Search

Mechanical Affective Touch Therapy (MATT) is a safe, novel form of noninvasive peripheral nerve stimulation. Although mechanical stimulation activates nerves, we know little about its impact on psychiatric symptoms and their underlying cortical mechanisms. We examined the effects of open-label MATT on resting state functional connectivity (RSFC) and its relationship with anxiety and affective symptomatology (clinical results in separate report).A total of 22 adults with an Axis I anxiety disorder were recruited from the community. After two initial sessions assisted by research staff, participants self-administered 20-minute sessions of MATT at home at least twice daily for four weeks. Self-report measures of mood and anxiety severity were collected at baseline, two weeks, and four weeks. Resting state functional magnetic resonance imaging was collected before the initial MATT session (n = 20), immediately after the first session (n = 18), and following four weeks of MATT (n = 14). Seed-based whole-brain functional connectivity analyses identified brain connectivity patterns correlated with responsiveness to MATT. Seeds were based on Neurosynth meta-analytic maps for "anxiety" and "pain" given MATT's hypothesized role in anxiety symptom amelioration and potential mechanism of action through C-tactile afferents, which play an important role in detecting pain and its affective components. Connectivity results were corrected for multiple comparisons (voxel p 0.005, cluster p-FDR 0.05).Baseline RSFC is predictive of symptom improvement with chronic MATT. Acute increases in insula connectivity were observed between mid-cingulate cortex and postcentral motor regions following the first MATT session. Chronic MATT was associated with increased connectivity between pain and anxiety regions of interest (ROIs) and posterior default mode network (DMN) regions involved in memory and self-reflection; the connectivity changes correlated with decreases in stress and depression symptoms.MATT is associated with alterations in RSFC in the DMN of anxiety disorder patients both acutely and after long-term administration, and baseline RSFC is predictive of post-treatment symptom improvement.

A variety of reports suggest that rhythmic auditory stimulation can entrain visual perception, inducing perceptual oscillations as a function of time relative to the auditory rhythm. These effects have, to date, been reported only for stimulation frequencies at and below 3 Hz. Here we investigate the effects of rhythmic auditory stimulation on the detection of masked visual targets when this stimulation occurs at frequencies to which the visual system has been shown to entrain (8-12 Hz). Across four experiments, we found no consistent evidence of poststimulation modulations in performance induced by 8.5, 10.6, or 12.1 Hz auditory stimulation. This absence of a consistent auditory-to-visual effect was paralleled by an absence of unimodal effects (oscillations in auditory performance) following 12.1 Hz auditory stimulation. In a fifth experiment, we found that although auditory stimulation alone did not induce oscillations in visual performance, auditory stimulation did enhance the effects of concurrent visual stimulation. Notably, this enhancement did not require synchronous presentation of stimuli. These observations are consistent with recent reports that passive auditory stimulation beyond 5 Hz induces neither auditory perceptual oscillations nor visual cortical oscillations and suggest limits to the extent of cross-modal entrainment. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Family caregivers of patients with cancer provide substantial physical, emotional, and functional care throughout the cancer trajectory. While caregiving can create employment and financial challenges, there is insufficient evidence to inform the development of caregiver-reported outcomes (CROs) that assess these experiences. The study purpose was to describe the occupational and financial consequences that were important to family caregivers of a patient with colorectal cancer (CRC) in the context of public health care, which represent potential considerations for CROs. In this qualitative Interpretive Description study, we analyzed interview data from 78 participants (25 caregivers, 37 patients, and 16 healthcare providers). Our findings point to temporary and long-term occupational and financial setbacks in the context of CRC. Caregiving for a person with CRC involved managing occupational implications, including (1) revamping employment arrangements, and (2) juggling work, family, and household demands. Caregiver financial struggles included (1) responding to financial demands at various stages of life, and (2) facing the spectre of lifelong expenses. Study findings offer novel insight into the cancer-related occupational and financial challenges facing caregivers, despite government-funded universal health care. Further research is warranted to develop CRO measures that assess the multifaceted nature of these challenges.

The right ventricle (RV) and pulmonary arterial (PA) tree are inextricably linked, continually transferring energy back and forth in a process known as RV-PA coupling. Healthy organisms maintain this relationship in optimal balance by modulating RV contractility, pulmonary vascular resistance, and compliance to sustain RV-PA coupling through life's many physiologic challenges. Early in states of adaptation to cardiovascular disease-for example, in diastolic heart failure-RV-PA coupling is maintained via a multitude of cellular and mechanical transformations. However, with disease progression, these compensatory mechanisms fail and become maladaptive, leading to the often-fatal state of "uncoupling." Noninvasive imaging modalities, including echocardiography, magnetic resonance imaging, and computed tomography, allow us deeper insight into the state of coupling for an individual patient, providing for prognostication and potential intervention before uncoupling occurs. In this review, we discuss the physiologic foundations of RV-PA coupling, elaborate on the imaging techniques to qualify and quantify it, and correlate these fundamental principles with clinical scenarios in health and disease. © 2022 American Physiological Society. Compr Physiol 12: 1-26, 2022.

Malnutrition is common among older adults and is related to quality of life, cognitive function, and depression. To what extent nutrition interventions can improve these outcomes remains unclear. The aim of this study was to investigate the effect of nutrition therapy on health-related quality of life (EQ-5D), self-rated health, cognitive function, and depression in community dwelling older adults recently discharged from hospital.Participants (65 years) were randomised into an intervention (n = 53) and a control group (n = 53). The intervention group received individualised nutrition therapy based on the nutrition care process including 5 home visits and 3 phone calls, in combination with freely delivered energy- and protein-rich foods and oral nutrition supplements for six months after hospital discharge. EQ-5D, self-rated health, Mini-Mental-State-Examination (MMSE), and the Centre for Epidemiologic Studies Depression - IOWA (CES-D) scale were measured at baseline and at endpoint.Two subjects dropped out, one from each arm. The control group experienced an increase in depressive symptoms and a decrease in self-rated health during the study period, while the intervention group experienced increases in cognitive function, self-rated health, and EQ-5D resulting in significant endpoint differences between the groups: EQ-5D (0.102, P = 0.001); self-rated health: 15.876 (P 0.001); MMSE: 1.701 (P 0.001); depressive symptoms: - 3.072 (P 0.001); all in favour of the intervention group. Improvements during the intervention in MMSE, self-rated health, and CES-D were significantly related to body weight gain in a linear way.Cognitive function and mental well-being worsen or stagnate in older adults who receive standard care after hospital discharge. However, a six-month nutrition therapy improves these outcomes leading to statistically and clinically significant endpoint differences between the groups. As improvements were related to body weight gain after hospital discharge, we conclude that the increase in dietary intake, with focus on energy and protein density, and changes in body weight might have contributed to better cognitive function and mental well-being in older adults after the intervention.

Purpose The purpose of this study was to investigate outcomes following arthroscopic elbow contracture release to describe the use of arthroscopy for improvement in extension/flexion and pronation/supination arcs of motion at a single institution for degenerative and posttraumatic etiologies. Methods Consecutive arthroscopic elbow arthrolysis performed between 2003 and 2015 were retrospectively reviewed. Basic patient demographics, indications for surgery, preoperative and postoperative elbow range of motion, postoperative patient outcome score, and all complications were recorded and analyzed. Results Fifty-two patients were included with an average follow-up of 5.1 years (range 1.4 to 9.4). Severe contractures made up 50% of cases, followed by 23% moderate, and 27% mild. Average extension/flexion for the post-traumatic group (n = 30) increased by 63° ± 31 and by 29° ± 24 for the degenerative group (n = 22). Average gain in pronosupination was 38° ± 62 in the post-traumatic group and 13°±23 in the degenerative group. Postoperative DASH scores were 17.5 ± 18.4 for post-traumatic cases and 12.8 ± 19.3 for degenerative cases. Conclusion Arthroscopic elbow contracture release is an effective intervention for degenerative and post-traumatic elbow contracture for both flexion/extension and pronosupination contracture. Furthermore, a two-stage release should be considered when both flexion and pronosupinaton contractures are present. Level of Evidence IV, case series, treatment study

OBJECTIVE To determine the number and species of animals cared for by the PetSafe program at the Purdue University College of Veterinary Medicine (a community service offered to meet the short-term housing needs of pets, especially pets owned by victims of intimate partner violence) from 2004 through 2019 and collect information on duration of stay, outcome, health problems, and expenses. ANIMALS 229 animals cared for by the PetSafe program. PROCEDURES Medical records were reviewed for information on species, breed, age, duration of stay, outcome of stay, client referral source, whether the animal had been cared for previously, health problems, medical interventions, and expenses incurred. RESULTS There were 124 dogs, 95 cats, 6 ferrets, and 4 sugar gliders; 187 of the animals were returned to their owners, 37 were rehomed, and 5 were euthanized because of medical conditions. The most common health problems were dental disease and dermatological complaints (eg, flea infestation and resulting fleabite dermatitis). None of the animals had physical evidence of abuse. Mean duration of stay was 22 days (range, 1 to 93 days), and mean ± SD cost per animal was $368 ± $341. CLINICAL RELEVANCE Over the 16-year period of the study, the number and species of animals cared for by the PetSafe program at Purdue and the health problems encountered in those animals were relatively stable, and the program was able to meet the relatively predictable financial costs incurred through existing sources of funding.

