and reinforces the importance of discussing prognostic testing options with newly diagnosed uveal melanoma patients.

Detecting blood transfusion reactions: What are vital signs anyway?

There is a lack of consistency in the scientific literature regarding what is included in vital signs and considered derangement in findings. We used vital signs during blood product administration as an exemplar to explore this controversy. Vital sign components varied across all studies when reviewed by a cohort of frontline nurses attempting to align institutional policy with current evidence. Only low-level data linking conventional approaches to vital sign monitoring for transfusion reaction detection were found.

Hemodynamic Abnormalities in the Aorta of Turner Syndrome Girls.

Congenital abnormalities in girls and women with Turner syndrome (TS), alongside an underlying predisposition to obesity and hypertension, contribute to an increased risk of cardiovascular disease and ultimately reduced life expectancy. We observe that children with TS present a greater variance in aortic arch morphology than their healthy counterparts, and hypothesize that their hemodynamics is also different. In this study, computational fluid dynamic (CFD) simulations were performed for four TS girls, and three age-matched healthy girls, using patient-specific inlet boundary conditions, obtained from phase-contrast MRI data. The visualization of multidirectional blood flow revealed an increase in vortical flow in the arch, supra-aortic vessels, and descending aorta, and a correlation between the presence of aortic abnormalities and disturbed flow. Compared to the relatively homogeneous pattern of time-averaged wall shear stress (TAWSS) on the healthy aortae, a highly heterogeneous distribution with elevated TAWSS values was observed in the TS geometries. Visualization of further shear stress parameters, such as oscillatory shear index (OSI), normalized relative residence time (RRTn), and transverse WSS (transWSS), revealed dissimilar heterogeneity in the oscillatory and multidirectional nature of the aortic flow. Taking into account the young age of our TS cohort (average age 13 ± 2 years) and their obesity level (75% were obese or overweight), which is believed to accelerate the initiation and progression of endothelial dysfunction, these findings may be an indication of atherosclerotic disease manifesting earlier in life in TS patients. Age, obesity and aortic morphology may, therefore, play a key role in assessing cardiovascular risk in TS children.

The Latest on Uveal Melanoma Research and Clinical Trials: Updates from the Cure Ocular Melanoma (CURE OM) Science Meeting (2019).

Uveal melanoma is a rare cancer in adults, but its treatment is one of the clinical unmet needs in the melanoma field. Metastatic disease develops in approximately 50% of patients and is associated with poor survival due to the lack of effective treatment options. It provides a paradigm for cancers that show evidence of aberrant G protein-coupled receptor signaling, tumor dormancy, and liver-selective metastatic tropism and are associated with the loss of the BAP1 tumor suppressor. At the Melanoma Research Foundation CURE OM Science Meeting at the Society for Melanoma Research Meeting held in Utah on November 20, 2019, clinicians and researchers presented findings from their studies according to three themes within uveal melanoma: (i) ongoing clinical trials, (ii) molecular determinants, and (iii) novel targets that could be translated into clinical trials. This meeting underscored the high interest in the uveal melanoma research field and the unmet need for effective treatment strategies for late-stage disease. Findings from ongoing clinical trials are promising, and multiple studies show how novel combinatorial strategies increase response rates. Novel targets and tumor vulnerabilities identified bioinformatically or through high-throughput screens also reveal new opportunities to target uveal melanoma. The future directions pursued by the uveal melanoma research field will likely have an impact on other cancer types that harbor similar genetic alterations and/or show similar biological properties.

Population structure of a vector-borne plant parasite.

Parasites are among the most diverse groups of life on Earth, yet complex natural histories often preclude studies of their speciation processes. The biology of parasitic plants facilitates in situ collection of data on both genetic structure and the mechanisms responsible for that structure. Here, we studied the role of mating, dispersal and establishment in host race formation of a parasitic plant. We investigated the population genetics of a vector-borne desert mistletoe (Phoradendron californicum) across two legume host tree species (Senegalia greggii and Prosopis velutina) in the Sonoran desert using microsatellites. Consistent with host race formation, we found strong host-associated genetic structure in sympatry, little genetic variation due to geographic site and weak isolation by distance. We hypothesize that genetic differentiation results from differences in the timing of mistletoe flowering by host species, as we found initial flowering date of individual mistletoes correlated with genetic ancestry. Hybrids with intermediate ancestry were detected genetically. Individuals likely resulting from recent, successful establishment events following dispersal between the host species were detected at frequencies similar to hybrids between host races. Therefore, barriers to gene flow between the host races may have been stronger at mating than at dispersal. We also found higher inbreeding and within-host individual relatedness values for mistletoes on the more rare and isolated host species (S. greggii). Our study spanned spatial scales to address how interactions with both vectors and hosts influence parasitic plant structure with implications for parasite virulence evolution and speciation.

Cardiac rehabilitation referral and enrolment across an academic health sciences centre with eReferral and peer navigation: a randomised controlled pilot trial.

