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The anemia of critical illness (ACI) is a nearly universal pathophysiological consequence of burn injury and a primary reason burn patients require massive quantities of transfused blood. Inflammatory processes are expected to drive postburn ACI and prevent meaningful erythropoietic stimulation through iron or erythropoietin supplementation, but to this day no specific inflammatory pathways have been identified as a critical mechanism. In this study, we examined whether secretion of G-CSF and IL-6 mediates distinct features of postburn ACI and interrogated inflammatory mechanisms that could be responsible for their secretion. Our analysis of mouse and human skin samples identified the burn wound as a primary source of G-CSF and IL-6 secretion. We show that G-CSF and IL-6 are secreted independently through an IL-1/MyD88-dependent mechanism, and we ruled out TLR2 and TLR4 as critical receptors. Our results indicate that IL-1/MyD88-dependent G-CSF secretion plays a key role in impairing medullary erythropoiesis and IL-6 secretion plays a key role in limiting the access of erythroid cells to iron. Importantly, we found that IL-1α/ß neutralizing Abs broadly attenuated features of postburn ACI that could be attributed to G-CSF or IL-6 secretion and rescued deficits of circulating RBC counts, hemoglobin, and hematocrit caused by burn injury. We conclude that wound-based IL-1/MyD88 signaling mediates postburn ACI through induction of G-CSF and IL-6 secretion.
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Anemia , Quemaduras , Humanos , Factor Estimulante de Colonias de Granulocitos/metabolismo , Interleucina-6/metabolismo , Factor 88 de Diferenciación Mieloide/metabolismo , Anemia/etiología , Quemaduras/complicaciones , Hierro/metabolismo , Interleucina-1/metabolismoRESUMEN
American bullfrog (Rana castesbeiana) saxiphilin (RcSxph) is a high-affinity "toxin sponge" protein thought to prevent intoxication by saxitoxin (STX), a lethal bis-guanidinium neurotoxin that causes paralytic shellfish poisoning (PSP) by blocking voltage-gated sodium channels (NaVs). How specific RcSxph interactions contribute to STX binding has not been defined and whether other organisms have similar proteins is unclear. Here, we use mutagenesis, ligand binding, and structural studies to define the energetic basis of Sxph:STX recognition. The resultant STX "recognition code" enabled engineering of RcSxph to improve its ability to rescue NaVs from STX and facilitated discovery of 10 new frog and toad Sxphs. Definition of the STX binding code and Sxph family expansion among diverse anurans separated by â¼140 My of evolution provides a molecular basis for understanding the roles of toxin sponge proteins in toxin resistance and for developing novel proteins to sense or neutralize STX and related PSP toxins.
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Neurotoxinas , Saxitoxina , Animales , Saxitoxina/genética , Ligandos , Guanidina , Proteínas Portadoras/metabolismo , Rana catesbeianaRESUMEN
Posterior fossa decompression for symptomatic Chiari malformation is an effective and frequently performed procedure, but it does carry risks of significant complications including cerebrospinal fluid leak and craniocervical instability. Patients sometimes do not improve or worsen after decompression, which may discourage neurosurgeons from performing Chiari decompression surgery. In this chapter, management strategies and surgical approaches are discussed that minimize the risks of complications and maximize favorable outcomes in Chiari malformation surgery.
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Malformación de Arnold-Chiari , Descompresión Quirúrgica , Complicaciones Posoperatorias , Malformación de Arnold-Chiari/cirugía , Humanos , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Descompresión Quirúrgica/métodos , Procedimientos Neuroquirúrgicos/métodos , Procedimientos Neuroquirúrgicos/efectos adversos , Pérdida de Líquido Cefalorraquídeo/prevención & control , Pérdida de Líquido Cefalorraquídeo/etiologíaRESUMEN
Phenomenon: Ownership of patient care is a key element of professional growth and professional identity formation, but its development among medical students is incompletely understood. Specifically, how attitudes surrounding ownership of patient care develop, what experiences are most influential in shaping them, and how educators can best support this growth are not well known. Therefore, we studied the longitudinal progression of ownership definitions and experiences in medical students across their core clerkship curriculum. Approach: We conducted a series of four longitudinal focus groups with the same cohort of medical students across their core clerkship curriculum. Using workplace learning theory as a sensitizing concept, we conducted semi-structured interviews to explore how definitions, experiences, and influencers of ownership developed and evolved. Results were analyzed inductively using thematic analysis. Findings: Fifteen students participated in four focus groups spanning their core clerkship curriculum. We constructed four themes from responses: (1) students' definitions of ownership of patient care evolved to include more central roles for themselves and more defined limitations; (2) student conceptions of patient care ownership became more relational and reciprocal over time as they ascribed a more active role to patients; (3) student assessment fostered ownership as an external motivator when it explicitly addressed ownership, but detracted from ownership if it removed students from patient care; and (4) structural and logistical factors impacted students' ability to display patient care ownership. Insights: Student conceptions of ownership evolved over their core clerkship curriculum to include more patient care responsibility and more meaningful relational connections with patients, including recognizing patients' agency in this relationship. This progression was contingent on interactions with real patients and students being afforded opportunities to play a meaningful role in their care. Rotation structures and assessment processes are key influencers of care ownership that merit further study, as well as the voice of patients themselves in these relationships.
