Infective endocarditis caused by penicillin-resistant viridans group streptococci: a series of nine cases from a Spanish cohort.

BACKGROUND: Infective endocarditis (IE) caused by viridans and gallolyticus group streptococci (VGS-GGS) resistant to penicillin (PEN-R; minimum inhibitory concentration ≥4 mg/L) is rare but poses therapeutic challenges. OBJECTIVES: To describe the characteristics of patients with IE caused by PEN-R VGS-GGS, focusing on antimicrobial management. METHODS: Retrospective analysis of a prospective cohort of definite IE caused by PEN-R VGS-GGS between 2008 and 2023 in 40 Spanish hospitals. We describe clinical characteristics, management and outcome of the cases, and compare them to IE caused by VGS-GGS with susceptibility or susceptibility with increased exposure to penicillin (PEN-I). RESULTS: We identified nine cases of PEN-R VGS-GGS IE in a cohort of 1563 streptococcal IE (0.58%). All isolates belonged to S. mitis group. Three cases died during hospitalization and no relapse occurred at 3 months of follow-up. Compared to cases with susceptibility or PEN-I, PEN-R showed a higher rate of mitral location (78% versus 51%), surgical indication (67% versus 51%), and in-hospital mortality (33% versus 12%). Most cases (86%) showed resistance to third-generation cephalosporins. The preferred antibiotic regimen was beta-lactam-based: ceftriaxone plus gentamicin, penicillin plus gentamicin, ceftriaxone plus levofloxacin, and ceftaroline plus daptomycin. Two cases received a combination of vancomycin plus gentamicin. Levofloxacin was used in two cases in combination with ceftriaxone or daptomycin. All patients that received cardiac surgery were cured at the end of follow-up. CONCLUSIONS: IE caused by PEN-R VGS-GGS was rare and only affected mitis group streptococci. Antibiotic combination including a beta-lactam seems to be effective in its management.

Introduction of nirsevimab in Catalonia, Spain: description of the incidence of bronchiolitis and respiratory syncytial virus in the 2023/2024 season.

Respiratory syncytial virus (RSV) causes most of the cases of bronchiolitis and thousands of deaths annually, particularly in infants less than 6 months old. In Catalonia (Spain), infants born between April 2023 and March 2024 aged 0-6 months during their first RSV season have been candidates to receive nirsevimab, the novel monoclonal antibody against RSV, since October 2023. We aimed to analyse the dynamics of all-causes bronchiolitis diagnoses and RSV community infections in the current season and compare them to pre-nirsevimab epidemics. We collected epidemiological data from the Information System for Surveillance of Infections in Catalonia (SIVIC) on daily all-causes bronchiolitis clinical diagnoses and RSV-confirmed cases provided by rapid antigen tests in primary care practices. We calculated the rate ratio (RR) for the incidence of all-causes bronchiolitis for children aged 0-11 m-old with respect to 12-35 m-old between September 2014 and January 2024. We analysed the RR of the incidence of RSV-confirmed infection for 0-11 m-old and 12-35 m-old with respect to the > 35 m-old, from January 2021 to January 2024. We then computed the relative difference of the RR, designated as percentage of reduction of risk, between season 2023/2024 and former epidemics. With a global coverage recorded rate for nirsevimab of 82.2% in January 2024, the age-specific 0-11 m-old RR (95% CI) of RSV infection incidence for > 35 m-old was 1.7 (1.5-2.0) in season 2023/2024. The RR (95% CI) had been 7.4 (5.6-9.9), 8.8 (6.9-11.3), and 7.1 (5.7-8.9) in 2020/2021, 2021/2022, and 2022/2023, respectively. Regarding the incidence of all-causes bronchiolitis for the 0-11 m-old group compared to the 12-35 m-old, the pre-pandemic (2014/2015-2019/2020) and 2022/2023 RR (95% CI) were 9.4 (9.2-9.6) and 6.0 (5.7-6.2), respectively, significantly higher than the RR of 3.6 (3.4-3.8) for the most recent season, 2023/2024. Conclusion: Concurring with the introduction of nirsevimab, the risk of RSV infection for infants aged 0-11 m-old compared to > 35 m-old has been reduced by 75.6% (73.4-77.5) in last season, and the risk for all-causes bronchiolitis for 12-35 m-old by 61.9% (60.9-62.9) from the pre-pandemic period and by 39.8% (39.3-40.2) from the 2022/2023 epidemic, despite high RSV community transmission, especially in older infants What is Known: • RSV is responsible for approximately 70% of bronchiolitis cases and causes severe disease, particularly in infants < 6 months of age. • Nirsevimab effectiveness against RSV-associated disease, particularly hospitalisations, was expected to be around 80%; other Spanish regions, such as Galicia and Valencia, and European countries including Luxembourg and Germany, have already reported good results in implementing nirsevimab to prevent RSV-associated hospitalisations and PICU stays. What is New: • We provide insight into the community incidence of RSV and all-causes bronchiolitis for season 2023/2024, when nirsevimab has been introduced to the Catalan population, using.   primary healthcare data, which enabled us to assess the burden of RSV infections and bronchiolitis in the commonly seasonally saturated primary healthcare practices. • Our study reveals that the risk of all-causes bronchiolitis for infants aged 0-11 m-old compared to older infants was reduced by 40% compared to the previous season and 62% compared to pre-pandemic standards, and for RSV infection it was reduced by 76%.

