Cell-type-specific cholinergic control of granular retrosplenial cortex with implications for angular velocity coding across brain states.

Cholinergic receptor activation enables the persistent firing of cortical pyramidal neurons, providing a key cellular basis for theories of spatial navigation involving working memory, path integration, and head direction encoding. The granular retrosplenial cortex (RSG) is important for spatially-guided behaviors, but how acetylcholine impacts RSG neurons is unknown. Here, we show that a transcriptomically, morphologically, and biophysically distinct RSG cell-type - the low-rheobase (LR) neuron - has a very distinct expression profile of cholinergic muscarinic receptors compared to all other neighboring excitatory neuronal subtypes. LR neurons do not fire persistently in response to cholinergic agonists, in stark contrast to all other principal neuronal subtypes examined within the RSG and across midline cortex. This lack of persistence allows LR neuron models to rapidly compute angular head velocity (AHV), independent of cholinergic changes seen during navigation. Thus, LR neurons can consistently compute AHV across brain states, highlighting the specialized RSG neural codes supporting navigation.

Effects of Preoperative Intravenous Versus Subcutaneous Tranexamic Acid on Postoperative Periorbital Ecchymosis and Edema Following Upper Eyelid Blepharoplasty: A Prospective, Randomized, Double-Blinded, Placebo-Controlled, Comparative Study.

PURPOSE: To compare the effects of preoperative tranexamic acid (TXA) administered intravenously (IV) versus subcutaneously on postoperative ecchymosis and edema in patients undergoing bilateral upper eyelid blepharoplasty. METHODS: A prospective, double-blinded, placebo-controlled study of patients undergoing bilateral upper eyelid blepharoplasty at a single-center. Eligible participants were randomized to preoperatively receive either (1) 1 g of TXA in 100 ml normal saline IV, (2) 50 µl/ml of TXA in local anesthesia, or (3) no TXA. Primary outcomes included ecchymosis and edema at postoperative day 1 (POD1) and 7 (POD7). Secondary outcomes included operative time, pain, time until resuming activities of daily living, patient satisfaction, and adverse events. RESULTS: By comparison (IV TXA vs. local subcutaneous TXA vs. no TXA), ecchymosis scores were significantly lower on POD1 (1.31 vs. 1.56 vs. 2.09, p = 0.02) and on POD7 (0.51 vs. 0.66 vs. 0.98, p = 0.04) among those that received TXA. By comparison (IV TXA vs. local subcutaneous TXA vs. no TXA), significant reductions in edema scores occurred in those that received TXA on POD1 (1.59 vs. 1.43 vs. 1.91, p = 0.005) and on POD7 (0.85 vs. 0.60 vs. 0.99, p = 0.04). By comparison (IV TXA vs. local subcutaneous TXA vs. no TXA) patients treated with intravenous and local subcutaneous TXA preoperatively were more likely to experience shorter operative times (10.8 vs. 11.8 vs. 12.9 minutes, p = 0.01), reduced time to resuming activities of daily livings (1.6 vs. 1.6 vs. 2.3 days, p < 0.0001), and higher satisfaction scores at POD1 (8.8 vs. 8.7 vs. 7.9, p = 0.0002). No adverse events occurred were reported. CONCLUSION: In an analysis of 106 patients, preoperative TXA administered either IV or subcutaneously safely reduced postoperative ecchymosis and edema in patients undergoing upper eyelid blepharoplasty. While statistical superiority between intravenous versus local subcutaneous TXA treatment was not definitively identified, our results suggest clinical superiority with IV dosing.

Interplay Between Ni and Brønsted and Lewis Acid Sites in the Hydrodesulfurization of Dibenzothiophene.

