Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults.

BACKGROUND: Therapies to interrupt the progression of early coronavirus disease 2019 (Covid-19) remain elusive. Among them, convalescent plasma administered to hospitalized patients has been unsuccessful, perhaps because antibodies should be administered earlier in the course of illness. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older adult patients within 72 hours after the onset of mild Covid-19 symptoms. The primary end point was severe respiratory disease, defined as a respiratory rate of 30 breaths per minute or more, an oxygen saturation of less than 93% while the patient was breathing ambient air, or both. The trial was stopped early at 76% of its projected sample size because cases of Covid-19 in the trial region decreased considerably and steady enrollment of trial patients became virtually impossible. RESULTS: A total of 160 patients underwent randomization. In the intention-to-treat population, severe respiratory disease developed in 13 of 80 patients (16%) who received convalescent plasma and 25 of 80 patients (31%) who received placebo (relative risk, 0.52; 95% confidence interval [CI], 0.29 to 0.94; P = 0.03), with a relative risk reduction of 48%. A modified intention-to-treat analysis that excluded 6 patients who had a primary end-point event before infusion of convalescent plasma or placebo showed a larger effect size (relative risk, 0.40; 95% CI, 0.20 to 0.81). No solicited adverse events were observed. CONCLUSIONS: Early administration of high-titer convalescent plasma against SARS-CoV-2 to mildly ill infected older adults reduced the progression of Covid-19. (Funded by the Bill and Melinda Gates Foundation and the Fundación INFANT Pandemic Fund; Dirección de Sangre y Medicina Transfusional del Ministerio de Salud number, PAEPCC19, Plataforma de Registro Informatizado de Investigaciones en Salud number, 1421, and ClinicalTrials.gov number, NCT04479163.).

The Cytoplasmic Region of SARAF Reduces Triple-Negative Breast Cancer Metastasis through the Regulation of Store-Operated Calcium Entry.

Triple-negative breast cancer has a poor prognosis and is non-responsive to first-line therapies; hence, new therapeutic strategies are needed. Enhanced store-operated Ca2+ entry (SOCE) has been widely described as a contributing factor to tumorigenic behavior in several tumor types, particularly in breast cancer cells. SOCE-associated regulatory factor (SARAF) acts as an inhibitor of the SOCE response and, therefore, can be a potential antitumor factor. Herein, we generated a C-terminal SARAF fragment to evaluate the effect of overexpression of this peptide on the malignancy of triple-negative breast cancer cell lines. Using both in vitro and in vivo approaches, we showed that overexpression of the C-terminal SARAF fragment reduced proliferation, cell migration, and the invasion of murine and human breast cancer cells by decreasing the SOCE response. Our data suggest that regulating the activity of the SOCE response via SARAF activity might constitute the basis for further alternative therapeutic strategies for triple-negative breast cancer.

KCTD5, a novel TRPM4-regulatory protein required for cell migration as a new predictor for breast cancer prognosis.

Transient receptor potential melastatin 4 (TRPM4) is a Ca2+ -activated nonselective cationic channel that regulates cell migration and contractility. Increased TRPM4 expression has been related to pathologies, in which cytoskeletal rearrangement and cell migration are altered, such as metastatic cancer. Here, we identify the K+ channel tetramerization domain 5 (KCTD5) protein, a putative adaptor of cullin3 E3 ubiquitin ligase, as a novel TRPM4-interacting protein. We demonstrate that KCTD5 is a positive regulator of TRPM4 activity by enhancing its Ca2+ sensitivity. We show that through its effects on TRPM4 that KCTD5 promotes cell migration and contractility. Finally, we observed that both TRPM4 and KCTD5 expression are increased in distinct patterns in different classes of breast cancer tumor samples. Together, these data support that TRPM4 activity can be regulated through expression levels of either TRPM4 or KCTD5, not only contributing to increased understanding of the molecular mechanisms involved on the regulation of these important ion channels, but also providing information that could inform treatments based on targeting these distinct molecules that define TRPM4 activity.

