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OBJECTIVE: This study aims to design and fabricate a 3D printed heterogeneous paediatric head phantom and to customize a thorax phantom for radiotherapy dosimetry. Approach: This study designed, fabricated, and tested 3D printed radiotherapy phantoms that can simulate soft tissue, lung, brain, and bone. Various polymers were considered in designing the phantoms. Polylactic acid+, nylon, and plaster were used in simulating different tissue equivalence. Dimensional accuracy, and CT number were investigated. The phantoms were subjected to a complete radiotherapy clinical workflow. Several treatment plans were delivered in both the head and the thorax phantom from a simple single 6 MV beam, parallel opposed beams, and five-field intensity modulated radiotherapy (IMRT) beams. Dose measurements using an ionization chamber and radiochromic films were compared with the calculated doses of the Varian Eclipse treatment planning system (TPS). Main results: The fabricated heterogeneous phantoms represent paediatric human head and adult thorax based on its radiation attenuation and anatomy. The measured CT number ranges are within -786.23 ± 10.55, 0.98 ± 3.86, 129.51 ± 12.83, and 651.14 ± 47.76 HU for lung, water/brain, soft tissue, and bone, respectively. It has a good radiological imaging visual similarity relative to a real human head and thorax depicting soft tissue, lung, bone, and brain. The accumulated dose readings for both conformal radiotherapy and IMRT match with the TPS calculated dose within ±2% and ±4% for head and thorax phantom, respectively. The mean pass rate for all the plans delivered are above 90% for gamma analysis criterion of 3% / 3 mm. Significance and conclusion: The fabricated heterogeneous paediatric head and thorax phantoms are useful in Linac end-to-end radiotherapy quality assurance based on its CT image and measured radiation dose. The manufacturing and dosimetry workflow of this study can be utilized by other institutions for dosimetry and trainings. .
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This Viewpoint discusses why it is important for psychiatry residency programs to continue to prioritize the training of psychiatrist-scientists.
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Hot Jupiters are among the best-studied exoplanets, but it is still poorly understood how their chemical composition and cloud properties vary with longitude. Theoretical models predict that clouds may condense on the nightside and that molecular abundances can be driven out of equilibrium by zonal winds. Here we report a phase-resolved emission spectrum of the hot Jupiter WASP-43b measured from 5 µm to 12 µm with the JWST's Mid-Infrared Instrument. The spectra reveal a large day-night temperature contrast (with average brightness temperatures of 1,524 ± 35 K and 863 ± 23 K, respectively) and evidence for water absorption at all orbital phases. Comparisons with three-dimensional atmospheric models show that both the phase-curve shape and emission spectra strongly suggest the presence of nightside clouds that become optically thick to thermal emission at pressures greater than ~100 mbar. The dayside is consistent with a cloudless atmosphere above the mid-infrared photosphere. Contrary to expectations from equilibrium chemistry but consistent with disequilibrium kinetics models, methane is not detected on the nightside (2σ upper limit of 1-6 ppm, depending on model assumptions). Our results provide strong evidence that the atmosphere of WASP-43b is shaped by disequilibrium processes and provide new insights into the properties of the planet's nightside clouds. However, the remaining discrepancies between our observations and our predictive atmospheric models emphasize the importance of further exploring the effects of clouds and disequilibrium chemistry in numerical models.
