Mediation effect of body mass index on the association between serum magnesium level and insulin resistance in children from Mexico City.

BACKGROUND/OBJECTIVES: Reduced serum magnesium (Mg) levels have been associated with obesity, insulin resistance (IR), type 2 diabetes, and metabolic syndrome in adults. However, in the children population, the evidence is still limited. In this cross-sectional study, we aimed to analyze the association of serum Mg levels with the frequency of overweight and obesity and cardiometabolic traits in 189 schoolchildren (91 girls and 98 boys) between 6 and 12 years old from Mexico City. SUBJECTS/METHODS: Anthropometrical data were collected and biochemical parameters were measured by enzymatic colorimetric assay. Serum Mg level was analyzed by inductively coupled plasma mass spectrometry (ICP-MS). The triglyceride-glucose (TyG) index was used as a surrogate marker to evaluate IR. RESULTS: Serum Mg level was negatively associated with overweight (Odds ratio [OR] = 0.377, 95% confidence interval [CI] 0.231-0.614, p < 0.001) and obesity (OR = 0.345, 95% CI 0.202-0.589, p < 0.001). Serum Mg level resulted negatively associated with body mass index (BMI, ß = -1.16 ± 0.26, p < 0.001), BMI z-score (ß = -0.48 ± 0.10, p < 0.001) and TyG index (ß = -0.04 ± 0.04, p = 0.041). Through a mediation analysis was estimated that BMI z-score accounts for 60.5% of the negative association of serum Mg level with IR (Sobel test: z = 2.761; p = 0.005). CONCLUSION: Our results evidence that BMI z-score mediate part of the negative association of serum Mg level and IR in Mexican schoolchildren.

Retromer-mediated recruitment of the WASH complex involves discrete interactions between VPS35, VPS29, and FAM21.

Endosomal trafficking ensures the proper distribution of lipids and proteins to various cellular compartments, facilitating intracellular communication, nutrient transport, waste disposal, and the maintenance of cell structure. Retromer, a peripheral membrane protein complex, plays an important role in this process by recruiting the associated actin-polymerizing WASH complex to establish distinct sorting domains. The WASH complex is recruited through the interaction of the VPS35 subunit of retromer with the WASH complex subunit FAM21. Here, we report the identification of two separate fragments of FAM21 that interact with VPS35, along with a third fragment that binds to the VPS29 subunit of retromer. The crystal structure of VPS29 bound to a peptide derived from FAM21 shows a distinctive sharp bend that inserts into a conserved hydrophobic pocket with a binding mode similar to that adopted by other VPS29 effectors. Interestingly, despite the network of interactions between FAM21 and retromer occurring near the Parkinson's disease-linked mutation (D620N) in VPS35, this mutation does not significantly impair the direct association with FAM21 in vitro.

Obesity Is Associated with Oxidative Stress Markers and Antioxidant Enzyme Activity in Mexican Children.

The relationship between metabolic disorders and oxidative stress is still controversial in the child population. The present cross-sectional study aimed to analyze the associations between obesity, cardiometabolic traits, serum level of carbonylated proteins (CPs), malondialdehyde (MDA), and the enzyme activity of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in children from Mexico City (normal weight: 120; obesity: 81). Obesity resulted in being positively associated with CAT (ß = 0.05 ± 0.01, p = 5.0 × 10-3) and GPx (ß = 0.13 ± 0.01, p = 3.7 × 10-19) enzyme activity. A significant interaction between obesity and sex was observed in MDA and SOD enzymatic activity (PMDA = 0.03; PSOD = 0.04). The associations between obesity, MDA level, and SOD enzyme activity were only significant in boys (boys: PMDA = 3.0 × 10-3; PSOD = 7.0 × 10-3; girls: p ≥ 0.79). In both children with normal weight and those with obesity, CP levels were positively associated with SOD enzyme activity (PNormal-weight = 2.2 × 10-3; PObesity = 0.03). In conclusion, in Mexican children, obesity is positively associated with CAT and GPx enzyme activity, and its associations with MDA levels and SOD enzyme activity are sex-specific. Therefore, CP level is positively related to SOD enzyme activity independently of body weight.