Inhibition of InsP3R with Xestospongin B Reduces Mitochondrial Respiration and Induces Selective Cell Death in T Cell Acute Lymphoblastic Leukemia Cells.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy whose chemoresistance and relapse persist as a problem despite significant advances in its chemotherapeutic treatments. Mitochondrial metabolism has emerged as an interesting therapeutic target given its essential role in maintaining bioenergetic and metabolic homeostasis. T-ALL cells are characterized by high levels of mitochondrial respiration, making them suitable for this type of intervention. Mitochondrial function is sustained by a constitutive transfer of calcium from the endoplasmic reticulum to mitochondria through the inositol 1,4,5-trisphosphate receptor (InsP3R), making T-ALL cells vulnerable to its inhibition. Here, we determine the bioenergetic profile of the T-ALL cell lines CCRF-CEM and Jurkat and evaluate their sensitivity to InsP3R inhibition with the specific inhibitor, Xestospongin B (XeB). Our results show that T-ALL cell lines exhibit higher mitochondrial respiration than non-malignant cells, which is blunted by the inhibition of the InsP3R. Prolonged treatment with XeB causes T-ALL cell death without affecting the normal counterpart. Moreover, the combination of XeB and glucocorticoids significantly enhanced cell death in the CCRF-CEM cells. The inhibition of InsP3R with XeB rises as a potential therapeutic alternative for the treatment of T-ALL.

[Extracorporeal cytokine hemadsorption for the treatment of refractory septic shock. Report of two cases]. / Adsorción extracorpórea de citoquinas en el tratamiento del shock séptico refractario. Casos clínicos.

If Septic shock (SS) evolves to refractory SS, mortality could reach 90%, despite giving an optimal treatment. Nowadays, extracorporeal devices which adsorb inflammatory cytokines are available, reducing the systemic inflammatory response syndrome. These devices can be used with continuous renal replacement therapy or conventional hemodialysis. We report two diabetic females aged 50 and 58 years, who underwent a total colectomy and amputation of diabetic foot and who developed a SS with high requirements of vasoactive drugs (norepinephrine and adrenaline) to maintain a mean arterial pressure about 60 mmHg. Both were subjected to hemodialysis, connected to a cytokine hemadsorption device. The most important finding was the progressive reduction of vasopressor doses, effect that was observed nine hours after the beginning of the hemadsorption and lasted until its removal at 26 hours. Both patients survived.

Genetic diversity of a late prehispanic group of the Quebrada de Humahuaca, northwestern Argentina.

This palaeogenetic study focused on the analysis of a late prehispanic Argentinean group from the Humahuaca valley, with the main aim of reconstructing its (micro)evolutionary history. The Humahuaca valley, a natural passageway from the eastern plains to the highlands, was the living environment of Andean societies whose cultural but especially biological diversity is still poorly understood. We analyzed the DNA extracted from 39 individuals who populated this upper valley during the Regional Development period (RDP) (between the 11th and 15th centuries CE), to determine their maternal and paternal genetic ancestry. Some mitochondrial and Y-chromosomal haplotypes specific to the Andean region are consistent with an origin in the highlands of Central Andes. On the other hand, a significant genetic affinity with contemporary admixed communities of the Chaco area was detected. Expectedly, recent demographic events, such as the expansion of the Inca Empire or the European colonization, have changed the original mitochondrial gene pool of the ancient Humahuaca Valley community. Finally, we identified a particular geographical organization of the prehispanic populations of Northwestern Argentina. Our results suggest that the communities of the region were divided between two different spheres of interaction, which is consistent with assumptions made by means of craniometric traits.

Emerging Challenges of Mpox Transmission: An In-depth Scoping Review and Evidence Mapping on Breastfeeding Practices in South America.

