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Objective: Poorly differentiated thyroid carcinomas (PDTCs) are rare and aggressive head and neck malignancies with a poor prognosis. Systemic treatment for incurable PDTC consists of multi-kinase inhibitors (MKIs) based on extrapolation from the experience with radioiodine refractory differentiated thyroid cancer (DTC). Cabozantinib is an approved second-line MKI therapy for DTC, but there are limited data regarding the safety and efficacy of cabozantinib for PDTC. Methods: We conducted a single-institution, retrospective analysis of patients with PDTC who received cabozantinib in any line of therapy. Baseline demographics, disease characteristics, treatment history, toxicity, and clinical outcomes were abstracted from the electronic medical record. Median progression-free survival (PFS) and overall survival (OS) were primary endpoints and estimated using Kaplan–Meier methodology. Results: Seven patients with PDTC who received cabozantinib were included. 4/7 (57%) patients had a partial response to cabozantinib, while 2/7 (29%) had stable disease (SD) as their best response. The median time on treatment for cabozantinib was 10.53 months. The median PFS from the start of cabozantinib was 12.9 months, and median OS was 14.21 months. Most adverse events to treatment (5/6) were low grade. Two (29%) patients were alive at the date of the last follow-up. Conclusion: Cabozantinib is an effective and reasonably well-tolerated treatment option for patients with PDTC. Prospective studies are needed to further investigate the role of cabozantinib in the treatment of PDTC, alone and in combination with other agents, including checkpoint inhibitors.

IntroductionAlcohol-related problems increase the probability of frequent emergency department (ED) use. In this study, we compared the direct healthcare expenses incurred during a single visit among frequent and non-frequent ED users and analyzed the impact of alcohol-related issues in healthcare costs arising from ED usage.MethodsThe study relied on secondary analyses of economic data from a 1:1 matched case–control study with the primary aim of identifying the clinical characteristics of hospital ED frequent users in a Mediterranean European environment with a public, universal, and tax-funded health system. The participants ranged in age from 18 to 65 years and underwent ED visits at a high-complexity Spanish hospital (cases ≥5 times, controls

Background Little is known about factors contributing to burnout and intent to leave in cardiologists and other cardiology health care workers. Methods and Results The Coping With COVID survey assessed work conditions, burnout, and intent to leave among physicians, nurses, advanced practice providers, and other clinical staff (OCS) from April 2020 to December 2020. Single‐item measures assessed work conditions, burnout (emotional exhaustion), and intent to leave. Multilevel logistic regression examined work life variables' relationships to burnout among role types and feeling valued as a mediator. Open‐ended comments analyzed via grounded theory contributed to a conceptual model. Coping With COVID was completed by 1199 US cardiology health care workers (354 physician/520 nurses/198 advanced practice providers/127 OCS). Nurses were most likely to report burnout (59% nurses, 57% OCS, 46% advanced practice providers, 40% physicians, P

Lipoarabinomannan (LAM) is a promising target biomarker for diagnosing subclinical and clinical tuberculosis (TB). Urine LAM (uLAM) testing using rapid diagnostic tests (RDTs) has been approved for people living with HIV (PLWH), however there is limited data regarding uLAM levels in HIV-negative (HIV-ve) adults with clinical TB. We conducted a clinical study of adults presenting with clinical TB-related symptoms at the National Lung Hospital in Hanoi, Vietnam. The uLAM concentrations were measured using electrochemiluminescent (ECL) immunoassays and compared to a microbiological reference standard (MRS) using GeneXpert Ultra and TB culture testing. Estimated uLAM concentrations above plate specific calculated limit of detection (LOD) were considered uLAM positive. Additional microbiological testing was conducted for possible extrapulmonary TB (EPTB). Among 745 participants enrolled, 335 (44.9%) participants with presumptive pulmonary TB (PTB) and 6 (11.3%) participants with presumptive EPTB had confirmed TB disease. Overall, the S/A antibody pair had a sensitivity of 39% (95% Confidence Interval [CI] 0.33, 0.44) and a specificity of 97% (95% CI 0.96, 0.99) compared to the MRS. The F/A antibody pair had a sensitivity of 41% (95% CI 0.35, 0.47) and a specificity of 79% (95% CI 0.75, 0.84). S/A provided greater discriminatory ability compared to F/A for both individuals with presumptive PTB (AUROC: 0.74 vs 0.63, p