Ni-MoS2/γ-Al2O3 catalysts are commonly used in hydrotreating to enhance fossil fuel quality. The extensive research on these catalysts reveals a gap in understanding the role of Ni, often underestimated as an inactive sulfide phase or just a MoS2 promoter. In this work, we focused on analyzing whether well-dispersed supported nickel nanoparticles can be active in the hydrodesulfurization of dibenzothiophene. We dispersed Ni by Strong Electrostatic Adsorption (SEA) method across four supports with different types of acidity: silica (~ neutral acidity), γ-Al2O3 (Lewis acidity), H+-Y zeolite, and microporous-mesoporous H+-Y zeolite (both with Brønsted-Lewis acidity). Our findings reveal that Ni is indeed active in dibenzothiophene hydrodesulfurization, even with alumina and silica as supports, although their catalytic activity declines abruptly in the first hours. Contrastingly, the acid nature of zeolites imparts sustained stability and performance, attributed to robust metal-support interactions. The efficacy of the SEA method and the added mesoporosity in zeolites further amplify catalytic efficiency. Overall, we demonstrate that Ni nanoparticles may perform as a hydrogenating metal in the same manner as noble metals such as Pt and Pd perform in hydrodesulfurization. We discuss some of the probable reasons for such performance and remark on the role of Ni in hydrotreatment.

Fibrosis avanzada asociada a esteatohepatitis no alcohólica (NASH) en España: resultados de un estudio Delphi / Advanced fibrosis associated with non-alcoholic steatohepatitis (NASH) in Spain: results of a Delphi study

Objetivo: Describir de manera detallada la epidemiología, diagnóstico, manejo clínico, opciones de tratamiento, impacto en la calidad de vida y necesidades no cubiertas de los pacientes con fibrosis hepática avanzada (F3-F4) asociada a esteatohepatitis no alcohólica (NASH) en España. Metodología: Estudio Delphi de dos rondas de consulta con 41 hepatólogos expertos de 16 comunidades autónomas para recoger su experiencia en práctica clínica. Resultados: La prevalencia estimada de pacientes adultos diagnosticados de fibrosis F3-F4 asociada a NASH en España es de 0,019% (intervalo de confianza [IC] 95%: 0,019-0,020%). Aproximadamente 7.588 adultos con este padecimiento están actualmente diagnosticados y son manejados en los Servicios de Aparato Digestivo de los hospitales españoles, y alrededor de 1.881 nuevos pacientes son diagnosticados cada año. El manejo es multidisciplinar e incluye las especialidades de Aparato Digestivo, Endocrinología y Medicina interna, considerando las frecuentes comorbilidades metabólicas asociadas (obesidad, diabetes mellitus tipo 2 o sobrecarga férrica dismetabólica). A pesar del claro impacto en la calidad de vida, este no se evalúa rutinariamente en la práctica clínica. Las técnicas diagnósticas no invasivas más utilizadas son la elastografía de transición y el índice de fibrosis hepática 4 (FIB-4). La ausencia de tratamientos eficaces y seguros se presenta como la principal necesidad no cubierta para el manejo de estos pacientes. Conclusiones: Este estudio proporciona una representación de la situación actual de los pacientes diagnosticados con fibrosis F3-F4 asociada a NASH en España, incrementando la evidencia disponible y contribuyendo a la toma de decisiones informadas por parte de los profesionales y el sistema sanitario. (AU)

Objective: To describe in detail the epidemiology, diagnosis, clinical management, treatment options, impact on quality of life and unmet needs of patients with advanced liver fibrosis (F3-F4) associated with non-alcoholic steatohepatitis (NASH) in Spain. Methodology: Delphi study of two rounds of consultation rounds with 41 expert hepatologists from 16 autonomous communities to collect their experience in clinical practice. Results: The estimated prevalence of adult patients diagnosed with F3-F4 fibrosis associated with NASH in Spain is 0.019% (95% confidence interval [CI]: 0.019-0.020%). Approximately 7,588 adults with this condition are currently diagnosed and managed in the Digestive System Services of Spanish hospitals, and around 1,881 new patients are diagnosed each year. Management is multidisciplinary and includes the specialties of Digestive System, Endocrinology and Internal Medicine, considering the frequently associated metabolic comorbidities (obesity, type 2 diabetes mellitus or dysmetabolic iron overload). Despite a clear impact on quality of life, this it is not routinely evaluated in clinical practice. The most widely used non-invasive diagnostic techniques are transitional elastography and liver fibrosis index 4 (FIB-4). The absence of effective and safe treatments appears as the main unmet need for the management of these patients. Conclusions: This study provides a representation of the current situation of patients diagnosed with F3-F4 fibrosis associated with NASH in Spain, increasing the evidence available and contributing to informed decision-making by professionals and the health system. (AU)

A novel approach to study multi-domain motions in JAK1's activation mechanism based on energy landscape.

