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Groove, or the pleasurable urge to move to music, offers unique insight into the relationship between emotion and action. The predictive coding of music model posits that groove is linked to predictions of music formed over time, with stimuli of moderate complexity rated as most pleasurable and likely to engender movement. At the same time, listeners vary in the pleasure they derive from music listening: individuals with musical anhedonia report reduced pleasure during music listening despite no impairments in music perception and no general anhedonia. Little is known about musical anhedonics' subjective experience of groove. Here we examined the relationship between groove and music reward sensitivity. Participants (n = 287) heard drum-breaks that varied in perceived complexity, and rated each for pleasure and wanting to move. Musical anhedonics (n = 13) had significantly lower ratings compared to controls (n = 13) matched on music perception abilities and general anhedonia. However, both groups demonstrated the classic inverted-U relationship between ratings of pleasure & move and stimulus complexity, with ratings peaking for intermediately complex stimuli. Across our entire sample, pleasure ratings were most strongly related with music reward sensitivity for highly complex stimuli (i.e., there was an interaction between music reward sensitivity and stimulus complexity). Finally, the sensorimotor subscale of music reward was uniquely associated with move, but not pleasure, ratings above and beyond the five other dimensions of musical reward. Results highlight the multidimensional nature of reward sensitivity and suggest that pleasure and wanting to move are driven by overlapping but separable mechanisms.
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Anhedonia , Percepción Auditiva , Música , Placer , Recompensa , Humanos , Música/psicología , Anhedonia/fisiología , Femenino , Masculino , Adulto , Placer/fisiología , Adulto Joven , Percepción Auditiva/fisiología , Emociones/fisiología , Adolescente , Estimulación AcústicaRESUMEN
Many amniote vertebrate species including humans can form identical twins from a single embryo, but this only occurs rarely. It has been suggested that the primitive-streak-forming embryonic region emits signals that inhibit streak formation elsewhere but the signals involved, how they are transmitted and how they act has not been elucidated. Here we show that short tracks of calcium firing activity propagate through extraembryonic tissue via gap junctions and prevent ectopic primitive streak formation in chick embryos. Cross-regulation of calcium activity and an inhibitor of primitive streak formation (Bone Morphogenetic Protein, BMP) via NF-κB and NFAT establishes a long-range BMP gradient spanning the embryo. This mechanism explains how embryos of widely different sizes can maintain positional information that determines embryo polarity. We provide evidence for similar mechanisms in two different human embryo models and in Drosophila, suggesting an ancient evolutionary origin.
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Proteínas Morfogenéticas Óseas , Calcio , Animales , Embrión de Pollo , Humanos , Calcio/metabolismo , Proteínas Morfogenéticas Óseas/metabolismo , Gastrulación/fisiología , Línea Primitiva , ReproducciónRESUMEN
The Pcf11 protein is an essential subunit of the large complex that cleaves and polyadenylates eukaryotic mRNA precursor. It has also been functionally linked to gene-looping, termination of RNA Polymerase II (Pol II) transcripts, and mRNA export. We have examined a poorly characterized but conserved domain (amino acids 142-225) of the Saccharomyces cerevisiae Pcf11 and found that while it is not needed for mRNA 3' end processing or termination downstream of the poly(A) sites of protein-coding genes, its presence improves the interaction with Pol II and the use of transcription terminators near gene promoters. Analysis of genome-wide Pol II occupancy in cells with Pcf11 missing this region, as well as Pcf11 mutated in the Pol II CTD Interacting Domain, indicates that systematic changes in mRNA expression are mediated primarily at the level of transcription. Global expression analysis also shows that a general stress response, involving both activation and suppression of specific gene sets known to be regulated in response to a wide variety of stresses, is induced in the two pcf11 mutants, even though cells are grown in optimal conditions. The mutants also cause an unbalanced expression of cell wall-related genes that does not activate the Cell Wall Integrity pathway but is associated with strong caffeine sensitivity. Based on these findings, we propose that Pcf11 can modulate the expression level of specific functional groups of genes in ways that do not involve its well-characterized role in mRNA 3' end processing.
