Repeated Maximal Exercise Measures are Very Reliable Among Healthy College-aged Individuals

The most common way to assess cardiovascular fitness is with a maximal graded exercise test (GXT) to determine the maximal rate of oxygen consumption (VO2 max). Maximal exercise efforts during GXT testing have been shown to be quite repeatable among active and sedentary adults, as well as cardiac patients and the elderly. With young, healthy participants, familiarization and motivation could result in improved performance measures with repeated testing. The reliability of maximal exercise measures among healthy college-aged individuals during repeated Bruce Protocol GXT assessments are yet unclear. PURPOSE: To determine how repeatable the VO2max and other maximal exercise indices were with repeated GXT measures among healthy, college-aged adults. METHODS: Thirty-six apparently healthy participants (20 men, 16 women) aged 21.47 ± 0.5 years completed three GXT testing sessions following the Bruce Protocol. The maximal values for VO2, blood lactate, VE, HR and Borg Rating of Perceived Exertion (RPE) as well as time to exhaustion were recorded at the end of each session. RESULTS: Statistical analysis of the data was conducted using a one-way ANOVA by order of visit and a Tukey post-hoc analysis. With all participants combined, there were no differences in measured variables with one exception. Maximal RPE was higher in Visit 3 compared to Baseline (p=0.02). When men and the women were analyzed separately, there were no differences in RPE values among the men. Women reported a higher Max RPE in both Visit 2 and Visit 3 compared to Baseline. Despite the higher RPE values no other maximal measures were significantly different across testing sessions. CONCLUSION: This research confirms that repeated maximal GXT measures are very reliable among healthy college-aged individuals. The exception being a small but significant difference in self-reported maximal RPE values among women compared to baseline measures. Future studies could address potential reasons for the significant difference in women’s self-reported RPE values

The Effects of Ox66TM Supplementation on Ventilatory Threshold Performance Measures

Ox66TM claims to be the only solid form of oxygen known to be in existence. It is an aluminum hydroxide clathrate that can trap oxygen molecules within its structure and when digested the oxygen molecules can be absorbed into the portal bloodstream. It has previously been implemented in clinical settings to reduce hypoxia related medical conditions. However, it is currently unknown whether Ox66TM has an effect on performance measures at or near the ventilatory threshold during high intensity exercise. PURPOSE: The purpose of this study was to evaluate the ergogenic impact of acute Ox66TM ingestion on submaximal aerobic performance measures and ventilatory threshold during exercise testing using Bruce protocol. METHODS: 36 college age participants (20 males and 16 females) were recruited to complete this study. Participants attended three testing sessions. During the first session, baseline measurements were acquired and participants were familiarized with the testing procedures. During the second and third tests participants were randomized to receive either a placebo or the Ox66TM supplement. Heart rate, ventilatory threshold, respiratory exchange ratio and rating of perceived exertion (RPE) were recorded throughout each test. RESULTS: Overall there were no consistent differences between the placebo and Ox66TM conditions for all participants combined. However, when men and women were evaluated separately, there were a few significant differences. Under the Ox66TM condition men had a slightly higher VO2 (p=0.045) and higher heart rate (p=0.046) at ventilatory threshold. Women had a slightly lower RPE (p=0.047) at ventilatory threshold with the Ox66TM supplement. CONCLUSION: Ox66TM supplementation resulted in small improvements in a few submaximal aerobic performance measures. Although these results are statistically significant, it is unlikely that Ox66TM supplementation actually causes ergogenic performance benefits

El delito de corrupción de personas con discapacidad a través del uso de las Tecnologías de la Información y Comunicación

