Precise Targeting of Autoantigen-Specific B Cells in Lupus Nephritis with Chimeric Autoantibody Receptor T Cells.

Despite conventional therapy, lupus nephritis (LN) remains a significant contributor to short- and long-term morbidity and mortality. B cell abnormalities and the production of autoantibodies against nuclear complexes like anti-dsDNA are recognised as key players in the pathogenesis of LN. To address the challenges of chronic immunosuppression associated with current therapies, we have engineered T cells to express chimeric autoantibody receptors (DNA-CAART) for the precise targeting of B cells expressing anti-dsDNA autoantibodies. T cells from LN patients were transduced using six different CAAR vectors based on their antigen specificity, including alpha-actinin, histone-1, heparan sulphate, or C1q. The cytotoxicity, cytokine production, and cell-cell contact of DNA-CAART were thoroughly investigated in co-culture experiments with B cells isolated from patients, both with and without anti-dsDNA positivity. The therapeutic effects were further evaluated using an in vitro immune kidney LN organoid. Among the six proposed DNA-CAART, DNA4 and DNA6 demonstrated superior selectively cytotoxic activity against anti-dsDNA+ B cells. Notably, DNA4-CAART exhibited improvements in organoid morphology, apoptosis, and the inflammatory process in the presence of IFNα-stimulated anti-dsDNA+ B cells. Based on these findings, DNA4-CAART emerge as promising candidates for modulating autoimmunity and represent a novel approach for the treatment of LN.

Identification of decreased intrinsic capacity: Performance of diagnostic measures of the ICOPE Screening tool in community dwelling older people in the VIMCI study.

BACKGROUND: The World Health Organization (WHO) has developed the Integrated Care for Older People (ICOPE) strategy to face the challenges of ageing societies. This strategy is focused on person centered care and the assessment intrinsic capacity (IC). Early identification of five domains of IC (cognition, locomotion, vitality, sensory (hearing and vision), and psychological) has been shown to be related with adverse outcomes and can guide actions towards primary prevention and healthy ageing. IC assessment proposed by the WHO ICOPE guidelines is composed by two steps: First, Screening for decreased IC by the ICOPE Screening tool; second, by the reference standard methods. The aim was to assess the performance of diagnostic measures (sensibility, specificity, diagnostic accuracy, and agreement of the ICOPE Screening tool) compared to the reference standard methods in European community-dwelling older adults. METHODS: Cross-sectional analysis of the baseline of the ongoing VIMCI (Validity of an Instrument to Measure Intrinsic Capacity) cohort study, which was carried out in Primary Care centers and outpatient clinics from 5 rural and urban territories in Catalonia (Spain). Participants were 207community dwelling persons ≥ 70-year-old with Barthel ≥ 90, without dementia or advanced chronic conditions who provided their consent to participate. The 5 IC domains were assessed by the ICOPE Screening tool and the reference methods (SPPB, gait speed, MNA, Snellen chart, audiometry, MMSE, GDS5) during patients' visit. Agreement was assessed with the Gwet AC1 index. RESULTS: ICOPE Screening tool sensitivity was higher for cognition (0.889) and ranged between 0.438 and 0.569 for most domains. Specificity ranged from 0.682 to 0.96, diagnostic accuracy from 0.627 to 0.879, Youden index from 0.12 to 0.619, and Gwet AC1 from 0.275 to 0.842. CONCLUSION: The ICOPE screening tool showed fair performance of diagnostic measures; it was helpful to identify those participants with satisfactory IC and showed a modest ability to identify decreased IC in older people with high degree of autonomy. Since low sensitivities were found, a process of external validation would be recommended to reach better discrimination. Further studies about the ICOPE Screening tool and its performance of diagnostic measures in different populations are urgently required.

Small-Extracellular-Vesicle-Derived miRNA Profile Identifies miR-483-3p and miR-326 as Regulators in the Pathogenesis of Antiphospholipid Syndrome (APS).

