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The Ti6Al4V alloy is widely recognized for its extensive industrial applications, particularly in the aeronautics sector, due to its exceptional strength to-weight ratio and corrosion resistance. In this context, many industrial processes depend critically on surface area, topology, and roughness. A promising approach involves combining Ti6Al4V alloy with polymer composites, which offers significant potential for engineers to design parts that are not only high-performing but also environmentally friendly. Friction stir spot welding (FSSW) emerges as a viable technique for achieving a robust bond between the metal and polymer composite materials. However, a critical factor in this process is the surface profile of the metal, which plays a pivotal role in ensuring strong adhesion between the polymer and the titanium substrate. The data provided focus on analyzing the surface profile and roughness achieved through laser ablation, an advanced technique used for surface texturing, and explores spark erosion as an alternative method.

Summary: Background: Anticipating the burden of intracerebral haemorrhage is crucial for proactive management and building resilience against future health challenges. Prior forecasts are based on population demography and to a lesser extent epidemiological trends. This study aims to utilise selected modifiable risk factors and socio-demographic indicators to forecast the incidence and mortality of intracerebral haemorrhage in Europe between 2019 and 2050. Methods: Three intracerebral haemorrhage risk factors identified in the Global Burden of Diseases, Injuries, and Risk Factors study (GBD 2019)—high systolic blood pressure, high fasting plasma glucose, and high body mass index—were utilised to predict the risk-attributable fractions between 2019 and 2050. Disease burden not attributable to these risk factors was then forecasted using time series models (autoregressive integrated moving average [ARIMA]), incorporating the Socio-demographic Index (SDI) as an external predictor. The optimal parameters of ARIMA models were selected for each age-sex-country group based on the Akaike Information Criterion (AIC). Different health scenarios were constructed by extending the past 85th and 15th percentiles of annualised rates of change in risk factors and SDI across all location-years, stratified by age and sex groups. A decomposition analysis was performed to assess the relative contributions of population size, age composition, and intracerebral haemorrhage risk on the projected changes. Findings: Compared with observed figures in 2019, our analysis predicts an increase in the burden of intracerebral haemorrhage in Europe in 2050, with a marginal rise of 0.6% (95% uncertainty interval [UI], −7.4% to 9.6%) in incident cases and an 8.9% (−2.8% to 23.6%) increase in mortality, reaching 141.2 (120.6–166.5) thousand and 144.2 (122.9–172.2) thousand respectively. These projections may fluctuate depending on trajectories of the risk factors and SDI; worsened trends could result in increases of 16.7% (8.7%–25.3%) in incidence and 31.2% (17.7%–48%) in mortality, while better trajectories may lead to a 10% (16.4%–2.3%) decrease in intracerebral haemorrhage cases with stabilised mortality. Individuals aged ≥80 years are expected to contribute significantly to the burden, comprising 62.7% of the cases in 2050, up from 40% in 2019, and 72.5% of deaths, up from 50.5%. Country-wide variations were noted in the projected changes, with decreases in the standardised rates across all nations but varying crude rates. The largest relative reductions in counts for both incidence and mortality are expected in Latvia, Bulgaria, and Hungary—ranging from −38.2% to −32.4% and −37.3% to −30.2% respectively. In contrast, the greatest increases for both measures were forecasted in Ireland (45.7% and 74.4%), Luxembourg (45% and 70.7%), and Cyprus (44.5% and 74.2%). The modelled increase in the burden of intracerebral haemorrhage could largely be attributed to population ageing. Interpretation: This study provides a comprehensive forecast of intracerebral haemorrhage in Europe until 2050, presenting different trajectories. The potential increase in the number of people experiencing and dying from intracerebral haemorrhage could have profound implications for both caregiving responsibilities and associated costs. However, forecasts were divergent between different scenarios and among EU countries, signalling the pivotal role of public health initiatives in steering the trajectories. Funding: The European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No. 754517. The National Institute for Health and Care Research (NIHR) under its Programme Grants for Applied Research (NIHR202339).

The growing use of redundant claims on food products pose a risk for organic and functional food producers among others, as it can mislead consumers in their products’ evaluations. Redundant claims refer to marketing statements that highlight qualities or attributes that are expected or should be inherent to the product. Previous studies reveal that consumers are generally willing to pay more for redundantly claimed products. In this study, preferences are analyzed for organic, functional, and redundantly labeled apple juice among specific consumer groups, namely young and old adults. To elicit individual monetary preferences a lab experiment and a field study were conducted with 147 younger (average age: 21 years) and 131 older participants (average age: 70 years), in both studies an incentive compatible technique was applied. Results showed that either younger and older consumers are willing to pay higher prices for organic, functional, and redundantly claimed apple juices. Perceived healthiness was a significant factor in increasing preferences for all the added valued products in the case of younger participants, but health only influenced preferences of organic and functional apple juice among older participants. Preferences of redundantly claimed and organic products were similar in the case of young participants, as functional and redundantly claimed juices preferences in the case of older participants.

Background: Mass vaccination against Covid-19 has been recognised as the most effective strategy for overcoming the pandemic emergency and remains crucial in the ongoing efforts to mitigate the impact of the virus. The present study aimed to test the efficacy of an extended Theory of Planned Behaviour (TPB) model in predicting vaccination intention in three different phases of the pandemic. Understanding how psychological drivers of vaccine acceptance may have changed throughout the pandemic is essential for informing public health strategies and addressing vaccine hesitancy, even in the current post-pandemic context. Methods: Using a repeated cross-sectional survey, we tested the hypothesised extended TPB model (intention, attitude, subjective norms, perceived behavioural control, anticipated affective reactions, risk perception, trust in science, trust in institutions and religiosity) across three independent samples: before (T1: November–December 2020; N = 657), during (T2: March–May 2021; N = 818), and after (T3: February–March 2022; N = 605) the start of the vaccination campaign in Italy. Results: Results indicated significant differences between the time points in all investigated variables, pointing to a general trend of improvement in vaccine acceptability levels at T2 compared to T1, and a worsening at T3 compared to the other two time points. Interestingly, net of these differences, a multi-group Structural Equation Modeling analysis supported the invariance, across time, of the structural relationships examined within the extended TPB. Conclusion: Findings demonstrated the efficacy of the TPB in predicting Covid-19 vaccination intention at different stages of the pandemic, suggesting that the model, in its extended version, represents a valuable framework for designing interventions aimed at promoting vaccine acceptance.

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health.

Studying interspecific interactions and community composition within carnivore guilds are often difficult to complete and is seldom done in North America. Here we used a historic camera trap database from 2009 to 2010 to describe the carnivore diversity and investigate the temporal niche partitioning of community members within the northern edge of the Sierra of Tamaulipas, México. We detected 15 different species of carnivores including six Felids, three Mephitids, as well as two Canids, Mustelids, and Procyonids each. In our diel activity analysis, we observed significant differences in diel activity between jaguars (Panthera onca) and mesocarnivores including ocelots (Leopardus pardalis), jaguarundis (Puma yagouroundi), and gray foxes (Urocyon cinereoargenteus). Ocelots, gray foxes, and white-nosed coatimundis (Nasua narica) had the highest occupancy rates across the study. Difficulty to understand temporal interactions between bobcats (Lynx rufus), pumas (Puma concolor), margay (Leopardus wiedii), coyote (Canis latrans), badgers (Taxidea taxus), three species of skunks (Mephitis sp; Conepatus sp.; Spilogale sp.), and long–tailed weasel (Neogale frenata) may have been related to habitat use, activity, low local populations, or reclusive behavior. This study illustrates the ecologically rich Sierra of Tamaulipas holds a diverse carnivore community and there is a need for continued monitoring to further understand the dynamics within this ecosystem.

