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Occupational therapy programs can use a variety of delivery modes for Level I fieldwork. All experiences aim to contribute to the clinical and professional preparation for Level II fieldwork. This study compared the Level II fieldwork outcomes for two cohorts of students, one that participated in simulation-based Level I fieldwork and one that completed community and clinic-based Level I fieldwork. The student outcomes on the American Occupational Therapy Association AOTA Fieldwork Performance Evaluation (FWPE) for the Occupational Therapy Student were used for comparative data. The results indicated no statistically significant difference in the two cohorts' midterm score ratings. Statistically significant differences with higher performance for the cohort that participated in simulation-based Level I fieldwork were noted in the areas of safety and use of occupation-based interventions. The results of this study support the effective use of high-fidelity simulation in preparing students for success on Level II fieldwork.

PURPOSE: To perform a descriptive epidemiologic analysis of National Basketball Association (NBA) injuries from 2016 to 2021, to evaluate the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (coronavirus disease 2019, or COVID-19) on injury patterns and performance statistics, and to determine the effect of infection with SARS-CoV-2 on individual performance statistics. METHODS: Injury epidemiology in the NBA from the 2016 to 2021 seasons was collected using a comprehensive online search. Injuries and time missed were categorized by injury location and type. Player positions and timing of injury were recorded. Performance statistics were collected including traditional game statistics and Second Spectrum (speed, distance) statistics. Comparisons were made over seasons and comparing the pre-COVID-19 pandemic seasons to the pandemic era seasons. Players diagnosed with COVID-19 were analyzed for changes in performance in the short or long term. RESULTS: Of the 3,040 injuries captured, 1,880 (61.84%) were in the lower extremity. Guards (77.44%) and forwards (75.88%) had a greater proportion of soft-tissue injuries (P < .001) than centers. Guards had the highest proportion of groin (3.27%, P = .001) and hamstring (6.21%, P < .001) injuries. Despite minor differences on a per-season basis, there were no differences in injury patterns identified between pre-COVID-19 and COVID-19 eras. Of players diagnosed with COVID-19 during the NBA Bubble, there were no detriments in short- or long-term performance identified, including traditional game statistics and speed and distance traveled. CONCLUSIONS: In the NBA seasons from 2016 to 2021, most injuries were to the lower extremity. The SARS-CoV-2 pandemic did not substantially impact injury patterns in the NBA, including locations of injury and type of injury (bony or soft tissue). Furthermore, infection with SARS-CoV-2 does not appear to have a significant impact on performance in basketball-specific or speed and distance measures. LEVEL OF EVIDENCE: Level IV, prognostic case series.

Follicle-stimulating hormone (FSH) is a dimeric glycoprotein secreted by the anterior pituitary gonadotrope that is necessary for reproductive function in mammals. FSH primarily regulates granulosa cells and follicular growth in females, and Sertoli cell function in males. Since its identification in the 1930s and sequencing in the 1970s, significant progress has been made in elucidating its regulation and downstream function. Recent advances provide deeper insight into FSH synthesis, and effects in the gonads suggest potential roles in extragonadal tissues and examine pharmacological approaches and clinical applications in infertility treatment that now affect 18% of couples. These advances were discussed in detail in a number of reviews published in the last 2 years in Endocrinology. In this brief commentary, we summarize these reviews and point to the outstanding questions that should be answered in the near future to bridge a gap in our understanding of this hormone.

Abstract Systemic lupus erythematosus (SLE) is a chronic autoimmune condition that can affect multiple organ systems and is heterogenous in its presentation and response to therapy. When diagnosed in childhood, SLE is associated with increased morbidity and mortality compared to adult SLE, often requiring substantial immunosuppression with the risk of significant side effects. There remains a significant unmet need for new therapies that can improve disease control and reduce glucocorticoid and other toxic medication exposure for patients with severe or refractory disease. The pathogenesis of SLE involves B cell dysregulation and autoantibody production, which are a hallmark of the disease. Currently approved B cell directed therapies often result in incomplete B cell depletion and may not target long-lived plasma cells responsible for SLE autoantibodies. It is hypothesized that by persistently eliminating both B cells and plasmablasts, CAR T therapy can halt autoimmunity and prevent organ damage in patient’s refractory to current B cell-depleting treatments. Herein we summarize the current preclinical and clinical data utilizing CAR T cells for SLE and discuss the future of this treatment modality for lupus.

Mutations in the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene are linked to Fragile X Syndrome, the most common monogenic cause of intellectual disability and autism. People affected with mutations in FMR1 have higher incidence of obesity, but the mechanisms are largely unknown. In the current study, we determined that male Fmr1 knockout mice (KO, Fmr1-/y), but not female Fmr1-/-, exhibit increased weight when compared to wild-type controls, similarly to humans with FMR1 mutations. No differences in food or water intake were found between groups; however, male Fmr1-/y display lower locomotor activity, especially during their active phase. Moreover, Fmr1-/y have olfactory dysfunction determined by buried food test, although they exhibit increased compulsive behavior, determined by marble burying test. Since olfactory brain regions communicate with hypothalamic regions that regulate food intake, including POMC neurons that also regulate locomotion, we examined POMC neuron innervation and numbers in Fmr1-/y mice. POMC neurons express Fmrp, and POMC neurons in Fmr1-/y have higher inhibitory GABAergic synaptic inputs. Consistent with increased inhibitory innervation, POMC neurons in the Fmr1-/y mice exhibit lower activity, based on cFOS expression. Notably, Fmr1-/y mice have fewer POMC neurons than controls, specifically in the rostral arcuate nucleus, which could contribute to decreased locomotion and increased body weight. These results suggest a role for Fmr1 in the regulation of POMC neuron function and the etiology of Fmr1-linked obesity.

Obesity incidence is increasing worldwide with the urgent need to identify new therapeutics. Sex differences in immune cell activation drive obesity-mediated pathologies where males are more susceptible to obesity comorbidities and exacerbated inflammation. Here, we demonstrate that the macrophage-secreted protein RELMα critically protects females against high-fat diet (HFD)-induced obesity. Compared to male mice, serum RELMα levels were higher in both control and HFD-fed females and correlated with frequency of adipose macrophages and eosinophils. RELMα-deficient females gained more weight and had proinflammatory macrophage accumulation and eosinophil loss in the adipose stromal vascular fraction (SVF), while RELMα treatment or eosinophil transfer rescued this phenotype. Single-cell RNA-sequencing of the adipose SVF was performed and identified sex and RELMα-dependent changes. Genes involved in oxygen sensing and iron homeostasis, including hemoglobin and lncRNA Gm47283/Gm21887, correlated with increased obesity, while eosinophil chemotaxis and response to amyloid-beta were protective. Monocyte-to-macrophage transition was also dysregulated in RELMα-deficient animals. Collectively, these studies implicate a RELMα-macrophage-eosinophil axis in sex-specific protection against obesity and uncover new therapeutic targets for obesity.

