Democratic quality and excess mortality during the COVID-19 pandemic.

The aim of this study is to analyse the relationship between democratic quality and excess mortality produced in the year 2020 before COVID-19 vaccinations were generalised. Using cross-sectional data from 80 countries on five continents, multiple linear regression models between excess mortality, the general democracy index and its disaggregation into five categories: electoral process and pluralism, government functioning, political participation, political culture and civil liberties were estimated. The analysis also considered, public health spending per capita, overweight inhabitants, the average temperature of the country, population over 65 years of age, The KOF Globalisation Index, and the Gross National Income per capita as control variables. It was possible to establish a strong inverse association between excess mortality per million inhabitants and the general democracy index and four of its five categories. There was a particularly strong relationship between excess mortality and the political culture dimension (-326.50, p < 0.001). The results suggest that the higher the democratic quality of the political institutions of a State and particularly of their political culture the more improved the response and management of the pandemic was in preventing deaths and protecting their citizens more effectively. Conversely, countries with lower democracy index values have higher excess mortality. Quality democratic political institutions provide more effective public health policies in the face of the COVID-19 pandemic.

Association of circulating biomarkers with illness severity measures differentiates myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID-19 condition: a prospective pilot cohort study.

BACKGROUND: Accumulating evidence suggests that autonomic dysfunction and persistent systemic inflammation are common clinical features in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID. However, there is limited knowledge regarding their potential association with circulating biomarkers and illness severity in these conditions. METHODS: This single-site, prospective, cross-sectional, pilot cohort study aimed to distinguish between the two patient populations by using self-reported outcome measures and circulating biomarkers of endothelial function and systemic inflammation status. Thirty-one individuals with ME/CFS, 23 individuals with long COVID, and 31 matched sedentary healthy controls were included. All study participants underwent non-invasive cardiovascular hemodynamic challenge testing (10 min NASA lean test) for assessment of orthostatic intolerance. Regression analysis was used to examine associations between outcome measures and circulating biomarkers in the study participants. Classification across groups was based on principal component and discriminant analyses. RESULTS: Four ME/CFS patients (13%), 1 with long COVID (4%), and 1 healthy control (3%) presented postural orthostatic tachycardia syndrome (POTS) using the 10-min NASA lean test. Compared with matched healthy controls, ME/CFS and long COVID subjects showed higher levels of ET-1 (p < 0.05) and VCAM-1 (p < 0.001), and lower levels of nitrites (NOx assessed as NO2- + NO3-) (p < 0.01). ME/CFS patients also showed higher levels of serpin E1 (PAI-1) and E-selectin than did both long COVID and matched control subjects (p < 0.01 in all cases). Long COVID patients had lower TSP-1 levels than did ME/CFS patients and matched sedentary healthy controls (p < 0.001). As for inflammation biomarkers, both long COVID and ME/CFS subjects had higher levels of TNF-α than did matched healthy controls (p < 0.01 in both comparisons). Compared with controls, ME/CFS patients had higher levels of IL-1ß (p < 0.001), IL-4 (p < 0.001), IL-6 (p < 0.01), IL-10 (p < 0.001), IP-10 (p < 0.05), and leptin (p < 0.001). Principal component analysis supported differentiation between groups based on self-reported outcome measures and biomarkers of endothelial function and inflammatory status in the study population. CONCLUSIONS: Our findings revealed that combining biomarkers of endothelial dysfunction and inflammation with outcome measures differentiate ME/CFS and Long COVID using robust discriminant analysis of principal components. Further research is needed to provide a more comprehensive characterization of these underlying pathomechanisms, which could be promising targets for therapeutic and preventive strategies in these conditions.

Transmissibility of Mycobacterium pinnipedii in a murine model.

