Cancer prevention in people experiencing homelessness: ethical considerations and experiences from the CANCERLESS project.

The incidence of cancer in Europe has been increasing in recent years. Despite this, cancer prevention has remained a low priority in health policies. Cancer is one of the main causes of mortality among people experiencing homelessness, who continue to have difficulties accessing prevention programs. A strategy that has been tested to favor cancer prevention is the health navigator figure. The objective of CANCERLESS project is to implement this model among populations experiencing homelessness in four European countries to foster the prevention and early detection of cancer. In this perspective, a presentation of CANCERLESS project is made, and its ethical aspects are discussed according to the ethics of public health, the ethics of care, solidarity, relational autonomy, and the social recognition of the virtue of just generosity. The ethical foundations of CANCERLESS project are rooted in social justice and in equity in access to health systems in general and cancer screening programs in particular. The ethics of public health guided by utilitarianism are insufficient in serving the interests of the most disadvantaged groups of the population. Hence, it is necessary to resort to relational bioethics that includes the ethics of care and solidarity and that recognizes the moral identity of socially excluded persons, reaffirming their position of equality in society. Relational autonomy therefore provides a broader conception by including the influence of living conditions in decisions. For this reason, the CANCERLESS project opts for a dialogue with those affected to incorporate their preferences and values into decisions about cancer prevention.

Intelligent micro/nanorobots based on biotemplates.

Intelligent micro/nanorobots based on natural materials as biotemplates are considered to be some of the most promising robots in the future in the microscopic field. Due to the advantages of biotemplates such as unique structure, abundant resources, environmental friendliness, easy removal, low price, easy access, and renewability, intelligent micro/nanorobots based on biotemplates can be endowed with both excellent biomaterial activity and unique structural morphology through biotemplates themselves and specific functions through artificial micro/nanotechnology. Thus, intelligent micro/nanorobots show excellent application potential in various fields from biomedical applications to environmental remediation. In this review, we introduce the advantages of using natural biological materials as biotemplates to build intelligent micro/nanorobots, and then, classify the micro/nanorobots according to different types of biotemplates, systematically detail their preparation strategies and summarize their application prospects. Finally, in order to further advance the development of intelligent micro/nanorobots, we discuss the current challenges and future prospects of biotemplates. Intelligent micro/nanorobots based on biotemplates are a perfect combination of natural biotemplates and micro/nanotechnology, which is an important trend for the future development of micro/nanorobots. We hope this review can provide useful references for developing more intelligent, efficient and safe micro/nanorobots in the future.

High-Throughput Screening Method Using Escherichia coli Keio Mutants for Assessing Primary Damage Mechanism of Antimicrobials.

The Escherichia coli Keio mutant collection has been a tool for assessing the role of specific genes and determining their role in E. coli physiology and uncovering novel functions. In this work, specific mutants in the DNA repair pathways and oxidative stress response were evaluated to identify the primary targets of silver nanoparticles (NPs) and their mechanism of action. The results presented in this work suggest that NPs mainly target DNA via double-strand breaks and base modifications since the recA, uvrC, mutL, and nfo mutants rendered the most susceptible phenotype, rather than involving the oxidative stress response. Concomitantly, during the establishment of the control conditions for each mutant, the katG and sodA mutants showed a hypersensitive phenotype to mitomycin C, an alkylating agent. Thus, we propose that KatG catalase plays a key role as a cellular chaperone, as reported previously for the filamentous fungus Neurospora crassa, a large subunit catalase. The Keio collection mutants may also be a key tool for assessing the resistance mechanism to metallic NPs by using their potential to identify novel pathways involved in the resistance to NPs.

CROCuS, a Phase II Study Evaluating the Antiviral Activity, Clinical Outcomes, and Safety of Rilematovir in Children Aged ≥ 28 Days and ≤ 3 Years with Acute Respiratory Tract Infection Due to Respiratory Syncytial Virus.