The family of Janus Kinases (JAKs) associated with the JAK-signal transducers and activators of transcription signaling pathway plays a vital role in the regulation of various cellular processes. The conformational change of JAKs is the fundamental steps for activation, affecting multiple intracellular signaling pathways. However, the transitional process from inactive to active kinase is still a mystery. This study is aimed at investigating the electrostatic properties and transitional states of JAK1 to a fully activation to a catalytically active enzyme. To achieve this goal, structures of the inhibited/activated full-length JAK1 were modelled and the energies of JAK1 with Tyrosine Kinase (TK) domain at different positions were calculated, and Dijkstra's method was applied to find the energetically smoothest path. Through a comparison of the energetically smoothest paths of kinase inactivating P733L and S703I mutations, an evaluation of the reasons why these mutations lead to negative or positive regulation of JAK1 are provided. Our energy analysis suggests that activation of JAK1 is thermodynamically spontaneous, with the inhibition resulting from an energy barrier at the initial steps of activation, specifically the release of the TK domain from the inhibited Four-point-one, Ezrin, Radixin, Moesin-PK cavity. Overall, this work provides insights into the potential pathway for TK translocation and the activation mechanism of JAK1.

Late Recurrence of Anisometropic Amblyopia.

A 15-year-old boy whose anisometropic amblyopia was effectively treated with glasses was examined. Despite years of stability, his visual acuity decreased from 20/20 to 20/60 with poor glasses compliance. Although amblyopia recurrence is well recognized, this case emphasizes potential late recurrence after prolonged success. Fortunately, he improved to 20/20 after improved compliance. [J Pediatr Ophthalmol Strabismus. 2024;61(1):e11-e12.].

Morbidity induced by the infiltration of foreign substances into the buttocks: A systematic review.

The infiltration of substances into the buttocks for esthetic purposes can cause local or systemic damage. These infiltrated substances, known as adjuvants, foreign substances, and polymers, often lack sufficient and frequently controversial evidence. To identify the systemic complications associated with substances locally infiltrated in the buttocks for treatment, we conducted a systematic review following the PRISMA criteria. Of 275 publications, 29 met the eligibility criteria: 3 systematic reviews, 6 case series, and 20 case reports. The study comprises 463 cases, mainly women (87%), with an average age of 39.94 years. The average time between infiltrations was 7.65 years. Infiltrated substances included silicone, oils, methyl methacrylate, guaiacol, sodium gadolinium, collagen, paraffin, and other unknown substances. The complications fell into three categories: local, systemic with inflammatory-immune response, and renal damage due to hypercalcemia induced by the granulomatosis caused by the substance. Treatment lacked uniformity, mainly focusing on the main effect. Surgical resection of affected tissue resulted in local and systemic improvement (renal, hypercalcemia, or inflammatory-immune) for most patients. Patients who received comprehensive treatment based on inflammatory-immune control, control of renal involvement, and resection of the tissue area that contained large amounts of the infiltrated substance had a better prognosis than those with diffuse infiltration and delayed treatment.

Association between COVID-19 vaccines and development of chronic morbidities: a cross-sectional study in the Jordanian population.

BACKGROUND: In Jordan, individuals recently diagnosed with chronic illnesses have expressed concerns with regard to COVID-19 vaccines. This study aims to investigate potential associations between COVID-19 vaccination and the likelihood of recipients developing chronic conditions such as autoimmune diseases, rheumatoid arthritis, diabetes, asthma, and hypertension. METHODOLOGY: Through a cross-sectional survey-based descriptive approach, this research was conducted to gather data within the Jordanian context. A web-based survey was utilized to collect demographic information, record vaccine-related side effects, and document the chronic disease status subsequent to COVID-19 vaccination. Statistical analysis was employed to reveal any potential associations between the vaccine, its side effects, and the emergence of chronic morbidities. RESULTS: The study involved 414 participants, among whom 10.4% exhibited pre-existing chronic diseases before vaccination. Remarkably, post-vaccination, 23.7% of participants were newly diagnosed with chronic illnesses. Statistical analysis indicated a significant correlation between COVID-19 vaccination and the subsequent development of chronic diseases (p-value ˂.01). the investigation found no significant association between vaccination and the emergence of diabetes, hypertension, or asthma (p-value ≥.01) However, an association was found between COVID-19 vaccination and the development of autoimmune diseases and rheumatoid arthritis (p-value ˂.01). CONCLUSIONS: This study highlights an association between the occurrence of autoimmune diseases and COVID-19 vaccination, while findings related to diabetes, asthma, and hypertension did not display significant associations. The results emphasize the necessity for further research to ascertain potential causal relationship.

