Impact of Increased Patient-Clinician Virtual Visits During the COVID-19 Pandemic on Medical Student Enthusiasm for Future General Practice Careers.

BACKGROUND: The COVID-19 pandemic restricted the availability of face-to-face primary care visits. This rapidly increased the proportion of primary care patient-clinician visits conducted virtually and asynchronously (remote consultations via video, telephone, and web-based text/email), altering the educational environment for medical students. Our study explored the impact of the increased proportion of primary care visits conducted virtually and asynchronously, on medical students' self-reported interest in pursuing a career in general (family) practice. METHODS: We conducted a cross-sectional survey study of medical students at six universities within England and Wales to explore the impact of the increased proportion of primary care visits conducted virtually and asynchronously on medical students' interest in pursuing a career in general practice. RESULTS: One hundred fifty-four medical students were recruited between December 2020 and May 2021; 79 (51%) of the participants reported being less interested in pursuing a career in general practice as a result of the increased proportion of virtual and asynchronous primary care visits during the COVID-19 pandemic. This increased to 104 (68%) of the participants reporting being less interested should primary care visits continue to be delivered virtually or asynchronously by default. Analysis of open-ended survey questions identified a poorer educational experience, concerns regarding the impact on patient care, an isolated working environment and technological challenges as key negative themes. CONCLUSIONS: Sociable, supportive working and learning environments and offering equitable care are important motivators for the future workforce. There is a need to develop robust training and assessment in patient-clinician virtual visits and asynchronous communication and to integrate this into curricula.

Combining a stellate ganglion block with prolonged exposure therapy for posttraumatic stress disorder: A nonrandomized clinical trial.

Prolonged exposure therapy (PE) is an efficacious treatment for active duty service members and veterans with posttraumatic stress disorder (PTSD). However, PE is sometimes associated with high dropout rates, limited tolerability, and temporary symptom exacerbation during treatment. Stellate ganglion blocks (SGBs) are an emerging treatment that has the potential to enhance outcomes for PTSD when combined with trauma-focused psychotherapy. To date, no study of which we are aware has examined the potential additive benefits of SGB injections when administered in conjunction with trauma-focused behavioral treatment for PTSD. Thus, we conducted a nonrandomized clinical trial to evaluate the use of an SGB combined with massed PE therapy for combat-related PTSD. Participants (N = 12) were treated with 10 daily 90-min PE sessions delivered over 2 weeks and received a single SGB injection between Sessions 1 and 2. PE sessions lasted 90 min each. Participants reported a mean posttreatment PTSD symptom reduction of 32 points on the PTSD Checklist for DSM-5 (PCL-5), Hedges' gs = 1.28-2.80. Most participants (90.9%) demonstrated clinically significant change on the PCL-5 (i.e., ≥10 points) by the final treatment session and 50.0% no longer met the diagnostic criteria for PTSD per the Clinician-Administered PTSD Scale for DSM-5 at 1-month follow-up. Adverse events for the combined treatment were consistent with those previously reported for standalone SGB and PE. This combined treatment approach provides promising results for improving the tolerability of trauma-focused therapies, reducing symptom severity, and increasing PTSD remission rates.

Shoulder, elbow, and wrist joint angle excursions vary by gesture during touchscreen interaction.

Repeated gesturing on touchscreen computing devices has become part of professional, personal, or school use by persons of all ages. Few studies have compared kinematics among joint motions and gestures during touchscreen interaction. We aimed to quantify the relative contributions of the shoulder, elbow and wrist to completion of several gestures to aid understanding of touchscreen ergonomics. Joint angles of the shoulder, elbow, and wrist were recorded for 22 seated participants while they interacted with a 10.1″ tablet computer held on an easel. Joint excursions at the shoulder, elbow, and wrist were all on average ≤20° during touchscreen interaction. The greatest excursion measured was shoulder rotation for swipe right with a mean of 15.5(±6.0)°. Index finger tap on a touchscreen was completed by participants with less than 5° of mean joint excursion at the shoulder, elbow and wrist. Tap, pinch and stretch gestures demonstrated significantly more wrist flexion/extension (p < 0.05) than shoulder flexion/extension, ab/adduction and rotation. Also, swipe left, right and up involved more shoulder rotation (p < 0.05) than wrist flexion/extension. These results suggest that when gestures are repeated frequently, the relative risk of overuse injury at the shoulder, elbow, or wrist may depend on the gesture being repeated.

