Effect of whole-body vibration stimulation on plasma soluble TNF receptors in elderly with sarcopenia: a randomized controlled trial.

Sarcopenia is a pathology resulting from a progressive and severe loss of muscle mass, strength, and function in the course of aging, which has deleterious consequences on quality of life. Among the most widespread studies on the issue are those focused on the effect of different types of physical exercise on patients with sarcopenia. This randomized controlled study aimed to compare the effects of a whole-body vibration exercise (WBV) session on the inflammatory parameters of non-sarcopenic (NSG, n=22) and sarcopenic elderly (SG, n=22). NSG and SG participants were randomly divided into two protocols: intervention (squat with WBV) and control (squat without WBV). After a one-week washout period, participants switched protocols, so that everyone performed both protocols. Body composition was assessed by dual-energy radiological absorptiometry (DXA) and function through the six-minute walk test (6MWD) and Short Physical Performance Battery (SPPB). Plasma soluble tumor necrosis factor receptors (sTNFR) were determined by enzyme-linked immunosorbent assay (ELISA) and measured before and immediately after each protocol. After exercise with WBV, there was an increase in sTNFR2 levels in the NSG (P<0.01; d=-0.69 (-1.30; -0.08) and SG (P<0.01, d=-0.95 (-1.57; -0.32) groups. In conclusion, an acute session of WBV influenced sTNFr2 levels, with sarcopenic individuals showing a greater effect. This suggested that WBV had a more pronounced impact on sTNFr2 in those with loss of muscle strength and/or physical performance. Additionally, WBV is gaining recognition as an efficient strategy for those with persistent health issues.

Performance in prognostic capacity and efficiency of the Thoracic Care Suite GE AI tool applied to chest radiography of patients with COVID-19 pneumonia.

OBJECTIVE: Rapid progression of COVID-19 pneumonia may put patients at risk of requiring ventilatory support, such as non-invasive mechanical ventilation or endotracheal intubation. Implementing tools that detect COVID-19 pneumonia can improve the patient's healthcare. We aim to evaluate the efficacy and efficiency of the artificial intelligence (AI) tool GE Healthcare's Thoracic Care Suite (featuring Lunit INSIGHT CXR, TCS) to predict the ventilatory support need based on pneumonic progression of COVID-19 on consecutive chest X-rays. METHODS: Outpatients with confirmed SARS-CoV-2 infection, with chest X-ray (CXR) findings probable or indeterminate for COVID-19 pneumonia, who required a second CXR due to unfavorableclinical course, were collected. The number of affected lung fields for the two CXRs was assessed using the AI tool. RESULTS: One hundred fourteen patients (57.4±14.2 years, 65-57%-men) were retrospectively collected. Fifteen (13.2%) required ventilatory support. Progression of pneumonic extension ≥0.5 lung fields per day compared to pneumonia onset, detected using the TCS tool, increased the risk of requiring ventilatory support by 4-fold. Analyzing the AI output required 26s of radiological time. CONCLUSIONS: Applying the AI tool, Thoracic Care Suite, to CXR of patients with COVID-19 pneumonia allows us to anticipate ventilatory support requirements requiring less than half a minute.

Inter-observer agreement on levels of evidence in radiology articles.

Levels of evidence (LE) are established through a hierarchical classification of studies according to their design. At present, there are many heterogeneous LE classifications, and this hampers their applicability. Our study aims to identify which LE classification has the best interobserver concordance for radiology articles. For this purpose, an interobserver agreement analysis were performed on 105 original articles applying two NE scales (Oxford Center of Evidence Based Medicine (OCEBM) y National Health and Medical Research Council (NHMRC)). The inter-rater agreement of the LE assigned after reading the abstracts was good when using the OCEBM scale (K = 0.679), and somewhat lower with the NHMRC (K = 0.577 -moderate-). All differences were statistically significant (P < .000). So, in conclusion, of the two scales analysed (OCEBM and NHMRC), the OCEBM led to the strongest level of inter-rater agreement.

Boosting cytotoxicity of adoptive allogeneic NK cell therapy with an oncolytic adenovirus encoding a human vIL-2 cytokine for the treatment of human ovarian cancer.