Primary antiphospholipid syndrome (PAPS) is a systemic autoimmune disease associated with recurrent thrombosis and/or obstetric morbidity with persistent antiphospholipid antibodies (aPL). Although these antibodies drive endothelial injury and thrombophilia, the underlying molecular mechanism is still unclear. Small extracellular vesicles (sEVs) contain miRNAs, key players in intercellular communication. To date, the effects of miRNA-derived sEVs in PAPS are not well understood. We characterised the quantity, cellular origin and miRNA profile of sEVs isolated from thrombotic APS patients (PAPS, n = 50), aPL-carrier patients (aPL, n = 30) and healthy donors (HD, n = 30). We found higher circulating sEVs mainly of activated platelet origin in PAPS and aPL patients compared to HD, that were highly engulfed by HUVECs and monocyte. Through miRNA-sequencing analysis, we identified miR-483-3p to be differentially upregulated in sEVs from patients with PAPS and aPL, and miR-326 to be downregulated only in PAPS sEVs. In vitro studies showed that miR-483-3p overexpression in endothelial cells induced an upregulation of the PI3K-AKT pathway that led to endothelial proliferation/dysfunction. MiR-326 downregulation induced NOTCH pathway activation in monocytes with the upregulation of NFKB1, tissue factor and cytokine production. These results provide evidence that miRNA-derived sEVs contribute to APS pathogenesis by producing endothelial cell proliferation, monocyte activation and adhesion/procoagulant factors.

Genotype and Phenotype Influence the Personal Response to Prostaglandin Analogues and Beta-Blockers in Spanish Glaucoma and Ocular Hypertension Patients.

Analysis of the genotype that predicts the phenotypic characteristics of a cohort of glaucoma and ocular hypertension patients, and the correlation with their personal pharmacological response to beta-blockers (BB) and prostaglandin analogues (PGA). Prospective study that included 139 eyes from 72 patients under BB and/or PGA treatment, and in some cases other types of ocular hypotensive treatments. Five single-nucleotide polymorphisms were genotyped by real-time PCR assays: prostaglandin-F2α receptor (rs3766355, rs3753380); cytochrome-P450 2D6 (rs16947, rs769258); and beta-2-adrenergic receptor (rs1042714). Other studied variables were mean deviation (MD) of visual field, previous ocular interventions, medical treatment, baseline (bIOP), and treated intraocular pressure (tIOP). From a total of 139 eyes, 71 (51.1%) were left eyes. The main diagnosis was primary open angle glaucoma (66.2%). A total of 57 (41%) eyes were under three or more medications (PGA + BB + other) and, additionally, 57 eyes (41%) had had some kind of glaucoma surgery. The mean bIOP and tIOP were 26.55 ± 8.19 and 21.01 ± 5.54 mmHg, respectively. Significant differences in tIOP were found between heterozygous (HT) (21.07 ± 0.607 mmHg) and homozygous (HM) (20.98 ± 0.639 mmHg) rs3766355 with respect to wildtype individuals (16 ± 1.08 mmHg) (p = 0.031). The MD values presented significant differences between wildtype rs3766355 (-2 ± 2.2 dB), HT (-3.87 ± 4 dB), and HM carriers (-9.37 ± 9.51 dB) (p = 0.009). Significant differences were also observed between the MD in wildtype rs3753380 (-6.1 ± 8.67 dB), HT (-9.02 ± 8.63 dB), and HM carriers (-9.51 ± 7.44 dB) (p = 0.017). Patients carrying the variant rs3766355 in HM or HT presented clinically-significantly higher tIOP than wildtype patients. Additionally, some differences in MD were found in rs3766355 and rs3753380 carriers, and the more alleles that were affected, the worse the MD value, meaning greater severity of the glaucoma. Poor response to treatment and more visual field damage may be associated with being a carrier of these mutated alleles.

A retention-release mechanism based on RAB11FIP2 for AMPA receptor synaptic delivery during long-term potentiation.