OBJECTIVES: To describe (1) cardiac rehabilitation (CR) referral across cardiac units in a tertiary centre with eReferral; (2) characteristics associated with CR referral and enrolment and (3) the effects of peer navigation (PN) on referral and enrolment. This pilot was a 2 parallel-arm, randomised, single-blind trial with allocation concealment. SETTING: 3 cardiac units (ie, interventional, general cardiology, and cardiac surgery) in 1 of 2 hospitals of a tertiary centre. PARTICIPANTS: CR-eligible adult cardiac inpatients were randomised to PN or usual care. 94 (54.7%) patients consented, of which 46 (48.9%) were randomised to PN. Outcomes were ascertained in 76 (80.9%) participants. INTERVENTION: The PN (1) visited participant at the bedside, (2) mailed a card to participant's home reminding about CR and (3) called participant 2 weeks postdischarge to discuss CR barriers. OUTCOME MEASURES: The primary outcome of enrolment was defined as participant attendance at a scheduled CR intake appointment (yes/no). The secondary outcome was referral. Blinded outcome assessment was conducted 12 weeks postdischarge, via CR chart extraction. RESULTS: Those who received care on the cardiac surgery unit (77.9%) were more likely to be referred than those treated on the general cardiology (61.1%) or interventional unit (33.3%; p=0.04). Patients who had cardiac surgery, hypertension and hyperlipidaemia were significantly more likely, and those with congenital heart disease, cancer and a previous cardiac diagnosis were less likely to be referred. Participants referred to a site closer to home (76.2% of those referred) were more likely to enrol than those not (23.7%, p<0.05). PN had no effect on referral (77.6%, p=0.45) or enrolment (46.0%, p=0.24). CONCLUSIONS: There is wide variability in CR referral, even within academic centres, and despite eReferral. Referral was quite high, and thus, PN did not improve CR utilisation. Results support triaging patients to the CR programme closest to their home. TRIAL REGISTRATION NUMBER: NCT02204449; Results.

The Rho guanine nucleotide exchange factor Syx regulates the balance of dia and ROCK activities to promote polarized-cancer-cell migration.

The role of RhoA in promoting directed cell migration has been complicated by studies showing that it is activated both in the front and the rear of migrating cells. We report here that the RhoA-specific guanine nucleotide exchange factor Syx is required for the polarity of actively migrating brain and breast tumor cells. This function of Syx is mediated by the selective activation of the RhoA downstream effector Dia1, the subsequent reorganization of microtubules, and the downregulation of focal adhesions and actin stress fibers. The data argue that directed cell migration requires the precise spatiotemporal regulation of Dia1 and ROCK activities in the cell. The recruitment of Syx to the cell membrane and the subsequent selective activation of Dia1 signaling, coupled with the suppression of ROCK and activation of cofilin-mediated actin reorganization, plays a key role in establishing cell polarity during directed cell migration.

A quantitative description of in vitro assembly of human papillomavirus 16 virus-like particles.

The full-length human papillomavirus 16 major capsid protein L1 is expressed in Saccharomyces cerevisiae as virus-like particles (VLPs). However, yeast-expressed human papillomavirus 16 particles are irregular in shape and are prone to aggregate. When disassembled and reassembled, the resulting particles have improved stability and solubility. We have examined VLP dissociation and reassembly to define the important features of the assembly mechanism. We found that the VLPs rapidly disassemble at pH 8.2 and low ionic strength in the presence of low concentrations of reducing agents. The pH dependence of assembly kinetics and extent of assembly under reducing conditions were differentially sensitive to ionic strength. Assembly at pH 5.2 was very fast and led to heavily aggregated particles. This sort of kinetic trap is expected for overinitiated assembly. We observed that reassembly at pH 6.2, 7.2, and 8.2 yielded regular particles over a broad range of ionic strength. At these three pH values, assembly was quantitative at 1 M NaCl. At pH 7.2, much more than at pH 6.2 or pH 8.2, assembly decreased monotonically with ionic strength. The free energy of association ranged from -8 to -10 kcal/mol per pentamer. The effect of pH on assembly was further investigated by examining dissociation of reassembled particles. Though indistinguishable by negative stain electron microscopy, particles assembled at pH 7.2 disassembled slower than pH 5.2, 6.2, or 8.2 VLPs. We hypothesize that pH 7.2 assembly reactions lead to formation of particles with conformationally different interactions.

Vitamin C transport and SVCT1 transporter expression in chick renal proximal tubule cells in culture.

The characteristics of vitamin C (ascorbic acid, ASC) transport were studied in polarized cultured monolayers of the chick (Gallus gallus) renal proximal tubule in Ussing chambers. Under voltage clamp conditions, monolayers responded to apical addition of ASC in a dose-dependent manner, with positive short circuit currents (I(SC)), ranging from 3 microA/cm(2) at 5 microM ASC to a maximal response of 27 microA/cm(2) at 200 microM, and a half-maximal response at 40 microM. There was no effect of basolateral addition of ASC, indicating a polarized transport process. The oxidized form of ASC, dehydroascorbic acid had negligible effects. The I(SC) response to ASC was completely eliminated with Na(+) ion replacement, and was also eliminated by bilateral reduction of bath Cl(-), from 137 to 2.6 mM. There was significant inhibition of the I(SC) responses to 30 microM ASC by the flavanoid quercetin (50 microM) and by 100 microM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and 5-ethylisopropylamiloride (EIPA), blockers of anion exchangers and sodium-proton exchangers, respectively. There was no inhibition, however, by the chloride channel blocker 5-nitro-2(3-phenylpropylamino)benzoic acid (NPPB). Phorbol 12-myristate 13 acetate (PMA), the phorbol ester activator of protein kinase C, caused a 37% decrease in the I(SC) response to ASC. Chicken-specific primers to an EST homolog of the human vitamin C transporter SVCT1 (SLC23A1) were designed and used to probe transporter expression in these cells. RT-PCR analysis demonstrated the presence of chicken SVCT1 in both cultured cells and in freshly isolated proximal tubule fragments. These data indicate the presence of an electrogenic, sodium-dependent vitamin C transporter (SVCT1) in the chick renal proximal tubule. Vitamin C transport and conservation by the kidney is likely to be especially critical in birds, due to high plasma glucose levels and resulting high levels of reactive oxygen species.