Detection of parechovirus A in respiratory, gastrointestinal, and neurological clinical samples of pediatric patients from Panama (2014-2015).

Parechovirus A (PeV-A, Parechovirus, Picornaviridae) are human pathogens associated with mild to severe gastrointestinal and respiratory diseases in young children. While several studies have investigated the association of PeV-A with human disease, little is known about its epidemiology or detection in Latin America. Between the years 2014 and 2015, a total of 200 samples were collected from Panamanian pediatric patients aged < 16 years old exhibiting symptoms associated with respiratory (n = 64), gastrointestinal (n = 68), or neurological (n = 68) diseases. These samples were gathered from patients who had previously received negative diagnoses for the main respiratory viruses, rotavirus, and neurological viruses like herpes virus, enterovirus, and cytomegalovirus. The presence of PeV-A was analyzed by real time RT-PCR.Eight positive PeV-A infections (4.0%, 95% CI: 1.7 to 7.7) were detected: two in respiratory samples (3.0%, 95% CI: 0.3 to 10.8), five in gastrointestinal samples (7.3%, 95% CI: 2.4 to 16.3), and one in cerebrospinal fluid (1.5%, 95% CI: 1.4 to 7.9). The study provides evidence of PeV-A circulation in Panama and the data collectively, remarked on the importance of considering PeV-A in the Panamanian pediatric diagnostic landscape, especially when conventional testing for more common viruses yields negative results.

Assessing the impact of transcatheter aortic valve replacement on myocardial work indices and left ventricular diastolic function in aortic valve stenosis patients.

BACKGROUND: Aortic valve stenosis (AS) is the most common valvular heart disease worldwide. When timely intervention is performed, aortic valve replacement can improve patients' quality and duration of life. Load-independent left ventricular (LV) functional assessments, such as myocardial work indices (MWIs) and LV diastolic function parameters, could help clinicians decide on the optimal timing of intervention. AIMS: To evaluate the reliability of MWI in AS patients and the changes in MWI and LV diastolic function after transcatheter aortic valve replacement (TAVR). METHODS: We enrolled 53 consecutive patients with severe AS undergoing TAVR admitted between March 2021 and November 2021. MWIs and LV diastolic function were assessed before and after TAVR for each patient. RESULTS: All MWIs and LV diastolic function indices improved after TAVR. The degree of MWIs improvement was higher in patients with lower prior-TAVR MWI values, while the more severe the impairment of diastolic function, the greater the post-TAVR benefit. CONCLUSION: The introduction of myocardial work parameters into the routine assessment of patients with AS could improve our understanding of cardiac performance and aid in identifying the optimal timing for surgical or percutaneous treatment.

Early Transmission Dynamics, Spread, and Genomic Characterization of SARS-CoV-2 in Panama.

We report an epidemiologic analysis of 4,210 cases of infection with severe acute respiratory syndrome coronavirus 2 and genetic analysis of 313 new near-complete virus genomes in Panama during March 9-April 16, 2020. Although containment measures reduced R0 and Rt, they did not interrupt virus spread in the country.

Anorexia nervosa-related cardiopathy in children with physical instability: prevalence, echocardiographic characteristics and reversibility at mid-term follow-up.