Background: Puerperal endometritis has not been recently investigated. We aimed to describe the current dimension of the endometritis in the context of other causes of puerperal fever and investigate the microbiology and need for curettage in these patients Methods: A retrospective cohort study was conducted based on a prospectively maintained database of patients with puerperal fever, (2014–2020) in which cases fulfilling criteria for endometritis were selected for further analysis. Description of clinical and microbiological features was performed and determination of the factors related with puerperal curettage requirement were studied using univariate and multivariate analysis through binary logistic regression. Results: From 428 patients with puerperal fever, endometritis was the main cause of puerperal fever (233 patients, 52.7 %). Curettage was required in 96 of them (41.2 %). Culture of endometrial samples were performed in 62 (64.5 %), of which 32 (51.6 %) yielded bacterial growth. Escherichia coli was the most common microorganism in curettage cultures (46.9 %). Multivariate analysis identified the following predictive factors for curettage: the presence of pattern compatible with retained products of conception (RPOC) in transvaginal ultrasonography (odds ratio [OR]: 17.6 [95 % confidence interval [CI]: 8.4–36.6]; P-value

Resumen: Introducción: Los errores congénitos del metabolismo son un grupo muy heterogéneo de enfermedades raras. La mayoría se pueden tratar con dieta y sustitución enzimática.Existen pocos pacientes y pocos estudios publicados en estas enfermedades. Por ello, se ha llevado a cabo un estudio con el objetivo de evaluar la efectividad de los medicamentos huérfanos utilizados en errores congénitos del metabolismo de un hospital general de 630 camas. Material y métodos: Estudio descriptivo restrospectivo de 24 meses de duración en un hospital general de 630 camas. Se incluyeron los pacientes diagnosticados durante la infancia de errores congénitos del metabolismo y que acudieron a Hospital de Día o a la consulta de Farmacia. Resultados: Se estudiaron 15 pacientes, con una edad media de 27,8 años, que recibieron tratamiento con nueve fármacos: sapropterina, fenilbutirato de sodio, miglustat, velaglucerasa, sebelipasa, idursulfasa, hidroxitriptófano, succinato y riboflavina. Presentaban siete errores congénitos del metabolismo diferentes: fenilcetonuria, trastorno del ciclo de la urea, Gaucher, Niemann-Pick, Hunter, déficit de lipasa ácida liposomal y defectos mitocondriales. Los medicamentos huérfanos para estos trastornos supusieron el 1,3% del gasto de farmacia. Algunos medicamentos huérfanos lograron que los pacientes estuvieran asintomáticos y otros, sólo produjeron una discreta mejoría. La efectividad de las fórmulas magistrales se evaluó mediante criterios subjetivos. En general, los pacientes presentaron buena tolerancia a estos tratamientos. Conclusiones: Los medicamentos huérfanos utilizados para errores congénitos del metabolismo presentan buen perfil de seguridad, pero gran disparidad en cuanto a su efectividad. Suponen un alto impacto económico.La incertidumbre en cuanto a la evidencia clínica de los medicamentos huérfanos junto con el elevado coste, hace que la relación coste-efectividad sea controvertida. Abstract: Introduction: Inborn errors of metabolism are a highly heterogeneous group of orphan diseases. Diet therapy and enzyme and coenzyme replacement are the most frequently used treatment. There are few patients and published studies about inborn errors of metabolism. The main objective of this study was to describe the effectiveness of orphan drugs in inborn errors of metabolism in paediatric patients. Material and Methods: Retrospective descriptive study of 24 months on patients diagnosed with inborn errors of metabolism during childhood and who attended the pharmacy clinic or Day-Care Unit of a 630-bed general hospital. Results: The study included 15 patients with a median age of 17.8 years and were treated with nine different drugs: sapropterin, sodium phenylbutyrate, miglustat, velaglucerase, sebelipase, idursulfase, 5-hydroxytryptophan, succinate, and riboflavin. Nine different inborn errors of metabolism were observed: phenylketonuria, defects of the urea cycle, Gaucher, Nieman-Pick, Hunter's disease, along with acid lipase deficiency, and mitochondrial diseases. Orphan drugs used for the treatment of inborn errors of metabolism accounted for 1.3% of hospital drug costs. Some orphan drugs achieved asymptomatic patients, but others just produced a modest symptomatic improvement. Most patients showed good tolerance to the treatment. Conclusions: Orphan drugs used in inborn errors of metabolism had an easy to manage toxicity profile, with many disparities in effectiveness. These drugs have a high economic impact. The cost-effectiveness ratio for orphan drugs is a controversial issue due to their high cost and the inconclusive clinical evidence.

Introduction: Inborn errors of metabolism are a highly heterogeneous group of orphan diseases. Diet therapy and enzyme and coenzyme replacement are the most frequently used treatment. There are few patients and published studies about inborn errors of metabolism. The main objective of this study was to describe the effectiveness of orphan drugs in inborn errors of metabolism in paediatric patients. Material and methods: Retrospective descriptive study of 24 months on patients diagnosed with inborn errors of metabolism during childhood and who attended the pharmacy clinic or Day-Care Unit of a 630-bed general hospital. Results: The study included 15 patients with a median age of 17.8 years and were treated with nine different drugs: sapropterin, sodium phenylbutyrate, miglustat, velaglucerase, sebelipase, idursulfase, 5-hydroxytryptophan, succinate, and riboflavin. Seven different inborn errors of metabolism were observed: phenylketonuria, defects of the urea cycle, Gaucher, Nieman-Pick, Hunter’s disease, along with acid lipase deficiency, and mitochondrial diseases. Orphan drugs used for the treatment of inborn errors of metabolism accounted for 1.3% of hospital drug costs. Some orphan drugs achieved asymptomatic patients, but others just produced a modest symptomatic improvement. Most patients showed good tolerance to the treatment. Conclusions: Orphan drugs used in inborn errors of metabolism had an easy to manage toxicity profile, with many disparities in effectiveness. These drugs have a high economic impact. The cost-effectiveness ratio for orphan drugs is a controversial issue due to their high cost and the inconclusive clinical evidence. Resumen: Introducción: Los errores congénitos del metabolismo son un grupo muy heterogéneo de enfermedades raras. La mayoría se pueden tratar con dieta y sustitución enzimática.Existen pocos pacientes y pocos estudios publicados en estas enfermedades. Por ello, se ha llevado a cabo un estudio con el objetivo de evaluar la efectividad de los medicamentos huérfanos utilizados en errores congénitos del metabolismo de un hospital general de 630 camas. Material y métodos: Estudio descriptivo restrospectivo de 24 meses de duración en un hospital general de 630 camas. Se incluyeron los pacientes diagnosticados durante la infancia de errores congénitos del metabolismo y que acudieron a Hospital de Día o a la consulta de Farmacia. Resultados: Se estudiaron 15 pacientes, con una edad media de 17,8 años, que recibieron tratamiento con 9 fármacos: sapropterina, fenilbutirato de sodio, miglustat, velaglucerasa, sebelipasa, idursulfasa, hidroxitriptófano, succinato y riboflavina. Presentaban 7 errores congénitos del metabolismo diferentes: fenilcetonuria, trastorno del ciclo de la urea, Gaucher, Niemann-Pick, Hunter, déficit de lipasa ácida liposomal y defectos mitocondriales. Los medicamentos huérfanos para estos trastornos supusieron el 1,3% del gasto de farmacia. Algunos medicamentos huérfanos lograron que los pacientes estuvieran asintomáticos y otros, sólo produjeron una discreta mejoría. La efectividad de las fórmulas magistrales se evaluó mediante criterios subjetivos. En general, los pacientes presentaron buena tolerancia a estos tratamientos. Conclusiones: Los medicamentos huérfanos utilizados para errores congénitos del metabolismo presentan buen perfil de seguridad pero gran disparidad en cuanto a su efectividad. Suponen un alto impacto económico.La incertidumbre en cuanto a la evidencia clínica de los medicamentos huérfanos junto con el elevado coste, hace que la relación coste-efectividad sea controvertida.

Hyperimmunoglobulin E syndrome or Job syndrome is defined as an immune and connective tissue disorder that results in complications such as invasive infections. On the other hand, Fournier gangrene is a rapidly progressive necrotizing fasciitis that affects the perineal area, has a polymicrobial etiology, and its treatment consists of rapid and aggressive surgical debridement, antibiotic therapy, and hemodynamic support. We present the case of Fournier gangrene in an 11-year-old boy with a diagnosis of hyperimmunoglobulinemia E. who was admitted with scrotal necrosis with favorable evolution after initial medical management.

Ureterocele is a cystic dilation of the distal ureter that exits into the urinary bladder. It is a rare condition in adults of which women are the most affected. Its clinical manifestations are very broad and among them the presence of a vulvar mass and symptoms of urinary obstruction stand out. We report the case of a strangulated ureterocele prolapse in a 54-year-old woman with a vulvar mass and signs of urinary obstruction. Initial management with reduction of the mass and finally decided to perform a ureteral reimplantation. Favorable evolution in medical follow-up.

Current study investigates whether a private, sustainability claim has an impact on individuals' sensory and non-sensory expectations (halo effect) and quantifies such impact on individual monetary preferences. An incentive-compatible artefactual field experiment was performed by recruiting regular buyers and consumers of the investigated product (cookies). Results reveal that the sustainable agriculture claim generates high (unrelated) expectations and a statistically significant premium price compared to the conventional counterpart. Additionally, these expectations, together with respondents’ trust in the claim, are the drivers of the price premium. Findings suggest the need for policy makers and consumer advocates to scrutinize the potential drawbacks of private sustainability claims on food products.

