Circulating long noncoding RNA PDE4DIPP6: A novel biomarker for improving the clinical management of non-ST-segment elevation myocardial infarction.

BACKGROUND: Long noncoding RNAs (lncRNAs) have emerged as promising diagnostic biomarkers. Here, we investigated the cardiac-expressed and plasma-detectable lncRNA PDE4DIPP6 as a biomarker for non-ST-segment elevation myocardial infarction (NSTEMI), specifically assessing its potential to enhance the diagnostic efficacy of high-sensitivity cardiac troponin (hs-cTnT). METHODS AND RESULTS: The study enrolled individuals presenting with suspected acute coronary syndrome (ACS). LncRNA quantification was performed in plasma samples using RT-qPCR. The discriminatory performance was assessed by calculating the Area Under the Curve (AUC). Reclassification metrics, including the Integrated Discrimination Improvement (IDI) and Net Reclassification Improvement (NRI) indexes, were utilized to evaluate enhancements in diagnostic accuracy. Among the 252 patients with suspected ACS, 50.8 % were diagnosed with ACS, and 13.9 % with NSTEMI. Initially, the association of lncRNA PDE4DIPP6 with ACS was investigated. Elevated levels of this lncRNA were observed in ACS patients compared to non-ACS subjects. No association was found between lncRNA PDE4DIPP6 levels and potential confounding factors, nor was a significant correlation with hs-cTnT levels (rho = 0.071). The inclusion of lncRNA PDE4DIPP6 on top of hs-cTnT significantly improved the discrimination and classification of ACS patients, as reflected by an enhanced AUC of 0.734, an IDI of 0.066 and NRI of 0.471. Subsequently, the lncRNA PDE4DIPP6 was evaluated as biomarker of NSTEMI. Elevated levels of the lncRNA were observed in NSTEMI patients compared to patients without NSTEMI. Consistent with previous findings, the addition of lncRNA PDE4DIPP6 to hs-cTnT improved the discrimination and classification of patients, increasing the AUC from 0.859 to 0.944, with an IDI of 0.237 and NRI of 0.658. CONCLUSION: LncRNA PDE4DIPP6 offers additional diagnostic insights beyond hs-cTnT, suggesting its potential to improve the clinical management of patients with NSTEMI.

Prospective Follow-Up of Adolescents With and at Risk for Depression: Protocol and Methods of the Identifying Depression Early in Adolescence Risk Stratified Cohort Longitudinal Assessments.

Objective: To present the protocol and methods for the prospective longitudinal assessments-including clinical and digital phenotyping approaches-of the Identifying Depression Early in Adolescence Risk Stratified Cohort (IDEA-RiSCo) study, which comprises Brazilian adolescents stratified at baseline by risk of developing depression or presence of depression. Method: Of 7,720 screened adolescents aged 14 to 16 years, we recruited 150 participants (75 boys, 75 girls) based on a composite risk score: 50 with low risk for developing depression (LR), 50 with high risk for developing depression (HR), and 50 with an active untreated major depressive episode (MDD). Three annual follow-up assessments were conducted, involving clinical measures (parent- and adolescent-reported questionnaires and psychiatrist assessments), active and passive data sensing via smartphones, and neurobiological measures (neuroimaging and biological material samples). Retention rates were 96% (Wave 1), 94% (Wave 2), and 88% (Wave 3), with no significant differences by sex or group (p > .05). Participants highlighted their familiarity with the research team and assessment process as a motivator for sustained engagement. Discussion: This protocol relied on novel aspects, such as the use of a WhatsApp bot, which is particularly pertinent for low- to-middle-income countries, and the collection of information from diverse sources in a longitudinal design, encompassing clinical data, self-reports, parental reports, Global Positioning System (GPS) data, and ecological momentary assessments. The study engaged adolescents over an extensive period and demonstrated the feasibility of conducting a prospective follow-up study with a risk-enriched cohort of adolescents in a middle-income country, integrating mobile technology with traditional methodologies to enhance longitudinal data collection.