Thermal nonequilibrium (TNE) is a condition of the plasma in the solar corona in which the local rate of energy loss due to radiation increases to the point that it cannot be sustained by the various heating terms acting on the plasma, precluding the existence of a steady state. The limit cycles of precipitation and evaporation that result from TNE have been simulated in 1D models of coronal loops, as well as 2D and 3D models of the solar chromosphere and lower corona. However, a careful study of TNE in the solar wind has not been performed until now. Here, we demonstrate that for suitable combinations of local and global heating rates, it is possible for the plasma to exhibit a TNE condition, even in the context of a transonic solar wind with appreciable mass and energy fluxes. This implies limits on the amount of footpoint heating that can be withstood under steady-state conditions in the solar wind, and may help to explain the variability of solar wind streams that emanate from regions of highly concentrated magnetic flux on the solar surface. The implications of this finding pertain to various sources of high-density solar wind, including plumes that form above regions of mixed magnetic polarity in polar coronal holes and the slow solar wind that emanates from coronal hole boundaries.

Spatial organizations, configurations and dynamics are founded on the arrangement of some elementary structures called choremes. The map-model allows to find out and emphasize the ordering and the part they play. It shows the uprise of a new cartographic language.

Background Despite therapeutic advances, the management of chronic obstructive pulmonary disease (COPD) remains complex. There is growing interest in multidimensional, mind-body exercises to improve both physical and psychosocial aspects of COPD burden. Few US data are available in this population on tai chi (TC) a mind-body exercise incorporating physical activity, breathing and mindful awareness. We explored feasibility and preliminary efficacy of TC in COPD in an US academic medical setting.Methods Patients with COPD Global Obstructive Lung Disease (GOLD) stages 2–4 were randomised to a 12-week TC programme or education control. At 12 weeks, those in TC were randomised again to continue in maintenance classes or not to further explore optimal duration. All groups were followed to 24 weeks. Feasibility/safety parameters were analysed descriptively. Preliminary between-group differences were estimated in symptoms (dyspnoea, fatigue), health-related quality-of-life (Chronic Respiratory Questionnaire CRQ), cognitive-emotional measures (mood, COPD self-efficacy) and functional status (6 min walk test, lower body strength, flexibility, physical activity).Results Ninety-two subjects were randomised (N=61 TC, N=31 education). Mean age was 68±8 years, 66% male, mean forced expiratory volume in 1 s % predicted 57±13, 28% were GOLD stage 3–4. Overall retention was 85%. Nineteen adverse events occurred, most being study-unrelated COPD exacerbations. From baseline to 12 weeks, there were between-group improvements favouring TC, in CRQ-total (Cohen’s d effect size (ES)=0.46; adj mean diff (AMD)=0.31), CRQ-emotion (ES=0.54; AMD=0.49), Centre for Epidemiologic Studies Depression (ES=−0.37; AMD=2.39) and Patient-Reported Outcome Measurement Information System (PROMIS)-fatigue (ES=−0.34; AMD=−0.17). From baseline to 24 weeks, there was an improvement favouring TC in CRQ-dyspnoea (ES=0.41; AMD=0.46). Among TC participants, there was a positive effect of maintenance classes on self-efficacy (ES=−0.69; AMD=−0.40), 6 min walk (ES=0.56; AMD=49.26 feet), PROMIS-fatigue (ES=−0.41; AMD=−0.28) and chair stand (0.43; AMD=0.56).Conclusion TC in patients with COPD is feasible and safe. Preliminary analyses support a potential modest role in improving quality-of-life, cognitive-emotional health and function that should be further studied.Trial registration number NCT01551953.IRB reference BIDMC 2010P-000412; VA 2540.

Introduction The intraoperative administration of dexamethasone for prophylaxis against postoperative nausea and vomiting is a common and recommended practice. The safety of the administration of this immunosuppressive agent at a time of significant immunological disruption has not been rigorously evaluated in terms of infective complications.Methods/analysis This is a pragmatic, multicentre, randomised, controlled, non-inferiority trial. A total of 8880 patients undergoing elective major surgery will be enrolled. Participants will be randomly allocated to receive either dexamethasone 8 mg or placebo intravenously following the induction of anaesthesia in a 1:1 ratio, stratified by centre and diabetes status. Patient enrolment into the trial is ongoing. The primary outcome is surgical site infection at 30 days following surgery, defined according to the Centre for Disease Control criteria.Ethics/dissemination The PADDI trial has been approved by the ethics committees of over 45 participating sites in Australia, New Zealand, Hong Kong, South Africa and the Netherlands. The trial has been endorsed by the Australia and New Zealand College of Anaesthetists Clinical Trials Network and the Australian Society for Infectious Diseases Clinical Research Network. Participant recruitment began in March 2016 and is expected to be complete in mid-2019. Publication of the results of the PADDI trial is anticipated to occur in early 2020.Trial registration number ACTRN12614001226695.