This article explores the experiences of a group of women who having achieved success in education and returned to the adult learning environment again. A creative methodological approach allows the women to describe in their own words experiences of educational success and motivations to return to learning. Discussion points predominantly focus on outcomes that fall outside those typically measured. These include alternative interpretations of success; benefits of diverse learning groups; personal growth and bias, and connections and friendship. Questions of success and outcomes in later life are also explored. Conclusions identify the importance of recognising the diversity of experience in adult education, the varying methods of measuring success and the need to ensure learner stories are heard.

INTRODUCTION: Mutations in the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene cause Fragile X Syndrome, the most common monogenic cause of intellectual disability. Mutations of FMR1 are also associated with reproductive disorders, such as early cessation of reproductive function in females. While progress has been made in understanding the mechanisms of mental impairment, the causes of reproductive disorders are not clear. FMR1-associated reproductive disorders were studied exclusively from the endocrine perspective, while the FMR1 role in neurons that control reproduction was not addressed. RESULTS: Here, we demonstrate that similar to women with FMR1 mutations, female Fmr1 null mice stop reproducing early. However, young null females display larger litters, more corpora lutea in the ovaries, increased inhibin, progesterone, testosterone, and gonadotropin hormones in the circulation. Ovariectomy reveals both hypothalamic and ovarian contribution to elevated gonadotropins. Altered mRNA and protein levels of several synaptic molecules in the hypothalamus are identified, indicating reasons for hypothalamic dysregulation. Increased vascularization of corpora lutea, higher sympathetic innervation of growing follicles in the ovaries of Fmr1 nulls, and higher numbers of synaptic GABAA receptors in GnRH neurons, which are excitatory for GnRH neurons, contribute to increased FSH and LH, respectively. Unmodified and ovariectomized Fmr1 nulls have increased LH pulse frequency, suggesting that Fmr1 nulls exhibit hyperactive GnRH neurons, regardless of the ovarian feedback. CONCLUSION: These results reveal Fmr1 function in the regulation of GnRH neuron secretion, and point to the role of GnRH neurons, in addition to the ovarian innervation, in the etiology of Fmr1-mediated reproductive disorders.

La industria pesquera genera subproductos que al acumularse causan problemas de contaminación ambiental; sin embargo, podrían ser una fuente de nutrientes para rumiantes. El objetivo de este estudio fue evaluar la respuesta sobre el microbioma ruminal, la digestibilidad aparente y productividad de borregos Katahdin alimentados con diferentes niveles de harina de caparazón de camarón (HCC). Cuatro borregos machos con peso vivo de 22 ± 2.5 kg fueron asignados en un diseño cuadrado latino (4 animales x 4 tratamientos) repetido. Los animales fueron asignados durante 16 días por periodo a dietas con 0, 5, 10 y 20 g 100 g -1 de MS de HCC, los tratamientos fueron: HCC0, HCC5, HCC10 y HCC20, respectivamente. La mayor ganancia diaria de peso se tuvo en los animales del tratamiento HCC5 (P ≤ 0.05). Sin embargo, el mayor consumo de materia seca se observó en los animales con la dieta HCC20 (P ≤ 0.05). En la digestibilidad aparente de la materia seca no hubo diferencia entre tratamientos (P > 0.05), ni en la concentración de bacterias totales (P > 0.05), mientras que la concentración de bacterias celulolíticas y de bacterias degradadoras de quitina, fue mayor en los animales del tratamiento con HCC20 (P ≤ 0.05). Los resultados indican una adaptación del microbioma ruminal a dosis altas de HCC, por tanto, se puede usar HCC en dietas para borregos sin efecto en el metabolismo y microbiana ruminal, la digestibilidad de los nutrientes y en el desempeño de los animales.

In student-teachers' education, it is fundamental to foster the intercultural communicative competence for them to express their views on cultural concepts and phenomena in written and orally, with native and non-native speakers of a foreign language. In the same vein, future foreign language teachers, particularly at an early stage of their learning process, are expected to possess some basic citizen competencies which allow them, amongst other things, to show an understanding of the country they live in, the cultural diversity it has, and the current situation they and their co-nationals are facing (cognitive dimension). Bering in mind the importance of competences mentioned before. This short-scale quantitative study set out to classify the perceptions that a group of student-teachers had on Colombia, their cultural identity, and Colombians' cultural identity in general. To that end, one oral and two written short narratives along with a final questionnaire were collected and analysed using Atlas TI. 8 and Excel spreadsheets. The counting and classification of prominent speech parts that conveyed perceptions (nouns, nouns plus adjectives and adjective per se) unveiled that participants held quite optimistic views on their nation, particularly in cultural, natural, geographic, and culinary aspects. It was also revealed that student-teachers had a high appreciation of themselves culturally speaking, praising their personality and mood as most important features. Furthermore, it was unveiled that participants held a positive view about their compatriots, highlighting their personality, mood, and character. It is important to remark that positive views about own identity were much higher than general views on Colombians.

BackgroundInternational orthopaedic resident rotations in low and middle-income countries (LMICs) are gaining popularity among high-income country (HIC) residency programs. While evidence demonstrates a benefit for the visiting residents, few studies have evaluated the impact of such rotations on the orthopaedic surgeons and trainees in LMICs. The purpose of this study was to further explore themes identified in a previous survey study regarding the local impact of visiting HIC resident rotations.MethodsUsing a semistructured interview guide, LMIC surgeons and trainees who had hosted HIC orthopaedic residents within the previous 10 years were interviewed until thematic saturation was reached.ResultsTwenty attending and resident orthopaedic surgeons from 8 LMICs were interviewed. Positive and negative effects of the visiting residents on clinical care, education, interpersonal relationships, and resource availability were identified. Seven recommendations for visiting resident rotations were highlighted, including a 1 to 2-month rotation length; visiting residents at the senior training level; site-specific prerotation orientation with an emphasis on resident attitudes, including the need for humility; creation of bidirectional opportunities; partnering with institutions with local training programs; and fostering mutually beneficial sustained relationships.ConclusionsThis study explores the perspectives of those who host visiting residents, a viewpoint that is underrepresented in the literature. Future research regarding HIC orthopaedic resident rotations in LMICs should include the perspectives of local surgeons and trainees to strive for mutually beneficial experiences to further strengthen and sustain such academic partnerships.