This article details the study protocol and methods used in the longitudinal assessment of 150 Brazilian teenagers with depression and at risk for depression as part of the Identifying Depression Early in Adolescence Risk Stratified Cohort (IDEA-RiSCo). Over 3 years, the authors collected clinical and digital data using innovative mobile technology, including a WhatsApp bot. Most adolescents participated in all the study phases, showing feasibility of prospective follow-up in a middle-income country. This approach allowed for a deeper understanding of depression in young populations, particularly in areas where mental health research is scarce.

Whole genome sequencing identifies elusive variants in genetically unsolved Italian inherited retinal disease patients.

Inherited retinal diseases (IRDs) are a group of rare monogenic diseases with high genetic heterogeneity (pathogenic variants identified in over 280 causative genes). The genetic diagnostic rate for IRDs is around 60%, mainly thanks to the routine application of next-generation sequencing (NGS) approaches such as extensive gene panels or whole exome analyses. Whole-genome sequencing (WGS) has been reported to improve this diagnostic rate by revealing elusive variants, such as structural variants (SVs) and deep intronic variants (DIVs). We performed WGS on 33 unsolved cases with suspected autosomal recessive IRD, aiming to identify causative genetic variants in non-coding regions or to detect SVs that were unexplored in the initial screening. Most of the selected cases (30 of 33, 90.9%) carried monoallelic pathogenic variants in genes associated with their clinical presentation, hence we first analyzed the non-coding regions of these candidate genes. Whenever additional pathogenic variants were not identified with this approach, we extended the search for SVs and DIVs to all IRD-associated genes. Overall, we identified the missing causative variants in 11 patients (11 of 33, 33.3%). These included three DIVs in ABCA4, CEP290 and RPGRIP1; one non-canonical splice site (NCSS) variant in PROM1 and three SVs (large deletions) in EYS, PCDH15 and USH2A. For the previously unreported DIV in CEP290 and for the NCCS variant in PROM1, we confirmed the effect on splicing by reverse transcription (RT)-PCR on patient-derived RNA. This study demonstrates the power and clinical utility of WGS as an all-in-one test to identify disease-causing variants missed by standard NGS diagnostic methodologies.

Next-generation sequencing to genetically diagnose a diverse range of inherited eye disorders in 15 consanguineous families from Pakistan.

Inherited retinal dystrophies (IRDs) are characterized by photoreceptor dysfunction or degeneration. Clinical and phenotypic overlap between IRDs makes the genetic diagnosis very challenging and comprehensive genomic approaches for accurate diagnosis are frequently required. While there are previous studies on IRDs in Pakistan, causative genes and variants are still unknown for a significant portion of patients. Therefore, there is a need to expand the knowledge of the genetic spectrum of IRDs in Pakistan. Here, we recruited 52 affected and 53 normal individuals from 15 consanguineous Pakistani families presenting non-syndromic and syndromic forms of IRDs. We employed single molecule Molecular Inversion Probes (smMIPs) based panel sequencing and whole genome sequencing to identify the probable disease-causing variants in these families. Using this approach, we obtained a 93% genetic solve rate and identified 16 (likely) causative variants in 14 families, of which seven novel variants were identified in ATOH7, COL18A1, MERTK, NDP, PROM1, PRPF8 and USH2A while nine recurrent variants were identified in CNGA3, CNGB1, HGSNAT, NMNAT1, SIX6 and TULP1. The novel MERTK variant and one recurrent TULP1 variant explained the intra-familial locus heterogeneity in one of the screened families while two recurrent CNGA3 variants explained compound heterozygosity in another family. The identification of variants in known disease-associated genes emphasizes the utilization of time and cost-effective screening approaches for rapid diagnosis. The timely genetic diagnosis will not only identify any associated systemic issues in case of syndromic IRDs, but will also aid in the acceleration of personalized medicine for patients affected with IRDs.

Psychometric Properties of the Spanish Version of the Parental Feeding Style Questionnaire.