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OBJECTIVES: To develop and validate classification criteria for axial disease in youth with juvenile spondyloarthritis (SpA; AxJSpA). METHODS: This international initiative consisted of four phases: 1) Item generation; 2) Item reduction; 3) Criteria development; and 4) Validation of the AxJSpA criteria by an independent team of experts in an internationally representative Validation cohort. RESULTS: These criteria are intended to be used on youth with a physician diagnosis of juvenile SpA and for whom axial disease is suspected. Item generation consisted of a systematic literature review and a free-listing exercise using input from international physicians and collectively resulted in 108 items. After the item reduction exercise and expert panel input, 37 items remained for further consideration. The final AxJSpA criteria domains included: imaging: active inflammation, imaging: structural lesions, pain chronicity, pain pattern, pain location, stiffness, and genetics. The most heavily weighted domains were active inflammation and structural lesions on imaging. Imaging typical of sacroiliitis was deemed necessary, but not sufficient, to classify a youth with AxJSpA. The threshold for classification of AxJSpA was a score of ≥55 (out of 100). When tested in the validation data set, the final criteria had a specificity of 97.5% (95% CI: 91.4-99.7), sensitivity of 64.3% (95% CI: 54.9-73.1) and Area Under the Receiver Operating Characteristic (AUROC) curve of 0.81 (95% CI: 0.76-0.86). CONCLUSIONS: The new AxJSpA classification criteria require an entry criterion, physician diagnosis of juvenile SpA, and include seven weighted domains. The AxJSpA classification criteria are validated and designed to identify participants for research studies.
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The impact of ocean warming on fish and fisheries is vigorously debated. Leading theories project limited adaptive capacity of tropical fishes and 14-39% size reductions by 2050 due to mass-scaling limitations of oxygen supply in larger individuals. Using the world's hottest coral reefs in the Persian/Arabian Gulf as a natural laboratory for ocean warming - where species have survived >35.0 °C summer temperatures for over 6000 years and are 14-40% smaller at maximum size compared to cooler locations - we identified two adaptive pathways that enhance survival at elevated temperatures across 10 metabolic and swimming performance metrics. Comparing Lutjanus ehrenbergii and Scolopsis ghanam from reefs both inside and outside the Persian/Arabian Gulf across temperatures of 27.0 °C, 31.5 °C and 35.5 °C, we reveal that these species show a lower-than-expected rise in basal metabolic demands and a right-shifted thermal window, which aids in maintaining oxygen supply and aerobic performance to 35.5 °C. Importantly, our findings challenge traditional oxygen-limitation theories, suggesting a mismatch in energy acquisition and demand as the primary driver of size reductions. Our data support a modified resource-acquisition theory to explain how ocean warming leads to species-specific size reductions and why smaller individuals are evolutionarily favored under elevated temperatures.
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Arrecifes de Coral , Animales , Tamaño Corporal/fisiología , Calentamiento Global , Océanos y Mares , Peces/fisiología , Océano Índico , Oxígeno/metabolismo , Temperatura , Calor , Explotaciones PesquerasRESUMEN
Objective: To describe the outcomes (change in functional independence and discharge disposition) of patients who after liver transplantation received acute inpatient rehabilitation in a freestanding rehabilitation hospital. Design: A retrospective chart review was conducted of patients admitted to an acute inpatient rehabilitation hospital within 6 months of undergoing liver transplantation between January 2014 and December 2018. Change in function from rehabilitation admission to discharge was measured using FIM Change and FIM Efficiency. Setting: A freestanding rehabilitation hospital. Participants: 107 patients who underwent acute inpatient rehabilitation at a freestanding rehabilitation hospital within 6 months after liver transplantation who met inclusion criteria (N=107). Most were men (71.96%), and the mean age of the patient population was 62.15 years. Interventions: Acute inpatient rehabilitation consisting of at least 3 hours of therapy 5 days a week split between physical therapy, occupational therapy, and speech language pathology services. Main Outcome Measure: FIM Change, FIM Efficiency, Discharge Disposition. Results: Participants were found to have statistically significant positive FIM Change (P<.00001) and FIM Efficiency (P<.00001). The mean FIM Change and Efficiency were 35.7±11.8 and 2.4±1.0, respectively. 83.2% (n = 89) were ultimately discharged to the community. Conclusion: Acute inpatient rehabilitation provides patients who have received a liver transplant with the opportunity to measurably improve their function and independence, with most patients being able to return home.