Prompt detection of cardiovascular abnormalities in children with anorexia nervosa and physical instability requiring hospitalization is essential to identify patients at higher cardiovascular risk. We studied all anorexia nervosa children requiring admission at Paediatric Institute in the period 2015-2019. Anorexia nervosa cardiopathy at admission was defined by the presence of at least two of the following clinical findings: pericardial effusion, mitral regurgitation, bradycardia, mitral billowing, aortic regurgitation, altered LV morphology and ECG abnormalities. Echocardiographic data were compared with those registered at 3-8-month follow-up and with data from a healthy population. Thirty-eight anorexia nervosa children were examined. Prevalence of anorexia nervosa cardiopathy at admission was 63% (24 patients). Pericardial effusion, bradycardia and mitral regurgitation were present together in 26% of patients. Most cardiovascular changes recovered at follow-up. Anorexia nervosa cardiopathy was associated with significantly lower left ventricle end-diastolic diameters and mass, and higher E wave, E/A and E/e' ratios and left ventricle sphericity index values vs healthy population and vs anorexia nervosa children without cardiopathy (p<0.05). Left ventricle global longitudinal strain was significantly reduced only in anorexia nervosa cardiopathy patients but recovered, whereas end-diastolic diameters, E/A ratio and sphericity index values remained impaired.Conclusion: Among anorexia nervosa children requiring hospitalization, those presenting several cardiac findings together express an acute anorexia nervosa cardiopathy which is characterized by worse LV filling, geometry and subclinical myocardial deformation impairment. Despite treatment, in those patients, some alterations persist at mid-term follow-up. What is Known: • Cardiac and electrocardiographic changes are present in anorexia nervosa children at diagnosis or during stable disease, and most recover after body-weight treatment. • It is unknown if anorexia nervosa children with more severe cardiac impairment during hospitalization present higher cardiovascular-risk profile despite treatment. What is New: • In anorexia nervosa children needing hospitalization for physical reasons, prevalence of acute anorexia nervosa cardiopathy at admission is high, around 60%. • By advanced echocardiography, children with anorexia nervosa cardiopathy at admission have a worse cardiac filling, impaired cardiac geometry and systolic deformation that only partially recover at mid-term follow-up.

Fractional flow reserve in patients with reduced ejection fraction.

AIMS: Fractional flow reserve (FFR) has never been investigated in patients with reduced ejection fraction and associated coronary artery disease (CAD). We evaluated the impact of FFR on the management strategies of these patients and related outcomes. METHODS AND RESULTS: From 2002 to 2010, all consecutive patients with left ventricular ejection fraction (LVEF) ≤50% undergoing coronary angiography with ≥1 intermediate coronary stenosis [diameter stenosis (DS)% 50-70%] treated based on angiography (Angiography-guided group) or according to FFR (FFR-guided group) were screened for inclusion. In the FFR-guided group, 433 patients were matched with 866 contemporary patients of the Angiography-guided group. For outcome comparison, 617 control patients with LVEF >50% were included. After FFR, stenotic vessels per patient were significantly downgraded compared with the Angiography-guided group (1.43 ± 0.98 vs. 1.97 ± 0.84; P < 0.001). This was associated with lower revascularization rate (52% vs. 62%; P < 0.001) in the FFR-guided vs. the Angiography-guided group. All-cause death at 5 years of follow-up was significantly lower in the FFR-guided as compared with Angiography-guided group [22% vs. 31%. HR (95% CI) 0.64 (0.51-0.81); P < 0.001]. Similarly, rate of major adverse cardiovascular and cerebrovascular events (MACCE: composite of all-cause death, myocardial infarction, revascularization, and stroke) was significantly lower in the FFR-guided group [40% vs. 46% in the Angiography-guided group. HR (95% CI) 0.81 (0.67-0.97); P = 0.019]. Higher rates of death and MACCE were observed in patients with reduced LVEF compared with the control cohort. CONCLUSIONS: In patients with reduced LVEF and CAD, FFR-guided revascularization was associated with lower rates of death and MACCE at 5 years as compared with the Angiography-guided strategy. This beneficial impact was observed in parallel with less coronary artery bypass grafting and more patients deferred to percutaneous coronary intervention or medical therapy.

Toward Learning Trustworthily from Data Combining Privacy, Fairness, and Explainability: An Application to Face Recognition.

In many decision-making scenarios, ranging from recreational activities to healthcare and policing, the use of artificial intelligence coupled with the ability to learn from historical data is becoming ubiquitous. This widespread adoption of automated systems is accompanied by the increasing concerns regarding their ethical implications. Fundamental rights, such as the ones that require the preservation of privacy, do not discriminate based on sensible attributes (e.g., gender, ethnicity, political/sexual orientation), or require one to provide an explanation for a decision, are daily undermined by the use of increasingly complex and less understandable yet more accurate learning algorithms. For this purpose, in this work, we work toward the development of systems able to ensure trustworthiness by delivering privacy, fairness, and explainability by design. In particular, we show that it is possible to simultaneously learn from data while preserving the privacy of the individuals thanks to the use of Homomorphic Encryption, ensuring fairness by learning a fair representation from the data, and ensuring explainable decisions with local and global explanations without compromising the accuracy of the final models. We test our approach on a widespread but still controversial application, namely face recognition, using the recent FairFace dataset to prove the validity of our approach.