COVID-19 vaccine was the rescue management offered during and after the pandemic times, however many patients complained from post-COVID vaccine side effects. Those side effects were either of short term or long term ones. People in Jordan are worried about the association of the COVID-19 vaccine and the occurrence of chronic morbidities just after vaccination. Therefore our study aimed to investigate any possible association of COVID-19 vaccines and increased tendency of chronic morbidities. In our research we chose the most common encountered post COVID-19 vaccine chronic diseases in clinical practice in Jordan; Diabetes, hypertension, asthma, rheumatoid arthritis and autoimmune diseases. The study participants (N = 414) were people in Jordan more than 18 years old and got vaccinated during the past three year 2020­2023.From our study we found that vaccinated participants suffered from many short term side effects, of which the most common were general fatigue and insomnia followed by headache and fever. As for the long term side effects of the COVID-19 vaccine we figured out an increase in the incidence of chronic morbidities in general post COVID-19 vaccine and an association between the occurrence of autoimmune diseases and rheumatoid arthritis and the COVID-19 vaccine. Therefore we concluded an important association between the COVID-19 vaccine and autoimmune diseases that should be taken into consideration in clinical practice or for future investigations.

Advanced fibrosis associated with non-alcoholic steatohepatitis (NASH) in Spain: results of a Delphi study. / Fibrosis avanzada asociada a esteatohepatitis no alcohólica (NASH) en España: resultados de un estudio Delphi.

OBJECTIVE: To describe in detail the epidemiology, diagnosis, clinical management, treatment options, impact on quality of life and unmet needs of patients with advanced liver fibrosis (F3-F4) associated with non-alcoholic steatohepatitis (NASH) in Spain. METHODOLOGY: Delphi study of two rounds of consultation rounds with 41 expert hepatologists from 16 autonomous communities to collect their experience in clinical practice. RESULTS: The estimated prevalence of adult patients diagnosed with F3-F4 fibrosis associated with NASH in Spain is 0.019% (95% confidence interval [CI]: 0.019-0.020%). Approximately 7,588 adults with this condition are currently diagnosed and managed in the Digestive System Services of Spanish hospitals, and around 1,881 new patients are diagnosed each year. Management is multidisciplinary and includes the specialties of Digestive System, Endocrinology and Internal Medicine, considering the frequently associated metabolic comorbidities (obesity, type 2 diabetes mellitus or dysmetabolic iron overload). Despite a clear impact on quality of life, this it is not routinely evaluated in clinical practice. The most widely used non-invasive diagnostic techniques are transitional elastography and liver fibrosis index 4 (FIB-4). The absence of effective and safe treatments appears as the main unmet need for the management of these patients. CONCLUSIONS: This study provides a representation of the current situation of patients diagnosed with F3-F4 fibrosis associated with NASH in Spain, increasing the evidence available and contributing to informed decision-making by professionals and the health system.

Developments in pancreatic cancer surgery.