BACKGROUND: In 2022, a marked escalation in Monkeypox (Mpox) cases was observed in nonendemic regions, notably South America, despite the virus being traditionally endemic to Central and West Africa. This unexpected shift necessitated a deeper exploration of the novel transmission dynamics, including breastfeeding, given the emerging evidence of potential horizontal and vertical Mpox transmission during mother-infant interactions. RESEARCH AIM: The study aimed to critically evaluate existing evidence on potential horizontal and vertical Mpox transmission related to breastfeeding and to assess guidelines in South American countries regarding Mpox prevention during breastfeeding. METHODS: A scoping review and evidence mapping were conducted, adhering to the PRISMA Extension for Scoping Reviews (PRISMA-ScR) guideline. Data extraction involved identifying primary studies evaluating breastfeeding as a transmission route. Additionally, official documents from South American Health Ministries detailing guidelines or policies on breastfeeding in the context of maternal Mpox infection were reviewed. RESULTS: Three out of 215 studies were found relevant; 2 were case reports, and 1 was a laboratory study. Available evidence suggests that contamination could likely occur horizontally through skin-to-skin contact. Six South American countries had issued guidelines on breastfeeding during Mpox infection, but the guidance varied and was not consistent across the region. CONCLUSIONS: The study emphasizes the need for clear and consistent guidelines on breastfeeding during Mpox outbreaks, particularly in South America. Collaborative strategies and regular research updates will be essential in addressing the ongoing public health challenge.

Conversion hip arthroplasty for failed internal fixation of ipsilateral femoral neck and shaft fractures: a case report.

BACKGROUND: Ipsilateral femoral neck and hip fractures are uncommon high energy injuries. In the literature no single method of treatment has emerged as superior to the others. A recent publication has documented the successful application of the rendezvous technique using dual-implants for treating these injuries. However in some cases, this technique may fail and revision surgery is required. CASE PRESENTATION: A 67-year old man sustained ipsilateral fractures of his femur and femoral neck in a road traffic accident. His injuries were treated by a dual construct consisting of a retrograde femoral nail and dynamic hip screw. Three months after surgery the hip screw cut out of the femoral head necessitating revision to a total hip arthroplasty. Surgery was carried out using a single stage two part procedure on a standard operating table without having to reposition or redrape the patient. There were no postoperative complications and at 1 year from surgery the patient is satisfied with the result and has returned to work. CONCLUSION: Conversion hip arthroplasty in the presence of dual implants is a technically challenging and unpredictable procedure, with an increased risk of complications. Our surgical approach provides a framework for orthopedic surgeons to safely perform this complex procedure.

Influence of Teachers' Vocal Quality on Students' Learning and/or Cognition: A Scoping Review.

OBJECTIVE: To verify if the teacher's vocal quality can influence the student's cognition. METHODS: The present study is a scoping review performed to answer the research question: Can the teacher's vocal quality influence the student's learning and cognition?. To verify if the teacher's vocal quality can influence the student's cognition. The electronic search was performed in PubMed, Lilacs, SciELO, Scopus, Web of Science, Embase, and databases, in addition to a manual search in citation and gray literature. Two independent authors performed selection and extraction. Data were extracted about the study design: the sample, the cognitive tests used, the assessed cognitive skills, the type of altered voice (real or simulated), the assessment of the vocal quality, alone or associated with environmental noise, and the main outcomes evaluated. RESULTS: The initial research identified 476 articles, and 13 were selected for analysis. Seven (54%) studies evaluated the impact of altered voices in an isolated way on cognitive abilities. From these, they verified that the altered voices could negatively influence children's cognitive performance. Other 6 studies (46%) associated altered voices with competitive noise in their analysis, and 4 concluded that competitive noise rather than altered voices influenced students' cognitive performance. CONCLUSION: The altered voice seems to affect the cognitive tasks involved in the learning process. The competitive noise associated with the presentation of deviant voices had a stronger influence on cognitive performance than altered voice alone, demonstrating that cognitive performance is sensitive to the stages of information acquisition (input of acoustic signals).

TRP Channels Interactome as a Novel Therapeutic Target in Breast Cancer.

Breast cancer is one of the most frequent cancer types worldwide and the first cause of cancer-related deaths in women. Although significant therapeutic advances have been achieved with drugs such as tamoxifen and trastuzumab, breast cancer still caused 627,000 deaths in 2018. Since cancer is a multifactorial disease, it has become necessary to develop new molecular therapies that can target several relevant cellular processes at once. Ion channels are versatile regulators of several physiological- and pathophysiological-related mechanisms, including cancer-relevant processes such as tumor progression, apoptosis inhibition, proliferation, migration, invasion, and chemoresistance. Ion channels are the main regulators of cellular functions, conducting ions selectively through a pore-forming structure located in the plasma membrane, protein-protein interactions one of their main regulatory mechanisms. Among the different ion channel families, the Transient Receptor Potential (TRP) family stands out in the context of breast cancer since several members have been proposed as prognostic markers in this pathology. However, only a few approaches exist to block their specific activity during tumoral progress. In this article, we describe several TRP channels that have been involved in breast cancer progress with a particular focus on their binding partners that have also been described as drivers of breast cancer progression. Here, we propose disrupting these interactions as attractive and potential new therapeutic targets for treating this neoplastic disease.