The causative agent of tuberculosis in pinnipeds is Mycobacterium pinnipedii, a member of the Mycobacterium tuberculosis complex (MTC). The natural hosts are pinnipeds; however, other non-marine mammals, including humans, can also be infected. The transmissibility of a pathogen is related to its virulence. The transmissibility of a M. pinnipedii strain (i.e., 1856) was investigated in a murine model and compared with that of two Mycobacterium bovis strains (i.e., 534 and 04-303) with different reported virulence. Non-inoculated mice (sentinels) were co-housed with intratracheally inoculated mice. Detailed inspection of mice to search for visible tuberculosis lesions in the lungs and spleen was performed, and bacillus viability at 30, 60, and 90 days post-inoculation (dpi) was assayed. A transmissibility of 100% was recorded at 30 dpi in sentinel mice co-housed with the inoculated mice from the M. pinnipedii and M. bovis 04-303 groups, as evidenced by the recovery of viable M. pinnipedii and M. bovis from the lungs of sentinel mice. Mice inoculated with M. pinnipedii (1856) and M. bovis (534) survived until euthanized, whereas five of the M. bovis 04-303-inoculated mice died at 17 dpi. This study constitutes the first report of the transmissibility of a M. pinnipedii strain in mice and confirms the utility of this experimental model to study virulence features such as the transmission of poorly characterized MTC species.

Impact of emotional intelligence and academic self-concept on the academic performance of educational sciences undergraduates.

Over the last few years, the inclusion of psychosocial factors in the teaching and learning processes has become increasingly important due to their proven influence on students' academic performance, especially at the university stage. In this regard, the aim of this study is to analyse the impact of emotional intelligence and academic self-concept on the students' academic achievement. The results obtained revealed some differences according to gender in all the variables considered. Specifically, women presented higher levels of emotional attention, academic self-concept and performance, while men stood out in emotional clarity and emotional repair. The findings obtained show the importance of including psychosocial factors in university training plans.

Impact of CFTR modulator therapy on body composition as assessed by thoracic computed tomography: A follow-up study.

OBJECTIVE: Treatment with cystic fibrosis transmembrane conductance regulator (CFTR) modulators in individuals with cystic fibrosis (CF) has brought a significant change in forced expiratory volume in 1 second (FEV1) and clinical parameters. However, it also results in weight gain. The aim of our study is to evaluate the effect of CFTR modulator treatment on body composition, measured by computed tomography (CT). METHODS: Adult subjects with CF under follow-up at La Princesa University Hospital were recruited. All of them were on elexacaftor-tezacaftor-ivacaftor (ELX/TEZ/IVA) treatment. Body composition analysis was conducted using CT scans and an open-source software. The results were then compared with bioimpedance estimations, as well as other clinical and spirometry data. RESULTS: Our sample consisted of 26 adult subjects. The fat mass compartments on CT scans correlated with similar compartments on bioimpedance, and normal-density muscle mass exhibited a strong correlation with phase angle. Higher levels of very low-density muscle prior to treatment were associated with lower final FEV1 and less improvement in FEV1 after therapy. We observed an increase in total body area (P < 0.001), driven by increases in total fat mass (P < 0.001), subcutaneous fat (P < 0.001), visceral fat (P = 0.002), and intermuscular fat (P = 0.022). The only muscle compartment that showed an increase after treatment was very low-density muscle (P = 0.032). CONCLUSIONS: CT scans represent an opportunity to assess body composition on CF. Combination treatment with CFTR modulators, leads to an improvement in FEV1 and to an increase in body mass in all compartments primarily at the expense of fat mass.

Correlation between estimated pulse wave velocity values from two equations in healthy and under cardiovascular risk populations.