Biochelates from Spent Coffee Grounds Increases Iron Levels in Dutch Cucumbers but Affects Their Antioxidant Capacity.

Spent coffee grounds (SCG) are a type of food waste and are produced in abundance around the world. However, their utilization as a soil organic amendment is challenging due to their phytotoxic effect. In the present work, the impact of agronomic biofortification on Dutch cucumbers was investigated using different chemically modified SCG and analyzing their effects on iron contents, their capacity for releasing antioxidants, and the production of short-chain fatty acids after in vitro digestion-fermentation. The results indicated variations in the iron contents and chemical compositions of cucumbers according to the treatment groups. Functionalized and activated hydrochar from SCG increased Fe levels in cucumbers. Although activated hydrochar obtained at 160 °C and functionalized with Fe showed the highest iron supply per serving, differences in antioxidant capacity and short-chain fatty acid production were observed between the groups. It is concluded that growing conditions and the presence of iron may significantly influence the contribution of these cucumbers to the dietary intake of nutrients and antioxidants, which could have important implications for human health and nutrition.

Zn Biofortification of Dutch Cucumbers with Chemically Modified Spent Coffee Grounds: Zn Enrichment and Nutritional Implications.

Spent coffee grounds (SCGs) are a food waste with a large generation around the world. However, their utilization as a soil organic amendment is difficult due to their phytotoxic effect. In the present work, the impact of agronomic biofortification on Dutch cucumbers was studied by using different chemically modified SCGs, analyzing their effects on Zn content, the release of antioxidant capacity and the production of short-chain fatty acids after in vitro digestion-fermentation. The results indicated variations in the Zn content and chemical composition of cucumbers according to the treatment groups. The functionalized with Zn and activated SCGs were able to increase Zn levels in cucumbers. Meanwhile, the activated hydrochar obtained at 160 °C and the activated and functionalized with Zn SCGs showed the highest Zn supply per serving. Differences in the antioxidant capacity and short-chain fatty acid production were observed between the groups. It is concluded that the growing conditions and the presence of Zn may significantly influence the contribution of these cucumbers to the dietary intake of nutrients and antioxidants, which could have important implications for human health and nutrition.

Implementing a Bundle for Evidence-based Cesarean Delivery May Not Be As Beneficial as Expected: A Multi-center, Pre- and Post- Study.

BACKGROUND: Standardization of procedures improves outcomes. Though systematic reviews have summarized the evidence-based steps (EBS) of cesarean delivery (CD), their bundled implementation has not been investigated. OBJECTIVE: In this pre- and post-implementation trial, we sought to ascertain if bundled EBS of CD, compared to surgeon's preference, improves outcomes. STUDY DESIGN: A StaRI (Standards for Reporting Implementation Studies) compliant, multi-center pre- and post-implementation trial at 4 teaching hospitals was conducted. The pre-implementation period consisted of CD done based on the physicians' preferences for 3 months; educational intervention (e.g., didactics, badge cards, posters, video) occurred at the 4th month. CDs in post-implementation period employed the bundled EBS. A pre-planned 10% randomized audit of both groups assessed adherence and uptake of EBS. The primary outcome was a composite maternal morbidity (CMM), which included estimated blood loss > 1,000 mL, blood transfusion, endometritis, post-partum fever, wound complications, sepsis, thrombosis, ICU admission, hysterectomy, or death. The secondary outcome was a composite neonatal morbidity (CNM) and some of its components were 5-min Apgar score < 7, positive pressure oxygen use, hypoglycemia, or sepsis. A priori Bayesian sample size calculation indicated 700 CD in each group was needed to demonstrate 20% relative reduction (from 15% to 12%) of CMM with 75% certainty. Bayesian logistic regression with neutral priors was used to calculate likelihood of net-improvement in adjusted relative risk (aRR) with 95% credible intervals (CrI). RESULTS: A total of 1,425 consecutive CD (721 in pre- and 704 in post-implementation group) were examined. Audited data indicated that the baseline EBS utilization rate during the pre-implementation period was 79%; after the implementation bundled EBS of CD the audited adherence was 89%-an uptake of 10.0% of the EBS. In four aspects, the maternal characteristics differed significantly in the pre- and post-implementation periods: race/ethnicity, hypertensive disorder, and the relative contribution of the 4 centers to the cohorts and the gestational age at delivery, but the indications for CD and whether its duration was < versus > 60 min did not. The rates of CMM in the pre- and post-implementation groups were 26% and 22%, respectively (aRR, 0.88; 95% CrI, 0.73-1.04), with a 94 % Bayesian probability of a reduction in CMM. The CNM occurred in 37% of the pre- and in 41% of the post-implementation group (aRR, 1.12; 95% CrI 0.98-1.39), with a 95% Bayesian probability of worsening in CNM. When CMM were segregated by preterm (<37 wks) and term (> 37 weeks) CD, the improvement in maternal outcomes persisted; when CNM were segregated by gestational age subgroupsthe potential for worsening neonatal outcomes persisted as well. CONCLUSIONS: Standardization of the evidence-based bundled steps of cesarean delivery resulted in a modest reduction of the composite maternal outcome; however, a paradoxical increase in neonatal composite morbidity was noted. Although individual evidence-based steps may be of value, while awaiting additional intervention trials a formal bundling of such steps is currently not recommended.