Pancreatic cancer surgery, with one of the worst prognoses in oncology, is a challenge to the surgical community. Centralization of pancreatic surgery has led to the foundation of high-volume centers, thereby greatly facilitating the successful performance of more radical approaches. This review spotlights on recent advances in surgical approaches to pancreatic cancer and the risks and benefits of vascular reconstruction to improve resectability. Surgery being the only modality to achieve cure, multivisceral and vascular resections are being incorporated to improve dismal operability rates of < 10%. Great leaps have been made in neoadjuvant and adjuvant treatment, as targeted and specific chemotherapeutic agents are being continually added. The concept of borderline and locally advanced pancreatic tumors and the use of neoadjuvant chemorad has extended the indications of oncological resection in such tumors. Venous resections are being routinely performed so as to facilitate en bloc removal of tumors, while arterial resections, owing to the increased morbidity and mortality, are offered to highly selective cases. New techniques like the triangle operation and periarterial divestment have opened new viable surgical options. Although laparoscopic approach is time consuming, it offers reduced operative blood loss and a shortened hospital stay at specialized centers. Robotic surgery may produce better results in patients needing vascular resection and reconstruction, but the expenses involved and limited availability are major deterrents. Advanced techniques of surgical resection and vessel reconstruction provide a repository for curative-intent surgery in borderline resectable and locally advanced pancreatic cancer.

Cellular rules underlying psychedelic control of prefrontal pyramidal neurons.

Classical psychedelic drugs are thought to increase excitability of pyramidal cells in prefrontal cortex via activation of serotonin 2A receptors (5-HT2ARs). Here, we instead find that multiple classes of psychedelics dose-dependently suppress intrinsic excitability of pyramidal neurons, and that extracellular delivery of psychedelics decreases excitability significantly more than intracellular delivery. A previously unknown mechanism underlies this psychedelic drug action: enhancement of ubiquitously expressed potassium "M-current" channels that is independent of 5-HT2R activation. Using machine-learning-based data assimilation models, we show that M-current activation interacts with previously described mechanisms to dramatically reduce intrinsic excitability and shorten working memory timespan. Thus, psychedelic drugs suppress intrinsic excitability by modulating ion channels that are expressed throughout the brain, potentially triggering homeostatic adjustments that can contribute to widespread therapeutic benefits.

The Emotional State of Second-Language Learners in a Research Writing Course: Do Academic Orientation and Major Matter?

This study examined whether differences exist in the emotional state of students whose approach to undergraduate courses is either preferentially learning-oriented or grade-oriented. It focused on an understudied population of female college students of Saudi Arabian descent who were enrolled in a challenging writing course. Their emotional state was assessed both globally, through the appraisal of their degree of happiness, and locally, through the appraisal of their writing anxiety (a task-specific emotional state). The study contributed to the extant literature by examining whether the association between goal orientation and emotional state, which is predicted by goal orientation theory, could be found in the selected understudied student population. Results illustrate differences between STEM and non-STEM learners. For STEM students, a grade orientation was associated with declining self-reported happiness and increasing writing anxiety. In contrast, for both STEM and non-STEM students, a learning orientation was associated with increasing happiness and declining writing anxiety. Differences existed in the particular type of writing anxiety that was experienced by STEM and non-STEM students. These findings suggest that interventions for students who are struggling academically may need to address personal dispositions if such interventions are to foster subjective well-being (including positive emotions).

Modern-Day Practice of DCD Liver Transplantation: Controversies, Innovations, and Future Directions.

PURPOSE OF REVIEW: Over the past decade, donation after circulatory death (DCD) liver transplantation has expanded in the United States due to improved surgical experience and perioperative management. Despite these advances, there remains a reluctance towards broader utilization of DCD liver allografts due to lack of standardized donation process, concern for inferior graft survival, and risk of ischemic cholangiopathy associated with temporary lack of oxygenated perfusion during withdrawal of life-supporting treatment during procurement. RECENT FINDINGS: New perfusion technologies offer potential therapeutic options to mitigate biliary complications and expand utilization of marginal DCD grafts. As these modalities enter routine clinical practice, DCD utilization will continue to increase, and liver allocation policies in turn will evolve to reflect this growing practice. This review describes recent progress in DCD LT, current challenges with utilization of DCD liver allografts, and how novel technologies and policies could impact the future of the field.

Structural Analysis of Janus Tyrosine Kinase Variants in Hematological Malignancies: Implications for Drug Development and Opportunities for Novel Therapeutic Strategies.