INTRODUCTION: Equations can calculate pulse wave velocity (ePWV) from blood pressure values (BP) and age. The ePWV predicts cardiovascular events beyond carotid-femoral PWV. We aimed to evaluate the correlation between four different equations to calculate ePWV. METHODS: The ePWV was estimated utilizing mean BP (MBP) from office BP (MBPOBP) or 24-hour ambulatory BP (MBP24-hBP). We separated the whole sample into two groups: individuals with risk factors and healthy individuals. The e-PWV was calculated as follows: [Formula: see text] [Formula: see text] We calculated the concordance correlation coefficient (Pc) between e1-PWVOBP vs e2-PWVOBP, e1-PWV24-hBP vs e2-PWV24-hBP, and mean values of e1-PWVOBP, e2-PWVOBP, e1-PWV24-hBP and e2-PWV24-hBP. The multilevel regression model determined how much the ePWVs are influenced by age and MBP values. RESULTS: We analyzed data from 1541 individuals; 1374 ones with risk factors and 167 healthy ones. The values are presented for the entire sample, for risk-factor patients and for healthy individuals respectively. The correlation between e1-PWVOBP with e2-PWVOBP and e1-PWV24-hBP with e2-PWV24-hBP was almost perfect. The Pc for e1-PWVOBP vs e2-PWVOBP was 0.996 (0.995-0.996), 0.996 (0.995-0.996), and 0.994 (0.992-0.995); furthermore, it was 0.994 (0.993-0.995), 0.994 (0.994-0.995), 0.987 (0.983-0.990) to the e1-PWV24-hBP vs e2-PWV24-hBP. There were no significant differences between mean values (m/s) for e1-PWVOBP vs e2-PWVOBP 8.98±1.9 vs 8.97±1.8; p = 0.88, 9.14±1.8 vs 9.13±1.8; p = 0.88, and 7.57±1.3 vs 7.65±1.3; p = 0.5; mean values are also similar for e1-PWV24-hBP vs e2-PWV24-hBP, 8.36±1.7 vs 8.46±1.6; p = 0.09, 8.50±1.7 vs 8.58±1.7; p = 0.21 and 7.26±1.3 vs 7.39±1.2; p = 0.34. The multiple linear regression showed that age, MBP, and age2 predicted more than 99.5% of all four e-PWV. CONCLUSION: Our data presents a nearly perfect correlation between the values of two equations to calculate the estimated PWV, whether utilizing office or ambulatory blood pressure.

Personalized Management of Fatigue in Individuals With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID Using a Smart Digital mHealth Solution: Protocol for a Participatory Design Approach.

BACKGROUND: Fatigue is the most common symptom in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID, impacting patients' quality of life; however, there is currently a lack of evidence-based context-aware tools for fatigue self-management in these populations. OBJECTIVE: This study aimed to (1) address fatigue in ME/CFS and long COVID through the development of digital mobile health solutions for self-management, (2) predict perceived fatigue severity using real-time data, and (3) assess the feasibility and potential benefits of personalized digital mobile health solutions. METHODS: The MyFatigue project adopts a patient-centered approach within the participatory health informatics domain. Patient representatives will be actively involved in decision-making processes. This study combines inductive and deductive research approaches, using qualitative studies to generate new knowledge and quantitative methods to test hypotheses regarding the relationship between factors like physical activity, sleep behaviors, and perceived fatigue in ME/CFS and long COVID. Co-design methods will be used to develop a personalized digital solution for fatigue self-management based on the generated knowledge. Finally, a pilot study will evaluate the feasibility, acceptance, and potential benefits of the digital health solution. RESULTS: The MyFatigue project opened to enrollment in November 2023. Initial results are expected to be published by the end of 2024. CONCLUSIONS: This study protocol holds the potential to expand understanding, create personalized self-management approaches, engage stakeholders, and ultimately improve the well-being of individuals with ME/CFS and long COVID. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/50157.

Kefir4All, a citizen science initiative to raise awareness of the roles that microbes play in food fermentation.

Microorganisms are ubiquitous in nature and are central to human, animal, environmental, and planetary health. They play a particularly important role in the food chain and the production of high-quality, safe, and health-promoting foods, especially fermented foods. This important role is not always apparent to members of the public. Here, we describe Kefir4All, a citizen science project designed to provide the general public with an opportunity to expand their awareness, knowledge, and practical skills relating to microbiology, introduced through the medium of producing fermented food, i.e., milk kefir or water kefir. During the course of Kefir4All, 123 citizen scientists, from second-level school and non-school settings, participated in a study to track changes in the microbial composition of kefirs, by performing and recording details of milk kefir or water kefir fermentations they performed in their homes or schools over the 21-week project. At the start of the study, the citizen scientists were provided with milk or water kefir grains to initiate the fermentations. Both types of kefir grain are semi-solid, gelatinous-like substances, composed of exopolysaccharides and proteins, containing a symbiotic community of bacteria and yeast. The experimental component of the project was complemented by a number of education and outreach events, including career talks and a site visit to our research center (Kefir Day). At the end of the study, a report was provided to each citizen scientist, in which individualized results of their fermenting activities were detailed. A number of approaches were taken to obtain feedback and other insights from the citizen scientists. Evaluations took place before and after the Kefir4All project to gauge the citizen scientist's self-reported awareness, knowledge, and interest in microbiology and fermented foods. Further insights into the level of citizen science participation were gained through assessing the number of samples returned for analysis and the level of participation of the citizen scientists throughout the project. Notably, the survey results revealed a self-reported, increased interest in, and general knowledge of, science among the Kefir4All citizen scientists after undertaking the project and a willingness to take part in further citizen science projects. Ultimately, Kefir4All represents an example of the successful integration of citizen science into existing education and research systems.