Despite good results in the treatment of hematological malignancies, Natural killer (NK) cells have shown limited effectiveness in solid tumors, such as ovarian cancer (OvCa). Here, we assessed the potential of an oncolytic adenovirus expressing a variant interleukin-2 (vIL-2) cytokine, Ad5/3-E2F-d24-vIL2 (vIL-2 virus), also known as TILT-452, to enhance NK cell therapy efficacy in human OvCa ex vivo. Human OvCa surgical specimens were processed into single-cell suspensions and NK cells were expanded from healthy blood donors. OvCa sample digests were co-cultured ex vivo with NK cells and vIL-2 virus and cancer cell killing potential assessed in real time through cell impedance measurement. Proposed therapeutic combination was evaluated in vivo with an OvCa patient-derived xenograft (PDX) in mice. Addition of vIL-2 virus significantly enhanced NK cell therapy killing potential in treated OvCa co-cultures. Similarly, vIL-2 virus in combination with NK cell therapy promoted the best in vivo OvCa tumor control. Mechanistically, vIL-2 virus induced higher percentages of granzyme B in NK cells, and CD8+ T cells, while T regulatory cell proportions remained comparable to NK cell monotherapy in vivo. Ad5/3-E2F-d24-vIL2 virus treatment represents a promising strategy to boost adoptive NK cell therapeutic effect in human OvCa.

Improving the cytotoxic response of tumor-infiltrating lymphocytes towards advanced stage ovarian cancer with an oncolytic adenovirus expressing a human vIL-2 cytokine.

While the presence of tumor-infiltrating lymphocytes (TILs) associates with improved survival prognosis in ovarian cancer (OvCa) patients, TIL therapy benefit is limited. Here, we evaluated an oncolytic adenovirus coding for a human variant IL-2 (vIL-2) cytokine, Ad5/3-E2F-d24-vIL2 (vIL-2 virus), also known as TILT-452, as an immunotherapeutic strategy to enhance TIL responsiveness towards advanced stage OvCa tumors. Fragments of resected human OvCa tumors were processed into single-cell suspensions, and autologous TILs were expanded from said samples. OvCa tumor specimens were co-cultured with TILs plus vIL-2 virus, and cell killing was assessed in real time through cell impedance measurement. Combination therapy was further evaluated in vivo through a patient-derived xenograft (PDX) ovarian cancer murine model. The combination of vIL-2 virus plus TILs had best cancer cell killing ex vivo compared to TILs monotherapy. These results were supported by an in vivo experiment, where the best OvCa tumor control was obtained when vIL-2 virus was added to TIL therapy. Furthermore, the proposed therapy induced a highly cytotoxic phenotype demonstrated by increased granzyme B intensity in NK cells, CD4+ T, and CD8+ T cells in treated tumors. Our results demonstrate that Ad5/3-E2F-d24-vIL2 therapy consistently improved TILs therapy cytotoxicity in treated human OvCa tumors.

[Impact of days elapsed from the onset of symptoms to hospitalization in COVID-19 in-hospital mortality: Time matters]. / Impacto de los días transcurridos desde el inicio de los síntomas hasta la hospitalización en la mortalidad hospitalaria por COVID-19: el tiempo importa.

Background: COVID-19 shows different clinical and pathophysiological stages over time. Theeffect of days elapsed from the onset of symptoms (DEOS) to hospitalization on COVID-19prognostic factors remains uncertain. We analyzed the impact on mortality of DEOS to hospital-ization and how other independent prognostic factors perform when taking this time elapsedinto account. Methods: This retrospective, nationwide cohort study, included patients with confirmed COVID-19 from February 20th and May 6th, 2020. The data was collected in a standardized online datacapture registry. Univariate and multivariate COX-regression were performed in the generalcohort and the final multivariate model was subjected to a sensitivity analysis in an earlypresenting (EP; < 5 DEOS) and late presenting (LP; ≥5 DEOS) group. Results: 7915 COVID-19 patients were included in the analysis, 2324 in the EP and 5591 in theLP group. DEOS to hospitalization was an independent prognostic factor of in-hospital mortalityin the multivariate Cox regression model along with other 9 variables. Each DEOS incrementaccounted for a 4.3% mortality risk reduction (HR 0.957; 95% CI 0.93---0.98). Regarding variationsin other mortality predictors in the sensitivity analysis, the Charlson Comorbidity Index onlyremained significant in the EP group while D-dimer only remained significant in the LP group. Conclusion: When caring for COVID-19 patients, DEOS to hospitalization should be consideredas their need for early hospitalization confers a higher risk of mortality. Different prognosticfactors vary over time and should be studied within a fixed timeframe of the disease.