Objective: To determine the prevalence and risk factors of sexually transmitted infections (STIs) including Chlamydia trachomatis, Ureaplasma urealyticum and Mycoplasma genitalium among asymptomatic women with human papillomavirus (HPV) infection. Methods: A cross-sectional study was performed in 842 asymptomatic women from Cajamarca, Peru. The pathogens were detected using polymerase chain reaction (PCR) and the results were analyzed according to the HPV status: high-risk HPV, low-risk HPV and negative for HPV. Demographical and gyneco-obstetric data was analyzed to identify risk factors. Results: We found that 23.99% (202/842) women were positive for HPV, of whom 79.21% (160/202) were infected with a high-risk genotype. Co-infections were evaluated and 14.38% (23/160) were positive for Ureaplasma urealyticum, 9.38% (15/160) for Chlamydia trachomatis and 1.25% (2/160) for Mycoplasma genitalium. We found a significant association between HPV genotype and the number of children, partners, and history of sexual abuse. The co-infection between high-risk HPV and Chlamydia trachomatis was associated with number of abortions, number of sexual partners and no use of condom. Finally, co-infection between high-risk HPV and Ureaplasma urealyticum was associated with no use of condom and history of STIs. Conclusion: HPV infection continues to be a highly relevant problem in Peru, particularly due to the high prevalence of high-risk genotypes. In addition, we report high rates of co-infections with other STIs, such as U. urealyticum and C. trachomatis. We highlight the importance of active surveillance to promptly diagnose these infections, since they may lead to persistent HPV infections.

Photoacoustic tomography (PAT), a hybrid imaging modality that acoustically detects the optical absorption contrast, is a promising technology for imaging hemodynamic functions in deep tissues far beyond the traditional optical microscopy. However, the most clinically compatible PAT often suffers from the poor image fidelity, mostly due to the limited detection view of the linear ultrasound transducer array. PAT can be improved by employing highly-absorbing contrast agents such as droplets and nanoparticles, which, however, have low clinical translation potential due to safety concerns and regulatory hurdles imposed by these agents. In this work, we have developed a new methodology that can fundamentally improve PAT’s image fidelity without hampering any of its functional capability or clinical translation potential. By using clinically-approved microbubbles as virtual point sources that strongly and isotropically scatter the local pressure waves generated by surrounding hemoglobin, we can overcome the limited-detection-view problem and achieve high-fidelity functional PAT in deep tissues, a technology referred to as virtual-point-source PAT (VPS-PAT). We have thoroughly investigated the working principle of VPS-PAT by numerical simulations and in vitro phantom experiments, clearly showing the signal origin of VPSs and the resultant superior image fidelity over traditional PAT. We have also demonstrated in vivo applications of VPT-PAT for functional small-animal studies with physiological challenges. We expect that VPS-PAT can find broad applications in biomedical research and accelerated translation to clinical impact.

Purpose: Corryocactus brevistylus (K. Schum. ex Vaupel) Britton & Rose, commonly referred to as Sanky, is a Peruvian Cactaceae grown in the Andean regions with antibacterial properties yet to be studied. This study aimed to determine the antibacterial effect of the Corryocactus brevistylus methanol extract, against Staphylococcus aureus and Enterococcus faecalis. Methods & Materials: For the preparation of the methanol extract, freeze-dried Sanky powder was immersed in absolute methanol (1:2, w/v). Bacterial strains of S. aureus (ATCC®23235) and E. faecalis (ATCC®29212) (Microbiologics, USA) were cultivated in Brain heart infusion (BHI) agar. Subsequently, one colony of each bacteria was resuspended in BHI broth and incubated aerobically. For the antibacterial activity assay, 20 uL of the culture in BHI broth was inoculated in 100 mL of BHI agar to an approximate standard density of 0.5 McFarland, to a concentration of approximately 1.5 × 108 CFU/ml. Agar diffusion test was used by preparing wells with the experimental solutions cultivated in aerobic conditions. Six independent tests were prepared for each type of bacteria, using penicillin-streptomycin and clorhexidine 12% as positive controls. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined using the microdilution method as described by the CLSI. Results: Antibacterial effect of the methanol extract was observed with inhibition halos of 23.33 ± 0.72 mm and 24.34 ± 0.55 mm against S. aureus and E. faecalis, respectively. Meanwhile, penicillin-streptomycin (10 U) showed an inhibition halo of 28.32 ± 2.6 mm and 22.84 ± 1.2 mm, respectively. Clorhexidine 12% produced halos of 26.8 ± 0.4 mm and 24.3 ± 0.4 mm, respectively. The MIC of the extract was 0.83 mg/mL for S. aureus and 0.21 mg/mL for E. faecalis. The MBC was 1.66 mg/mL on S. aureus and 0.42 mg/mL on E. faecalis. The MBC/MIC ratio was calculated as 2 for both bacteria, indicating a bactericidal effect of the compound (MBC/MIC

Purpose: The rapid expansion of the novel SARS-CoV-2 virus has raised serious public health concerns due to the possibility of misdiagnosis in regions where arboviral diseases are endemic. We performed the first study in northern Peru to describe the detection SARS-CoV-2 IgM antibodies in febrile patients from an endemic zone for dengue virus (DENV) and chikungunya virus (CHIKV). Methods & Materials: A cross-sectional study was performed in febrile patients attending primary healthcare centers from April 2020 through March 2021. This study was carried out jointly with the national surveillance system for the etiological identification of acute febrile illness (AFI). Patients are included if they attended outpatient clinics with AFI (axillary temperature greater than or equal to 38°C in the previous 7 days) along with one or more of the following symptoms: headache, myalgias, arthralgias, retro-ocular pain, lumbar pain, arthritis, nausea, rash, among others. Serum samples were collected from each patient, for the molecular and serological detection of DENV and CHIKV by RT-PCR and IgM ELISA-based assay, respectively. Also, the detection of IgM antibodies against SARS-CoV-2 with an ELISA-based assay was performed. Results: 464 patients were included during the study period, of which 188 (40.51%) were positive for one pathogen, meanwhile 32 (6.90%) presented co-infections between 2 or more pathogens. The majority of patients with monoinfections were positive for SARS-CoV-2 IgM with 73.40%, followed by DENV 18.09% and CHIKV 8.51%. The most frequent co-infection was DENV + SARS-CoV-2 with 65.63%, followed by DENV + CHIKV and DENV + CHIKV + SARS-CoV-2, both with 12.50%. The presence of polyarthralgias in hands (p

Purpose: The impact of respiratory coinfections in COVID-19 is still not well understood. This study sought to identify the respiratory pathogens causing coinfections in patients with moderate/severe SARS-CoV-2 pneumonia from a hospital in Peru. Also, to describe the clinical characteristics and outcomes of coinfected and non-coinfected patients. Methods & Materials: A descriptive study was conducted on hospitalized patients with a confirmed diagnosis of moderate/severe pneumonia due to SARS-CoV-2 infection. The selection criteria included patients older than 18 years of age who were admitted to the Guillermo Almenara Irigoyen Hospital in Lima, Peru during the period July-November 2020. Pregnant women were excluded from the study. A nasopharyngeal swab sample was obtained from the patients included in the study. Diagnosis of SARS-CoV-2 infection was performed by reverse-transcriptase polymerase chain reaction (RT-PCR). The detection of the following respiratory viruses was performed by RT-PCR: Influenza A and B, Respiratory syncitial virus (RSV) A and B; and Adenovirus. The detection of atypical bacteria, Mycoplasma pneumoniae and Chlamydia pneumoniae was carried out using conventional polymerase chain reaction. Results: A total of 295 patients with confirmed SARS-CoV-2 infection were enrolled during the study period. A coinfection with one or more respiratory pathogen was detected in 154 (52.20%) patients at hospital admission. The most common coinfections were Mycoplasma pneumoniae (28.12%), Chlamydia pneumoniae (8.81%) and with both bacteria (11.53%); followed by Adenovirus (1.70%), Mycoplasma pneumoniae/Adenovirus (0.71%), Chlamydia pneumoniae/Adenovirus (0.71%), RSV-B/Chlamydia pneumoniae (0.32%), Mycoplasma pneumoniae/Chlamydia pneumoniae/Adenovirus (0.32%). Sepsis was more frequent among coinfected patients than non coinfected (33.12% vs 20.57%, p = 0.018). Expectoration was less frequent in coinfected individuals compared to non coinfected (5.84% vs 12.77%, p = 0.045). We could highlight that the majority of patients were administered an antibiotic (69.50%). The correlation between the empirical use of macrolides in patients with Mycoplasma pneumoniae and Chlamydia pneumoniae was observed in 41% of the cases. Conclusion: Mycoplasma pneumoniae and Chlamydia pneumoniae were the main microorganisms associated with SARS-CoV-2 coinfection at hospital admission. The presence of multiple coinfections was described in some patients. Antibiotics should be carefully prescribed, as high rates of antibiotic use was found, particularly with macrolides.