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The aim was to examine the effect of focus of attention cues on foot angle for retraining movement purposes. Twenty (females: 8) rearfoot-striking recreational runners (mass: 72.5 ± 11.8 kg; height: 1.73 ± 0.09 m; age: 32.9 ± 11.3 years) were randomly assigned to an internal focus (IF) (n = 10) or external focus (EF) (n = 10) verbal cue group. Participants performed 5 × 6 minute blocks of treadmill running (control run, 3 × cued running, retention run) at a self-selected running velocity (9.4 ± 1.1 kmâh-1) during a single laboratory visit. Touchdown foot angle, mechanical efficiency, internal and external work were calculated and, centre of mass (COM) and foot movement smoothness was quantified. Linear-mixed effect models showed an interaction for foot angle (p < 0.001, ηp2 = 0.35) and mechanical efficiency (p < 0.001, ηp2 = 0.40) when comparing the control to the cued running. Only the IF group reduced foot angle and mechanical efficiency during cued running, but not during the retention run. The IF group produced less external work during the 1st cued run than the control run. COM and foot smoothness were unaffected by cueing. Only an IF produced desired technique changes but at the cost of reduced mechanical efficiency. Movement smoothness was unaffected by cue provision. Changes to foot angle can be achieved within 6 minutes of gait retraining.
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Atención , Señales (Psicología) , Pie , Marcha , Carrera , Humanos , Carrera/fisiología , Masculino , Adulto , Femenino , Fenómenos Biomecánicos , Marcha/fisiología , Pie/fisiología , Atención/fisiología , Adulto Joven , Movimiento/fisiologíaRESUMEN
The barramundi (Lates calcarifer), a significant aquaculture species, typically displays silver to bronze coloration. However, attention is now drawn to rare variants like the "panda" phenotype, characterized by blotch-like patterns of black (PB) and golden (PG) patches. This phenotype presents an opportunity to explore the molecular mechanisms underlying color variations in teleosts. Unlike stable color patterns in many fish, the "panda" variant demonstrates phenotypic plasticity, responding dynamically to unknown cues. We propose a complex interplay of genetic factors and epigenetic modifications, focusing on DNA methylation. Through a multiomics approach, we analyze transcriptomic and methylation patterns between PB and PG patches. Our study reveals differential gene expression related to melanosome trafficking and chromatophore differentiation. Although the specific gene responsible for the PB-PG difference remains elusive, candidate genes like asip1, asip2, mlph, and mreg have been identified. Methylation emerges as a potential contributor to the "panda" phenotype, with changes in gene promoters like hand2 and dynamin possibly influencing coloration. This research lays the groundwork for further exploration into rare barramundi color patterns, enhancing our understanding of color diversity in teleosts. Additionally, it underscores the "panda" phenotype's potential as a model for studying adult skin coloration.