BACKGROUND: Respiratory syncytial virus (RSV) causes significant morbidity and mortality in children aged ≤ 5 years and adults aged ≥ 60 years worldwide. Despite this, RSV-specific therapeutic options are limited. Rilematovir is an investigational, orally administered inhibitor of RSV fusion protein-mediated viral entry. OBJECTIVE: To establish the antiviral activity, clinical outcomes, safety, and tolerability of rilematovir (low or high dose) in children aged ≥ 28 days and ≤ 3 years with RSV disease. METHODS: CROCuS was a multicenter, international, double-blind, placebo-controlled, randomized, adaptive phase II study, wherein children aged ≥ 28 days and ≤ 3 years with confirmed RSV infection who were either hospitalized (Cohort 1) or treated as outpatients (Cohort 2) were randomized (1:1:1) to receive rilematovir (low or high dose) or placebo. Study treatment was administered daily as an oral suspension from days 1 to 7, with dosing based on weight and age groups. The primary objective was to establish antiviral activity of rilematovir by evaluating the area under the plasma concentration-time curve of RSV viral load in nasal secretions from baseline through day 5. Severity and duration of RSV signs and symptoms and the safety and tolerability of rilematovir were also assessed through day 28 (± 3). RESULTS: In total, 246 patients were randomized, treated, and included in the safety analysis population (Cohort 1: 147; Cohort 2: 99). Of these, 231 were included in the intent-to-treat-infected analysis population (Cohort 1: 138; Cohort 2: 93). In both cohorts, demographics were generally similar across treatment groups. In both cohorts combined, the difference (95% confidence interval) in the mean area under the plasma concentration-time curve of RSV RNA viral load through day 5 was - 1.25 (- 2.672, 0.164) and - 1.23 (- 2.679, 0.227) log10 copies∙days/mL for the rilematovir low-dose group and the rilematovir high-dose group, respectively, when compared with placebo. The estimated Kaplan-Meier median (95% confidence interval) time to resolution of key RSV symptoms in the rilematovir low-dose, rilematovir high-dose, and placebo groups of Cohort 1 was 6.01 (4.24, 7.25), 5.82 (4.03, 8.18), and 7.05 (5.34, 8.97) days, respectively; in Cohort 2, estimates were 6.45 (4.81, 9.70), 6.26 (5.41, 7.84), and 5.85 (3.90, 8.27) days, respectively. A similar incidence of adverse events was reported in patients treated with rilematovir and placebo in Cohort 1 (rilematovir: 61.9%; placebo: 58.0%) and Cohort 2 (rilematovir: 50.8%; placebo: 47.1%), with most reported as grade 1 or 2 and none leading to study discontinuation. The study was terminated prematurely, as the sponsor made a non-safety-related strategic decision to discontinue rilematovir development prior to full recruitment of Cohort 2. CONCLUSIONS: Data from the combined cohort suggest that rilematovir has a small but favorable antiviral effect of indeterminate clinical relevance compared with placebo, as well as a favorable safety profile. Safe and effective therapeutic options for RSV in infants and young children remain an unmet need. CLINICAL TRIAL REGISTRATION: EudraCT Number: 2016-003642-93; ClinicalTrials.gov Identifier: NCT03656510. First posted date: 4 September, 2018.

Cilastatin as a Potential Anti-Inflammatory and Neuroprotective Treatment in the Management of Glaucoma.

Glaucoma is a neurodegenerative disease that causes blindness. In this study, we aimed to evaluate the protective role of cilastatin (CIL), generally used in the treatment of nephropathologies associated with inflammation, in an experimental mouse model based on unilateral (left) laser-induced ocular hypertension (OHT). Male Swiss mice were administered CIL daily (300 mg/kg, i.p.) two days before OHT surgery until sacrifice 3 or 7 days later. Intraocular Pressure (IOP), as well as retinal ganglion cell (RGC) survival, was registered, and the inflammatory responses of macroglial and microglial cells were studied via immunohistochemical techniques. Results from OHT eyes were compared to normotensive contralateral (CONTRA) and naïve control eyes considering nine retinal areas and all retinal layers. OHT successfully increased IOP values in OHT eyes but not in CONTRA eyes; CIL did not affect IOP values. Surgery induced a higher loss of RGCs in OHT eyes than in CONTRA eyes, while CIL attenuated this loss. Similarly, surgery increased macroglial and microglial activation in OHT eyes and to a lesser extent in CONTRA eyes; CIL prevented both macroglial and microglial activation in OHT and CONTRA eyes. Therefore, CIL arises as a potential effective strategy to reduce OHT-associated damage in the retina of experimental mice.

WIC staff and healthcare professional perceptions of an EHR intervention to facilitate referrals to and improve communication and coordination with WIC: A qualitative study.