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Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Factores de Escisión y Poliadenilación de ARNm , Factores de Escisión y Poliadenilación de ARNm/genética , Factores de Escisión y Poliadenilación de ARNm/metabolismo , Mutación , ARN Polimerasa II/metabolismo , ARN Mensajero/genética , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Transcripción GenéticaRESUMEN
Primordial germ cells (PGCs) are the early embryonic precursors of gametes - sperm and egg cells. PGC-like cells (PGCLCs) can currently be derived in vitro from pluripotent cells exposed to signalling cocktails and aggregated into large embryonic bodies, but these do not recapitulate the native embryonic environment during PGC formation. Here, we show that mouse gastruloids, a three-dimensional in vitro model of gastrulation, contain a population of gastruloid-derived PGCLCs (Gld-PGCLCs) that resemble early PGCs in vivo. Importantly, the conserved organisation of mouse gastruloids leads to coordinated spatial and temporal localisation of Gld-PGCLCs relative to surrounding somatic cells, even in the absence of specific exogenous PGC-specific signalling or extra-embryonic tissues. In gastruloids, self-organised interactions between cells and tissues, including the endodermal epithelium, enables the specification and subsequent maturation of a pool of Gld-PGCLCs. As such, mouse gastruloids represent a new source of PGCLCs in vitro and, owing to their inherent co-development, serve as a novel model to study the dynamics of PGC development within integrated tissue environments.
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Células Germinativas , Semen , Masculino , Ratones , Animales , Endodermo , Células Cultivadas , Transducción de Señal , Diferenciación Celular/genéticaRESUMEN
Pharmaceuticals intended for use in patients of childbearing potential need to be tested for teratogenicity before marketing. Several pharmaceutical companies use animal-free in vitro models which allow a more rapid selection of lead compounds and contribute to 3Rs principles ('replace, reduce and refine') by streamlining the selection of promising compounds submitted to further regulatory studies in animals. Currently available in vitro models typically rely on adherent monolayer cultures or disorganized 3D structures, both of which lack the spatiotemporal and morphological context of the developing embryo. A newly developed 3D 'gastruloid' model has the potential to achieve a more reliable prediction of teratogenicity by providing a robust recapitulation of gastrulation-like events alongside morphological coordination at relatively high-throughput. In this first proof-of-concept study, we used both mouse and human gastruloids to examine a panel of seven reference compounds, with associated in vivo data and known teratogenic risk, to quantitatively assess in vitro teratogenicity. We observed several gross morphological effects, including significantly reduced elongation or decreased size of the gastruloids, upon exposure to several of the reference compounds. We also observed aberrant gene expression using fluorescent reporters, including SOX2, BRA, and SOX17, suggestive of multi-lineage differentiation defects and disrupted axial patterning. Finally, we saw that gastruloids recapitulated some of the known in vivo species-specific susceptibilities between their mouse and human counterparts. We therefore suggest that gastruloids represent a powerful tool for teratogenicity assessment by enabling relevant physiological recapitulation of early embryonic development, demonstrating their use as a novel in vitro teratogenic model system.
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Gástrula/efectos de los fármacos , Organoides/efectos de los fármacos , Teratógenos/toxicidad , Animales , Células Cultivadas , Embrión de Mamíferos , Gastrulación , Células Madre Embrionarias Humanas , Humanos , Ratones , Células Madre Embrionarias de RatonesRESUMEN
Metal-organic frameworks (MOFs), especially those made by biological molecules (bio-MOFs), have been proved to be prospective candidates for biomedical applications. However, a simple and universal bio-MOF to load different substances for precise targeting is still lacking. In this work, we propose a facile one-pot method to prepare a peptide-doped bio-MOF for general encapsulation and targeted delivery. This bio-MOF is constructed by 9-fluorenylmethyloxycarbonyl-modified histidine (Fmoc-His) as a bridging linker that coordinates with Zn2+ ions, denoted as ZFH. The Fmoc-His-Asp-Gly-Arg peptide (Fmoc-HDGR) can be easily doped into the ZFH structure with different ratios to modulate the targeting ability of ZFH-DGR. Containing both hydrophobic Fmoc and hydrophilic His moieties, this framework is compatible with encapsulating various types of payloads, including hydrophobic chemotherapeutic, hydrophilic protein, and positively/negatively charged inorganic nanoparticles. It has also been proved to be highly biocompatible and stable in circulation, exhibit the capabilities to target ανß3 integrin overexpressed on tumor cells, and trigger drug release in a low pH microenvironment at the tumor site. As a proof of concept, Doxorubicin (Dox)-loaded ZFH-DGR (ZFH-DGR/Dox) demonstrated high cell selectivity between liver hepatocellular carcinoma (HepG2) cells and normal liver (L02) cells, which express high and low ανß3 integrin, respectively. This selectivity endows ZFH-DGR/Dox precise treatment and low toxicity in Heps-bearing liver cancer mice. This work develops a de novo approach to construct a peptide-doped bio-MOF system for universal load, precise delivery, and peptide drug combination therapy in the future.