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Metilación de ADN , Perciformes , Fenotipo , Pigmentación , Transcriptoma , Animales , Perciformes/genética , Perciformes/fisiología , Pigmentación/genética , Epigénesis Genética , Pigmentación de la Piel/genética , MultiómicaRESUMEN
Activity of dorsal raphe neurons is controlled by noradrenaline afferents. In this brain region, noradrenaline activates Gαq-coupled α1-adrenergic receptors (α1-AR), causing action potential (AP) firing and serotonin release. In vitro, electrical stimulation elicits vesicular noradrenaline release and subsequent activation of α1-AR to produce an EPSC (α1-AR-EPSC). The duration of the α1-AR-EPSC (â¼27 s) is much longer than that of most other synaptic currents, but the factors that govern the spatiotemporal dynamics of α1-AR are poorly understood. Using an acute brain slice preparation from adult male and female mice and electrophysiological recordings from dorsal raphe neurons, we found that the time course of the α1-AR-EPSC was slow, but highly consistent within individual serotonin neurons. The amount of noradrenaline released influenced the amplitude of the α1-AR-EPSC without altering the time constant of decay suggesting that once released, extracellular noradrenaline was cleared efficiently. Reuptake of noradrenaline via noradrenaline transporters was a primary means of terminating the α1-AR-EPSC, with little evidence for extrasynaptic diffusion of noradrenaline unless transporter-dependent reuptake was impaired. Taken together, the results demonstrate that despite slow intrinsic signaling kinetics, noradrenaline-dependent synaptic transmission in the dorsal raphe is temporally and spatially controlled and noradrenaline transporters are critical regulators of serotonin neuron excitability. Given the functionally distinct types of neurons intermingled in the dorsal raphe nucleus and the unique roles of these neural circuits in physiological responses, transporters may preserve independence of each synapse to encode a long-lasting but discrete signal.SIGNIFICANCE STATEMENT The dorsal raphe nucleus is the predominant source of serotonin in the brain and is controlled by another monoamine, noradrenaline. In this brain region, noradrenaline activates G-protein-coupled α1-adrenergic receptors (α1-AR) causing action potential (AP) firing and serotonin release. Despite high interest in pharmacotherapies to enhance serotonin signaling, the factors that govern noradrenaline α1-AR signaling have received little attention. Here, we show using mouse brain slices that the time course of α1-AR signaling is slow, persisting for tens of seconds. Despite slow intrinsic signaling kinetics, noradrenaline-dependent synaptic transmission in the dorsal raphe is controlled temporally and spatially by efficient noradrenaline transporter-dependent clearance of extracellular noradrenaline. Thus, noradrenaline transporters are critical regulators of serotonin neuron excitability.
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Núcleo Dorsal del Rafe/fisiología , Norepinefrina/metabolismo , Receptores Adrenérgicos alfa 1/metabolismo , Neuronas Serotoninérgicas/fisiología , Transmisión Sináptica/fisiología , Animales , Potenciales Postsinápticos Excitadores/fisiología , Femenino , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
Developing and implementing the scientific agenda of the Antibacterial Resistance Leadership Group (ARLG) by soliciting input and proposals, transforming concepts into clinical trials, conducting those trials, and translating trial data analyses into actionable information for infectious disease clinical practice is the collective role of the Scientific Leadership Center, Clinical Operations Center, Statistical and Data Management Center, and Laboratory Center of the ARLG. These activities include shepherding concept proposal applications through peer review; identifying, qualifying, training, and overseeing clinical trials sites; recommending, developing, performing, and evaluating laboratory assays in support of clinical trials; and designing and performing data collection and statistical analyses. This article describes key components involved in realizing the ARLG scientific agenda through the activities of the ARLG centers.
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Manejo de Datos , Liderazgo , Humanos , Recolección de Datos , Farmacorresistencia Bacteriana , Antibacterianos/farmacología , Antibacterianos/uso terapéuticoRESUMEN
PURPOSE: To determine the effect of an off-protocol meal during a long-term ad libitum feeding study on changes in total caloric consumption and ratings of hunger and satiety. METHODS: During the ad libitum portion of a 16 weeks research high-protein feeding study, 19 participants were allowed to eat up to one self-selected meal (SSM) a week instead of an intervention diet meal. The SSM was assessed for total caloric and macronutrient composition and compared to the intervention diet for 3 days before and after the SSM day. Visual analog scores rating daily hunger and fullness were collected and compared as well. RESULTS: On the SSM day, the mean ± SD daily caloric intake increased by 262 ± 332 kcal compared to the previous study days (P < 0.001), with no changes in subjective appetite scores. The following day there was a slight but significant reduction in intake (- 58 ± 85 kcal, P = 0.008) compared to the average pre-SSM day with no change in appetite scores. On the SSM day, percent protein intake was inversely associated mean daily caloric intake (r2 = 0.22, P = 0.03). CONCLUSIONS: During a long-term, ad-libitum high-protein feeding study, one SSM lower in protein increased daily total caloric consumption with no impact on appetite ratings and incomplete caloric consumption during subsequent days. These data suggest that during ad-libitum feeding, a single meal change in protein content impacts the relationships between daily level of hunger, satiety and calorie intake. GOV ID: NCT05002491 (retrospectively registered 07/20/2021).