Introduction: Chronic idiopathic constipation (CIC) negatively impacts quality of life and increases healthcare costs. Lubiprostone stimulates the secretion of intestinal fluid, in turn facilitating the passage of stools and alleviating associated symptoms. Lubiprostone has been available in Mexico since 2018, but its clinical efficacy has not been studied in a Mexican population. Aim: To evaluate the efficacy of lubiprostone, assessed by changes in spontaneous bowel movement (SBM) frequency after one week of treatment with 24 μg oral lubiprostone (b.i.d.), as well as its safety, over four weeks of treatment. Study: Randomized, double-blind, placebo-controlled study on 211 adults with CIC in Mexico. Results: The increase in SBM frequency, after one week of treatment, was significantly higher in the lubiprostone group than in the placebo group (mean: 4.9 [SD: 4.45] vs. 3.0 [3.14], p = 0.020). Secondary efficacy endpoints revealed a significantly higher proportion of SBM frequency/week in the lubiprostone group at weeks 2, 3, and 4. There was a better response within 24 h after the first dose with lubiprostone vs. placebo (60.0% vs. 41.5%; OR: 2.08, CI95%: [1.19, 3.62], p = 0.009) and the lubiprostone group also had significant improvement, with respect to straining, stool consistency, abdominal bloating, and Satisfaction Index. The main adverse events were gastrointestinal disorders in 13 (12.4%) lubiprostone-treated subjects and 4 (3.8%) control subjects. Conclusions: Our data confirm the efficacy and safety of lubiprostone for the treatment of CIC in a Mexican population. Lubiprostone treatment induces relief from the most bothersome symptoms associated with constipation. Resumen: Introducción: El estreñimiento crónico idiopático (ECI) impacta de manera negativa la calidad de vida e incrementa los costos de los sistemas de salud. La lubiprostona estimula la secreción de fluido intestinal, lo cual facilita el paso de las heces y alivia síntomas asociados. La lubiprostona ha estado disponible en México desde 2018, pero su eficacia clínica no ha sido estudiada en una población mexicana. Objetivo: Evaluar la eficacia de la lubiprostona, por medio de la observación de los cambios en la frecuencia de evacuaciones espontáneas completas (EEC), después de una semana de tratamiento con 24 μg de lubiprostona oral dos veces al día, al igual que su seguridad, después de cuatro semanas de tratamiento. Estudio: Estudio aleatorizado, doble ciego, controlado con placebo, en 211 adultos con ECI en México. Resultados: El incremento de frecuencia de EEC tras una semana de tratamiento, fue significativamente más alto en el grupo de lubiprostona que en el grupo placebo (media: 4.9 [DE: 4.45] vs. 3.0 [3.14], p = 0.020). Los criterios de valoración secundarios de eficacia revelaron una proporción significativamente más alta de frecuencia EEC/semana en el grupo lubiprostona a las semanas 2, 3 y 4. Hubo una mejor respuesta dentro de 24 horas de la primera dosis de lubiprostona vs. placebo (60.0% vs. 41.5%; OR: 2.08, CI95%: [1.19, 3.62], p = 0.009), y el grupo de lubiprostona también presentó mejoría significativa respecto al pujo, la consistencia de las heces, la inflamación abdominal y el Índice de Satisfacción. Los principales eventos adversos fueron trastornos gastrointestinales en 13 (12.4%) de los sujetos tratados con lubiprostona y 4 (3.8%) de los sujetos control. Conclusiones: Nuestros datos confirman la eficacia y seguridad de la lubiprostona para el tratamiento del ECI en una población mexicana. El tratamiento con lubiprostona induce alivio de los síntomas más molestos asociados con la constipación.

Introduction: Gastroesophageal reflux disease (GERD) is very prevalent in the general population, with a broad spectrum of clinical manifestations, requiring accurate diagnosis and treatment. Aim: The aim of this expert review is to establish good clinical practice recommendations for the diagnosis and personalized treatment of GERD. Methods: The good clinical practice recommendations were produced by a group of experts in GERD, members of the Asociación Mexicana de Gastroenterología (AMG), after carrying out an extensive review of the published literature and discussing each recommendation at a face-to-face meeting. This document does not aim to be a clinical practice guideline with the methodology such a document requires. Results: Fifteen experts on GERD formulated 27 good clinical practice recommendations for recognizing the symptoms and complications of GERD, the rational use of diagnostic tests and medical treatment, the identification and management of refractory GERD, the overlap with functional disorders, endoscopic and surgical treatment, and GERD in the pregnant woman, older adult, and the obese patient. Conclusions: An accurate diagnosis of GERD is currently possible, enabling the prescription of a personalized treatment in patients with this condition. The goal of the good clinical practice recommendations by the group of experts from the AMG presented in this document is to aid both the general practitioner and specialist in the process of accurate diagnosis and treatment, in the patient with GERD. Resumen: Antecedentes: La enfermedad por reflujo gastroesofágico (ERGE) es muy prevalente en población general, con un amplio espectro de manifestaciones clínicas que requiere de un diagnóstico y tratamiento de precisión. Objetivo: Esta es una revisión de expertos que establece recomendaciones de buena práctica clínica para el diagnóstico y tratamiento personalizado de la ERGE. Métodos: Las recomendaciones de buena práctica clínica se generaron por un grupo de expertos en ERGE, miembros de la Asociación Mexicana de Gastroenterología (AMG), después de hacer una extensa revisión de la literatura publicada y la discusión de cada recomendación en una reunión presencial. Este documento no pretende ser una guía de práctica clínica con la metodología que este formato requiere. Resultados: Quince expertos en ERGE elaboraron 27 recomendaciones de buena práctica clínica para el reconocimiento de síntomas y complicaciones de la ERGE, uso racional de pruebas diagnósticas y tratamiento médico de los diferentes fenotipos, identificación y manejo de la ERGE refractaria, de la sobreposición con trastornos funcionales, del tratamiento endoscópico y quirúrgico y sobre la ERGE en el embarazo, adulto mayor y en el paciente obeso. Conclusiones: Actualmente es posible un diagnóstico de precisión en la ERGE que permite prescribir un tratamiento personalizado en los pacientes con esta condición. Las recomendaciones de buena práctica clínica del grupo de expertos de la AMG presentadas en este documento pretender ayudar al médico general y al especialista en el proceso del diagnóstico y tratamiento de precisión del paciente con ERGE.