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Antineoplásicos/uso terapéutico , Doxorrubicina/uso terapéutico , Portadores de Fármacos/química , Estructuras Metalorgánicas/química , Neoplasias/tratamiento farmacológico , Oligopéptidos/química , Animales , Antineoplásicos/química , Doxorrubicina/química , Portadores de Fármacos/síntesis química , Portadores de Fármacos/metabolismo , Liberación de Fármacos , Endocitosis/fisiología , Células Hep G2 , Humanos , Concentración de Iones de Hidrógeno , Estructuras Metalorgánicas/síntesis química , Estructuras Metalorgánicas/metabolismo , Ratones Endogámicos ICR , Neoplasias/patología , Oligopéptidos/síntesis química , Oligopéptidos/metabolismo , Prueba de Estudio Conceptual , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Gastruloids are embryonic organoids made from small, defined numbers of mouse embryonic stem cells (mESCs) aggregated in suspension culture, which over time form 3D structures that mimic many of the features of early mammalian development. Unlike embryoid bodies that are usually disorganized when grown over several days, gastruloids display distinct, well-organized gene expression domains demarcating the emergence of the three body axes, anteroposterior axial elongation, and implementation of collinear Hox transcriptional patterns over 5-7 days of culture. As such gastruloids represent a useful experimental system that is complementary to in vivo approaches in studying early developmental patterning mechanisms regulating the acquisition of cell fates. In this protocol, we describe the most recent method for generating gastruloids with high reproducibility, and provide a comprehensive list of possible challenges as well as steps for protocol optimization.
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Tipificación del Cuerpo , Diferenciación Celular , Linaje de la Célula , Gastrulación , Células Madre Embrionarias de Ratones/fisiología , Animales , Técnicas de Cultivo de Célula , Células Cultivadas , Regulación del Desarrollo de la Expresión Génica , Ratones , Microscopía , Organoides , Transducción de Señal , Factores de TiempoRESUMEN
Pluripotent stem cells derived from the early mammalian embryo offer a convenient model system for studying cell fate decisions in embryogenesis. The last 10 years have seen a boom in the popularity of two-dimensional micropatterns and three-dimensional stem cell culture systems as a way to recreate the architecture and interactions of particular cell populations during development. These methods enable the controlled exploration of cellular organization and patterning during development, using cell lines instead of embryos. They have established a new class of in vitro model system for pre-implantation and peri-implantation embryogenesis, ranging from models of the blastocyst stage, through gastrulation and toward early organogenesis. This review aims to set these systems in context and to highlight the strengths and suitability of each approach in modelling early mammalian development.
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Embrión de Mamíferos/citología , Desarrollo Embrionario , Mamíferos/embriología , Modelos Biológicos , Células Madre Pluripotentes/metabolismo , Animales , Humanos , Organoides/citología , Organoides/embriologíaRESUMEN
Mitochondria, the energy supply factories for cell-life activities, play important roles in controlling epigenetics, differentiation and initiation, and the execution of apoptosis. These functions of the mitochondria contribute to cell adaptation to challenging microenvironment conditions. In past decades, mitochondrial malfunction has been revealed to be closely related to the occurrence and development of a variety of human disorders, including cancer and multiple neurodegenerative diseases. The disturbance of the mitochondrial genome (mtDNA) or mitochondrial vital functions, e.g., the production of adenosine triphosphate (ATP) and the generation of reactive oxygen species (ROS), can potentially be involved in disease pathogenesis. Recent research has shown that the precise monitoring of mitochondrial environments can provide potential directions for cancer diagnosis. Furthermore, mitochondrial-targeted cancer treatment exhibits unparalleled superiority for enhanced tumor therapy. Therefore, in this review, we focus on mitochondrial-based cancer diagnosis via monitoring mitochondrial respiration or mitophagy. Current approaches using mitochondrial-based cancer treatments, including targeting mitochondrial ATP, mitochondrial membrane permeability, and mitochondrial ROS levels and mtDNA, are also summarized. This review will provide insights into mitochondrial-mediated tumor monitoring and mitochondrial-based therapy.