RBD-specific polyclonal F(ab´)2 fragments of equine antibodies in patients with moderate to severe COVID-19 disease: A randomized, multicenter, double-blind, placebo-controlled, adaptive phase 2/3 clinical trial.

BACKGROUND: passive immunotherapy is a therapeutic alternative for patients with COVID-19. Equine polyclonal antibodies (EpAbs) could represent a source of scalable neutralizing antibodies against SARS-CoV-2. METHODS: we conducted a double-blind, randomized, placebo-controlled trial to assess efficacy and safety of EpAbs (INM005) in hospitalized adult patients with moderate and severe COVID-19 pneumonia in 19 hospitals of Argentina. Primary endpoint was improvement in at least two categories in WHO ordinal clinical scale at day 28 or hospital discharge (ClinicalTrials.gov number NCT04494984). FINDINGS: between August 1st and October 26th, 2020, a total of 245 patients were enrolled. Enrolled patients were assigned to receive two blinded doses of INM005 (n = 118) or placebo (n = 123). Median age was 54 years old, 65•1% were male and 61% had moderate disease at baseline. Median time from symptoms onset to study treatment was 6 days (interquartile range 5 to 8). No statistically significant difference was noted between study groups on primary endpoint (risk difference [95% IC]: 5•28% [-3•95; 14•50]; p = 0•15). Rate of improvement in at least two categories was statistically significantly higher for INM005 at days 14 and 21 of follow-up. Time to improvement in two ordinal categories or hospital discharge was 14•2 (± 0•7) days in the INM005 group and 16•3 (± 0•7) days in the placebo group, hazard ratio 1•31 (95% CI 1•0 to 1•74). Subgroup analyses showed a beneficial effect of INM005 over severe patients and in those with negative baseline antibodies. Overall mortality was 6•9% the INM005 group and 11•4% in the placebo group (risk difference [95% IC]: 0•57 [0•24 to 1•37]). Adverse events of special interest were mild or moderate; no anaphylaxis was reported. INTERPRETATION: Albeit not having reached the primary endpoint, we found clinical improvement of hospitalized patients with SARS-CoV-2 pneumonia, particularly those with severe disease.

Mapping past human land use using archaeological data: A new classification for global land use synthesis and data harmonization.

In the 12,000 years preceding the Industrial Revolution, human activities led to significant changes in land cover, plant and animal distributions, surface hydrology, and biochemical cycles. Earth system models suggest that this anthropogenic land cover change influenced regional and global climate. However, the representation of past land use in earth system models is currently oversimplified. As a result, there are large uncertainties in the current understanding of the past and current state of the earth system. In order to improve representation of the variety and scale of impacts that past land use had on the earth system, a global effort is underway to aggregate and synthesize archaeological and historical evidence of land use systems. Here we present a simple, hierarchical classification of land use systems designed to be used with archaeological and historical data at a global scale and a schema of codes that identify land use practices common to a range of systems, both implemented in a geospatial database. The classification scheme and database resulted from an extensive process of consultation with researchers worldwide. Our scheme is designed to deliver consistent, empirically robust data for the improvement of land use models, while simultaneously allowing for a comparative, detailed mapping of land use relevant to the needs of historical scholars. To illustrate the benefits of the classification scheme and methods for mapping historical land use, we apply it to Mesopotamia and Arabia at 6 kya (c. 4000 BCE). The scheme will be used to describe land use by the Past Global Changes (PAGES) LandCover6k working group, an international project comprised of archaeologists, historians, geographers, paleoecologists, and modelers. Beyond this, the scheme has a wide utility for creating a common language between research and policy communities, linking archaeologists with climate modelers, biodiversity conservation workers and initiatives.

TRP Channels Regulation of Rho GTPases in Brain Context and Diseases.