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Transmission spectroscopy has been a workhorse technique over the past two decades to constrain the physical and chemical properties of exoplanet atmospheres 1-5. One of its classical key assumptions is that the portion of the atmosphere it probes - the terminator region - is homogeneous. Several works in the past decade, however, have put this into question for highly irradiated, hot (Teq â³ 1000 K) gas giant exoplanets both empirically 6-10 and via 3-dimensional modelling 11-17. While models predict clear differences between the evening (day-to-night) and morning (night-to-day) terminators, direct morning/evening transmission spectra in a wide wavelength range has not been reported for an exoplanet to date. Under the assumption of precise and accurate orbital parameters on WASP-39 b, here we report the detection of inhomogeneous terminators on the exoplanet WASP-39 b, which allows us to retrieve its morning and evening transmission spectra in the near-infrared (2 - 5 µm) using JWST. We observe larger transit depths in the evening which are, on average, 405±88 ppm larger than the morning ones, also having qualitatively larger features than the morning spectrum. The spectra are best explained by models in which the evening terminator is hotter than the morning terminator by 177 - 57 + 65 K with both terminators having C/O ratios consistent with solar. General circulation models (GCMs) predict temperature differences broadly consistent with the above value and point towards a cloudy morning terminator and a clearer evening terminator.
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MRI, ultrasound, and conventional radiography each play distinct roles in the evaluation of juvenile idiopathic arthritis (JIA), with MRI being the preferred imaging modality of choice for assessing both inflammatory and destructive changes. These various imaging modalities provide valuable insights into JIA in pediatric patients. However, challenges persist in terms of achieving precision, ensuring validity, and distinguishing between pathologic findings and normal anatomic variations. Establishing normal reference values and implementing scoring systems can aid in the precise evaluation of disease activity and provide information to assist treatment decisions for children with JIA. Ongoing advancements in imaging techniques and standardization initiatives aim to bolster the accuracy of JIA diagnosis and assessment, ultimately leading to enhanced patient care and treatment outcomes.
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Artritis Juvenil , Imagen por Resonancia Magnética , Ultrasonografía , Humanos , Artritis Juvenil/diagnóstico por imagen , Niño , Imagen por Resonancia Magnética/métodos , Ultrasonografía/métodos , Radiografía/métodos , Articulaciones/diagnóstico por imagenRESUMEN
The pyrazolo[1,5-a]pyrimidine scaffold is a promising scaffold to develop potent and selective CSNK2 inhibitors with antiviral activity against ß-coronaviruses. Herein, we describe the discovery of a 1,2,4-triazole group to substitute a key amide group for CSNK2 binding present in many potent pyrazolo[1,5-a]pyrimidine inhibitors. Crystallographic evidence demonstrates that the 1,2,4-triazole replaces the amide in forming key hydrogen bonds with Lys68 and a water molecule buried in the ATP-binding pocket. This isosteric replacement improves potency and metabolic stability at a cost of solubility. Optimization for potency, solubility, and metabolic stability led to the discovery of the potent and selective CSNK2 inhibitor 53. Despite excellent in vitro metabolic stability, rapid decline in plasma concentration of 53 in vivo was observed and may be attributed to lung accumulation, although in vivo pharmacological effect was not observed. Further optimization of this novel chemotype may validate CSNK2 as an antiviral target in vivo.