Purpose: The inflammatory response in COVID-19 among people living at different altitudes has not been studied. Given that chronic hypoxia promotes cytokines production in the absence of disease, the inflammatory response against SARS-CoV-2 may also be different in these populations. The aim of this study was to compare pro-inflammatory cytokine levels among healthy and COVID-19 patients living at different altitudes above sea level. Methods & Materials: A descriptive cross-sectional study was performed in two Peruvian cities at different altitudes for comparison: Lima (sea level) and Huaraz (3052 meters above sea level). Patients with COVID-19 diagnosis confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR) were compared to healthy subjects, according to their residing location. Five important proinflammatory cytokines were measured including: IL-6, IL-2, IL-10, IFN-γ and TNF-α using ELISA-based assays. Cytokines levels were calculated and their mean, maximum and minimum levels were reported according to each study group. The difference between means was compared using the ANOVA and post-hoc Turkey Test, a signifiant value of p

Purpose: Increasing evidence indicates a possible relationship between the pathogenesis of COVID-19 and the nasopharyngeal microbiota. This study aimed to compare the nasopharyngeal microbiota of COVID-19 patients with different disease severity. Methods & Materials: A comparative study was performed on patients classified into four groups according to their disease severity. A total of 26 patients were recruited for each of the following study groups. Group 1 (G1): patients with a confirmatory diagnosis of SARS-CoV-2 and hospitalized in the ICU. Group 2 (G2): patients with a confirmatory diagnosis of SARS-CoV-2 and hospitalized in regular hospitalization wards. Group 3 (G3): patients with a confirmatory diagnosis of SARS-CoV-2 who were not hospitalized and had mild or no symptoms. Group 4 (G4): healthy patients with a negative result for SARS-CoV-2. The diagnosis of SARS-CoV-2 was performed by reverse-transcriptase polymerase chain reaction (RT-PCR). The nasopharyngeal microbiota was characterized using polymerase chain reaction (PCR) targeting 13 representative bacteria genus. Results: The detection of some bacteria genus was significantly more frequent in the hospitalized groups compared to healthy subjects. This is the case of Lactobacillus with 96.15% in G1, 96.15% in G2, 23.08% in G3 and 15.38% in G4. Similarly, Prevotella presented 96.15% in G1, 80.77 in G2, 0.00% in G3 and 19.23% in G4. Veilonella, Bacteroidetes and Firmicutes presented a similar prevalence. On the other hand, the detection of Eubacterium was more frequent among asymptomatic and healthy subjects, with 3.85% in G1, 19.23% in G2, 50.00% in G3 and 30.77% in G4. The relative abundance of the bacteria was evaluated and Lactobacillus and Veilonella were predominant in both of the hospitalized groups (G1 and G2). On the other hand, Actinobacteria and Eubacterium were predominant in the asymptomatic and healthy groups (G3 and G4) Conclusion: In conclusion a unique nasopharyngeal microbiota profile was found in COVID-19 patients with different disease severity. Lactobacillus, Prevotella, Veilonella, Bacteroidetes and Firmicutes were the predominant bacteria genus in critical and hospitalized patients. While. Eubacterium and Actinobacteria were predominant in the groups of asymptomatic and healthy subjects. Further longitudinal studies are required to determine the prognostic role of the nasopharyngeal microbiota.

Purpose: The epidemiology of human papillomavirus (HPV) and co-infections with other sexually transmitted infections (STIs) remains poorly characterized in Peru. The aim of this study was to identify HPV infections and the presence of co-infections by other important STIs (Chlamydia trachomatis, Trichomonas vaginalis, and Herpes simplex virus) in women attending the public health system in northern Peru. Methods & Materials: We conducted a prospective cross-sectional study in asymptomatic women attending the cervical cancer screening program in a public hospital of Cajamarca, Peru. Exclusion criteria were: pregnancy, recent gynecological bleeding, previous hysterectomy, previous history of HPV-related disease including cervical intraepithelial lesions, cancer, warts and cutaneous manifestations. A cervical swab was collected from each patient using a disposable cytobrush. Detection of sexually transmitted pathogens was performed by polymerase chain reaction (PCR). The pathogens evaluated were: HPV, Chlamydia trachomatis, Trichomonas vaginalis, and Herpes simplex virus 1 (HSV-1) and 2 (HSV-2). Results: A total of 300 asymptomatic women were enrolled in the current study. The pooled prevalence of HPV detected in our study was 19.33% (16.33% as single infection and 3.00% in co-infections) from the total samples. Co-infections between the different pathogens were also observed in 15 cases, being HPV and T. vaginalis the most frequent with 10 cases (66.67%). The most frequent type identified in HPV monoinfections were HPV-16 (16.33%), HPV-52 (14.29%) and HPV-31 (8.16%). Co-infection by multiple HPV types were also identified with up to 4 genotypes at the same time in a single patient The majority of patients with high-risk HPV were between 18 - 39 years old (60.87%) and had a sexual partner in the last 6 months (93.48%). Also, the majority of the patients with high-risk types did not report frequent condom use (89.13%). Conclusion: We found an important prevalence of HPV in asymptomatic women from northern Peru. The most common genotypes were HPV-16, HPV-52 and HPV-31. Among the STIs studied, T. vaginalis was the most common pathogen detected in co-infections with HPV. Education on condom use and timely screening should be encouraged in the Peruvian population to prevent the expansion of HPV and other sexually transmitted pathogens.

Purpose: Acute respiratory infections (ARIs) remain the leading cause of death in children in Peru; however, the epidemiology of many respiratory pathogens has not been described. The objective of this study was to assess the prevalence of Rhinovirus and its most common genotypes in nasopharyngeal swab samples of children with a clinical diagnosis of acute respiratory infection (ARI) in Lima, Peru. Methods & Materials: We performed a secondary analysis on nasopharyngeal swab samples collected from a cross-sectional study in children younger than 17 years old with a clinical diagnosis of ARI from the Hospital Nacional Cayetano Heredia between the years 2009-2010 in Lima, Peru. The original study recruited 767 hospitalized patients with ARI; however, due to conservation of the samples only 559 samples were included in the current study. The detection of Rhinovirus (RV) and their specific genotypes (RVA, RVB and RVC) was performed by RT-PCR. Epidemiological and clinical characteristics were registered using the clinical charts. Results: A total of 234 (41.86%) cases were diagnosed with RV, of which 73.07% were RVC, 16.67% were RVB and 10.26% were RVA. Infections caused by RV were more common in male patients (57.26%) and in the 0 - 5 months group (48.72%). The group with the least cases detected was 11- 17 years old (3.76%). The 88.46% (207/234) of positive cases for RV were hospitalized. The most common clinical symptoms found in the present study were cough 73.08% (171/234), followed by fever 68.80% (161/234), rhinorrea 67.95% (159/234) and respiratory distress 61.54% (144/234). An association between RVC infection and some signs and symptoms were found: cough (p= 0.012), wheezing (p=0.003) and headache (p=0.030). A peak in the cases of infections was observed in March (42 cases of RV and 32 RVC) and June (38 cases of RV and 27 RVC). Conclusion: In conclusion, we found a high prevalence of Rhinovirus in pediatric patients, being RVC the most common genotype. The majority of cases corresponded to male pediatric patients younger than 6 months old. A peak in the cases of infections was observed in March and June, which corresponds to the fall season in Peru.