BACKGROUND: There are no validated instruments in Spain for measuring parental feeding styles. The aim was to validate the Parental Feeding Styles Questionnaires (PFSQ) in a Spanish sample. METHOD: A total of 523 mothers of 523 school-children participated. The children had a mean age of 4.4 years (SD = 1.3), with 51% being boys (M = 4.3 years, SD = 1.4) and 49% girls (M = 4.5 years, = SD 1.3). The PFSQ and the Comprehensive General Parenting Styles Questionnaire (CGPQ) were used. RESULTS: A model of four correlated factors was identified: Prompting/encouraging eating, emotional feeding, instrumental feeding, and control over eating. Cronbach's alpha for the subscales ranged from 0.64 to 0.86, and McDonald's Omega coefficient ranged from 0.66 to 0.86. Emotional feeding and prompting/encouraging eating had values above 0.70, control over eating had a value of 0.68 and instrumental feeding had an alpha coefficient of 0.64 and omega coefficient of 0.66. The factor structure was similar to the original and to other adapted versions. The Spanish sample used more control over eating and prompting/encouraging to eat. CONCLUSIONS: The adapted PFSQ is a suitable instrument for assessing the feeding styles of Spanish parents.

An Undergraduate Course in CRISPR/Cas9-Mediated Gene Editing in Zebrafish.

We have developed a one-credit semester-long research experience for undergraduate students that involves the use of CRISPR/Cas9 to edit genes in zebrafish. The course is available to students at all stages of their undergraduate training and can be taken up to four times. Students select a gene of interest to edit as the basis of their semester-long project. To select a gene, exploration of developmental processes and human disease is encouraged. As part of the course, students use basic bioinformatic tools, design guide RNAs, inject zebrafish embryos, and analyze both the molecular consequences of gene editing and phenotypic outcomes. Over the 10 years we have offered the course, enrollment has grown from less than 10 students to more than 60 students per semester. Each year, we choose a different gene editing strategy to explore based on recent publications of gene editing methodologies. These have included making CRISPants, targeted integrations, and large gene deletions. In this study, we present how we structure the course and our assessment of the course over the past 3 years.

Assessing the Psychometric Properties of the Illness Management and Recovery Scale: A Systematic Review Using the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN).

The Illness Management and Recovery Scale (IMR-S) is based on the IMR program, developed to assess the recovery process for people with severe mental disorders by considering the perceptions of clients and clinicians involved in it. The aim of this study was to analyze the psychometric properties of the IMR-S so as to determine the reliability and suitability of its scores for evaluating recovery. Two coders searched five databases for studies, published between January 2004 and May 2023, that describe the psychometric assessment of the IMR-S. Studies were assessed using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) Risk of Bias checklist. Finally, 46 papers were included. Methodological quality was very good for most of the studies that provide information on internal validity, and limited for those that report on responsiveness. Measurement properties were positive for convergent validity and measurement error. The quality of evidence was high for structural validity studies. Although this study only includes research published in English and may have overlooked certain psychometric properties evaluated in studies published in other languages, our findings suggest that the IMR-S is a valid and reliable instrument, demonstrating its potential to offer guidance for clinical practice.

Addressing the unsolved challenges in microRNA-based biomarker development: Suitable endogenous reference microRNAs for SARS-CoV-2 infection severity.

Circulating cell-free microRNAs (miRNAs) are promising biomarkers for medical decision-making. Suitable endogenous controls are essential to ensure reproducibility. We aimed to identify and validate endogenous reference miRNAs for qPCR data normalization in samples from SARS-CoV-2-infected hospitalized patients. We used plasma samples (n = 170) from COVID-19 patients collected at hospital admission (COVID-Ponent project, www.clinicaltrials.gov/NCT04824677). First, 179 miRNAs were profiled using RT-qPCR. After stability assessment, candidates were validated using the same methodology. miRNA stability was analyzed using the geNorm, NormFinder and BestKeeper algorithms. Stability was further evaluated using an RNA-seq dataset derived from COVID-19 hospitalized patients, along with plasma samples from patients with critical COVID-19 profiled using RT-qPCR. In the screening phase, after strict control of expression levels, stability assessment selected eleven candidates (miR-17-5p, miR-20a-5p, miR-30e-5p, miR-106a-5p, miR-151a-5p, miR-185-5p, miR-191-5p, miR-423-3p, miR-425-5p, miR-484 and miR-625-5p). In the validation phase, all algorithms identified miR-106a-5p and miR-484 as top endogenous controls. No association was observed between these miRNAs and clinical or sociodemographic characteristics. Both miRNAs were stably detected and showed low variability in the additional analyses. In conclusion, a 2-miRNA panel composed of miR-106a-5p and miR-484 constitutes a first-line normalizer for miRNA-based biomarker development using qPCR in hospitalized patients infected with SARS-CoV-2.