Chemical Bonding, 10Dq Parameter and Superexchange in the Model Compound KNiF3.

The cubic field splitting parameter, 10Dq, plays a central role in the ligand field theory on insulating transition metal compounds. Experimental data obtained in the last 50 years prove that 10Dq is highly dependent on changes of the metal-ligand distance, R, induced by chemical or applied pressures. Despite this fact has important consequences on optical and magnetic properties of such compounds, its actual origin is still controversial. Seeking to clarify that crucial issue, this work is focused on KNiF3, a reference system among insulating transition metal compounds. By means of first principles calculations we show that, contrary to what is usually thought, the R-dependence of 10Dq arises neither from the crystal field contribution nor from the covalent admixture of 3d(Ni) with valence 2p(F) orbitals. Indeed, we prove that it is mainly due to the residual covalency with deep 2s(F) orbitals, highly sensitive to R variations. As a salient feature the present calculations show that the 3d-2pσ and 3d-2pπ admixtures raise practically equal the energy of antibonding eg and t2g orbitals of NiF6 4- units in KNiF3 thus leading to a null contribution to 10Dq. This conclusion is not significantly altered when considering the change of covalency on passing from the ground state 3A2(t2g 6eg 2) to the excited state 3T2(t2g 5eg 3). The different influence of chemical bonding on the superexchange constant, J, and 10Dq is also discussed in a second step. It is pointed out that the strong dependence of J upon R can hardly be explained through the behavior of the 3d-2pσ covalency derived for a single NiF6 4- unit. For the sake of clarity, the meaning of 10Dq is also briefly analyzed.

[Use of clinical ultrasound in primary care: Multicenter prospective study]. / Uso de la ecografía clínica en Atención Primaria. Estudio prospectivo multicéntrico.

OBJECTIVE: The objective was to describe the characteristics of the use of clinical ultrasound in two health centers (SC) of Health Area VII of the Region of Murcia (CS Murcia-Sur and CS Floridablanca). DESIGN: Observational, descriptive, longitudinal, prospective and multicenter study. SITE: CS Murcia-Sur and CS Floridablanca (Health Area VII of the Region of Murcia). PARTICIPANTS: One hundred and thirty-five patients were included. INTERVENTIONS: Performance of clinical ultrasound in the primary care (PC) consultation. MAIN MEASUREMENTS: Demographic variables (age, sex), as well as clinical variables (reason for consultation, type of ultrasound, results, referrals to the second hospital level, degree of diagnostic agreement) were collected. RESULTS: One hundred and thirty-five patients were included, more than 50% were female. The main reason for consultation was musculoskeletal and soft tissue symptoms (44.4%), followed by digestive symptoms (21.5%). 44.4% of the ultrasounds were classified as normal, while pathological findings were found in 55.6%. Confirmatory tests were requested in 43.7% and the findings were confirmed in 67% of the patients. CONCLUSIONS: The use of ultrasound in PC allows to show the high prevalence of pathological findings in the examination of patients. In a technique that helps the clinician in his diagnostic-therapeutic process. The integration of clinical ultrasound in the PC consultation can save complementary studies and referrals to a second level of care. Its implementation in PC requires proper training of professionals.