Purpose: Acute respiratory infections (ARIs) continue to be the leading cause of child mortality in Peru. Data on the epidemiology of Acinetobacter baumannii and its role in respiratory infection among pediatric patients is still scarce. This study aimed to determine the prevalence of A. baumannii in children aged less than one year hospitalized with a clinical diagnosis of whooping cough. Methods & Materials: A prospective cross-sectional study was conducted in five hospitals in Lima, Peru. Patients under 1 year old admitted with a clinical diagnosis of whooping cough were included in the study. Nasopharyngeal samples were obtained from each patient upon admission and the presence of A. baumanii was determined using a polymerase chain reaction (PCR) assay for the detection of the OXA-51 gene. Also co-infections with other respiratory pathogens was evaluated by molecular methods, including Bordetella pertussis, Mycoplasma pneumoniae, Chlamydia pneumoniae, Influenza A and B and Adenovirus. Results: A total of 225 nasopharyngeal samples were studied. The presence of A. baumanii was detected in 20.89% (47/225) of the nasopharyngeal swab samples. The samples were obtained upon admission to the hospital, therefore, infection by A. baumanii may have occurred in the community. Among the 47 patients with A. baumanii: 5 were diagnosed with A. baumanii monoinfection, 17 co-infection with bacteria, 7 co-infection with virus and 18 co-infection with bacteria + virus. It was observed that children between 29 days and 3 months old had the highest prevalence with 53.3%. The most common co-infecting pathogens were Bordetella pertussis in 55.3%, Adenovirus in 42.6% and Mycoplasma pneumoniae in 23.4%. Conclusion: In conclusion, this is the first report describing the presence of community-acquired A. baumannii in nasopharyngeal samples of children under 1 year old with whooping cough. Co-detection with multiple pathogens is frequent, with up to 6 respiratory infectious agents at the same time, being A. baumannii and B. pertussis co-infection the most prevalent. Further studies are required to determine the role of A. baumannii infections in acute respiratory infections in young children, particularly in those with non-critical disease and outside of intensive care units.

Purpose: Dengue virus (DENV) is the most common mosquito-borne disease worldwide. This study aimed to characterize an outbreak of DENV infection in Cajamarca, Peru. Also, to identify the most common serotypes involved and describe the applicability of different diagnostic tests in the diagnosis of primary and secondary cases. Methods & Materials: The study was performed in the region of Cajamarca, in northern Peru. We included patients attending outpatient health centers with an acute febrile illness (AFI), defined as a temperature of 38°C or higher for up to 7 days, without an identifiable source of infection and presenting at least one of the following symptoms: arthralgia, myalgia, headache, retro-ocular pain, low back pain, cutaneous rash, nausea, vomiting, diarrhea, and conjunctival injection. Serum samples were collected and diagnostic tests were performed including: reverse-transcriptase polymerase chain reaction (RT-PCR), NS1 antigen, IgM and IgG antibodies ELISA-based assays. Primary infection was diagnosed by the detection of NS1 antigen ELISA and/or RT-PCR and/or IgM ELISA in the absence of IgG ELISA. Secondary infection was determined by the presence of IgG ELISA and a positive NS1 antigen ELISA and/or RT-PCR and/or IgM ELISA. Results: A total of 359 serum samples were collected in the study period. Dengue infection was diagnosed in 37.9% (136/359) of the patients, being 107 primary infections and 29 secondary infections. The most common serotype was DENV-3 in 77.5% of the cases. Differences were observed in the diagnostic performance of IgM ELISA (17.6% vs 55.2%, p≤0.01) and RT-PCR (74.8% and 31.0%, p≤0.01) in primary and secondary infections respectively. The combination of NS1 and IgM performed better than the other assays in detecting primary (91.9%) and secondary infections (96.6%). The most frequent symptoms associated with DENV infection were headaches, myalgias, and arthralgias. Conclusion: We report an important outbreak of dengue infection caused by DENV-3 in Cajamarca, Peru. Our findings encourage the use of NS1 antigen and IgM co-detection. These findings demonstrate an increasing expansion of DENV-3 in Peru and highlight the importance of molecular diagnosis and serotype characterization among febrile patients to strengthen the Peruvian epidemiological surveillance.

Purpose: The Chikungunya virus (CHIKV) is an arboviral disease with increasing expansion in Peru. The aim of this study was to evaluate the prevalence, clinical presentation, and seasonality of acute febrile illness (AFI) due to Chikungunya virus in Jaen-Cajamarca, Peru. Methods & Materials: A consecutive cross-sectional study was performed in febrile patients attending primary healthcare centers from April 2020 through June 2021. This study was performed alongside the epidemiological surveillance of acute febrile illness (AFI). Patients were included if they presented with AFI, defined as an axillary temperature greater than or equal to 38°C within at least 7 days prior to consultation without an identifiable source of infection. The signs and symptoms were assessed and recorded by the attending physician in a standardized questionnaire. Blood samples were collected and sent to a central laboratory, where PCR analysis for the molecular detection of CHIKV was performed. Results: A total of 88 CHIKV cases were identified from 1047 patients with acute febrile illness, with a prevalence of (8.40%). The main clinical characteristics identified in CHIKV positive patients were headache 81.82%, myalgia 70.45%, arthralgia 65.91% and retro-ocular pain 48.86%. No cases of severe disease were identified. Most of the infected patients were adults between 18-39 years (45.45%) and 40-59 years (25.00%). A 50% were male and 44.32% female, the rest were not classified in the clinical record. The majority of the CHIKV cases occurred in February-March (32.95%), May (14.77%) and July (13.64%). Conclusion: The Chikungunya virus is still an ongoing emerging disease at the high jungle of northern Peru. It is an important cause of AFI, presenting non-specific clinical symptoms, thus the development of accurate and precise molecular techniques is important. Patients require precise and point of care laboratory diagnosis. The seasonality is probably related to the rain season and its consequence on the life cycle of the vector. Infections by this virus may go unnoticed in the national surveillance system.

Summary: Background: It is not known whether to continue or temporarily stop existing antihypertensive drugs in patients with acute stroke. Methods: We performed a prospective subgroup analysis of patients enrolled into the Efficacy of Nitric Oxide in Stroke (ENOS) trial who were randomised to continue vs stop prior antihypertensive therapy within 12 h of stroke onset. The primary outcome was functional outcome, assessed with the modified Rankin Scale at 90 days by observers blinded to treatment assignment, and analysed with ordinal logistic regression. Findings: Of 4011 patients recruited into ENOS from 2001 to 2014, 2097 patients were randomised to continue vs stop prior antihypertensive treatment, and 384 (18.3%, continue 185, stop 199) were enrolled within 12 h of ictus: mean (SD) age 71.8 (11.8) years, female 193 (50.3%), ischaemic stroke 342 (89.1%) and total anterior circulation syndrome 114 (29.7%). As compared with stopping, continuing treatment within 12 h of onset lowered blood pressure by 15.5/9.6 mmHg (p

Nocardia beijingensis é um patógeno humano oportunista, Gram-positivo, fracamente resistente ao álcool-ácido. Essa bactéria cresce aerobicamente, geralmente dentro de 2 a 14 dias e é encontrada principalmente no solo. As infecções por Nocardia afetam principalmente indivíduos com imunossupressão sistêmica, especialmente aqueles com imunidade celular comprometida. O estudo foi aprovado pelo Comitê de Ética em Pesquisa da Universidade Federal de Mato Grosso do Sul (parecer no 08915612.80000.0021) e o sujeito aceitou participar e assinou o Termo de Consentimento Livre e Esclarecido. Relatamos aqui o primeiro caso latino-americano de nocardiose associada a N. beijingensis em paciente com AIDS em terapia antirretroviral regular com carga viral indetectável. Paciente com 37 anos, sexo masculino, diagnosticado com AIDS em 2014 e em tratamento regular com tenofovir, lamivudina e efavirenz desde dezembro de 2015. Desenvolveu múltiplos abscessos cutâneos que não responderam à terapia antimicrobiana inicial. Concomitantemente, o paciente apresentava múltiplos nódulos no ápice pulmonar direito e tinha comprometimento do sistema nervoso central sem melhora após terapia empírica para tuberculose. O diagnóstico de nocardiose por N. beijingensis foi obtido pela cultura do líquido contido no abscesso cutâneo seguido da identificação da espécie por meio de técnicas de biologia molecular pelo sequenciamento do gene hsp65 e do gene16S rRNA, permitindo, por fim, a implantação da terapia com sulfametoxazol/trimetoprima com evolução clínica positiva, com resolução da nocardiose e sem recidiva da infecção. O diagnóstico incorreto de tuberculose e a prescrição de tuberculostáticos pode ser comum devido à sobreposição de sinais e sintomas entre as duas doenças. Entre os casos de formação de abscesso bacteriano que não respondem aos regimes de tratamento da tuberculose, pode ser necessário realizar um exame de cultura para o crescimento de Nocardia. Isso, juntamente com o sequenciamento das regiões do gene hsp65 e 16S rRNA em conjunto com testes fenotípicos, permite a identificação de espécies emergentes e a suscetibilidade antimicrobiana, a fim de fornecer terapias personalizadas que resolvam a infecção com sucesso.

Primitive neuroectodermal tumor (PNET) is part of the Ewing sarcoma family of tumors. The present case reports a primitive neuroectodermal tumor (PNET) of rare location in the bladder in a newborn. It was evaluated with prenatal ultrasound and postnatal tomography that revealed a mass in the posterior wall of the bladder.The patient underwent partial cystectomy with subsequent analysis of the surgical piece removed, the histopathological study indicated a tumor of mesenchymal origin, and immunohistochemical staining confirmed the diagnosis of PNET of the bladder. Satisfactory result and short-term follow-up.