Janus tyrosine kinase (JAK) variants are known drivers for hematological disorders. With the full-length structure of mouse JAK1 being recently resolved, new observations on the localization of variants within closed, open, and dimerized JAK structures are possible. Full-length homology models of human wild-type JAK family members were developed using the Glassman et al. reported mouse JAK1 containing the V658F structure as a template. Many mutational sites related to proliferative hematological disorders reside in the JH2 pseudokinase domains facing the region important in dimerization of JAKs in both closed and open states. More than half of all JAK gain of function (GoF) variants are changes in polarity, while only 1.2% are associated with a change in charge. Within a JAK1-JAK3 homodimer model, IFNLR1 (PDB ID7T6F) and the IL-2 common gamma chain subunit (IL2Rγc) were aligned with the respective dimer implementing SWISS-MODEL coupled with ChimeraX. JAK3 variants were observed to encircle the catalytic site of the kinase domain, while mutations in the pseudokinase domain align along the JAK-JAK dimerization axis. FERM domains of JAK1 and JAK3 are identified as a hot spot for hematologic malignancies. Herein, we propose new allosteric surfaces for targeting hyperactive JAK dimers.

Gynecologic oncology fellowship leadership trends by gender.

Our objective was to examine the educational, research, and leadership trends among gynecologic oncology (GYO) fellowship program directors (PD) and how these vary by gender. PDs were identified using the Society of Gynecologic Oncology Fellowship Directory. Surveys were sent to PDs' emails to obtain information about demographics, education, and research background. Publicly available data and institutional biographies were used to supplement primary survey data for incomplete responses or survey non-responders. Scopus was used to determine the h-index and number of publications and citations for each PD. Parametric data were compared using unpaired two-tailed t-tests. Chi-square and Fisher's exact tests were performed for categorical data. The significance level was p < 0.05. Approximately one-half of PDs were female (50.8%). Female PDs had a younger mean age than male PDs (46.4 years vs 51.9 years, p = 0.0014). The average overall h-index was 22 (SD = 14.5) and the average number of publications was 71.2 (SD = 63.3). The average h-index was higher in male PDs than females (27.8 vs 16.3, p = 0.0012), as were the number of publications (97.3 vs 45.8, p = 0.0008). Differences exist among GYO PDs by gender. While research productivity may be reflective of age, gender-based equity in research time should be further explored.

Serum Procalcitonin (PCT) - Is there a Role as an Early Biomarker in Infected Diabetic Foot Ulcer (IDFU) Patients?

Introduction: Infected diabetic foot ulcers may lead to serious complications if not recognised in the early stage. Diagnosis of infection is particularly challenging at that stage; thus, a sensitive inflammatory biomarker may be helpful. We aimed to evaluate the role of procalcitonin (PCT) as an early biomarker for infected diabetic foot ulcers (IDFU). Materials and method: This cross-sectional study was conducted at Klinik Rawatan Keluarga (KRK), Orthopedic clinic and wards in Hospital Universiti Sains Malaysia (USM) from May 2020 to December 2020. A total of 264 participants were recruited and divided into three groups: 50 diabetic patients with no ulcers (control), 107 patients with non-infected diabetic foot ulcers (NIDFU), and 107 patients with infected diabetic foot ulcers (IDFU). The level of PCT was taken for all patients. Total white count (TWC) and C-reactive protein (CRP) were taken only for IDFU patients. Diagnosis of infection was based on the Infectious Disease Society of America-International Working Group of Diabetic Foot (IDSA-IMWGDF), and the severity of infection was graded according to the Wagner Classification. Results: The level of PCT was higher in IDFU than in NIDFU and diabetic patient, with a median (IQR) of 0.355 (0.63) ng/mL, 0.077 (0.15) ng/mL and 0.028 (0.02) ng/mL, respectively. PCT and CRP showed moderate positive correlations in IDFU patients (p<0.001). The sensitivity and specificity were 63.6% and 83.2%, respectively, at the best cut-off at 0.25 ng/mL. Conclusion: PCT is a valuable biomarker for the diagnosis of infection; however, it adds little value in the early diagnosis of IDFU in view of its low sensitivity.

Perceptions and attitudes of medical students towards student evaluation of teaching: A cross-sectional study.

