Rectus Femoris Muscle and Phase Angle as Prognostic Factor for 12-Month Mortality in a Longitudinal Cohort of Patients with Cancer (AnyVida Trial)

Background: Cancer-related malnutrition is still unrecognized and undertreated in clinical practice. The morphofunctional assessment of disease-related malnutrition (DRM) is a new approach that focuses on evaluating changes in body composition and function. The aim of this study is to evaluate the prognostic value of classic and emerging assessment of malnutrition at 12-months survival in cancer patients. Methods. We conducted a prospective study on cancer outpatients. Bioelectrical impedance with phase angle (PhA), nutritional ultrasound by rectus femoris cross-sectional area (RFCSA), hand grip strength, and “Timed Up and Go Test” (TUG) were evaluated as predictors of mortality. Results. Fifty-seven patients were included. The non-survivors had lower PhA values than the survivors (4.7° vs. 5.4°; p < 0.001), and we had the same results with RFCSA 2.98 cm2/m2 vs. 4.27 cm2/m2 (p = 0.03). Cut-off points were identified using the ROC (receiver operating characteristic) curves for PhA (≤5.6° cancer patients, ≤5.9° men, ≤5.3° women), RFCSA (≤4.47 cm2/m2 cancer patients, ≤4.47° men, ≤2.73° women) and rectus femoris-Y-axis (RF-Y-axis; ≤1.3 cm cancer patients, ≤1.06 men, ≤1 women). In multivariate logistic regression analysis, we found that high PhA was significantly associated with a lower mortality hazard ratio (HR: 0.42 95% CI: 0.21–0.84, p = 0.014). Likewise, high RFCSA was associated with a decrease in mortality risk in the crude model (HR: 0.61 95% CI: 0.39–0.96, p = 0.031). This trend was also maintained in the adjusted models by the confounding variables. Conclusions. Low PhA and RFCSA values are significant independent predictors of mortality in cancer patients. These cut-off points are clinical data that can be used for nutritional assessment and the prediction of clinical outcomes.This study is part of a Ph.D. Program in Biomedicine, Translational Research, and New Health Technologies in the Faculty of Medicine of the University of Málaga in Spain. The Andalusian Public Foundation for Biomedical Research in Malaga (FIMABIS) covered the publication cost. This study was also supported by the Juan Rodés program from Instituto de Salud Carlos III (JR20-00040 to MM-V), the Juan de la Cierva program from the Ministerio de Ciencia e Innovación (IJCI-2017-33065 to CG-R) and the Miguel Servet Type I program from the Instituto de Salud Carlos III cofounded by the Fondo Europeo de Desarrollo Regional (CP16/00163 to IM-I). In addition, this study was supported by the “Centros de Investigación Biomédica en Red” (CIBERobn) of the Instituto de Salud Carlos III (ISCIII) (CB06/03/0018), and research grants from the ISCIII (PI18/01160; PI21/01677) and co-financed by the European Regional Development Fund (ERDF). Partial funding for open access charge: Universidad de Málag

Predictors of Sarcopenia in Outpatients with Post-Critical SARS-CoV2 Disease. Nutritional Ultrasound of Rectus Femoris Muscle, a Potential Tool

Background and Objectives: The loss of muscle mass in post-critical COVID-19 outpatients is difficult to assess due to the limitations of techniques and the high prevalence of obesity. Ultrasound is an emerging technique for evaluating body composition. The aim is to evaluate sarcopenia and its risk factors, determining ultrasound usefulness as a potential tool for this purpose according to established techniques, such as the bioimpedance vector analysis (BIVA), handgrip strength, and timed up-and-go test. Methods: This is a transversal study of 30 post-critical COVID-19 outpatients. We evaluated nutritional status by ultrasound (Rectus Femoris-cross-sectional-area (RF-CSA), thickness, and subcutaneous-adipose-tissue), BIVA, handgrip strength, timed up-and-go test, and clinical variables during admission. Results: According to The European Society for Clinical Nutrition and Metabolism and the European Association for the Study of Obesity (ESPEN&EASO) Consensus for Sarcopenic and Obesity, in terms of excess fat mass and decreased lean mass, the prevalence of class-1 sarcopenic obesity was 23.4% (n = 7), and class-2 sarcopenic obesity was 33.3% (n = 10) in our study. A total of 46.7% (n = 14) of patients had a handgrip strength below the 10th percentile, and 30% (n = 9) achieved a time greater than 10s in the timed up-and-go test. There were strong correlations between the different techniques that evaluated the morphological (BIVA, Ultrasound) and functional measurements of muscle. Intensive care unit stay, mechanical ventilation, and age all conditioned the presence of sarcopenia in COVID-19 outpatients (R2 = 0.488, p = 0.002). Predictive models for sarcopenic diagnosis based on a skeletal muscle index estimation were established by RF-CSA (R2 0.792, standard error of estimate (SEE) 1.10, p < 0.001), muscle-thickness (R2 0.774, SEE 1.14, p < 0.001), and handgrip strength (R2 0.856, SEE 0.92, p < 0.001). RF-CSA/weight of 5.3 cm2/kg × 100 (...)I.C.-P. was the recipient of a postdoctoral grant (Río Hortega CM 17/00169) and is now the recipient of a postdoctoral grant (Juan Rodes JR 19/00054) from the Instituto de Salud Carlos III and co-funded by Fondo Europeo de Desarrollo Regional-FEDER. Partial funding for open access charge: Universidad de Málag