Previous work has claimed that canonical viewpoints of objects are more readily perceived than noncanonical viewpoints. However, all of these studies required participants to identify the object, a late perceptual process at best and arguably a cognitive process (Pylyshyn, 1999). Here, we extend this work to early vision by removing the explicit need to identify the objects. In particular, we asked participants to make an intact/scrambled discrimination of briefly presented objects that were viewed from either typical or atypical viewpoints. Notably, participants did not have to identify the object; only discriminate it from noise (scrambled). Participants were more sensitive in discriminating objects presented in typically encountered orientations than when objects were presented in atypical depth rotations (Experiment 1). However, the same effect for objects presented in atypical picture plane rotations (as opposed to typical ones) did not reach statistical significance (Experiments 2 and 3), suggesting that particular informative views may play a critical role in this effect. We interpret this enhanced perceptibility, for both these items and good exemplars and probable scenes, as deriving from their high real-world statistical regularity.

Background The COVID-19 pandemic resulted in public health and policy measures to reduce in-person contact and the transmission of the virus. These measures impacted daily life and mental well-being (MWB). The aims of this study were to explore the MWB impacts of COVID-19 on children and assess the associations among perceived changes in physical activity (PA) and sedentary behaviors (SB), with perceived MWB changes, using a mixed-methods approach. Methods A convergent parallel mixed-methods design consisting of an online survey with a convenience sample and interviews was conducted from May through July 2020 with parents/caregivers of kindergarten through 5th graders in the St. Louis region. Survey domains assessed included child MWB, PA, and SB. Interviews were recorded, transcribed, and qualitatively analyzed using a code book developed to elicit themes. Survey data was analyzed with chi-squared tests and logistic regressions. The dependent variable was perceived change in child MWB due to the impact of COVID-19. Independent variables included perceived changes in PA, SB, and child concerns about COVID-19. Results Sample size consisted of 144 surveys and 16 interviews. Most parents reported a perceived decrease in child MWB (74%), a decrease in child PA (61%), and an increase in child SB (91%). Discontentment with stay-at-home orders and concern about COVID-19 were associated with a perceived decrease in MWB. Children whose PA decreased were 53% less likely to have the same or better MWB (OR 0.47) and children whose outside PA decreased were 72% less likely to have the same or better MWB (OR 0.28). Common qualitative themes included difficulty in adjusting to COVID-19 restrictions due to school closures and lack of socializing, child concerns about family getting sick, and PA benefits for improving MWB. Conclusions Based on parent perceptions, MWB decreased with COVID-19. Maintained or increased child PA improved the chances MWB would remain the same or improve. Parent interviews provide context to these findings by showing how COVID-19 impacted MWB and the associations between PA and MWB. Understanding protective factors for child MWB during COVID-19 is important to offset negative long-term health outcomes from this ongoing pandemic.

OBJECTIVE To summarize and describe the current US surveillance systems that assess physical activity (PA) for work and commuting. METHODS An expert group conducted an environmental scan, generating a list (n = 18) which was ultimately reduced to 12, based on the inclusion of PA and/or sedentary behavior data. RESULTS The 12 surveys or surveillance systems summarized provide nationally representative data on occupational-level PA or individual-level PA at work, data on active commuting, some are scorecards that summarize workplace health best practices and allow benchmarking, and one is a comprehensive nationally representative survey of employers assessing programs and practices in different worksites. CONCLUSIONS The various surveillance systems and surveys/scorecards are disparate and need to be better analyzed and summarized to understand the impact of occupational-level PA and commuting on population health and well-being, life expectancy, and workforce productivity.

Background Increasing physical activity (PA) in rural communities is a vital prevention tactic in multiple chronic diseases; however, little is known on the multilevel correlates of PA rural areas. A better understanding of domain-specific PA adds context for promoting PA in rural communities. The current study sought to determine factors associated with domain-specific and overall moderate-vigorous physical activity (MVPA) in rural communities. Methods Surveys were conducted across 14 rural mid-Western communities, with the final analytical sample including 1241 adults (ages 19–96, M = 57.0 [SD = 16.7], 67.8% female, 83.8% white). Generalized linear models with negative binomial distributions examined the relation between demographics, trail use, and perceptions of the neighborhood environment, with domain-specific and overall MVPA, measured via the Global Physical Activity Questionnaire. Results Rural residents reported an average of 617 total minutes of weekly MVPA (SD = 1141), with 58.5% meeting MVPA guidelines. Higher age, female gender, and higher educated individuals had lower levels of overall and occupational MVPA. Females, higher education, and perceived indoor recreational access were associated with lower levels of transportation-related MVPA, while trail use was associated with increased transportation MVPA. Higher age and female gender respondents had lower levels of recreational MVPA, while trail users and those who perceived favorable indoor recreational access had higher levels of recreational MVPA. Conclusions PA primarily occurred in the occupational domain among this sample of rural mid-Western adults. Findings highlight the need for multilevel interventions to address PA across multiple domains in rural communities, especially among females and older adults.

Objective To adapt the Boston Assessment of TBI-Lifetime (BAT-L) interview specifically for female survivors of intimate partner violence (IPV), validate the adapted BAT-L/IPV, and report the prevalence of head injury. Setting The BAT-L is the first validated instrument to diagnose traumatic brain injuries (TBIs) throughout the life span for post-9/11 veterans. The BAT-L/IPV was adapted to target diagnostic issues belonging exclusively to IPV while maintaining its life span approach. Participants Community-dwelling convenience sample of 51 female survivors of IPV with subthreshold (n = 10) or full diagnostic criteria (n = 41) of posttraumatic stress disorder. Design Standard TBI criteria were evaluated using a semistructured clinical interview. Main measures The BAT-L/IPV is compared with the Ohio State University TBI Identification Method (OSU-TBI-ID) scoring approach as the criterion standard. Results Correspondence between the BAT-L/IPV and the OSU-TBI-ID score was excellent (Cohen κ = 0.86; Kendall τ-b = 0.89). Sensitivity = 89.3% (95% CI, 81.2-97.4); specificity = 98.3% (95% CI, 95.0-100); positive predictive value = 98.0% (95% CI, 94.2-100); and negative predictive value = 90.6% (95% CI, 83.5-97.7). On the BAT-L/IPV, more than one-third (35.3%) of IPV survivors reported TBI secondary to an IPV-related assault, 76.5% reported IPV subconcussive head injury, 31.4% reported attempted strangulation, and 37.3% reported non-IPV TBI. Conclusions The BAT-L/IPV performed well in diagnosing TBI in female IPV survivors as compared with the criterion standard. The prevalence of TBI was frequent; subconcussive head injury was pervasive. Greater awareness for head injury risk and increased diagnostic specificity of TBI in IPV survivors is needed.

Binocular rivalry occurs when incompatible images are presented simultaneously but separately to each eye. Perceptual dominance reverses over time such that one image temporarily dominates perception, while the other image is suppressed. Prior research has shown that briefly-presented probes modulate perception such that probes presented to the suppressed eye tend to produce shorter percept durations relative to when probes are presented to the dominant eye. This pattern suggests that probes strengthen the competitive strength of the image over which they appear. However, it remains unclear whether probe-modulated effects on binocular rivalry are equivalent across the visual field, in particular as a function of whether probes appear within the region of interocular conflict (i.e on-object) or outside the region of interocular conflict (i.e. off-object). We tested this by manipulating whether probes appeared on-object or off-object. We replicate prior work showing that suppressed-eye probes produce shorter percept durations relative to dominant-eye probes. Critically, however, we show that percept duration also varies as a function of whether probes appear on vs. off the rivalry objects; that is, differences in percept duration between suppressed-eye and dominant-eye probes were much larger for on-object than off-object probes. Importantly, however, the difference between suppressed-eye and dominant-eye probes was still significant for off-object probes. Together these results suggest dynamic mechanisms at work in probe-mediated rivalry, such that on-object probe effects are larger relative to smaller, yet reliable off-object effects.