Assessing the equity and coverage policy sensitivity of financial protection indicators in Europe.

Progress towards universal health coverage is monitored by the incidence of catastrophic spending. Two catastrophic spending indicators are commonly used in Europe: Sustainable Development Goal (SDG) indicator 3.8.2 and the WHO Regional Office for Europe (WHO/Europe) indicator. The use of different indicators can cause confusion, especially if they produce contradictory results and policy implications. We use harmonised household budget survey data from 27 European Union countries covering 505,217 households and estimate the risk of catastrophic spending, conditional on household characteristics and the design of medicines co-payments. We calculate the predicted probability of catastrophic spending for particular households, which we call LISAs, under combinations of medicines co-payment policies and compare predictions across the two indicators. Using the WHO/Europe indicator, any combination of two or more protective policies (i.e. low fixed co-payments instead of percentage co-payments, exemptions for low-income households and income-related caps on co-payments) is associated with a statistically significant lower risk of catastrophic spending. Using the SDG indicator, confidence intervals for every combination of protective policies overlap with those for no protective policies. Although out-of-pocket medicines spending is a strong predictor of catastrophic spending using both indicators, the WHO/Europe indicator is more sensitive to medicines co-payment policies than the SDG indicator, making it a better indicator to monitor health system equity and progress towards UHC in Europe.

Epidemiology of sarcoptic mange in free-ranging vicuñas (Vicugna vicugna): a cross-sectional study in Andean highland communities in Peru.

Sarcoptic mange or scabies is a contagious parasitic skin disease that affects a wide range of domestic and wildlife species. A cross-sectional study was carried out to determine the prevalence, molecular identification, and characteristics of sarcoptic mange in vicuñas. A total of 3,274 vicuñas were examined. Following ritual harvesting events ("chaccus") in 13 Andean communities. The presence of mange mites was determined by the skin scraping technique and confirmed by PCR analysis using specific primers for the ITS2 gene of Sarcoptes scabiei. The presence of mange mites was also confirmed by microscopy using samples taken from wallows. A data collection form was used to register the characteristics of the vicuñas sampled. The prevalence of sarcoptic mange was 4.9% (95% CI: 4.1 - 5.6%). All samples from wallows tested positive (9/9). Importantly, the presence of the species S. scabiei was molecularly confirmed. Adult females with regular body condition were more susceptible to sarcoptic mange, although the lesions were mild. This study confirms the presence of S. scabiei in semi-captive vicuñas and points to the possible role of wallows in the dissemination of Sarcoptes mites.

Effectiveness of nirsevimab immunoprophylaxis against respiratory syncytial virus-related outcomes in hospital and primary care settings: a retrospective cohort study in infants in Catalonia (Spain).