This study explores the marketing in a multinational professional services organization and attempts to identify marketing factors relevant to the organization. The main objective is to identify critical factors that influence the successful marketing of professional services. To accomplish this objective, research is undertaken as a case study with a quantitative survey of employees from the professional services organization. The main finding was that the 7P framework (product/service, price, place, promotion, physical evidence, people, process) was applicable and that place, physical evidence and product components were seen as most critical, with promotion and price appearing to be least critical, maybe because conservative attitudes to marketing still exist within professional service organizations. The study added to the literature on professional services marketing, giving insight into the marketing of professional services in today’s dynamic and changing economic environment. Our findings will, therefore, assist professional service organizations to utilize their marketing resources more effectively and efficiently

Une lecture de Boulle.

Dans cet entretien, Roger Bozzetto retrace sa carrière de critique littéraire et de chercheur, spécialisé en science-fiction et fantastique. Il revient sur les évolutions de la science-fiction en France, ainsi que sur les perspectives critiques propres à l’université, d’une part, et au domaine de la science-fiction, de l’autre.

Abstract Objective Lower socioeconomic status (SES) is a risk factor for poorer pain-related outcomes. Further, the neighborhood environments of disadvantaged communities can create a milieu of increased stress and deprivation that adversely affects pain-related and other health outcomes. Socioenvironmental variables such as the Area Deprivation Index, which ranks neighborhoods based on socioeconomic factors could be used to capture environmental aspects associated with poor pain outcomes. However, it is unclear whether the ADI could be used as a risk assessment tool in addition to individual-level SES. Methods The current study investigated whether neighborhood-level disadvantage impacts knee pain-related outcomes above sociodemographic measures. Participants were 188 community-dwelling adults who self-identified as non-Hispanic Black or non-Hispanic White and reported knee pain. Area Deprivation Index (ADI; measure of neighborhood-level disadvantage) state deciles were derived for each participant. Participants reported educational attainment and annual household income as measures of SES, and completed several measures of pain and function: Short-form McGill Pain Questionnaire, Western Ontario and McMaster Universities Osteoarthritis Index, and Graded Chronic Pain Scale were completed, and movement-evoked pain was assessed following the Short Physical Performance Battery. Hierarchical linear regression analyses were used to assess whether environmental and sociodemographic measures (i.e., ADI 80/20 [80% least disadvantaged and 20% most disadvantaged]; education/income, race) were associated with pain-related clinical outcomes. Results Living in the most deprived neighborhood was associated with poorer clinical knee pain-related outcomes compared to living in less deprived neighborhoods (ps

BACKGROUND: Studies show the potential deterioration of brain vascularization and probable involvement of hypertension in Alzheimer disease (AD). OBJECTIVE: The objective was to evaluate the potential impact of hypertension on cerebral vascular flows in a sample of Alzheimer's patients. METHODS: 19 patients with AD, including 10 with hypertension (aHT+) and 9 without hypertension (aHT-) were recruited. They underwent clinical evaluation and phase-contrast MRI protocol for flow assessment. Cerebral arterial flow distributions were evaluated using kurtosis and skewness indices at the intracranial and extracranial levels. RESULTS: No significant differences were found in the mean arterial flow, pulse flow and kurtosis between the levels in the AD aHT+ population. There was a significant difference in skewness between extra- and intracranial levels (p = 0.01). No significant differences were found in the mean arterial flow between the levels in the AD aHT- population. A significant difference was observed in the pulse flow (p = 0.03), kurtosis (p = 0.02) and skewness (p = 0.008) between the levels. At the extracranial level we did not find any significant differences in the mean arterial flow, pulse flow or skewness between aHT+ and aHT-. There was a significant difference in kurtosis at the extracranial level between the aHT+ and aHT- (p = 0.03). At the intracranial level, there were no significant differences in all parameters. CONCLUSION: Results showed a difference between cerebral vasculature in AD for aHT+ and aHT- groups. This is probably related to the loss of arterial compliance induced by the degradation of the vascular system.