It is well--established that Rab11-dependent recycling endosomes drive the activity-dependent delivery of AMPA receptors (AMPARs) into synapses during long-term potentiation (LTP). Nevertheless, the molecular basis for this specialized function of recycling endosomes is still unknown. Here, we have investigated RAB11FIP2 (FIP2 hereafter) as a potential effector of Rab11-dependent trafficking during LTP in rat hippocampal slices. Surprisingly, we found that FIP2 operates independently from Rab11 proteins, and acts as a negative regulator of AMPAR synaptic trafficking. Under basal conditions, FIP2 associates with AMPARs at immobile compartments, separately from recycling endosomes. Using shRNA-mediated knockdown, we found that FIP2 prevents GluA1 (encoded by the Gria1 gene) AMPARs from reaching the surface of dendritic spines in the absence of neuronal stimulation. Upon induction of LTP, FIP2 is rapidly mobilized, dissociates from AMPARs and undergoes dephosphorylation. Interestingly, this dissociation of the FIP2-AMPAR complex, together with FIP2 dephosphorylation, is required for LTP, but the interaction between FIP2 and Rab11 proteins is not. Based on these results, we propose a retention-release mechanism, where FIP2 acts as a gate that restricts the trafficking of AMPARs, until LTP induction triggers their release and allows synaptic delivery.

A Comparative Study of Treatment Interventions for Patellar Tendinopathy: A Randomized Controlled Trial.

OBJECTIVES: To determine the additional effect of dry needling (DN) or percutaneous needle electrolysis (PNE) combined with eccentric exercise (EE) and determine which is the most effective for patients with patellar tendinopathy (PT). DESIGN: Blinded, randomized controlled trial, with follow-up at 10 and 22 weeks. SETTINGS: Recruitment was performed in sport clubs. Diagnosis and intervention were conducted at San Jorge University. PARTICIPANTS: Patients (N=48) with PT with pain for at least 3 months between the ages of 18 and 45 years. INTERVENTIONS: Three interventions were carried out: DN and EE, PNE and EE, and EE with sham needle as the control group. MAIN OUTCOME MEASURES: Disability was measured using the Victorian Institute of Sports Assessment Questionnaire, patellar tendon. Visual analog scale was used to measure pain over time, the Short Form-36 was used to measure quality of life, and ultrasound was used to measure structural abnormalities. RESULTS: A total of 48 participants (42 men, 6 women; average age, 32.46y; SD, 7.14y) were enrolled. The improvement in disability and pain in each group between baseline and post-treatment and baseline and follow-up was significant (P≤.05), without differences among groups. CONCLUSION: DN or PNE combined with an EE program has not shown to be more effective than a program of only EE to improve disability and pain in patients with PT in the short (10wk) and medium (22wk) terms. Clinical improvements were not associated with structural changes in the tendon.

Low-dose vaginal misoprostol vs vaginal dinoprostone insert for induction of labor beyond 41st week: A randomized trial.

INTRODUCTION: The aim of this study was to compare the efficacy and safety of a low-dose protocol of vaginal misoprostol and vaginal dinoprostone insert for induction of labor in women with post-term pregnancies. MATERIAL AND METHODS: We designed a prospective, randomized, open-labeled trial with evaluators blinded to the end-point, including women of at least 41 weeks of gestational age with uncomplicated singleton pregnancies and a Bishop score <6. They were randomized into dinoprostone or misoprostol groups in a 1:1 ratio. Baseline maternal data and perinatal outcomes were recorded for statistical analysis. Successful vaginal delivery within 24 hours was the primary outcome variable. A P value <0.05 was considered statistically significant. This study was registered in ClinicalTrials.gov (number NTC03744364). RESULTS: We included 198 women for analysis (99 women in each group). Vaginal birth rate within 24 hours did not differ between groups (49.5% vs 42.4%; P = 0.412). When the Bishop score was <4, dinoprostone insert showed a higher probability of vaginal delivery within 12 hours (17.8% vs 4%; P = 0.012). In the dinoprostone group, removal of the insert was more likely to be due to an adverse event (5.1% vs 14.1%; P = 0.051) and an abnormal fetal heart rate pattern during active labor (44.4% vs 58.6%; P = 0.047). Both groups were similar in neonatal outcomes including Apgar score, umbilical cord pH and neonatal intensive care unit admission. CONCLUSIONS: Low-dose vaginal misoprostol and vaginal dinoprostone insert seem to be equally effective and safe for induction of labor in pregnant women with a gestational age beyond 41 weeks.