SARS-CoV-2 Vaccine-Elicited Immunity after B Cell Depletion in Multiple Sclerosis.

The impact of B cell deficiency on the humoral and cellular responses to SARS-CoV2 mRNA vaccination remains a challenging and significant clinical management question. We evaluated vaccine-elicited serological and cellular responses in 1) healthy individuals who were pre-exposed to SARS-CoV-2 (n = 21), 2) healthy individuals who received a homologous booster (mRNA, n = 19; or Novavax, n = 19), and 3) persons with multiple sclerosis on B cell depletion therapy (MS-αCD20) receiving mRNA homologous boosting (n = 36). Pre-exposure increased humoral and CD4 T cellular responses in immunocompetent individuals. Novavax homologous boosting induced a significantly more robust serological response than mRNA boosting. MS-α CD20 had an intact IgA mucosal response and an enhanced CD8 T cell response to mRNA boosting compared with immunocompetent individuals. This enhanced cellular response was characterized by the expansion of only effector, not memory, T cells. The enhancement of CD8 T cells in the setting of B cell depletion suggests a regulatory mechanism between B and CD8 T cell vaccine responses.

URI-CADS: A Fully Automated Computer-Aided Diagnosis System for Ultrasound Renal Imaging.

Ultrasound is a widespread imaging modality, with special application in medical fields such as nephrology. However, automated approaches for ultrasound renal interpretation still pose some challenges: (1) the need for manual supervision by experts at various stages of the system, which prevents its adoption in primary healthcare, and (2) their limited considered taxonomy (e.g., reduced number of pathologies), which makes them unsuitable for training practitioners and providing support to experts. This paper proposes a fully automated computer-aided diagnosis system for ultrasound renal imaging addressing both of these challenges. Our system is based in a multi-task architecture, which is implemented by a three-branched convolutional neural network and is capable of segmenting the kidney and detecting global and local pathologies with no need of human interaction during diagnosis. The integration of different image perspectives at distinct granularities enhanced the proposed diagnosis. We employ a large (1985 images) and demanding ultrasound renal imaging database, publicly released with the system and annotated on the basis of an exhaustive taxonomy of two global and nine local pathologies (including cysts, lithiasis, hydronephrosis, angiomyolipoma), establishing a benchmark for ultrasound renal interpretation. Experiments show that our proposed method outperforms several state-of-the-art methods in both segmentation and diagnosis tasks and leverages the combination of global and local image information to improve the diagnosis. Our results, with a 87.41% of AUC in healthy-pathological diagnosis and 81.90% in multi-pathological diagnosis, support the use of our system as a helpful tool in the healthcare system.

GrimAge is elevated in older adults with mild COVID-19 an exploratory analysis.

COVID-19 has been contained; however, the side effects associated with its infection continue to be a challenge for public health, particularly for older adults. On the other hand, epigenetic status contributes to the inter-individual health status and is associated with COVID-19 severity. Nevertheless, current studies focus only on severe COVID-19. Considering that most of the worldwide population developed mild COVID-19 infection. In the present exploratory study, we aim to analyze the association of mild COVID-19 with epigenetic ages (HorvathAge, HannumAge, GrimAge, PhenoAge, SkinAge, and DNAmTL) and clinical variables obtained from a Mexican cohort of older adults. We found that all epigenetic ages significantly differ from the chronological age, but only GrimAge is elevated. Additionally, both the intrinsic epigenetic age acceleration (IEAA) and the extrinsic epigenetic age acceleration (EEAA) are accelerated in all patients. Moreover, we found that immunological estimators and DNA damage were associated with PhenoAge, SkinBloodHorvathAge, and HorvathAge, suggesting that the effects of mild COVID-19 on the epigenetic clocks are mainly associated with inflammation and immunology changes. In conclusion, our results show that the effects of mild COVID-19 on the epigenetic clock are mainly associated with the immune system and an increase in GrimAge, IEAA, and EEAA.