Abstract Background It is difficult to distinguish between the brain metastasis progression (BMP) and brain radionecrosis (BRN) on the basis of 18F-3,4-dihydroxyphenylalanine positron emission tomography/computed-tomography (18F-FDOPA PET/CT) data. The advent of silicon photomultiplier (SiPM) PET technology makes it possible to study dynamic volumes and potentially improve diagnostic accuracy. We developed a method for processing 18F-FDOPA PET/CT in the differential diagnosis between BMP and BRN. The method involves a short (3-second) sampling time during a 4-minute acquisition on a SiPM-PET/CT machine. We prospectively included 15 patients and 19 metastases. All acquisitions were performed in list mode acquisition for 25 min on a four-ring SiPM PET/CT system. We calculated the ratios between the maximum activity in the lesion’s voxel and the mean activity in the contralateral region (VOImax/CLmean) or the mean activity in the white matter (VOImax/WMmean). Results Seven lesions were classified as BMP and twelve were classified as BRN. Statistically significant intergroup differences in the VOImax/CLmean and VOImax/WMmean activity ratios were observed for both the clinical volume and the early acquisition. The best performing quantitative variable was the VOImax/CLmean ratio on early acquisition, with a diagnostic accuracy of 94.7%, a sensitivity of 100%, and a specificity of 91.7%. Conclusion The 18F-FDOPA PET/CT data acquired a few minutes after the bolus injection confirms its value in differentiating between BMP and BRN, compared to the much longer classic clinical protocol.

Abstract Here we describe a dataset of freely available, readily processed, whole-body μCT-scans of 56 species (116 specimens) of Lake Malawi cichlid fishes that captures a considerable majority of the morphological variation present in this remarkable adaptive radiation. We contextualise the scanned specimens within a discussion of their respective ecomorphological groupings and suggest possible macroevolutionary studies that could be conducted with these data. In addition, we describe a methodology to efficiently μCT-scan (on average) 23 specimens per hour, limiting scanning time and alleviating the financial cost whilst maintaining high resolution. We demonstrate the utility of this method by reconstructing 3D models of multiple bones from multiple specimens within the dataset. We hope this dataset will enable further morphological study of this fascinating system and permit wider-scale comparisons with other cichlid adaptive radiations.

The Language Center offers standardized tests for Arabic and English in the form of IKLA and TOEC exams. When conducted on paper, they are corrected manually and can have problems such as being less efficient, effective, and accurate. This research aims to design an online test application for TOEC/IKLA that can overcome these problems. This research uses a specific method called a waterfall. The research stages include needs analysis, design, implementation, and testing. A need analysis is carried out to understand the necessity of the application from the user’s perspective. Design is carried out to produce an application design that meets user needs. Implementation is carried out to build applications according to the design that has been created. Testing is carried out to ensure that the application can function properly and meet user needs. The research results show that the designed TOEC/IKLA online test application can overcome the problems found in the manual TOEC/IKLA test. This application can provide more efficient, effective, and accurate exam services. This application is a new and better service that UIN Sunan Kalijaga Yogyakarta delivers for everyone, whether internal or external test takers. This application can even be utilized by other institutions that require online examination services. Abstrak Tes standar untuk bahasa Arab dan Inggris ditawarkan oleh Pusat Pengembangan Bahasa (P2B) dalam bentuk ujian IKLA dan TOEC. Ketika dilakukan di atas kertas, tes tersebut dikoreksi secara manual dan memiliki beberapa masalah seperti kurang efisien, efektif, dan akurat. Tujuan penelitian ini fokus pada merancang sebuah aplikasi tes online TOEC/IKLA. Penelitian ini menggunakan metode khusus yang disebut waterfall. Model pengembangan waterfall terdiri dari tahap analisis kebutuhan, desain, implementasi, pengujian, dan pemeliharaan. Analisis kebutuhan dilakukan untuk memahami kebutuhan aplikasi dari sudut pandang pengguna. Desain dilakukan untuk menghasilkan rancangan aplikasi yang sesuai dengan kebutuhan pengguna. Implementasi dilakukan untuk membangun aplikasi sesuai dengan desain yang telah dibuat. Pengujian dilakukan untuk memastikan aplikasi dapat berfungsi dengan baik dan memenuhi kebutuhan pengguna. Hasil penelitian menunjukkan bahwa system aplikasi ujian online TOEC/IKLA ini merupakan layanan baru yang disediakan P2B UIN Sunan Kalijaga Yogyakarta untuk semua orang, baik peserta ujian internal maupun eksternal. Desain system aplikasi ujian TOEC/IKLA online dikembangkan sesuai dengan tahap pengembangan. Namun, belum dilakukan pengujian untuk melihat efisiensi, efektifitas dan akurasi karena keterbatasan penulis. Oleh karena itu rekomendasi penelitian lebih lanjut tentang system aplikasi ini untuk melihat efektivatas, efisiensi, dan akurasi secara lebih valid. Rancangan ini juga dapat dimanfaatkan oleh institusi lain yang membutuhkan layanan ujian secara online.

