During summer 2007 Italy has experienced an epidemic caused by Chikungunya virus - the first large outbreak documented in a temperate climate country - with approximately 161 laboratory confirmed ...cases concentrated in two bordering villages in North-Eastern Italy comprising 3,968 inhabitants. The seroprevalence was recently estimated to be 10.2%. In this work we provide estimates of the transmission potential of the virus and we assess the efficacy of the measures undertaken by public health authorities to control the epidemic spread. To such aim, we developed a model describing the temporal dynamics of the competent vector, known as Aedes albopictus, explicitly depending on climatic factors, coupled to an epidemic transmission model describing the spread of the epidemic in both humans and mosquitoes. The cumulative number of notified cases predicted by the model was 185 on average (95% CI 117-278), in good agreement with observed data. The probability of observing a major outbreak after the introduction of an infective human case was estimated to be in the range of 32%-76%. We found that the basic reproduction number was in the range of 1.8-6 but it could have been even larger, depending on the density of mosquitoes, which in turn depends on seasonal meteorological effects, besides other local abiotic factors. These results confirm the increasing risk of tropical vector-borne diseases in temperate climate countries, as a consequence of globalization. However, our results show that an epidemic can be controlled by performing a timely intervention, even if the transmission potential of Chikungunya virus is sensibly high.
Intellectual disability (ID) is characterized by impairments in the cognitive processes and in the tasks of daily life. It encompasses a clinically and genetically heterogeneous group of ...neurodevelopmental disorders often associated with autism spectrum disorder (ASD). Social and communication abilities are strongly compromised in ASD. The prevalence of ID/ASD is 1-3%, and approximately 30% of the patients remain without a molecular diagnosis. Considering the extreme genetic locus heterogeneity, next-generation sequencing approaches have provided powerful tools for candidate gene identification. Molecular diagnosis is crucial to improve outcome, prevent complications, and hopefully start a therapeutic approach. Here, we performed parent-offspring trio whole-exome sequencing (WES) in a cohort of 60 mostly syndromic ID/ASD patients and we detected 8 pathogenic variants in genes already known to be associated with ID/ASD (
,
,
,
,
,
,
, and
. We found four de novo disruptive variants of four novel candidate ASD/ID genes:
,
,
,
. We additionally selected via bioinformatic tools many variants in unknown genes that alone or in combination can contribute to the phenotype. In conclusion, our data confirm the efficacy of WES in detecting pathogenic variants of known and novel ID/ASD genes.
Describing and understanding close proximity interactions between infant and family members can provide key information on transmission opportunities of respiratory infections within households. ...Among respiratory infections, pertussis represents a public health priority. Pertussis infection can be particularly harmful to young, unvaccinated infants and for these patients, family members represent the main sources of transmission. Here, we report on the use of wearable proximity sensors based on RFID technology to measure face-to-face proximity between family members within 16 households with infants younger than 6 months for 2-5 consecutive days of data collection. The sensors were deployed over the course of approximately 1 year, in the context of a national research project aimed at the improvement of infant pertussis prevention strategies. We investigated differences in close-range interactions between family members and we assessed whether demographic variables or feeding practices affect contact patterns between parents and infants. A total of 5,958 contact events were recorded between 55 individuals: 16 infants, 4 siblings, 31 parents and 4 grandparents. The aggregated contact networks, obtained for each household, showed a heterogeneous distribution of the cumulative time spent in proximity with the infant by family members. Contact matrices defined by age and by family role showed that most of the contacts occurred between the infant and other family members (70%), while 30% of contacts was among family members (infants excluded). Many contacts were observed between infants and adults, in particular between infant and mother, followed by father, siblings and grandparents. A larger number of contacts and longer contact durations between infant and other family members were observed in families adopting exclusive breastfeeding, compared to families in which the infant receives artificial or mixed feeding. Our results demonstrate how a high-resolution measurement of contact matrices within infants' households is feasible using wearable proximity sensing devices. Moreover, our findings suggest the mother is responsible for the large majority of the infant's contact pattern, thus being the main potential source of infection for a transmissible disease. As the contribution to the infants' contact pattern by other family members is very variable, vaccination against pertussis during pregnancy is probably the best strategy to protect young, unvaccinated infants.
Despite thousands of influenza cases annually recorded by surveillance systems around the globe, estimating the transmission patterns of seasonal influenza is challenging.
We develop an ...age-structured mathematical model to influenza transmission to analyze ten consecutive seasons (from 2010 to 2011 to 2019-2020) of influenza epidemiological and virological data reported to the Italian surveillance system.