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Mitocondrias/efectos de los fármacos , Terapia Molecular Dirigida/métodos , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológico , Animales , Humanos , Neoplasias/patologíaRESUMEN
BACKGROUND: Early resuscitation and damage control surgery (DCS) are critical components of modern combat casualty care. Early and effective DCS capabilities can be delivered in a variety of settings through the use of a mobile surgical resuscitation team (SRT). METHODS: Twelve years of after-action reports from SRTs were reviewed. Demographics, interventions, and outcomes were analyzed. RESULTS: Data from 190 casualties (185 human, five canine) were reviewed. Among human casualties, 12 had no signs of life at intercept and did not survive. Of the remaining 173 human casualties, 96.0% were male and 90.8% sustained penetrating injuries. Interventions by the SRT included intravascular access (50.9%) and advanced airway establishment (29.5%). Resuscitation included whole blood (3.5%), packed red blood cells (20.8%), and thawed plasma (11.0%). Surgery was provided for 63 of the 173 human casualties (36.4%), including damage control laparotomy (23.8%) and arterial injury shunting or repair (19.0%). SRTs were effectively used to augment an existing medical treatment facility (70.5%), to facilitate casualty transport (13.3%), as an independent surgical entity at a forward ground structure (9.2%), and in mobile response directly to the point of injury (6.9%). Overall survival was 97.1%. CONCLUSION: An SRT provides a unique DCS capability that can be successfully used in a variety of flexible roles.
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Personal Militar , Resucitación , Traumatología/estadística & datos numéricos , Heridas Relacionadas con la Guerra/cirugía , Heridas Penetrantes/cirugía , Manejo de la Vía Aérea/estadística & datos numéricos , Animales , Cateterismo Periférico/estadística & datos numéricos , Perros , Transfusión de Eritrocitos/estadística & datos numéricos , Femenino , Humanos , Infusiones Intraóseas/estadística & datos numéricos , Masculino , Grupo de Atención al Paciente/organización & administración , Tasa de Supervivencia , Traumatología/organización & administración , Estados UnidosRESUMEN
Upregulation of programmed death ligand 1 (PD-L1) is a mechanism of immune escape utilized by a variety of tumors. PD-L1 expression in tumor cells or in the surrounding infiltrate correlates with clinical responsiveness to novel therapies targeting the PD-1/PD-L1 immune checkpoint. In the context of HIV-1 infection, Kaposi's sarcoma (KS) is largely responsive to restoration of immunity following combination antiretroviral therapy (cART), but there is a subset that is not. We hypothesized that this subset of cART-refractory KS may utilize the PD-L1 pathway of immune escape. We found that PD-L1 expressing KS had a denser CD8+ T cell (p = 0.03) and PD-L1 positive macrophage peritumoral infiltrate (p = 0.04) to suggest the involvement of PD-L1 in shaping an immune-tolerogenic microenvironment in cART-refractory KS. The presence of PD-L1 expression in association with immune-infiltrating cells provides rationale for the clinical development PD-1/PD-L1-targeted checkpoint inhibitors in cART-refractory KS.
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INTRODUCTION: The California Prehospital Antifibrinolytic Therapy (Cal-PAT) study seeks to assess the safety and impact on patient mortality of tranexamic acid (TXA) administration in cases of trauma-induced hemorrhagic shock. The current study further aimed to assess the feasibility of prehospital TXA administration by paramedics within the framework of North American emergency medicine standards and protocols. METHODS: This is an ongoing multi-centered, prospective, observational cohort study with a retrospective chart-review comparison. Trauma patients identified in the prehospital setting with signs of hemorrhagic shock by first responders were administered one gram of TXA followed by an optional second one-gram dose upon arrival to the hospital, if the patient still met inclusion criteria. Patients administered TXA make up the prehospital intervention group. Control group patients met the same inclusion criteria as TXA candidates and were matched with the prehospital intervention patients based on mechanism of injury, injury severity score, and age. The primary outcomes were mortality, measured at 24 hours, 48 hours, and 28 days. Secondary outcomes measured included the total blood products transfused and any known adverse events associated with TXA administration. RESULTS: We included 128 patients in the prehospital intervention group and 125 in the control group. Although not statistically significant, the prehospital intervention group trended toward a lower 24-hour mortality rate (3.9% vs 7.2% for intervention and control, respectively, p=0.25), 48-hour mortality rate (6.3% vs 7.2% for intervention and control, respectively, p=0.76), and 28-day mortality rate (6.3% vs 10.4% for intervention and control, respectively, p=0.23). There was no significant difference observed in known adverse events associated with TXA administration in the prehospital intervention group and control group. A reduction in total blood product usage was observed following the administration of TXA (control: 6.95 units; intervention: 4.09 units; p=0.01). CONCLUSION: Preliminary evidence from the Cal-PAT study suggests that TXA administration may be safe in the prehospital setting with no significant change in adverse events observed and an associated decreased use of blood products in cases of trauma-induced hemorrhagic shock. Given the current sample size, a statistically significant decrease in mortality was not observed. Additionally, this study demonstrates that it may be feasible for paramedics to identify and safely administer TXA in the prehospital setting.
