A comprehensive study of source apportionment, spatial distribution, and health risks assessment of heavy metal(loid)s in the surface soils of a semi-arid mining region in Matehuala, Mexico.

BACKGROUND: This study investigates the contamination level, spatial distribution, pollution sources, potential ecological risks, and human health risks associated with heavy metal(loid)s (i.e., arsenic (As), copper (Cu), iron (Fe), manganese (Mn), lead (Pb), and zinc (Zn)) in surface soils within the mining region of Matehuala, located in central Mexico. OBJECTIVES: The primary objectives are to estimate the contamination level of heavy metal(loid)s, identify pollution sources, assess potential ecological risks, and evaluate human health risks associated with heavy metal(loid) contamination. METHODS: Soil samples from the study area were analysed using various indices including Igeo, Cf, PLI, mCd, EF, and PERI to evaluate contamination levels. Source apportionment of heavy metal(loid)s was conducted using the APCS-MLR and PMF receptor models. Spatial distribution patterns were determined using the most efficient interpolation technique among five different approaches. The total carcinogenic risk index (TCR) and total non-carcinogenic index (THI) were used in this study to assess the potential carcinogenic and non-carcinogenic hazards posed by heavy metal(loid)s in surface soil to human health. RESULTS: The study reveals a high contamination level of heavy metal(loid)s in the surface soil, posing considerable ecological risks. As was identified as a priority metal for regulatory control measures. Mining and smelting activities were identified as the primary factors influencing heavy metal(loid) distributions. Based on spatial distribution mapping, concentrations were higher in the northern, western, and central regions of the study area. As and Fe were found to pose considerable and moderate ecological risks, respectively. Health risk evaluation indicated significant levels of carcinogenic risks for both adults and children, with higher risks for children. CONCLUSION: This study highlights the urgent need for monitoring heavy metal(loid) contamination in Matehuala's soils, particularly in regions experiencing strong economic growth, to mitigate potential human health and ecological risks associated with heavy metal(loid) pollution.

Has the COVID-19 pandemic changed existing patterns of non-COVID-19 health care utilization? A retrospective analysis of six regions in Europe.

BACKGROUND: Resilience of national health systems in Europe remains a major concern in times of multiple crises and as more evidence is emerging relating to the indirect effects of the COVID-19 pandemic on health care utilization (HCU), resulting from de-prioritization of regular, non-pandemic healthcare services. Most extant studies focus on regional, disease specific or early pandemic HCU creating difficulties in comparing across multiple countries. We provide a comparatively broad definition of HCU across multiple countries, with potential to expand across regions and timeframes. METHODS: Using a cross-country federated research infrastructure (FRI), we examined HCU for acute cardiovascular events, elective surgeries and serious trauma. Aggregated data were used in forecast modelling to identify changes from predicted European age-standardized counts via fitted regressions (2017-19), compared against post-pandemic data. RESULTS: We found that elective surgeries were most affected, universally falling below predicted levels in 2020. For cardiovascular HCU, we found lower-than-expected cases in every region for heart attacks and displayed large sex differences. Serious trauma was the least impacted by the COVID-19 pandemic. CONCLUSION: The strength of this study comes from the use of the European Population Health Information Research Infrastructure's (PHIRI) FRI, allowing for rapid analysis of regional differences to assess indirect impacts of events such as pandemics. There are marked differences in the capacity of services to return to normal in terms of elective surgery; additionally, we found considerable differences between men and women which requires further research on potential sex or gender patterns of HCU during crises.

Characterization of Microalgae Biomass-Based Composites Obtained through Rotational Molding.

The wide range of applications and the numerous advantages of plastics have led to their excessive use, with subsequent damage to ecosystems. As an environmentally friendly alternative, biocomposites have gained much attention, and microalgae have become a potential source for their production. In this study, the use of washed and unwashed Spirulina in polyethylene-based composites has been evaluated as a way to prevent the thermooxidation of polyethylene, while at the same time, reducing the amount of virgin plastic used. Biocomposites were produced by rotomolding, testing different biomass contents and determining their mechanical and thermal performances as well as their water uptake level. Composites with up to 15% of biomass (by weight), a particularly high ratio for rotomolding, were satisfactorily produced. Using 5% of both biomasses did not significantly modify the behavior when compared with the neat PE samples' properties. For higher loadings, the use of non-washed biomass allowed us to obtain better properties, with added benefits related to using an unwashed biomass (less water consumption, lower costs and fewer environmental impacts). On the other hand, this study showed a promising beneficial effect on the thermooxidative resistance of composites, as the oxidation induction times were notably increased with biomass addition.

Delayed treatment in breast cancer patients during the COVID-19 pandemic: a population health information research infrastructure (PHIRI) case study.

BACKGROUND: The indirect impact of the coronavirus disease 2019 pandemic on healthcare services was studied by assessing changes in the trend of the time to first treatment for women 18 or older who were diagnosed and treated for breast cancer between 2017 and 2021. METHODS: An observational retrospective longitudinal study based on aggregated data from four European Union (EU) countries/regions investigating the time it took to receive breast cancer treatment. We compiled outputs from a federated analysis to detect structural breakpoints, confirming the empirical breakpoints by differences between the trends observed and forecasted after March 2020. Finally, we built several segmented regressions to explore the association of contextual factors with the observed changes in treatment delays. RESULTS: We observed empirical structural breakpoints on the monthly median time to surgery trend in Aragon (ranging from 9.20 to 17.38 days), Marche (from 37.17 to 42.04 days) and Wales (from 28.67 to 35.08 days). On the contrary, no empirical structural breakpoints were observed in Belgium (ranging from 21.25 to 23.95 days) after the pandemic's beginning. Furthermore, we confirmed statistically significant differences between the observed trend and the forecasts for Aragon and Wales. Finally, we found the interaction between the region and the pandemic's start (before/after March 2020) significantly associated with the trend of delayed breast cancer treatment at the population level. CONCLUSIONS: Although they were not clinically relevant, only Aragon and Wales showed significant differences with expected delays after March 2020. However, experiences differed between countries/regions, pointing to structural factors other than the pandemic.

PHIRI: lessons for an extensive reuse of sensitive data in federated health research.

BACKGROUND: The extensive and continuous reuse of sensitive health data could enhance the role of population health research on public decisions. This paper describes the design principles and the different building blocks that have supported the implementation and deployment of Population Health Information Research Infrastructure (PHIRI), the strengths and challenges of the approach and some future developments. METHODS: The design and implementation of PHIRI have been developed upon: (i) the data visiting principle-data does not move but code moves; (ii) the orchestration of the research question throughout a workflow that ensured legal, organizational, semantic and technological interoperability and (iii) a 'master-worker' federated computational architecture that supported the development of four uses cases. RESULTS: Nine participants nodes and 28 Euro-Peristat members completed the deployment of the infrastructure according to the expected outputs. As a consequence, each use case produced and published their own common data model, the analytical pipeline and the corresponding research outputs. All the digital objects were developed and published according to Open Science and FAIR principles. CONCLUSION: PHIRI has successfully supported the development of four use cases in a federated manner, overcoming limitations for the reuse of sensitive health data and providing a methodology to achieve interoperability in multiple research nodes.

A full-head model to investigate intra and extracochlear electric fields in cochlear implant stimulation.

OBJECTIVE: Despite the widespread use and technical improvement of cochlear implant (CI) devices over past decades, further research into the bioelectric bases of CI stimulation is still needed. Various stimulation modes implemented by different CI manufacturers coexist, but their true clinical benefit remains unclear, probably due to the high inter-subject variability reported, which makes the prediction of CI outcomes and the optimal fitting of stimulation parameters challenging. A highly detailed full head model that includes a cochlea and an electrode array is developed in this study to emulate intracochlear voltages and extracochlear current pathways through the head in CI stimulation. APPROACH: Simulations based on the finite element method were conducted under monopolar, bipolar, tripolar, and partial tripolar modes, as well as for apical, medial, and basal electrodes. Variables simulated included: intracochlear voltages, electric field (EF) decay, electric potentials at the scalp and extracochlear currents through the head. To better understand CI side effects such as facial nerve stimulation, caused by spurious current leakage out from the cochlea, special emphasis is given to the analysis of the EF over the facial nerve. MAIN RESULTS: The model reasonably predicts EF magnitudes and trends previously reported in CI users. New relevant extracochlear current pathways through the head and brain tissues have been identified. Simulated results also show differences in the magnitude and distribution of the EF through different segments of the facial nerve upon different stimulation modes and electrodes, dependent on nerve and bone tissue conductivities. SIGNIFICANCE: Full head models prove useful tools to model intra and extracochlear EFs in CI stimulation. Our findings could prove useful in the design of future experimental studies to contrast FNS mechanisms upon stimulation of different electrodes and CI modes. The full-head model developed is freely available for the CI community for further research and use.

The biobehavioural pain and movement questionnaire (BioPMovQ): development and psychometric validation of a new questionnaire.

Objective: The purpose of this research was to design and psychometrically validate a new instrument (the Biobehavioural Pain and Movement Questionnaire/BioPMovQ), which assesses the relationship between pain and various factors related to motor behaviour from a biobehavioural perspective. Methods: A mixed-method design combining a qualitative study with an observational and cross-sectional study was employed to develop (content validity) and psychometrically validate (construct validity, reliability and concurrent/discriminant validity) a new instrument. A total of 200 patients with chronic musculoskeletal pain were recruited. Results: According to the exploratory factor analysis, the final version of the BioPMovQ consists of 16 items distributed across 4 subscales (1, disability, 2, self-efficacy for physical activity; 3, movement avoidance behaviours; and 4, self-perceived functional ability), all with an eigen value greater than 1, explaining 55.79% of the variance. The BioPMovQ showed high internal consistency (Cronbach's α = 0.82; McDonald's ω = 0.83). The intraclass correlation coefficient was 0.86 (95% confidence interval 0.76 to 0.91), which was considered to demonstrate excellent test-retest reliability. The standard error of measurement and minimal detectable change were 3.43 and 8.04 points, respectively. No floor or ceiling effects were identified. There was a positive, significant and moderate magnitude correlation with the Graded Chronic Pain Scale (r = 0.54), kinesiophobia (r = 0.60), pain catastrophising (r = 0.44) and chronic pain self-efficacy (r = -0.31). Conclusion: The BioPMovQ showed good psychometric properties. Based on the findings of this study, the BioPMovQ can be used in research and clinical practice to assess patients with chronic musculoskeletal pain.

Rev1Δwzm vaccine candidate is safe in young and adult sheep and protects against Brucella ovis infection in rams.

Small ruminants affected by brucellosis, caused mainly by Brucella melitensis and B. ovis, suffer reproductive disorders, leading to significant economic losses worldwide. Vaccination is an essential tool to prevent the disease in ovine and caprine livestock, but the only vaccine recommended to date is B. melitensis Rev1, which in sheep is only safe for use in lambs aged 3-4 months. This restriction poses considerable practical challenges for the implementation of Rev1 in countries with endemic brucellosis and/or limited resources, where there is a need for mass vaccination with a safe vaccine to control the disease in both animals and humans. We recently developed a B. melitensis strain Rev1Δwzm showing superior vaccine properties in mice and safety in pregnant ewes. Here, we report that Rev1Δwzm (i) is safe in young and adult sheep, both male and female; (ii) induces a transient serological response in the Rose Bengal test in ≤50 % of sheep, confirmed to some extent by the complement fixation test, and a stronger, more persistent anti- rough-LPS response; and (iii) protects rams against a B. ovis challenge 25 weeks after vaccination. To resolve the problem of serological interference, the use of green fluorescent protein tagging strategy allowed us to identify vaccinated sheep with only a single inoculation. These results, together with the previously reported safety in pregnant ewes, position Rev1Δwzm as a firm vaccine candidate and a promising alternative to Rev1. Further experiments are warranted to assess its efficacy against B. melitensis in pregnant ewes.

Hydrogen-bonded assemblies of iron(II) spin crossover complexes.

The paper reports on the synthesis, crystal structure, thermal and magnetic properties of spin crossover (SCO) salts containing the [Fe(bpp)2]2+ cation (bpp = 2,6-bis(pyrazol-3-yl)pyridine) and different rigid polycarboxylate anions, such as anthracene-9,10-dicarboxylate (ADC), benzene-1,3,5-tricarboxylate (BTC) and biphenyl-4,4'-dicarboxylate (BPDC). Compound [Fe(bpp)2](ADC)·9H2O (1) shows a porous hydrogen-bonded structure with water molecules sitting in the channels. It contains low-spin (LS) Fe2+ cations that undergo crossover to the high-spin (HS) state upon dehydration. Anhydrous 1 remains HS on cooling at low temperatures. A similar magnetic behaviour is obtained for the partially protonated BTC salt [Fe(bpp)2](HBTC)·5H2O (2), showing a spin change concomitant with dehydration to a HS phase that undergoes gradual and partial SCO on cooling, affecting 25% of the Fe2+ cations. Instead, the BPDC salt [Fe(bpp)2](BPDC)·5H2O (3) has a ground HS state in its fully hydrated form.

Invertebrados (Echinodermata, Brachiopoda, Bryozoa, Cnidaria, Porifera) del Carbonífero de Sierra Santa Teresa, Sonora, México: Consideraciones paleoecológicas y paleogeográficas / Invertebrates (Echinodermata, Brachiopoda, Bryozoa, Cnidaria, Porifera) from the Carboniferous of Sierra Santa Teresa, Sonora, Mexico: Paleoecological and paleogeographic considerations

Resumen Introducción: La Sierra Santa Teresa se encuentra a 20 km al sureste de Hermosillo en la región central del estado de Sonora, México. Los estratos sedimentarios corresponden principalmente a textura de piedra caliza, mudstone, wackestone y packstone del Paleozoico superior. La biota está representada por crinoideos de las morfoespecies Baryschyr anosus, Cyclocaudex insaturatus, Floricyclus angustimargo, Cyclocion distictus, Lamprosterigma erathense y Preptopremnum rugosum en asociación con algas, foraminíferos fusulínidos, esponjas coralinas (Chaetetes sp), corales solitarios (Lophophyllidium sp., Fomichevella sp.), briozoos fenestélidos (Archimedes stoyanowi) y braquiópodos (Antiquatonia sp.). Objetivo: El objetivo principal de este estudio es dar a conocer la composición biótica de la Sierra Santa Teresa y sus consideraciones paleoecológicas y paleogeográficas. Métodos: En este estudio se sintetiza la información sobre las principales taxas recolectadas en afloramientos del Carbonífero de la Sierra, Santa Teresa. Resultados: La distribución de la biota, y particularmente de las morfoespecies de crinoideos, permitió hacer correlaciones paleobiogeográficas con otras localidades del Misisípico-Pensilvánico de México y de distintas regiones de los Estados Unidos de América, principalmente en Texas, Colorado, Illinois y Oklahoma, que se encontraban ubicadas al suroeste del Cratón norteamericano. Conclusiones: Se considera que el paleoambiente inferido con base en los registros paleontológicos de la Sierra Santa Teresa se trataba de mares someros que permitieron el desarrollo de comunidades de crinoideos, así como otros invertebrados como esponjas coralinas, corales solitarios, briozoos fenestélidos y braquiópodos, con un rango estratigráfico del Misisípico Medio-Superior (Chesteriano) al Pensilvánico Medio (Desmoinesiano).

Abstract Introduction: The Sierra Santa Teresa is located 20 km southeast of Hermosillo in the central region of Sonora state, Mexico. The sedimentary strata mainly correspond to limestone, mudstone, wackestone and packstone texture, from the upper Paleozoic. The biota is represented by crinoids of the morphospecies Baryschyr anosus, Cyclocaudex insaturatus, Floricyclus angustimargo, Cyclocion distictus, Lamprosterigma erathense, Preptopremnum rugosum in association with algae, fusulinid foraminifera, coralline sponges (Chaetetes sp.), solitary corals (Lophophyllidium sp., Fomichevella sp.), fenestellid bryozoans (Archimedes stoyanowi), and brachiopods (Antiquatonia sp.). Objective: The principal aim of this study is to analyze the biotic composition in the Sierra Santa Teresa and its paleoecological and paleogeographical considerations. Methods: In this study we synthetize information about the principal taxa collected in outcrops of the Carboniferous of the Sierra, Santa Teresa. Results: The distribution of the biota, and particularly the crinoid morphospecies, allowed paleobiogeographical correlations to be made with other Mississippian-Pennsylvanian localities of Mexico and different regions of the United States of America in Texas, Colorado, Illinois and Oklahoma, which were located in the southwestern of the North American Craton. Conclusions: It is considered that the paleoenvironment inferred based on the paleontological records of the Sierra Santa Teresa were shallow seas that allowed the development of communities of crinoids, as well as other invertebrates such as coralline sponges, solitary corals, fenestellid bryozoans and brachiopods, with a range stratigraphic from the Middle-Upper Mississippian (Chesterian) to the Middle Pennsylvanian (Desmoinesian).

Prognostic Value of D-dimer to Lymphocyte Ratio (DLR) in Hospitalized Coronavirus Disease 2019 (COVID-19) Patients: A Validation Study in a National Cohort.

BACKGROUND: This study aimed to validate the role of the D-dimer to lymphocyte ratio (DLR) for mortality prediction in a large national cohort of hospitalized coronavirus disease 2019 (COVID-19) patients. METHODS: A retrospective, multicenter, observational study that included hospitalized patients due to SARS-CoV-2 infection in Spain was conducted from March 2020 to March 2022. All biomarkers and laboratory indices analyzed were measured once at admission. RESULTS: A total of 10,575 COVID-19 patients were included in this study. The mean age of participants was 66.9 (±16) years, and 58.6% (6202 patients) of them were male. The overall mortality rate was 16.3% (n = 1726 patients). Intensive care unit admission was needed in 10.5% (n = 1106 patients), non-invasive mechanical ventilation was required in 8.8% (n = 923 patients), and orotracheal intubation was required in 7.5% (789 patients). DLR presented a c-statistic of 0.69 (95% CI, 0.68-0.71) for in-hospital mortality with an optimal cut-off above 1. Multivariate analysis showed an independent association for in-hospital mortality for DLR > 1 (adjusted OR 2.09, 95% CI 1.09-4.04; p = 0.03); in the same way, survival analysis showed a higher mortality risk for DLR > 1 (HR 2.24; 95% CI 2.03-2.47; p < 0.01). Further, no other laboratory indices showed an independent association for mortality in multivariate analysis. CONCLUSIONS: This study confirmed the usefulness of DLR as a prognostic biomarker for mortality associated with SARS-CoV-2 infection, being an accessible, cost-effective, and easy-to-use biomarker in daily clinical practice.

Clinical practice guideline on the management of vestibular schwannoma.

INTRODUCTION: Vestibular schwannoma (VS) is the most common tumour of the cerebellopontine angle. The greater accessibility to radiological tests has increased its diagnosis. Taking into account the characteristics of the tumour, the symptoms and the age of the patient, three therapeutic strategies have been proposed: observation, surgery or radiotherapy. Choosing the most appropriate for each patient is a frequent source of controversy. MATERIAL AND METHODS: This paper includes an exhaustive literature review of issues related to VS that can serve as a clinical guide in the management of patients with these lesions. The presentation has been oriented in the form of questions that the clinician usually asks himself and the answers have been written and/or reviewed by a panel of national and international experts consulted by the Otology Commission of the SEORL-CCC. RESULTS: A list has been compiled containing the 13 most controversial thematic blocks on the management of VS in the form of 50 questions, and answers to all of them have been sought through a systematic literature review (articles published on PubMed and Cochrane Library between 1992 and 2023 related to each thematic area). Thirty-three experts, led by the Otology Committee of SEORL-CCC, have analyzed and discussed all the answers. In Annex 1, 14 additional questions divided into 4 thematic areas can be found. CONCLUSIONS: This clinical practice guideline on the management of VS offers agreed answers to the most common questions that are asked about this tumour. The absence of sufficient prospective studies means that the levels of evidence on the subject are generally medium or low. This fact increases the interest of this type of clinical practice guidelines prepared by experts.

Impact of telenurse-led intervention in clinical trials on health literacy, empowerment, and health outcomes in patients with solid tumours: a pilot quasi-experimental study.

BACKGROUND: During the COVID-19 pandemic, decentralised clinical trials incorporated self-monitoring, self-reporting, and telenursing tools to address health literacy and health empowerment of patients enrolled in clinical trials. We aimed to determine the impact of an educational intervention using telenursing consultations on health literacy, health empowerment, and health-related quality of life in cancer patients enrolled in clinical trials by measuring the level of satisfaction with the care received and assessing the views of healthcare professionals concerning the advanced practice nurse (APN) role in oncology clinical trials. METHODS: In this pilot analytical, descriptive, longitudinal, quasi-experimental, and pre-post test study, an educational intervention was conducted by 5 visits with an APN using synchronous teleconsultation in patients starting cancer treatment for the first time in a clinical trial (n = 60), and health professionals working with the APN (n = 31). A descriptive analysis of the samples and questionnaires were utilised along with statistical comparisons. RESULTS: After the intervention, patients' health literacy (31.7%), health empowerment (18.3%), and health-related quality of life (33.3%) increased (p < 0.05), with a decrease and trend towards resolution of care needs (p < 0.05). Satisfaction with the quality and care received in terms of perceived convenience, transition, and continuity of care showed positive results in 64.9 ± 20.7, 77.6 ± 19.5, and 72.1 ± 20.4 of respondents, respectively. On the overall assessment of the APN role, healthcare professionals expressed a high level of agreement with the statements related to their work performance. CONCLUSIONS: The data indicates that a clinical trial APN-led telenursing educational intervention results in an overall increase in health literacy, an improvement in health empowerment and health-related quality of life, and a decrease in care needs of oncology clinical trials patients. Patients stated that they received a high quality of care and health professionals indicated high levels of acceptance with APNs. Based on these results, we suggest that the APN role should gain more recognition in the Spanish healthcare system and their professional competencies should be aligned with those of other countries.

Spanish version of the short European Health Literacy Survey Questionnaire HLS-Q12: Transcultural adaptation and psychometric properties.

BACKGROUND: Health literacy has a direct impact on the health of populations. It is related to education, capacity for self-care, and management of health resources. The Health Literacy Survey Questionnaire HLS-Q12 is one of the reference instruments but has not yet been adapted to Spanish. The aims of the study were to cross-culturally adapt and evaluate the psychometric properties of the Spanish version of the HLS-Q12. METHODS: Data was collected from June 2020 to March 2022. The sample consisted of 60 patients who initiated cancer treatment for the first time within a clinical trial. Double direct translation, back-translation, cognitive debriefing with a 10-patient sample, and an expert committee were used for cross-cultural adaptation. For validation of the HLS-Q12, a psychometric analysis was performed to assess feasibility, reliability, sensitivity to change and construct validity with other measures such as health-related quality of life, empowerment, and health needs. RESULTS: The HLS-Q12 is equivalent at the semantic, conceptual, and content level to the original version and its psychometric properties demonstrated good internal consistency with a Cronbach's alpha of 0.88 and a McDonald´s omega of 0.91, a high degree of fit for the confirmatory factor analysis, and a statistically significant sensitivity to change (p = 0.025). CONCLUSIONS: Based on robust psychometric values, the Spanish version of HLS-Q12 was found to be a good cross-culturally adapted tool for collecting correct information on health literacy in cancer patients regardless of tumour type or stage. Although more studies are needed, this version of HLS-Q12 could be used in research for collecting data on the health literacy needs of Spanish-speaking patients.

Small Extracellular Vesicles and Oxidative Pathophysiological Mechanisms in Retinal Degenerative Diseases.

This review focuses on the role of small extracellular vesicles in the pathophysiological mechanisms of retinal degenerative diseases. Many of these mechanisms are related to or modulated by the oxidative burden of retinal cells. It has been recently demonstrated that cellular communication in the retina involves extracellular vesicles and that their rate of release and cargo features might be affected by the cellular environment, and in some instances, they might also be mediated by autophagy. The fate of these vesicles is diverse: they could end up in circulation being used as markers, or target neighbor cells modulating gene and protein expression, or eventually, in angiogenesis. Neovascularization in the retina promotes vision loss in diseases such as diabetic retinopathy and age-related macular degeneration. The importance of micro RNAs, either as small extracellular vesicles' cargo or free circulating, in the regulation of retinal angiogenesis is also discussed.

STIM1 translocation to the nucleus protects cells from DNA damage.

DNA damage represents a challenge for cells, as this damage must be eliminated to preserve cell viability and the transmission of genetic information. To reduce or eliminate unscheduled chemical modifications in genomic DNA, an extensive signaling network, known as the DNA damage response (DDR) pathway, ensures this repair. In this work, and by means of a proteomic analysis aimed at studying the STIM1 protein interactome, we have found that STIM1 is closely related to the protection from endogenous DNA damage, replicative stress, as well as to the response to interstrand crosslinks (ICLs). Here we show that STIM1 has a nuclear localization signal that mediates its translocation to the nucleus, and that this translocation and the association of STIM1 to chromatin increases in response to mitomycin-C (MMC), an ICL-inducing agent. Consequently, STIM1-deficient cell lines show higher levels of basal DNA damage, replicative stress, and increased sensitivity to MMC. We show that STIM1 normalizes FANCD2 protein levels in the nucleus, which explains the increased sensitivity of STIM1-KO cells to MMC. This study not only unveils a previously unknown nuclear function for the endoplasmic reticulum protein STIM1 but also expands our understanding of the genes involved in DNA repair.

Methods for Studying Swimming and Surface Motilities in Rhizobia.

Rhizobia are soil proteobacteria able to establish a nitrogen-fixing interaction with legumes. In this interaction, rhizobia must colonize legume roots, infect them, and become hosted inside new organs formed by the plants and called nodules. Rhizobial motility, not being essential for symbiosis, might affect the degree of success of the interaction with legumes. Because of this, the study of rhizobial motility (either swimming or surface motility) might be of interest for research teams working on rhizobial symbiotic performance. In this chapter, we describe the protocols we use in our laboratories for studying the different types of motilities exhibited by Sinorhizobium fredii and Sinorhizobium meliloti, as well as for analyzing the presence of flagella in these bacteria. All these protocols might be used (or adapted) for studying bacterial motility in rhizobia.

Exploring long-term breast cancer survivors' care trajectories using dynamic time warping-based unsupervised clustering.

OBJECTIVES: Long-term breast cancer survivors (BCS) constitute a complex group of patients, whose number is estimated to continue rising, such that, a dedicated long-term clinical follow-up is necessary. MATERIALS AND METHODS: A dynamic time warping-based unsupervised clustering methodology is presented in this article for the identification of temporal patterns in the care trajectories of 6214 female BCS of a large longitudinal retrospective cohort of Spain. The extracted care-transition patterns are graphically represented using directed network diagrams with aggregated patient and time information. A control group consisting of 12 412 females without breast cancer is also used for comparison. RESULTS: The use of radiology and hospital admission are explored as patterns of special interest. In the generated networks, a more intense and complex use of certain healthcare services (eg, radiology, outpatient care, hospital admission) is shown and quantified for the BCS. Higher mortality rates and numbers of comorbidities are observed in various transitions and compared with non-breast cancer. It is also demonstrated how a wealth of patient and time information can be revealed from individual service transitions. DISCUSSION: The presented methodology permits the identification and descriptive visualization of temporal patterns of the usage of healthcare services by the BCS, that otherwise would remain hidden in the trajectories. CONCLUSION: The results could provide the basis for better understanding the BCS' circulation through the health system, with a view to more efficiently predicting their forthcoming needs and thus designing more effective personalized survivorship care plans.

How satisfied are patients with nursing care and why? A comprehensive study based on social media and opinion mining.

To assess the overall experience of a patient in a hospital, many factors must be analyzed; nonetheless, one of the key aspects is the performance of nurses as they closely interact with patients on many occasions. Nurses carry out many tasks that could be assessed to understand the patient's satisfaction and consequently, the effectiveness of the offered services. To assess their performance, traditionally, expensive, and time-consuming methods such as questionnaires and interviews have been used; nevertheless, the development of social networks has allowed the patients to convey their opinions in a free and public manner. For that reason, in this study, a comprehensive analysis has been performed based on patients' opinions collected from a feedback platform for health and care services, to discover the topics about nurses the patients are more interested in. To do so, a topic modeling technique has been proposed. After this, sentiment analysis has been applied to classify the topics as satisfactory or unsatisfactory. Finally, the results have been compared with what the patients think about doctors. The results highlight what topics are most relevant to assess the patient satisfaction and to what extent. The results remark that the opinion about nurses is, in general, more positive than about doctors.

Perfil de seguridad y satisfacción con la combinación fija de memantina-donepezilo en pacientes con diagnóstico de Alzheimer moderado a severo / Safety and satisfaction profile with the fixed combination of memantine-donepezil in patients diagnosed with moderate to severe Alzheimer's disease

Introducción: La enfermedad de Alzheimer es un trastorno neurodegenerativo de inicio insidioso y progresión lenta. Epidemiológicamente representa 60% a 70% de los casos de demencia.Objetivo: Determinar el grado de satisfacción y seguridad con la combinación fija de memantina-donepezilo durante 6 meses.Material y métodos: Se llevó a cabo un estudio observacional, transversal y analítico con base a un diseño de Real World Evidence (RWE), para evaluar la satisfacción del tratamiento a través de preguntas con una escala de Likert para la valoración de la satisfacción de 31 pacientes que recibieron como parte de su tratamiento habitual la combinación fija de memantina + donepezilo una vez al día durante seis meses previos a la aplicación de la escala de satisfacción. La información se recopiló de febrero a noviembre del 2021. Resultados: 60% de los eventos adversos fueron leves, 40% moderados. La tolerabilidad luego de 3 meses fue percibida como muy buena o excelente por 81% de pacientes. A seis meses 87,1% calificó como muy bueno o excelente el tratamiento. Satisfacción con el tratamiento a 3 meses fue, "satisfecho en su mayoría" o "totalmente satisfecho" para el 87,1%. Discusión: Prevalencia en el género femenino de 77,4% mayor a la reportada para todo el país de 54,8%, comorbilidades reportadas similares a las descritas por la literatura. Tolerabilidad calificada como excelente en comparación con otros estudios que calificaron como buena tolerabilidad. Conclusión: La administración de la combinación fija de memantina 14 mg + donepezilo 10 mg o memantina 28 mg + donepezilo 10 mg, fue una opción segura y bien tolerada.

Introduction:Alzheimer's disease is a neurodegenerative disorder of insidious onset and slow progression. Epidemiologically it accounts for 60% to 70% of cases of dementia.Objective:Determine the degree of satisfaction and safety with the fixed combination of memantine-donepezil for 6 months.Materials and methods: A cross-sectional, observational, and analytical study was conducted based on a Real World Evidence (RWE) design to assess treatment satisfaction through Likert-scale questions of 31 patients who, as part of their regular treatment, received the fixed combination of memantine + donepezil once daily for six months before the administration of the satisfaction scale. Data collection took place from February to November 2021.Results: 60% of adverse events were mild, 40% moderate. Tolerability after 3 months was perceived as very good or excellent by 81% of patients. At six months 87,1% rated the treatment as very good or excellent. Satisfaction with treatment at 3 months was, "mostly satisfied" or "totally satisfied" for 87,1%. Discussion: Prevalence in the female gender of 77,4% higher than that reported for the whole country of 54,8%, reported comorbidities similar to those described in the literature. Tolerability rated as excellent compared to other studies which rated as good tolerability. Conclusions:Administration of the fixed combination of memantine 14 mg + donepezil 10 mg or memantine 28 mg + donepezil 10 mg was a safe and well-tolerated option.