Cultural evolution: A review of theoretical challenges.

The rapid growth of cultural evolutionary science, its expansion into numerous fields, its use of diverse methods, and several conceptual problems have outpaced corollary developments in theory and philosophy of science. This has led to concern, exemplified in results from a recent survey conducted with members of the Cultural Evolution Society, that the field lacks 'knowledge synthesis', is poorly supported by 'theory', has an ambiguous relation to biological evolution and uses key terms (e.g. 'culture', 'social learning', 'cumulative culture') in ways that hamper operationalization in models, experiments and field studies. Although numerous review papers in the field represent and categorize its empirical findings, the field's theoretical challenges receive less critical attention even though challenges of a theoretical or conceptual nature underlie most of the problems identified by Cultural Evolution Society members. Guided by the heterogeneous 'grand challenges' emergent in this survey, this paper restates those challenges and adopts an organizational style requisite to discussion of them. The paper's goal is to contribute to increasing conceptual clarity and theoretical discernment around the most pressing challenges facing the field of cultural evolutionary science. It will be of most interest to cultural evolutionary scientists, theoreticians, philosophers of science and interdisciplinary researchers.

Clinical features and disease progression of elderly patients at the ICU setting.

OBJECTIVE: To describe and characterize a cohort of octogenarian patients admitted to the ICU of the University Central Hospital of Asturias (HUCA). DESIGN: Retrospective, observational and descriptive study of 14 months' duration. SETTING: Cardiac and Medical intensive care units (ICU) of the HUCA (Oviedo). PARTICIPANTS: Patients over 80 years old who were admitted to the ICU for more than 24 h. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Age, sex, comorbidity, functional dependence, treatment, complications, evolution, mortality. RESULTS: The most frequent reasons for admission were cardiac surgery and pneumonia. The average admission stay was significantly longer in patients under 85 years of age (p = 0,037). 84,3% of the latter benefited from invasive mechanical ventilation compared to 46,2% of older patients (p = <0,001). Patients over 85 years of age presented greater fragility. Admission for cardiac surgery was associated with a lower risk of mortality (HR = 0,18; 95% CI (0,062-0,527; p = 0,002). CONCLUSIONS: The results have shown an association between the reason for admission to the ICU and the risk of mortality in octogenarian patients. Cardiac surgery was associated with a better prognosis compared to medical pathology, where pneumonia was associated with a higher risk of mortality. Furthermore, a significant positive association was observed between age and frailty.

Ductal Adenocarcinoma of the Prostate with Novel Genetic Alterations Characterized by Next-Generation Sequencing.

Ductal adenocarcinoma of the prostate (DAP) is an uncommon variant of prostate cancer associated with aggressive disease and poor outcome. It presents most frequently as a mixed tumor combined with acinar adenocarcinoma. Although the histopathological features of DAP are well known, its genomic characteristics are still evolving, prompting the suggestion that all DAP would benefit from molecular analysis with the purpose of improving tumor recognition, genetic classification, and, ultimately, personalized therapy. Herein, we report a case of DAP with novel genetic alterations (BCOR P1153S, ERG M219I, KDR A750E, POLE S1896P, and RAD21 T461del).

"I'm Not Only a Body": Change in Thoughts about the Body after Mirror Exposure Treatment in Women with Obesity-An Exploratory Study.

Nowadays, obesity (OB) is one of the most important health problems in population-wide health. In addition to its physical consequences, it is a risk factor for the development of psychological problems, including body dissatisfaction (BD). This is why the treatment of BD is essential for its prevention. However, this has mostly been studied from a quantitative perspective, without focusing on the discomfort experienced by the person and the accompanying thoughts and emotions. In this study, 26 women with obesity (BMI > 30 kg/m2) participated, of whom 16 had high BD and 10 had low BD, as measured by the BSQ questionnaire. The women with high BD underwent six sessions of exposure to their own body in front of a mirror, recording the discomfort experienced with this vision during the session. In addition, all participants recorded positive and negative thoughts towards their body before and after these sessions. After the exposure treatment sessions, a reduction in symptomatology (BD, discomfort when visualizing one's own body) was observed, as well as a change in the thoughts expressed by the participants, both in quantity (fewer negative thoughts) and in quality (a more positive self-perception and/or in more respectful terms used towards themselves). In conclusion, such treatments prove to be effective in reducing subjective discomfort and body-related thoughts in women with obesity.

Effects of Mindful Eating in Patients with Obesity and Binge Eating Disorder.

INTRODUCTION: Binge eating disorder (BED) is a psychiatric illness related to a high frequency of episodes of binge eating, loss of control, body image dissatisfaction, and suffering caused by overeating. It is estimated that 30% of patients with BED are affected by obesity. "Mindful eating" (ME) is a promising new eating technique that can improve self-control and good food choices, helping to increase awareness about the triggers of binge eating episodes and intuitive eating training. OBJECTIVES: To analyze the impact of ME on episodes of binge eating, body image dissatisfaction, quality of life, eating habits, and anthropometric data [weight, Body Mass Index (BMI), and waist circumference] in patients with obesity and BED. METHOD: This quantitative, prospective, longitudinal, and experimental study recruited 82 patients diagnosed with obesity and BED. The intervention was divided into eight individual weekly meetings, guided by ME sessions, nutritional educational dynamics, cooking workshops, food sensory analyses, and applications of questionnaires [Body Shape Questionnaire (BSQ); Binge Eating Scale (BES); Quality of Life Scale (WHOQOL-BREF)]. There was no dietary prescription for calories, carbohydrates, proteins, fats, and fiber. Patients were only encouraged to consume fewer ultra-processed foods and more natural and minimally processed foods. The meetings occurred from October to November 2023. STATISTICAL ANALYSIS: To carry out inferential statistics, the Shapiro-Wilk test was used to verify the normality of variable distribution. All variables were identified as non-normal distribution and were compared between the first and the eighth week using a two-tailed Wilcoxon test. Non-Gaussian data were represented by median ± interquartile range (IQR). Additionally, α < 0.05 and p < 0.05 were adopted. RESULTS: Significant reductions were found from the first to the eighth week for weight, BMI, waist circumference, episodes of binge eating, BSQ scale score, BES score, and total energy value (all p < 0.0001). In contrast, there was a significant increase in the WHOQOL-BREF score and daily water intake (p < 0.0001). CONCLUSIONS: ME improved anthropometric data, episodes of binge eating, body image dissatisfaction, eating habits, and quality of life in participants with obesity and BED in the short-term. However, an extension of the project will be necessary to analyze the impact of the intervention in the long-term.

State-of-the-art silicon carbide diode dosimeters for ultra-high dose-per-pulse radiation at FLASH radiotherapy.

Objective.The successful implementation of FLASH radiotherapy in clinical settings, with typical dose rates >40 Gy s-1, requires accurate real-time dosimetry.Approach.Silicon carbide (SiC) p-n diode dosimeters designed for the stringent requirements of FLASH radiotherapy have been fabricated and characterized in an ultra-high pulse dose rate electron beam. The circular SiC PiN diodes were fabricated at IMB-CNM (CSIC) in 3µm epitaxial 4H-SiC. Their characterization was performed in PTB's ultra-high pulse dose rate reference electron beam. The SiC diode was operated without external bias voltage. The linearity of the diode response was investigated up to doses per pulse (DPP) of 11 Gy and pulse durations ranging from 3 to 0.5µs. Percentage depth dose measurements were performed in ultra-high dose per pulse conditions. The effect of the total accumulated dose of 20 MeV electrons in the SiC diode sensitivity was evaluated. The temperature dependence of the response of the SiC diode was measured in the range 19 °C-38 °C. The temporal response of the diode was compared to the time-resolved beam current during each electron beam pulse. A diamond prototype detector (flashDiamond) and Alanine measurements were used for reference dosimetry.Main results.The SiC diode response was independent both of DPP and of pulse dose rate up to at least 11 Gy per pulse and 4 MGy s-1, respectively, with tolerable deviation for relative dosimetry (<3%). When measuring the percentage depth dose under ultra-high dose rate conditions, the SiC diode performed comparably well to the reference flashDiamond. The sensitivity reduction after 100 kGy accumulated dose was <2%. The SiC diode was able to follow the temporal structure of the 20 MeV electron beam even for irregular pulse estructures. The measured temperature coefficient was (-0.079 ± 0.005)%/°C.Significance.The results of this study demonstrate for the first time the suitability of silicon carbide diodes for relative dosimetry in ultra-high dose rate pulsed electron beams up to a DPP of 11 Gy per pulse.

The Longitudinal Microbial and Metabolic Landscape of infant Cystic Fibrosis: The gut-lung axis.

BACKGROUND AND AIM: : In cystic fibrosis (CF), gastrointestinal dysfunction and lower airway infection occur early and are independently associated with poorer outcomes in childhood. This study aimed to define the relationship between the microbiota at each niche during the first 2-years of life, its association with growth and airway inflammation, and explanatory features in the metabolome. MATERIALS AND METHODS: Sixty-seven bronchoalveolar lavage (BAL), 62 plasma and 105 stool samples were collected from 39 infants with CF between 0-24-months who were treated with prophylactic antibiotics. 16S rRNA amplicon and shotgun metagenomic sequencing were performed on BAL and stool respectively; metabolomic analyses were performed on all sample types. Sequencing data from healthy age-matched infants were used as controls. RESULTS: Bacterial diversity increased over the first 2-years in both BAL and stool, and microbial maturation was delayed in comparison to healthy controls from the RESONANCE cohort. Correlations between their respective abundances in both sites suggest stool may serve as a non-invasive alternative for detecting BAL Pseudomonas and Veillonella. Multi-site metabolomic analyses revealed age- and growth-related changes, associations with neutrophilic airway inflammation, and a set of core systemic metabolites. BAL Pseudomonas abundance was correlated with altered stool microbiome composition and systemic metabolite alterations, highlighting a complex gut-plasma-lung interplay and new targets with therapeutic potential. CONCLUSION: Exploration of the gut-lung microbiome and metabolome reveals diverse multi-site interactions in CF that emerge in early life. Gut-lung metabolomic links with airway inflammation and Pseudomonas abundance warrant further investigation for clinical utility, particularly in non-expectorating patients.

Novel Biomarkers of Bone Metabolism.

Bone represents a metabolically active tissue subject to continuous remodeling orchestrated by the dynamic interplay between osteoblasts and osteoclasts. These cellular processes are modulated by a complex interplay of biochemical and mechanical factors, which are instrumental in assessing bone remodeling. This comprehensive evaluation aids in detecting disorders arising from imbalances between bone formation and reabsorption. Osteoporosis, characterized by a reduction in bone mass and strength leading to heightened bone fragility and susceptibility to fractures, is one of the more prevalent chronic diseases. Some epidemiological studies, especially in patients with chronic kidney disease (CKD), have identified an association between osteoporosis and vascular calcification. Notably, low bone mineral density has been linked to an increased incidence of aortic calcification, with shared molecules, mechanisms, and pathways between the two processes. Certain molecules emerging from these shared pathways can serve as biomarkers for bone and mineral metabolism. Detecting and evaluating these alterations early is crucial, requiring the identification of biomarkers that are reliable for early intervention. While traditional biomarkers for bone remodeling and vascular calcification exist, they suffer from limitations such as low specificity, low sensitivity, and conflicting results across studies. In response, efforts are underway to explore new, more specific biomarkers that can detect alterations at earlier stages. The aim of this review is to comprehensively examine some of the emerging biomarkers in mineral metabolism and their correlation with bone mineral density, fracture risk, and vascular calcification as well as their potential use in clinical practice.

Soluble Klotho, a Potential Biomarker of Chronic Kidney Disease-Mineral Bone Disorders Involved in Healthy Ageing: Lights and Shadows.