Objectives: Participation in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) has numerous benefits, yet many eligible children remain unenrolled. This qualitative study sought to explore perceptions of a novel electronic health record (EHR) intervention to facilitate referrals to WIC and improve communication/coordination between WIC staff and healthcare professionals. Methods: WIC staff in three counties were provided EHR access and recruited to participate. An automated, EHR-embedded WIC participation screening and referral tool was implemented within 8 healthcare clinics; healthcare professionals within these clinics were eligible to participate. The interview guide was developed using the Consolidated Framework for Implementation Research to elicit perceptions of this novel EHR-based intervention. Semi-structured interviews were conducted via telephone. Interviews were recorded, transcribed, coded, and analyzed using thematic analysis. Results: Twenty semi-structured interviews were conducted with eight WIC staff, seven pediatricians, four medical assistants, and one registered nurse. Most participants self-identified as female (95%) and White (55%). We identified four primary themes: (1) healthcare professionals had a positive view of WIC but communication and coordination between WIC and healthcare professionals was limited prior to WIC having EHR access; (2) healthcare professionals favored WIC screening using the EHR but workflow challenges existed; (3) EHR connections between WIC and the healthcare system can streamline referrals to and enrollment in WIC; and (4) WIC staff and healthcare professionals recommended that WIC have EHR access. Conclusions: A novel EHR-based intervention has potential to facilitate healthcare referrals to WIC and improve communication/coordination between WIC and healthcare systems.

Utilization of Primary Healthcare Services in Patients with Multimorbidity According to Their Risk Level by Adjusted Morbidity Groups: A Cross-Sectional Study in Chamartín District (Madrid).

Patients with multimorbidity have increased and more complex healthcare needs, posing their management a challenge for healthcare systems. This study aimed to describe their primary healthcare utilization and associated factors. A population-based cross-sectional study was conducted in a Spanish basic healthcare area including all patients with chronic conditions, differentiating between having multimorbidity or not. Sociodemographic, functional, clinical and service utilization variables were analyzed, stratifying the multimorbid population by the Adjusted Morbidity Groups (AMG) risk level, sex and age. A total of 6036 patients had multimorbidity, 64.2% being low risk, 28.5% medium risk and 7.3% high risk. Their mean age was 64.1 years and 63.5% were women, having on average 3.5 chronic diseases, and 25.3% were polymedicated. Their mean primary care contacts/year was 14.9 (7.8 with family doctors and 4.4 with nurses). Factors associated with primary care utilization were age (B-coefficient [BC] = 1.15;95% Confidence Interval [CI] = 0.30-2.01), female sex (BC = 1.04; CI = 0.30-1.78), having a caregiver (BC = 8.70; CI = 6.72-10.69), complexity (B-coefficient = 0.46; CI = 0.38-0.55), high-risk (B-coefficient = 2.29; CI = 1.26-3.32), numerous chronic diseases (B-coefficient = 1.20; CI = 0.37-2.04) and polypharmacy (B-coefficient = 5.05; CI = 4.00-6.10). This study provides valuable data on the application of AMG in multimorbid patients, revealing their healthcare utilization and the need for a patient-centered approach by primary care professionals. These results could guide in improving coordination among professionals, optimizing multimorbidity management and reducing costs derived from their extensive healthcare utilization.

Spanish Cross-Cultural Adaptation and Validation of the Kerlan-Jobe Orthopaedic Clinic Shoulder and Elbow Score.

CONTEXT: There are no available questionnaires in Spanish that assess the function and performance of shoulder and elbow in overhead sports. The Kerlan-Jobe Orthopaedic Clinic (KJOC) score is a reference tool for this purpose. We aimed to cross-culturally adapt and investigate its measurement properties in Spanish overhead athletes. DESIGN: Cross-cultural adaptation followed the steps of direct translation, back translation, comprehensibility analysis, and review by the Committee of Experts. Then, symptomatic and asymptomatic overhead athletes were invited to complete an electronic version of the Spanish adaptation (KJOC-Sp). The structural validity was evaluated through an exploratory factor analysis with principal axis factoring. Hypotheses were tested for known-groups and convergent validity, studying the correlation with the Shoulder Pain and Disability Index and the Disabilities of the Arm, Shoulder, and Hand Sports Module questionnaires in symptomatic athletes. Cronbach alpha was calculated for internal consistency and intraclass correlation coefficient (ICC)2,1 for test-retest reliability. Floor and ceiling effects and time to completion were also calculated. RESULTS: The KJOC-Sp maintained the content of the original version and was adapted to the new population. One hundred participants (41 females and 59 males) with a mean age of 22.4 (5.9) years participated in the study of measurement properties. The factor analysis revealed a 1-factor solution. Symptomatic participants scored significantly lower than asymptomatic, with a large effect size (P < .001; r = .67). Correlations were of -.60 (P < .05) with the Shoulder and Pain Disability Index questionnaire and -0.66 (P < .05) with the Disabilities of the Arm, Shoulder, and Hand Sports Module questionnaire. Cronbach alpha was .98 (95% confidence interval, .97-.98) and the ICC2,1 was .96 (95% confidence interval .93-.98). No floor or ceiling effects were observed among the symptomatic athletes, while mean time to completion was 121 seconds. CONCLUSION: The KJOC-Sp is equivalent to the original score, aside from valid and reliable, without floor or ceiling effects in symptomatic athletes and with a low time consumption.