Resumen: Antecedentes: La enfermedad por reflujo gastroesofágico (ERGE) es muy prevalente en la población general, se presenta con un amplio espectro de manifestaciones clínicas que requiere de un diagnóstico y tratamiento de precisión. Objetivo: Esta es una revisión de expertos que establece recomendaciones de buena práctica clínica para el diagnóstico y tratamiento personalizado de la ERGE. Métodos: Las recomendaciones de buena práctica clínica se generaron por un grupo de expertos en ERGE, miembros de la Asociación Mexicana de Gastroenterología (AMG), después de hacer una extensa revisión de la literatura publicada y de discutir cada recomendación en una reunión presencial. Este documento no pretende ser una guía de práctica clínica con la metodología que este formato requiere. Resultados: Un total de 15 expertos en ERGE elaboraron 27 recomendaciones de buena práctica clínica para el reconocimiento de síntomas y complicaciones, uso racional de pruebas diagnósticas y tratamiento médico de los diferentes fenotipos, identificación y manejo de la enfermedad refractaria, de la sobreposición con trastornos funcionales, del tratamiento endoscópico y quirúrgico, así como sobre la ERGE en el embarazo, el adulto mayor y el paciente obeso. Conclusiones: Actualmente, es posible un diagnóstico de precisión en la ERGE que permite prescribir una terapia personalizada en los sujetos con esta condición. Las recomendaciones de buena práctica clínica del grupo de expertos de la AMG presentadas en este documento pretenden ayudar al médico general y al especialista en el proceso del diagnóstico y tratamiento de precisión del paciente con ERGE. Abstract: Introduction: Gastroesophageal reflux disease (GERD) is very prevalent in the general population, with a broad spectrum of clinical manifestations, requiring accurate diagnosis and treatment. Aim: The aim of this expert review is to establish good clinical practice recommendations for the diagnosis and personalized treatment of GERD. Methods: The good clinical practice recommendations were produced by a group of experts in GERD, members of the Asociación Mexicana de Gastroenterología (AMG), after carrying out an extensive review of the published literature and discussing each recommendation at a face-to-face meeting. This document does not aim to be a clinical practice guideline with the methodology such a document requires. Results: Fifteen experts on GERD formulated 27 good clinical practice recommendations for recognizing the symptoms and complications of GERD, the rational use of diagnostic tests and medical treatment, the identification and management of refractory GERD, the overlap with functional disorders, endoscopic and surgical treatment, and GERD in the pregnant woman, older adult, and the obese patient. Conclusions: An accurate diagnosis of GERD is currently possible, enabling the prescription of a personalized treatment in patients with this condition. The goal of the good clinical practice recommendations by the group of experts from the AMG presented in this document is to aid both the general practitioner and specialist in the process of accurate diagnosis and treatment, in the patient with GERD.

Resumen: Introducción: El estreñimiento crónico idiopático (ECI) impacta de manera negativa la calidad de vida e incrementa los costos de los sistemas de salud. La lubiprostona estimula la secreción de fluido intestinal, lo cual facilita el paso de las heces y alivia síntomas asociados. La lubiprostona ha estado disponible en México desde 2018, pero su eficacia clínica no ha sido estudiada en una población mexicana. Objetivo: Evaluar la eficacia de la lubiprostona, por medio de la observación de los cambios en la frecuencia de evacuaciones espontáneas completas (EEC), después de una semana de tratamiento con 24 μg de lubiprostona oral dos veces al día, al igual que su seguridad, después de cuatro semanas de tratamiento. Estudio: Estudio aleatorizado, doble ciego, controlado con placebo, en 211 adultos con ECI en México. Resultados: El incremento de frecuencia de EEC tras una semana de tratamiento fue significativamente más alto en el grupo de lubiprostona que en el grupo placebo (media: 4.9 [DE: 4.45] vs. 3.0 [3.14], p = 0.020). Los criterios de valoración secundarios de eficacia revelaron una proporción significativamente más alta de frecuencia EEC/semana en el grupo lubiprostona a las semanas 2, 3 y 4. Hubo una mejor respuesta dentro de 24 horas de la primera dosis de lubiprostona vs. placebo (60.0% vs. 41.5%; OR: 2.08 [IC 95%: 1.19, 3.62], p = 0.009), y el grupo de lubiprostona también presentó mejoría significativa respecto al pujo, la consistencia de las heces, la inflamación abdominal y el índice de satisfacción. Los principales eventos adversos fueron trastornos gastrointestinales en 13 (12.4%) de los sujetos tratados con lubiprostona y 4 (3.8%) de los sujetos control. Conclusiones: Nuestros datos confirman la eficacia y la seguridad de la lubiprostona para el tratamiento del ECI en una población mexicana. El tratamiento con lubiprostona induce alivio de los síntomas más molestos asociados con la constipación. Abstract: Introduction: Chronic idiopathic constipation (CIC) negatively impacts quality of life and increases healthcare costs. Lubiprostone stimulates the secretion of intestinal fluid, in turn facilitating the passage of stools and alleviating associated symptoms. Lubiprostone has been available in Mexico since 2018, but its clinical efficacy has not been studied in a Mexican population. Aim: To evaluate the efficacy of lubiprostone, assessed by changes in spontaneous bowel movement (SBM) frequency after one week of treatment with 24 μg oral lubiprostone (b.i.d.), as well as its safety, over four weeks of treatment. Study: Randomized, double-blind, placebo-controlled study on 211 adults with CIC in Mexico. Results: The increase in SBM frequency, after one week of treatment, was significantly higher in the lubiprostone group than in the placebo group (mean: 4.9 [SD: 4.45] vs. 3.0 [3.14], P = .020). Secondary efficacy endpoints revealed a significantly higher proportion of SBM frequency/week in the lubiprostone group at weeks 2, 3, and 4. There was a better response within 24 hours after the first dose with lubiprostone vs. placebo (60.0% vs. 41.5%; OR: 2.08, [95% CI: 1.19, 3.62], P = .009) and the lubiprostone group also had significant improvement, with respect to straining, stool consistency, abdominal bloating, and satisfaction index. The main adverse events were gastrointestinal disorders in 13 (12.4%) lubiprostone-treated subjects and 4 (3.8%) control subjects. Conclusions: Our data confirm the efficacy and safety of lubiprostone for the treatment of CIC in a Mexican population. Lubiprostone treatment induces relief from the most bothersome symptoms associated with constipation.

Abstract Achalasia is a rare esophageal motility disorder for which the etiology is not fully understood. Evidence suggests that autoimmune inflammatory infiltrates, possibly triggered by a viral infection, may lead to a degeneration of neurons within the myenteric plexus. While the infection is eventually resolved, genetically susceptible individuals may still be at risk of developing achalasia. This study aimed to determine whether immunological and physiological networks differ between male and female patients with achalasia. This cross-sectional study included 189 preoperative achalasia patients and 500 healthy blood donor volunteers. Demographic, clinical, laboratory, immunological, and tissue biomarkers were collected. Male and female participants were evaluated separately to determine the role of sex. Correlation matrices were constructed using bivariate relationships to generate complex inferential networks. These matrices were filtered based on their statistical significance to identify the most relevant relationships between variables. Network topology and node centrality were calculated using tools available in the R programming language. Previous occurrences of chickenpox, measles, and mumps infections have been proposed as potential risk factors for achalasia, with a stronger association observed in females. Principal component analysis (PCA) identified IL-22, Th2, and regulatory B lymphocytes as key variables contributing to the disease. The physiological network topology has the potential to inform whether a localized injury or illness is likely to produce systemic consequences and the resulting clinical presentation. Here we show that immunological involvement in achalasia appears localized in men because of their highly modular physiological network. In contrast, in women the disease becomes systemic because of their robust network with a larger number of inter-cluster linkages.