[Factors determining irregular attendance to follow-up visits among human immunodeficiency virus patients: results of the hospital survey of patients infected with human immunodeficiency virus]. / Determinantes de la asistencia irregular a consulta médica en pacientes con infección por el virus de la inmunodeficiencia humana: resultados de la Encuesta Hospitalaria de pacientes con el virus de la inmunodeficiencia humana, 2002-2012.

INTRODUCTION: To describe the occurrence of non-regular attendance to follow-up visits among HIV patients and to analyze the determining factors. METHODS: One-day survey carried out annually (2002-2012) in public hospitals. Epidemiological, clinical and behavioral data are collected in all HIV-infected inpatients and outpatients receiving HIV-related care on the day of the survey. "Non-regular attendance to a follow-up visit" was defined as sporadic attendance to the medical appointments, according to the judgment of the attending physician. Descriptive and bivariate analyses were performed, and factors associated to non-regular attendance to follow-up visits were estimated using logistic regression. RESULTS: A total of 7,304 subjects were included, of whom 13.7% did not attend medical appointments regularly. Factors directly associated with non-regular attendance were: age between 25-49 years; birth in Sub-Saharan Africa or Latin-America; low educational level; being homeless or in prison; living alone or in closed institutions; being unemployed or retired; being an intravenous drug user; not using a condom at last sexual encounter, and injecting drugs in the last 30 days. Conversely, HIV diagnosis within the last year and being men who have sex with men were factors inversely associated with non-regular attendance to follow-up visits. CONCLUSION: In spite of health care beings free of charge for everyone in Spain, social factors can act as barriers to regular attendance to medical appointments, which, in turn, can endanger treatment effectiveness in some population groups. This should be taken into account when planning HIV policies in Spain.

Assessment of social behavior and chemosensory cue detection in an animal model of neurodegeneration.

Numerous studies have shown that aging in humans leads to a decline in olfactory function, resulting in deficits in acuity, detection threshold, discrimination, and olfactory-associated memories. Furthermore, impaired olfaction has been identified as a potential indicator for the onset of age-related neurodegenerative diseases, including Alzheimer's disease (AD). Studies conducted on mouse models of AD have largely mirrored the findings in humans, thus providing a valuable system to investigate the cellular and circuit adaptations of the olfactory system during natural and pathological aging. However, the majority of previous research has focused on assessing the detection of neutral or synthetic odors, with little attention given to the impact of aging and neurodegeneration on the recognition of social cues-a critical feature for the survival of mammalian species. Therefore, in this study, we present a battery of olfactory tests that use conspecific urine samples to examine the changes in social odor recognition in a mouse model of neurodegeneration.

Placebo and nocebo effects of percutaneous needle electrolysis and dry-needling: an intra and inter-treatment sessions analysis of a three-arm randomized double-blinded controlled trial in patients with patellar tendinopathy.