Background: Traditionally, treatment with the excimer laser requires determining the minimal erythema dose on healthy skin or using plaque-based induration; however, these protocols often lead to underdosing of psoriatic plaques and reduced treatment efficacy. Objective: To prospectively evaluate the effect of the excimer laser on plaque psoriasis using an optimal therapeutic dose (OTD) protocol. Methods: Subjects with stable plaque psoriasis were tested with the Multi-Microdose (MMD) tip on the XTRAC excimer laser to determine a minimum blistering dose (MBD). Treatment was then initiated at 20% less than the MBD. A single psoriatic lesion was treated once weekly for up to 11 sessions. The change from baseline of the target lesion's modified psoriasis area severity index (mPASI), quality of life and safety were evaluated. Results: Thirteen subjects with a mean age of 48.9±14.9 years and Fitzpatrick skin types I-IV participated in the study. Target plaque mPASI significantly decreased at all time points relative to baseline with significant improvement by the second treatment. Patients reached mPASI-75 within 5±2 sessions. By the end of the study 92% of patients achieved mPASI-75. On average, patients maintained an mPASI score ≥50% for 60 days. Treatment was well tolerated with no erosions or hyperpigmentation. Erythema was the most common adverse event. Conclusion: The OTDTM protocol with the MMD® tip allows determining the optimal dose locally on the psoriatic plaque itself. Consequently, ineffectual dosing levels and treatments are minimized. The OTD protocol reduces treatment frequency from 2-3 times per week to once weekly. J Drugs Dermatol. 2020;19(4):349-354. doi:10.36849/JDD.2020.4891.

Introduction Post-traumatic stress disorder (PTSD) is associated with an increased risk of cardiovascular and metabolic diseases and physical inactivity. Cardiorespiratory fitness (CRF), which is modifiable by physical activity, is a strong independent predictor of cardiometabolic health. However, the relationship between CRF and cardiometabolic health in veterans with PTSD is unknown. Thus, this study aimed to explore the cross-sectional relationships among CRF, indices of cardiometabolic health (ie, HbA1c, blood lipids, blood pressure, waist-hip ratio, and body mass index), and PTSD severity in veterans with PTSD. Materials and Methods This study was approved by the local Institutional Review Board. All participants were informed of the study risks and provided consent prior to participation. Participants (n = 13) completed a cardiopulmonary exercise test, a fasting blood draw, and the Clinician Administered PTSD Scale. Correlations between CRF and cardiometabolic health were examined with Spearman’s rank correlations, and differences in PTSD symptom severity were explored as a function of CRF (ie, low-to-moderate vs. high CRF), using multiple linear regression. Results Peak oxygen uptake ($\dot{\mathrm{V}}$O2peak) was correlated with high-density lipoproteins rho = 0.60, P = 0.04 and diastolic blood pressure rho = −0.56, P = 0.05. Ventilatory threshold was correlated with HbA1c rho = −0.61, P = 0.03 and diastolic blood pressure rho = −0.56, P = 0.05. Higher CRF was associated with lower total PTSD severity standardized β = −0.84, P = 0.01, adjusted R2 = 0.47, total Cluster C symptoms (avoidance/numbing) β = −0.71, P = 0.02, adjusted R2 = 0.49, and total Cluster D symptoms (hyperarousal) β = −0.89, P = 0.01, adjusted R2 = 0.41, while adjusting for age and smoking status. Conclusions These preliminary findings suggest that CRF and by proxy physical activity may be important factors in understanding the increased risk of cardiovascular and metabolic disease associated with PTSD.

Background: Incisional hernias can be associated with pain or discomfort. Surgical repair especially mesh reinforcement, may likewise induce pain. The primary objective was to assess the incidence of pain after hernia repair in patients with and without pre-operative pain or discomfort. The secondary objectives were to determine the preferred mesh type, mesh location and surgical technique in minimizing postoperative pain or discomfort. Materials and methods: A registry-based prospective cohort study was performed, including patients undergoing incisional hernia repair between September 2011 and May 2019. Patients with a minimum follow-up of 3–6 months were included. The incidence of hernia related pain and discomfort was recorded perioperatively. Results: A total of 1312 patients were included. Pre-operatively, 1091 (83%) patients reported pain or discomfort. After hernia repair, 961 (73%) patients did not report pain or discomfort (mean follow-up = 11.1 months). Of the pre-operative asymptomatic patients (n = 221), 44 (20%, moderate or severe pain: n = 14, 32%) reported pain or discomfort after mean follow-up of 10.5 months. Of those patients initially reporting pain or discomfort (n = 1091), 307 (28%, moderate or severe pain: n = 80, 26%) still reported pain or discomfort after a mean follow-up of 11.3 months postoperatively. Conclusion: In symptomatic incisional hernia patients, hernia related complaints may be resolved in the majority of cases undergoing surgical repair. In asymptomatic incisional hernia patients, pain or discomfort may be induced in a considerable number of patients due to surgical repair and one should be aware if this postoperative complication.

Robust dynamic contrast-enhanced T1-weighted images are crucial for accurate detection and categorization of focal liver lesions in liver/abdominal magnetic resonance imaging (MRI). As optimal dynamic imaging usually requires multiple breath-holds, its inherent susceptibility to motion artifacts frequently results in degraded image quality in incompliant patients. Because free-breathing imaging may overcome this drawback, the intention of this study was to evaluate a dynamic MRI sequence acquired during free breathing using the variable density, elliptical centric golden angle radial stack-of-stars radial sampling scheme, which so far has not been implemented in 4-dimensional applications.In a prospective pilot study, 27 patients received a routine abdominal MRI protocol including the prototype free-breathing sequence (4DFreeBreathing) for dynamic imaging. This enables more convenient and faster reconstruction through variable density, elliptical centric golden angle radial stack-of-stars without the use of additional reconstruction hardware, and even higher motion robustness through soft-gating. A standard breath-hold sequence performed subsequently served as reference standard. Of the continuous dynamic data sets, each dynamic phase was analyzed regarding image quality, motion artifacts and vessel conspicuity using 5-point Likert scales. Furthermore, correct timing of the late arterial phase was compared with the preexaminations.4DFreeBreathing delivered motion-free dynamic images with high temporal resolution in each subject. Overall image quality scores were rated good or excellent for 4DFreeBreathing and the gold standard without significant differences (P = 0.34). There were significantly less motion artifacts in the 4DFreeBreathing sequence (P0.0001), whereas vessel conspicuity in each dynamic phase was comparable for both groups (P = 0.45, P0.99, P = 0.22, respectively). Correct timing of the late arterial phase could be achieved in 27 of 27 (100%) examinations using 4DFreeBreathing versus 35 of 53 (66%) preexaminations using gold standard (P0.001).The benefit of convenient and fast image reconstruction combined with the superiority in motion robustness and timing compared with standard breath hold sequences renders 4DFreeBreathing an attractive alternative to existing free-breathing techniques in dynamic liver MRI.

Phase amplitude coupling (PAC) is thought to play a fundamental role in the dynamic coordination of brain circuits and systems. There are however growing concerns that existing methods for PAC analysis are prone to error and misinterpretation. Improper frequency band selection can render true PAC undetectable, while non-linearities or abrupt changes in the signal can produce spurious PAC. Current methods require large amounts of data and lack formal statistical inference tools. We describe here a novel approach for PAC analysis that substantially addresses these problems. We use a state space model to estimate the component oscillations, avoiding problems with frequency band selection, nonlinearities, and sharp signal transitions. We represent cross-frequency coupling in parametric and time-varying forms to further improve statistical efficiency and estimate the posterior distribution of the coupling parameters to derive their credible intervals. We demonstrate the method using simulated data, rat local field potentials (LFP) data, and human EEG data.