BACKGROUND: Faculty evaluation surveys in the frame of student evaluation of teaching (SETs) are a widely utilized tool to assess faculty teaching. Although SETs are used regularly to evaluate teaching effectiveness, their sole use for making administrative decisions and as an indicator of teaching quality has been controversial. METHODS: A survey containing 22 items assessing demographics, perception, and factors for evaluating faculty was distributed to medical students at our institute. Statistical analyses were conducted using Microsoft Excel and R Software utilizing regression analysis and ANOVA test. RESULTS: The survey received 374 responses consisting of 191 (51.1%) male students and 183 (48.9%) female students. In all, 178 (47.5%) students considered the optimal time for providing faculty evaluation to be after the release of the exam results, compared to 127 (33.9%) students, who chose the after the exam but before the release of exam results option. When asked what happens whenever the tutor is aware about the SETs data, 273 (72.9%) and 254 (67.9%) students believed that it would influence the difficulty of the exam and grading/curving of the exam results, respectively. Better teaching skills (93%, 348), being responsive and open to student feedback and suggestions (84.7%, 317), being committed to class time and schedule (80.1%, 300), and an easier exam (68.6%, 257) were considered important factors to acquire a positive evaluation by a considerable proportion of students. Fewer lectures (P < 0.05), decreased number of slides per lecture (P < 0.01), easier exam (P < 0.05), and giving clues to students about the exam (P < 0.05) were found to be very important to obtain a positive tutor evaluation by students. CONCLUSIONS: Institutions ought to continue exploring areas of improvement in the faculty evaluation process while raising awareness among students about the importance and administrative implications of their feedback.

Clinical Characteristics and Computed Tomography Findings in Adult Patients With an Aberrant Right Subclavian Artery: A Single-Center Retrospective Cohort Study.

OBJECTIVE: We sought to determine the prevalence and possible features associated with symptoms in adult patients diagnosed with an aberrant right subclavian artery (ARSA). METHODS: In this single-center retrospective study, 386 adult patients were diagnosed with ARSA on chest CT scans performed between June 2016 and April 2021. Patients were grouped by the presence of symptoms, which included dysphagia, shortness of breath, cough, and upper airway wheezing. Four cardiothoracic radiologists reviewed the chest CT scans to assess features of ARSA. Agreement and multivariable logistic regression analyses were performed to determine interobserver variability and features associated with the presence of symptoms, respectively. RESULTS: The prevalence of ARSA was 1.02% and 81.3% of patients were asymptomatic. Shortness of breath (74.6%) was the most common symptom. Interobserver agreement was acceptable with most variables having an interclass correlation coefficient or κ >0.80. A patient's height > 158 cm (OR: 2.50, P = 0.03), cross-sectional area > 60 mm 2 of ARSA at the level of the esophagus (OR: 2.39, P = 0.046), and angle >108 degrees formed with the aortic arch (OR: 1.99, P = 0.03) were associated with the presence of symptoms on multivariable logistic regression. A distance increase per 1 mm between ARSA and trachea (OR: 0.85, P = 0.02) was associated with decreased odds of symptoms. CONCLUSIONS: Aberrant right subclavian artery is an incidental finding in most adult patients. The cross-sectional area at the level of the esophagus, angle formed with the medial wall of the aortic arch, distance between the ARSA and the trachea, and a patient's height were features associated with the presence of symptoms.

JAK1 Pseudokinase V666G Mutant Dominantly Impairs JAK3 Phosphorylation and IL-2 Signaling.

Overactive Janus kinases (JAKs) are known to drive leukemia, making them well-suited targets for treatment. We sought to identify new JAK-activating mutations and instead found a JAK1-inactivating pseudokinase mutation, V666G. In contrast to other pseudokinase mutations that canonically lead to an active kinase, the JAK1 V666G mutation led to under-activation seen by reduced phosphorylation. To understand the functional role of JAK1 V666G in modifying kinase activity we investigated its influence on other JAK kinases and within the Interleukin-2 pathway. JAK1 V666G not only inhibited its own activity, but its presence could inhibit other JAK kinases. These findings provide new insights into the potential of JAK1 pseudokinase to modulate its own activity, as well as of other JAK kinases. Thus, the features of the JAK1 V666 region in modifying JAK kinases can be exploited to allosterically inhibit overactive JAKs.