Abstract Across development, experience has a strong impact on the way we think and adapt. School experience affects academic and social-emotional outcomes, yet whether differences in pedagogical experience modulate underlying brain network development is still unknown. In this study, we compared the brain network dynamics of students with different pedagogical backgrounds. Specifically, we characterized the diversity and stability of brain activity at rest by combining both resting-state fMRI and diffusion-weighted structural imaging data of 87 4–18 years old students experiencing either the Montessori pedagogy (i.e., student-led, trial-and-error pedagogy) or the traditional pedagogy (i.e., teacher-led, test-based pedagogy). Our results revealed spatiotemporal brain dynamics differences between students as a function of schooling experience at the whole-brain level. Students from Montessori schools showed overall higher functional integration (higher system diversity) and neural stability (lower spatiotemporal diversity) compared to traditionally schooled students. Higher integration was explained mainly through the cerebellar (CBL) functional network. In contrast, higher temporal stability was observed in the ventral attention, dorsal attention, somatomotor, frontoparietal, and CBL functional networks. This study suggests a form of experience-dependent dynamic functional connectivity plasticity, in learning-related networks.

Abstract. Introduction:. Chronic overlapping pain conditions (COPCs), such as chronic low back pain (cLBP) and fibromyalgia, frequently cooccur and incur substantial healthcare costs. However, to date, much focus has been placed on individual anatomically based chronic pain conditions, whereas little is known about the mechanisms underlying progression to multiple (more than 1) COPCs. This study aims to address the gap by investigating the role of common and modifiable risk factors, specifically sleep and circadian rhythm disturbances, in the development of multiple COPCs. Methods:. The study will enroll 300 participants with cLBP, including 200 with cLBP only and 100 with cLBP plus other COPCs (ie, fibromyalgia, temporomandibular disorders, irritable bowel syndrome, and chronic headaches) and follow them up for 12 months. Sleep and circadian rhythms will be assessed using wireless sleep electroencephalography, 24-hour evaluation of the rhythm of urinary 6-sulfatoxymelatonin, actigraphy, and sleep diaries. Pain amplification using quantitative sensory testing, psychological distress using validated self-report measures, and the number of pain sites using a pain body map will also be assessed. Perspectives:. This research aims to (1) comprehensively characterize sleep/circadian disturbances in individuals with single and multiple COPCs using multimodal in-home assessments; (2) examine the associations between sleep/circadian disturbances, changes in pain amplification, and psychological distress; and (3) investigate the relationship among these factors and the progression in the number of pain sites, a proxy for multiple COPCs. The findings will provide insights into the mechanisms leading to multiple COPCs, potentially informing treatment and prevention strategies for these complex conditions.

In this qualitative study, preservice early childhood education teachers created block-based code to control robots and used the robots in field experience at local preschools. The study is grounded in a conceptual framework that weaves together playful programing and resilience, interlocking concepts that can explain sustained engagement during times of challenge. We investigated how and why preservice early childhood teachers exhibit resilience during collaborative programing. We analyzed their debugging processes, reflections, and interviews using a phenomenological lens. We conducted open and axial coding and analysis of discourse and actions during debugging episodes. Results suggest that teachers exhibited resilience due to the following three reasons: through playful coding, preservice early childhood teachers (a) learned that computer science is approachable and fun, (b) engaged in adaptive attribution, and (c) engaged in joint celebration when they observed each other’s successes during collaborative tinkering. These findings provide potential insights for teacher learning of computing but also for novices learning to program.