«Banderas rojas» de amiloidosis cardiaca en pacientes con estenosis de canal lumbar e hipertrofia de ligamento amarillo / Red flags of cardiac amyloidosis in patients with spinal stenosis and yellow ligament hypertrophy

Introducción Carecemos de estudios que evalúen la presencia de amiloidosis cardiaca (AC) en pacientes con estenosis de canal lumbar (ECL). La identificación de banderas rojas (BR) asociadas a la enfermedad podría identificar casos de AC. Nuestro objetivo principal fue determinar la prevalencia de BR de AC. Métodos Estudio transversal de casos consecutivos que presentaban ECL e hipertrofia del ligamento amarillo (HLA). Se realizó una valoración que incluía electrocardiograma, ecocardiograma y análisis de sangre y orina. Se definió como sospecha de AC la presencia de hipertrofia ventricular y alguna BR. Resultados Se evaluaron 103 pacientes con ECL y HLA. La prevalencia de BR de AC fue elevada: insuficiencia cardiaca, 18,4%; estenosis aórtica, 1,9%; síndrome del túnel carpiano, 7,8%; rotura tendinosa bicipital, 1,9%; hipotensión arterial, 17,4%; clínica de neuropatía, 51,5%; patrón de pseudoinfarto, 3,9%; bajos voltajes, 15,5%; trastorno de la conducción, 15,5%; disminución del strain longitudinal, 25,3%; preservación apical del strain, 3,9%. El 57,3% de los pacientes presentaron sospecha de AC. Conclusión La prevalencia de BR de AC en pacientes con ECL es alta. Un elevado número de pacientes presentaron criterios de sospecha de AC. (AU)

Introduction Studies addressing the prevalence of cardiac amyloidosis (CA) among patients with spinal stenosis (SS) are lacking. The identification of the red flags (RF) of CA could lead to early detection of cases of CA. The primary objective of this study was to address the prevalence of RF of CA among patients with SS. Methods Transversal study including consecutive cases with SS and yellow ligament hypertrophy (YLH). A clinical assessment that included electrocardiogram, echocardiogram and urine and blood test was performed. A clinical suspicion of CA was defined by the presence of left ventricular hypertrophy plus any RF. Results One hundred and three patients with SS and YLH were assessed. The prevalence of RF was high: heart failure: 18.4%; aortic stenosis: 1.9%; carpal tunnel syndrome: 7.8%; bicipital tendon rupture: 1.9%; arterial hypotension: 17.4%; polyneuropathy symptoms: 51.5%; pseudoinfarction pattern: 3.9%; low voltages: 15.5%; conduction abnormalities: 15.5%; decreased longitudinal strain: 25.3%; apical sparing pattern: 3.9%. The 57.3% of the cohort met the CA suspicion criteria. Conclusion The prevalence of RF of CA is high among patients with SS and YLH. A high proportion of patients met the CA suspicion criteria. (AU)

«Banderas rojas» de amiloidosis cardiaca en pacientes con estenosis de canal lumbar e hipertrofia de ligamento amarillo / Red flags of cardiac amyloidosis in patients with spinal stenosis and yellow ligament hypertrophy