New records of Rhipicephalus linnaei infected by Rickettsia massiliae from Central Mexico.

BACKGROUND: On the American continent, Rhipicephalus sanguineus s.l. comprises two species: Rhipicephalus linnaei and R. sanguineus s.s. Each species has been identified as a potential vector of at least one of five species of pathogenic bacteria of the genus Rickettsia. In particular, Rickettsia massiliae is one of three species with the greatest importance in public health at the continental level. In Mexico, this species is reported exclusively in the Nearctic states of Baja California and Chihuahua. AIM: For this reason, the aim of this work was to provide new records of R. massiliae for the centre of the country derived from active acarological surveillance. MATERIALS AND METHODS: During the period of February-October 2019, 29 dogs from six municipalities in the state of Morelos were sampled. Hosts were visually inspected, and ticks were recovered and identified morphologically and molecularly by amplification of the 16S rDNA gene. Subsequently, five genes from members of the genus Rickettsia were amplified and sequenced. RESULTS: A total of 229 (117♀, 98♂ and 14 N) ticks identified as R. linnaei were recovered, two of which were positive for R. massiliae strains related to those recovered from Argentina and the United States. CONCLUSIONS: This work provides the second record of R. massiliae infecting R. linnaei in Mexico and the Americas, increasing the geographic distribution of this Rickettsia species in the Neotropical region, and providing information on the possible role of R. linnaei as a potential vector of this microorganism.

Reliability, validity and distribution of the Spanish female sexual function index in women with relapsing multiple sclerosis.

BACKGROUND: The Female Sexual Function Index (FSFI) is a widely recognized tool for assessing sexual dysfunction (SD). However, its validation for Spanish women suffering from multiple sclerosis (MS) has not yet been conducted. AIM: The study aimed to examine the psychometric properties of the 19-item Spanish version of the FSFI (svFSFI) in women with relapsing MS. METHOD: A total of 137 women with relapsing MS from three Spanish centers participated in the study and completed the svFSFI. The psychometric properties of the questionnaire were evaluated. The prevalence of SD in the study cohort was determined, and its association with clinical and sociodemographic variables was analyzed using bi- and multivariate regression analyses. RESULTS: The svFSFI demonstrated excellent test-retest reliability and substantial-to-excellent internal consistency in the context of relapsing MS. There was significant convergent validity in the intercorrelations of domains. Discriminant validity showed differences in SD between women with high and low neurological disability, as measured by the Expanded Disability Status Scale (EDSS) scores. An exploratory factor analysis indicated a five-factor structure for the svFSFI. The prevalence of SD in the MS cohort was found to be 42.6%, with the 'desire' and 'arousal' domains being the most affected. Factors such as EDSS score, fatigue, depression, and having a stable partner were found to influence the total svFSFI score. CONCLUSION: The study validates the svFSFI as a reliable and valid instrument for evaluating sexual dysfunction in Spanish women with MS.

Surface Functionalization and Escherichia coli Detection Using Surface-Enhanced Raman Spectroscopy Driven by Functional Organic Polymer/Gold Nanofilm-Based Microfluidic Chip.