Summary: Background: Prognostic factors for ambulatory oncology patients have been described, including Eastern Cooperative Oncology Group (ECOG), tumor stage and malnutrition. However, there is no firm evidence on which variables best predict mortality in hospitalized patients receiving active systemic treatment. Our main goal was to develop a predictive model for 90-day mortality upon admission. Methods: Between 2020 and 2022, we prospectively collected data from three sites for cancer patients with hospitalizations. Those with metastatic disease receiving systemic therapy in the 6 months before unplanned admission were eligible to this study. The least absolute shrinkage and selection operator (LASSO) method was used to select the most relevant factors to predict 90-day mortality at admission. A multivariable logistic regression was fitted to create the PROgnostic Score for Hospitalized Cancer Patients (PROMISE) score. The score was developed in a single-center training cohort and externally validated. Findings: Of 1658 hospitalized patients, 1009 met eligibility criteria. Baseline demographics, patient and disease characteristics were similar across cohorts. Lung cancer was the most common tumor type in both cohorts. Factors associated with higher 90-day mortality included worse ECOG, stable/progressive disease, low levels of albumin, increased absolute neutrophil count, and high lactate dehydrogenase. The c-index after bootstrap correction was 0.79 (95% CI, 0.75–0.82) and 0.74 (95% CI, 0.68–0.80) in the training and validation cohorts, respectively. A web tool (https://promise.vhio.net/) was developed to facilitate the clinical deployment of the model. Interpretation: The PROMISE tool demonstrated high performance for identifying metastatic cancer patients who are alive 90 days after an unplanned hospitalization. This will facilitate healthcare providers with rational clinical decisions and care planning after discharge. Funding: Merck S.L.U., Spain.

We present a genome assembly from an individual leaf beetle, Galeruca laticollis (Arthropoda; Insecta; Coleoptera; Chrysomelidae). The genome sequence has a total length of 2,154.60 megabases. Most of the assembly (99.92%) is scaffolded into 12 chromosomal pseudomolecules, including the X and Y sex chromosomes. The mitochondrial genome has also been assembled and is 19.98 kilobases in length. Gene annotation of this assembly on Ensembl identified 32,229 protein-coding genes.

We present a genome assembly from an individual male Pseudeuparius sepicola (Arthropoda; Insecta; Coleoptera; Anthribidae). The genome sequence has a total length of 769.10 megabases. Most of the assembly (99.99%) is scaffolded into 12 chromosomal pseudomolecules, including the X and Y sex chromosomes. The mitochondrial genome has also been assembled and is 17.55 kilobases in length.

To extend the shelf life and make efficient use of the fruit requires industrial processing, transforming the fresh fruit into a dehydrated product. Therefore, the objective of this research was to determine the optimal technological process for the dehydration of tree bread (Artocarpus altilis) by combined methods, osmodeshidratado (OD) and hot air drying (HAD) showing its effect on the kinetics of OD, sensory and physicochemical characteristics. The Taguchi design was used with 8 treatments that were formulated through the following factors: OD concentration (40-60°Brix), OD temperature (20-40°C), OD time (1-8hr), HAD temperature (45-65°C) and HAD time (1-2hr), at 5% significance. The products with the lowest %H, which were obtained from the treatments with the best results in the first stage, were sensorially evaluated using a hedonic scale (1-7) and Friedman's nonparametric test. The results indicated that at a concentration of 60 ºBrix, time 8 hr and temperature 65 ºC in OD and at a time of 2 hr in HAD, obtaining a product with 16.2% moisture, with better sensory and physicochemical results with 76.5% carbohydrates, 8% protein, 1.7 % fat, 1.0 % ash, 0.9 % crude fiber and total energy of 353.3 Kcal. Therefore, the study demonstrated that the combined OD and HAD methods reduce heat stress, stabilize sensory parameters and maintain the nutritional value of arbor bread.

The neurocardiac axis constitutes the neuronal circuits between the arteries, heart, brain, and immune organs (including thymus, spleen, lymph nodes, and mucosal associated lymphoid tissue) that together form the cardiovascular brain circuit. This network allows the individual to maintain homeostasis in a variety of environmental situations. However, in dysfunctional states, such as exposure to environments with chronic stressors and sympathetic activation, this axis can also contribute to the development of atherosclerotic vascular disease as well as other cardiovascular pathologies and it is increasingly being recognized as an integral part of the pathogenesis of cardiovascular disease. This review article focuses on 1) the normal functioning of the neurocardiac axis; 2) pathophysiology of the neurocardiac axis; 3) clinical implications of this axis in hypertension, atherosclerotic disease, and heart failure with an update on treatments under investigation; and 4) quantification methods in research and clinical practice to measure components of the axis and future research areas.