Genotypes of human metapneumovirus circulating during 2010-2012 in children from Panama.

Human metapneumovirus (HMPV) is a common causative agent of severe respiratory tract infections in children under 5 years old, the elderly and immunocompromised patients, being responsible for 5-15% of all viral respiratory infections requiring hospitalization. Though HMPV was included in the surveillance program for respiratory viruses in 2010, its genotype distribution remains unknown. Herein, 45 positive samples to HMPV from children ≤5 years old were characterized by phylogenetic analysis based on N gene sequence. Results showed the co-circulation of four sub-lineages: A2a (8.8%), A2b (55.5%), B1 (15.6%), and B2 (20%), demonstrating the genetic heterogeneity of HMPV circulating in Panamá.

Genetic variability of human respiratory syncytial virus group B in Panama reveals a novel genotype BA14.

In Panama, human respiratory syncytial virus (HRSV) is responsible of 20-40% of acute respiratory infections in children under 5 years old. Currently, little is known about the genetic variability of HRSV in Central America and the Caribbean. Recently, we reported the genetic variability of HRSV-A, however; no studies on HRSV-B in Panama have been described yet. In this study, 24 sequences of Panamanian HRSV-B, from children (<5 years) with acute respiratory infections (ARI), collected from July 2008 to November 2012 were analyzed. All sequences share the characteristic 60-nt duplication of the BA strains. Six Panamanian strains grouped with the BA10 genotype and 12 samples clustered together in a separate monophyletic clade with an aLRT support value of 0.92 and an intra-group p-distance less than 0.07. This fulfills the criteria to consider a new genotype in HRSV, which we named BA14 genotype. Another six strains remain unclassified, but closely related to BA9, BA11, or the new BA14 genotypes, according to their genetic p-distance. Different amino acid substitutions in the Panamanian HRSV-B strains were observed, some previously described and others found only on Panamanian strains. This study contributes to the knowledge of the genetic variability and evolution of HRSV in Central America.

Oligomerization and Membrane-binding Properties of Covalent Adducts Formed by the Interaction of α-Synuclein with the Toxic Dopamine Metabolite 3,4-Dihydroxyphenylacetaldehyde (DOPAL).

Oxidative deamination of dopamine produces the highly toxic aldehyde 3,4-dihydroxyphenylacetaldehyde (DOPAL), enhanced production of which is found in post-mortem brains of Parkinson disease patients. When injected into the substantia nigra of rat brains, DOPAL causes the loss of dopaminergic neurons accompanied by the accumulation of potentially toxic oligomers of the presynaptic protein α-synuclein (aS), potentially explaining the synergistic toxicity described for dopamine metabolism and aS aggregation. In this work, we demonstrate that DOPAL interacts with aS via formation of Schiff-base and Michael-addition adducts with Lys residues, in addition to causing oxidation of Met residues to Met-sulfoxide. DOPAL modification leads to the formation of small aS oligomers that may be cross-linked by DOPAL. Both monomeric and oligomeric DOPAL adducts potently inhibit the formation of mature amyloid fibrils by unmodified aS. The binding of aS to either lipid vesicles or detergent micelles, which results in a gain of α-helix structure in its N-terminal lipid-binding domain, protects the protein against DOPAL adduct formation and, consequently, inhibits DOPAL-induced aS oligomerization. Functionally, aS-DOPAL monomer exhibits a reduced affinity for small unilamellar vesicles with lipid composition similar to synaptic vesicles, in addition to diminished membrane-induced α-helical content in comparison with the unmodified protein. These results suggest that DOPAL could compromise the functionality of aS, even in the absence of protein oligomerization, by affecting the interaction of aS with lipid membranes and hence its role in the regulation of synaptic vesicle traffic in neurons.