Objective: We evaluated the value of resting-state EEG source biomarkers to characterize mild cognitive impairment (MCI) subjects with an Alzheimer’s disease (AD)-like cerebrospinal fluid (CSF) profile and to track neurodegeneration throughout the AD continuum. We further applied a resting-state functional MRI (fMRI)-driven model of source reconstruction and tested its advantage in terms of AD diagnostic accuracy. Methods: Thirty-nine consecutive patients with AD dementia (ADD), 86 amnestic MCI, and 33 healthy subjects enter the EEG study. All ADD subjects, 37 out of 86 MCI patients and a distinct group of 53 healthy controls further entered the fMRI study. MCI subjects were divided according to the CSF phosphorylated tau/β amyloid-42 ratio (MCIpos: ≥ 0.13, MCIneg: < 0.13). Using Exact low-resolution brain electromagnetic tomography (eLORETA), EEG lobar current densities were estimated at fixed frequencies and analyzed. To combine the two imaging techniques, networks mostly affected by AD pathology were identified using Independent Component Analysis applied to fMRI data of ADD subjects. Current density EEG analysis within ICA-based networks at selected frequency bands was performed. Afterwards, graph analysis was applied to EEG and fMRI data at ICA-based network level. Results: ADD patients showed a widespread slowing of spectral density. At a lobar level, MCIpos subjects showed a widespread higher theta density than MCIneg and healthy subjects; a lower beta2 density than healthy subjects was also found in parietal and occipital lobes. Evaluating EEG sources within the ICA-based networks, alpha2 band distinguished MCIpos from MCIneg, ADD and healthy subjects with good accuracy. Graph analysis on EEG data showed an alteration of connectome configuration at theta frequency in ADD and MCIpos patients and a progressive disruption of connectivity at alpha2 frequency throughout the AD continuum. Conclusions: Theta frequency is the earliest and most sensitive EEG marker of AD pathology. Furthermore, EEG/fMRI integration highlighted the role of alpha2 band as potential neurodegeneration biomarker.

Innovation is fundamental for all agri-food companies to increase competitiveness. Being extra-virgin olive oil (EVOO) a traditional food product (TFP), the main obstacle to innovation is its traditional nature. This study evaluated consumers’ acceptance for an EVOO with a naturally increased content of poliphenols, as it has been extracted through ultrasounds. This product has been compared with a set of emerging innovations that may be introduced in the next future. To this end, a choice experiment was carried out bent on the estimation of a Latent Class Model (LCM). A nationally-representative sample of EVOO consumers were involved in a web-based interview. The LCM analysis highlighted three segments of consumers: (1) innovative; (2) traditionalist; (3) cautious. Results showed that there is cluster of consumers willing to accept this innovation, therefore its introduction on the market appears to be possibly successful.

We report the first case of Myroides phaeus isolated from blood, causing bacteremia in an immunocompromised patient using the automated MicroScan Walk Away 96 system, followed by bacterial identification by amplification-sequencing of the 16S rDNA. The sequences obtained were compared with the reference sequence of the BLAST ® platform - National Library of Medicine, USA, and the isolation was identified as Myroides phaeus strain with 99.67 % identity in Blast report. In the literature we did not find previous reported cases of infections by this bacterium, however its pathogenic role is still controversial; therefore, this isolation alerts us to carry out an exhaustive surveillance of other possible acquisition routes. Keywords: Myroides, Bacteremia

Summary: Background: Through a comprehensive analysis of Italy's estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, we aimed to understand the patterns of health loss and response of the health-care system, and offer evidence-based policy indications in light of the demographic transition and government health spending in the country. Methods: Estimates for Italy were extracted from GBD 2017. Data on Italy are presented for 1990 and 2017, on prevalence, causes of death, years of life lost, years lived with disability, disability-adjusted life-years (DALYs), life expectancy at birth and at age 65 years, healthy life expectancy, and Healthcare Access and Quality (HAQ) Index. We compared the estimates for Italy with those of 15 other western European countries. Findings: The quality of the universal health system and healthy behaviours contribute to favourable overall health, even in comparison with other western European countries. In 2017, life expectancy and HAQ Index score in Italy were among the highest globally, with life expectancy at birth reaching 85·3 years for females and 80·8 for males in 2017, ranking Italy eighth globally for females and sixth for males, and an HAQ Index score of 94·9 in 2016 compared with 81·54 in 1990, keeping Italy ranked as ninth globally. Between 1990 and 2017 age-standardised death rates for cardiovascular diseases decreased by 53·7% (95% uncertainty interval −56·1 to −51·4), for neoplasms decreased by 28·2% (−32·3 to −24·6), and for transport injuries decreased by 62·1% (−64·6 to −59·2). However, population ageing is causing an increase in the burden of specific diseases, such as Alzheimer's disease and other dementias (DALYs increased by 77·9% [68·4 to 87·2]) and pancreatic (DALYs increased by 39·7% [28·4 to 51·7]) and uterine cancers (DALYs increased by 164·7% [129·7 to 202·5]). Behavioural risk factors, which are potentially modifiable, still have a strong effect, particularly on cardiovascular diseases and neoplasms. For instance, in 2017, 44 400 (41 200 to 47 800) cancer deaths were attributed to smoking, 12 000 (9600 to 14 800) to alcohol use, and 9500 (5400 to 14 200) to high body-mass index, while 47 000 (31 100 to 65 700) deaths due to cardiovascular diseases could be attributed to high LDL cholesterol, 28 700 (19 700 to 38 500) to diets low in whole grains, and 15 900 (8500 to 24 900) to low physical activity. Interpretation: Italy provides an interesting example of the results that can be achieved by a mix of relatively healthy lifestyles and a universal health system. Two main issues require attention, population ageing and gradual decrease of public health financing, which both pose several challenges to the future of Italy's health status. Our findings should be useful to Italy's policy makers and health system experts elsewhere. Funding: Bill & Melinda Gates Foundation.

Background: The infection caused by Mayaro virus (MAYV), which presents as an acute febrile illness, is considered a neglected tropical disease. The virus is an endemic and emerging pathogen in South America and the Caribbean, responsible for occasional and poorly characterized outbreaks. Currently there is limited information about its expansion and risk areas. Methods: A cross-sectional study was performed in 10 urban primary care health centers in the Cajamarca region of Peru from January to June 2017. A total of 359 patients with suspected febrile illness were assessed. RNA was extracted from serum samples, following which MAYV real-time reverse transcriptase PCR (RT-PCR) for the detection of the nsP1 gene was performed. Results: MAYV was detected in 11.1% (40/359) of samples after RT-PCR amplification and confirmatory DNA sequencing. Most infections were detected in the adult population aged 18–39 years (40%) and 40–59 years (32.5%). Headache was the most frequent symptom in patients with MAYV infection (77.5%), followed by fever (72.5%), myalgia (55.0%), and arthralgia (50.0%). During the study, most of the MAYV cases were seen in May (47.5%) and April (35.0%), corresponding to the dry season (months without rain). Conclusions: This study is novel in describing the presence of MAYV in Cajamarca, an Andean region of Peru. Symptoms are non-specific and can be confused with those of other arbovirus or bacterial infections. Molecular biology methods such as RT-PCR allow the timely and accurate detection of MAYV and could thus be considered as a tool for surveillance in endemic areas. Keywords: Mayaro virus, MAYV, RT-PCR, Togaviridae, Jungle fever

Introduction: Oropouche fever is an under-reported and emerging infectious disease caused by Oropouche virus (OROV). Its incidence is under-estimated mainly due to clinical similarities with other endemic arboviral diseases and the lack of specific diagnostic tests. We report the first outbreak of Oropouche fever in a western region of the Peruvian Amazon in Huanuco, Peru. Methods: A transversal study was carried out during an outbreak in the western Region of Huanuco, Peru between January and July of 2016. Blood samples of 268 patients with acute febrile syndrome were collected and analyzed for OROV via RT- PCR and genetic sequencing. Results: Of all 268 patients, 46 (17%) cases tested positive for OROV. The most common symptoms reported were headache with a frequency of 87% (n = 40) followed by myalgia with 76% (n = 35), arthralgia with 65.2% (n = 30), retro-ocular pain 60.8% (n = 28) and hyporexia with 50% (n = 23). Some patients showed a clinical presentation suggestive of severe OROV infection, of which 4.3% (n = 2) had low platelet count, 8.6% (n = 4) had intense abdominal pain, and 2.1% (n = 1) had a presentation with thoracic pain. Conclusion: This study reports an outbreak of OROV in a region where this virus was not previously identified. The disease caused by OROV is an emerging, underdiagnosed infection that requires further research to determine its virulence, pathogenesis, host range and vectors involved in the urban and sylvatic cycles as well as identifying new genotypes to implement sensitive and specific diagnostic tools that can be applied to endemic regions. Keywords: Oropouche, OROV, Peruvian Amazon, Infectious disease