Forces at the Feet, Gait Timing, and Trunk Flexion/Extension Excursion While Walking with a Gear Belt or Gear Vest Load.

Law enforcement personnel often carry gear loads, which have a history of causing low back pain. The aim of this study was to evaluate the differences in gait and trunk posture for gear load carried on a gear belt and a gear vest. Twenty-nine participants performed load carriage in three conditions: a no load control trial (C), a symmetrically loaded gear belt (GB), and an anterior-loaded gear vest (ALV). Gear conditions had 9.07 kg of additional mass. Motion capture and insole force sensors were used to collect data while participants walked on a treadmill for three minutes per condition. Mean insole reaction force was significantly greater in both GB and ALV conditions as compared to C (p < 0.001). Mean gait cadence in the GB or ALV condition were not significantly different from the C condition. However, double support time in the ALV condition was significantly longer compared to C condition (p = 0.023). Stance duration on the left foot was significantly longer with the GB (p = 0.001) and ALV (p = 0.028) when compared to C. Results showed trunk flexion/extension excursion was significantly less in the GB condition when compared to the C condition (p = 0.002). These findings demonstrate that law enforcement and other personnel who walk while carrying gear loads may experience altered biomechanics compared to unloaded walking. Altered biomechanics and increased forces on the feet could potentially increase risk of musculoskeletal injury while carrying gear loads.

Upper limb manual dexterity, strength and blood flow after walking with backpack load.

This study aimed to characterize the effects of walking with backpack load on upper limb function. Fifteen males participated in 3 conditions: no load, 40% body weight loaded backpack (BP) and loaded backpack with simulated rifle (BRC). Pinch strength, grip strength, sensory threshold, blood flow volume, and a manual dexterity test were assessed before and after a 45-min walking trial. Pinch strength in the BP condition was significantly different than the control (p < 0.05). Grooved pegboard times were faster after a seated recovery (p = 0.026) than immediately after walking with load. Blood flow was significantly decreased to <53% of baseline (p ≤ 0.001) in BP and BRC immediately after donning the backpack. No significant changes in grip strength or sensory threshold were measured among conditions or time points. In conclusion, pinch strength, manual dexterity and blood flow were affected by backpack carriage, but other upper limb measures remained unaffected.

Manganese transport and toxicity in polarized WIF-B hepatocytes.

Manganese (Mn) toxicity arises from nutritional problems, community and occupational exposures, and genetic risks. Mn blood levels are controlled by hepatobiliary clearance. The goals of this study were to determine the cellular distribution of Mn transporters in polarized hepatocytes, to establish an in vitro assay for hepatocyte Mn efflux, and to examine possible roles the Mn transporters would play in metal import and export. For these experiments, hepatocytoma WIF-B cells were grown for 12-14 days to achieve maximal polarity. Immunoblots showed that Mn transporters ZIP8, ZnT10, ferroportin (Fpn), and ZIP14 were present. Indirect immunofluorescence microscopy localized Fpn and ZIP14 to WIF-B cell basolateral domains whereas ZnT10 and ZIP8 associated with intracellular vesicular compartments. ZIP8-positive structures were distributed uniformly throughout the cytoplasm, but ZnT10-positive vesicles were adjacent to apical bile compartments. WIF-B cells were sensitive to Mn toxicity, showing decreased viability after 16 h exposure to >250 µM MnCl2. However, the hepatocytes were resistant to 4-h exposures of up to 500 µM MnCl2 despite 50-fold increased Mn content. Washout experiments showed time-dependent efflux with 80% Mn released after a 4 h chase period. Hepcidin reduced levels of Fpn in WIF-B cells, clearing Fpn from the cell surface, but Mn efflux was unaffected. The secretory inhibitor, brefeldin A, did block release of Mn from WIF-B cells, suggesting vesicle fusion may be involved in export. These results point to a possible role of ZnT10 to import Mn into vesicles that subsequently fuse with the apical membrane and empty their contents into bile. NEW & NOTEWORTHY Polarized WIF-B hepatocytes express manganese (Mn) transporters ZIP8, ZnT10, ferroportin (Fpn), and ZIP14. Fpn and ZIP14 localize to basolateral domains. ZnT10-positive vesicles were adjacent to apical bile compartments, and ZIP8-positive vesicles were distributed uniformly throughout the cytoplasm. WIF-B hepatocyte Mn export was resistant to hepcidin but inhibited by brefeldin A, pointing to an efflux mechanism involving ZnT10-mediated uptake of Mn into vesicles that subsequently fuse with and empty their contents across the apical bile canalicular membrane.