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Antivirales , Quinasa de la Caseína II , Pirimidinas , Triazoles , Replicación Viral , Triazoles/farmacología , Triazoles/química , Triazoles/síntesis química , Pirimidinas/farmacología , Pirimidinas/química , Pirimidinas/síntesis química , Antivirales/farmacología , Antivirales/química , Antivirales/síntesis química , Animales , Humanos , Replicación Viral/efectos de los fármacos , Quinasa de la Caseína II/antagonistas & inhibidores , Quinasa de la Caseína II/metabolismo , Pirazoles/farmacología , Pirazoles/química , Pirazoles/síntesis química , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/síntesis química , Amidas/química , Amidas/farmacología , Amidas/síntesis química , Relación Estructura-Actividad , Ratones , Ratas , SARS-CoV-2/efectos de los fármacos , Descubrimiento de Drogas , MasculinoRESUMEN
ABSTRACT: Jagim, AR, Luedke, J, Erickson, JL, Fields, JB, and Jones, MT. Validation of bioelectrical impedance devices for the determination of body fat percentage in firefighters. J Strength Cond Res 38(8): e448-e453, 2024-To cross-validate bioelectrical impedance devices for the determination of body fat percentage (BF%) in firefighters. Twenty-eight structural firefighters were evaluated (female, n = 2; male, n = 26 [mean ± SD] age: 38.2 ± 8.3 years; height: 180.2 ± 7.5 cm; body mass: 86.7 ± 20.8 kg; body mass index: 25.8 ± 7.8 kg·m-2) using multifrequency bioelectrical impedance analysis (MFBIA) hand-to-foot device, and single-frequency BIA foot scale (F2FBIA), and a single-frequency handheld BIA device (HHBIA). Dual X-ray absorptiometry served as the criterion. Validity metrics were examined to establish each method's performance. Body fat % values produced by MFBIA (r = 0.913), F2FBIA (r = 0.695), and HHBIA (r = 0.876) were strongly associated (p < 0.001) with criterion BF% measures. However, MFBIA, F2FBIA, and HHBIA all significantly (p < 0.001) underestimated BF% when compared with the criterion measure. Constant error ranged between 4.0 and 5.5% across all BIA devices. Despite strong associations between the BIA devices included in the current study and the criterion measure, all BIA devices underestimated BF%, which resulted in an overestimation of fat-free mass. In addition, proportional bias was observed in which BF% was overestimated at lower values and underestimated at higher values.
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Absorciometría de Fotón , Impedancia Eléctrica , Bomberos , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Tejido Adiposo/fisiología , Reproducibilidad de los Resultados , Composición Corporal/fisiología , Índice de Masa CorporalRESUMEN
Magnetic resonance-guided focused ultrasound (MRgFUS) is a non-invasive lesioning technique used to treat movement disorders such as essential tremor (ET), Parkinson's disease (PD), and X-linked dystonia-parkinsonism (XDP). We would like to report our experience in establishing and developing our MRgFUS program and preliminary results. Adult patients with tremor-dominant PD (TDPD), ET, and XDP were considered for initial screening (neurologic evaluation, skull density ratio [SDR] determination). Eligible patients underwent secondary screening (neurosurgical and neuropsychological evaluation, psychiatric and medical clearance). During the procedure, a neuro-anesthesiologist and neurologist were also present to monitor the patient and perform neurologic evaluation, respectively. Clinical follow-up was scheduled at 2 weeks post-treatment, then at every 3 months. A total of 30 patients underwent MRgFUS treatment: 22 TDPD, 6 XDP, and 2 ET. The mean age was 55.7 years, and majority were male (86.7%). Mean disease duration was 8.6 years. Mean SDR was 0.46. The targets for TDPD and ET were the contralateral ventral intermediate nucleus of the thalamus; for XDP, it was the pallidothalamic tract. The mean maximum temperature was 59.8oC; number of sonocations, 7.3; and treatment time, 64.6 min. Majority of patients improved after the procedure. Transient intraprocedural adverse events (headache, dizziness) were reported in 20% of patients while post-procedural events (mild weakness, numbness) were seen in 16.7%. Only 26.7% of patients had follow-up data. Despite the unique challenges encountered, MRgFUS treatment is feasible in resource-limited settings. Additional steps would have to be made to develop and improve the program.