Impact of days elapsed from the onset of symptoms to hospitalization in COVID-19 in-hospital mortality: time matters.

BACKGROUND: COVID-19 shows different clinical and pathophysiological stages over time. The effect of days elapsed from the onset of symptoms (DEOS) to hospitalization on COVID-19 prognostic factors remains uncertain. We analyzed the impact on mortality of DEOS to hospitalization and how other independent prognostic factors perform when taking this time elapsed into account. METHODS: This retrospective, nationwide cohort study, included patients with confirmed COVID-19 from February 20th and May 6th, 2020. The data was collected in a standardized online data capture registry. Univariate and multivariate COX-regression were performed in the general cohort and the final multivariate model was subjected to a sensitivity analysis in an early presenting (EP; <5 DEOS) and late presenting (LP; ≥5 DEOS) group. RESULTS: 7915 COVID-19 patients were included in the analysis, 2324 in the EP and 5591 in the LP group. DEOS to hospitalization was an independent prognostic factor of in-hospital mortality in the multivariate Cox regression model along with other 9 variables. Each DEOS increment accounted for a 4.3% mortality risk reduction (HR 0.957; 95% CI 0.93-0.98). Regarding variations in other mortality predictors in the sensitivity analysis, the Charlson Comorbidity Index only remained significant in the EP group while D-dimer only remained significant in the LP group. CONCLUSION: When caring for COVID-19 patients, DEOS to hospitalization should be considered as their need for early hospitalization confers a higher risk of mortality. Different prognostic factors vary over time and should be studied within a fixed timeframe of the disease.

Cold thermopeaking-induced drift of nase Chondrostoma nasus larvae.

Research on how intermittent water releases from hydropower plants affect the early life stages of fish has advanced in the last years, focusing not only on the direct impacts of rapid flow changes (hydropeaking), but also on the short-term fluctuations in water temperature (thermopeaking). Flow and thermal fluctuations caused by hydropeaking may affect fish movement patterns and migration at critical stages of a species' life cycle, e.g., by inducing passive downstream drift. Using two experimental outdoor channels, we investigated how nase (Chondrostoma nasus, Cypriniformes) larvae respond to a rapid drop in water temperature during hydropeaking (simulating a cold thermopeaking event), reaching on average 5.5 °C under peak flow (maximum discharge) conditions, in comparison with a hydropeaking treatment with a constant water temperature regime. Responses of fish larvae were analyzed during acclimation, up-ramping (increase in discharge), peak flow and down-ramping (decrease in discharge) phases. Fish drift increased during peak flow in the cold thermopeaking treatment compared to hydropeaking. Higher drift rates were also negatively associated with pronounced water temperature drops during peak flow conditions. In addition, the starting temperature of the experiment influenced drift during up-ramping. Overall, the results suggest that cold thermopeaking may increase drift in the early life stages of cypriniform fish compared with hydropeaking with stable water temperature. Hence, monitoring and active water temperature adjustments following hydropower releases should be adopted as strategies to mitigate power plant-related impacts on aquatic organisms. Supplementary Information: The online version contains supplementary material available at 10.1007/s00027-023-00955-x.

Evaluation of the Impact of Exposure To Heat and to By-Products of Combustion on the Health of Firefighters.

Firefighters are often exposed to high temperatures and by-products of combustion, which can affect their health. In this study, we assessed the impact of acute exposure of firefighters in fire simulators. Twenty male firefighters were exposed to fire simulators, and observed in four phases: pre-exposure (group 0, control) and after the end of the first (group 1), second (group 2), and fourth (group 3) weeks of training. Blood samples were collected and dosed to evaluate the response of the immune, inflammatory (C-reactive protein, IL6, and IL10), and endocrine systems (cortisone, total testosterone, free testosterone, SHBG, bioavailable testosterone, TSH, and free T4). In groups 0, 1, and 3, a thermographic evaluation was also carried out to study the temperature and body heat flow of the participants. Regarding the inflammatory process, an increase in C-reactive protein and a reduction in IL-10 were observed. With respect to hormonal markers, an increase in cortisol and reduced levels of free T4 and bioavailable testosterone were found after exposure, with recovery of testosterone levels in the final week of training. Thermoregulatory adaptation of the organism has been associated with changes in heat flow in the organism in people subjected to extreme temperatures, with emphasis on the performance of the lower limbs. Our findings demonstrate an inflammatory response with hormonal changes after exposure to fire and an adaptive response of thermal balance, which could aid understanding of the physiology of the human body in extreme situations.