Abstract Microglia are important players in surveillance and repair of the brain. Implanting an electrode into the cortex activates microglia, produces an inflammatory cascade, triggers the foreign body response, and opens the blood-brain barrier. These changes can impede intracortical brain-computer interfaces performance. Using two-photon imaging of implanted microelectrodes, we test the hypothesis that low-intensity pulsed ultrasound stimulation can reduce microglia-mediated neuroinflammation following the implantation of microelectrodes. In the first week of treatment, we found that low-intensity pulsed ultrasound stimulation increased microglia migration speed by 128%, enhanced microglia expansion area by 109%, and a reduction in microglial activation by 17%, indicating improved tissue healing and surveillance. Microglial coverage of the microelectrode was reduced by 50% and astrocytic scarring by 36% resulting in an increase in recording performance at chronic time. The data indicate that low-intensity pulsed ultrasound stimulation helps reduce the foreign body response around chronic intracortical microelectrodes.

Purpose: In incomplete spinal cord injury (SCI), there is a partial decrease in motor or sensory or autonomic function. Mainly due to the motor impairment in SCI, a muscle–machine interface is a tool that can bring functional benefits to this population. Objective: To investigate the feasibility of the non-invasive myoelectric signal–functional electrical stimulation (MES-FES) interface on the response of the quadriceps muscle in an individual with incomplete SCI. Methods: This is a quasi-experimental, uncontrolled, longitudinal case report study carried out with an individual with incomplete SCI in the chronic phase. The assessments performed before (pre) and after eight (post8) interventions were neuromuscular assessment (surface electromyography (EMG) in rectus femoris (RF) and vastus lateralis (VL) muscles); muscle strength (load cell); knee extension range of motion (goniometry); spasticity (Modified Ashworth Scale); and quality of life (Spinal Cord Injury Quality-of-Life Questionnaire (SCI-QoL.Br)). The MES-FES interface was associated with physical therapy exercises on the extension knee joint muscle group. Results: Improvement in neuromuscular activation (normalized increase in EMGRMS of 2% (RF) and 3.3% (VL)) and synchronism of the motor units (normalized reduction in EMGMDF of 22.8% (RF) and 5.9% (VL)); 1.4 kgf increase in quadriceps strength; 10.6° increase in knee joint extension amplitude; 1 point spasticity reduction; improved quality of life, confirmed by a 12-point reduction in the SCI-QoL.Br score. Moreover, along with interventions, the participant increased the correct FES activation rate, indicating a user learning curve (ρ = 0.78, p-value = 0.04). Conclusions: The MES-FES interface associated with physical therapy promotes neuromuscular and quality of life improvements in the SCI participant.

Abstract Background System contributors to resident burnout and well-being have been under-studied. We sought to determine factors associated with resident burnout and identify at risk groups. Methods We performed a US national survey between July 15 2022 and April 21, 2023 of residents in 36 specialties in 14 institutions, using the validated Mini ReZ survey with three 5 item subscales: 1) supportive workplace, 2) work pace/electronic medical record (EMR) stress, and 3) residency-specific factors (sleep, peer support, recognition by program, interruptions and staff relationships). Multilevel regressions and thematic analysis of 497 comments determined factors related to burnout. Results Of 1118 respondents (approximate median response rate 32%), 48% were female, 57% White, 21% Asian, 6% LatinX and 4% Black, with 25% PGY 1 s, 25% PGY 2 s, and 22% PGY 3 s. Programs included internal medicine (15.1%) and family medicine (11.3%) among 36 specialties. Burnout (found in 42%) was higher in females (51% vs 30% in males, p = 0.001) and PGY 2’s (48% vs 35% in PGY-1 s, p = 0.029). Challenges included chaotic environments (41%) and sleep impairment (32%); favorable aspects included teamwork (94%), peer support (93%), staff support (87%) and program recognition (68%). Worklife subscales were consistently lower in females while PGY-2’s reported the least supportive work environments. Worklife challenges relating to burnout included sleep impairment (adjusted Odds Ratio (aOR) 2.82 (95% CIs 1.94, 4.19), absolute risk difference (ARD) in burnout 15.9%), poor work control (aOR 2.25 (1.42, 3.58), ARD 12.2%) and chaos (aOR 1.73 (1.22, 2.47), ARD 7.9%); program recognition was related to lower burnout (aOR 0.520 (0.356, 0.760), ARD 9.3%). These variables explained 55% of burnout variance. Qualitative data confirmed sleep impairment, lack of schedule control, excess EMR and patient volume as stressors. Conclusions These data provide a nomenclature and systematic method for addressing well-being during residency. Work conditions for females and PGY 2’s may merit attention first.