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Temblor Esencial , Imagen por Resonancia Magnética , Humanos , Masculino , Femenino , Persona de Mediana Edad , Temblor Esencial/terapia , Anciano , Adulto , Filipinas , Enfermedad de Parkinson/terapia , Resultado del Tratamiento , Configuración de Recursos LimitadosRESUMEN
Despite the wide effects of cardiorespiratory fitness (CRF) on metabolic, cardiovascular, pulmonary and neurological health, challenges in the feasibility and reproducibility of CRF measurements have impeded its use for clinical decision-making. Here we link proteomic profiles to CRF in 14,145 individuals across four international cohorts with diverse CRF ascertainment methods to establish, validate and characterize a proteomic CRF score. In a cohort of around 22,000 individuals in the UK Biobank, a proteomic CRF score was associated with a reduced risk of all-cause mortality (unadjusted hazard ratio 0.50 (95% confidence interval 0.48-0.52) per 1 s.d. increase). The proteomic CRF score was also associated with multisystem disease risk and provided risk reclassification and discrimination beyond clinical risk factors, as well as modulating high polygenic risk of certain diseases. Finally, we observed dynamicity of the proteomic CRF score in individuals who undertook a 20-week exercise training program and an association of the score with the degree of the effect of training on CRF, suggesting potential use of the score for personalization of exercise recommendations. These results indicate that population-based proteomics provides biologically relevant molecular readouts of CRF that are additive to genetic risk, potentially modifiable and clinically translatable.
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Capacidad Cardiovascular , Proteómica , Humanos , Proteómica/métodos , Masculino , Femenino , Persona de Mediana Edad , Factores de Riesgo , Adulto , Anciano , Estudios de Cohortes , Ejercicio Físico/fisiologíaRESUMEN
Diabetic foot ulcers represent a significant complication of diabetes mellitus, characterized by mechanical changes of bony architecture often leading to chronic wounds with increased risk of infection and impaired healing. Morganella morganii, a Gram-negative bacterium, is one of the pathogens found in infected diabetic foot ulcers. It is a human gastrointestinal commensal organism that may cause widespread deadly infections. This report discusses the case of a 76-year-old male with diabetes mellitus who presented with M. morganii diabetic foot ulcer to an in-patient rehabilitation facility. Despite conventional wound care and antibiotic therapy, the ulcer failed to improve. The management approach for this patient consisted of a rehabilitation modality called Vaporox, a machine that utilizes vaporous hyperoxia therapy (VHT), as it combines ultrasonic mist and high concentration of oxygen to fasten revascularization and healing. This case highlights the potential efficacy of VHT as an adjunctive therapy for the management of diabetic foot ulcers, particularly those complicated by pathogens, such as M. morganii.
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Gene gains and losses are a major driver of genome evolution; their precise characterization can provide insights into the origin and diversification of major lineages. Here, we examined gene family evolution of 1,154 genomes from nearly all known species in the medically and technologically important yeast subphylum Saccharomycotina. We found that yeast gene family and genome evolution are distinct from plants, animals, and filamentous ascomycetes and are characterized by small genome sizes and smaller gene numbers but larger gene family sizes. Faster-evolving lineages (FELs) in yeasts experienced significantly higher rates of gene losses-commensurate with a narrowing of metabolic niche breadth-but higher speciation rates than their slower-evolving sister lineages (SELs). Gene families most often lost are those involved in mRNA splicing, carbohydrate metabolism, and cell division and are likely associated with intron loss, metabolic breadth, and non-canonical cell cycle processes. Our results highlight the significant role of gene family contractions in the evolution of yeast metabolism, genome function, and speciation, and suggest that gene family evolutionary trajectories have differed markedly across major eukaryotic lineages.