In this work, a microfluidic prototype based on polymeric materials was developed to monitor surface processes using surface-enhanced Raman spectroscopy (SERS), keeping the reagents free of environmental contamination. The prototype was fabricated on poly(methyl methacrylic acid) (PMMA). A micrometric membrane of a functional organic polymer (FOP) based on p-terphenyl and bromopyruvic acid monomers was formed on the PMMA surface to promote the formation of metal nanoclusters. Au nanosized film was deposited on the FOP membrane to give rise to the SERS effect. A microchannel was formed on another piece of PMMA using micromachining. A representative 3D model of the prototype layer arrangement was built and simulated in COMSOL Multiphysics® to approximate the electric field distribution and calculate the power enhancement factor as the Au film changes over time. The fabrication process was characterized using UV-visible and Raman spectroscopies and XPS. The prototype was tested using a Raman microscope and liquid solutions of cysteamine and Escherichia coli (E. coli). The simulation results demonstrated that the morphological characteristics of the Au layer give rise to the SERS effect, and the power enhancement factor reaches values as high as 8.8 × 105 on the FOP surface. The characterization results showed the formation of the FOP and the Au film on PMMA and the surface functionalization with amine groups. The Raman spectra of the prototype showed temporal evolution as different compounds were deposited on the upper wall of the microchannel. Characteristic peaks associated with these compounds were detected with continuous monitoring over time. This prototype offers many benefits for applications like monitoring biological processes. Some advantages include timely surface evaluation while avoiding environmental harm, decreased use of reagents and samples, minimal interference with the process by measuring, and detecting microorganisms in just 1 h, as demonstrated with the E. coli sample.

Differences in healthcare service utilization in patients with polypharmacy according to their risk level by adjusted morbidity groups: a population-based cross-sectional study.

BACKGROUND: Patients with polypharmacy suffer from complex medical conditions involving a large healthcare burden. This study aimed to describe the characteristics and utilization of primary care (PC) and hospital care (HC) and factors associated in chronic patients with polypharmacy, stratifying by adjusted morbidity groups (AMG) risk level, sex and age, and comparing with non-polypharmacy. METHODS: Cross-sectional study conducted in a Spanish basic healthcare area. Studied patients were those over 18 years with chronic diseases identified by the AMG tool from Madrid electronic clinical record, which was the data source. Sociodemographic, sociofunctional, clinical and healthcare utilization variables were described and compared by risk level, sex, age and having or not polypharmacy. Factors associated with healthcare utilization in polypharmacy patients were determined by a negative binomial regression model. RESULTS: In the area studied, 61.3% patients had chronic diseases, of which 16.9% had polypharmacy vs. 83.1% without polypharmacy. Patients with polypharmacy (vs. non-polypharmacy) mean age was 82.7 (vs. 52.7), 68.9% (vs. 60.7%) were women, and 22.0% (vs. 1.2%) high risk. Their average number of chronic diseases was 4.8 (vs. 2.2), and 95.6% (vs. 56.9%) had multimorbidity. Their mean number of annual healthcare contacts was 30.3 (vs. 10.5), 25.9 (vs. 8.8) with PC and 4.4 (vs. 1.7) with HC. Factors associated with a greater PC utilization in patients with polypharmacy were elevated complexity, high risk level and dysrhythmia. Variables associated with a higher HC utilization were also increased complexity and high risk, in addition to male sex, being in palliative care, having a primary caregiver, suffering from neoplasia (specifically lymphoma or leukaemia) and arthritis, whereas older age and immobilization were negatively associated. CONCLUSIONS: Polypharmacy population compared to non-polypharmacy was characterized by a more advanced age, predominance of women, high-risk, complexity, numerous comorbidities, dependency and remarkable healthcare utilization. These findings could help healthcare policy makers to optimize the distribution of resources and professionals within PC and HC systems, aiming for the improvement of polypharmacy management and rational use of medicines while reducing costs attributed to healthcare utilization by these patients.

Machine-learning prediction of thermal expansion coefficient for perovskite oxides with experimental validation.

Perovskite oxides have been of high-interest and relatively well studied over the last 20 years due to their various applications, specifically for solid oxide fuel cells (SOFCs) and solid oxide electrolysis cells (SOECs). One of the key properties for a perovskite to perform well as a component in SOFCs, SOECs, and other high-temperature applications is its thermal expansion coefficient (TEC). The use of machine learning (ML) to predict material properties has greatly increased over the years and has proven to be a very useful tool for materials screening. The process of synthesizing and testing perovskite oxides is laborious and costly, and the use of physics-based models is often highly computationally expensive. Due to the amount of elements able to be accommodated in the ABO3 structure and the ability for crystallographic mixing in both the A and B-sites, there are a massive amount of possible ABO3 perovskites. In this paper, a ML model for the prediction of the TECs of AA'BB'O3 perovskites is produced and applied to millions of potential compositions resulting in reliable TEC predictions for 150 451 of the compositions.