'Intracranial mesenchymal tumor, FET-CREB fusion-positive' occurs primarily in children and young adults and has previously been termed intracranial angiomatoid fibrous histiocytoma (AFH) or intracranial myxoid mesenchymal tumor (IMMT). Here we performed genome-wide DNA methylation array profiling of 20 primary intracranial mesenchymal tumors with FET-CREB fusion to further study their ontology. These tumors resolved into two distinct epigenetic subgroups that were both divergent from all other analyzed intracranial neoplasms and soft tissue sarcomas, including meningioma, clear cell sarcoma of soft tissue (CCS), and AFH of extracranial soft tissue. The first subgroup (Group A, 16 tumors) clustered nearest to but independent of solitary fibrous tumor and AFH of extracranial soft tissue, whereas the second epigenetic subgroup (Group B, 4 tumors) clustered nearest to but independent of CCS and also lacked expression of melanocytic markers (HMB45, Melan A, or MITF) characteristic of CCS. Group A tumors most often occurred in adolescence or early adulthood, arose throughout the neuroaxis, and contained mostly EWSR1-ATF1 and EWSR1-CREB1 fusions. Group B tumors arose most often in early childhood, were located along the cerebral convexities or spinal cord, and demonstrated an enrichment for tumors with CREM as the fusion partner (either EWSR1-CREM or FUS-CREM). Group A tumors more often demonstrated stellate/spindle cell morphology and hemangioma-like vasculature, whereas Group B tumors more often demonstrated round cell or epithelioid/rhabdoid morphology without hemangioma-like vasculature, although robust comparison of these clinical and histologic features requires future study. Patients with Group B tumors had inferior progression-free survival relative to Group A tumors (median 4.5 vs. 49 months, p = 0.001). Together, these findings confirm that intracranial AFH-like neoplasms and IMMT represent histologic variants of a single tumor type ('intracranial mesenchymal tumor, FET-CREB fusion-positive') that is distinct from meningioma and extracranial sarcomas. Additionally, epigenomic evaluation may provide important prognostic subtyping for this unique tumor entity.

Disparities exist in treatment modalities, including arthroscopic surgery, for orthopaedic injuries between high-income countries (HICs) and low- and middle-income countries (LMICs). Arthroscopy training is a self-identified goal of LMIC surgeons to meet the burden of musculoskeletal injury. The aim of this study was to determine the necessary "key ingredients" for establishing arthroscopy centers in LMICs in order to build capacity and expand training in arthroscopy in lower-resource settings.MethodsThis study utilized semi-structured interviews with orthopaedic surgeons from both HICs and LMICs who had prior experience establishing arthroscopy efforts in LMICs. Participants were recruited via referral sampling. Interviews were qualitatively analyzed in duplicate via a coding schema based on repeated themes from preliminary interview review. Subgroup analysis was conducted between HIC and LMIC respondents.ResultsWe identified perspectives shared between HIC and LMIC stakeholders and perspectives unique to 1 group. Both groups were motivated by opportunities to improve patients' lives; the LMIC respondents were also motivated by access to skills and equipment, and the HIC respondents were motivated by teaching opportunities. Key ingredients identified by both groups included an emphasis on teaching and the need for high-cost equipment, such as arthroscopy towers. The LMIC respondents reported single-use materials as a key ingredient, while the HIC respondents reported local champions as crucial. The LMIC respondents cited the scarcity of implants and shaver blades as a barrier to the continuity of arthroscopy efforts.ConclusionsIncorporation of the identified key ingredients, along with leveraging the motivations of the host and the visiting participant, will allow future international arthroscopy partnerships to better match proposed interventions with the host-identified needs.Clinical relevanceArthroscopy is an important tool for treatment of musculoskeletal injury. Increasing access to arthroscopy is an important goal to achieve greater equity in musculoskeletal care globally. Developing successful partnerships between HICs and LMICs to support arthroscopic surgery requires sustained relationships that address local needs.

Gastrointestinal amyloidosis is a rare condition commonly found in the setting of systemic AL amyloidosis. Amyloid can deposit throughout the gastrointestinal tract and the resulting symptoms vary depending on the site of deposition. Gastrointestinal (GI) manifestations can range from weight loss or abdominal pain, to more serious complications like gastrointestinal bleeding, malabsorption, dysmotility, and obstruction. This case describes a patient with known history of IgG lambda AL amyloidosis, presenting with epigastric pain and unintentional weight loss found to have gastroduodenal amyloidosis. The definitive diagnosis of GI amyloidosis requires endoscopic biopsy with Congo red staining and visualization under polarized light microscopy. There are currently no specific guidelines for the management of GI amyloidosis. Generally, the goal is to treat the underlying cause of the amyloidosis along with symptom management. Our patient is being treated with cyclophosphamide, bortezomib, and dexamethasone (CyBorD) and started on hemodialysis due to progression of renal disease.

PurposeThe British Columbia COVID-19 Cohort (BCC19C) was developed from an innovative, dynamic surveillance platform and is accessed/analyzed through a cloud-based environment. The platform integrates recently developed provincial COVID-19 datasets (refreshed daily) with existing administrative holdings and provincial registries (refreshed weekly/monthly). The platform/cohort were established to inform the COVID-19 response in near “real-time” and to answer more in-depth epidemiologic questions.ParticipantsThe surveillance platform facilitates the creation of large, up-to-date analytic cohorts of people accessing COVID-19 related services and their linked medical histories. The program of work focused on creating/analyzing these cohorts is referred to as the BCC19C. The administrative/registry datasets integrated within the platform are not specific to COVID-19 and allow for selection of “control” individuals who have not accessed COVID-19 services.Findings to dateThe platform has vastly broadened the range of COVID-19 analyses possible, and outputs from BCC19C analyses have been used to create dashboards, support routine reporting and contribute to the peer-reviewed literature. Published manuscripts (total of 15 as of July, 2023) have appeared in high-profile publications, generated significant media attention and informed policy and programming. In this paper, we conducted an analysis to identify sociodemographic and health characteristics associated with receiving SARS-CoV-2 laboratory testing, testing positive, and being fully vaccinated. Other published analyses have compared the relative clinical severity of different variants of concern; quantified the high “real-world” effectiveness of vaccines in addition to the higher risk of myocarditis among younger males following a 2nd dose of an mRNA vaccine; developed and validated an algorithm for identifying long-COVID patients in administrative data; identified a higher rate of diabetes and healthcare utilization among people with long-COVID; and measured the impact of the pandemic on mental health, among other analyses.Future plansWhile the global COVID-19 health emergency has ended, our program of work remains robust. We plan to integrate additional datasets into the surveillance platform to further improve and expand covariate measurement and scope of analyses. Our analyses continue to focus on retrospective studies of various aspects of the COVID-19 pandemic, as well as prospective assessment of post-acute COVID-19 conditions and other impacts of the pandemic.