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Apetito , Ingestión de Energía , Humanos , Estudios Cruzados , Dieta , Hambre , SaciedadRESUMEN
Phenomenon: As new faculty members begin their careers in Graduate Medical Education, each begins a journey of Professional Identity Formation from the periphery of their educational communities. The trajectories traveled vary widely, and full participation in a given educational community is not assured. While some medical school and post-graduate training programs may nurture Professional Identity Formation, there is scant support for faculty. To date, the trajectories that Graduate Medical Education faculty travel, what may derail inbound trajectories, and what tools Graduate Medical Education faculty use to navigate these trajectories have not been explicitly described. We explore these three questions here. Approach: Communities of Practice, a component of Situated Learning Theory, serves as a helpful framework to explore trajectories of educator identity development among Graduate Medical Educators. We used a inductive and deductive approach to Thematic Analysis, with Situated Learning Theory as our interpretive frame. Semi-structured interviews of faculty members of GME programs matriculating into a Health Professions Education Program were conducted, focusing on participants' lived experiences in medical education and how these experiences shaped their Professional Identity Formation. Findings: Participants noted peripheral, inbound, boundary, and outbound trajectories, but not an insider trajectory. Trajectory derailment was attributed to competing demands, imposter syndrome and gendered marginality. Modes of belonging were critical tools participants used to shape PIF, not only engagement with educator roles but disengagement with other roles; imagination of future roles with the support of mentors; and fluid alignment with multiple mutually reinforcing identities. Participants identified boundary objects like resumes and formal roles that helped them negotiate across Community of Practice boundaries. Insights: Despite a desire for full participation, some clinical educators remain marginal, struggling along a peripheral trajectory. Further research exploring this struggle and potential interventions to strengthen modes of belonging and boundary objects is critical to create equitable access to the inbound trajectory for all of our colleagues, leaving the choice of trajectories up to them.
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Mitigation translocation is a subgroup of conservation translocation, categorized by a crisis-responsive time frame and the immediate goal of relocating individuals threatened with death. However, the relative successes of conservation translocations with longer time frames and broader metapopulation- and ecosystem-level considerations have been used to justify the continued implementation of mitigation translocations without adequate post hoc monitoring to confirm their effectiveness as a conservation tool. Mitigation translocations now outnumber other conservation translocations, and understanding the effectiveness of mitigation translocations is critical given limited global conservation funding especially if the mitigation translocations undermine biodiversity conservation by failing to save individuals. We assessed the effectiveness of mitigation translocations by conducting a quantitative review of the global literature. A total of 59 mitigation translocations were reviewed for their adherence to the adaptive scientific approach expected of other conservation translocations and for the testing of management options to continue improving techniques for the future. We found that mitigation translocations have not achieved their potential as an effective applied science. Most translocations focused predominantly on population establishment- and persistence-level questions, as is often seen in translocations more broadly, and less on metapopulation and ecosystem outcomes. Questions regarding the long-term impacts to the recipient ecosystem (12% of articles) and the carrying capacity of translocation sites (24% of articles) were addressed least often, despite these factors being more likely to influence ultimate success. Less than half (47%) of studies included comparison of different management techniques to facilitate practitioners selecting the most effective management actions for the future. To align mitigation translocations with the relative success of other conservation translocations, it is critical that future mitigation translocations conform to an established experimental approach to improve their effectiveness. Effective mitigation translocations will require significantly greater investment of time, expertise, and resources in the future.