Neurological and neuropsychiatric disorders are mediated by several pathophysiological mechanisms, including developmental and degenerative abnormalities caused primarily by disturbances in cell migration, structural plasticity of the synapse, and blood-vessel barrier function. In this context, critical pathways involved in the pathogenesis of these diseases are related to structural, scaffolding, and enzymatic activity-bearing proteins, which participate in Ca2+- and Ras Homologs (Rho) GTPases-mediated signaling. Rho GTPases are GDP/GTP binding proteins that regulate the cytoskeletal structure, cellular protrusion, and migration. These proteins cycle between GTP-bound (active) and GDP-bound (inactive) states due to their intrinsic GTPase activity and their dynamic regulation by GEFs, GAPs, and GDIs. One of the most important upstream inputs that modulate Rho GTPases activity is Ca2+ signaling, positioning ion channels as pivotal molecular entities for Rho GTPases regulation. Multiple non-selective cationic channels belonging to the Transient Receptor Potential (TRP) family participate in cytoskeletal-dependent processes through Ca2+-mediated modulation of Rho GTPases. Moreover, these ion channels have a role in several neuropathological events such as neuronal cell death, brain tumor progression and strokes. Although Rho GTPases-dependent pathways have been extensively studied, how they converge with TRP channels in the development or progression of neuropathologies is poorly understood. Herein, we review recent evidence and insights that link TRP channels activity to downstream Rho GTPase signaling or modulation. Moreover, using the TRIP database, we establish associations between possible mediators of Rho GTPase signaling with TRP ion channels. As such, we propose mechanisms that might explain the TRP-dependent modulation of Rho GTPases as possible pathways participating in the emergence or maintenance of neuropathological conditions.

K+ Channel Tetramerization Domain 5 (KCTD5) Protein Regulates Cell Migration, Focal Adhesion Dynamics and Spreading through Modulation of Ca2+ Signaling and Rac1 Activity.

Cell migration is critical for several physiological and pathophysiological processes. It depends on the coordinated action of kinases, phosphatases, Rho-GTPases proteins, and Ca2+ signaling. Interestingly, ubiquitination events have emerged as regulatory elements of migration. Thus, the role of proteins involved in ubiquitination processes could be relevant to a complete understanding of pro-migratory mechanisms. KCTD5 is a member of Potassium Channel Tetramerization Domain (KCTD) proteins that have been proposed as a putative adaptor for Cullin3-E3 ubiquitin ligase and a novel regulatory protein of TRPM4 channels. Here, we study whether KCTD5 participates in cell migration-associated mechanisms, such as focal adhesion dynamics and cellular spreading. Our results show that KCTD5 CRISPR/Cas9- and shRNA-based depletion in B16-F10 cells promoted an increase in cell migration and cell spreading, and a decrease in the focal adhesion area, consistent with an increased focal adhesion disassembly rate. The expression of a dominant-negative mutant of Rho-GTPases Rac1 precluded the KCTD5 depletion-induced increase in cell spreading. Additionally, KCTD5 silencing decreased the serum-induced Ca2+ response, and the reversion of this with ionomycin abolished the KCTD5 knockdown-induced decrease in focal adhesion size. Together, these data suggest that KCTD5 acts as a regulator of cell migration by modulating cell spreading and focal adhesion dynamics through Rac1 activity and Ca2+ signaling, respectively.

Cancer cells with defective oxidative phosphorylation require endoplasmic reticulum-to-mitochondria Ca2+ transfer for survival.