Aim In the CheckRad-CD8 trial patients with locally advanced head and neck squamous cell cancer are treated with a single cycle of induction chemo-immunotherapy (ICIT). Patients with pathological complete response (pCR) in the re-biopsy enter radioimmunotherapy. Our goal was to study the value of F-18-FDG PET/CT in the prediction of pCR after induction therapy. Methods Patients treated within the CheckRad-CD8 trial that additionally received FDG- PET/CT imaging at the following two time points were included: 3–14 days before (pre-ICIT) and 21–28 days after (post-ICIT) receiving ICIT. Tracer uptake in primary tumors (PT) and suspicious cervical lymph nodes (LN +) was measured using different quantitative parameters on EANM Research Ltd (EARL) accredited PET reconstructions. In addition, mean FDG uptake levels in lymphatic and hematopoietic organs were examined. Percent decrease (Δ) in FDG uptake was calculated for all parameters. Biopsy of the PT post-ICIT acquired after FDG-PET/CT served as reference. The cohort was divided in patients with pCR and residual tumor (ReTu). Results Thirty-one patients were included. In ROC analysis, ΔSUVmax PT performed best (AUC = 0.89) in predicting pCR (n = 17), with a decline of at least 60% (sensitivity, 0.77; specificity, 0.93). Residual SUVmax PT post-ICIT performed best in predicting ReTu (n = 14), at a cutpoint of 6.0 (AUC = 0.91; sensitivity, 0.86; specificity, 0.88). Combining two quantitative parameters (ΔSUVmax ≥ 50% and SUVmax PT post-ICIT ≤ 6.0) conferred a sensitivity of 0.81 and a specificity of 0.93 for determining pCR. Background activity in lymphatic organs or uptake in suspected cervical lymph node metastases lacked significant predictive value. Conclusion FDG-PET/CT can identify patients with pCR after ICIT via residual FDG uptake levels in primary tumors and the related changes compared to baseline. FDG-uptake in LN + had no predictive value. Trial registry ClinicalTrials.gov identifier: NCT03426657.

Copyright © 2022 The Author(s) and International Federation of Clinical Neurophysiology. Transcranial (electro)magnetic stimulation (TMS) is currently the method of choice to non-invasively induce neural activity in the human brain. A single transcranial stimulus induces a time-varying electric field in the brain that may evoke action potentials in cortical neurons. The spatial relationship between the locally induced electric field and the stimulated neurons determines axonal depolarization. The induced electric field is influenced by the conductive properties of the tissue compartments and is strongest in the superficial parts of the targeted cortical gyri and underlying white matter. TMS likely targets axons of both excitatory and inhibitory neurons. The propensity of individual axons to fire an action potential in response to TMS depends on their geometry, myelination and spatial relation to the imposed electric field and the physiological state of the neuron. The latter is determined by its transsynaptic dendritic and somatic inputs, intrinsic membrane potential and firing rate. Modeling work suggests that the primary target of TMS is axonal terminals in the crown top and lip regions of cortical gyri. The induced electric field may additionally excite bends of myelinated axons in the juxtacortical white matter below the gyral crown. Neuronal excitation spreads ortho- and antidromically along the stimulated axons and causes secondary excitation of connected neuronal populations within local intracortical microcircuits in the target area. Axonal and transsynaptic spread of excitation also occurs along cortico-cortical and cortico-subcortical connections, impacting on neuronal activity in the targeted network. Both local and remote neural excitation depend critically on the functional state of the stimulated target area and network. TMS also causes substantial direct co-stimulation of the peripheral nervous system. Peripheral co-excitation propagates centrally in auditory and somatosensory networks, but also produces brain responses in other networks subserving multisensory integration, orienting or arousal. The complexity of the response to TMS warrants cautious interpretation of its physiological and behavioural consequences, and a deeper understanding of the mechanistic underpinnings of TMS will be critical for advancing it as a scientific and therapeutic tool. Aman S. Aberra was supported by a U. S. A. National Science Foundation Graduate Research Fellowship (No. DGF 1106401). Andrea Antal has been supported by a grant of the Federal Ministry of Education and Research (BMBF) of Germany (Grant 01GP2124B) and by a grant of the Lower Saxony Ministry of Science and Culture (Grant 76251-12-7/19 ZN 3456). Marco Davare has been supported by a BBSRC responsive mode grant. Klaus Funke has been supported by a grant of the Federal Ministry of Education and Research (BMBF) of Germany (Grant 01EE1403B) as part of the German Center for Brain Stimulation (GCBS) and by the Deutsche Forschungsgemeinschaft (DFG) (Grants FU256/3-2; 122679504–SFB874). Mark Hallett is supported by the NINDS Intramural Program. Anke N. Karabanov holds a 4-year Sapere Aude Fellowship which is sponsored by the Independent Research Fund Denmark (Grant Nr. 0169-00027B). The sponsor had no direct involvement in the collection, analysis and interpretation of data and in the writing of the manuscript. Giacomo Koch has been supported by na EU grant H2020-EU.1.2.2. - FET Proactive (Neurotwin ID: 101017716). Sabine Meunier is Emeritus Research Director at INSERM, this has no direct involvement in the collection, analysis and interpretation of data and in the writing of the manuscript. Carlo Miniussi has been supported by a grant of the Caritro Foundation, Italy. Walter Paulus received grants from the Deutsche Forschungsgemeinschaft and BMBF. Angel V. Peterchev was supported by grants from the U. S. A. National Institutes of Health (Grants Nos. R01NS117405, R01NS088674, RF1MH114268, R01MH111865). Traian Popa has been supported by the Defitech Foundation and NIBS-iCog grant from the Swiss National Science Foundation. Hartwig R. Siebner holds a 5-year professorship in precision medicine at the Faculty of Health Sciences and Medicine, University of Copenhagen which is sponsored by the Lundbeck Foundation (Grant Nr. R186-2015-2138). The salary for Janine Kesselheim (PhD project) has been covered by a project grant “Biophysically adjusted state-informed cortex stimulation” (BASICS) funded by a synergy grant from Novo Nordisk Foundation (PI: Hartwig R Siebner, Interdisciplinary Synergy Program 2014; grant number NNF14OC001). Axel Thielscher has been supported by grants of the Lundbeck foundation (R118-A11308, R244-2017-196 and R313-2019-622). Yoshikazu Ugawa has been supported in part by grants from the Research Project Grant-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (Grants 15H05881, 16H05322, 19H01091, 20K07866). Ulf Ziemann received grants from the German Ministry of Education and Research (BMBF), European Research Council (ERC), and German Research Foundation (DFG).

In the face of multiple sensory streams, there may be competition for processing resources in multimodal cortical area devoted to establishing representations. In such cases, alpha oscillations may serve to maintain the relevant representations and protect them from interference, whereas theta oscillations may facilitate their updating when needed. It can be hypothesized that these oscillations would differ in response to an auditory stimulus when the eyes are open or closed, as intermodal resource competition may be more prominent in the former than in the latter case. Across two studies we investigated the role of alpha and theta power in multimodal competition using an auditory task with the eyes open and closed, respectively enabling and disabling visual processing in parallel with the incoming auditory stream. In a passive listening task (Study 1a), we found alpha suppression following a pip tone with both eyes open and closed, but subsequent alpha enhancement only with closed eyes. We replicated this eyes-closed alpha enhancement in an independent sample (Study 1b). In an active auditory oddball task (Study 2), we again observed the eyes open/eyes closed alpha pattern found in Study 1 and also demonstrated that the more attentionally demanding oddball trials elicit the largest oscillatory effects. Theta power did not interact with eye status in either study. We propose a hypothesis to account for the findings in which alpha may be endemic to multimodal cortical areas in addition to visual ones.

Single-visit “screen-and-treat” strategies using visual inspection with acetic acid (VIA) and cryotherapy (liquid nitrous oxide ablation) in low-resource settings are commonly used to detect and treat precancerous lesions for cervical cancer prevention. This study compared VIA sensitivity and specificity in rural indigenous Guatemalan communities, to that of oncogenic human papillomavirus (HPV) testing for detection of precancerous changes, using cytology as the reference standard. Between 3–8 September 2017, trained nurses examined 222 women aged 23–58 years with VIA. Specimens for liquid-based cytology and HPV testing were obtained prior to VIA with a cytobrush and transported in PreservCyt to a US clinical laboratory. VIA and HPV test sensitivities were assessed as proportions of women with abnormal cytology that had abnormal VIA or HPV results, respectively, and specificities, as proportions with normal cytology with normal VIA or negative HPV tests. Of 222 women, 18 (8.1%) had abnormal cytology (1 carcinoma in a participant who received VIA-based cryotherapy in 2015, 4 high- and 5 low-grade squamous intraepithelial lesions, and 8 atypical squamous cells of undetermined significance (ASCUS)). Excluding ASCUS, sensitivities of VIA and HPV were 20.0% and 100%, respectively. VIA-based screening may not be acceptable for detecting precancerous lesions, and field cryotherapy for preventing malignancy. The World Health Organization recommended in 2021 “…using HPV DNA detection as the primary screening test rather than VIA or cytology”.