Detection of human bocavirus type 1 infection in Panamanian children with respiratory illness.

The human bocavirus (HBoV) was added as a new member of the Parvoviridae family in 2005 upon its discovery in nasopharyngeal aspirates from children with respiratory infection. Recently, there has been increasing evidence of worldwide circulation of HBoV; however, in Latin America few studies have been conducted. In order to detect the circulation of HBoV in Panama, based on the National Flu Surveillance System, we developed this retrospective, cross-sectional study, from January 2011 to January 2012. Children younger than 6 years old who presented with respiratory disease were enrolled in this study. Nasopharyngeal swabs were taken in sentinel surveillance sites. Samples were tested to detect mRNA from HBoV, as well as viral RNA and DNA from others respiratory viruses. A total of 1078 patients were enrolled in this study. Overall, 44 (4.1%) of the patients presented HBoV. The most common symptoms were cough (84.6%), fever (82.1%), rhinorrhea (74.4%), and sore throat (38.5%). Less than half (45.5%) of HBoV infected patients presented with monoinfection while 54.5% of cases presented with coinfection with others respiratory viruses. Both, outpatients and inpatients were included in this study. Outpatients corresponded to 52.3% of the cases and 47.7% were inpatients. Coinfection was observed in the 50% of the inpatient cases. Phylogenetic analyses indicated that the circulating strains belonged to different clades of HBoV genotype 1. Taken together, our results support the pathogenic nature of this viral agent, especially in younger children.

What Is the Added Benefit of Oropharyngeal Swabs Compared to Nasal Swabs Alone for Respiratory Virus Detection in Hospitalized Children Aged <10 Years?

We evaluated the added value of collecting both nasal and oropharyngeal swabs, compared with collection of nasal swabs alone, for detection of common respiratory viruses by reverse transcription-polymerase chain reaction in hospitalized children aged <10 years. Nasal swabs had equal or greater sensitivity than oropharyngeal swabs for detection of respiratory syncytial virus, adenovirus, human metapneumovirus, rhinovirus, and influenza virus but not parainfluenza virus. The addition of an oropharyngeal swab, compared with use of a nasal swab alone, increased the frequency of detection of each respiratory virus by no more than 10% in children aged <10 years.

Early unfractionated heparin treatment in patients with STEMI - trial design and rationale.

The early unfractionated heparin (UFH) treatment in patients with ST-elevation myocardial infarction (STEMI) is a single-center, open-label, randomized controlled trial. The study population are patients with STEMI that undergo primary percutaneous coronary intervention (PPCI). The trial was designed to investigate whether early administration of unfractionated heparin immediately after diagnosis of STEMI is beneficial in terms of patency of infarct-related coronary artery (IRA) when compared to established UFH administration at the time of coronary intervention. The patients will be randomized in 1:1 fashion in one of the two groups. The primary efficacy endpoint of the study is Thrombolysis in myocardial infarction (TIMI) flow grades 2 and 3 on diagnostic coronary angiography. Secondary outcome measures are: TIMI flow after PPCI, progression to cardiogenic shock, 30-day mortality, ST-segment resolution, highest Troponin I and Troponin I values at 24 hours. The safety outcome is bleeding complications. The study of early heparin administration in patients with STEMI will address whether pretreatment with UFH can increase the rate of spontaneous reperfusion of infarct-related coronary artery.

Experiences in the use of multiple doses of convalescent plasma in critically ill patients with COVID-19: An early phase 1 descriptive study.