Greater within- and between-day instability is associated with worse anxiety and depression symptoms.

BACKGROUND: Depression and anxiety affect hundreds of millions of people worldwide, and their prevalence increased during the COVID-19 pandemic as social schedules were disrupted. This study explores the associations between anxiety and depression and within- and between-day instability of affective, somatic, and cognitive symptoms during the early pandemic stages. METHODS: Participants (n = 153, ages 18-77, 72 % female) reported daily levels of affective (anxiety/sadness), somatic (appetite/sleepiness), and cognitive (concentration/energy) symptoms for 14-44 days at five timepoints: 0, 3, 6, 9, and 12 h after awakening. At the end of the study, participants completed validated scales for anxiety (GAD-7) and depression (PHQ-9). Symptom instability was assessed using the Absolute Real Variability (ARV) index. Regression models examined within-day instability (WD-I) and between-day instability (BD-I) with GAD-7 and PHQ-9 scores as outcomes. RESULTS: Greater instability (both WD-I and BD-I) of affective symptoms correlated with elevated GAD-7 and PHQ-9 scores. For somatic and cognitive symptoms, greater BD-I was associated with higher scores. LIMITATIONS: The study used retrospective daily data, which could benefit from real-time assessments for improved accuracy. CONCLUSIONS: This study provides empirical evidence of a connection between greater anxiety and depression severity and increased instability in daily mood and physiological symptoms. The findings underscore the importance of consistent symptom monitoring to understand overall mental health trajectories. Additionally, it highlights the role of daily routines in stabilizing the circadian system, potentially regulating physiological and psychological processes and reducing symptom instability.

[Barriers and facilitators in accessing and using primary health care centers for people experiencing homelessness]. / Barreras y facilitadores en el acceso y la utilización de los centros de atención primaria para las personas en situación de sinhogarismo.

OBJECTIVE: To identify barriers and facilitators for the access and use of primary care centers for people experiencing homelessness. DESIGN: Qualitative study, phenomenological theoretical-methodological approach. Between May 19 and July 27, 2023. LOCATION: Besòs Primary Health Care Center and Gregal social dining (Besòs and Maresme neighborhood, Barcelona). PARTICIPANTS: People experiencing homelessness attending the Gregal social dining and professionals from the Besòs Primary Health Care Center. METHOD: Theoretical purposive sampling. Individual and group interviews and open non-participant observation. Thematic content analysis, triangulation by independent analysis of three members of the research team and triangulation of methods. Discourse saturation was achieved through variability of discourse and techniques. RESULTS: Eleven individual interviews, three group interviews and two observations. Different barriers and facilitators were identified. These were classified into five categories: (1)concept and identification of people experiencing homelessness; (2)personal factors of people experiencing homelessness; (3)behaviors and attitudes of professionals; (4)structural factors related to health system regulation, anf (5)internal organizational factors of primary health care centers. CONCLUSIONS: People experiencing homelessness face multiple barriers to access primary health care, although there are also facilitators such as trusting relationships and multidisciplinary and intersectoral work that can be enhanced from primary health care centers to contribute to health equity.

Andrographolide Ameliorates Inflammatory Changes Induced by D-Lactate in Bovine Fibroblast-like Synoviocytes.