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Antifibrinolíticos/uso terapéutico , Choque Hemorrágico/tratamiento farmacológico , Ácido Tranexámico/uso terapéutico , Adulto , California , Servicios Médicos de Urgencia , Estudios de Factibilidad , Femenino , Hemorragia/tratamiento farmacológico , Hemorragia/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Choque Hemorrágico/etiología , Choque Hemorrágico/mortalidad , Resultado del Tratamiento , Heridas y Lesiones/complicaciones , Heridas y Lesiones/mortalidad , Adulto JovenRESUMEN
In this article, we draw on the theoretical and empirical literature to name what appear to be core dimensions of successful young adult development. We also describe some possible indicators and measures of those dimensions and sketch the kinds of developmental relationships and opportunities young people need in adolescence to effectively transition to a successful young adulthood, as well as the developmental relationships and opportunities young adults need for continued well-being. We name eight social, psychological, behavioral, educational, occupational, health, ethical, and civic dimensions of successful young adult development, and suggest that only a minority of adolescents are well-prepared to make a transition to successful young adulthood. The goal of the article is twofold: to contribute to the articulation of and consensus on the dimensions of successful young adult development, and to lay the groundwork for subsequent research to empirically validate both those core dimensions, as well as developmental indicators of progress toward attainment of these proposed dimensions of well-being.
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Female boxing debuted at the 2012 London Olympic Games. To better understand the performance aspects of the sport, video footage of eighteen 4 × 2-min bouts were analyzed. The boxers involved in the competition were of an elite level (mean ± SD), age 26.4 ± 4.6 y, height 169.3 ± 6.2 cm, and weight 60.3 ± 10.0 kg. Analysis revealed an activity rate of ~1.6 actions/s, including ~16 punches, ~3.3 defensive movements, and ~63 vertical hip movements, all per minute, over the 4 × ~132-s rounds (R). A 2 × 4 (outcome × round) ANOVA with repeated measures over the rounds was used to analyze the data. Winners maintained a higher activity rate in round 1 (R1) and R2; a higher movement rate in R2, R3, and R4; and an increased punch accuracy including the ratio of total punches to punches landed in R3 and air punches as a percentage of punches missed in R1 and R3. Specific techniques that discriminate between successful and unsuccessful female amateur boxers include the straight rear-hand and body punches, higher for winners in R1, as well as uppercut punches and defensive foot movements, higher for winners in R4. Findings highlight the current demands of elite amateur female boxing. These data will be useful for those designing training programs and may also be useful for guiding sport-specific fitness testing.