We estimate that 18.4-29.3% of influenza infections are detected by the surveillance system. Influenza infection attack rate varied between 12.7 and 30.5% and is generally larger for seasons characterized by the circulation of A/H3N2 and/or B types/subtypes. Individuals aged 14 years or less are the most affected age-segment of the population, with A viruses especially affecting children aged 0-4 years. For all influenza types/subtypes, the mean effective reproduction number is estimated to be generally in the range 1.09-1.33 (9 out of 10 seasons) and never exceeding 1.41. The age-specific susceptibility to infection appears to be a type/subtype-specific feature.
The results presented in this study provide insights on type/subtype-specific transmission patterns of seasonal influenza that could be instrumental to fine-tune immunization strategies and non-pharmaceutical interventions aimed at limiting seasonal influenza spread and burden.
Rett syndrome (RTT) is a severe neurodevelopmental disorder associated with mutations in either MECP2, CDKL5 or FOXG1. The precise molecular mechanisms that lead to the pathogenesis of RTT have yet ...to be elucidated. We recently reported that expression of GluD1 (orphan glutamate receptor δ-1 subunit) is increased in iPSC-derived neurons obtained from patients with mutations in either MECP2 or CDKL5. GluD1 controls synaptic differentiation and shifts the balance between excitatory and inhibitory synapses toward the latter. Thus, an increase in GluD1 might be a critical factor in the etiology of RTT by affecting the excitatory/inhibitory balance in the developing brain. To test this hypothesis, we generated iPSC-derived neurons from FOXG1(+/-) patients. We analyzed mRNA and protein levels of GluD1 together with key markers of excitatory and inhibitory synapses in these iPSC-derived neurons and in Foxg1(+/-) mouse fetal (E11.5) and adult (P70) brains. We found strong correlation between iPSC-derived neurons and fetal mouse brains, where GluD1 and inhibitory synaptic markers (GAD67 and GABA AR-α1) were increased, whereas the levels of a number of excitatory synaptic markers (VGLUT1, GluA1, GluN1 and PSD-95) were decreased. In adult mice, GluD1 was decreased along with all GABAergic and glutamatergic markers. Our findings further the understanding of the etiology of RTT by introducing a new pathological event occurring in the brain of FOXG1(+/-) patients during embryonic development and its time-dependent shift toward a general decrease in brain synapses.
Nosocomial infections place a substantial burden on health care systems and represent one of the major issues in current public health, requiring notable efforts for its prevention. Understanding the ...dynamics of infection transmission in a hospital setting is essential for tailoring interventions and predicting the spread among individuals. Mathematical models need to be informed with accurate data on contacts among individuals.
We used wearable active Radio-Frequency Identification Devices (RFID) to detect face-to-face contacts among individuals with a spatial resolution of about 1.5 meters, and a time resolution of 20 seconds. The study was conducted in a general pediatrics hospital ward, during a one-week period, and included 119 participants, with 51 health care workers, 37 patients, and 31 caregivers. Nearly 16,000 contacts were recorded during the study period, with a median of approximately 20 contacts per participants per day. Overall, 25% of the contacts involved a ward assistant, 23% a nurse, 22% a patient, 22% a caregiver, and 8% a physician. The majority of contacts were of brief duration, but long and frequent contacts especially between patients and caregivers were also found. In the setting under study, caregivers do not represent a significant potential for infection spread to a large number of individuals, as their interactions mainly involve the corresponding patient. Nurses would deserve priority in prevention strategies due to their central role in the potential propagation paths of infections.
Our study shows the feasibility of accurate and reproducible measures of the pattern of contacts in a hospital setting. The obtained results are particularly useful for the study of the spread of respiratory infections, for monitoring critical patterns, and for setting up tailored prevention strategies. Proximity-sensing technology should be considered as a valuable tool for measuring such patterns and evaluating nosocomial prevention strategies in specific settings.
Providing understandable information to patients is necessary to achieve the aims of the Informed Consent process: respecting and promoting patients' autonomy and protecting patients from harm. In ...recent decades, new, primarily digital technologies have been used to apply and test innovative formats of Informed Consent. We conducted a systematic review to explore the impact of using digital tools for Informed Consent in both clinical research and in clinical practice. Understanding, satisfaction and participation were compared for digital tools versus the non-digital Informed Consent process.
We searched for studies on available electronic databases, including Pubmed, EMBASE, and Cochrane. Studies were identified using specific Mesh-terms/keywords. We included studies, published from January 2012 to October 2020, that focused on the use of digital Informed Consent tools for clinical research, or clinical procedures. Digital interventions were defined as interventions that used multimedia or audio-video to provide information to patients. We classified the interventions into 3 different categories: video only, non-interactive multimedia, and interactive multimedia.