Objective: This study aimed to investigate the influence of potential placebo and nocebo effects on pain perception of percutaneous needle electrolysis (PNE) in individuals with patellar tendinopathy. Methods: In this secondary analysis of a three-arm randomized double-blinded controlled trial, intra and inter-session pain perception data from 48 sporting participants with patellar tendinopathy between 18 and 45 years were investigated. Participants were divided into 3 parallel groups: "no-sham group" [PNE intervention], "single-sham group" [sham PNE by using dry needling], and "double-sham group" [sham PNE by using sham needles]. Every group received 4 sessions of the needling therapies targeting the patellar tendon over 8 weeks and was instructed to perform a unilateral eccentric exercise program of the quadriceps muscle on the affected side. Clinical and needle-related pain was assessed before, during, and after each treatment session using a visual analog scale. Results: No differences were found between groups intra- or inter-session in terms of pain reduction (P = 0.424) despite clinical pain decreased in all groups since the first treatment session (P < 0.001). Furthermore, although the double-sham group showed a lower percentage of participants reporting needle-related pain during needle intervention (P = 0.005), the needle-related pain intensity after needle intervention was similar between groups (P = 0.682). Moreover, there were no group differences for the duration of pain sensation after any needle intervention (P = 0.184), extending in many cases beyond 24 h. Conclusion: Needling therapies for individuals with patellar tendinopathy are prone to elicit placebo effects regarding clinical pain and nocebo effects regarding needling-related pain. Clinicians and physical therapists treating musculoskeletal pain conditions should consider the added value and potential mechanisms of action before routinely using needle techniques.

Physical Therapist Interventions Versus or Combined With Surgical Treatment in Nontraumatic Degenerative Meniscal Pathology: A Systematic Review and Network Meta-Analysis.

OBJECTIVE: This study aimed to synthesize the evidence from randomized clinical trials in people with nontraumatic degenerative meniscal pathology by comparing physical therapist interventions versus or combined with arthroscopic partial meniscectomy (APM). METHODS: Seven electronic databases were searched. Methodological quality was evaluated using the Physiotherapy Evidence Database scale. Data synthesis was performed with random-effects network meta-analysis, and results were summarized using the standardized mean differences. RESULTS: From 2103 studies, 10 randomized clinical trials comprising 1411 individuals were included. Ninety percent of the selected randomized clinical trials were classified as good quality according to the Physiotherapy Evidence Database scale. All interventions (physical therapist interventions, APM, and APM plus physical therapist interventions) showed reduced pain and physical impairments at 3-month follow-up. However, when a physical therapist intervention was included, greater reductions in pain at rest (APM vs physical therapist interventions: 0.73 [95% CI = 0.20 to 1.26]; APM vs APM plus physical therapist interventions: 0.59 [95% CI = 0.15 to 1.03]) and greater increases in the strength of knee extensor muscles (APM vs physical therapist interventions: 0.44 [95% CI = 0.07 to 0.80]; APM vs APM plus physical therapist interventions: 0.73 [95% CI = 0.29 to 1.16]) were observed at 3 months. By contrast, no differences were found between treatments beyond 3 months. CONCLUSION: Physical therapist interventions based on exercise programs demonstrate superior short-term outcomes in pain reduction and knee extensor strength compared to surgical treatment. IMPACT: For nontraumatic degenerative meniscal pathology, conservative treatment utilizing a physical therapist intervention approach should be prioritized as the first choice over surgical treatment. It offers comparable or superior short-term pain reduction and strength improvements, with a lower risk of side effects. In cases where surgery is deemed necessary, including postsurgical, physical therapist interventions are highly recommended to enhance muscle strength and alleviate pain.

The relationship between levels of physical activity and participation in everyday life in stroke survivors: A systematic review and meta-analysis.