Background Many orthopedic practices routinely code hip fracture hemiarthroplasty as Current Procedural Terminology (CPT) 27125 even though 27236 is the correct CPT code. Our objective is to determine the financial impact this simple mistake has on surgeon reimbursement. Methods Our data comprised cases assigned International Classification of Diseases, Tenth Revision code S72.001A through S72.035A and CPT code 27125 or 27236 within the American College of Surgeons National Surgical Quality Improvement Program 2016-2017 database. Relative value units (RVUs) per CPT code and the Centers for Medicare and Medicaid Services reported that RVU conversion factor of $36.0896 per 1 RVU was used to calculate reimbursement per case. The dollar difference and percent difference per case was then calculated between cases assigned CPT code 27125 and those assigned 27236. Results Our total sample consisted of 12,287 National Surgical Quality Improvement Program cases. Of those, 4185 (34%) were cases of a hip fracture treated with hemiarthroplasty that were incorrectly coded as CPT code 27125. That error in coding results in a decrease in reimbursement of $35.01 per case, a 5.51% difference. Conclusion Since the current healthcare reimbursement model relies solely on CPT codes to determine RVUs, it is imperative that orthopedic surgeons understand the financial impact of incorrect coding. Although correct coding of hemiarthroplasty procedures for hip fractures is an easy task to fix in the future, we hope that through this study a greater emphasis is placed on coding in orthopedic surgery.

Vector-borne parasites must succeed at three scales to persist: they must proliferate within a host, establish in vectors, and transmit back to hosts. Ecology outside the host undergoes dramatic seasonal and human-induced changes, but predicting parasite evolutionary responses requires integrating their success across scales. We develop a novel, data-driven model to titrate the evolutionary impact of ecology at multiple scales on human malaria parasites. We investigate how parasites invest in transmission versus proliferation, a life-history trait that influences disease severity and spread. We find that transmission investment controls the pattern of host infectiousness over the course of infection: a trade-off emerges between early and late infectiousness, and the optimal resolution of that trade-off depends on ecology outside the host. An expanding epidemic favors rapid proliferation, and can overwhelm the evolutionary influence of host recovery rates and mosquito population dynamics. If transmission investment and recovery rate are positively correlated, then ecology outside the host imposes potent selection for aggressive parasite proliferation at the expense of transmission. Any association between transmission investment and recovery represents a key unknown, one that is likely to influence whether the evolutionary consequences of interventions are beneficial or costly for human health.

Background:We describe a thick fascial band arising from the medial aspect of the lateral plantar aponeurosis diving deep into the forefoot crossing over a branch of the lateral plantar nerve. Because a review of current literature resulted in limited and outdated sources, we sought to first determine the frequency of this fascial band and the location where it crosses the lateral plantar nerve and, second, discuss the clinical applications these anatomical findings could have.Methods:50 pairs of cadaveric feet (n = 100) were dissected to investigate for presence of the fascial band and its interaction with the lateral plantar nerve. Images were taken of each foot with the fascial band. ImageJ was used to take 2 measurements assessing the relationship of the tuberosity of the base of the fifth metatarsal to where the nerve crossed deep to the fascial band.Results:Overall, 38% of the feet possessed the fascial band. It was found unilaterally in 10 pairs and bilaterally in 14 pairs. On average, the point at which the lateral plantar nerve passed deep to the fascial band was 2.0 cm medial and 1.7 cm anterior to the tuberosity of the base of the fifth metatarsal.Conclusion:When present, the deep band of the lateral plantar aponeurosis (PA) was consistently found to be crossing the lateral plantar nerve. The discovery of the location where this most commonly occurs has not been previously reported and adds an interesting dimension that elevates an anatomical study to one that has clinical potential.Clinical Relevance:The established target zone gives a precise location for where the relationship between the deep band of the lateral PA and the lateral plantar nerve exists when evaluating the foot. The target zone provides a potential springboard for future investigations concerning said relationship clinically.

Background. Physical activity (PA) rates are lower in rural populations, compared to urban and suburban counterparts. Since PA is shown to decrease the risk of cancers and chronic diseases, increasing PA in rural environments is an important disease-prevention strategy. However, in order to develop effective interventions for rural populations, more research is needed. The purpose of the study was to elicit rural residents’ thoughts and perceptions related to PA and walking trail use. Methods. Key informant interviews were conducted via telephone, with 62 adults, living in six rural communities in southeast Missouri, who identified as stakeholders, walking trail users, and nontrail users. Participants were recruited through word of mouth and snowball sampling. Interviews were digitally audio-recorded, transcribed, and qualitatively analyzed. Findings. Analysis revealed variation within the rural population, with each town unique in what constituted barriers and facilitators to PA. Life priorities other than physical health were found to be important motivators to PA and also influenced how PA was obtained. Community size was found to impact community resources and infrastructure, although this was mitigated by poverty rates. Conclusion. Rural communities are distinct from one another with different views and approaches to PA. Future interventions designed to increase PA should be mindful of differences at the individual and town levels and avoid a one-size-fits-all approach. Interventions would benefit from insight and support from community members and stakeholders, to facilitate a tailored approach to increase PA.

There is no therapy currently available for fully repairing articular cartilage lesions. Our laboratory has recently developed a visible light-activatable methacrylated gelatin (mGL) hydrogel, with the potential for cartilage regeneration. In this study, we further optimized mGL scaffolds by supplementing methacrylated hyaluronic acid (mHA), which has been shown to stimulate chondrogenesis via activation of critical cellular signalling pathways. We hypothesized that the introduction of an optimal ratio of mHA would enhance the biological properties of mGL scaffolds and augment chondrogenesis of human bone marrow-derived mesenchymal stem cells (hBMSCs). To test this hypothesis, hybrid scaffolds consisting of mGL and mHA at different weight ratios were fabricated with hBMSCs encapsulated at 20 × 106 cells/ml and maintained in a chondrogenesis-promoting medium. The chondrogenenic differentiation of hBMSCs, within different scaffolds, was estimated after 8 weeks of culture. Our results showed that mGL/mHA at a 9:1 (%, w/v) ratio resulted in the lowest hBMSC hypertrophy and highest glycosaminoglycan production, with a slightly increased volume of the entire construct. The applicability of this optimally designed mGL/mHA hybrid scaffold for cartilage repair was then examined in vivo. A full-thickness cylindrical osteochondral defect was surgically created in the rabbit femoral condyle, and a three-dimensional cell-biomaterial construct was fabricated by in situ photocrosslinking to fully fill the lesion site. The results showed that implantation of the mGL/mHA (9:1) construct resulted in both cartilage and subchondral bone regeneration after 12 weeks, supporting its use as a promising scaffold for repair and resurfacing of articular cartilage defects, in the clinical setting.

Background Intramedullary fixation of a comminuted subcapital metacarpal fracture using a headless compression screw was first described in 2010. The purpose of this study was to identify and evaluate all studies reporting clinical outcomes of intramedullary screw fixation of metacarpal fractures. Methods A comprehensive search of the literature was performed under Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines to identify all relevant studies. Outcome measures included mean follow-up, evidence of radiographic union, functional outcomes, and quality-of-life measures. Results Nine articles for a total of 169 metacarpal fractures were identified. Average patient age was 32 years; 86.5 percent of the patients were men; and the majority of fractures occurred in the small finger (74 percent). Most fractures occurred in the neck (n = 66), followed by shaft (n = 31) and head (n = 10). The average follow-up was 11 months, with an average metacarpophalangeal joint flexion of 86 degrees (n = 83) and digit total active motion of 251 degrees (n = 72). Radiographic union was achieved in 100% of reported cases (n = 132) at or before the latest follow-up. Grip strength in four studies showed an average of 96 percent compared to the contralateral hand. No serious complications were reported. Nine minor complications were reported, including four cases of hardware removal in asymptomatic patients. Conclusion The review of the literature suggests intramedullary fixation of metacarpal neck and shaft fractures using headless compression screws has thus far proven to be a safe and successful surgical treatment option resulting in excellent clinical outcomes.