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BACKGROUND: Penile squamous cell carcinoma (PSCC) carries significant morbidity and mortality. Literature is limited regarding prognostic factors, especially prognostic factors for development of metastasis. OBJECTIVES: To identify independent prognostic factors associated with poor outcomes, defined as local recurrence (LR), metastasis and disease-specific death (DSD) in clinically node-negative PSCC undergoing local therapy. METHODS: Thirty-two-year Retrospective Multicenter Cohort Study of 265 patients with histologically diagnosed PSCC at three tertiary care centres. Predictive models based on patient or tumour characteristics were developed. RESULTS: Local recurrence occurred in 56 patients, metastasis in 52 patients and DSD in 40 patients. In multivariable models, the following five factors were independent prognostic factors based on subhazard ratio (SHR): history of balanitis (LR SHR: 2.3; 95% CI 1.2-4.2), poor differentiation (metastasis SHR 1.9; 95% CI 1.0-3.6), invasion into the corpora (metastasis SHR: 3.0; 95% CI 1.5-5.8 and DSD SHR: 4.5; 95% CI 1.7-12.1), perineural invasion (PNI) (metastasis SHR: 2.8; 95% CI 1.4-5.5 and DSD SHR: 3.5; 95% CI, 1.6-7.8) and a history of phimosis (DSD SHR: 2.5; 95% CI 1.2-5.3). The 5-year cumulative incidence of metastasis was higher for tumours with PNI [cumulative incidence function (CIF) = 55%, 95% CI 38-75 vs. CIF 15%, 95% CI 11-22], corporal invasion (CIF: 35%, 95% CI 26-47 vs. 12%, 95% CI 7-19) and poorly differentiated tumours (CIF = 46%, 95% CI 31-64 vs. CIF 15%, 95% CI 11-22). CONCLUSIONS: History of balanitis, history of phimosis, PNI, corporal invasion and poor differentiation are independent risk factors associated with poor outcomes. Since poor differentiation and PNI currently constitute only T1b disease, prognostic staging can likely be improved.
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BACKGROUND: This research aims to determine the influence of industry on the outcomes of randomized controlled trials (RCTs) for Mesenchymal Stem Cell (MSC) treatments in knee osteoarthritis (OA). METHODS: PubMed, Scopus, and Web of Science were searched from 2010 onwards using the terms "knee osteoarthritis" and "mesenchymal stem cells". After identifying relevant RCTs, studies were categorized as industry-affiliated or non-industry-affiliated. They were also classified as favorable if they achieved statistically significant (p < 0.05) results with MSC injections compared to control. Chi-squared tests were employed to analyze the relationship between industry affiliation and study outcome. RESULTS: Post exclusion criteria, 38 studies were analyzed. Of these, there were 20 (52.6%) industry affiliated (IA) and 18 (47.4%) non-industry affiliated (NIA) studies. Among the 20 IA studies, 17 (85.0%) reported favorable outcomes for MSC treatment arm, with the remaining 3 (15.0%) showing analogous (no difference between treatment arms) results. For the 18 NIA studies, 15 (83.3%) were favorable, and 3 (16.6%) were analogous. No significant difference in outcomes was observed between IA and NIA studies (p = 0.888). Analysis of patient reported outcomes also revealed no significant difference. Of note, studies using allogeneic MSCs were more likely to be IA than studies using autologous MSCs (p = 0.005) CONCLUSION: This study demonstrated no strong association between industry affiliation and the outcomes of RCTs for MSC treatments in knee OA. Despite this, the potential influence of industry ties should always be considered when applying study findings to new treatment modalities for patient care.
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The human forearm model is commonly employed in physiological investigations exploring local vascular function and oxygen delivery; however, the effect of arm dominance on exercising forearm hemodynamics and skeletal muscle oxygen saturation (SmO2) in untrained individuals is poorly understood. Therefore, the purpose of this study was to explore the effect of self-identified arm dominance on forearm hemodynamics and SmO2 in untrained individuals during submaximal, non-ischemic forearm exercise. Twenty healthy individuals (23±4 years, 50% female; 80% right-handed) completed three-minute bouts of supine rhythmic (1 second contraction: 2 second relaxation duty cycle) forearm handgrip exercise at both absolute (10kg; 98N) and relative (30% of maximal voluntary contraction) intensities in each forearm. Beat-by-beat measures of forearm blood flow (FBF; ml/min), mean arterial blood pressure (MAP; mmHg) and flexor digitorum superficialis SmO2 (%) were obtained throughout and averaged during the final 30 seconds of rest, exercise, and recovery while forearm vascular conductance was calculated (FVC; ml/min/100mmHg). Data are Δ from rest (mean±SD). Absolute force production did not differ between non-dominant and dominant arms (97±11 vs. 98±13 N, p = 0.606) whereas relative force production in females did (69±24 vs. 82±25 N, p = 0.001). At both exercise intensities, FBFRELAX, FVCRELAX, MAPRELAX, and the time constant tau for FBF and SmO2 were unaffected by arm dominance (all p>0.05). While arm dominance did not influence SmO2 during absolute intensity exercise (p = 0.506), the non-dominant arm in females experienced an attenuated reduction in SmO2 during relative intensity exercise (-14±10 vs. -19±8%, p = 0.026)-though exercise intensity was also reduced (p = 0.001). The present investigation has demonstrated that arm dominance in untrained individuals does not impact forearm hemodynamics or SmO2 during handgrip exercise.