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Boxeo/fisiología , Conducta Competitiva/fisiología , Destreza Motora/fisiología , Análisis y Desempeño de Tareas , Adulto , Rendimiento Atlético/fisiología , Femenino , Pie/fisiología , Cadera/fisiología , Humanos , Masculino , Movimiento , Educación y Entrenamiento Físico , Factores Sexuales , Grabación en VideoRESUMEN
BACKGROUND: The effects of mild traumatic brain injury (mTBI) have received significant attention since the beginning of the conflicts in Afghanistan and Iraq. Surprisingly, little is known about the temporal nature of neurocognitive impairment, mTBI, and posttraumatic stress (PTS) symptoms following combat-related mTBI. It is also unclear as to the role that blast exposure history has on mTBI and PTS impairments and symptoms. The purposes of this study were to examine prospectively the effects of mTBI on neurocognitive performance as well as mTBI and PTS symptoms among US Army Special Operations Command personnel and to study the influence of history of blast mTBI on these effects. METHODS: Eighty US Army Special Operations Command personnel with (n = 19) and without (n = 61) a history of blast-related mTBI completed the military version of the Immediate Post-concussion Assessment Cognitive Test (ImPACT), Post Concussion Symptom Scale (PCSS), and the PTSD Checklist (PCL) at baseline as well as 1 day to 7 days and 8 days to 20 days following a combat-related mTBI. RESULTS: Results indicated that verbal memory (p = 0.002) and processing speed (p = 0.003) scores were significantly lower and mTBI symptoms (p = 0.001) were significantly higher at 1 day to 7 days after injury compared with both baseline and 8 days to 20 days after injury. PTS remained stable across the three periods. Participants with a history of blast mTBI demonstrated lower verbal memory at 1 day to 7 days after mTBI compared with participants without a history of blast mTBI (p = 0.02). CONCLUSION: Decreases in neurocognitive performance and increased mTBI symptoms are evident in the first 1 day to 7 days following combat-related mTBI, and a history of blast-related mTBI may influence these effects. LEVEL OF EVIDENCE: Epidemiologic/prognostic study, level II.
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Traumatismos por Explosión/psicología , Lesiones Encefálicas/psicología , Trastornos del Conocimiento/psicología , Personal Militar/psicología , Adulto , Traumatismos por Explosión/fisiopatología , Lesiones Encefálicas/fisiopatología , Trastornos del Conocimiento/fisiopatología , Humanos , Masculino , Estudios ProspectivosRESUMEN
PURPOSE: The interaction of programmed death-1 ligand (PD-L1) with its receptor (PD-1) on T cells inactivates antitumor immune responses. PD-L1 expression has been associated with poor outcomes in renal cell carcinoma (RCC) but has not been investigated in advanced RCC patients receiving VEGF-targeted therapy. EXPERIMENTAL DESIGN: Formalin-fixed paraffin-embedded specimens were collected at baseline from patients in the COMPARZ trial. Tumor cell PD-L1 expression by IHC was evaluated using H-score (HS). Dual PD-L1/CD68 staining was used to differentiate PD-L1 tumor expression from tumor-associated macrophages. Intratumor CD8-positive T cells were quantified morphometrically. Associations between biomarkers and survival were investigated using the log-rank test. RESULTS: HS data were available from 453 of 1,110 patients. Sixty-four percent of patients had negative PD-L1 expression (HS = 0). Patients with HS > 55 (n = 59, 13%) had significantly shorter overall survival (OS) than those with HS ≤ 55 in both pazopanib and sunitinib arms (median 15.1 vs. 35.6 and 15.3 vs. 27.8 months, respectively, P = 0.03). In both arms, median OS was shortest in patients with HS > 55 and intratumor CD8-positive T-cell counts > 300 (9.6 and 11.9 months with pazopanib and sunitinib, respectively). Median OS in patients with HS ≤ 55 and CD8-positive T-cell counts ≤ 300 was 36.8 and 28.0 months with pazopanib and sunitinib, respectively. Progression-free survival results were similar to OS results. CONCLUSIONS: Increased tumor cell PD-L1, or PD-L1 plus tumor CD8-positive T-cell counts, were associated with shorter survival in patients with metastatic RCC receiving VEGF-targeted agents. These findings may have implications for future design of randomized clinical trials in advanced RCC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígeno B7-H1/metabolismo , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/metabolismo , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Antígeno B7-H1/genética , Linfocitos T CD8-positivos/inmunología , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/patología , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Indazoles , Indoles/administración & dosificación , Neoplasias Renales/genética , Neoplasias Renales/inmunología , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Recuento de Linfocitos , Macrófagos/inmunología , Macrófagos/metabolismo , Masculino , Persona de Mediana Edad , Pronóstico , Pirimidinas/administración & dosificación , Pirroles/administración & dosificación , Sulfonamidas/administración & dosificación , SunitinibRESUMEN
An activity profile of competitive 3 × 3-min elite-level amateur boxing was created from video footage of 29 Olympic final and semifinal bouts in 39 male boxers (mean ± SD) age 25.1 ± 3.6 y, height 178.3 ± 10.4 cm, and body mass 69.7 ± 16.5 kg. Boxing at this level requires the ability to maintain an activity rate of ~1.4 actions/s, consisting of ~20 punches, ~2.5 defensive movements, and ~47 vertical hip movements, all per minute, over 3 subsequent rounds lasting ~200 s each. Winners had higher total punches landed (P = .041) and a lower ratio of punches thrown to landed (P = .027) than losers in round 3. The hook rear-hand landed was also higher for winners than losers in round 2 (P = .038) and round 3 (P = .016), and defensive movements were used less by winners (P = .036). However, the results suggest that technical discrimination between winners and losers is difficult; bout outcome may be more dependent on which punch is "lucky" enough to be scored by the judges or who appears to be dominant on the day. This study gives both boxers and coaches a good idea of where subelite boxers need to aim if they want to become among the best amateur boxers in the world.