Antimicrobial activity of Myrtus communis l. and Rosmarinus officinalis l. essential oils against listeria monocytogenes in cheese

Listeria monocytogenes has been referred to as a concern microorganism in cheese making due to its ability to survive and grow in a wide range of environmental conditions, such as refrigeration temperatures, low pH and high salt concentration at the end of the production process. Since cheese may be a potential hazard for consumers, especially high-risk consumers (e.g., pregnant, young children, the elderly, people with medical conditions), efforts of the dairy industry have been aimed at investigating new conservation techniques based on natural additives to meet consumers’ demands on less processed foods without compromising the food safety. Thus, the aim of this study was to evaluate the efficacy of Myrtus communis L. (myrtle) and Rosmarinus officinalis L. (rosemary) essential oils (EO) against Listeria monocytogenes ATCC 679 spiked in sheep cheese before ripening. After the cheesemaking process, the samples were stored at 8 C for 2 h, 1 d, 3 d, 14 d and 28 d. The composition of EO was identified by gas chromatography-mass spectrometry (GC-MS) analysis. Constituents such as 1,8-cineole, limonene, methyl-eugenol, -pinene, -terpineol, -terpinolene and -pinene were present in both EO, accounting for 44.61% and 39.76% from the total of chemical compounds identified for myrtle and rosemary EO, respectively. According to the chemical classification, both EO were mainly composed of monoterpenes. Minimum inhibitory concentration (MIC) against L. monocytogenes was obtained at 31.25 L/mL to myrtle EO and at 0.40 L/mL to rosemary EO. Then, cheeses were inoculated with L. monocytogenes (Ca. 6 log CFU/mL) and EO was added at MIC value. The addition of rosemary and myrtle EO displayed lower counts of L. monocytogenes (p < 0.01) (about 1–2 log CFU/g) during the ripening period compared to control samples. Ripening only influences (p < 0.001) the growth of L. monocytogenes in control samples. Since rosemary and myrtle EO do not exert any negative impact on the growth of native microflora (p > 0.05), their use as natural antimicrobial additives in cheese demonstrated a potential for dairy processors to assure safety against L. monocytogenes.The Fundação para a Ciência e Tecnologia (FCT).https://www.mdpi.com/journal/foodsParaclinical Science

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO

Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy

We measure the energy emitted by extensive air showers in the form of radio emission in the frequency range from 30 to 80 MHz. Exploiting the accurate energy scale of the Pierre Auger Observatory, we obtain a radiation energy of 15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV arriving perpendicularly to a geomagnetic field of 0.24 G, scaling quadratically with the cosmic-ray energy. A comparison with predictions from state-of-the-art first-principle calculations shows agreement with our measurement. The radiation energy provides direct access to the calorimetric energy in the electromagnetic cascade of extensive air showers. Comparison with our result thus allows the direct calibration of any cosmic-ray radio detector against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI. Supplemental material in the ancillary file

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER), "A way of making Europe".Copy number (CN) polymorphisms of complement C4 play distinct roles in many conditions, including immune-mediated diseases. We investigated the association of C4 CN with systemic sclerosis (SSc) risk. Imputed total C4, C4A, C4B, and HERV-K CN were analyzed in 26,633 individuals and validated in an independent cohort. Our results showed that higher C4 CN confers protection to SSc, and deviations from CN parity of C4A and C4B augmented risk. The protection contributed per copy of C4A and C4B differed by sex. Stronger protection was afforded by C4A in men and by C4B in women. C4 CN correlated well with its gene expression and serum protein levels, and less C4 was detected for both in SSc patients. Conditioned analysis suggests that C4 genetics strongly contributes to the SSc association within the major histocompatibility complex locus and highlights classical alleles and amino acid variants of HLA-DRB1 and HLA-DPB1 as C4-independent signals

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe