Strategies to improve cardiovascular health and treatment of dyslipidemia in Spain. Expert Insights Project. / Estrategias de mejora en la salud cardiovascular y el tratamiento de la dislipidemia en España. Proyecto Expert Insights.

OBJECTIVES: To gather opinions, recommendations, and proposals for improvement from Spanish clinicians on cardiovascular (CV) health, with particular focus on dyslipidemia management. METHODS: The Expert Insights project involved 8face-to-face sessions held throughout Spain, attended by 138 CV health experts. Clinicians answered to 25 questions survey related to CV health and dyslipidemia control. Each session included an analysis and a discussion on the perceived realities and areas for improvement. RESULTS: 72% of centers have a standardized process for monitoring patients after a CV episode at discharge, but only 37% during their clinical follow-up. Patient care and management are dependent on the physician, with a lack of coordination between hospital specialties and primary care (PC). 95% of clinicians believe it is necessary to standarize treatment optimization. 65% of centers prescribe combined lipid-lowering treatment after a CV episode. Updating cLDL levels in the Therapeutic Positioning Report and standardizing and globalizing the prescription document would reduce iPCSK9 prescription barriers and lead to more equitable access. CONCLUSIONS: In Spain, there are significant deficiencies in the management of dyslipidemia, with a great need for a consensus on standardizing management processes and optimizing patient treatment. The opinions, recommendations, and improvement proposals from Spanish clinicians on CV health are an important starting point to improve the situation.

Understanding Macrophage Interaction with Antimony-Doped Tin Oxide Plasmonic Nanoparticles.

Antimony-doped tin oxide nanoparticles (ATO NPs) have emerged as a promising tool in biomedical applications, namely robust photothermal effects upon near-infrared (NIR) light exposure, enabling controlled thermal dynamics to induce spatial cell death. This study investigated the interplay between ATO NPs and macrophages, understanding cellular uptake and cytokine release. ATO NPs demonstrated biocompatibility with no impact on macrophage viability and cytokine secretion. These findings highlight the potential of ATO NPs for inducing targeted cell death in cancer treatments, leveraging their feasibility, unique NIR properties, and safe interactions with immune cells. ATO NPs offer a transformative platform with significant potential for future biomedical applications by combining photothermal capabilities and biocompatibility.

PCSK9 inhibitors on the management of primary and secondary cardiovascular prevention.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have represented an important change in the management of hypercholesterolemia, although, until now, they have barely been used. Without PCSK9i, many patients with atherosclerotic cardiovascular disease (CVD) or those at very high risk do not reach their therapeutic LDLc objectives. OBJECTIVE: The analysis aimed to examine the clinical and biochemical characteristics of subjects receiving PCSK9i treatment in the Dyslipidemia Registry of the Spanish Atherosclerosis Society. METHODS: All consecutive subjects aged ≥ 18 years from different Lipid Units included in the Dyslipidemia Registry of the SEA were analyzed. Inclusion criteria consisted of unrelated patients aged ≥ 18 at the time of inclusion with hypercholesterolemia (LDL-C ≥ 130 mg/dL or non-HDL-C ≥ 160 mg/dL after the exclusion of secondary causes) who were studied for at least two years after inclusion. Participants' baseline and final visit clinical and biochemical characteristics were analyzed based on whether they were on primary or secondary prevention and whether they were taking PCSK9i at the end of follow-up. RESULTS: Eight hundred twenty-nine patients were analyzed, 7014 patients in primary prevention and 1281 in secondary prevention at baseline. 4127 subjects completed the required follow-up for the final analysis. The median follow-up duration was 7 years (IQR 3.0-10.0). Five hundred patients (12.1%) were taking PCSK9i at the end of the follow-up. The percentage of PCSK9i use reached 35.6% (n = 201) and 8.7% (n = 318) in subjects with and without CVD, respectively. Subjects on PCSK9i and oral lipid-lowering agents with and without CVD achieved LDLc reductions of 80.3% and 75.1%, respectively, concerning concentrations without lipid-lowering drugs. Factors associated with PCSK9i use included increasing age, LDLc without lipid-lowering drugs and the Dutch Lipid Clinic Network (DLCN) score. However, hypertension, diabetes, smoking, and LDLc after oral lipid-lowering drugs were not independent factors associated with PCSK9i prescription. In subjects with CVD, the use of PCSK9i was higher in men than in women (an odds ratio of 1.613, P = 0.048). CONCLUSIONS: Approximately one-third of CVD patients received PCSK9i at the end of follow-up. The use of PCSK9i was more focused on baseline LDLc concentrations rather than on CVD risk. Women received less PCSK9i in secondary prevention compared to men.

Challenges and Opportunities with at-Home Blood Collection for HIV-1 Viral Load Monitoring among Sexual Minoritized Men who use Stimulants.

Sexually minoritized men (SMM) with HIV who use stimulants experience difficulties achieving and maintaining an undetectable viral load (VL). Home-based VL monitoring could augment HIV care by supporting interim, early identification of detectable VL. We describe implementation challenges associated with a home-collection device for laboratory-based VL testing among SMM with HIV who use stimulants. From March-May 2022, cisgender SMM with HIV reporting moderate-to-severe stimulant use disorder and suboptimal (< 90%) past-month antiretroviral therapy (ART) adherence were recruited via a consent-to-contact participant registry. Eligible men completed teleconference-based informed consent and were mailed a HemaSpot-HD blood collection device (volume capacity 160 µL; lower limit of detection 839 copies/mL) with detailed instructions for home blood self-collection and return shipment. Implementation process measures included estimated blood volume and VL quantification. Among 24 participants, 21 (88%) returned specimens with a median duration of 23 days (range: 10-71 days) between sending devices to participants and receiving specimens. Of these, 13/21 (62%) included enough blood (≥ 40 µL) for confidence in detectable/undetectable results; 10/13 (77%) had detectable VL, with 4/10 (40%) were quantifiable at ≥ 839 copies/mL. The remaining 8/21 had low blood volume (< 40 µL), but 3/8 (38%) still had detectable VL, with 1/3 (33%) quantifiable at ≥ 839 copies/mL. Home blood collection of ≥ 40 µL using HemaSpot-HD was feasible among this high-priority population, with > 50% having a VL detected. However, interim VL monitoring using HemaSpot-HD among those experiencing difficulties with ART adherence may be strengthened by building rapport via teleconferencing and providing detailed instructions to achieve adequate sample volume.

Microbiome mapping in dairy industry reveals new species and genes for probiotic and bioprotective activities.

The resident microbiome in food industries may impact on food quality and safety. In particular, microbes residing on surfaces in dairy industries may actively participate in cheese fermentation and ripening and contribute to the typical flavor and texture. In this work, we carried out an extensive microbiome mapping in 73 cheese-making industries producing different types of cheeses (fresh, medium and long ripened) and located in 4 European countries. We sequenced and analyzed metagenomes from cheese samples, raw materials and environmental swabs collected from both food contact and non-food contact surfaces, as well as operators' hands and aprons. Dairy plants were shown to harbor a very complex microbiome, characterized by high prevalence of genes potentially involved in flavor development, probiotic activities, and resistance to gastro-intestinal transit, suggesting that these microbes may potentially be transferred to the human gut microbiome. More than 6100 high-quality Metagenome Assembled Genomes (MAGs) were reconstructed, including MAGs from several Lactic Acid Bacteria species and putative new species. Although microbial pathogens were not prevalent, we found several MAGs harboring genes related to antibiotic resistance, highlighting that dairy industry surfaces represent a potential hotspot for antimicrobial resistance (AR) spreading along the food chain. Finally, we identified facility-specific strains that can represent clear microbial signatures of different cheesemaking facilities, suggesting an interesting potential of microbiome tracking for the traceability of cheese origin.

Importance of local and systemic factors in preventing implant displacement in the mandibular body: a scoping review of existing literature.

BACKGROUND: The aim of this research was to analyse the current literature on displaced dental implants in the mandibular body, including local and systemic variables related to their cause, and to identify the most frequent location. METHODS: The study conducted a search of three databases (Pubmed, Scopus, and Web of Science) using specific index terms such as 'dental implant', 'displacement', 'dislocation', 'displaced', and 'mandible'. The analysis focused on the direction of displacement and the characteristics of the bone tissue (bone quality, density, and quantity) in cases where dental implants were displaced. RESULTS: A total of 371 articles were obtained. Thirteen of these articles were selected and read in full. To define bone quality, the Lekholm and Zarb classification, modified by Rosas et al., was used. The type II-B bone, which is characterized by thick cortical bone surrounding cancellous bone with extremely wide medullary spaces, presented the largest number of complications. Twenty-two cases were found in which the displacement direction was horizontal. Of these, four were displaced vestibularly, fourteen lingually, and four remained in the center. Additionally, 24 cases presented vertical displacement, with 12 displaced towards the inferior border of the mandible, 9 towards the middle or adjacent to the inferior dental nerve canal, and 3 above the inferior dental nerve canal. CONCLUSION: The accidental displacement of implants within the mandibular body is associated with various risk factors, including the characteristics of the bony trabeculum and the size of the medullary spaces. It is reasonable to suggest that only an adequate pre-surgical diagnostic evaluation, with the help of high-resolution tomographic images that allow a previous evaluation of these structures, will help to have better control over the other factors, thus minimizing the risk of displacement.

Long-term sex differences in atherosclerotic cardiovascular disease in individuals with heterozygous familial hypercholesterolaemia in Spain: a study using data from SAFEHEART, a nationwide, multicentre, prospective cohort study.

BACKGROUND: Sex differences in atherosclerotic cardiovascular disease (ASCVD) in familial hypercholesterolaemia have been reported but are not fully established. We aimed to assess sex differences in the risk of ASCVD and life-time burden of ASCVD in patients with heterozygous familial hypercholesterolaemia. METHODS: SAFEHEART is a nationwide, multicentre, long-term prospective cohort study conducted in 25 tertiary care hospitals and one regional hospital in Spain. Participants in the SAFEHEART study aged 18 years or older with genetically confirmed familial hypercholesterolaemia were included in our analysis. Data were obtained between Jan 26, 2004, and Nov 30, 2022. ASCVD and age at onset were documented at enrolment and at follow-up. Our aim was to investigate the differences by sex in the risk and burden of ASCVD in patients with heterozygous familial hypercholesterolaemia, over the study follow-up and over the life course. The SAFEHEART study is registered with ClinicalTrials.gov, NCT02693548. FINDINGS: Of the 5262 participants in SAFEHEART at the time of analysis, 3506 (1898 [54·1%] female and 1608 [45·9%] male participants) met the inclusion criteria and were included in the current study. Mean age was 46·1 years (SD 15·5) and median follow-up was 10·3 years (IQR 6·4-13·0). Mean on-treatment LDL-cholesterol at follow-up was 3·1 mmol/L (SD 1·4) in females and 3·0 mmol/L (1·5) in males. LDL-cholesterol reductions over time were similar in both sexes (1·39 mmol/L [95% CI 1·30-1·47] absolute reduction in females vs 1·39 mmol/L [1·29-1·48] in males; p=0·98). At enrolment, 130 (6·8%) females and 304 (18·9%) males (p<0·0001) had cardiovascular disease. During follow-up, 134 (7·1%) females and 222 (13·8%) males (p<0·0001) had incident cardiovascular events. Median age at first ASCVD event (mostly due to coronary artery disease) was 61·6 years (IQR 50·0-71·4) in females and 50·6 years (42·0-58·6) in males (p<0·0001). The adjusted hazard ratio for ASCVD in males compared with females during follow-up was 1·90 (95% CI 1·49-2·42) and for cardiovascular death was 1·74 (1·11-2·73). Major adverse cardiovascular disease event (MACE)-free survival from birth was lower in males than females (hazard ratio 3·52 [95% CI 2·98-4·16]; p<0·0001). Median MACE-free survival time was 90·1 years (95% CI 86·5-not estimable) in females and 71·0 years (69·2-74·6) in males. The age at which 25% of female participants have had a MACE event was 74·9 years, this figure was 55·5 years in male participants. INTERPRETATION: Our findings suggest that the burden and risk of ASCVD are markedly lower in females than males with familial hypercholesterolaemia. The impact of sex needs to be considered to improve risk stratification and personalised management in patients with heterozygous familial hypercholesterolaemia. FUNDING: Fundación Hipercolesterolemia Familiar, the Instituto de Salud Carlos III, and Next Generation EU funds from the Recovery and Resilience Mechanism Program. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Supporting treatment adherence for resilience and thriving (START): protocol for a mHealth randomized controlled trial.

BACKGROUND: Although behavioral interventions show some promise for reducing stimulant use and achieving durable viral suppression in sexual minority men (SMM) with HIV, scalable mHealth applications are needed to optimize their reach and cost-effectiveness. METHODS: Supporting Treatment Adherence for Resilience and Thriving (START) is a randomized controlled trial (RCT) testing the efficacy and cost-effectiveness of a mHealth application that integrates evidence-based positive affect regulation skills with self-monitoring of adherence and mood. The primary outcome is detectable HIV viral load (i.e., > 300 copies/mL) from self-collected dried blood spot (DBS) specimens at 6 months. Secondary outcomes include detectable DBS viral load at 12 months, self-reported stimulant use severity, anti-retroviral therapy (ART) adherence, and positive affect over 12 months. A national sample of up to 250 SMM with HIV who screen positive for stimulant use disorder and reporting suboptimal ART adherence is being recruited via social networking applications through April of 2024. After providing informed consent, participants complete a run-in period (i.e., waiting period) including two baseline assessments with self-report measures and a self-collected DBS sample. Those who complete the run-in period are randomized to either the START mHealth application or access to a website with referrals to HIV care and substance use disorder treatment resources. Participants provide DBS samples at baseline, 6, and 12 months to measure HIV viral load as well as complete self-report measures for secondary outcomes at quarterly follow-up assessments over 12 months. DISCUSSION: To date, we have paid $117,500 to advertise START on social networking applications and reached 1,970 eligible participants ($59.77 per eligible participant). Although we identified this large national sample of potentially eligible SMM with HIV who screen positive for a stimulant use disorder and report suboptimal ART adherence, only one-in-four have enrolled in the RCT. The run-in period has proven to be crucial for maintaining scientific rigor and reproducibility of this RCT, such that only half of consented participants complete the required study enrollment activities and attended a randomization visit. Taken together, findings will guide adequate resource allocation to achieve randomization targets in future mHealth research SMM with HIV who use stimulants. TRIAL REGISTRATION: This protocol was registered on clinicaltrials.gov (NCT05140876) on December 2, 2021.

Unexplored microbial diversity from 2,500 food metagenomes and links with the human microbiome.

Complex microbiomes are part of the food we eat and influence our own microbiome, but their diversity remains largely unexplored. Here, we generated the open access curatedFoodMetagenomicData (cFMD) resource by integrating 1,950 newly sequenced and 583 public food metagenomes. We produced 10,899 metagenome-assembled genomes spanning 1,036 prokaryotic and 108 eukaryotic species-level genome bins (SGBs), including 320 previously undescribed taxa. Food SGBs displayed significant microbial diversity within and between food categories. Extension to >20,000 human metagenomes revealed that food SGBs accounted on average for 3% of the adult gut microbiome. Strain-level analysis highlighted potential instances of food-to-gut transmission and intestinal colonization (e.g., Lacticaseibacillus paracasei) as well as SGBs with divergent genomic structures in food and humans (e.g., Streptococcus gallolyticus and Limosilactobabillus mucosae). The cFMD expands our knowledge on food microbiomes, their role in shaping the human microbiome, and supports future uses of metagenomics for food quality, safety, and authentication.

Teleworking for medical reasons. Evidence from a Spanish multinational company.

OBJECTIVES: The aim of the study is to describe the most common medical grounds for requesting or extending teleworking and to examine which requests are typically approved. This study also investigates whether there is a correlation with gender, age, or job location. METHODS: A prevalence study of 33,190 Spanish employees found that last year, 106 teleworking requests were addressed exclusively for medical reasons. RESULTS: The most frequent cause was musculoskeletal issues (30%). Of all the requests, 58% were denied, 33% were temporarily approved, primarily for musculoskeletal reasons (p < 0.05), and 8% were indefinitely approved. Requests were predominantly made by women (p < 0.05). Indefinite approvals were more prevalent among male employees (p < 0.05). CONCLUSIONS: Musculoskeletal reasons were the primary cause for teleworking applications and for the temporary granting of teleworking. Teleworking appears to be associated with gender and job location.

Evolutionary drivers of reproductive fitness in two endangered forest trees.

Population genetics theory predicts a relationship between fitness, genetic diversity (H0) and effective population size (Ne), which is often tested through heterozygosity-fitness correlations (HFCs). We tested whether population and individual fertility and heterozygosity are correlated in two endangered Mexican spruces (Picea martinezii and Picea mexicana) by combining genomic, demographic and reproductive data (seed development and germination traits). For both species, there was a positive correlation between population size and seed development traits, but not germination rate. Individual genome-wide heterozygosity and seed traits were only correlated in P. martinezii (general-effects HFC), and none of the candidate single nucleotide polymorphisms (SNPs) associated with individual fertility showed heterozygote advantage in any species (no local-effects HFC). We observed a single and recent (c. 30 thousand years ago (ka)) population decline for P. martinezii; the collapse of P. mexicana occurred in two phases separated by a long period of stability (c. 800 ka). Recruitment always contributed more to total population census than adult trees in P. mexicana, while this was only the case in the largest populations of P. martinezii. Equating fitness to either H0 or Ne, as traditionally proposed in conservation biology, might not always be adequate, as species-specific evolutionary factors can decouple the expected correlation between these parameters.

MRI for the diagnosis of limb girdle muscular dystrophies.

PURPOSE OF REVIEW: In the last 30 years, there have many publications describing the pattern of muscle involvement of different neuromuscular diseases leading to an increase in the information available for diagnosis. A high degree of expertise is needed to remember all the patterns described. Some attempts to use artificial intelligence or analysing muscle MRIs have been developed. We review the main patterns of involvement in limb girdle muscular dystrophies (LGMDs) and summarize the strategies for using artificial intelligence tools in this field. RECENT FINDINGS: The most frequent LGMDs have a widely described pattern of muscle involvement; however, for those rarer diseases, there is still not too much information available. patients. Most of the articles still include only pelvic and lower limbs muscles, which provide an incomplete picture of the diseases. AI tools have efficiently demonstrated to predict diagnosis of a limited number of disease with high accuracy. SUMMARY: Muscle MRI continues being a useful tool supporting the diagnosis of patients with LGMD and other neuromuscular diseases. However, the huge variety of patterns described makes their use in clinics a complicated task. Artificial intelligence tools are helping in that regard and there are already some accessible machine learning algorithms that can be used by the global medical community.

Uncovering the Expression Pattern of the Costimulatory Receptors ICOS, 4-1BB, and OX-40 in Exhausted Peripheral and Tumor-Infiltrating Natural Killer Cells from Patients with Cervical Cancer.

Cervical cancer (CC) poses a significant health burden, particularly in low- and middle-income countries. NK cells play a crucial role against CC; however, they can become exhausted and lose their cytotoxic capacity. This work explores the expression of costimulatory receptors (ICOS, 4-1BB, OX-40) in exhausted NK cells from CC patients. Peripheral blood and tumor biopsies were collected, and flow cytometry was used to evaluate the expression of costimulatory receptors in exhausted NK cells. There is an increase of peripheral exhausted NK cells (PD-1+TIGIT+) in CC patients; this subpopulation has a selectively increased expression of the costimulatory receptors ICOS and 4-1BB. An exhausted population is also highly increased in tumor-infiltrating NK cells, and it shows a dramatically increased expression of the costimulatory receptors ICOS (>15×) and 4-1BB (>10×) compared to peripheral NK cells. The exhausted cells, both in the periphery and in the tumor infiltrating lymphocytes (TILs), are also more likely than non-exhausted NK cell populations (PD-1-TIGIT-) to express these costimulatory receptors; increases ranging from 2.0× ICOS, 2.4× 4-1BB, and 2.6× OX-40 in CD56dim PBMCs to 1.5× ICOS, 5× 4-1BB, and 10× OX-40 in TILs were found. Our study demonstrates for the first time the increased expression of the costimulatory receptors ICOS, 4-1BB, and OX-40 in peripheral CD56dim, CD56bright, and tumor-infiltrating NK cells in CC. Targeting these receptors for stimulation could reverse exhaustion and be a promising immunotherapy strategy.

Bound Water Enhances the Ion Selectivity of Highly Charged Polymer Membranes.

Electrochemical technologies for water treatment, resource recovery, energy generation, and energy storage rely on charged polymer membranes to selectively transport ions. With the rise of applications involving hypersaline brines, such as management of desalination brine or the recovery of ions from brines, there is an urgent need for membranes that can sustain high conductivity and selectivity under such challenging conditions. Current membranes are constrained by an inherent trade-off between conductivity and selectivity, alongside concerns regarding their high costs. Moreover, a gap in the fundamental understanding of ion transport within charged membranes at high salinities prevents the development of membranes that could meet these stringent requirements efficiently. Here, we present the synthesis of scalable, highly charged membranes that demonstrate high conductivity and selectivity while contacting 1 and 5 molal NaCl solutions. A detailed analysis of the membrane transport properties reveals that the high proportion of bound water in the membranes, enabled by the high charge content and hydrophilic structure of the polymers, enhances both the ion partitioning and diffusion selectivities of the membranes. These structure/property relationships derived from this study offer valuable guidance for designing next-generation membranes that simultaneously achieve exceptional conductivity and selectivity in high-salinity conditions.

Association of CTLA-4 (AT)n Variants in Basal Cell Carcinoma and Squamous Cell Carcinoma Patients from Western Mexico.

The incidence of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) is constantly increasing, becoming a significant health problem. CTLA-4 is a critical immune checkpoint, and it has been suggested that a variant of variable-number tandem repeat in the 3'-UTR of its gene, known as (AT)n, may be associated with a higher susceptibility to some cancers; however, little is known about genetic variants of the CTLA-4 gene in NMSC. To establish the association of this genetic variant in the CTLA-4 gene with the susceptibility of NMSC carcinogenesis in the Western Mexican population, samples from 150 BCC patients, 150 SCC patients, and 150 healthy individuals as the reference group (RG) were analyzed by endpoint PCR, followed by electrophoresis to genotype the samples. We found that the short-repeat 104/104 bp genotype may be a risk factor for BBC carcinogens (OR = 2.92, p = 0.03), whereas the long-repeat 106/106 bp genotype may be a protective factor for both BCC (OR = 0.13, p = 0.01) and SCC (OR = 0.32, p = 0.01) susceptibility. Our results show that in the Western Mexican population, long-repeat (AT)n variants in the CTLA-4 gene are associated with a protective factor in BCC and SCC. In contrast, short repeats are associated with a risk factor.

The resistome of the food chain: A One Health perspective.

Antimicrobial resistance (AMR) represents a significant global health problem which challenges Sustainable Development Goal 3 of the United Nations, with growing concerns about the possibility of AMR transmission through the food chain. The indiscriminate use of antimicrobials for the treatment of food production animals and for agricultural crop improvement, in addition to the direct discharge of livestock farm residues to sewage and the use of animal manure in agriculture, are among the factors that can facilitate the selection and transmission of AMR throughout the food chain. The study of food microbiomes has been boosted by the advent of next-generation sequencing techniques, which have enabled gaining in-depth understanding of the diversity of antimicrobial resistance genes present in food and associated environments (the so-called resistome). The aim of this review is to provide an accurate and comprehensive overview of the knowledge currently available on the resistome of the most frequently consumed foods worldwide, from a One Health perspective. To this end, the different metagenomic studies which have been conducted to characterize the resistome of foods are compiled and critically discussed.