Shortly after the discovery of Klotho, interest grew in its potential role in chronic kidney disease (CKD). There are three isoforms of the Klotho protein: αKlotho, ßKlotho and γKlotho. This review will focus on αKlotho due to its relevance as a biomarker in CKD. αKlotho is synthesized mainly in the kidneys, but it can be released into the bloodstream and urine as soluble Klotho (sKlotho), which undertakes systemic actions, independently or in combination with FGF23. It is usually accepted that sKlotho levels are reduced early in CKD and that lower levels of sKlotho might be associated with the main chronic kidney disease-mineral bone disorders (CKD-MBDs): cardiovascular and bone disease. However, as results are inconsistent, the applicability of sKlotho as a CKD-MBD biomarker is still a matter of controversy. Much of the inconsistency can be explained due to low sample numbers, the low quality of clinical studies, the lack of standardized assays to assess sKlotho and a lack of consensus on sample processing, especially in urine. In recent decades, because of our longer life expectancies, the prevalence of accelerated-ageing diseases, such as CKD, has increased. Exercise, social interaction and caloric restriction are considered key factors for healthy ageing. While exercise and social interaction seem to be related to higher serum sKlotho levels, it is not clear whether serum sKlotho might be influenced by caloric restriction. This review focuses on the possible role of sKlotho as a biomarker in CKD-MBD, highlighting the difference between solid knowledge and areas requiring further research, including the role of sKlotho in healthy ageing.

Effect of Christmas Holidays on Type 1 Diabetes Mellitus in Users of Glucose Flash Systems.

OBJECTIVE: Christmas holidays can impact weight and glycemic control in type 2 diabetes, but their effect on type 1 diabetes (T1D) remains understudied. This study assessed how Christmas holidays affect individuals with T1D who use flash continuous glucose monitoring systems. METHODS: This retrospective study involved 812 adults diagnosed with T1D recruited from 3 hospitals. Clinical, anthropometric, and socioeconomic data were collected. Glucose metrics from 14 days before January 1st, and before December 1st and February 1st as control periods, were recorded. Analyses adjusted for multiple variables were conducted to assess the holiday season's impact on glycemic control. RESULTS: The average time in range during the holidays (60.0 ± 17.2%) was lower compared to December (61.9 ± 17.2%, P < .001) and February (61.7 ± 17.7%, P < .001). Time above range (TAR > 180 mg/dL) was higher during Christmas (35.8 ± 18.2%) compared to December (34.1 ± 18.3%, P < .001) and February (34.2 ± 18.4%, P < .001). Differences were also observed in TAR >250 mg/dL, coefficient of variation, and average glucose (P < .05). No differences were found in time below range or other metrics. Linear regression models showed that the holidays reduced time in range by 1.9% (ß = -1.92, P = .005) and increased TAR >180 mg/dL by 1.8% (ß = 1.75, P = .016). CONCLUSION: Christmas holidays are associated with a mild and reversible deterioration in glucose metrics among individuals with T1D using flash continuous glucose monitoring, irrespective of additional influencing factors. These discoveries can be useful to advise individuals with diabetes during the festive season and to recognize potential biases within studies conducted during this timeframe.

Akkermansia muciniphila-induced trained immune phenotype increases bacterial intracellular survival and attenuates inflammation.

The initial exposure to pathogens and commensals confers innate immune cells the capacity to respond distinctively upon a second stimulus. This training capacity might play key functions in developing an adequate innate immune response to the continuous exposure to bacteria. However, the mechanisms involved in induction of trained immunity by commensals remain mostly unexplored. A. muciniphila represents an attractive candidate to study the promotion of these long-term responses. Here, we show that priming of macrophages with live A. muciniphila enhances bacterial intracellular survival and decreases the release of pro- and anti-inflammatory signals, lowering the production of TNF and IL-10. Global transcriptional analysis of macrophages after a secondary exposure to the bacteria showed the transcriptional rearrangement underpinning the phenotype observed compared to acutely exposed cells, with the increased expression of genes related to phagocytic capacity and those involved in the metabolic adjustment conducing to innate immune training. Accordingly, key genes related to bacterial killing and pro-inflammatory pathways were downregulated. These data demonstrate the importance of specific bacterial members in the modulation of local long-term innate immune responses, broadening our knowledge of the association between gut microbiome commensals and trained immunity as well as the anti-inflammatory probiotic potential of A. muciniphila.