Les sapeurs-pompiers (SP) sont régulièrement exposés à la chaleur et aux produits de combustion, qui peuvent avoir un retentissement sur leur santé. Nous avons évalué l'effet d'une exposition aiguë de 22 SP (tous des hommes) à incendie simulé grâce à la répétition à 4 reprises d'une même batterie d'examens (avant- T0, et à la fin des 1ère -T1 2ème - T2 et 3ème - T3 semaines d'entraînement). Des paramètres sanguins relatifs à l'inflammation et l'immunité (CRP, IL6, IL10) ainsi qu'au système endocrinien (cortisol, testostérones totale, libre et biodisponible, SHBG, TSH et T4 libre) étaient prélevés à chaque évaluation. Une étude thermographique, évaluant la température corporelle et le flux thermique corporel était réalisée à T0, T1 et T3. On constatait une augmentation de la CRP et une baisse de IL10. On observait une augmentation de la cortisolémie ainsi qu'une baisse de thyroxine libre et testostérone biodisponible, cette dernière se normalisant à T3. L'adaptation corporelle à la chaleur se traduit par une augmentation du flux thermique, en particulier aux membres inférieurs. Nous observons donc des réponses inflammatoire comme endocrinienne et une adaptation de la thermorégulation en cas d'exposition à un incendie, constatations pouvant contribuer à la compréhension de la physiologie humaine en situations extrêmes.

Histopathological Features of Pendred Syndrome Thyroids Align with Differences in the Expression of Thyroid-Specific Markers, Apical Iodide Transporters, and Ciliogenesis Process.

Pendred syndrome (PDS) is an autosomal recessive disorder caused by mutations in the gene that encodes pendrin. Pendred thyroid tissue is supposedly altered by the absence of functional pendrin, but it is still unknown whether other iodide exchangers could compensate for the loss of the protein. Moreover, we have recently described that primary cilium, a conserved structure present at the apical surface of normal follicular cells, suffers different alterations in functional thyroid diseases. We aimed (1) to better understand the histopathological changes experienced by PDS thyroids, (2) to analyze the expression of different thyroid-specific genes and alternative iodide transporters and, finally, (3) to determine whether those changes may alter the morphological pattern of primary cilia in follicular cells. Thyroid samples from a series of four PDS patients were analyzed by immunohistochemistry, double immunofluorescence, and morphometry to evaluate changes in primary cilia frequency and length. We found thyroid follicular nodular disease in all PDS thyroids, frequently in association with follicular adenomas. There were only slight changes in the expression of thyroid-specific markers. Although no positivity for pendrin was found, cytoplasmic immunostaining for ANO-1, CLC-5, and CFTR was stronger in diffuse hyperplastic areas when compared to areas with highly cellular follicular nodules (HCFNs). HCFNs and follicular adenomas always showed diminished ciliary frequency and length. Our results suggest a direct relationship between the absence of functional pendrin and the loss of the normal thyroid architecture in PDS patients, which was also accompanied by differences in the expression of specific immunohistochemical markers and altered ciliogenesis. The present data may help the pathologist in screening for PDS.

The relationship between academics' strategic research agendas and their preferences for basic research, applied research, or experimental development.

In this study, we assess the association between academics' research agendas and their preferences for basic research, applied research, or experimental development. Using a sample of Mexican academics working in some of the country's most research-oriented universities, we identify three clusters. The largest is composed of applied research-oriented academics, the second largest is composed of basic research-oriented academics, and the smallest is composed of academics who engage in both basic and applied research, and experimental development. The strategic research agendas of the three clusters are distinguished from each other along four main dimensions: Divergence, Discovery, Mentor Influence, and Social Orientation. These findings show that strategic research agendas are associated with preferences for basic research, applied research, or experimental development, but only to some extent. We also extend the Multi-Dimensional Research Agendas Inventory - Revised, a widely used instrument for measuring strategic research agendas, by adding a new dimension, "Government," and validating the instrument in a new context. We also make the scale available in Spanish for use by academics, practitioners, managers, and administrators in Spanish-speaking countries.