BACKGROUND: Stroke survivors demonstrate decreased physical activity (PA) and take time to return to participation in everyday life, but the relationship between the two variables is unknown. OBJECTIVE: To investigate the correlation and trajectory over time between levels of PA and participation in everyday life in stroke survivors. METHODS: PubMed, Web of Science, Scopus, SPORTDiscus, Rehabilitation&Sport Medicine Source, and PEDro databases were searched from inception to January 2024. Cross-sectional and prospective studies evaluating both levels of PA and participation in stroke survivors were included. Two reviewers independently conducted the study selection, data extraction, and quality assessment. Meta-analyses of pooled correlation coefficients were calculated when at least two studies reported a correlation coefficient between the same PA and participation outcomes. RESULTS: Of 4962 studies identified, 49 were included in the systematic review. Studies were rated high (55%%) or fair (45%) quality. A wide range of monitoring methodologies for assessing PA and participation were found in the 23 prospective studies. Seven studies were included in the meta-analyses, showing a positive moderate correlation between PA time and participation in activities of daily living (n = 148; r = 0.52; P < 0.01; I2 = 81%) in participants <6 months post-stroke, and between PA time and the participation in all areas (n = 126; r = 0.44; P < 0.01; I2 = 0%) in participants ≥6 months post-stroke. Overall, while PA showed significant improvements over time, participation only showed a tendency. CONCLUSIONS: Despite the heterogeneity, consistent positive associations were found between PA time and participation levels in some areas. Establishing consensus is crucial to reduce heterogeneity and facilitate data pooling.

The balance between receptor recycling and trafficking toward lysosomes determines synaptic strength during long-term depression.

The strength of excitatory synaptic transmission depends partly on the number of AMPA receptors (AMPARs) at the postsynaptic surface and, thus, can be modulated by membrane trafficking events. These processes are critical for some forms of synaptic plasticity, such as long-term potentiation and long-term depression (LTD). In the case of LTD, AMPARs are internalized and dephosphorylated in response to NMDA receptor activation. However, the fate of the internalized receptors upon LTD induction and its relevance for synaptic function is still a matter of debate. Here we examined the functional contribution of receptor recycling versus degradation for LTD in rat hippocampal slices, and their correlation with receptor dephosphorylation. We observed that GluA1 undergoes sequential dephosphorylation and degradation in lysosomes after LTD induction. However, this degradation does not have functional consequences for the regulation of synaptic strength, and therefore, for the expression of LTD. In contrast, the partition of internalized AMPARs between Rab7-dependent trafficking (toward lysosomes) or Rab11-dependent endosomes (recycling back toward synapses) is the key factor determining the extent of synaptic depression upon LTD induction. This sorting decision is related to the phosphorylation status of GluA1 Ser845, the dephosphorylated receptors being those preferentially targeted for lysosomal degradation. Altogether, these new data contribute to clarify the fate of AMPARs during LTD and emphasize the importance of membrane sorting decisions to determine the outcome of synaptic plasticity.

Multidimensional analysis of sedentary behaviour and participation in Spanish stroke survivors (Part&Sed-Stroke): a protocol for a longitudinal multicentre study.

INTRODUCTION: Stroke survivors usually experience long-lasting functional, emotional and social consequences that might contribute to sedentary behaviour and participation restrictions, which are important targets to address during rehabilitation. However, the trajectory and inter-relationship between these factors are unknown. METHODS AND ANALYSIS: Part&Sed is a research project based on an observational study design with 6 and 12 months of follow-ups in stroke survivors. In addition, a qualitative analysis of the impact of the stroke on the stroke survivor, validation of the Satisfaction with Daily Occupation-Occupational Balance assessment tool and analysis of the reliability of the Fitbit Inspire 2 activity tracker wristband will be carried out. Participants will be chronic stroke survivors with independent walking capacity. Sociodemographic and clinical data, physical activity, ambulation, sleep, quality of life, anxiety and depression, community participation, and occupational satisfaction and balance, as well as data provided by the activity tracker wristband, will be collected. In addition, if the participant has a primary caregiver, the caregiver will also be monitored. A minimum of 130 participants will be recruited to conduct a random-effects multiple regression model. Mixed models for repeated measures will assess the variation over time of the different variables associated with participation and sedentary behaviour. Psychometric properties (eg, internal consistency, construct validity, test-retest reliability) of the Satisfaction with Daily Occupation-Occupational Balance will be determined. Additionally, intraclass correlation coefficients and minimum detectable change will be calculated to assess intrasubject reliability of physical activity and sleep parameters recorded by the Fitbit Inspire 2. The qualitative analysis process will be carried out using the analysis proposed by Giorgi. ETHICS AND DISSEMINATION: The study received ethical approval from the Spanish Regional Ethics Committee 'Comité de Ética de la Investigación de la Comunidad de Aragón' (PI21/333). The results will be made available via peer-reviewed publications, international conferences and official channels.