During acute ruminal acidosis, the manifestation of aseptic polysynovitis and lameness in cattle has been observed. Evidence suggests that joint inflammation can be attributed to the metabolic alterations induced by D-lactate in fibroblast-like synoviocytes (FLSs). We aimed to investigate whether andrographolide could mitigate the inflammation and metabolic alterations induced by D-lactate in bovine fibroblast-like synoviocytes (bFLSs). To assess this, bFLSs were cultured in the presence or absence of andrographolide. We evaluated its potential interference with the expression of proinflammatory cytokines, COX-2, HIF-1α, and LDHA using RT-qPCR. Furthermore, we investigated its potential interference with PI3K/Akt signaling and IκBα degradation through immunoblotting and flow cytometry, respectively. Our observations revealed that andrographolide reduced the elevation of IL-6, IL-8, COX-2, HIF-1α, and LDHA induced by D-lactate. Additionally, andrographolide demonstrated interference with the PI3K/Akt and NF-κB pathways in bFLSs. In conclusion, our findings suggest that andrographolide can potentially reverse the inflammatory effects and metabolic changes induced by D-lactate in bFLSs, showing promise as a therapeutic intervention for managing these conditions associated with lameness.

MicroRNA-centered theranostics for pulmoprotection in critical COVID-19.

Elucidating the pathobiological mechanisms underlying post-acute pulmonary sequelae following SARS-CoV-2 infection is essential for early interventions and patient stratification. Here, we investigated the potential of microRNAs (miRNAs) as theranostic agents for pulmoprotection in critical illness survivors. Multicenter study including 172 ICU survivors. Diffusion impairment was defined as a lung-diffusing capacity for carbon monoxide (DLCO) <80% within 12 months postdischarge. A disease-associated 16-miRNA panel was quantified in plasma samples collected at ICU admission. Bioinformatic analyses were conducted using KEGG, Reactome, GTEx, and Drug-Gene Interaction databases. The results were validated using an external RNA-seq dataset. A 3-miRNA signature linked to diffusion impairment (miR-27a-3p, miR-93-5p, and miR-199a-5p) was identified using random forest. Levels of miR-93-5p and miR-199a-5p were independently associated with the outcome, improving patient classification provided by the electronic health record. The experimentally validated targets of these miRNAs exhibited enrichment across diverse pathways, with telomere length quantification in an additional set of samples (n = 83) supporting the role of cell senescence in sequelae. Analysis of an external dataset refined the pathobiological fingerprint of pulmonary sequelae. Gene-drug interaction analysis revealed four FDA-approved drugs. Overall, this study advances our understanding of lung recovery in postacute respiratory infections, highlighting the potential of miRNAs and their targets for pulmoprotection.

Routine regularity during a global pandemic: Impact on mental health outcomes and influence of chronotype.

Among the public health recommendations for supporting mental health during the COVID-19 pandemic, many strategies had an impact on biological rhythms, like sleep hygiene, physical exercise and healthy eating habits. Considering the known relationship between circadian organization and mental health, our aim was to test the association between behavioral regularity and mental health, and its interaction with chronotype, in a large sample surveyed in Brazil. We collected longitudinal data using online questionnaires that assessed sociodemographic characteristics, behavioral routines, mental health (PHQ-9, GAD-7, WHO-5 scales), and chronotype estimation based on midpoint of sleep on free days - MSF (µMCTQ), in a sample of 1390 participants (81% females). We computed a Routine Regularity Score (RRS) that reflects regularity across four behaviors: sleep, eating, working, exercising. There was a strong negative association between RRS and the severity of anxiety and depressive symptoms (GAD-7 and PHQ-9 scores), which was weaker among participants with late MSF, and a strong positive association with well-being (WHO-5 scores). RRS was a mediator of the MSF-mental health association and a predictor of mental health states. This study provides empirical evidence that maintaining behavioral routines during times of hardship may serve as tools to alleviate the negative impact on mental health.

MicroRNA-guided drug discovery for mitigating persistent pulmonary complications in critical COVID-19 survivors: A longitudinal pilot study.