Introducción Carecemos de estudios que evalúen la presencia de amiloidosis cardiaca (AC) en pacientes con estenosis de canal lumbar (ECL). La identificación de banderas rojas (BR) asociadas a la enfermedad podría identificar casos de AC. Nuestro objetivo principal fue determinar la prevalencia de BR de AC. Métodos Estudio transversal de casos consecutivos que presentaban ECL e hipertrofia del ligamento amarillo (HLA). Se realizó una valoración que incluía electrocardiograma, ecocardiograma y análisis de sangre y orina. Se definió como sospecha de AC la presencia de hipertrofia ventricular y alguna BR. Resultados Se evaluaron 103 pacientes con ECL y HLA. La prevalencia de BR de AC fue elevada: insuficiencia cardiaca, 18,4%; estenosis aórtica, 1,9%; síndrome del túnel carpiano, 7,8%; rotura tendinosa bicipital, 1,9%; hipotensión arterial, 17,4%; clínica de neuropatía, 51,5%; patrón de pseudoinfarto, 3,9%; bajos voltajes, 15,5%; trastorno de la conducción, 15,5%; disminución del strain longitudinal, 25,3%; preservación apical del strain, 3,9%. El 57,3% de los pacientes presentaron sospecha de AC. Conclusión La prevalencia de BR de AC en pacientes con ECL es alta. Un elevado número de pacientes presentaron criterios de sospecha de AC. (AU)

Introduction Studies addressing the prevalence of cardiac amyloidosis (CA) among patients with spinal stenosis (SS) are lacking. The identification of the red flags (RF) of CA could lead to early detection of cases of CA. The primary objective of this study was to address the prevalence of RF of CA among patients with SS. Methods Transversal study including consecutive cases with SS and yellow ligament hypertrophy (YLH). A clinical assessment that included electrocardiogram, echocardiogram and urine and blood test was performed. A clinical suspicion of CA was defined by the presence of left ventricular hypertrophy plus any RF. Results One hundred and three patients with SS and YLH were assessed. The prevalence of RF was high: heart failure: 18.4%; aortic stenosis: 1.9%; carpal tunnel syndrome: 7.8%; bicipital tendon rupture: 1.9%; arterial hypotension: 17.4%; polyneuropathy symptoms: 51.5%; pseudoinfarction pattern: 3.9%; low voltages: 15.5%; conduction abnormalities: 15.5%; decreased longitudinal strain: 25.3%; apical sparing pattern: 3.9%. The 57.3% of the cohort met the CA suspicion criteria. Conclusion The prevalence of RF of CA is high among patients with SS and YLH. A high proportion of patients met the CA suspicion criteria. (AU)

Effects of 4 Different Velocity-Based Resistance-Training Programming Models on Physical Performance.

PURPOSE: To examine the effects of 4 programming models (linear [LP], undulating [UP], reverse [RP], and constant [CP]) on physical performance. METHODS: Forty-eight moderately strength-trained men were randomly assigned to LP, UP, RP, and CP groups according to their 1-repetition maximum (1RM) in the full-squat exercise (SQ) and followed an 8-week training intervention using the SQ and monitoring movement velocity for every repetition. All groups trained with similar mean relative intensity (65% 1RM), number of repetitions (240), sets (3), and interset recovery (4 min) throughout the training program. Pretraining and posttraining measurements included, in the SQ, 1RM load, the average velocity attained for all absolute loads common to pretests and posttests (AV), and the average velocity for loads that were moved faster (AV > 1) and slower (AV < 1) than 1 m·s-1 at pretraining tests. Moreover, countermovement jump height and 20-m running sprint time were measured. RESULTS: A significant time effect was found for all variables analyzed (P < .05), except for 20-m running sprint time. Significant group × time interactions were observed for 1RM, AV > 1, and AV (P < .05). After training, all groups attained significant strength gains on 1RM, AV, AV > 1, and AV < 1 (P < .001-.01). LP and RP groups improved their countermovement jump height (P < .01), but no significant changes were observed for UP and CP. No significant improvements were achieved in 20-m running sprint time for any groups. CONCLUSIONS: These different programming models are all suitable for improving physical performance. LP and RP induce similar or greater gains in physical performance than UP and CP.

Targeting cancer stem cell OXPHOS with tailored ruthenium complexes as a new anti-cancer strategy.