BACKGROUND: In Catalonia, infants under 6 months old were eligible to receive nirsevimab, a novel monoclonal antibody against respiratory syncytial virus (RSV). We aimed to analyse nirsevimab's effectiveness across primary and hospital care outcomes. METHODS: Retrospective cohort study from 1 October 2023 to 31 January 2024, including all infants born between April and September 2023. We established two cohorts based on nirsevimab administration (immunised and non-immunised). We followed individuals until the earliest moment of an outcome-RSV infection, primary care attended bronchiolitis and pneumonia, hospital emergency visits due to bronchiolitis, hospital admission or intensive care unit (ICU) admission due to RSV bronchiolitis-death or the end of the study. We used the Kaplan-Meier estimator and fitted Cox regression models using a calendar time scale to estimate HRs and their 95% CIs. RESULTS: Among 26 525 infants, a dose of nirsevimab led to an adjusted HR for hospital admission due to RSV bronchiolitis of 0.124 (95% CI: 0.086 to 0.179) and an adjusted HR for ICU admission of 0.099 (95% CI: 0.041 to 0.237). Additionally, the adjusted HRs observed for emergency visits were 0.446 (95% CI: 0.385 to 0.516) and 0.393 (95% CI: 0.203 to 0.758) for viral pneumonia, 0.519 (95% CI: 0.467 to 0.576) for bronchiolitis attended in primary care and 0.311 (95% CI: 0.200 to 0.483) for RSV infection. CONCLUSION: We demonstrated nirsevimab's effectiveness with reductions of 87.6% and 90.1% in hospital and ICU admissions, respectively. These findings offer crucial guidance for public health authorities in implementing RSV immunisation campaigns.

Fungal composition associated with host tree identity mediates nutrient addition effects on wood microbial respiration.

Fungi are key decomposers of deadwood, but the impact of anthropogenic changes in nutrients and temperature on fungal community and its consequences for wood microbial respiration are not well understood. Here, we examined how nitrogen and phosphorus additions (field experiment) and warming (laboratory experiment) together influence fungal composition and microbial respiration from decomposing wood of angiosperms and gymnosperms in a subtropical forest. Nutrient additions significantly increased wood microbial respiration via fungal composition, but effects varied with nutrient types and taxonomic groups. Specifically, phosphorus addition significantly increased wood microbial respiration (65%) through decreased acid phosphatase activity and increased abundance of fast-decaying fungi (e.g., white rot), while nitrogen addition marginally increased it (30%). Phosphorus addition caused a greater increase in microbial respiration in gymnosperms than in angiosperms (83.3% vs. 46.9%), which was associated with an increase in Basidiomycota:Ascomycota operational taxonomic unit abundance in gymnosperms but a decrease in angiosperms. The temperature dependencies of microbial respiration were remarkably constant across nutrient levels, consistent with metabolic scaling theory hypotheses. This is because there was no significant interaction between temperature and wood phosphorus availability or fungal composition, or the interaction among the three factors. Our results highlight the key role of tree identity in regulating nutrient response of wood microbial respiration through controlling fungal composition. Given that the range of angiosperm species may expand under climate warming and forest management, our data suggest that expansion will decrease nutrient effects on forest carbon cycling in forests previously dominated by gymnosperm species.

A comprehensive study of the academic benefits and practical recommendations to include resistance training programs in institutional education.

The connection between physical activity and cognitive function has become a focus of attention in educational research in recent years. Regular exercise has been shown to have significant positive effects on physical health, but it also appears to have a significant impact on cognitive function and academic performance. Of all the exercise modalities, resistance training has drawn interest for its ability to improve cerebral abilities in addition to physical well-being. However, there is limited available knowledge exploring the relationship between resistance training regimens and academic performance. This narrative review aims to investigate the underlying mechanisms linking resistance training to academic performance. Firstly, we will examine the biological mechanisms and psychosocial links that potentially connect resistance training to academic performance to find and describe the different mechanisms by which resistance training improves academic performance. In the next part of the work, we delve into the existing observational and intervention studies that have explored the relationship between resistance training and academic performance. Lastly, we provide practical recommendations for including resistance training in institutional education settings, emphasizing the need of dispelling myths and addressing barriers to increase participation as well as the relevance of considering key training variables and adaptation of protocols to developmental stages, always guided by a properly trained professional. Overall, the available evidence supports that resistance training provides potential benefits to the academic performance of youth students with many biological and psychosocial factors that explain this relationship. However, most of the studies are observational, and broader interventional studies are needed to understand and maximize the benefits of this type of physical exercise.

Family Caregivers' Experiences during the COVID-19 Pandemic: Qualitative Study.