Background: At the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, transfusion of coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) emerged as a potential therapeutic strategy to help patients severely afflicted by COVID-19. The efficacy of CCP has been controversial as it depends on many variables pertaining to the plasma donor and the patient with COVID-19, for example, time of convalescence or symptoms onset. This feasibility and descriptive study aimed to assess the safety of multiple doses of CCP in mechanically ventilated, intubated patients with respiratory failure due to COVID-19. Methods: A cohort of 30 patients all experiencing severe respiratory failure and undergoing invasive mechanical ventilation in an intensive care unit, received up to five doses of 300-600 mL of CCP on alternate days (0, 2, 4, 6, and 8) until extubation, futility, or death. Results: Nineteen patients received five doses, seven received four, and four received two or three doses. At 28-day follow-up mark, 57% of patients recovered and were sent home, and the long-term mortality rate was 27%. Ten severe adverse events reported in the study were unrelated to CCP transfusion. Independent of the number of transfused doses, most patients had detectable levels of total and neutralizing antibodies in plasma. Conclusion: This study suggests that transfusion of multiple doses of CCP is safe. This strategy may represent a viable option for future studies, given the potential benefit of CCP transfusions during the early stages of infection in unvaccinated populations and in settings where monoclonal antibodies or antivirals are contraindicated or unavailable.

Coronary disease in refractory cardiac arrest undergoing resuscitation with extracorporeal membrane oxygenation.

AIMS: Because re-establishment of spontaneous circulation (ROSC) in patients with cardiac arrest is frequently not achieved by conventional cardiopulmonary resuscitation (C-CPR), selected patients may undergo resuscitation with extracorporeal membrane oxygenation (E-CPR). We compared angiographic features and percutaneous coronary intervention (PCI) between patients undergoing E-CPR and those with ROSC after C-CPR. METHODS AND RESULTS: Forty-nine consecutive E-CPR patients undergoing immediate coronary angiography admitted between August 2013 and August 2022 were matched to 49 patients with ROSC after C-CPR. Multivessel disease (69.4% vs. 34.7%; P = 0.001), ≥ 50% unprotected left main (ULM) stenosis (18.4% vs. 4.1%; P = 0.025), and ≥1 chronic total occlusion (CTO) (28.6% vs. 10.2%; P = 0.021) were more often documented in E-CPR group. There was no significant differences in the incidence, features, and distribution of acute culprit lesion which was present in >90%. Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) (27.6 vs. 13.4; P = 0.002) and GENSINI (86.2 vs. 46.0; P = 0.001) scores were increased in E-CPR group. Optimal cut-off predicting E-CPR was 19.75 for SYNTAX (sensitivity 74%, specificity 87%) and 60.50 (sensitivity 69%, specificity 75%) for GENSINI score. More lesions were treated (1.3 vs. 1.1 lesions/patient; P = 0.002) and stents implanted (2.0 vs. 1.3/patient; P < 0.001) in E-CPR group. Final TIMI three flow was comparable (88.6% vs. 95.7%; P = 0.196) but residual SYNTAX (13.6 vs. 3.1; P < 0.001) and GENSINI (36.7 vs. 10.9; P < 0.001) scores remained increased in E-CPR group. CONCLUSION: Extracorporeal membrane oxygenation patients have more multivessel disease, ULM stenosis, and CTO but similar incidence, features, and distribution of acute culprit lesion. Despite more complex PCI, revascularization is less complete.

Coronary features across the spectrum of out-of-hospital cardiac arrest with ST-elevation myocardial infarction (CAD-OHCA study).