Background: Huánuco is a central eastern region of Peru whose geography includes high forest and low jungle, as well as a mountain range that constitutes the inter-Andean valleys. It is considered a region endemic for dengue due to the many favorable conditions that facilitate transmission of the virus. Methods: A total of 268 serum samples from patients in Huánuco, Peru with an acute febrile illness were assessed for the presence of dengue virus (DENV) via RT-PCR and NS1, IgM, and IgG ELISA during December 2015 and March 2016. Results: DENV was detected in 25% of samples via RT-PCR, 19% of samples by NS1 antigen ELISA, and 10.5% of samples by IgM ELISA. DENV IgG was detected in 15.7% of samples by ELISA. The most frequent symptoms associated with fever across all groups were headache, myalgia, and arthralgia, with no significant difference between the four test methods Conclusions: In this study, DENV was identified in up to 25% of the samples using the standard laboratory method. In addition, a correlation was established between the frequency of positive results and the serological tests that determine NS1, IgM, and IgG. There is an increasing need for point-of-care tests to strengthen epidemiological surveillance in Peru. Keywords: Dengue, DENV, Arbovirus, Diagnosis, Peru

This study identified structural and functional brain connectivity alterations in two independent samples of patients along the posterior cortical atrophy (PCA) disease course. Twenty-one PCA patients and 44 controls were recruited from two expert centres. Microstructural damage of white matter (WM) tracts was assessed using probabilistic tractography; resting state (RS) functional connectivity of brain networks was explored using a model free approach; grey matter (GM) atrophy was investigated using voxel-based morphometry. Compared with controls, common patterns of damage across PCA patients included: GM atrophy in the occipital-temporal-parietal regions; diffusion tensor (DT) MRI alterations of the corpus callosum and superior (SLF) and inferior longitudinal fasciculi (ILF) bilaterally; and decreased functional connectivity of the occipital gyri within the visual network and the precuneus and posterior cingulum within the default mode network (DMN). In PCA patients with longer disease duration and greater disease severity, WM damage extended to the cingulum and RS functional connectivity alterations spread within the frontal, dorsal attentive and salience networks. In PCA, reduced DMN functional connectivity was associated with SLF and ILF structural alterations. PCA patients showed distributed WM damage. Altered RS functional connectivity extends with disease worsening from occipital to temporo-parietal and frontostriatal regions, and this is likely to occur through WM connections. Future longitudinal studies are needed to establish trajectories of damage spreading in PCA and whether a combined DT MRI/RS functional MRI approach is promising in monitoring the disease progression. Keywords: Posterior cortical atrophy, White matter, Diffusion tensor MRI, Resting state functional connectivity, Default mode network, Visual network

Objetivos: Estimar la proporción de personas que precisan cuidados paliativos y de soporte de atención primaria en su domicilio y describir sus características. Métodos: Estudio descriptivo de las Redes Centinelas Sanitarias de cinco comunidades autónomas, entre octubre de 2007 y marzo de 2008, en 282.216 personas atendidas por 218 profesionales de atención primaria. Se incluyeron pacientes que recibían en el domicilio un cuidado integral, activo y continuado, en quienes la expectativa médica no era prolongar la supervivencia sino conseguir la más alta calidad de vida para el paciente, la familia y el entorno de cuidadores. En un cuestionario estándar se recogieron la edad, el sexo, el tipo de paciente, la enfermedad subyacente y otras variables relacionadas con el proceso. Se estimaron las prevalencia crudas y ajustadas por edad. Resultados: De los 400 hombres y las 792 mujeres que cumplían los criterios de inclusión, el 12,5% eran terminales en sentido estricto. La media de edad fue de 82,4 años, mayor en los pacientes con incapacidad funcional (82,9 años) que los terminales (78,9 años) (pObjectives: To estimate the proportion of people requiring palliative and support care at home in primary care and to describe their characteristics. Methods: A descriptive study was carried out by five Spanish sentinel networks between October 2007 and March 2008 in 282,216 people attended by 218 general practitioners and nurses. Patients receiving comprehensive, active and continued care at home were included if the aim was not to prolong life but to achieve the best quality of life for the patient, the family and the carers. A standard form was used to collect data on age, sex, type of patient, underlying diseases and other variables related to the process. Crude and age-adjusted rates were estimated. Results: Of the 400 men and 792 women registered, 12% were strictly terminal. The mean age was 82.4years and was higher in patients with functional disability (82.9years) than in terminally-ill patients (78.9 years) (p

Background: Although transthoracic echocardiography (TTE) is an excellent noninvasive screening test for pulmonary hypertension, the physiologic range of Doppler echocardiography-derived pulmonary pressures remains not completely investigated. The aim of the present study was, therefore, to explore the full spectrum of pulmonary pressures and right ventricular (RV) functional indexes by TTE in healthy subjects and to investigate clinical and echocardiographic correlates., Methods: A random sample of 1,480 healthy individuals (mean age, 36.1 ± 15.5 years; range, 20-80 years; 905 men) underwent a comprehensive TTE. Pulmonary artery systolic pressure (PASP), mean pressure, and pulmonary vascular resistance were estimated by standard Doppler echocardiography formulas. In addition, RV diastolic (Doppler transtricuspid inflow measurements) and systolic indexes (RV fractional area change, RV tissue Doppler peak systolic velocity, tricuspid annular plane systolic excursion) were calculated., Results: PASP and mean pulmonary artery pressure values were significantly higher in subjects aged &gt; 50 years and in those with a BMI &gt; 30 kg/m2. In particular, a PASP &gt; 40 mm Hg was found in 118 subjects (8%) of those aged &gt; 50 years and in 103 (7%) of those with a BMI &gt; 30 kg/m2. No differences by age were registered in RV systolic indexes and in pulmonary vascular resistances. On multivariate analysis, in the overall study population, age, BMI, mitral E/e' ratio, and left ventricular stroke volume were the only independent predictors of PASP., Conclusions: This study delineates an estimate of pulmonary hemodynamics in a wide age range cohort of healthy subjects. Pulmonary pressures increased with age and BMI, as expected.