Purpose: To perform a descriptive epidemiologic analysis of National Basketball Association (NBA) injuries from 2016 to 2021, to evaluate the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (coronavirus disease 2019, or COVID-19) on injury patterns and performance statistics, and to determine the effect of infection with SARS-CoV-2 on individual performance statistics. Methods: Injury epidemiology in the NBA from the 2016 to 2021 seasons was collected using a comprehensive online search. Injuries and time missed were categorized by injury location and type. Player positions and timing of injury were recorded. Performance statistics were collected including traditional game statistics and Second Spectrum (speed, distance) statistics. Comparisons were made over seasons and comparing the pre-COVID-19 pandemic seasons to the pandemic era seasons. Players diagnosed with COVID-19 were analyzed for changes in performance in the short or long term. Results: Of the 3,040 injuries captured, 1,880 (61.84%) were in the lower extremity. Guards (77.44%) and forwards (75.88%) had a greater proportion of soft-tissue injuries (P < .001) than centers. Guards had the highest proportion of groin (3.27%, P = .001) and hamstring (6.21%, P < .001) injuries. Despite minor differences on a per-season basis, there were no differences in injury patterns identified between pre-COVID-19 and COVID-19 eras. Of players diagnosed with COVID-19 during the NBA Bubble, there were no detriments in short- or long-term performance identified, including traditional game statistics and speed and distance traveled. Conclusions: In the NBA seasons from 2016 to 2021, most injuries were to the lower extremity. The SARS-CoV-2 pandemic did not substantially impact injury patterns in the NBA, including locations of injury and type of injury (bony or soft tissue). Furthermore, infection with SARS-CoV-2 does not appear to have a significant impact on performance in basketball-specific or speed and distance measures. Level of Evidence: Level IV, prognostic case series.

Fecal incontinence is the involuntary passage or the incapacity to control the release of fecal matter through the anus. It is a condition that significantly impairs quality of life in those that suffer from it, given that it affects body image, self-esteem, and interferes with everyday activities, in turn, favoring social isolation. There are no guidelines or consensus in Mexico on the topic, and so the Asociación Mexicana de Gastroenterología brought together a multidisciplinary group (gastroenterologists, neurogastroenterologists, and surgeons) to carry out the «Mexican consensus on fecal incontinence» and establish useful recommendations for the medical community.The present document presents the formulated recommendations in 35 statements. Fecal incontinence is known to be a frequent entity whose incidence increases as individuals age, but one that is under-recognized. The pathophysiology of incontinence is complex and multifactorial, and in most cases, there is more than one associated risk factor. Even though there is no diagnostic gold standard, the combination of tests that evaluate structure (endoanal ultrasound) and function (anorectal manometry) should be recommended in all cases. Treatment should also be multidisciplinary and general measures and drugs (lidamidine, loperamide) are recommended, as well as non-pharmacologic interventions, such as biofeedback therapy, in selected cases. Likewise, surgical treatment should be offered to selected patients and performed by experts. Resumen: La incontinencia fecal es el paso involuntario o la incapacidad de controlar la descarga de materia fecal a través del ano, siendo una condición que deteriora significativamente la calidad de vida de los sujetos que la padecen, ya que afecta la imagen corporal, la autoestima e interfiere con las actividades cotidianas favoreciendo el aislamiento social. En nuestro país no existe una guía o consenso al respecto, por lo que la Asociación Mexicana de Gastroenterología reunió a un grupo multidisciplinario (gastroenterólogos, neurogastroenterológos y cirujanos), para que realizaran el Consenso mexicano sobre incontinencia fecal y se establecieran recomendaciones de utilidad para la comunidad médica.Las recomendaciones emitidas fueron a través de 35 enunciados que se presentan en este documento. Se reconoce que la incontinencia fecal es una entidad frecuente, y cuya incidencia se incrementa conforme aumenta la edad, sin embargo, es poco reconocida. La fisiopatología de la incontinencia es compleja y multifactorial y en la mayoría de los casos existe más de un factor de riesgo asociado. Respecto al diagnóstico, se considera que, si bien no existe un estándar de oro, la combinación de pruebas que evalúen la estructura (p. ej., ultrasonido endoanal) y la función (manometría anorrectal) se debe de recomendar en todos los casos. El tratamiento debe ser también multidisciplinario, y se recomiendan medidas generales, fármacos (lidamidina, loperamida), y en casos seleccionados intervenciones no farmacológicas como la terapia de biorretroalimentación. De igual manera, el tratamiento quirúrgico debe ofrecerse a los pacientes seleccionados y debe ser brindado por los expertos.

