The care of non-institutionalized ADL-dependent people in the Orcasitas neighborhood of Madrid (Spain) during the Covid-19 pandemic and its relationship with social inequalities, intergenerational dependency and survival.

Background: Mortality among people with dependency to perform basic activities of daily living (ADL) is higher than that of non-dependent people of the same age. Understanding the evolutionary course and factors involved in non-institutionalized ADL dependency, including the influence of the family structure that supports this population, would contribute to improved health planning. Methods: A longitudinal study carried out in the ADL-dependent population of the Orcasitas neighborhood, Madrid (Spain), between June 2020, when the nationwide COVID-19 lockdown ended, and June 2023. A total of 127 patients participated in the study, 78.7% of whom were women and 21.3% were men. Risk analysis was performed via odds ratios (OR) and hazard ratios (HR). Survival analysis was performed using Cox regression. Results: A total of 54.33% of the ADL-dependent persons did not live with their adult children and 45.67% did, being associated living independently with economic capacity and the married marital status but not with the dependency level. In women, being married increased the probability of living independently of their adult children (OR = 12.632; 95% CI = 3.312-48.178). Loss of mobility (OR = 0.398; 95% CI = 0.186-0.853), economic capacity of the dependent (HR = 0.596; 95% CI = 0.459-0.774), and living independently and having better economic capacity (HR = 0.471; 95% CI = 0.234-0.935) were associated with 3-year survival. Those who lived with their adult children had a worse autonomy profile and higher mortality (HR = 1.473; 95% CI = 1.072-2.024). Not being employed, not being married, and not owning a home were significantly associated with being an essential family caregiver. Caregivers were mostly women (OR = 1.794; 95% CI = 1.011-3.182). Conclusion: Among ADL-dependent persons, economic capacity influenced the ability to living independently and affected survival after 3 years. Loss of mobility (wheelchair use) was a predictor of mortality. Social inequalities promote that adult children end up as essential family caregivers. This generates reverse dependency and maintains a vulnerability that is transmitted from generation to generation, perpetuating social and gender inequalities. Dependent parent care in this cohort maintained an archaic pattern in which the eldest daughter cared for her parents. This study made it possible to show that ADL dependence is accompanied by complex interrelationships that must be considered in socio-health planning.

The influence of nationwide COVID-19 lockdown on the functional impairment and long-term survival of dependent people for carrying out basic activities of daily living in a neighborhood of the city of Madrid, Spain: Orcasitas Cohort Longitudinal Study.

Background: Prolonged confinement can lead to personal deterioration at various levels. We studied this phenomenon during the nationwide COVID-19 lockdown in a functionally dependent population of the Orcasitas neighborhood of Madrid, Spain, by measuring their ability to perform basic activities of daily living and their mortality rate. Methods: A total of 127 patients were included in the Orcasitas cohort. Of this cohort, 78.7% were female, 21.3% were male, and their mean age was 86 years. All participants had a Barthel index of ≤ 60. Changes from pre- to post-confinement and 3 years afterward were analyzed, and the effect of these changes on survival was assessed (2020-2023). Results: The post-confinement functional assessment showed significant improvement in independence over pre-confinement for both the Barthel score (t = -5.823; p < 0.001) and the classification level (z = -2.988; p < 0.003). This improvement progressively disappeared in the following 3 years, and 40.9% of the patients in this cohort died during this period. These outcomes were associated with the Barthel index (z = -3.646; p < 0.001) and the level of dependence (hazard ratio 2.227; CI 1.514-3.276). Higher mortality was observed among men (HR 1.745; CI 1.045-2.915) and those with severe dependence (HR 2.169; CI 1.469-3.201). Setting the cutoff point of the Barthel index at 40 provided the best detection of the risk of death associated with dependence. Conclusions: Home confinement and the risk of death due to the COVID-19 pandemic awakened a form of resilience in the face of adversity among the population of functionally dependent adults. The Barthel index is a good predictor of medium- and long-term mortality and is a useful method for detecting populations at risk in health planning. A cutoff score of 40 is useful for this purpose. To a certain extent, the non-institutionalized dependent population is an invisible population. Future studies should analyze the causes of the high mortality observed.

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.

SARS-CoV-2 Viremia Precedes an IL6 Response in Severe COVID-19 Patients: Results of a Longitudinal Prospective Cohort.