Erratum: Substrate Grain-Dependent Chemistry of Carburized Planar Anodic TiO2 on Polycrystalline Ti.

[This corrects the article DOI: 10.1021/acsomega.6b00472.].

Substrate Grain-Dependent Chemistry of Carburized Planar Anodic TiO2 on Polycrystalline Ti.

Mixtures or composites of titania and carbon have gained considerable research interest as innovative catalyst supports for low- and intermediate-temperature proton-exchange membrane fuel cells. For applications in electrocatalysis, variations in the local physicochemical properties of the employed materials can have significant effects on their behavior as catalyst supports. To assess microscopic heterogeneities in composition, structure, and morphology, a microscopic multitechnique approach is required. In this work, compact anodic TiO2 films on planar polycrystalline Ti substrates are converted into carbon/titania composites or multiphase titanium oxycarbides through carbothermal treatment in an acetylene/argon atmosphere in a flow reactor. The local chemical composition, structure, and morphology of the converted films are studied with scanning photoelectron microscopy, micro-Raman spectroscopy, and scanning electron microscopy and are related with the crystallographic orientations of the Ti substrate grains by means of electron backscatter diffraction. Different annealing temperatures, ranging from 550 to 850 °C, are found to yield different substrate grain-dependent chemical compositions, structures, and morphologies. The present study reveals individual time scales for the carbothermal conversion and subsequent surface re-oxidation on substrate grains of a given orientation. Furthermore, it demonstrates the power of a microscopic multitechnique approach for studying polycrystalline heterogeneous materials for electrocatalytic applications.

Invasive swimbladder parasite Anguillicoloides crassus: infection status 15 years after discovery in wild populations of American eel Anguilla rostrata.

A year-round survey of American eels Anguilla rostrata was performed at 5 localities in South Carolina (SC), USA, 15 yr after the first infection by the nematode Anguillicoloides crassus was reported from Winyah Bay, SC. Infections by adult stages of A. crassus in the swimbladder lumen occurred with a prevalence of 45% (n = 479), a mean intensity (± SE) of 2.3 ± 0.2 worms per infected eel (range = 1-22), and a mean abundance of 2.0 ± 0.1 among all eels. Infections by larval stages of A. crassus in the swimbladder wall occurred with a prevalence, intensity, and abundance of 29%, 2.4 ± 0.3 (range = 1-15), and 0.7 ± 0.1, respectively (n = 471). Overall prevalence of the parasite (any stage) was 58%, with a mean intensity ± SE of 3.0 ± 0.2 and a mean abundance of 1.8 ± 0.2. Biomass of the adult parasite stage varied significantly with eel body length, but the direction of the effect depended on salinity. Prevalence and intensity of infection by adult nematodes varied by locality but not by eel total length, salinity, or season. Larval prevalence was significantly greater in the winter and spring and also differed among localities. The lack of seasonal effects on infection by the adult worm stage contrasts with studies from higher latitudes in North America and Europe and may be due to the warmer winter temperatures at southern latitudes. Significant variation in infection among localities reflects possible differences in abundance of intermediate and/or paratenic hosts. Overall, infection levels were higher than previous reports for eels in SC but comparable to more recent reports from other areas in North America.