Resumen: La incontinencia fecal es el paso involuntario o la incapacidad de controlar la descarga de materia fecal a través del ano, siendo una condición que deteriora significativamente la calidad de vida de los sujetos que la padecen, ya que afecta la imagen corporal, la autoestima e interfiere con las actividades cotidianas favoreciendo el aislamiento social. En nuestro país no existe una guía o consenso al respecto, por lo que la Asociación Mexicana de Gastroenterología reunió a un grupo multidisciplinario (gastroenterólogos, neurogastroenterológos y cirujanos), para que realizaran el Consenso mexicano sobre incontinencia fecal y se establecieran recomendaciones de utilidad para la comunidad médica.Las recomendaciones emitidas fueron a través de 35 enunciados que se presentan en este documento. Se reconoce que la incontinencia fecal es una entidad frecuente, y cuya incidencia se incrementa conforme aumenta la edad, sin embargo, es poco reconocida. La fisiopatología de la incontinencia es compleja y multifactorial y en la mayoría de los casos existe más de un factor de riesgo asociado. Respecto al diagnóstico, se considera que, si bien no existe un estándar de oro, la combinación de pruebas que evalúen la estructura (p. ej., ultrasonido endoanal) y la función (manometría anorrectal) se debe de recomendar en todos los casos. El tratamiento debe ser también multidisciplinario, y se recomiendan medidas generales, fármacos (lidamidina, loperamida), y en casos seleccionados intervenciones no farmacológicas como la terapia de biorretroalimentación. De igual manera, el tratamiento quirúrgico debe ofrecerse a los pacientes seleccionados y debe ser brindado por los expertos. Abstract: Fecal incontinence is the involuntary passage or the incapacity to control the release of fecal matter through the anus. It is a condition that significantly impairs quality of life in those that suffer from it, given that it affects body image, self-esteem, and interferes with everyday activities, in turn, favoring social isolation. There are no guidelines or consensus in Mexico on the topic, and so the Asociación Mexicana de Gastroenterología brought together a multidisciplinary group (gastroenterologists, neurogastroenterologists, and surgeons) to carry out the «Mexican consensus on fecal incontinence» and establish useful recommendations for the medical community.The present document presents the formulated recommendations in 35 statements. Fecal incontinence is known to be a frequent entity whose incidence increases as individuals age, but one that is under-recognized. The pathophysiology of incontinence is complex and multifactorial, and in most cases, there is more than one associated risk factor. Even though there is no diagnostic gold standard, the combination of tests that evaluate structure (endoanal ultrasound) and function (anorectal manometry) should be recommended in all cases. Treatment should also be multidisciplinary and general measures and drugs (lidamidine, loperamide) are recommended, as well as non-pharmacologic interventions, such as biofeedback therapy, in selected cases. Likewise, surgical treatment should be offered to selected patients and performed by experts.

Abstract Digital health technologies (DHTs) should expand access to clinical research to represent the social determinants of health (SDoH) across the population. The frequency of reporting participant SDoH data in clinical publications is low and is not known for studies that utilize DHTs. We evaluated representation of 11 SDoH domains in 126 DHT-enabled clinical research publications and proposed a framework under which these domains could be captured and subsequently reported in future studies. Sex, Race, and Education were most frequently reported (in 94.4%, 27.8%, and 20.6% of publications, respectively). The remaining 8 domains were reported in fewer than 10% of publications. Medical codes were identified that map to each of the proposed SDoH domains and the resulting resource is suggested to highlight that existing infrastructure could be used to capture SDoH data. An opportunity exists to increase reporting on the representation of SDoH among participants to encourage equitable and inclusive research progress through DHT-enabled clinical studies.

Abstract Mutations in the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene are linked to Fragile X Syndrome, the most common monogenic cause of intellectual disability and autism. People affected with mutations in FMR1 have higher incidence of obesity, but the mechanisms are largely unknown. In the current study, we determined that male Fmr1 knockout mice (KO, Fmr1 −/y ), but not female Fmr1 −/−, exhibit increased weight when compared to wild-type controls, similarly to humans with FMR1 mutations. No differences in food or water intake were found between groups; however, male Fmr1 −/y display lower locomotor activity, especially during their active phase. Moreover, Fmr1 −/y have olfactory dysfunction determined by buried food test, although they exhibit increased compulsive behavior, determined by marble burying test. Since olfactory brain regions communicate with hypothalamic regions that regulate food intake, including POMC neurons that also regulate locomotion, we examined POMC neuron innervation and numbers in Fmr1 −/y mice. POMC neurons express Fmrp, and POMC neurons in Fmr1 −/y have higher inhibitory GABAergic synaptic inputs. Consistent with increased inhibitory innervation, POMC neurons in the Fmr1 −/y mice exhibit lower activity, based on cFOS expression. Notably, Fmr1 −/y mice have fewer POMC neurons than controls, specifically in the rostral arcuate nucleus, which could contribute to decreased locomotion and increased body weight. These results suggest a role for Fmr1 in the regulation of POMC neuron function and the etiology of Fmr1-linked obesity.

We report a dengue outbreak in Key Largo, Florida, USA, from February through August 2020, during the COVID-19 pandemic. Successful community engagement resulted in 61% of case-patients self-reporting. We also describe COVID-19 pandemic effects on the dengue outbreak investigation and the need to increase clinician awareness of dengue testing recommendations.

Over the course of human evolution, the successful detection of drinking water in arid environments mitigated the physiological stress of dehydration and acted as a strong source of natural selection for recognizing the optical cues for water and perhaps physiological indices of relief. The current research consisted of two studiesinvestigating whether viewing water in outdoor settings affected autonomic tone and subjective ratings of relaxation. The first study examined blood pressure and heart rate of 32 participants who focused their attention on water in a swimming pool, a tree in a parking lot, and a small sign over a busy street. The results of this studyshowed that viewing water for 1 min 40 s reduced blood pressure reliably compared with viewing the tree and sign. Heart rate was also lower reliably while viewing water than the sign. The second study extended this research to a university arboretum, recording blood pressure, heart rate, and subjective ratings of relaxation of 73 participants successively at six sites along a 1.62 km path next to a creek, two small lakes, and the adjacent ground with open grassy areas and trees. At each site, participants alternated randomly in viewing the water or the ground first. Averaged for the six sites, analyses showed that the systolic/diastolic ratio for blood pressureand heart rate were reliably lower when viewing the water compared with the adjacent ground, an effect associated with the subjective rating of relaxation. Together, these findings indicate that viewing water can affect autonomic tone in a way that might account for the subjective rating of relaxation.

The literature on the nutritional needs and outcomes of critically ill children is scarce, especially on those with critical neurological illnesses (CNIs). Current evidence shows a lower mortality in patients who achieve two-thirds of their nutritional needs during the first week of pediatric intensive care unit (PICU) admission. We hypothesized that achieving 60% of the recommended dietary intake during the first week of a PICU stay is not feasible in patients with CNI. We designed an observational retrospective cohort study where we included all index admissions to the PICU in our institution of children (1 month to 18 years) with CNI from January 2018 to June 2021. We collected patient demographics, anthropometric measures, and caloric and protein intake (enteral and parenteral) information during the first week of PICU admission. Goal adequacy for calories and protein was defined as [(intake/recommended) × 100] ≥ 60%. A total of 1112 patients were included in the nutrition assessment, 12% of whom were underweight (weight for age z score < −2). Of this group, 180 met the criteria for nutrition support evaluation. On the third day of admission, 50% of the patients < 2 years achieved caloric and protein goal adequacy, compared to 25% of patients > 2 years, with p-values of 0.0003 and 0.0004, respectively. Among the underweight patients, 60% achieved both caloric and protein goal adequacy by day 3 vs. 30% of non-underweight patients with p-values of 0.0006 and 0.002, respectively. The results show that achieving 60% of the recommended dietary intake by days 5 and 7 of admission was feasible in more than half of the patients in this cohort. Additionally, children who were evaluated by a clinical dietician during the first 48 h of PICU admission reached higher nutrition adequacy.