Radiology volunteers to support a breast cancer screening program in Peru: Description of the project, preliminary results, and impressions.

Breast cancer is the second most common cancer in Peruvian women. Due to limitations in national breast cancer screening programs, especially in rural areas, more than 50% of cases of breast cancer in Peru are diagnosed in advanced stages. In collaboration with a local clinic registered as a nongovernmental organization (CerviCusco), RAD-AID International aims to create a sustainable diagnostic structure to improve breast cancer screening in Cuzco. With the support of local, national, and international partners that have collaborated in analyzing radiological resources, raising awareness in the population, acquiring equipment, training clinical staff, and building referral networks, our teams of radiologists, included in the RAD-AID team, have participated in training CerviCusco staff in breast ultrasound, thus enabling additional training for radiology residents through a regulated international collaboration.

Influence of environmental variability and Emiliania huxleyi ecotypes on alkenone-derived temperature reconstructions in the subantarctic Southern Ocean.

Long-chain unsaturated alkenones produced by haptophyte algae are widely used as paleotemperature indicators. The unsaturation relationship to temperature is linear at mid-latitudes, however, non-linear responses detected in subpolar regions of both hemispheres have suggested complicating factors in these environments. To assess the influence of biotic and abiotic factors in alkenone production and preservation in the Subantarctic Zone, alkenone fluxes were quantified in three vertically-moored sediment traps deployed at the SOTS observatory (140°E, 47°S) during a year. Alkenone fluxes were compared with coccolithophore assemblages, satellite measurements and surface-water properties obtained by sensors at SOTS. Alkenone-based temperature reconstructions generally mirrored the seasonal variations of SSTs, except for late winter when significant deviations were observed (3-10 °C). Annual flux-weighted averages in the 3800 m trap returned alkenone-derived temperatures ~1.5 °C warmer than those derived from the 1000 m trap, a distortion attributed to surface production and signal preservation during its transit through the water column. Notably, changes in the relative abundance of E. huxleyi var. huxleyi were positively correlated with temperature deviations between the alkenone-derived temperatures and in situ SSTs (r = 0.6 and 0.7 at 1000 and 2000 m, respectively), while E. huxleyi var. aurorae, displayed an opposite trend. Our results suggest that E. huxleyi var. aurorae produces a higher proportion of C37:3 relative to C37:2 compared to its counterparts. Therefore, the dominance of var. aurorae south of the Subtropical Front could be at least partially responsible for the less accurate alkenone-based SST reconstructions in the Southern Ocean using global calibrations. However, the observed correlations were largely influenced by the samples collected during winter, a period characterized by low particle fluxes and slow sinking rates. Thus, it is likely that other factors such as selective degradation of the most unsaturated alkenones could also account for the deviations of the alkenone paleothermometer.

Nonlinear optical conductivity of a two-band crystal I.

The structure of the electronic nonlinear optical conductivity is elucidated in a detailed study of the time-reversal symmetric two-band model. The nonlinear conductivity is decomposed as a sum of contributions related with different regions of the first Brillouin zone, defined by single or multiphoton resonances. All contributions are written in terms of the same integrals, which contain all information specific to the particular model under study. In this way, ready-to-use formulas are provided that reduce the often tedious calculations of the second and third order optical conductivity to the evaluation of a small set of similar integrals. In the scenario where charge carriers are present prior to optical excitation, Fermi surface contributions must also be considered and are shown to have an universal frequency dependence, tunable by doping. General characteristics are made evident in this type of resonance-based analysis: the existence of step functions that determine the chemical potential dependence of electron-hole symmetric insulators; the determination of the imaginary part by Hilbert transforms, simpler than those of the nonlinear Kramers-Krönig relations; the absence of Drude peaks in the diagonal elements of the second order conductivity, among others. As examples, analytical expressions are derived for the nonlinear conductivities of some simple systems: a very basic model of direct gap semiconductors and the Dirac fermions of monolayer graphene.