BACKGROUND AND PURPOSE: The post-acute sequelae of SARS-CoV-2 infection pose a significant global challenge, with nearly 50% of critical COVID-19 survivors manifesting persistent lung abnormalities. The lack of understanding about the molecular mechanisms and effective treatments hampers their management. Here, we employed microRNA (miRNA) profiling to decipher the systemic molecular underpinnings of the persistent pulmonary complications. EXPERIMENTAL APPROACH: We conducted a longitudinal investigation including 119 critical COVID-19 survivors. A comprehensive pulmonary evaluation was performed in the short-term (median = 94.0 days after hospital discharge) and long-term (median = 358 days after hospital discharge). Plasma miRNAs were quantified at the short-term evaluation using the gold-standard technique, RT-qPCR. The analyses combined machine learning feature selection techniques with bioinformatic investigations. Two additional datasets were incorporated for validation. KEY RESULTS: In the short-term, 84% of the survivors exhibited impaired lung diffusion (DLCO  < 80% of predicted). One year post-discharge, 54.4% of this patient subgroup still presented abnormal DLCO . Four feature selection methods identified two specific miRNAs, miR-9-5p and miR-486-5p, linked to persistent lung dysfunction. The downstream experimentally validated targetome included 1473 genes, with heterogeneous enriched pathways associated with inflammation, angiogenesis and cell senescence. Validation studies using RNA-sequencing and proteomic datasets emphasized the pivotal roles of cell migration and tissue repair in persistent lung dysfunction. The repositioning potential of the miRNA targets was limited. CONCLUSION AND IMPLICATIONS: Our study reveals early mechanistic pathways contributing to persistent lung dysfunction in critical COVID-19 survivors, offering a promising approach for the development of targeted disease-modifying agents.

La equidad en la campaña de vacunación COVID de la Provincia de Buenos Aires (Argentina): un análisis del Municipio de Quilmes.

INTRODUCCIÓN: la pandemia de la COVID-19 ha acentuado las desigualdades sociales, económicas y relacionadas con la salud, afectando desproporcionadamente a las personas en situación de vulnerabilidad y perpetuando la inequidad en salud. En Argentina se implementó una campaña nacional gratuita de vacunación contra la COVID-19 con una perspectiva de equidad. OBJETIVO: identificar desigualdades territoriales en el acceso a la vacunación contra la COVID-19 en Quilmes. MÉTODOS: se analizó la información referida a la vacunación contra la COVID-19 de personas residentes en el Municipio. Se efectuó la georreferenciación de cada vacunatorio y de cada persona a partir del domicilio declarado en el momento de la vacunación. Para caracterizar el grado de vulnerabilidad de las personas vacunadas, a cada una se le asignó el índice de carencias múltiples (ICM) correspondiente al radio censal de residencia. RESULTADOS: al menos el 82 % de la población completó el esquema primario de vacunación (dosis 1 y dosis 2), porcentaje que alcanzó el 97 % en los mayores de 65 años. Analizando la media de dosis aplicadas se observa algo similar con un gradiente hacia los quintiles más altos pero con una mínima diferencia entre sí, situación que también se corrobora en todos los grupos etarios. DISCUSIÓN: no se observaron brechas significativas entre los diferentes niveles socioeconómicos. Si bien se observó un mínimo gradiente en el promedio de dosis recibidas, el tiempo de acceso a las diferentes vacunas y el porcentaje de esquemas primarios completos recibidos, las mismas tienen escasa relevancia clínica y sanitaria.

Standard of care plus telmisartan on respiratory failure due to COVID-19 (STAR-COVID trial).

BACKGROUND: The potential influence of renin-angiotensin inhibitors on the severity of SARS-CoV-2 infection has been considered in preclinical and observational studies with contradictory results. Therefore, we investigated the effect of telmisartan in reducing lung injury among hospitalized COVID-19 patients. METHODS: The STAR-COVID trial was conducted as a prospective, parallel-group, randomized, open-label study involving hospitalized adult patients with severe COVID-19 (NCT04510662). Sixty-six patients were enrolled: 33 were assigned to the telmisartan group and 33 to the control group. The mean age of participants was 48.8 years, with 62.5% being male. Participants were randomly assigned in a 1:1 ratio to receive either telmisartan (40 mg daily for 14 days or until discharge) plus standard of care or standard of care alone. The primary outcome assessed was the initiation of mechanical ventilation within 14 days. Secondary outcomes included 30-day mortality, the need for vasopressors, hemodialysis requirements, and length of hospital stay. RESULTS: Comparison between the telmisartan group and the control group revealed no significant difference in the occurrence of mechanical ventilation at 14 days (25% with telmisartan vs. 18.7% with control, P=0.579). Additionally, there were no significant differences observed in terms of mortality (25% vs. 21.9%, P=0.768), the need for vasopressors (18.8% in both groups, P=1.000), hemodialysis requirements (6.3% vs. 3.1%, P=0.500), and length of hospital stay (median of 7 days in both groups, P=0.962). CONCLUSIONS: Compared with the standard of care, telmisartan therapy demonstrated no significant impact on respiratory failure in hospitalized patients with severe COVID-19.