Background: Interleukin 6 (IL6) levels and SARS-CoV-2 viremia have been correlated with COVID-19 severity. The association over time between them has not been assessed in a prospective cohort. Our aim was to evaluate the relationship between SARS-CoV-2 viremia and time evolution of IL6 levels in a COVID-19 prospective cohort. Methods: Secondary analysis from a prospective cohort including COVID-19 hospitalized patients from Hospital Universitario La Princesa between November 2020 and January 2021. Serial plasma samples were collected from admission until discharge. Viral load was quantified by Real-Time Polymerase Chain Reaction and IL6 levels with an enzyme immunoassay. To represent the evolution over time of both variables we used the graphic command twoway of Stata. Results: A total of 57 patients were recruited, with median age of 63 years (IQR [53-81]), 61.4% male and 68.4% Caucasian. The peak of viremia appeared shortly after symptom onset in patients with persistent viremia (more than 1 sample with > 1.3 log10 copies/ml) and also in those with at least one IL6 > 30 pg/ml, followed by a progressive increase in IL6 around 10 days later. Persistent viremia in the first week of hospitalization was associated with higher levels of IL6. Both IL6 and SARS-CoV-2 viral load were higher in males, with a quicker increase with age. Conclusion: In those patients with worse outcomes, an early peak of SARS-CoV-2 viral load precedes an increase in IL6 levels. Monitoring SARS-CoV-2 viral load during the first week after symptom onset may be helpful to predict disease severity in COVID-19 patients.

Modeling Living Cells Within Microfluidic Systems Using Cellular Automata Models.

Several computational models, both continuum and discrete, allow for the simulation of collective cell behaviors in connection with challenges linked to disease modeling and understanding. Normally, discrete cell modelling employs quasi-infinite or boundary-less 2D lattices, hence modeling collective cell behaviors in Petri dish-like environments. The advent of lab- and organ-on-a-chip devices proves that the information obtained from 2D cell cultures, upon Petri dishes, differs importantly from the results obtained in more biomimetic micro-fluidic environments, made of interconnected chambers and channels. However, discrete cell modelling within lab- and organ-on-a-chip devices, to our knowledge, is not yet found in the literature, although it may prove useful for designing and optimizing these types of systems. Consequently, in this study we focus on the establishment of a direct connection between the computer-aided designs (CAD) of microfluidic systems, especially labs- and organs-on-chips (and their multi-chamber and multi-channel structures), and the lattices for discrete cell modeling approaches aimed at the simulation of collective cell interactions, whose boundaries are defined directly from the CAD models. We illustrate the proposal using a quite straightforward cellular automata model, apply it to simulating cells with different growth rates, within a selected set of microsystem designs, and validate it by tuning the growth rates with the support of cell culture experiments and by checking the results with a real microfluidic system.

Female germ cell mutagenicity of model chemicals in Drosophila melanogaster: mechanistic information and analysis of repair systems.

In spite of differences between female and male germ cells, and although both of them contribute to the gene pool of future generations, most germ cell mutagenicity studies in higher eukaryotes have been carried out on males. To study the response of female germ cells to mutagen/carcinogen exposure, the mutagenicity of two model chemicals like diethyl sulfate (DES) and hexamethylphosphoramide (HMPA), and the monofunctional methylating chemotherapeutic drug streptozotocin (STZ), has been analysed on repair efficient females of Drosophila melanogaster. Results previously obtained with N-ethyl-N-nitrosourea (ENU), another model chemical, have also been included in the analysis. The activity of bypass tolerance mechanism (BTM; represented by the mus308 locus) and nucleotide excision repair (NER) on the removal of oxygen and nitrogen ethylations was studied by determining DES mutagenicity in NER deficient females, comparing it with existing results for ENU, and by analysing both chemicals on BTM deficient females. Results indicate that (1) all chemicals are mutagenic on repair efficient females; (2) a measure of mutagenic activity ranked from the lowest DES to STZ, HMPA, and ENU as the highest. This order correlates with the repair of the respectively induced DNA damages, and with the mutagenic and carcinogenic potency of these compounds, considering the toxicity of cross-linking agents; (3) NER efficiently repairs nitrogen ethylation damage and seems to contribute to the processing of oxygen damage in female germ cells; and (4) BTM is involved on the processing of oxygen ethylation damage, whereas the results on nitrogen ethylation are not clear. Finally, these results indicate that differences between male and female germ cells affect the response to chemical exposure, and therefore demonstrate the necessity of analysing also female cells in germinal mutagenicity studies. In addition, these studies can provide important mechanistic information about germ cell chemical mutagenesis, and even when the analysis of oogonia is not possible, since all female germ cells are pre-meiotic, studies of oocytes could be a model for pre-meiotic cells.