Relationship between Participation in Daily Life Activities and Physical Activity in Stroke Survivors: A Protocol for a Systematic Review and Meta-Analysis.

Stroke survivors undertake low levels of physical activity and participation in daily life activities, but the correlation between these two domains still carries some degree of uncertainty. This systematic review and meta-analyses-based data synthesis will aim to describe and estimate the relationship between participation in daily life activities and physical activity in stroke survivors. Six databases (MEDLINE/PubMed, Web of Science, Scopus, PEDro, SPORTDiscus, and Rehabilitation & Sport Medicine Source) will be searched. Studies assessing participation alongside physical activity levels in adult stroke survivors in English or Spanish will be included. The study selection, assessment of the risk of bias, and data extraction will be conducted independently by two investigators. If available, correlation values between physical activity and participation outcomes will be extracted. The Hedges-Olkin method will be used for pooling correlation values between participation and physical activity measures. Subgroup analyses will be performed according to the time elapsed since the stroke (i.e., ≤6 months and >6 months). This will be the first systematic review with a meta-analysis to provide information on the relationship between physical activity and participation in stroke survivors. Findings are likely to inform the design of health prevention protocols and the development of healthy behavior change interventions.

[Impact of the smoke-free legislation on the prevalence and referred time exposure to the environmental tobacco smoke in Zaragoza]. / Impacto de la regulación de espacios sin humo en la exposición referida al humo ambiental de tabaco en Zaragoza.

OBJECTIVES: To assess the impact of the Law 42/2010, on the health measures on smoking, on the prevalence of the exposure to environmental tobacco smoke (ETS), the repercussions in frequently visited places, and support of the new legislation. DESIGN: A before-after evaluation by comparing two cross-sectional studies the comparison of two transverse surveys. PLACE: Primary Care, Delicias district (115,446 inhabitants) of Zaragoza city, including the Delicias Sur, Delicias Norte, Bombarda and Univérsitas basic health districts. PARTICIPANTS: A total of 387 users in 2009, and 400 in 2011 with ages between 20 and 79 years old assigned to the participating Primary Care Centres. MAIN MEASUREMENTS: Prevalences and mean exposure times, with their confidence intervals (CI). The differences were then calculated using the Chi-squared test and Analysis of Variance (ANOVA). RESULTS: The exposure prevalence to the ETS in 2011 was shown to be lower and statistically significant than that found before the implementation of the new legislative measure, falling from the 61.9% to the 40.5% (CI 95%=35.8-45.4%), with 61.5% of those polled being in favour of the new law (CI 95%=59.2-68.75), and 80.5% (79,08-86.44) mentioned still going to the same places with the same frequency. CONCLUSIONS: The impact has been favourable, decreasing the exposure by more than 20%, with this fall being more marked in the population that currently define themselves as non-smokers. There is population support for the new legislation. Finally, there has been no observed fall in the frequency of visits to the same places.

AMPA Receptor Function in Hypothalamic Synapses.

AMPA receptors (AMPARs) are critical for mediating glutamatergic synaptic transmission and plasticity, thus playing a major role in the molecular machinery underlying cellular substrates of memory and learning. Their expression pattern, transport and regulatory mechanisms have been extensively studied in the hippocampus, but their functional properties in other brain regions remain poorly understood. Interestingly, electrophysiological and molecular evidence has confirmed a prominent role of AMPARs in the regulation of hypothalamic function. This review summarizes the existing evidence on AMPAR-mediated transmission in the hypothalamus, where they are believed to orchestrate the role of glutamatergic transmission in autonomous, neuroendocrine function, body homeostasis, and social behavior.

A comparative study of treatment interventions for patellar tendinopathy: a secondary cost-effectiveness analysis.