BACKGROUND: Previous studies by our group have shown that oxidative phosphorylation (OXPHOS) is the main pathway by which pancreatic cancer stem cells (CSCs) meet their energetic requirements; therefore, OXPHOS represents an Achille's heel of these highly tumorigenic cells. Unfortunately, therapies that target OXPHOS in CSCs are lacking. METHODS: The safety and anti-CSC activity of a ruthenium complex featuring bipyridine and terpyridine ligands and one coordination labile position (Ru1) were evaluated across primary pancreatic cancer cultures and in vivo, using 8 patient-derived xenografts (PDXs). RNAseq analysis followed by mitochondria-specific molecular assays were used to determine the mechanism of action. RESULTS: We show that Ru1 is capable of inhibiting CSC OXPHOS function in vitro, and more importantly, it presents excellent anti-cancer activity, with low toxicity, across a large panel of human pancreatic PDXs, as well as in colorectal cancer and osteosarcoma PDXs. Mechanistic studies suggest that this activity stems from Ru1 binding to the D-loop region of the mitochondrial DNA of CSCs, inhibiting OXPHOS complex-associated transcription, leading to reduced mitochondrial oxygen consumption, membrane potential, and ATP production, all of which are necessary for CSCs, which heavily depend on mitochondrial respiration. CONCLUSIONS: Overall, the coordination complex Ru1 represents not only an exciting new anti-cancer agent, but also a molecular tool to dissect the role of OXPHOS in CSCs. Results indicating that the compound is safe, non-toxic and highly effective in vivo are extremely exciting, and have allowed us to uncover unprecedented mechanistic possibilities to fight different cancer types based on targeting CSC OXPHOS.

Results of phase 2 randomized multi-center study to evaluate the safety and efficacy of infusion of memory T cells as adoptive therapy in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia and/or lymphopenia (RELEASE NCT04578210).

BACKGROUND AIMS: There are currently no effective anti-viral treatments for coronavirus disease 2019 (COVID-19)-hospitalized patients with hypoxemia. Lymphopenia is a biomarker of disease severity usually present in patients who are hospitalized. Approaches to increasing lymphocytes exerting an anti-viral effect must be considered to treat these patients. Following our phase 1 study, we performed a phase 2 randomized multicenter clinical trial in which we evaluated the efficacy of the infusion of allogeneic off-the-shelf CD45RA- memory T cells containing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells from convalescent donors plus the standard of care (SoC) versus just the SoC treatment. METHODS: Eighty-four patients were enrolled in three Spanish centers. The patients were randomized into the infusion of 1 × 106/kg CD45RA- memory T cells or the SoC. We selected four unvaccinated donors based on the expression of interferon gamma SARS-CoV-2-specific response within the CD45RA- memory T cells and the most frequent human leukocyte antigen typing in the Spanish population. RESULTS: We analyzed data from 81 patients. The primary outcome for recovery, defined as the proportion of participants in each group with normalization of fever, oxygen saturation sustained for at least 24 hours and lymphopenia recovery through day 14 or at discharge, was met for the experimental arm. We also observed faster lymphocyte recovery in the experimental group. We did not observe any treatment-related adverse events. CONCLUSIONS: Adoptive cell therapy with off-the-shelf CD45RA- memory T cells containing SAR-CoV-2-specific T cells is safe, effective and accelerates lymphocyte recovery of patients with COVID-19 pneumonia and/or lymphopenia. TRIAL REGISTRATION: NCT04578210.

Dysfunction of Drosophila mitochondrial carrier homolog (Mtch) alters apoptosis and disturbs development.

Mitochondrial carrier homologs 1 (MTCH1) and 2 (MTCH2) are orphan members of the mitochondrial transporter family SLC25. Human MTCH1 is also known as presenilin 1-associated protein, PSAP. MTCH2 is a receptor for tBid and is related to lipid metabolism. Both proteins have been recently described as protein insertases of the outer mitochondrial membrane. We have depleted Mtch in Drosophila and show here that mutant flies are unable to complete development, showing an excess of apoptosis during pupation; this observation was confirmed by RNAi in Schneider cells. These findings are contrary to what has been described in humans. We discuss the implications in view of recent reports concerning the function of these proteins.

[Red flags of cardiac amyloidosis in patients with spinal stenosis and yellow ligament hypertrophy]. / «Banderas rojas¼ de amiloidosis cardiaca en pacientes con estenosis de canal lumbar e hipertrofia de ligamento amarillo.