Objectives: To explore the full range of right heart dimensions and the impact of long-term intensive training in athletes., Background: Although echocardiography has been widely used to distinguish the athlete's heart from pathologic left ventricular (LV) hypertrophy, only few reports have described right ventricular (RV) and right atrial (RA) adaptations to extensive physical exercise., Methods: 650 top-level athletes [395 endurance- (ATE) and 255 strength-trained (ATS); 410 males (63.1%); mean age 28.4 ± 10.1; 18-40 years] and 230 healthy age- and sex-comparable controls underwent a transthoracic echocardiographic exam. Along with left heart parameters, right heart measurements included: RV end-diastolic diameters at the basal and mid-cavity level; RV base-to-apex length; RV proximal and distal outflow tract diameters; RA long and short diameters; and RA area. Tricuspid annular plane systolic excursion and RV tissue Doppler systolic peak velocity were assessed as indexes of RV systolic function. Pulmonary artery systolic pressure (PASP) was estimated from the peak tricuspid regurgitant velocity., Results: ATS showed increased sum of wall thickness and relative wall thickness, whereas left atrial volume, LV end-diastolic volume, LV stroke volume and PASP were significantly higher in ATE. RV and RA measurements were all significantly greater in ATE than in ATS and controls. ATE also showed improved early diastolic RV function, whereas RV systolic indexes were comparable among groups. On multivariate analysis, type and duration of training (p<0.01), PASP (p<0.01) and LV stroke volume (p<0.001) were the only independent predictors of the main RV and RA dimensions in athletes., Conclusions: This study delineates the upper limits of RV and RA dimensions in highly-trained athletes. Right heart measurements were all significantly greater in elite endurance-trained athletes than in age- and sex-matched strength athletes and controls. This should be considered as a "physiologic phenomenon" when evaluating athletes for sports eligibility., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Aims: To test whether two-dimensional longitudinal strain (2DSE) performed after revascularization by percutaneous coronary intervention (PCI) could predict left ventricular (LV) remodeling in patients with recent non-ST elevation myocardial infarction (NSTEMI)., Methods: In 70 patients (62.7 ± 8.7 years) with recent NSTEMI (between 72 hours and 14 days), undergoing coronary angiography for recurrent angina, myocardial deformation parameters were measured by 2DSE before and 24 hours after reperfusion therapy. Strain in all LV segments was averaged to obtain a global value (Global longitudinal Strain--GLS). Infarct size was estimated by clinical parameters and cardiac markers. After 6 months from intervention, LV negative remodeling was defined as lack of improvement of LV function, with increase in LV end-diastolic volume of greater than or equal than 15%., Results: At follow-up, patients were subdivided into remodeled (n=32) and non-remodeled (n = 38) groups. Patients with negative LV remodeling had significantly lower baseline LV ejection fraction (44.8±6.9 vs. 48.7 ± 5.5 %; p < 0.05), higher peak troponin I (p < 0.001) and reduced GLS (- 10.6±6.1 vs - 17.6 ± 6.7 % p < 0.001) than those without LV remodeling. GLS showed a close correlation with peak troponin I after PCI (r = 0.64, P < 0.0001) and LV WMSI (r = 0.42, p < 0.01). By multivariable analysis, diabetes mellitus (P < 0.005), peak of Troponin I after PCI (P < 0.0005), GLS at baseline (OR: 4.3; p < 0.0001), and lack of improvement of GLS soon after PCI (OR: 1.45, P < 0.01) were powerful independent predictors of negative LV remodelling at follow-up. In particular, a GLS ≤ 12 % showed a sensitivity and a specificity respectively of 84.8% and 87.8% to predict negative LV remodelling at follow-up., Conclusions: in patients with recent NSTEMI, longitudinal LV global and regional speckle-tracking strain measurements are powerful independent predictors of LV remodeling after reperfusion therapy., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: Although the physiologic range of pulmonary artery systolic pressure (PASP) has been reported, data on how it is manifested in athletes are limited. The aim of the present study was to explore the full spectrum of PASP and the long-term training impact in a large population of highly trained athletes., Methods: Six hundred fifteen consecutive athletes (370 endurance-trained athletes [ATEs] vs 245 strength-trained athletes [ATSs]; 28.4 ± 10.1 years old) and 230 healthy control subjects (27.5 ± 11.3 years old) underwent transthoracic echocardiography. PASP was estimated by measuring maximal tricuspid regurgitant jet velocity (TRV) with the modified Bernoulli equation. The ratio of TRV to right ventricular outflow tract time-velocity integral (TRV/RVOTTVI) was obtained as a correlate of pulmonary vascular resistance (PVR)., Results: Left ventricular (LV) mass index and ejection fraction did not differ significantly between the two groups of athletes. Conversely, ATSs showed an increased sum of wall thickness and relative wall thickness, whereas LV end-diastolic diameter, LV stroke volume, peak TRV, and PASP were significantly higher in ATEs. The ratio between transmitral E wave and tissue Doppler e' wave was not different among the three groups. The ratio TRV/RVOTTVI was ≤ 0.2 (ie, normal PVR) in all subjects. A TRV value > 2.5 m/s was observed in 76 athletes (12.3%). By multivariable analysis, age (P < .01), type and duration of training (P < .01), and LV stroke volume (P < .001) were the only independent predictors of PASP in athletes., Conclusions: This study delineates the full range of resting TRV and derived PASP in highly trained athletes. The upper physiologic limit of PASP in endurance athletes may reach 40 mm Hg, in line with the greater increase in stroke volume. This should be considered a "physiologic phenomenon" when evaluating athletes for sports eligibility.

Background: In patients with idiopathic dilated cardiomyopathy (DCM) a more depressed left atrial (LA) booster pump function has been observed compared to ischemic patients although under similar loading conditions, and attributed both to altered LA overload and to LA larger involvement in the myopathic process., Aim of the Study: To detect by speckle-tracking two-dimensional strain (2DSE) LA systolic dysfunction in patients with either idiopathic or ischemic DCM, and to assess in these patients possible correlation between LA myocardial function and exercise capacity during cardiopulmonary test., Methods: Three-hundred-fourteen patients (52.4+/-11.2 years) with either idiopathic (160 patients) or ischemic (154 patients) DCM underwent cardiopulmonary stress test, standard Doppler echo and 2DSE analysis of atrial longitudinal strain in the basal segments of LA septum and LA lateral wall, and in LA roof., Results: The two groups were comparable for most of clinical variables. LV volumes, ejection fraction, stroke volume, and mitral valve effective regurgitant orifice were similar between the two groups. No significant differences were evidenced in Doppler transmitral inflow measurements. Also LA diameter and maximal volume were similar between the two groups. Conversely, LA active empting volume and fraction were both lower in patients with idiopathic DCM (<0.001). Peak systolic myocardial atrial strain was significantly reduced in patients with idiopathic DCM compared with ischemic DCM at the level of all the analyzed atrial segments (p<0.0001). By multivariable analysis, in the overall population, ischemic aetiology of DCM (p<0.0001) and LA volume (p<0.001) were the only independent determinants of LA lateral wall systolic strain. On the other hand, LA lateral wall systolic strain (p<0.0001) and LA volume (p<0.001) were powerful independent predictors of peak oxygen consumption during cardiopulmonary exercise testing., Conclusions: Two-dimensional strain represents a promising non-invasive technique to assess LA atrial myocardial function in patients with DCM. LA systolic deformation is more depressed in idiopathic compared with ischemic DCM, and is closely associated with functional capacity during effort. Future longitudinal studies are warranted to further our understanding of the natural history of LA myocardial function, the extent of reversibility of LA dysfunction with therapy, and the possible prognostic impact of such indexes in patients with congestive heart failure.

Background: Conflicting data have been reported about the nature (physiologic versus pathologic) of left ventricular (LV) hypertrophy in master athletes., Aim of the Study: To analyze LV and right ventricular (RV) myocardial function in master athletes with LV hypertrophy induced by either endurance or strength training., Methods: Standard Doppler echo and colour Doppler Myocardial Imaging (DMI) of LV and of RV basal lateral walls were performed in 40 competitive master (>45 years) endurance athletes (ATE), in 20 master strength-trained athletes (ATS) and 25 age-matched healthy sedentary subjects, all males. By use of DMI, the following parameters of myocardial function were assessed: systolic peak velocities, precontraction time, contraction time, early (E(m)) and late (A(m)) diastolic peak velocities, E(m)/A(m) ratio, relaxation time., Results: The two groups were comparable for age, but ATS at rest showed higher heart rate, systolic blood pressure, and body surface area. LV mass index did not significantly differ between the two groups of athletes. However, ATS showed increased wall thickness and relative wall thickness, while LV stroke volume and both LV and RV end-diastolic diameters were greater in ATE. All transmitral and transtricuspid Doppler indexes were higher in ATE. DMI analysis showed in ATE higher E(m) and E(m)/A(m) ratio at the level of both RV and LV lateral walls. In the overall population of athletes, linear regression models evidenced independent positive association of RV peak E(m) velocity with both LV stroke volume and maximal workload achieved by bicycle ergometer (both p<0.001)., Conclusions: RV early diastolic myocardial function is positively influenced by preload increase in master athletes and represents an independent determinant of cardiac performance during physical effort. Therefore, colour DMI may be taken into account to distinguish different cardiac adaptation to either endurance or strength sport training in master athletes.

Background: Transthoracic Doppler echocardiography of internal mammary artery grafts (MAGs) has been tested by the supraclavicular approach, but little information is available about the parasternal approach., Objective: To evaluate the usefulness of parasternal transthoracic Doppler echocardiography to assess the patency of left and right MAGs., Patients and Methods: Forty-eight patients with previous MAGs were divided into two groups on the basis of coronary angiography: 42 patients had patent MAGs and six patients had severe MAG stenosis. Doppler echocardiography of MAGs was performed on all patients, both at baseline and after low-dose dipyridamole infusion. Systolic and diastolic time-velocity integrals and their ratios were obtained, and MAG flow reserve was calculated., Results: Patients with patent MAGs had a predominant diastolic flow, while a prominent systolic pattern was found in the presence of MAG stenosis. In patients with stenosis, baseline Doppler analysis showed a lower diastolic peak velocity (DPV) (P<0.01), diastolic time-velocity integral (P<0.05), and diastolic and systolic time-velocity integral ratios (both P<0.005), and a reduced MAG flow reserve (P<0.001). In the overall population, when adjusting for clinical variables, a multilinear regression analyis underscored MAG flow reserve (beta=0.38, P<0.01) and baseline DPV (beta=0.29, P<0.05) as independent determinants of MAG stenosis (cumulative R2=0.25, P<0.005)., Conclusions: Doppler echocardiographic evaluation of MAGs is a reliable, noninvasive tool to assess MAG patency and functional status of the vessel. MAG blood flow reserve and baseline DPV are independent determinants of MAG stenosis.