Background: The COVID-19 pandemic imposed lockdown measures that affected caregiving. Understanding caregivers' context provides reveals their adaptive strategies to continue caring in this situation of uncertainty and isolation. Objective: To better understand the caregiving experiences of caregivers looking after dependent individuals living in the community during the pandemic. Design: Qualitative research, phenomenological approach. Setting: Primary healthcare centers in Madrid region (Spain). Participants: 21 family caregivers. Methods: Purposive and theoretical sampling was used to recruit caregivers across nurses from primary healthcare centers. Participants were interviewed using a semi-structured interview guide to explore the caring experience. Interview transcripts were evaluated using thematic analysis. Results: The findings were categorized into two themes: "Caregivers during lockdown-providing care in a time of adversity" and "Caregiving toward normality". The sub-themes identified were the re-structuring of before-care services and the introduction of new care approaches, managing the dependent person's health problems, looking after oneself, and dealing with adversity. To adapt to the new normal, strategies were put in place designed to recover confidence and trust, reincorporate assistance, and reconnect with others. Conclusions: Care intensified during the pandemic. Caregivers took on the task without assistance, focusing on preventing contagion and protecting themselves to be able to continue giving care.

Measles, mumps, and rubella vaccination coverage: an ecological study of primary health care and socio-economic factors in Catalonia, Spain.

This study examined the association of socio-economic factors and the structure of primary care centres (PCCs) with measles, mumps, and rubella (MMR) vaccination coverage among the 8-year-old population in Catalonia, Spain. We conducted an ecological study to retrospectively assess the MMR vaccination-recorded status of children born in 2012, using public health data extracted in December 2020. For each of 300 PCCs serving 70,498 children, we calculated vaccination coverage rates from electronic health records and linked these rates to a composite deprivation index corresponding to the territory served by each PCC. We identified a relationship between unfavourable socio-economic factors and higher recorded vaccination coverage. On average, directly managed PCCs had higher vaccination coverage rates than indirectly managed PCCs. Greater utilisation of primary care services by the population was also associated with higher vaccination coverage rates. Further research is needed to generate knowledge valuable for informing more equitable child-vaccination service delivery models.

Differential accumulation of human ß-amyloid and tau from enriched extracts in neuronal and endothelial cells.

While Aß and Tau cellular distribution has been largely studied, the comparative internalization and subcellular accumulation of Tau and Aß isolated from human brain extracts in endothelial and neuronal cells has not yet been unveiled. We have previously demonstrated that controlled enrichment of Aß from human brain extracts constitutes a valuable tool to monitor cellular internalization in vitro and in vivo. Herein, we establish an alternative method to strongly enrich Aß and Tau aggregates from human AD brains, which has allowed us to study and compare the cellular internalization, distribution and toxicity of both proteins within brain barrier endothelial (bEnd.3) and neuronal (Neuro2A) cells. Our findings demonstrate the suitability of human enriched brain extracts to monitor the intracellular distribution of human Aß and Tau, which, once internalized, show dissimilar sorting to different organelles within the cell and differential toxicity, exhibiting higher toxic effects on neuronal cells than on endothelial cells. While tau is strongly concentrated preferentially in mitochondria, Aß is distributed predominantly within the endolysosomal system in endothelial cells, whereas the endoplasmic reticulum was its preferential location in neurons. Altogether, our findings display a picture of the interactions that human Aß and Tau might establish in these cells.

Biopolymeric 3D printed implantable scaffolds as a potential adjuvant treatment for acute post-operative pain management.

BACKGROUND: Pain is characterized as a major symptom induced by tissue damage occurring from surgical procedures, whose potency is being experienced subjectively, while current pain relief strategies are not always efficient in providing individualized treatment. 3D printed implantable devices hold the potential to offer a precise and customized medicinal approach, targeting both tissue engineering and drug delivery. RESEARCH DESIGN AND METHODS: Polycaprolactone (PCL) and PCL - chitosan (CS) composite scaffolds loaded with procaine (PRC) were fabricated by bioprinting. Geometrical features including dimensions, pattern, and infill of the scaffolds were mathematically optimized and digitally determined, aiming at developing structurally uniform 3D printed models. Printability studies based on thermal imaging of the bioprinting system were performed, and physicochemical, surface, and mechanical attributes of the extruded scaffolds were evaluated. The release rate of PRC was examined at different time intervals up to 1 week. RESULTS: Physicochemical stability and mechanical integrity of the scaffolds were studied, while in vitro drug release studies revealed that CS contributes to the sustained release dynamic of PRC. CONCLUSIONS: The printing extrusion process was capable of developing implantable devices for a local and sustained delivery of PRC as a 7-day adjuvant regimen in post-operative pain management.

Monitoring progress towards universal health coverage in Europe: a descriptive analysis of financial protection in 40 countries.