AIM: We hypothesized that adult patients with out-of-hospital cardiac arrest (OHCA) and ST-elevation myocardial infarction (STEMI) requiring prolonged resuscitation have more severe coronary artery disease (CAD) than those responding rapidly, and more severe CAD than patients with STEMI without OHCA. METHODS: Consecutive conscious and comatose OHCA patients with STEMI after reestablishment of spontaneous circulation (ROSC), and patients with refractory OHCA undergoing veno-arterial extracorporeal membrane oxygenation (E-CPR OHCA) were compared to STEMI without OHCA (STEMI no OHCA). CAD severity was assessed by a single physician blinded to the resuscitation method, time to ROSC and level of consciousness. RESULTS: Between 2016 and 2022, 71 conscious OHCA, 157 comatose OHCA, 50 E-CPR OHCA and 101 STEMI no OHCA underwent immediate coronary angiography. Acute culprit lesion was documented less often in OHCA (88.1% vs 97%; p = 0.009) but complete occlusion was more frequent (68.8% vs 58.4%; p = 0.038) than in STEMI no OHCA. SYNTAX score was 5.6 in STEMI no OHCA, 10.2 in conscious OHCA, 13.4 in comatose OHCA and 26.8 in E-CPR OHCA (p < 0.001). There was a linear correlation between SYNTAX score and delay to ROSC/ECMO initiation (r2 = 0.61; p < 0.001). Post PCI culprit TIMI 3 flow was comparable between the groups (≥86%). SYNTAX score was among independent predictors of 5-year survival which was significantly decreased in comatose OHCA (56.1%) and E-CPR OHCA (36.0%) compared to conscious OHCA (83.1%) and STEMI no OHCA (88.1%). CONCLUSION: Compared to STEMI no OHCA, OHCA was associated with increased incidence of acute coronary occlusion and more complex non culprit CAD which progressively increased from conscious OHCA to E-CPR OHCA. Severity of CAD was associated with increased delays to ROSC/ECMO initiation and decreased long term survival.

High genetic diversity and predominance of Rhinovirus A and C from Panamanian hospitalized children under five years with respiratory infections.

BACKGROUND: Human Rhinoviruses (HRVs) have high genetic diversity and three species have been described: HRV-A, HRV-B, and the recently recognized HRV-C, which has been rapidly identified worldwide. FINDINGS: In the present study, we report the frequency and diversity of Human Rhinovirus (HRV) strains circulating in Panama from children hospitalized with respiratory infections. CONCLUSIONS: HRVs of species A, B and C have been identified with a predominance of HRV-A and HRV-C over HRV-B, and marked genetic diversity within each species.

Incidence of influenza and other respiratory viruses among pregnant women: A multi-country, multiyear cohort.

OBJECTIVE: To quantify rates of influenza illness and assess value of influenza vaccination among pregnant women in Panama and El Salvador. METHODS: Pregnant women were enrolled and followed each week in a prospective cohort study to identify acute respiratory illnesses (ARI). Nasopharyngeal swabs obtained from women with febrile ARI were tested by reverse-transcription polymerase chain reaction for influenza and other respiratory viruses. RESULTS: We enrolled 2556 women between October 2014 and April 2017. Sixteen percent developed at least one ARI; 59 had two ARI, and five had three ARI for a total of 463 ARI. Women in El Salvador and Panama contributed 297 person-years (py) and 293 py, respectively, during influenza circulation. Twenty-one (11%) of 196 sampled women tested positive for influenza. Influenza incidence was 5.0/100 py (5.7/100 py in El Salvador and 4.3/100 py in Panama). Only 13% of women in El Salvador and 43% in Panama had been vaccinated against influenza before influenza epidemics (P < 0.0001). CONCLUSIONS: One in six pregnant women developed ARI and more than one in ten ARI were attributable to vaccine-preventable influenza. While women were at risk of influenza, few had been vaccinated before each epidemic. Such findings suggest the utility of evaluations to optimize vaccine timing and coverage.

Lower cognitive scores among toddlers in birth cohorts with acute respiratory illnesses, fevers, and laboratory-confirmed influenza.

BACKGROUND: We established cohorts to assess associations between viral influenza and cognitive development to inform the value proposition of vaccination. METHODS: From 2014 through 2017, we called women seeking care at four prenatal clinics in Panama and El Salvador to identify acute respiratory illnesses (ARIs). Within 2 weeks of childbirth, mothers were asked to enroll their neonates in the cognitive development study. Staff obtained nasopharyngeal swabs from children with febrile ARIs for real-time reverse transcription polymerase chain reaction (rtPCR) detection of viral RNA. Toddlers were administered Bayley developmental tests at ages 12 and 18-24 months. We used multilevel linear regression to explore associations between Bayley scores, ARIs, fever, and laboratory-confirmed influenza, controlling for maternal respiratory or Zika illnesses, infant influenza vaccination, birth during influenza epidemics, and the number of children in households. RESULTS: We enrolled 1567 neonates of which 68% (n = 1062) underwent developmental testing once and 40% (n = 623) twice. Children with previous ARIs scored an average of 3 points lower on their cognitive scores than children without ARIs (p = 0.001). Children with previous fevers scored an average of 2.1 points lower on their cognitive scores than afebrile children (p = 0.02). In the second year, children with previous laboratory-confirmed influenza scored 4 points lower on their cognitive scores than children without influenza (p = 0.04, after controlling for first Bayley cognitive scores). CONCLUSIONS: ARIs and fever during infancy were associated with lower Bayley scores at 12 months, and laboratory-confirmed influenza was associated with lower cognitive scores at 24 months suggesting the potential value of vaccination to prevent non-respiratory complications of influenza.