Spontaneous Ca2+ signaling from the InsP3R intracellular Ca2+ release channel to mitochondria is essential for optimal oxidative phosphorylation (OXPHOS) and ATP production. In cells with defective OXPHOS, reductive carboxylation replaces oxidative metabolism to maintain amounts of reducing equivalents and metabolic precursors. To investigate the role of mitochondrial Ca2+ uptake in regulating bioenergetics in these cells, we used OXPHOS-competent and OXPHOS-defective cells. Inhibition of InsP3R activity or mitochondrial Ca2+ uptake increased α-ketoglutarate (αKG) abundance and the NAD+/NADH ratio, indicating that constitutive endoplasmic reticulum (ER)-to-mitochondria Ca2+ transfer promoted optimal αKG dehydrogenase (αKGDH) activity. Reducing mitochondrial Ca2+ inhibited αKGDH activity and increased NAD+, which induced SIRT1-dependent autophagy in both OXPHOS-competent and OXPHOS-defective cells. Whereas autophagic flux in OXPHOS-competent cells promoted cell survival, it was impaired in OXPHOS-defective cells because of inhibition of autophagosome-lysosome fusion. Inhibition of αKGDH and impaired autophagic flux in OXPHOS-defective cells resulted in pronounced cell death in response to interruption of constitutive flux of Ca2+ from ER to mitochondria. These results demonstrate that mitochondria play a fundamental role in maintaining bioenergetic homeostasis of both OXPHOS-competent and OXPHOS-defective cells, with Ca2+ regulation of αKGDH activity playing a pivotal role. Inhibition of ER-to-mitochondria Ca2+ transfer may represent a general therapeutic strategy against cancer cells regardless of their OXPHOS status.

Leaf traits capture the effects of land use changes and climate on litter decomposability of grasslands across Europe.

Land use and climate changes induce shifts in plant functional diversity and community structure, thereby modifying ecosystem processes. This is particularly true for litter decomposition, an essential process in the biogeochemical cycles of carbon and nutrients. In this study, we asked whether changes in functional traits of living leaves in response to changes in land use and climate were related to rates of litter potential decomposition, hereafter denoted litter decomposability, across a range of 10 contrasting sites. To disentangle the different control factors on litter decomposition, we conducted a microcosm experiment to determine the decomposability under standard conditions of litters collected in herbaceous communities from Europe and Israel. We tested how environmental factors (disturbance and climate) affected functional traits of living leaves and how these traits then modified litter quality and subsequent litter decomposability. Litter decomposability appeared proximately linked to initial litter quality, with particularly clear negative correlations with lignin-dependent indices (litter lignin concentr tion, lignin:nitrogen ratio, and fiber component). Litter quality was directly related to community-weighted mean traits. Lignin-dependent indices of litter quality were positively correlated with community-weighted mean leaf dry matter content (LDMC), and negatively correlated with community-weighted mean leaf nitrogen concentration (LNC). Consequently, litter decomposability was correlated negatively with community-weighted mean LDMC, and positively with community-weighted mean LNC. Environmental factors (disturbance and climate) influenced community-weighted mean traits. Plant communities experiencing less frequent or less intense disturbance exhibited higher community-weighted mean LDMC, and therefore higher litter lignin content and slower litter decomposability. LDMC therefore appears as a powerful marker of both changes in land use and of the pace of nutrient cycling across 10 contrasting sites.

Functional traits as indicators of fodder provision over a short time scale in species-rich grasslands.

BACKGROUND AND AIMS: Fodder provision in species-rich grasslands, i.e. herbage growth, proportion of leaf, and leaf and stem digestibility, is difficult to predict for short periods of time, such as between two defoliations or less. The value of two methods based on plant traits for evaluating these agronomic properties was examined. METHODS: One method is based on plant trait measurements on the plant community (leaf dry matter content, plant height, flowering date); the other is on vegetation composition expressed as plant functional types (acquisitive versus conservative PFTs) established by measuring leaf dry matter content on pure grass stands. The experiment consisted of 18 fields with three different defoliation regimes (combinations of cutting and grazing) and two levels of fertilization. To establish a growth curve over the first growth cycle, herbage was sampled about 10 times in spring. KEY RESULTS: Coefficients of correlation between agronomic properties of the vegetation and its functional composition were higher when the latter was assessed through PFT and an indicator of the plant nutrient status (Ni) instead of measured plant traits. The date at which the ceiling yield occurred for the standing herbage mass or only the leaf component, which varied by up to 500 degree-days between treatments, and the leaf proportion, depended entirely on the PFT, and largely so for the leaf digestibility. The standing herbage mass at the time of ceiling yield depended only on Ni, or mainly so in the case of the daily herbage growth rate. Similar plant digestibility between plant communities was found at flowering time, although there were big differences in PFT composition. The shape of the growth curve was flatter when there was great functional diversity in the plant community. CONCLUSIONS: The PFT composition and the Ni were more reliable than the plant functional traits measured in the field for evaluating herbage growth pattern and digestibility in spring.