Background: Ensuring that access to health care is affordable for everyone-financial protection-is central to universal health coverage (UHC). Financial protection is commonly measured using indicators of financial barriers to access (unmet need for health care) and financial hardship caused by out-of-pocket payments for health care (impoverishing and catastrophic health spending). We aim to assess financial hardship and unmet need in Europe and identify the coverage policy choices that undermine financial protection. Methods: We carry out a cross-sectional study of financial hardship in 40 countries in Europe in 2019 (the latest available year of data before COVID-19) using microdata from national household budget surveys. We define impoverishing health spending as out-of-pocket payments that push households below or further below a relative poverty line and catastrophic health spending as out-of-pocket payments that exceed 40% of a household's capacity to pay for health care. We link these results to survey data on unmet need for health care, dental care, and prescribed medicines and information on two aspects of coverage policy at country level: the main basis for entitlement to publicly financed health care and user charges for covered services. Findings: Out-of-pocket payments for health care lead to financial hardship and unmet need in every country in the study, particularly for people with low incomes. Impoverishing health spending ranges from under 1% of households (in six countries) to 12%, with a median of 3%. Catastrophic health spending ranges from under 1% of households (in two countries) to 20%, with a median of 6%. Catastrophic health spending is consistently concentrated in the poorest fifth of the population and is largely driven by out-of-pocket payments for outpatient medicines, medical products, and dental care-all forms of treatment that should be an essential part of primary care. The median incidence of catastrophic health spending is three times lower in countries that cover over 99% of the population than in countries that cover less than 99%. In 16 out of the 17 countries that cover less than 99% of the population, the basis for entitlement is payment of contributions to a social health insurance (SHI) scheme. Countries that give greater protection from user charges to people with low incomes have lower levels of catastrophic health spending. Interpretation: It is challenging to identify with certainty the coverage policy choices that undermine financial protection due to the complexity of the policies involved and the difficulty of disentangling the effects of different choices. The conclusions we draw are therefore tentative, though plausible. Countries are more likely to move towards UHC if they reduce out-of-pocket payments in a progressive way, decreasing them for people with low incomes first. Coverage policy choices that seem likely to achieve this include de-linking entitlement from payment of SHI contributions; expanding the coverage of outpatient medicines, medical products, and dental care; limiting user charges; and strengthening protection against user charges, particularly for people with low incomes. Funding: The European Union (DG SANTE and DG NEAR) and the Government of the Autonomous Community of Catalonia, Spain.

Proteomic analysis identifies HSP90AA1, PTK2B, and ANXA2 in the human entorhinal cortex in Alzheimer's disease: Potential role in synaptic homeostasis and Aß pathology through microglial and astroglial cells.

Alzheimer's disease (AD), the most prevalent neurodegenerative disorder worldwide, is clinically characterized by cognitive deficits. Neuropathologically, AD brains accumulate deposits of amyloid-ß (Aß) and tau proteins. Furthermore, these misfolded proteins can propagate from cell to cell in a prion-like manner and induce native proteins to become pathological. The entorhinal cortex (EC) is among the earliest areas affected by tau accumulation along with volume reduction and neurodegeneration. Neuron-glia interactions have recently come into focus; however, the role of microglia and astroglia in the pathogenesis of AD remains unclear. Proteomic approaches allow the determination of changes in the proteome to better understand the pathology underlying AD. Bioinformatic analysis of proteomic data was performed to compare ECs from AD and non-AD human brain tissue. To validate the proteomic results, western blot, immunofluorescence, and confocal studies were carried out. The findings revealed that the most disturbed signaling pathway was synaptogenesis. Because of their involvement in synapse function, relationship with Aß and tau proteins and interactions in the pathway analysis, three proteins were selected for in-depth study: HSP90AA1, PTK2B, and ANXA2. All these proteins showed colocalization with neurons and/or astroglia and microglia and with pathological Aß and tau proteins. In particular, ANXA2, which is overexpressed in AD, colocalized with amoeboid microglial cells and Aß plaques surrounded by astrocytes. Taken together, the evidence suggests that unbalanced expression of HSP90AA1, PTK2B, and ANXA2 may play a significant role in synaptic homeostasis and Aß pathology through microglial and astroglial cells in the human EC in AD.

Knowledge and Perceived Emotions Regarding an Anal Cancer Preventive Program in People Diagnosed With HIV: A Qualitative Study.