Abstract Chronic musculoskeletal pain including knee osteoarthritis (OA) is a leading cause of disability worldwide. Previous research indicates ethnic-race groups differ in the pain and functional limitations experienced with knee OA. However, when socioenvironmental factors are included in analyses, group differences in pain and function wane. Pain-related brain structures are another area where ethnic-race group differences have been observed. Environmental and sociocultural factors e.g., income, education, experiences of discrimination, and social support influence brain structures. We investigate if environmental and sociocultural factors reduce previously observed ethnic-race group differences in pain-related brain structures. Data were analyzed from 147 self-identified non-Hispanic black (NHB) and non-Hispanic white (NHW), middle and older aged adults with knee pain in the past month. Information collected included health and pain history, environmental and sociocultural resources, and brain imaging. The NHB adults were younger and reported lower income and education compared to their NHW peers. In hierarchical multiple regression models, sociocultural and environmental factors explained 6–37% of the variance in pain-related brain regions. Self-identified ethnicity-race provided an additional 4–13% of explanatory value in the amygdala, hippocampus, insula, bilateral primary somatosensory cortex, and thalamus. In the rostral/caudal anterior cingulate and dorsolateral prefrontal cortex, self-identified ethnicity-race was not a predictor after accounting for environmental, sociocultural, and demographic factors. Findings help to disentangle and identify some of the factors contributing to ethnic-race group disparities in pain-related brain structures. Numerous arrays of environmental and sociocultural factors remain to be investigated. Further, the differing sociodemographic representation of our NHB and NHW participants highlights the role for intersectional considerations in future research.

Background The brain reserve hypothesis posits that larger maximal lifetime brain growth (MLBG) may confer protection against physical disability in multiple sclerosis (MS). Larger MLBG as a proxy for brain reserve, has been associated with reduced progression of physical disability in patients with early MS; however, it is unknown whether this association remains once in the secondary progressive phase of MS (SPMS). Our aim was to assess whether larger MLBG is associated with decreased physical disability progression in SPMS.Methods We conducted a post hoc analysis of participants in the MS-Secondary Progressive Multi-Arm Randomisation Trial (NCT01910259), a multicentre randomised placebo-controlled trial of the neuroprotective potential of three agents in SPMS. Physical disability was measured by Expanded Disability Status Scale (EDSS), 9-hole peg test (9HPT) and 25-foot timed walk test (T25FW) at baseline, 48 and 96 weeks. MLBG was estimated by baseline intracranial volume (ICV). Multivariable time-varying Cox regression models were used to investigate the association between MLBG and physical disability progression.Results 383 participants (mean age 54.5 years, 298 female) were followed up over 96 weeks. Median baseline EDSS was 6.0 (range 4.0–6.5). Adjusted for covariates, larger MLBG was associated with a reduced risk of EDSS progression (HR 0.84,95% CI:0.72 to 0.99;p=0.04). MLBG was not independently associated with time to progression as measured by 9HPT or T25FW.Conclusion Larger MLBG is independently associated with physical disability progression over 96 weeks as measured by EDSS in SPMS. This suggests that MLBG as a proxy for brain reserve may continue to confer protection against disability when in the secondary progression phase of MS.Trail registration number NCT01910259.

Abstract Chronic pain is a prevalent condition with enormous economic burden. Opioids such as tramadol, codeine, and hydrocodone are commonly used to treat chronic pain; these drugs are activated to more potent opioid receptor agonists by the hepatic CYP2D6 enzyme. Results from clinical studies and mechanistic understandings suggest that CYP2D6‐guided therapy will improve pain control and reduce adverse drug events. However, CYP2D6 is rarely used in clinical practice due in part to the demand for additional clinical trial evidence. Thus, we designed the ADOPT‐PGx (A Depression and Opioid Pragmatic Trial in Pharmacogenetics) chronic pain study, a multicenter, pragmatic, randomized controlled clinical trial, to assess the effect of CYP2D6 testing on pain management. The study enrolled 1048 participants who are taking or being considered for treatment with CYP2D6‐impacted opioids for their chronic pain. Participants were randomized to receive immediate or delayed (by 6 months) genotyping of CYP2D6 with clinical decision support (CDS). CDS encouraged the providers to follow the CYP2D6‐guided trial recommendations. The primary study outcome is the 3‐month absolute change in the composite pain intensity score assessed using Patient‐Reported Outcomes Measurement Information System (PROMIS) measures. Follow‐up will be completed in July 2024. Herein, we describe the design of this trial along with challenges encountered during enrollment.