Our search yielded 19,579 publications. After title and abstract screening 100 studies were retained for full-text analysis, of which 73 publications were included. Studies examined interactive multimedia (29/73), non-interactive multimedia (13/73), and videos (31/73), and most (34/38) studies were conducted on adults. Innovations in consent were tested for clinical/surgical procedures (26/38) and clinical research (12/38). For research IC, 21 outcomes were explored, with a positive effect on at least one of the studied outcomes being observed in 8/12 studies. For clinical/surgical procedures 49 outcomes were explored, and 21/26 studies reported a positive effect on at least one of the studied outcomes.
Digital technologies for informed consent were not found to negatively affect any of the outcomes, and overall, multimedia tools seem desirable. Multimedia tools indicated a higher impact than videos only. Presence of a researcher may potentially enhance efficacy of different outcomes in research IC processes. Studies were heterogeneous in design, making evaluation of impact challenging. Robust study design including standardization is needed to conclusively assess impact.
The last 2019/20 northern hemisphere influenza season overlapped with the first wave of coronavirus disease 2019 (COVID-19) pandemic. Italy was the first western country where severe acute ...respiratory syndrome coronavirus 2 (SARS-CoV-2) spread to a significant extent. In this representative cross-sectional survey, we aimed to describe some opinions and attitudes of the Italian general population towards both influenza vaccination and the COVID-19 pandemic, and to identify potential modifiers of the decision-making process regarding the uptake of the 2020/21 influenza vaccine. A total of 2543 responses were analyzed. Although most (74.8%) participants valued influenza vaccination positively and declared that it should be mandatory, some misconceptions around influenza persist. The general practitioner was the main source of trusted information on influenza vaccines, while social networks were judged to be the least reliable. Younger and less affluent individuals, subjects not vaccinated in the previous season, and those living in smaller communities showed lower odds of receiving the 2020/21 season influenza vaccination. However, the COVID-19 pandemic may have positively influenced the propensity of being vaccinated against 2020/21 seasonal influenza. In order to increase influenza vaccination coverage rates multidisciplinary targeted interventions are needed. The role of general practitioners remains crucial in increasing influenza vaccine awareness and acceptance by effective counselling.
The research on the anti-SARS-CoV-2 vaccines and their commercialization is an opportunity to test and consolidate the current knowledge along with the diverse available tools related to vaccine ...communication.
In this paper we explore the value of a multidisciplinary approach in this field: vaccine communication activities can be combined with insights from data science, risk communication, behavior change, design thinking and digital marketing. Methodologies derived from innovation and human-centered design can contribute to the development and testing of vaccine promotion campaigns, speeding up processes and streamlining the production of evidence in this area. The multiple activities involving the anti-SARS-CoV-2 vaccine could be the fertile ground in which to develop, test and refine effective frameworks to transfer data acquired through listening strategies into effective vaccine promotion campaigns. The World Health Organization's Vaccine Safety Net is an interesting example of trusted information sources that aim toward using digital tools and innovative methodologies for communicating science-based information on vaccine safety at the global level.
Iron deficiency (ID) is one of the most frequent comorbidities in patients with heart failure (HF). ID is estimated to be present in up to 50% of outpatients and is a strong independent predictor of ...HF outcomes. ID has been shown to reduce quality of life, exercise capacity and survival, in both the presence and absence of anemia. The most recent 2016 guidelines recommend starting replacement treatment at ferritin cutoff value <100 mcg/l or between 100 and 299 mcg/l when the transferrin saturation is <20%. Beyond its effect on hemoglobin, iron plays an important role in oxygen transport and in the metabolism of cardiac and skeletal muscles. Mitochondria are the most important sites of iron utilization and energy production. These factors clearly have roles in the diminished exercise capacity in HF. Oral iron administration is usually the first route used for iron repletion in patients. However, the data from the IRONOUT HF study do not support the use of oral iron supplementation in patients with HF and a reduced ejection fraction, because this treatment does not affect peak VO
2
(the primary endpoint of the study) or increase serum ferritin levels. The FAIR-HF and CONFIRM-HF studies have shown improvements in symptoms, quality of life and functional capacity in patients with stable, symptomatic, iron-deficient HF after the administration of intravenous iron (i.e., FCM). Moreover, they have shown a decreased risk of first hospitalization for worsening of HF, as later confirmed in a subsequent meta-analysis. In addition, the EFFECT-HF study has shown an improvement in peak oxygen consumption at CPET (a parameter generally considered the gold standard of exercise capacity and a predictor of outcome in HF) in patients randomized to receive ferric carboxymaltose. Finally, the AFFIRM AHF trial evaluating the effects of FCM administration on the outcomes of patients hospitalized for acute HF has found significantly fewer hospital readmissions due to HF among patients treated with FCM rather than placebo.
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