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Ejercicio Físico , Antebrazo , Hemodinámica , Músculo Esquelético , Humanos , Femenino , Músculo Esquelético/fisiología , Músculo Esquelético/irrigación sanguínea , Antebrazo/irrigación sanguínea , Antebrazo/fisiología , Hemodinámica/fisiología , Masculino , Ejercicio Físico/fisiología , Adulto , Adulto Joven , Fuerza de la Mano/fisiología , Brazo/fisiología , Brazo/irrigación sanguínea , Flujo Sanguíneo Regional/fisiología , Oxígeno/metabolismo , Consumo de Oxígeno/fisiologíaRESUMEN
Malic Enzyme 1 (ME1) plays an integral role in fatty acid synthesis and cellular energetics through its production of NADPH and pyruvate. As such, it has been identified as a gene of interest in obesity, type 2 diabetes, and an array of epithelial cancers, with most work being performed in vitro. The current standard model for ME1 loss in vivo is the spontaneous Mod-1 null allele, which produces a canonically inactive form of ME1. Herein, we describe two new genetically engineered mouse models exhibiting ME1 loss at dynamic timepoints. Using murine embryonic stem cells and Flp/FRT and Cre/loxP class switch recombination, we established a germline Me1 knockout model (Me1 KO) and an inducible conditional knockout model (Me1 cKO), activated upon tamoxifen treatment in adulthood. Collectively, neither the Me1 KO nor Me1 cKO models exhibited deleterious phenotype under standard laboratory conditions. Knockout of ME1 was validated by immunohistochemistry and genotype confirmed by PCR. Transmission patterns favor Me1 loss in Me1 KO mice when maternally transmitted to male progeny. Hematological examination of these models through complete blood count and serum chemistry panels revealed no discrepancy with their wild-type counterparts. Orthotopic pancreatic tumors in Me1 cKO mice grow similarly to Me1 expressing mice. Similarly, no behavioral phenotype was observed in Me1 cKO mice when aged for 52 weeks. Histological analysis of several tissues revealed no pathological phenotype. These models provide a more modern approach to ME1 knockout in vivo while opening the door for further study into the role of ME1 loss under more biologically relevant, stressful conditions.
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Malato Deshidrogenasa , Ratones Noqueados , Fenotipo , Animales , Malato Deshidrogenasa/metabolismo , Malato Deshidrogenasa/genética , Masculino , Ratones , Femenino , Células Germinativas/metabolismo , Ratones Endogámicos C57BLRESUMEN
ABSTRACT: Hip pain is a common concern among athletes. With gluteal tendinopathy, femoroacetabular impingement, and osteoarthritis predominating sports medicine and musculoskeletal practices, less common etiologies may be overlooked. Complex pelvic anatomy and variable pain referral patterns may make identifying an accurate diagnosis challenging. Employing a systematic approach to evaluation and having a thorough understanding of hip region anatomy are essential. A potentially overlooked cause of anterolateral hip pain is iliotibial band origin tendinopathy. Patients often present with pain around the anterolateral hip and tenderness to palpation at the anterolateral iliac crest. While patients with iliotibial band origin tendinopathy usually respond to nonsurgical intervention, there is little literature to guide evaluation and treatment, highlighting a gap in the recognition of this condition. The purpose of this narrative review is to describe the anatomy of the proximal iliotibial band origin, outline the clinical diagnosis and imaging findings of ITBOT, and summarize current treatment options.