Incidence of respiratory virus illness and hospitalizations in a Panama and El Salvador birth cohort, 2014-2018.

Background: Respiratory viruses remain a key cause of early childhood illness, hospitalization, and death globally.The recent pandemic has rekindled interest in the control of respiratory viruses among paediatric populations. We estimate the burden of such viruses among children <2 years. Methods: Enrolled neonates were followed until two years of age. Weekly active symptom monitoring for the development of acute respiratory illnesses (ARI) defined as cough, rhinorrhoea, difficulty breathing, asthenia, anorexia, irritability, or vomiting was conducted. When the child had ARI and fever, nasopharyngeal swabbing was performed, and samples were tested through singleplex RT-PCR. Incidence of respiratory viruses was calculated by dividing the number of laboratory-confirmed detections by the person-time accrued during weeks when that virus was detectable through national surveillance then corrected for under-ascertainment among untested children. Findings: During December 2014-November 2017, 1567 enrolled neonates contributed 2,186.9 person-years (py). Six in ten (64·4%) children developed ARI (total 2493 episodes). Among children <2 years, incidence of respiratory syncytial virus (RSV)-associated ARI episodes (21·0, 95%CI 19·3-22·8, per 100py) and rhinovirus-associated (20·5, 95%CI 20·4-20·7) were similar and higher than parainfluenza 1-3-associated (14·2, 95%CI 12·2-16·1), human metapneumovirus-associated (9·2, 95%CI 7·7-10·8), influenza-associated (5·9, 95%CI 4·4-7·5), and adenovirus-associated ARI episodes (5·1, 95%CI 5·0-5·2). Children aged <3 months had the highest rates of RSV ARI (49·1, 95%CI 44·0-54·1 per 100py) followed by children aged 3-5 (25·1, 95%CI 20·1-30·0), 6-11 (17·6, 95%CI 13·2-21·9), and 12-23 months (11·9, 95%CI 10·8-12·9). One in ten children with RSV was referred to the hospital (2·5, 95%CI 2·1-2·8, per 100py). Interpretation: Children frequently developed viral ARI and a substantive proportion required hospital care. Such findings suggest the importance of exploring the value of new interventions and increasing uptake of existing prevention measures to mitigate burden of epidemic-prone respiratory viruses. Funding: The study was supported by the Centers for Disease Control and Prevention.

Modulation of Insulin Sensitivity by Exercise Training: Implications for Cardiovascular Prevention.

The beneficial effects of physical activity on the cardiovascular system nowadays have achieved the relevance of clinical evidence. In fact, several studies have documented the benefits of exercise training in the prevention of the cardiovascular risk. Abnormalities of insulin signaling transduction account for the impairment of insulin sensitivity and development of insulin resistance, which, in turn, is responsible for the enhancement of cardiovascular risk. Insulin sensitivity is related to the degree of physical activity, and physical training has been shown to ameliorate insulin action in insulin-resistant subjects. This effect is mediated by the improvement of the molecular abnormalities that are responsible of the insulin resistance, contributing in this way to restore the physiological insulin sensitivity. However, it should be underlined that mechanisms that account for this phenomenon are extremely complex and still unclear. Further studies are required to better clarify the molecular basis of the exercise-evoked improvement of insulin signal. Graphical abstract.