Dupilumab is a fully human monoclonal IgG4 antibody directed against the alpha subunit of the IL-4 receptor and prevents the signaling of IL-4 and IL-13, two type 2 cytokines known to be important drivers of atopic diseases. In March of 2017, the United States Food and Drug Administration (FDA) approved dupilumab for the treatment of moderate-to-severe atopic dermatitis in adults that is uncontrolled with topical medications, becoming the first biologic agent approved to treat this chronic skin condition. In October of 2018, Dupilumab received approval by the FDA as an add-on maintenance therapy in patients with moderate-to-severe asthma aged 12years or older with an eosinophilic phenotype or with oral corticosteroid-dependent asthma. This review summarizes the characteristics of dupilumab and the clinical research that has been published to date, including treatment efficacy and adverse events.

Brodalumab is one of the most efficacious biologic agents available for psoriasis. It also has a unique mechanism; it is the only agent that blocks the entire interleukin 17 receptors instead of blocking individual cytokines. However, the main drawback is that brodalumab has an FDA mandated black box warning regarding suicide. This is an up-to-date article reviews the scientific validity of this issue with brodalumab and suicide. Areas covered: A worldwide literature search was conducted on the above issue regarding suicide risk and brodalumab. All relevant articles on this topic searchable in public domain were utilized. Expert opinion: The FDA black box warning is based on three completed suicides that happened in one research location out of 390 research sites worldwide. All three completed suicides have alternative explanations unrelated to brodalumab. The overall data from phase III clinical trials shows that psoriasis patients recorded significant improvement in depression after treatment with brodalumab. The overall impression is that the suicide issue is far from being scientifically validated and this is why the FDA itself stated in the package insert that "the cause and effect relationship these suicides and brodalumab has not been established."

Organophosphorus (OP) nerve agents and pesticides present significant threats to civilian and military populations. OP compounds include the nefarious G and V chemical nerve agents, but more commonly, civilians are exposed to less toxic OP pesticides, resulting in the same negative toxicological effects and thousands of deaths on an annual basis. After decades of research, no new therapeutics have been realized since the mid-1900s. Upon phosphylation of the catalytic serine residue, a process known as inhibition, there is an accumulation of acetylcholine (ACh) in the brain synapses and neuromuscular junctions, leading to a cholinergic crisis and eventually death. Oxime nucleophiles can reactivate select OP-inhibited acetylcholinesterase (AChE). Yet, the fields of reactivation of AChE and butyrylcholinesterase encounter additional challenges as broad-spectrum reactivation of either enzyme is difficult. Additional problems include the ability to cross the blood brain barrier (BBB) and to provide therapy in the central nervous system. Yet another complication arises in a competitive reaction, known as aging, whereby OP-inhibited AChE is converted to an inactive form, which until very recently, had been impossible to reverse to an active, functional form. Evaluations of uncharged oximes and other neutral nucleophiles have been made. Non-oxime reactivators, such as aromatic general bases and Mannich bases, have been developed. The issue of aging, which generates an anionic phosphylated serine residue, has been historically recalcitrant to recovery by any therapeutic approach—that is, until earlier this year. Mannich bases not only serve as reactivators of OP-inhibited AChE, but this class of compounds can also recover activity from the aged form of AChE, a process referred to as resurrection. This review covers the modern efforts to address all of these issues and notes the complexities of therapeutic development along these different lines of research.

Post-9/11 U.S. veterans are clinically complex with multiple co-occurring health conditions that lead to increased morbidity and mortality, risk for suicide, and decreased quality of life, but underutilization and resistance to treatment remain significant problems. Increased isolation and decreased community and social support due to coronavirus disease (COVID-19) have exacerbated mental health risk. This study evaluated the safety and feasibility of home-based telemental health group workshops to improve reintegration and social connection in post-9/11 U.S. military personnel. Seventy-four (61 males/13 females) post-9/11 U.S. military veterans were randomized to receive 12 sessions of STEP-Home cognitive-behavioral group workshop or present-centered group therapy. Treatment was delivered either in person (traditional medical center setting, treatment as usual [TAU]), or via home-based synchronous videoconferencing (VC). The change to VC occurred due to social distancing guidelines during COVID-19. Mean age was 41.0 years (SD = 11.5, range 24-65). Forty-five (36 males/9 females) participated in VC and 29 (25 males/4 females) in TAU. Demographics were similar across treatment milieu. There were no differences in therapist treatment adherence for TAU versus VC. Therapist satisfaction was higher for TAU groups (q value.05). Veterans showed higher enrollment, attendance, group cohesion, and veteran-to-veteran support for VC compared to TAU (q values.05). Safety procedures were successfully implemented via VC. Results demonstrate the safety, feasibility, and high satisfaction of group telemental health in U.S. veterans. Higher enrollment and treatment adherence for telemental health delivery resulted in a greater likelihood of receiving an effective treatment dose than TAU. Strong group cohesion and veteran-to-veteran support were achievable via telehealth. Telemental health offers convenient, efficient, and cost-effective care options for veterans and may be particularly helpful for patients with high psychiatric burden.

Making good decisions requires updating beliefs according to new evidence. This is a dynamical process that is prone to biases: in some cases, beliefs become entrenched and resistant to new evidence (leading to primacy effects), while in other cases, beliefs fade over time and rely primarily on later evidence (leading to recency effects). How and why either type of bias dominates in a given context is an important open question. Here, we study this question in classic perceptual decision-making tasks, where, puzzlingly, previous empirical studies differ in the kinds of biases they observe, ranging from primacy to recency, despite seemingly equivalent tasks. We present a new model, based on hierarchical approximate inference and derived from normative principles, that not only explains both primacy and recency effects in existing studies, but also predicts how the type of bias should depend on the statistics of stimuli in a given task. We verify this prediction in a novel visual discrimination task with human observers, finding that each observer’s temporal bias changed as the result of changing the key stimulus statistics identified by our model. The key dynamic that leads to a primacy bias in our model is an overweighting of new sensory information that agrees with the observer’s existing belief—a type of ‘confirmation bias’. By fitting an extended drift-diffusion model to our data we rule out an alternative explanation for primacy effects due to bounded integration. Taken together, our results resolve a major discrepancy among existing perceptual decision-making studies, and suggest that a key source of bias in human decision-making is approximate hierarchical inference., Author summary When humans and animals accumulate evidence over time, they are often biased. Identifying the mechanisms underlying these biases can lead to new insights into principles of neural computation. The confirmation bias, in which new evidence is given more weight when it agrees with existing beliefs, is a ubiquitous yet poorly understood example of such biases. Here we report that a confirmation bias arises even during perceptual decision-making, and propose an approximate hierarchical inference model as the underlying mechanism. Our model correctly predicts for what stimuli and tasks this bias will be strong, and when it will be weak, a critical prediction that we confirm using old and new data. A quantitative model comparison clearly favors our model over a key alternative: integration to bound. The key dynamic driving the confirmation bias in our model is an interaction between inferences on different timescales, a common scenario in decision-making more generally.

Purpose: The purpose of this study was to explore parent perceptions of changes in child physical activity during COVID-19 stay-at-home orders.Design: A cross-sectional study.Setting: The research team used social media, relevant organizations, and neighborhood groups to distribute the survey link in May and June of 2020.Subjects: A convenience sample of parents of children aged 5–12.Measures: Survey to assess parental perceptions of changes in children's physical activity before and during stay-at-home orders, and environmental and social barriers to physical activity.Analysis: Results were analyzed using descriptive statistics, bivariate comparisons, and multinomial-logistic regression models with covariates of environmental factors, social factors, and frequency of factors as barriers on association with perceived physical activity change.Results: Data from 245 parents were analyzed. A majority (63.7%) of parents reported a decrease in children's physical activity during stay-at-home orders. More parents indicated social barriers (e.g., lack of access to playmates) than environmental barriers (e.g., lack of access to neighborhood play spaces) to children's physical activity. In multivariate analyses, the odds of parents reporting decreased physical activity was greater for those reporting lack of playmates (OR = 4.72; 95% CI: 1.99–11.17) and lack of adult supervision (OR = 11.82; 95% CI: 2.48–56.28) as barriers. No environmental barriers were significantly associated with decreased children's physical activity.Conclusion: The unique aspects of the COVID-19 pandemic provide a natural experiment for developing social and environmental strategies to improve children's overall physical activity. Assessing parental perceptions is a way to inform these future efforts.