La Translocación para Mitigación como una Herramienta de Gestión Resumen La translocación para mitigación es un subgrupo de la translocación para la conservación, caracterizada por un marco de tiempo que responda a la crisis y la meta inmediata de reubicar a individuos amenazados de muerte. Sin embargo, el éxito relativo de las traslocaciones para conservación con marcos de tiempo mayores y consideraciones a nivel metapoblación y ecosistema más amplias han sido utilizadas para justificar la implementación de translocaciones para mitigación sin monitoreo post hoc adecuado para confirmar su efectividad como herramienta de conservación. Las translocaciones para mitigación ahora son más numerosas que otras translocaciones, por lo que es fundamental entender la efectividad de las translocaciones para mitigación debido a las limitaciones en el financiamiento para la conservación global - especialmente si las translocaciones para mitigación socavan la conservación de la biodiversidad al fallar en salvar individuos. Evaluamos la efectividad de translocaciones para mitigación mediante una revisión cuantitativa de la literatura global. Revisamos un total de 59 translocaciones para mitigación para analizar su adhesión al método científico adaptativo esperado de otras translocaciones de conservación y para probar las opciones de gestión para mejorar las técnicas en el futuro. Encontramos que las mitigaciones para translocación no han alcanzado su potencial como una ciencia aplicada efectiva. La mayoría de las translocaciones se centraron predominantemente en preguntas relacionadas con el establecimiento y nivel de persistencia de la población, como se observa en translocaciones más generales, y menos en resultados a nivel metapoblación y ecosistema. Aspectos relacionados con los impactos a largo plazo sobre el ecosistema recipiente (12% de los artículos) y la capacidad de carga de los sitios de translocación (24% de los artículos) fueron poco abordados, no obstante que es más probable que estos factores influyan en el éxito final. Menos de la mitad (47%) de los estudios incluyó la comparación de métodos de gestión diferentes para facilitar que los practicantes selecciones las acciones de gestión más efectivas para el futuro. Para alinear las translocaciones para mitigación con el éxito relativo de otras translocaciones para conservación, es crítico que las futuras translocaciones para mitigación se apeguen a un método experimental establecido para incrementar su efectividad. Para ser efectivas, las translocaciones para mitigación requerirán una inversión de tiempo, conocimientos técnicos y recursos significativamente mayores.
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Conservación de los Recursos Naturales , Ecosistema , Biodiversidad , Conservación de los Recursos Naturales/métodos , Humanos , MotivaciónRESUMEN
PURPOSE: To measure the incidence and severity of urinary tract infections (UTI) in intermittent catheter (IC) users with neurogenic and non-neurogenic diagnoses. MATERIALS AND METHODS: Administrative health insurance claims data from the IBM MarketScan® Database between January 1, 2015 and December 31, 2019, were analyzed. New IC-users with neurogenic lower urinary tract dysfunction (NLUTD); IC-users without NLUTD (non-NLUTD); and age-and-sex-matched general population without IC use (GEN) were compared. Individuals were followed for one year after initial IC utilization or random index date for GEN. The primary outcome was a patient seeing a physician or attending a hospital for a UTI (measured with a primary or secondary diagnosis code related to a UTI). UTI incidence, hospitalizations, and length of hospital stay were compared. RESULT: We identified 6944 NLUTD, 5102 non-NLUTD, and 120 426 GEN individuals. The annualized UTI incidence was higher in IC-users (54.9% NLUTD IC-users and 38.9% non-NLUTD IC-users) compared to GEN individuals (9.8%) (p < 0.001 between groups). Hospitalization for UTI was more common in NLUTD and non-LUTD (11.3% and 4.0%, respectively) compared with GEN individuals (1.0%) (p < 0.001 between groups). NLUTD individuals had a greater average length of hospital stay than non-NLUTD (2.2 ± 3.6 vs. 1.6 ± 2.1 days, p < 0.001). CONCLUSION: IC users had a significantly higher incidence of UTIs than the general population. NLUTD IC-users had a higher incidence of UTIs that required hospitalization compared to non-NLUTD individuals. Strategies to decrease the patient and healthcare burden of UTIs in those that catheterize should be prioritized.
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Cateterismo Uretral Intermitente , Vejiga Urinaria Neurogénica , Infecciones Urinarias , Femenino , Humanos , Incidencia , Cateterismo Uretral Intermitente/efectos adversos , Masculino , Vejiga Urinaria Neurogénica/terapia , Infecciones Urinarias/epidemiologíaRESUMEN
Infectious diarrhea is caused by a variety of pathogens, including viruses, bacteria, and parasitic organisms. Though the causative agent of diarrhea has historically been evaluated via stool cultures, recently, culture-independent diagnostic tests (CIDT) have been developed and utilized with increasing frequency. Current practice guidelines recommend their use as adjuncts to stool cultures for diagnosing acute and chronic diarrhea. The three principal CIDT are microscopy, enzyme-based immunoassays (EIAs), and molecular based polymerase chain reaction (PCR). This review explores the common causes of infectious diarrhea, the basics of stool culture, the diagnostic utility of these three culture-independent modalities, and the strengths and weaknesses of all currently available clinical techniques. It also outlines considerations for specific populations including returning travelers and those with inflammatory bowel disease.