Photoactive Au@MoS2 Micromotors for Dynamic Surface-Enhanced Raman Spectroscopy Sensing.

Photophoretic Au@MoS2 micromotors are used as smart mobile substrates for dynamic surface-enhanced Raman spectroscopy (SERS) sensing. The photophoretic capabilities and swarming-like propulsion of the micromotors allow for their schooling and accumulation in the measuring spot, increasing the density of SERS-active gold nanoparticles for Raman mapping and, simultaneously, the preconcentration of the target analyte. The generation of "hot-microflake spots" directly in the Raman irradiation point results in a 15-18-fold enhancement in the detection of crystal violet without the requirement for additional external sources for propulsion. Moreover, the reproducible collective micromotor motion does not depend on the exact position of the laser spot concerning individual micromotors, which greatly simplifies the experimental setup, avoiding the requirements of sophisticated equipment. The strategy was further applied for the detection of malachite green and paraquat with a good signal enhancement. The new on-the-move-based SERS strategy holds great promise for on-site detection with portable instrumentation in a myriad of environmental monitoring and clinical applications.

Peptides with biological and technofunctional properties produced by bromelain hydrolysis of proteins from different sources: A review.

Bromelains are cysteine peptidases with endopeptidase action (a subfamily of papains), obtained from different parts of vegetable belonging to the Bromeliaceae family. They have some intrinsic medical activity, but this review is focused on their application (individually or mixed with other proteases) to produce bioactive peptides. When compared to other proteases, perhaps due to the fact that they are commercialized as an extract containing several proteases, the hydrolysates produced by this enzyme tends to have higher bioactivities than other common proteases. The peptides and the intensity of their final properties depend on the substrate protein and reaction conditions, being the degree of hydrolysis a determining parameter (but not always positive or negative). The produced peptides may have diverse activities such as antioxidant, antitumoral, antihypertensive or antimicrobial ones, among others or they may be utilized to improve the organoleptic properties of foods and feeds. Evolution of the use of this enzyme in this application is proposed to be based on a more intense direct application of Bromeliaceae extract, without the cost associated to enzyme purification, and the use of immobilized biocatalysts of the enzyme by simplifying the enzyme recovery and reuse, and also making the sequential hydrolysis using diverse proteases possible.

Valorization of Prunus Seed Oils: Fatty Acids Composition and Oxidative Stability.

Prunus fruit seeds are one of the main types of agri-food waste generated worldwide during the processing of fruits to produce jams, juices and preserves. To valorize this by-product, the aim of this work was the nutritional analysis of peach, apricot, plum and cherry seeds using the official AOAC methods, together with the extraction and characterization of the lipid profile of seed oils using GC-FID, as well as the measurement of the antioxidant activity and oxidative stability using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical scavenging method. Chemometric tools were required for data evaluation and the obtained results indicated that the main component of seeds were oils (30-38%, w). All seed oils were rich in oleic (C18:1n9c) and linoleic (C18:2n6c) acids and presented heart-healthy lipid indexes. Oil antioxidant activity was estimated in the range IC50 = 20-35 mg·mL-1, and high oxidative stability was observed for all evaluated oils during 1-22 storage days, with the plum seed oil being the most antioxidant and stable over time. Oxidative stability was also positively correlated with oleic acid content and negatively correlated with linoleic acid content. Therefore, this research showed that the four Prunus seed oils present interesting healthy characteristics for their use and potential application in the cosmetic and nutraceutical industries.

Occurrence of SARS-CoV-2 viremia is associated with genetic variants of genes related to COVID-19 pathogenesis.