Background Psoriasis is an inflammatory, IL-17–driven skin disease in which autoantigen-induced CD8+ T cells have been identified as pathogenic drivers. Objective Our study focused on comprehensively characterizing the phenotypic variation of CD8+ T cells in psoriatic lesions. Methods We used single-cell RNA sequencing to compare CD8+ T-cell transcriptomic heterogeneity between psoriatic and healthy skin. Results We identified 11 transcriptionally diverse CD8+ T-cell subsets in psoriatic and healthy skin. Among several inflammatory subsets enriched in psoriatic skin, we observed 2 Tc17 cell subsets that were metabolically divergent, were developmentally related, and expressed CXCL13, which we found to be a biomarker of psoriasis severity and which achieved comparable or greater accuracy than IL17A in a support vector machine classifier of psoriasis and healthy transcriptomes. Despite high coinhibitory receptor expression in the Tc17 cell clusters, a comparison of these cells with melanoma-infiltrating CD8+ T cells revealed upregulated cytokine, cytolytic, and metabolic transcriptional activity in the psoriatic cells that differed from an exhaustion program. Conclusion Using high-resolution single-cell profiling in tissue, we have uncovered the diverse landscape of CD8+ T cells in psoriatic and healthy skin, including 2 nonexhausted Tc17 cell subsets associated with disease severity.

Physical activity (PA) pre-COVID-19 was lower in rural areas compared to non-rural areas. The purpose of this study was to determine COVID-19’s impact on PA in rural and non-rural residents. A cross-sectional study consisting of a convenience sample of 278 participants (50% rural, 50% non-rural) from 25 states completed an online survey describing their PA behaviors and perceptions during COVID-19. The global physical activity questionnaire was used to determine PA in various domains and summed to determine if the participant met the PA guidelines. Rural participants had a significantly higher body mass index, lower income, and a lower educational attainment. Conversely, non-rural participants reported more barriers to PA. There was no difference in the perception of COVID-19’s impact on PA, specifically, however, rural participants were significantly less likely to meet cardiorespiratory PA recommendations compared to non-rural participants. Conclusions: This study demonstrates the continued disparity in PA between rural and non-rural residents, despite the supposition of COVID-19 being less impactful in rural areas due to sparse populations. Efforts should be pursued to close the PA gap between rural and non-rural residents.

Background: Injuries of the distal syndesmosis in ankle fractures are traditionally treated with a temporary adjusting screw fixation. Conventional fluoroscopic and X-ray examinations cannot reliably diagnose malpositions of the fixed tibiofibular syndesmosis. Postoperative computer tomography allows a reliable control of the transfixed region.The aim of the retrospective single-study was to clarify whether an intraoperative 3D image intensifier examination can detect malpositions of the syndesmosis already intraoperatively and whether the examination has an influence on the postoperative revision rate.Methods: In 200 patients with tibiofibular syndesmosis injuries, an intraoperative 3D scan was performed after reduction of the distal tibiofibular syndesmosis and placement of the adjusting screw. Postoperative computer tomography of both ankle joints was performed in all patients. Results: 15% of all intraoperative 3D scans (30 patients) showed a finding requiring correction in the area of the ankle joint. In 7% of the cases, a malposition of the fibula in the tibial incisura requiring correction was found. Further corrections were necessary due to the extent and position of the osteosynthesis material (7%) and for the removal of joint bodies (1%). Postoperative computer tomographies of the ankle joints showed no deformities requiring revision. Conclusion: An intraoperative 3D scan allows a reliable assessment of the injured ankle region and reduces the postoperative revision rate. This makes a postoperative routine CT examination of the ankle joint dispensable.

Red tide blooms of the dinoflagellate Karenia brevis (K. brevis) produce toxic coastal conditions that can impact marine organisms and human health, while also affecting local economies. During the extreme Florida red tide event of 2017–2019, residents and visitors turned to social media platforms to both receive disaster-related information and communicate their own sentiments and experiences. This was the first major red tide event since the ubiquitous use of social media, thus providing unique crowd-sourced reporting of red tide impacts. We evaluated the spatial and temporal accuracy of red tide topic activity on Twitter, taking tweet sentiments and user types (e.g. media, citizens) into consideration, and compared tweet activity with reported red tide conditions, such as K. brevis cell counts, levels of dead fish and respiratory irritation on local beaches. The analysis was done on multiple levels with respect to both locality (e.g., entire Gulf coast, county-level, city-level, zip code tabulation areas) and temporal frequencies (e.g. daily, every three days, weekly), resulting in strong correlations between local per-capita Twitter activity and the actual red tide conditions observed in the area. Moreover, an association was observed between proximity to the affected coastal areas and per-capita counts for relevant tweets. Results show that Twitter presents a trustworthy reflection of the red tide’s local impacts and development over time, and can potentially augment the already existing tools for efficient assessment and a more coordinated response to the disaster.

Purpose To investigate, if patients with complex proximal tibial fracture have realistic expectations on open reduction and internal fixation. Methods 114 patients (mean 49 years, SD ± 13) with closed AO-type B and C proximal tibial fracture were grouped (group B, respectively C). Prior to surgery expectations concerning knee function, pain, return to work/sports, and the risk for osteoarthritis was assessed with the Hospital for Special Surgery-Knee Surgery Expectations Survey (HFSS-KSE) and a non-validated ten-item survey. Results 92% of patients expected at least an almost natural knee postoperatively. All items regarding restoring knee function were ranked to be at least important in both groups. 65% in group B and 47% in group C expected at most occasional pain. 83% in group B and 67% in group C expected full return to work without any limitations. Patients with low physical work intensity expected significantly shorter incapacity to work in both groups (7.8, respectively 8.9 weeks). 71% in group B and 60% in group C expected to return to sports with at most small limitations. 33% in group B and 22% in group C assumed risk for osteoarthritis will be prevented by surgery. Conclusion Expectations on surgery for complex proximal tibial fracture are high regardless of fracture type. The prognosis of many health and lifestyle domains was overestimated. The risk for osteoarthritis was underestimated. This study should sensitize surgeons to discuss realistic expectations. This may help to improve patient comprehension what leads to sensible expectations, resulting in improved patients´ satisfaction. Level of evidence IV. Trial registration number 14104, Date of registration: 06/2015.

Background Interest in nephrology as a career has declined dramatically over the past several years. Only 62% of nephrology fellowship positions are filled for the upcoming 2020 appointment year. The purpose of this study was to identify perceptions, attitudes, motivators, and barriers to a career in nephrology among internal medicine residents. Methods We recruited focus groups of internal medicine residents (N=25) from the University of Colorado, and asked questions aimed at exploring perceptions, attitudes, and barriers to a career in nephrology, and ways to increase interest in nephrology. All focus groups were conducted on the University of Colorado Denver Anschutz Medical Campus. Focus group sessions were recorded and transcribed. Thematic analysis was used to identify key concepts and themes. Results Residents described many barriers to a career in nephrology, including lack of exposure, lack of advances in the field, low monetary compensation, high complexity, lack of role models/mentors, and low-prestige/noncompetitive nature of the field. Most residents had no exposure to outpatient nephrology. Lack of new therapeutics was a significant deterrent to nephrology. Nephrology teaching in medical school was described as not clinically relevant and too complicated. Several residents felt they were not smart enough for nephrology. Only three residents had a role model within nephrology. Residents used the word “stigmatized” to describe nephrology, and discussed how low prestige decreased their interest in a field. Participants expressed suggestions to increase interest in nephrology through earlier and more outpatient nephrology exposure, enhanced interactions with nephrologists, and research and advancements in the field. Conclusions Residents identified several modifiable barriers to a career in nephrology. Changing how nephrology is taught in medical school, enhancing interactions with nephrologists through increased exposure, and highlighting research and advancements in nephrology may change the perception of nephrology and increase the number of residents entering the field.

In most cases periprosthetic fractures of the acetabulum are complex injuries and are extremely challenging for the treating medical team. Over the years the frequency of this overall rare entity has increased due to demographic changes. In recent years several treatment algorithms were published and provided the possibility of developing standardized treatment concepts. The classification of the fractures and a dedicated preoperative strategy are highly important for the quality of patient-centered care. In the literature the frequency of intraoperative fractures was initially given as 0.4%; however, several studies have been published in which a far higher rate of intraoperative fractures was detected by computed tomography (CT), often referred to as so-called occult fractures. The causes are multifactorial and there is significant association with whether cement-free press-fit acetabular cups were used or cemented forms. In approximately 75% of the cases a low energy impact was the cause of the fracture. In these patients systemic processes, such as osteoporotic alterations of the bony substance or the possible presence of low-grade infections should be considered. This article gives an overview of the diagnostics, planning, challenges and osteosynthetic treatment options for periprosthetic fractures of the acetabulum.