BACKGROUND: To the best of our knowledge, no studies have yet examined the emotional repercussions of the care processes among people infected with the human immunodeficiency virus who participate in preventive anal cancer screening programs. OBJECTIVE: This study aimed to explore the knowledge, emotions, sexuality, barriers, and facilitators perceived by this patient group during the process of anal cancer screening and diagnosis. METHODS: Detailed, semistructured, qualitative interviews were completed with 17 men and 3 women to explore their knowledge, experiences, and emotions regarding the screening process. Purposive sampling was conducted on the basis of age, gender, and type of lesion diagnosed in the anal biopsy. RESULTS: Four major themes were identified: 1) knowledge of the disease and its treatment, 2) emotions perceived by the patients, 3) the influence of screening on sexual practices, and 4) facilitators and obstacles during the care provision process. Patients reported appropriate knowledge of anal cancer and human papillomavirus. Predominant emotions were worry and fear with avoidance as one of the coping strategies. CONCLUSION: These results suggest that communication of information and clinical results can be improved. IMPLICATION FOR PRACTICE: Understanding the facilitators and barriers to the program will allow the integration of interventions designed to improve healthcare provision into direct care.

Epidemiology of sarcoptic mange in free-ranging vicuñas (Vicugna vicugna): a cross-sectional study in Andean highland communities in Peru / Epidemiologia da sarna sarcóptica em vicunhas de vida livre (Vicugna vicugna): um estudo transversal em comunidades rurais alto andinas do Peru

Abstract Sarcoptic mange or scabies is a contagious parasitic skin disease that affects a wide range of domestic and wildlife species. A cross-sectional study was carried out to determine the prevalence, molecular identification, and characteristics of sarcoptic mange in vicuñas. A total of 3,274 vicuñas were examined. Following ritual harvesting events ("chaccus") in 13 Andean communities. The presence of mange mites was determined by the skin scraping technique and confirmed by PCR analysis using specific primers for the ITS2 gene of Sarcoptes scabiei. The presence of mange mites was also confirmed by microscopy using samples taken from wallows. A data collection form was used to register the characteristics of the vicuñas sampled. The prevalence of sarcoptic mange was 4.9% (95% CI: 4.1 - 5.6%). All samples from wallows tested positive (9/9). Importantly, the presence of the species S. scabiei was molecularly confirmed. Adult females with regular body condition were more susceptible to sarcoptic mange, although the lesions were mild. This study confirms the presence of S. scabiei in semi-captive vicuñas and points to the possible role of wallows in the dissemination of Sarcoptes mites.

Resumo A sarna sarcóptica é uma doença parasitária contagiosa da pele que afeta uma ampla gama de espécies domésticas e selvagens. Um estudo transversal foi realizado para determinar a prevalência, identificação molecular e características da sarna sarcóptica em vicunhas. Foram avaliadas 3.274 vicunhas, capturadas durante o "Chaccus", em 13 comunidades rurais alto andinas do Peru. A presença do ácaro da sarna foi determinada pelo raspado de pele e confirmada pela técnica de PCR, com iniciadores específicos para o gene ITS2 de Sarcoptes scabiei e por microscopia nos chafurdeiros. Foi preenchida uma ficha de coleta de dados com as características das vicunhas analisadas. A prevalência de sarna sarcóptica em vicunhas foi de 4,9% (95% IC: 4,1 - 5,6%). Todas as amostras de chafurda testadas (9/9) foram positivas, e a presença de S. scabiei foi confirmada molecularmente. Fêmeas adultas com condições corporais regulares foram mais suscetíveis à sarna sarcóptica, embora as lesões fossem leves. O estudo confirma a presença de S. scabiei em vicunhas em semicativeiro de comunidades camponesas alto andinas do Peru que sofrem de sarna. Destaca-se, ainda, o papel das chafurdas das vicunhas na disseminação da sarna.

Synaptic Involvement of the Human Amygdala in Parkinson's Disease.