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Boxeo/fisiología , Conducta Competitiva/fisiología , Destreza Motora/fisiología , Adulto , Fenómenos Biomecánicos , Humanos , Masculino , Análisis y Desempeño de Tareas , Grabación en Video , Adulto JovenRESUMEN
Musculoskeletal injuries have long been a problem in general purpose forces, yet anecdotal evidence provided by medical, human performance, and training leadership suggests musculoskeletal injuries are also a readiness impediment to Special Operations Forces (SOF). The purpose of this study was to describe the injury epidemiology of SOF utilizing self-reported injury histories. Data were collected on 106 SOF (age: 31.7 ± 5.3 years, height: 179.0 ± 5.5 cm, mass: 85.9 ± 10.9 kg) for 1 year before the date of laboratory testing and filtered for total injuries and those with the potential to be preventable based on injury type, activity, and mechanism. The frequency of musculoskeletal injuries was 24.5 injuries per 100 subjects per year for total injuries and 18.9 injuries per 100 subjects per year for preventable injuries. The incidence of musculoskeletal injuries was 20.8 injured subjects per 100 subjects per year for total injuries and 16.0 injured subjects per 100 subjects per year for preventable injuries. Preventable musculoskeletal injuries comprised 76.9% of total injuries. Physical training (PT) was the most reported activity for total/preventable injuries (PT Command Organized: 46.2%/60.0%, PT Noncommand Organized: 7.7%/10.0%, PT Unknown: 3.8%/5.0%). Musculoskeletal injuries impede optimal physical readiness/tactical training in the SOF community. The data suggest a significant proportion of injuries are classified as preventable and may be mitigated with human performance programs.
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Personal Militar/estadística & datos numéricos , Sistema Musculoesquelético/lesiones , Adolescente , Adulto , Fracturas Óseas/epidemiología , Humanos , Incidencia , Traumatismos de la Rodilla/epidemiología , Ligamentos Articulares/lesiones , Extremidad Inferior/lesiones , Masculino , Persona de Mediana Edad , Personal Militar/educación , Acondicionamiento Físico Humano/estadística & datos numéricos , Desempeño Psicomotor , Carrera/lesiones , Autoinforme , Lesiones del Hombro , Esguinces y Distensiones/epidemiología , Estados Unidos/epidemiología , Adulto JovenRESUMEN
PROBLEM: Guatemala is experiencing an increasing burden of cancer but lacks capacity for cancer prevention, control and research. APPROACH: In partnership with a medical school in the United States of America, a multidisciplinary Cancer Control Research Training Institute was developed at the Instituto de Cancerología (INCAN) in Guatemala City. This institute provided a year-long training programme for clinicians that focused on research methods in population health and sociocultural anthropology. The programme included didactic experiences in Guatemala and the United States as well as applied training in which participants developed research protocols responsive to Guatemala's cancer needs. LOCAL SETTING: Although INCAN is the point of referral and service for Guatemala's cancer patients, the institute's administration is also interested in increasing cancer research - with a focus on population health. INCAN is thus a resource for capacity building within the context of cancer prevention and control. RELEVANT CHANGES: Trainees increased their self-efficacy for the design and conduct of research. Value-added benefits included establishment of an annual cancer seminar and workshops in cancer pathology and qualitative analysis. INCAN has recently incorporated some of the programme's components into its residency training and established a research department. LESSONS LEARNT: A training programme for clinicians can build cancer research capacity in low- and middle-income countries. Training in population-based research methods will enable countries such as Guatemala to gather country-specific data. Once collected, such data can be used to assess the burden of cancer-related disease, guide policy for reducing it and identify priority areas for cancer prevention and treatment.