Patients admitted to a pediatric intensive care unit (PICU) need individualized nutrition support that is tailored to their particular disease severity, nutritional status, and therapeutic interventions. We aim to evaluate how calories and proteins are provided during the first seven days of hospitalization for children in critical condition with organ dysfunction (OD). A single-center retrospective cohort study of children aged 2–18 years, mechanically ventilated > 48 h, and admitted > 7 days to a PICU from 2016 to 2017 was carried out. Nutrition support included enteral and parenteral nutrition. We calculated scores for the Pediatric Sequential Organ Failure Assessment (pSOFA) on days 1 and 3 of admission, with OD defined as a score > 5. Of 4199 patient admissions, 164 children were included. The prevalence of OD for days 1 and 3 was 79.3% and 78.7%, respectively. On day 3, when pSOFA scores trended upward, decreased, or remained unchanged, median (IQR) caloric intake was 0 (0–15), 9.2 (0–25), and 22 (1–43) kcal/kg/day, respectively (p = 0.0032); when pSOFA scores trended upward, decreased, or remained unchanged, protein intake was 0 (0–0.64), 0.44 (0–1.25), and 0.66 (0.04–1.67) g/kg/day, respectively (p = 0.0023). Organ dysfunction was prevalent through the first 72 h of a PICU stay. When the pSOFA scores trended downward or remained unchanged, caloric and protein intakes were higher than those that trended upward.

Young children frequently report imaginary scary things in their bedrooms at night. This study examined the remembrances of 140 preschool children and 404 adults selecting either above, side, or below locations for a scary thing relative to their beds. The theoretical framework for this investigation posited that sexual-size dimorphism in Australopithecus afarensis, the presumed human ancestor in the Middle Pliocene, constrained sleeping site choice to mitigate predation. Smaller-bodied females nesting in trees would have anticipated predatory attacks from below, while male nesting on the ground would have anticipated attacks from their side. Such anticipation of nighttime attacks from below is present in many arboreal primates and might still persist as a cognitive relict in humans. In remembrances of nighttime fear, girls and women were predicted to select the below location and males the side location. Following interviews of children and adult questionnaires, multinomial log-linear analyses indicated statistically significant interactions (p

Introduction: Age-related macular degeneration (AMD) is the leading cause of central vision loss in the elderly. One-third of the genetic contribution to this disease remains unexplained.Methods: We analyzed targeted sequencing data from two independent cohorts (4,245 cases, 1,668 controls) which included genomic regions of known AMD loci in 49 genes.Results: At a false discovery rate of

High baseline clearance of immune checkpoint inhibitors (ICIs), independent of dose or systemic exposure, is associated with cachexia and poor outcomes in cancer patients. Mechanisms linking ICI clearance, cachexia and ICI therapy failure are unknown. Here, we evaluate in four murine models and across multiple antibodies whether altered baseline catabolic clearance of administered antibody requires a tumor and/or cachexia and whether medical reversal of cachexia phenotype can alleviate altered clearance. Key findings include mild cachexia phenotype and lack of elevated pembrolizumab clearance in the MC38 tumor-bearing model. We also observed severe cachexia and decreased, instead of increased, baseline pembrolizumab clearance in the tumor-free cisplatin-induced cachexia model. Liver Fcgrt expression correlated with altered baseline catabolic clearance, though elevated clearance was still observed with antibodies having no (human IgA) or reduced (human H310Q IgG1) FcRn binding. We conclude cachexia phenotype coincides with altered antibody clearance, though tumor presence is neither sufficient nor necessary for altered clearance in immunocompetent mice. Magnitude and direction of clearance alteration correlated with hepatic Fcgrt, suggesting changes in FcRn expression and/or recycling function may be partially responsible, though factors beyond FcRn also contribute to altered clearance in cachexia.

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the “Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion.

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the “Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion.

Intracranial mesenchymal tumors with FET-CREB fusions are a recently described group of neoplasms in children and young adults characterized by fusion of a FET family gene (usually EWSR1, but rarely FUS) to a CREB family transcription factor (ATF1, CREB1, or CREM), and have been variously termed intracranial angiomatoid fibrous histiocytoma or intracranial myxoid mesenchymal tumor. The clinical outcomes, histologic features, and genomic landscape are not well defined. Here, we studied 20 patients with intracranial mesenchymal tumors proven to harbor FET-CREB fusion by next-generation sequencing (NGS). The 16 female and four male patients had a median age of 14 years (range 4-70). Tumors were uniformly extra-axial or intraventricular and located at the cerebral convexities (n = 7), falx (2), lateral ventricles (4), tentorium (2), cerebellopontine angle (4), and spinal cord (1). NGS demonstrated that eight tumors harbored EWSR1-ATF1 fusion, seven had EWSR1-CREB1, four had EWSR1-CREM, and one had FUS-CREM. Tumors were uniformly well circumscribed and typically contrast enhancing with solid and cystic growth. Tumors with EWSR1-CREB1 fusions more often featured stellate/spindle cell morphology, mucin-rich stroma, and hemangioma-like vasculature compared to tumors with EWSR1-ATF1 fusions that most often featured sheets of epithelioid cells with mucin-poor collagenous stroma. These tumors demonstrated polyphenotypic immunoprofiles with frequent positivity for desmin, EMA, CD99, MUC4, and synaptophysin, but absence of SSTR2A, myogenin, and HMB45 expression. There was a propensity for local recurrence with a median progression-free survival of 12 months and a median overall survival of greater than 60 months, with three patients succumbing to disease (all with EWSR1-ATF1 fusions). In combination with prior case series, this study provides further insight into intracranial mesenchymal tumors with FET-CREB fusion, which represent a distinct group of CNS tumors encompassing both intracranial myxoid mesenchymal tumor and angiomatoid fibrous histiocytoma-like neoplasms.

Follicle-stimulating hormone (FSH) is a dimeric glycoprotein secreted by the anterior pituitary gonadotrope that is necessary for reproductive function in mammals. FSH primarily regulates granulosa cells and follicular growth in females, and Sertoli cell function in males. Since its identification in the 1930s and sequencing in the 1970s, significant progress has been made in elucidating its regulation and downstream function. Recent advances provide deeper insight into FSH synthesis, and effects in the gonads suggest potential roles in extragonadal tissues and examine pharmacological approaches and clinical applications in infertility treatment that now affect 18% of couples. These advances were discussed in detail in a number of reviews published in the last 2 years in Endocrinology. In this brief commentary, we summarize these reviews and point to the outstanding questions that should be answered in the near future to bridge a gap in our understanding of this hormone.