α-Synuclein, a protein mostly present in presynaptic terminals, accumulates neuropathologically in Parkinson's disease in a 6-stage sequence and propagates in the nervous system in a prion-like manner through neurons and glia. In stage 3, the substantia nigra are affected, provoking motor symptoms and the amygdaloid complex, leading to different nonmotor symptoms; from here, synucleinopathy spreads to the temporal cortex and beyond. The expected increase in Parkinson's disease incidence accelerates the need for detection biomarkers; however, the heterogeneity of this disease, including pathological aggregates and pathophysiological pathways, poses a challenge in the search for new therapeutic targets and biomarkers. Proteomic analyses are lacking, and the literature regarding synucleinopathy, neural and glial involvement, and volume of the human amygdaloid complex is controversial. Therefore, the present study combines both proteomic and stereological probes. Data-independent acquisition-parallel accumulation of serial fragmentation proteomic analysis revealed a remarkable proteomic impact, especially at the synaptic level in the human amygdaloid complex in Parkinson's disease. Among the 199 differentially expressed proteins, guanine nucleotide-binding protein G(i) subunit alpha-1 (GNAI1), elongation factor 1-alpha 1 (EEF1A1), myelin proteolipid protein (PLP1), neuroplastin (NPTN), 14-3-3 protein eta (YWHAH), gene associated with retinoic and interferon-induced mortality 19 protein (GRIM19), and orosomucoid-2 (ORM2) stand out as potential biomarkers in Parkinson's disease. Stereological analysis, however, did not reveal alterations regarding synucleinopathy, neural or glial populations, or volume changes. To our knowledge, this is the first proteomic study of the human amygdaloid complex in Parkinson's disease, and it identified possible biomarkers of the disease. Lewy pathology could not be sufficient to cause neurodegeneration or alteration of microglial and astroglial populations in the human amygdaloid complex in Parkinson's disease. Nevertheless, damage at the proteomic level is manifest, showing up significant synaptic involvement.

Non-nosocomial Healthcare-Associated Infective Endocarditis: A Distinct Entity? Data From the GAMES Series (2008-2021).

Background: Patients who acquire infective endocarditis (IE) following contact with the healthcare system, but outside the hospital, are classified as having non-nosocomial healthcare-associated IE (HCIE). Our aim was to characterize HCIE and establish whether its etiology, diagnosis, and therapeutic approach suggest it should be considered a distinct entity. Methods: This study retrospectively analyzes data from a nationwide, multicenter, prospective cohort including consecutive cases of IE at 45 hospitals across Spain from 2008 to 2021. HCIE was defined as IE detected in patients in close contact with the healthcare system (eg, patients receiving intravenous treatment, hemodialysis, or institutionalized). The prevalence and main characteristics of HCIE were examined and compared with those of community-acquired IE (CIE) and nosocomial IE (NIE) and with literature data. Results: IE was diagnosed in 4520 cases, of which 2854 (63%) were classified as CIE, 1209 (27%) as NIE, and 457 (10%) as HCIE. Patients with HCIE showed a high burden of comorbidities, a high presence of intravascular catheters, and a predominant staphylococcal etiology, Staphylococcus aureus being identified as the most frequent causative agent (35%). They also experienced more persistent bacteremia, underwent fewer surgeries, and showed a higher mortality rate than those with CIE (32.4% vs 22.6%). However, mortality in this group was similar to that recorded for NIE (32.4% vs 34.9%, respectively, P = .40). Conclusions: Our data do not support considering HCIE as a distinct entity. HCIE affects a substantial number of patients, is associated with a high mortality, and shares many characteristics with NIE.

Evaluation of the validity of the HPV viral load compared to conventional techniques for the detection of high-grade anal intraepithelial lesions in men with HIV who have sex with men.

Background: The incidence of high-grade anal intraepithelial lesions (HSILs) has increased in recent years among men who have sex with men with human immunodeficiency virus (HIV). This work evaluated the validity of the human papilloma virus viral load (HPV-VL) versus cytological and qualitative HPV results to detect HSILs. Methods: From May 2017 to January 2020, 93 men who have sex with men and HIV were included in an anal cancer screening program from the Infectious Diseases Unit at a tertiary-care hospital in Alicante (Spain). The gold-standard for the screening of anal HSILs is the anal biopsy using high-resolution anoscopy. The diagnostic methods compared against gold-standard were HPV-16-VL, HPV-18-VL, and HPV-16-18-VL co-testing, anal cytology, and qualitative HPV detection. The receiver operating characteristic (ROC) curve and cut-off points for HPV-VL were calculated. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Cohen's Kappa coefficient (κ) were also calculated. Results: The mean patient age was 44.6 ± 9.5 years. All of them received antiretroviral treatment, 96.8% had an HIV viral load of <50 copies/mL and 17.2% had a previous diagnosis of AIDS. The diagnosis of the anal biopsies were: 19.4% (n = 18) HSIL, 29.1% (n = 27) LSIL, and 51.6% (n = 48) negative. An HPV-16-VL >6.2 copies/cell was detected in the HSIL biopsy samples (p = 0.007), showing a sensitivity of 100% and a specificity of 46.2%. HPV-18-VL and HPV16-18-VL co-testing showed a sensitivity of 75% and 76.9% and a specificity of 72.7% and 61.3%, respectively. The highest PPV was 50% obtained with the cytology and HPV-18-VL. The HPV-16-VL showed a NPV of 100%, followed by 88.9% in the HPV-18-VL and 87% in the abnormal cytology. Cohen's Kappa coefficient were: HPV-18-VL (κ = 0.412), abnormal cytology (κ = 0.353) and HPV-16-VL (κ = 0.338). Conclusions: HPV-VL testing improved the detection sensitivity but not the specificity for HSIL biopsies compared to anal cytology and the qualitative detection of HPV. In men who have sex with men and HIV the HPV-VL could be an useful tool for diagnosis of HSILs in anal cancer screening programs. Further studies will be needed to evaluate the clinical implications of HPV-VL in these programs.