Background The decision as to whether or not to resurface the patella in revision total knee arthroplasty (TKA) is affected by the amount of patellar bone stock remaining; however, the impact of the cancellous bone status on patellar component fixation has not been studied. Therefore, we conducted a biomechanical study of patellar component fixation with varying degrees of cancellous bone loss. Methods Sixty pairs of cadaveric patellae were randomly assigned between 3 groups and prepared in similar manner to a TKA with the standard 3-hole configuration. A control patella and an experimental patella were designated in each pair. To simulate bone loss in the experimental patellae, 1, 2, and 3 of the standard drill holes were uniformly enlarged to 12 mm in group 1, group 2, and group 3, respectively. Afterward, an all-polyethylene patellar component was cemented to each patella, as done intraoperatively. Patellar components were then sheared off using a materials testing system. The resulting mean offset yield force was analyzed within each group using paired t-tests. Results The mean offset yield force for the control patellae was greater than the experimental patellae in group 1. In groups 2 and 3, the experimental patellae produced a greater mean offset yield force than the control patellae. Comparison within each group did not demonstrate a statistically significant difference. Conclusion Bone loss with enlargement of the patellar fixation holes, as is frequently seen in revision TKA, with holes up to 12 mm, does not significantly decrease patellar component fixation shear strength in this biomechanical cadaveric study.

Plastic surgeons have the unique perspective of working with all types of patients and care teams from almost all specialties in surgery and medicine, which creates unique challenges in times of distress. As the initial epicenter of coronavirus disease 2019 cases in the United States, the University of Washington program was required to rapidly develop strategies to deal with the escalating crisis. All aspects of the program were affected, including the need to triage the urgency of plastic surgery care, safe staffing of plastic surgery teams, and the role of plastic surgery in the greater hospital community. In addition, as a residency training program, limiting the impact of resident education and maintaining a sense of community and connection among members of the program developed into important considerations. The authors hope that the narrative of their experience will provide insight into the decisions made in the University of Washington health care system but also remind others that they are not alone in dealing with the challenges of this pandemic.

Despite the increasing proportion of women in U.S. medical schools, there are relatively few women in leadership positions, and a number of recent publications have highlighted many factors that could contribute to gender inequity and inequality in medicine. The Association of Pulmonary, Critical Care, and Sleep Division Directors, an organization of Division Directors from across the United States, convened a workshop to review data and obtain input from leaders on the state of gender equity in our field. The workshop identified a number of factors that could contribute to gender inequality and inequity: gender climate (including implicit and perceived biases); disproportionate family responsibilities; lack of women in leadership positions; poor retention of women; and lack of gender equality in compensation. The panel members developed a roadmap of concrete recommendations for societies, leaders, and individuals that should promote gender equity to achieve gender equality and improve retention of women in the field of pulmonary, critical care, and sleep medicine.

Objective Paclitaxel, a microtubule inhibitor, is subject to tumor resistance while treating high-grade serous ovarian and uterine cancer. This study aims to directly compare the effects of SQ1274, a novel microtubule inhibitor that binds to the colchicine-binding site on tubulin, and paclitaxel in high-grade serous ovarian and uterine cancer cell lines both in vitro and in vivo. Methods We assessed the sensitivity of ovarian (OVCAR8) and uterine (ARK1) cancer cell lines to SQ1274 and paclitaxel using XTT assays. We used western blot and quantitative real-time PCR to analyze changes in AXL RNA and protein expression by SQ1274 and paclitaxel. Differences in cell-cycle arrest and apoptosis were investigated using flow cytometry. Finally, we treated ovarian and uterine xenograft models with vehicle, paclitaxel, or SQ1274. Results First, we demonstrate that SQ1274 has a much lower IC50 than paclitaxel in both ARK1 (1.26 nM vs. 15.34 nM, respectively) and OVCAR8 (1.34 nM vs. 10.29 nM, respectively) cancer cell lines. Second, we show SQ1274 decreases both RNA and protein expression of AXL. Third, we show that SQ1274 causes increased cell-cycle arrest and apoptosis compared to paclitaxel. Finally, we report that SQ1274 more effectively inhibits tumor growth in vivo compared to paclitaxel. Conclusions SQ1274 presents as a viable alternative to paclitaxel for treating ovarian and uterine cancer. This study supports the development of SQ1274 as a chemotherapeutic to treat ovarian and uterine cancer.

Background We hypothesized that propofol, a unique general anesthetic that engages N-methyl-D-aspartate and gamma-aminobutyric acid receptors, has antidepressant properties. This open-label trial was designed to collect preliminary data regarding the feasibility, tolerability, and efficacy of deep propofol anesthesia for treatment-resistant depression. Methods Ten participants with moderate-to-severe medication-resistant depression (age 18–45 years and otherwise healthy) each received a series of 10 propofol infusions. Propofol was dosed to strongly suppress electroencephalographic activity for 15 minutes. The primary depression outcome was the 24-item Hamilton Depression Rating Scale. Self-rated depression scores were compared with a group of 20 patients who received electroconvulsive therapy. Results Propofol treatments were well tolerated by all subjects. No serious adverse events occurred. Montreal Cognitive Assessment scores remained stable. Hamilton scores decreased by a mean of 20 points (range 0–45 points), corresponding to a mean 58% improvement from baseline (range 0–100%). Six of the 10 subjects met the criteria for response (>50% improvement). Self-rated depression improved similarly in the propofol group and electroconvulsive therapy group. Five of the 6 propofol responders remained well for at least 3 months. In posthoc analyses, electroencephalographic measures predicted clinical response to propofol. Conclusions These findings demonstrate that high-dose propofol treatment is feasible and well tolerated by individuals with treatment-resistant depression who are otherwise healthy. Propofol may trigger rapid, durable antidepressant effects similar to electroconvulsive therapy but with fewer side effects. Controlled studies are warranted to further evaluate propofol’s antidepressant efficacy and mechanisms of action. ClinicalTrials.gov: NCT02935647.

The American Academy of Dermatology (AAD) has prioritized skin cancer prevention efforts in 2018, as photoprotection measures adopted by the general public remain suboptimal. A large proportion of patients lack understanding of primary prevention methods for skin cancer, and mistruths in advertising may contribute significantly to this deficit. Sunscreen labels are often stacked with multiple claims of seemingly high significance, making it difficult for patients to differentiate their validity when selecting a sunscreen. The United States Food and Drug Administration (FDA) published its monograph in 2011 to address these controversies in sunscreen labeling, but the reliability of several other claims remain unclear. In this article, we discuss several claims commonly made on sunscreen labels, and address the truths and mistruths surrounding them.

Background Recently, there has been growing interest in the involvement of the posterior bundle of the medial ulnar collateral ligament (pMUCL) in varus posteromedial rotatory instability (PMRI). Varus PMRI has been observed clinically, but the degree of involvement of the pMUCL remains unclear. This study assessed the degree to which the pMUCL is involved in stabilizing the elbow and the feasibility of a pMUCL reconstruction to restore stability. Methods Movements simulating PMRI were performed in 8 cadaveric elbows. Joint gapping values were obtained by 3-dimensional motion capture for the proximal and distal aspects of the ulnohumeral joint. Specimens were assessed at “intact,” “cut coronoid + pMUCL,” “reconstruction,” and “cut anterior aspect MUCL + reconstruction” conditions with mechanical testing at 30°, 60°, and 90° of elbow flexion. Results Proximal joint gapping significantly increased from intact to cut coronoid + pMUCL at 60° and 90°, and distal joint gapping significantly increased at 90°. In the reconstruction condition, joint gapping across the proximal joint at 60° and 90° significantly recovered, as did distal joint gapping at 90°. In the cut anterior aspect MUCL + reconstruction condition, no significant increase occurred in proximal or distal joint gapping. Conclusions Transection of the pMUCL with a coronoid fracture leads to increased joint gapping, suggesting the presence of PMRI. PMRI can still occur with an intact lateral ligamentous complex. A pMUCL tendon graft reconstruction confers some elbow stability in this injury mechanism.