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Diarrea , Heces/microbiología , Técnicas para Inmunoenzimas/métodos , Técnicas Microbiológicas , Microscopía/métodos , Reacción en Cadena de la Polimerasa/métodos , Medios de Cultivo , Diarrea/diagnóstico , Diarrea/microbiología , Humanos , Técnicas Microbiológicas/métodosRESUMEN
There are currently a multitude of tests used to assess readiness to return to sport (RTS) following anterior cruciate ligament reconstruction (ACLR). The aim of this study was to establish the extent to which movement strategies transfer between three common assessment tasks to help improve design of athlete testing batteries following ACLR. A cohort of 127 male patients 8-10 months post-ACLR and 45 non-injured controls took part in the study. Three movement tasks were completed (unilateral and bilateral drop jump, and 90° pre-planned cut), while ground reaction forces and three-dimensional kinematics (250 Hz) were recorded. Compared to the bilateral drop jump and cut, the unilateral drop jump had a higher proportion of work done at the ankle (d = 0.29, p < 0.001 and d = -1.87, p < 0.001, respectively), and a lower proportion of work done at the knee during the braking phase of the task (d = 0.447, p < 0.001 and d = 1.56, p < 0.001, respectively). The ACLR group had higher peak hip moments than the non-injured controls, although the proportion of work done at the ankle, knee and hip joints were similar. Movement strategies were moderately and positively related at the ankle (rs = 0.728, p < 0.001), knee (rs = 0.638, p < 0.001) and hip (rs = 0.593, p < 0.001) between the unilateral and bilateral drop jump, but there was no relationship at the ankle (rs = 0.10, p = 0.104), knee (rs = 0.106, p = 0.166) and hip (rs = -0.019, p = 0.808) between the unilateral drop jump and the cut. Clinicians could therefore consider omitting one of the drop jumps from assessment batteries but should include both jumping and cutting tasks.
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Lesiones del Ligamento Cruzado Anterior , Reconstrucción del Ligamento Cruzado Anterior , Lesiones del Ligamento Cruzado Anterior/cirugía , Fenómenos Biomecánicos , Humanos , Articulación de la Rodilla/cirugía , Masculino , Movimiento , Volver al DeporteRESUMEN
Recreational fisheries are valued at $190B globally and constitute the predominant way in which people use wild fish stocks in developed countries, with inland systems contributing the main fraction of recreational fisheries. Although inland recreational fisheries are thought to be highly resilient and self-regulating, the rapid pace of environmental change is increasing the vulnerability of these fisheries to overharvest and collapse. Here we directly evaluate angler harvest relative to the biomass production of individual stocks for a major inland recreational fishery. Using an extensive 28-y dataset of the walleye (Sander vitreus) fisheries in northern Wisconsin, United States, we compare empirical biomass harvest (Y) and calculated production (P) and biomass (B) for 390 lake year combinations. Production overharvest occurs when harvest exceeds production in that year. Biomass and biomass turnover (P/B) declined by â¼30 and â¼20%, respectively, over time, while biomass harvest did not change, causing overharvest to increase. Our analysis revealed that â¼40% of populations were production-overharvested, a rate >10× higher than estimates based on population thresholds often used by fisheries managers. Our study highlights the need to adapt harvest to changes in production due to environmental change.
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Conservación de los Recursos Naturales/métodos , Explotaciones Pesqueras/organización & administración , Perciformes , Dinámica Poblacional/estadística & datos numéricos , Recreación/economía , Animales , Biomasa , Conservación de los Recursos Naturales/estadística & datos numéricos , Conjuntos de Datos como Asunto , Explotaciones Pesqueras/economía , Explotaciones Pesqueras/estadística & datos numéricos , Lagos , WisconsinRESUMEN
BACKGROUND: Mutations in COL4A5 are responsible for 80% of cases of X-linked Alport Syndrome (XLAS). Although genes that cause AS are well characterized, people with AS who have similar genetic mutations present with a wide variation in the extent of kidney impairment and age of onset, suggesting the activities of modifier genes. METHODS: We created a cohort of genetically diverse XLAS male and female mice using the Diversity Outbred mouse resource and measured albuminuria, GFR, and gene expression. Using a quantitative trait locus approach, we mapped modifier genes that can best explain the underlying phenotypic variation measured in our diverse population. RESULTS: Genetic analysis identified several loci associated with the variation in albuminuria and GFR, including a locus on the X chromosome associated with X inactivation and a locus on chromosome 2 containing Fmn1. Subsequent analysis of genetically reduced Fmn1 expression in Col4a5 knockout mice showed a decrease in albuminuria, podocyte effacement, and podocyte protrusions in the glomerular basement membrane, which support the candidacy of Fmn1 as a modifier gene for AS. CONCLUSION: With this novel approach, we emulated the variability in the severity of kidney phenotypes found in human patients with Alport Syndrome through albuminuria and GFR measurements. This approach can identify modifier genes in kidney disease that can be used as novel therapeutic targets.