Dalbavancin as suppressive antibiotic therapy in patients with prosthetic infections: efficacy and safety.

Suppressive antibiotic therapy (SAT) is a strategy to alleviate symptoms and/or to reduce the progression of an infection when other treatment options cannot be used. Dalbavancin, due to its prolonged half-life, enables (bi) weekly dosing. Here, we report our multicenter real-life clinical experience with dalbavancin used as SAT in patients with prosthetic joint or vascular infections. Medical records of all adult patients with documented vascular or orthopedic chronic prosthetic infections, who received dalbavancin as SAT between 2016 and 2018 from four Spanish hospitals were reviewed for inclusion. Descriptive analysis of demographic characteristics, Charlson Comorbidity index, Barthel index, isolated pathogens and indication, concomitant antibiotic use, adverse events, and clinical outcome of SAT were performed. Eight patients were eligible for inclusion, where six patients had prosthetic vascular infections (aortic valve) and two patients had knee prosthetic joint infections. The most common pathogens were methicillin-susceptible Staphylococcus aureus and Enterococcus faecium. All patients had a history of prior antibiotic treatment for the prosthetic infection [median duration of antibiotic days 125 days (IQR, 28-203 days)]. The median number of dalbavancin doses was 29 (IQR, 9-61) and concomitant antibiotic use (n = 5, 62.5%). Clinical success was reported in 75% (n = 6) of patients. Adverse events were reported in two patients (mild renal and hepatic impairment). The median estimated cost savings due to the avoided hospital days was €60185 (IQR, 19,916-94984) per patient. Despite the limitations of our study, this preliminary data provides valuable insight to support further evaluation of dalbavancin for SAT in patients with prosthetic infections in the outpatient setting when alternative treatments are not feasible.

EN-DALBACEN 2.0 Cohort: real-life study of dalbavancin as sequential/consolidation therapy in patients with infective endocarditis due to Gram-positive cocci.

OBJECTIVES: Infective endocarditis (IE) has high mortality and morbidity and requires long hospital stays to deliver the antibiotic treatment recommended in clinical practice guidelines. We aimed to analyse the health outcomes of the use of dalbavancin (DBV) in the consolidation treatment of IEs caused by Gram-positive cocci and to perform a pharmacoeconomic study. MATERIALS AND METHODS: This observational, retrospective, Spanish multicentre study in patients with IE who received DBV as part of antibiotic treatment in consolidation phase were followed for at least 12 months. The study was approved by the Provincial Committee of the coordinating centre. RESULTS: The study included 124 subjects, 70.2% male, with a mean age of 67.4 years and median Charlson index of 4 (interquartile range: 2.5-6). Criteria for definite IE were met by 91.1%. Coagulase-negative staphylococci (38.8%), Staphylococcus aureus (22.6%), Enterococcus faecalis (19.4%), and Streptococcus Spp. (9.7%) were isolated more frequently, all susceptible to vancomycin. Before DVB administration, 91.2% had undergone surgery; 60.5% had received a second regimen for 24.5 d (16.6-56); and 20.2% had received a third regimen for 14.5 d (12-19.5). DBV was administered to facilitate discharge in 95.2% of cases. At 12 months, the effectiveness was of 95.9%, and there was 0.8% loss to follow-up, 0.8% IE-related death, and 3.2% relapse. Adverse events were recorded in 3.2%. The hospital stay was reduced by 14 d, and there was a mean savings of 5548.57 €/patient vs. conventional treatments. CONCLUSION: DBV is highly effective, safe, and cost-effective as consolidation therapy in patients with IE by Gram-positive cocci, with few adverse events.