Merkel cell polyomavirus large T antigen disrupts lysosome clustering by translocating human Vam6p from the cytoplasm to the nucleus.

Merkel cell polyomavirus (MCV) has been recently described as the cause for most human Merkel cell carcinomas. MCV is similar to simian virus 40 (SV40) and encodes a nuclear large T (LT) oncoprotein that is usually mutated to eliminate viral replication among tumor-derived MCV. We identified the hVam6p cytoplasmic protein involved in lysosomal processing as a novel interactor with MCV LT but not SV40 LT. hVam6p binds through its clathrin heavy chain homology domain to a unique region of MCV LT adjacent to the retinoblastoma binding site. MCV LT translocates hVam6p to the nucleus, sequestering it from involvement in lysosomal trafficking. A naturally occurring, tumor-derived mutant LT (MCV350) lacking a nuclear localization signal binds hVam6p but fails to inhibit hVam6p-induced lysosomal clustering. MCV has evolved a novel mechanism to target hVam6p that may contribute to viral uncoating or egress through lysosomal processing during virus replication.

Multiple DNA damage signaling and repair pathways deregulated by simian virus 40 large T antigen.

We demonstrated previously that expression of simian virus 40 (SV40) large T antigen (LT), without a viral origin, is sufficient to induce the hallmarks of a cellular DNA damage response (DDR), such as focal accumulation of gamma-H2AX and 53BP1, via Bub1 binding. Here we expand our characterization of LT effects on the DDR. Using comet assays, we demonstrate that LT induces overt DNA damage. The Fanconi anemia pathway, associated with replication stress, becomes activated, since FancD2 accumulates in foci, and monoubiquitinated FancD2 is detected on chromatin. LT also induces a distinct set of foci of the homologous recombination repair protein Rad51 that are colocalized with Nbs1 and PML. The FancD2 and Rad51 foci require neither Bub1 nor retinoblastoma protein binding. Strikingly, wild-type LT is localized on chromatin at, or near, the Rad51/PML foci, but the LT mutant in Bub1 binding is not localized there. SV40 infection was previously shown to trigger ATM activation, which facilitates viral replication. We demonstrate that productive infection also triggers ATR-dependent Chk1 activation and that Rad51 and FancD2 colocalize with LT in viral replication centers. Using small interfering RNA (siRNA)-mediated knockdown, we demonstrate that Rad51 and, to a lesser extent, FancD2 are required for efficient viral replication in vivo, suggesting that homologous recombination is important for high-level extrachromosomal replication. Taken together, the interplay of LT with the DDR is more complex than anticipated, with individual domains of LT being connected to different subcomponents of the DDR and repair machinery.

Simian virus 40 large T antigen disrupts genome integrity and activates a DNA damage response via Bub1 binding.

Simian virus 40 (SV40) large T antigen (LT) is a multifunctional protein that is important for viral replication and oncogenic transformation. Previously, infection of monkey or human cells with SV40 was shown to lead to the induction of DNA damage response signaling, which is required for efficient viral replication. However, it was not clear if LT is sufficient to induce the damage response and, if so, what the genetic requirements and functional consequences might be. Here, we show that the expression of LT alone, without a replication origin, can induce key DNA damage response markers including the accumulation of gamma-H2AX and 53BP1 in nuclear foci. Other DNA damage-signaling components downstream of ATM/ATR kinases were induced, including chk1 and chk2. LT also bound the Claspin mediator protein, which normally facilitates the ATR activation of chk1 and monitors cellular replication origins. Stimulation of the damage response by LT depends mainly on binding to Bub1 rather than to the retinoblastoma protein. LT has long been known to stabilize p53 despite functionally inactivating it. We show that the activation of a DNA damage response by LT via Bub1 appears to play a major role in p53 stabilization by promoting the phosphorylation of p53 at Ser15. Accompanying the DNA damage response, LT induces tetraploidy, which is also dependent on Bub1 binding. Taken together, our data suggest that LT, via Bub1 binding, breaches genome integrity mechanisms, leading to DNA damage responses, p53 stabilization, and tetraploidy.