Introduction: SARS-CoV-2 viral load has been related to COVID-19 severity. The main aim of this study was to evaluate the relationship between SARS-CoV-2 viremia and SNPs in genes previously studied by our group as predictors of COVID-19 severity. Materials and methods: Retrospective observational study including 340 patients hospitalized for COVID-19 in the University Hospital La Princesa between March 2020 and December 2021, with at least one viremia determination. Positive viremia was considered when viral load was above the quantifiable threshold (20 copies/ml). A total of 38 SNPs were genotyped. To study their association with viremia a multivariate logistic regression was performed. Results: The mean age of the studied population was 64.5 years (SD 16.6), 60.9% patients were male and 79.4% white non-Hispanic. Only 126 patients (37.1%) had at least one positive viremia. After adjustment by confounders, the presence of the minor alleles of rs2071746 (HMOX1; T/T genotype OR 9.9 p < 0.0001), rs78958998 (probably associated with SERPING1 expression; A/T genotype OR 2.3, p = 0.04 and T/T genotype OR 12.9, p < 0.0001), and rs713400 (eQTL for TMPRSS2; C/T + T/T genotype OR 1.86, p = 0.10) were associated with higher risk of viremia, whereas the minor alleles of rs11052877 (CD69; A/G genotype OR 0.5, p = 0.04 and G/G genotype OR 0.3, p = 0.01), rs2660 (OAS1; A/G genotype OR 0.6, p = 0.08), rs896 (VIPR1; T/T genotype OR 0.4, p = 0.02) and rs33980500 (TRAF3IP2; C/T + T/T genotype OR 0.3, p = 0.01) were associated with lower risk of viremia. Conclusion: Genetic variants in HMOX1 (rs2071746), SERPING1 (rs78958998), TMPRSS2 (rs713400), CD69 (rs11052877), TRAF3IP2 (rs33980500), OAS1 (rs2660) and VIPR1 (rs896) could explain heterogeneity in SARS-CoV-2 viremia in our population.

Predicting the onset of diabetes-related complications after a diabetes diagnosis with machine learning algorithms.

AIMS: Using machine learning algorithms and administrative data, we aimed to predict the risk of being diagnosed with several diabetes-related complications after one-, two- and three-year post-diabetes diagnosis. METHODS: We used longitudinal data from administrative registers of 610,019 individuals in Catalonia with a diagnosis of diabetes and checked the presence of several complications after diabetes onset from 2013 to 2017: hypertension, renal failure, myocardial infarction, cardiovascular disease, retinopathy, congestive heart failure, cerebrovascular disease, peripheral vascular disease and stroke. Four different machine learning (ML) algorithms (logistic regression (LR), Decision tree (DT), Random Forest (RF), and Extreme Gradient Boosting (XGB)) will be used to assess their prediction performance and to evaluate the prediction accuracy of complications changes over the period considered. RESULTS: 610,019 people with diabetes were included. After three years since diabetes diagnosis, the area under the curve values ranged from 60% (retinopathy) to 69% (congestive heart failure), whereas accuracy rates varied between 60% (retinopathy) to 75% (hypertension). RF was the most relevant technique for hypertension, myocardial and retinopathy, and LR for the rest of the comorbidities. The Shapley additive explanations values showed that age was associated with an elevated risk for all diabetes-related complications except retinopathy. Gender, other comorbidities, co-payment levels and age were the most relevant factors for comorbidity diagnosis prediction. CONCLUSIONS: Our ML models allow for the identification of individuals newly diagnosed with diabetes who are at increased risk of developing diabetes-related complications. The prediction performance varied across complications but within acceptable ranges as prediction tools.

Sex-Dependent Altered Expression of Cannabinoid Signaling in Hippocampal Astrocytes of the Triple Transgenic Mouse Model of Alzheimer's Disease: Implications for Controlling Astroglial Activity.

Alzheimer's disease (AD) is a common neurodegenerative disease. In AD-associated neuroinflammation, astrocytes play a key role, finding glial activation both in patients and in animal models. The endocannabinoid system (ECS) is a neurolipid signaling system with anti-inflammatory and neuroprotective properties implicated in AD. Astrocytes respond to external cannabinoid signals and also have their own cannabinoid signaling. Our main objective is to describe the cannabinoid signaling machinery present in hippocampal astrocytes from 3×Tg-AD mice to determine if they are actively involved in the neurodegenerative process. Primary cultures of astrocytes from the hippocampus of 3×Tg-AD and non-Tg offspring were carried out. We analyzed the gene expression of astrogliosis markers, the main components of the ECS and Ca2+ signaling. 3×Tg-AD hippocampal astrocytes show low inflammatory activity (Il1b, Il6, and Gls) and Ca2+ flow (P2rx5 and Mcu), associated with low cannabinoid signaling (Cnr1 and Cnr2). These results were more evident in females. Our study corroborates glial involvement in AD pathology, in which cannabinoid signaling plays an important role. 3×Tg-AD mice born with hippocampal astrocytes with differential gene expression of the ECS associated with an innate attenuation of their activity. In addition, we show that there are sex differences from birth in this AD animal, which should be considered when investigating the pathogenesis of the disease.