Effects of a Primary Care Antimicrobial Stewardship Program on Meticillin-Resistant Staphylococcus aureus Strains across a Region of Catalunya (Spain) over 5 Years.

Primary care antimicrobial stewardship program (ASP) interventions can reduce the over-prescription of unnecessary antibiotics, but the impact on the reduction in bacterial resistance is less known, and there is a lack of available data. We implemented a prolonged educational counseling ASP in a large regional outpatient setting to assess its feasibility and effectiveness. Over a 5-year post-implementation period, which was compared to a pre-intervention period, a significant reduction in antibiotic prescriptions occurred, particularly those associated with greater harmful effects and resistance selection. There was also a decrease in methicillin-resistant Staphylococcus aureus (MRSA) strains and in their co-resistance to other antibiotics, particularly those with an ecological impact.

Assesment of Hypoderma infestation in a wild population of Cervus elaphus from mountains Atlantic ecosystems in southwestern Europe (Spain).

Hypodermosis in Cervus elaphus was studied in the Riaño Regional Hunting Reserve, Province of León, north-western Spain. One hundred and ten red deer were examined for the presence of warble fly larvae. They were analyzed by PCR analysis of the COI region of mt-DNA and identified as Hypoderma actaeon. The prevalence of larvae was 42.7% with a mean intensity of 12.5 ± 18 (range 1-80) warbles/deer infested. The distribution of larvae in the infested animals showed an aggregated/overdispersed pattern (aggregation index = 25.84), where the larvae are not randomly or uniformly distributed, but strongly aggregated among their hosts. Larvae were found in all three states. First and second-instars were observed mainly in the autumn until the end of winter (November-March) and third-instars in late winter until mid-spring (March-May). The adult animals and the males had a higher prevalence than the young and the females, finding statistically significant differences only according to the sex of the animals. Seasonal variations were observed in the prevalence with the highest number of infested animals in winter and autumn, but not in terms of the mean intensity of parasites. Additionally, we assessed the presence of anti-Hypoderma antibodies in serum by means of indirect ELISA tests, using a crude larval extract (CLE) and a purified fraction the hypodermin C (HyC) obtained from first instars of Spanish isolates of Hypoderma lineatum (cattle). These findings confirm that H. actaeon is widely distributed in northern Spain, and provide new information about its chronobiology in mountainous Atlantic ecosystems from southwestern Europe.

Use of Light Protection Equipment at Night Reduces Time Until Discharge From the Neonatal Intensive Care Unit: A Randomized Interventional Study.

Newborn infants' circadian systems are not completely developed and rely on external temporal cues for synchronizing their biological rhythms to the environment. In neonatal intensive care units (NICUs), lighting is usually continuous or irregular and infants are exposed to artificial light at night, which can have negative health consequences. Therefore, the aim of this study was to evaluate the impact of the use of individual light protection equipment at night on the development and growth of preterm neonates. Infants born at less than 37 gestational weeks who no longer needed constant intensive care were admitted into a newborn nursery and randomized to either use eye masks at night (intervention, n = 21) or not (control, n = 20). Infants who used eye protection at night were discharged earlier than those in the control group (8 [5] vs 12 [3.75] days; p < 0.05). A greater variation within the day in heart rate was observed in the intervention group, with lower values of beats per minute at 1400 and 2000 h. There was no significant difference in weight gain between groups. In view of our results and of previous findings present in the literature, we suggest that combining a darkened environment at night with individual light protection devices creates better conditions for the development of preterm infants in the NICU. In addition, eye masks are an affordable and simple-to-use tool that can reduce hospitalization costs by decreasing the number of days spent in the NICU.