OBJECTIVE: To compare the cost-effectiveness of three patellar tendinopathy treatments. DESIGN: Secondary (cost-effectiveness) analysis of a blinded, randomised controlled trial, with follow-up at 10 and 22 weeks. SETTINGS: Recruitment was performed in sport clubs. The diagnosis and the intervention were carried out at San Jorge University. PARTICIPANTS: The participants were adults between 18 and 45 years (n = 48) with patellar tendinopathy. INTERVENTIONS: Participants received percutaneous needle electrolysis, dry needling or sham needling, all of which were combined with eccentric exercise. MAIN OUTCOME MEASURES: Costs, quality-adjusted life years and incremental cost-effectiveness ratio were calculated for each group. RESULTS: The total cost per session was similar in the three groups: €9.46 for the percutaneous needle electrolysis group; €9.44 for the dry needling group; and €8.96 for the sham group. The percutaneous needle electrolysis group presented better cost-effectiveness in terms of quality-adjusted life years and 96% and 93% probability of being cost-effective compared to the sham and dry needling groups, respectively. CONCLUSION: Our study shows that percutaneous needle electrolysis has a greater probability of being cost-effective than sham or dry needling treatment.

The diversity of effects of yeast derivatives during sparkling wine aging.

This study shows the monitoring of the physical, chemical and sensorial changes that occur in the sparkling wine along 18 months of aging due to different typology yeast-derived products; dry inactivated yeast from Saccharomyces (Saccharomyces cerevisiae) and non-Saccharomyces (Torulaspora delbrueckii) yeast strains, yeast autolysate, and yeast protein extract tested at two different doses. The addition of 5 g/hL yeast protein extract and inactivated yeast from T. delbrueckii helped to preserve esters in wines with 9 and 18 months of aging on lees. The addition of yeast autolysate achieved greater polysaccharide enrichment and gave rise to sparkling wines with the highest antioxidant activity. Effects on foaming properties were quite different depending on the aging time. Despite this, sparkling wines treated with 10 g/hL of yeast autolysate and Optimum White™ generally exhibited the highest foamability and foam stability. Further experiments with higher doses are needed to observe clear effects on sensory profile.

Peripartum anesthetic management of women with SARS-CoV-2 infection in eight medical centers across three European countries: prospective cohort observation study.

OBJECTIVE: Several reports of obstetric anesthesia management have been published since the onset of the COVID-19 pandemic. We aimed to collect high-quality broad and detailed data from different university medical centers in several European Society of Anesthesiologist countries. METHODS: This prospective observational survey was performed in eight medical centers in Spain, Israel and Portugal from 1st April to 31st July 2020. Institutional review board approval was received at each participating center. Inclusion criteria: all women with a positive test for COVID-19. Retrieved data included maternal, delivery, anesthetic, postpartum details, and neonatal outcomes. Descriptive data are presented, and outcomes were compared for women with versus without respiratory signs and symptoms. RESULTS: Women with respiratory symptoms (20/12.1%) had significantly higher mean (standard deviation) temperature (37.2 °C (0.8) versus 36.8 °C (0.6)), were older (34.1 (6.7) years versus 30.5 (6.6)) and had higher body mass index kg m-2 - (29.5 (7.5) versus 28.2 (5.1)). Women with respiratory symptoms delivered at a significantly earlier gestational age (50% < 37 weeks) with a 65% cesarean delivery rate (versus 22.1% in the group without respiratory symptoms) and 5-fold increased rate of emergency cesarean delivery, 30% performed under general anesthesia. A higher rate of intrauterine fetal death (3%) was observed than expected from the literature (0.2-0.3%) in developed countries. There was no evidence of viral vertical transmission. CONCLUSION: Well-functioning neuraxial analgesia should be available to manage laboring women with respiratory symptoms, as there is a higher frequency of emergency cesarean delivery. We report a higher rate of undiagnosed parturient and intrauterine fetal death.