INTRODUCTION: Studies addressing the prevalence of cardiac amyloidosis (CA) among patients with spinal stenosis (SS) are lacking. The identification of the red flags (RF) of CA could lead to early detection of cases of CA. The primary objective of this study was to address the prevalence of RF of CA among patients with SS. METHODS: Transversal study including consecutive cases with SS and yellow ligament hypertrophy (YLH). A clinical assessment that included electrocardiogram, echocardiogram and urine and blood test was performed. A clinical suspicion of CA was defined by the presence of left ventricular hypertrophy plus any RF. RESULTS: One hundred and three patients with SS and YLH were assessed. The prevalence of RF was high: heart failure: 18.4%; aortic stenosis: 1.9%; carpal tunnel syndrome: 7.8%; bicipital tendon rupture: 1.9%; arterial hypotension: 17.4%; polyneuropathy symptoms: 51.5%; pseudoinfarction pattern: 3.9%; low voltages: 15.5%; conduction abnormalities: 15.5%; decreased longitudinal strain: 25.3%; apical sparing pattern: 3.9%. The 57.3% of the cohort met the CA suspicion criteria. CONCLUSION: The prevalence of RF of CA is high among patients with SS and YLH. A high proportion of patients met the CA suspicion criteria.

Developing critical HIV health literacy: insights from interviews with priority migrant communities in Queensland, Australia.

In Australia, surveillance data establish that there are higher rates of late HIV diagnoses among heterosexual migrants from Sub-Saharan Africa and new HIV diagnoses among gay and bisexual men (GBM) from Southeast and Northeast Asia and Latin America. Together, these groups are identified as priority migrant communities in current efforts to eliminate HIV transmissions. HIV health literacy is recognised as a key means of improving access to services and health outcomes. This qualitative paper explores critical HIV health literacy among priority migrant communities in Queensland, Australia. To foreground community voices, peer researchers from priority migrant communities participated in the project design, data collection and analysis, with 20 interviews completed. The findings demonstrate how participants' engagement with HIV health information and services is highly relational and situated within the framework of sexual health and wellbeing. Participants strategically selected where to seek information and who they trusted to help them appraise this information. They further demonstrated reflective capacities in identifying the contextual barriers that inhibit the development of their HIV health literacy. The findings highlight the need for HIV health promotion strategies that embrace a sex positive approach, promote cultural change, and involve collaboration with general practitioners (GPs).

Effect of Nutrition Education on Health Science University Students to Improve Cardiometabolic Profile and Inflammatory Status.

The inadequate lifestyle associated with university life may have a negative impact on various cardiometabolic factors. The aim of this study was to evaluate the effect of a one-year nutrition education course on cardiometabolic parameters in undergraduate health science students. During the 2021-22 academic year, 1.30 h nutrition sessions were conducted twice a week. Capillary blood samples were collected and centrifuged to measure cardiometabolic and inflammatory biomarkers in serum. The sample studied consisted of 49 students: 20.4% male and 79.6% female. The nutritional intervention resulted in changes in dietary patterns, with increased consumption of vegetables, nuts and legumes. After the course, females showed an increase in HDL-cholesterol levels (p = 0.007) and no change in LDL-cholesterol levels (p = 0.189). On the other hand, males showed significant changes in HDL-cholesterol (p = 0.001) and LDL-cholesterol (p = 0.043) levels. The atherogenic index was also significantly reduced (p < 0.001) in both males (p = 0.009) and females (p = 0.002). Differences were also observed in the increase in vitamin D levels in both males and females, although the magnitude of the increase was greater in the men (Δ = 7.94, p = 0.016 in men vs. Δ = 4.96, p = 0.001 in women). The monocyte-to-HDL ratio (MHR) showed a significant reduction, although these differences were only significant in males. Students with low vitamin D levels had higher LDL-cholesterol values (p = 0.01) and atherogenic index (p = 0.029). Adjusted linear regression analysis showed a significant association between post-course vitamin D MHR (ß = -0.42, IC: -0.29, -0.06, p < 0.01). These findings suggest the importance of including nutrition education programs during the university stage for the prevention of long-term health problems.