RESUMEN: En la historia de la humanidad las Personas con Discapacidad han sido invisibilidades en los diferentes ámbitos del desarrollo humano, cuestión que, ha posibilitado la vulneración de sus derechos, pese a esto, en los últimos años se han implementado políticas internacionales y estatales, con la finalidad de posibilitar el ejercicio de sus derechos y de protegerles ante cualquier amenaza; como con la creación de la Convención sobre los Derechos de las Personas con Discapacidad y la aprobación de la Ley Especial de las Personas con Discapacidad; en el derecho penal, por su calidad de indemnes sexualmente y con la finalidad de asegurar el normal desarrollo de su sexualidad, se les ha reconocido como víctimas de diversos delitos de naturaleza sexual, tipificados en el Código Penal y en otras Leyes Especiales. En el Art 31 del capítulo IV de la Ley Especial de Delitos Informáticos, se tipifica la Corrupción de Personas con Discapacidad a través de las TIC, delito que aún no ha sido sometido al control judicial, debido a que, los operadores de justicia desconocen la estructura y clasificación del delito, generando con esto desprotección en las Personas con Discapacidad, ya que, los hechos suelen catalogarse como de atípicos o adecuarse incorrectamente a otros tipos penales. Por los obstáculos indicados, se produce la necesidad de investigar el conocimiento constitucional, legal, doctrinario y convencional, existente sobre este delito, para interpretar y analizar sus elementos, y que esto contribuya a la solución de la problemática planteada. ABSTRACT: In the history of humanity, Persons with Disabilities have been invisible in the different areas of human development, an issue that has made it possible to violate their rights, despite this, in recent years international and state policies have been implemented, with the purpose of enabling the exercise of their rights and protecting them against any threat; as with the creation of the Convention on the Rights of Persons with Disabilities and the approval of the Special Law for Persons with Disabilities; in criminal law, due to their quality of sexually harmless and in order to ensure the normal development of their sexuality, they have been recognized as victims of various crimes of a sexual nature, typified in the Penal Code and in other Special Laws. In ¬Art 31 of Chapter IV of the Special Law on Computer Crimes, the Corruption of Persons with Disabilities through ICTs is typified, a crime that has not yet been subject to judicial control, due to the fact that justice operators are unaware the structure and classification of the crime, generating with this lack of protection in Persons with Disabilities, since the facts are usually classified as atypical or incorrectly adapted to other criminal types. Due to the indicated obstacles, there is a need to investigate the existing constitutional, legal, doctrinal and conventional knowledge about this crime, to interpret and analyze its elements, and that this contributes to the solution of the problem raise

Plan de gestión de los beneficios a empleados, implicaciones financieras y técnicas aplicados en la Sociedad Educativa Salvadoreña Inglesa S.A de C.V. ubicada en el municipio de San Salvador, departamento de San Salvador.

En agosto del año 1983 nace el Colegio Salvadoreño Ingles, gracias a la visión de un Ingeniero Ingles y la Salvadoreña Concepción de Paz, el propósito de ellos fue abrir un colegio totalmente bilingüe en El Salvador que les permitiera a los estudiantes graduarse bilingües. Actualmente se tiene un convenio con la embajada de Cambridge, esto brinda grandes oportunidades a los estudiantes que se gradúan, cómo realizar estudios superiores en el extranjero y garantizar una alta calidad de vida. La investigación surge al momento de la identificación de una serie de factores tales como: la complicada relación entre los colaboradores y la dirección, dado que, no existe un área encargada del plan de implementación adecuado respecto a los beneficios identificables en la normativa técnica y legal salvadoreña. El área de recursos humanos es la encargada de realizar ciertos procesos de selección de personal y contrataciones, sin embargo, no tiene la dedicación y conocimientos respecto a los beneficios cómo el cálculo de los sueldos y salarios, horas extras, bonificaciones, entre otros, dando como resultado errores en los cálculos de las prestaciones a los empleados, falta de comunicación directa a los colaboradores y una alta rotación de personal. El principal objetivo del trabajo es la elaboración de un plan de beneficios a empleados en el Colegio Salvadoreño Ingles para contribuir a la disminución del índice de rotación de capital humano, tomando en cuenta las implicaciones financieras y técnicas que esto requiere. Se utilizó el método científico empleando los procedimientos clave: el análisis y la síntesis, que se llevaron a cabo mediante una entrevista a la directora de la institución, con el fin de II conocer los procedimientos relacionados al cálculo de las remuneraciones de planillas de sueldos y los beneficios de la ley, también se realizó una encuesta a los colaboradores seleccionados a través de una muestra, para recopilar información clave que refleje la situación en que se encuentra actualmente el colegio respecto a los beneficios, la comunicación y la estabilidad laboral. Los instrumentos que se utilizaron para la recopilación de datos fue una guía de entrevista que se realizó vía zoom, y un cuestionario de Google forms proporcionado a los colaboradores vía electrónica. De acuerdo con los resultados obtenidos, el diagnostico determinado es que la institución no brinda beneficios sociales adicionales a los establecidos por la ley, los colaboradores se motivarían más si hubiese novedades en dichos beneficios. Así mismo, se concluye que existen problemas de comunicación entre la dirección y los colaboradores, errores en el cálculo de los beneficios sociales, entre otros. Por lo tanto, se recomienda llevar a cabo la implementación del plan de beneficios a empleados propuesto en el que el personal de contabilidad, recursos humanos y dirección en conjunto hagan uso de procedimientos conforme a las recomendaciones brindadas en el presente trabajo

Tumor-Immune Signatures of Treatment Resistance to Brentuximab Vedotin with Ipilimumab and/or Nivolumab in Hodgkin Lymphoma

To investigate the cellular and molecular mechanisms associated with targeting CD30-expressing Hodgkin lymphoma (HL) and immune checkpoint modulation induced by combination therapies of CTLA4 and PD1, we leveraged Phase 1/2 multicenter open-label trial NCT01896999 that enrolled patients with refractory or relapsed HL (R/R HL). Using peripheral blood, we assessed soluble proteins, cell composition, T-cell clonality, and tumor antigen-specific antibodies in 54 patients enrolled in the phase 1 component of the trial. NCT01896999 reported high (\u3e75%) overall objective response rates with brentuximab vedotin (BV) in combination with ipilimumab (I) and/or nivolumab (N) in patients with R/R HL. We observed a durable increase in soluble PD1 and plasmacytoid dendritic cells as well as decreases in plasma CCL17, ANGPT2, MMP12, IL13, and CXCL13 in N-containing regimens (BV + N and BV + I + N) compared with BV + I (P \u3c 0.05). Nonresponders and patients with short progression-free survival showed elevated CXCL9, CXCL13, CD5, CCL17, adenosine-deaminase, and MUC16 at baseline or after one treatment cycle and a higher prevalence of NY-ESO-1-specific autoantibodies (P \u3c 0.05). The results suggest a circulating tumor-immune-derived signature of BV ± I ± N treatment resistance that may be useful for patient stratification in combination checkpoint therapy. Significance: Identification of multi-omic immune markers from peripheral blood may help elucidate resistance mechanisms to checkpoint inhibitor and antibody-drug conjugate combinations with potential implications for treatment decisions in relapsed HL

Multi-omics Analysis Reveals Immune Features Associated with Immunotherapy Benefit in Patients with Squamous Cell Lung Cancer from Phase III Lung-MAP S1400I Trial

PURPOSE: Identifying molecular and immune features to guide immune checkpoint inhibitor (ICI)-based regimens remains an unmet clinical need. EXPERIMENTAL DESIGN: Tissue and longitudinal blood specimens from phase III trial S1400I in patients with metastatic squamous non-small cell carcinoma (SqNSCLC) treated with nivolumab monotherapy (nivo) or nivolumab plus ipilimumab (nivo+ipi) were subjected to multi-omics analyses including multiplex immunofluorescence (mIF), nCounter PanCancer Immune Profiling Panel, whole-exome sequencing, and Olink. RESULTS: Higher immune scores from immune gene expression profiling or immune cell infiltration by mIF were associated with response to ICIs and improved survival, except regulatory T cells, which were associated with worse overall survival (OS) for patients receiving nivo+ipi. Immune cell density and closer proximity of CD8+GZB+ T cells to malignant cells were associated with superior progression-free survival and OS. The cold immune landscape of NSCLC was associated with a higher level of chromosomal copy-number variation (CNV) burden. Patients with LRP1B-mutant tumors had a shorter survival than patients with LRP1B-wild-type tumors. Olink assays revealed soluble proteins such as LAMP3 increased in responders while IL6 and CXCL13 increased in nonresponders. Upregulation of serum CXCL13, MMP12, CSF-1, and IL8 were associated with worse survival before radiologic progression. CONCLUSIONS: The frequency, distribution, and clustering of immune cells relative to malignant ones can impact ICI efficacy in patients with SqNSCLC. High CNV burden may contribute to the cold immune microenvironment. Soluble inflammation/immune-related proteins in the blood have the potential to monitor therapeutic benefit from ICI treatment in patients with SqNSCLC

Metabolic and Growth Rate Alterations in Lymphoblastic Cell Lines Discriminate between Down Syndrome and Alzheimer's Disease

Deficits in mitochondrial function and oxidative stress play pivotal roles in Down syndrome (DS) and Alzheimer's disease (AD) and these alterations in mitochondria occur systemically in both conditions. Objective: We hypothesized that peripheral cells of elder subjects with DS exhibit disease-specific and dementia-specific metabolic features. To test this, we performed a comprehensive analysis of energy metabolism in lymphoblastic-cell-lines (LCLs) derived from subjects belonging to four groups: DS-with-dementia (DSAD), DS-without-dementia (DS), sporadic AD, and age-matched controls. Methods: LCLs were studied under regular or minimal feeding regimes with galactose or glucose as primary carbohydrate sources. We assessed metabolism under glycolysis or oxidative phosphorylation by quantifying cell viability, oxidative stress, ATP levels, mitochondrial membrane potential (MMP), mitochondrial calcium uptake, and autophagy. DS and DSAD LCLs showed slower growth rates under minimal feeding. DS LCLs mainly dependent on mitochondrial respiration exhibited significantly slower growth and higher levels of oxidative stress compared to other groups. While ATP levels (under mitochondrial inhibitors) and mitochondrial calcium uptake were significantly reduced in DSAD and AD cells, MMP was decreased in DS, DSAD, and AD LCLs. Finally, DS LCLs showed markedly reduced levels of the autophagy marker LC3-II, underscoring the close association between metabolic dysfunction and impaired autophagy in DS. Conclusion: There are significant mitochondrial functional changes in LCLs derived from DS, DSAD, and AD patients. Several parameters analyzed were consistently different between DS, DSAD, and AD lines suggesting that metabolic indicators between LCL groups may be utilized as biomarkers of disease progression and/or treatment outcomes.Fil: Coskun, Pinar. University of California at Irvine; Estados UnidosFil: Helguera, Pablo Rodolfo. University of California at Irvine; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Nemati, Zahra. University of California at Irvine; Estados UnidosFil: Bohannan, Ryan C.. University of California at Irvine; Estados UnidosFil: Thomas, Jean. University of California at Irvine; Estados UnidosFil: Samuel, Schriner E.. University of California at Irvine; Estados UnidosFil: Argueta, Jocelyn. University of California at Irvine; Estados UnidosFil: Doran, Eric. University of California at Irvine; Estados UnidosFil: Wallace, Douglas C.. University of Pennsylvania; Estados UnidosFil: Lott, Ira T.. University of California at Irvine; Estados UnidosFil: Busciglio, Jorge. University of California at Irvine; Estados Unido

Implantable niche with local immunosuppression for islet allotransplantation achieves type 1 diabetes reversal in rats

Islet transplantation for type 1 diabetes management is hindered by the life-long need for immunosuppressive medications. Here, the authors report an islet encapsulation device with local anti-rejection drug release that achieves long-term diabetes reversal in male rats and reduces drug-related toxicity

Multi-omics Analysis Reveals Immune Features Associated with Immunotherapy Benefit in Patients with Squamous Cell Lung Cancer from Phase III Lung-MAP S1400I Trial.

PURPOSE: Identifying molecular and immune features to guide immune checkpoint inhibitor (ICI)-based regimens remains an unmet clinical need. EXPERIMENTAL DESIGN: Tissue and longitudinal blood specimens from phase III trial S1400I in patients with metastatic squamous non-small cell carcinoma (SqNSCLC) treated with nivolumab monotherapy (nivo) or nivolumab plus ipilimumab (nivo+ipi) were subjected to multi-omics analyses including multiplex immunofluorescence (mIF), nCounter PanCancer Immune Profiling Panel, whole-exome sequencing, and Olink. RESULTS: Higher immune scores from immune gene expression profiling or immune cell infiltration by mIF were associated with response to ICIs and improved survival, except regulatory T cells, which were associated with worse overall survival (OS) for patients receiving nivo+ipi. Immune cell density and closer proximity of CD8+GZB+ T cells to malignant cells were associated with superior progression-free survival and OS. The cold immune landscape of NSCLC was associated with a higher level of chromosomal copy-number variation (CNV) burden. Patients with LRP1B-mutant tumors had a shorter survival than patients with LRP1B-wild-type tumors. Olink assays revealed soluble proteins such as LAMP3 increased in responders while IL6 and CXCL13 increased in nonresponders. Upregulation of serum CXCL13, MMP12, CSF-1, and IL8 were associated with worse survival before radiologic progression. CONCLUSIONS: The frequency, distribution, and clustering of immune cells relative to malignant ones can impact ICI efficacy in patients with SqNSCLC. High CNV burden may contribute to the cold immune microenvironment. Soluble inflammation/immune-related proteins in the blood have the potential to monitor therapeutic benefit from ICI treatment in patients with SqNSCLC