Complex I and II are required for normal mitochondrial Ca2+ homeostasis.

Cytosolic calcium (cCa2+) entry into mitochondria is facilitated by the mitochondrial membrane potential (ΔΨm), an electrochemical gradient generated by the electron transport chain (ETC). Is has been assumed that as long as mutations that affect the ETC do not affect the ΔΨm, the mitochondrial Ca2+ (mCa2+) homeostasis remains normal. We show that knockdown of NDUFAF3 and SDHB reduce ETC activity altering mCa2+ efflux and influx rates while ΔΨm remains intact. Shifting the equilibrium toward lower [Ca2+]m accumulation renders cells resistant to death. Our findings reveal an unexpected relationship between complex I and II with the mCa2+ homeostasis independent of ΔΨm.

[The demedicalisation of women's daily lives: socio-educational groups in the Andalusian Public Health System]. / La desmedicalización de la vida cotidiana de las mujeres: los grupos socioeducativos en el Sistema Sanitario Público Andaluz.

The socio-educational groups (GRUSE) are a health and emotional well-being promotion strategy, from an asset-based positive health approach. They principally target women who attend health centres with signs of discomfort with no organic basis finding. The strategy was evaluated through a quasi-experimental longitudinal design, with a mixed methodology. Information was collected from 228 women with a battery of scales and from an analysis of health system databases. Ten in-depth interviews with women were conducted, and 3 discussion groups with professionals. The aim of this article was to introduce the GRUSE strategy as a non-medical alternative intervention and to present the research design, seeking to identify the evidence of this practice implemented in primary health centres of Andalusia (Spain).

Quality of life and metamemory in higher education students during the COVID-19 pandemic / Qualidade de vida e metamemória em estudantes do nível superior durante a pandemia da COVID-19

ABSTRACT Purpose: to analyze the quality of life and metamemory and verify their predictors in students during the COVID-19 pandemic. Methods: a cross-sectional survey carried out through online collection with the application of an initial questionnaire to characterize the sample, the WHOQOL-brief to investigate the quality of life, and the Metamemory Questionnaire in Adults (short version) - MIAr to evaluate metamemory in a group of undergraduate and postgraduate students. Data were analyzed using descriptive and inferential statistics. Multiple linear regression was performed to verify the predictor variables. A significance level of 5% (p ≤ 0.05) was considered. Results: 977 university students participated in the study, the majority (70.73%) of whom were females and with an income range below three minimum wages (63.56%). For quality of life, income range, being in the risk group for COVID-19, and age were predictors for both the undergraduate and postgraduate groups. In contrast, on an excellent metamemory, the predictors were male gender and age. Conclusion: for students, during the COVID-19 pandemic, the main predictor of quality of life was having a higher income bracket, and the main predictor of metamemory was being a male.

RESUMO Objetivo: analisar a qualidade de vida e a metamemória e verificar seus preditores em estudantes durante a pandemia da COVID-19. Métodos: trata-se de uma pesquisa transversal realizada por meio de coleta online com a aplicação de um questionário inicial para caracterizar a amostra, do WHOQOL-bref para investigar a qualidade de vida e do Questionário de Metamemória em Adultos (versão reduzida) - MIAr para avaliar a metamemória, em um grupo de estudantes de graduação e outro de pós-graduação. Os dados foram analisados por meio de estatística descritiva e inferencial. Realizou-se a regressão linear múltipla para verificar as variáveis preditoras. Foi considerado o nível de significância de 5% (p≤0,05). Resultados: participaram do estudo 977 universitários, sendo a maioria (70,73%) do gênero feminino e com faixa de renda menor que três salários-mínimos (63,56%). Para a qualidade de vida, tanto para o grupo de graduandos quanto de pós-graduandos, a faixa de renda, o grupo de risco para COVID-19 e a idade foram preditores, enquanto para uma boa metamemória os preditores foram o gênero masculino e a idade. Conclusão: para os estudantes, durante a pandemia da COVID-19, o principal preditor da qualidade de vida foi possuir maior faixa de renda e o da metamemória foi ser do gênero masculino.