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Albuminuria/orina , Colágeno Tipo IV/genética , Creatinina/orina , Forminas/genética , Nefritis Hereditaria/genética , Albuminuria/etiología , Animales , Mapeo Cromosómico , Modelos Animales de Enfermedad , Femenino , Forminas/ultraestructura , Expresión Génica , Tasa de Filtración Glomerular , Masculino , Ratones , Ratones Noqueados , Microscopía Electrónica de Transmisión , Mutación , Nefritis Hereditaria/complicaciones , Nefritis Hereditaria/fisiopatología , Fenotipo , Podocitos/patología , Prueba de Estudio Conceptual , Sitios de Carácter Cuantitativo , RNA-Seq , Factores Sexuales , Secuenciación Completa del GenomaRESUMEN
PHENOMENON: Teaching medical students how to teach is a growing and essential focus of medical education, which has given rise to student teaching programs. Educating medical students on how to teach can improve their own learning and lay the foundation for a professional identity rooted in teaching. Still, medical student-as-teacher (MSAT) programs face numerous obstacles including time constraints, prioritizing curriculum, and determining effective evaluation techniques. The purpose of this scoping review is to map the current landscape of the literature on medical school initiatives designed to train students to teach to describe why medical student teaching programs are started; the benefits and barriers; who teaches them; what content is taught; and how content is delivered. With this new map, the authors aimed to facilitate the growth of new programs and provide a shared knowledge of practices derived from existing programs. APPROACH: The authors conducted a scoping review, guided by Arksey and O'Malley's framework, to map the literature of MSAT training programs. Six databases were searched using combinations of keywords and controlled vocabulary terms. Data were charted in duplicate using a collaboratively designed data charting tool. This review builds on the Marton et al. review and includes articles published from 2014 to 2020. FINDINGS: Of the 1,644 manuscripts identified, the full-text of 57 were reviewed, and ultimately 27 were included. Articles included empirical research, synthetic reviews, opinion pieces, and a descriptive study. Analysis focused on modalities for teaching medical students how to teach; content to teach medical students about teaching; benefits and barriers to starting teaching programs; and the value of teaching programs for medical students. INSIGHTS: The rapid growth of MSAT programs suggests that this curricular offering is of great interest to the field. Literature shows an increase in evaluative efforts among programs, benefits for students beyond learning to teach, and evidence of effective engagement in medical students' designing and implementing programs.
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Educación Médica , Estudiantes de Medicina , Curriculum , Humanos , Aprendizaje , Facultades de Medicina , EnseñanzaRESUMEN
OBJECTIVES: Seasonal variation in emergency department (ED) visits has been shown for a variety of pediatric conditions, but previous studies have not considered how geographic location may also influence when and why these patients present to the ED. Our study examined the demographic and clinical characteristics as well as the seasonal variation among 3 patient populations (locals, in-state nonlocals, and out-of-state visitors) presenting to our pediatric ED (PED), which is located in a coastal, destination city. METHODS: This was a retrospective chart review of PED visits from June 2014 to June 2019 at the Medical University of South Carolina Children's Hospital, a tertiary care facility located in Charleston, SC. Pediatric ED encounters were divided into 3 groups, depending on the patient's home address: local patients residing in the 3 surrounding metro counties, in-state but nonlocal patients, and out-of-state patients. Demographic and clinical information was abstracted for each visit and compared among the 3 patient groups. Seasonal variation among PED visits was determined by recording the week of the year during which each visit occurred. RESULTS: Local patients accounted for more than 90% of PED visits with increases in visits from October to April. In-state nonlocal patients presented at consistent rates throughout the year, whereas out-of-state ED utilization peaked significantly during the summer months, Spring Break, Thanksgiving, and Christmas. Our local patient population was majority African American; our in-state nonlocal patients roughly matched our state's racial demographics, and our out-of-state population was predominantly White. Compared with in-state nonlocal patients, our local patients were more likely to present with an infection-related complaint and be diagnosed with lower-acuity conditions such as viral infection, otitis media, upper respiratory infection, cough, fever, and gastroenteritis. In-state nonlocal patients had the highest average triage acuity, more frequently had laboratory tests and imaging ordered, and were more than 4.5 times as likely to be admitted to the hospital compared with our local patients. In-state nonlocal patients were also more likely to present with a psychiatric chief complaint compared with our local patients. Out-of-state patients had a similar overall acuity to local patients but were more likely to have imaging ordered and be diagnosed with injuries such as fractures. CONCLUSION: At our institution, local patients, in-state nonlocal patients, and out-of-state patients exhibited 3 distinct patterns of PED utilization. Knowledge of these trends can be used to optimize resource allocation and follow-up planning, particularly for our out-of-state patient population.
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Servicio de Urgencia en Hospital , Triaje , Niño , Demografía , Hospitalización , Humanos , Estudios Retrospectivos , Triaje/métodosRESUMEN
Given the high rates of both primary and secondary anterior cruciate ligament (ACL) injuries in multidirectional field sports, there is a need to develop easily accessible methods for practitioners to monitor ACL injury risk. Field-based methods to assess knee variables associated with ACL injury are of particular interest to practitioners for monitoring injury risk in applied sports settings. Knee variables or proxy measures derived from wearable inertial measurement units (IMUs) may thus provide a powerful tool for efficient injury risk management. Therefore, the aim of this study was to identify whether there were correlations between laboratory-derived knee variables (knee range of motion (RoM), change in knee moment, and knee stiffness) and metrics derived from IMUs (angular velocities and accelerations) placed on the tibia and thigh, across a range of movements performed in practitioner assessments used to monitor ACL injury risk. Ground reaction forces, three-dimensional kinematics, and triaxial IMU data were recorded from nineteen healthy male participants performing bilateral and unilateral drop jumps, and a 90° cutting task. Spearman's correlations were used to examine the correlations between knee variables and IMU-derived metrics. A significant strong positive correlation was observed between knee RoM and the area under the tibia angular velocity curve in all movements. Significant strong correlations were also observed in the unilateral drop jump between knee RoM, change in knee moment, and knee stiffness, and the area under the tibia acceleration curve (rs = 0.776, rs = -0.712, and rs = -0.765, respectively). A significant moderate correlation was observed between both knee RoM and knee stiffness, and the area under the thigh angular velocity curve (rs = 0.682 and rs = -0.641, respectively). The findings from this study suggest that it may be feasible to use IMU-derived angular velocities and acceleration measurements as proxy measures of knee variables in movements included in practitioner assessments used to monitor ACL injury risk.
Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Traumatismos de la Rodilla , Masculino , Humanos , Lesiones del Ligamento Cruzado Anterior/diagnóstico , Articulación de la Rodilla , Rodilla , Fenómenos BiomecánicosRESUMEN
PURPOSE: The primary purpose of this study was to evaluate the impact of a patient-centered, chronic care self-management support program of clean intermittent catheterization (CIC) on emergency department (ED) visits and hospitalizations within the first 30 days of starting CIC. Secondary research objectives were to compare reuse of catheters, adherence to healthcare provider-instructed frequency of CIC, and reasons for nonadherence. DESIGN: A correlational survey design with 2 respondent groups. SUBJECTS AND SETTING: Four hundred forty-five respondents met inclusion criteria for this study; 321 respondents enrolled in an intermittent catheter manufacturer-supported CIC support program, and 124 respondents were not enrolled in a support program (comparison group). METHODS: Participants completed a 37-item online questionnaire designed for purposes of this study. Chi-square test was used to assess differences in the proportions of patients with ED visits and overnight hospital admissions comparing respondents enrolled in the patient support program to those not enrolled. Regression analyses were performed to estimate the effect of the CIC support program on ED visit events and on hospital overnight stays. RESULTS: Within the first month of CIC initiation, 16.1% and 10.2% of the respondents in the comparison group reported at least 1 ED visit and at least 1 overnight hospital stay, respectively. Respondents participating in the CIC support program experienced a 47% decrease in ED visits (adjusted rate ratio: 0.53; 95% confidence interval: 0.30-0.94, P = .036) and a 77% decrease (adjusted rate ratio: 0.24; 95% confidence interval: 0.10-0.62, P = .002) in hospital overnight stays within the first month of CIC initiation, while controlling for age, sex, education, duration of CIC use, region, health insurance status, and medical conditions necessitating CIC. Respondents in the CIC support program group reported an 8% higher adherence rate with the healthcare provider-instructed frequency of CIC usage compared to the comparison group (88% vs 80%, P = .039). CONCLUSIONS: The burden of CIC-related complications within the first month of CIC initiation is significant. A patient-centered, chronic care self-management program for CIC was associated with fewer ED visits and overnight hospital stays during the first month of CIC and improved adherence to prescribed frequency of CIC use.