Controlled mitral valvuloplasty using steerable catheter- waist- formed balloon system: A clinical case series.

As the general population ages, the incidence of degenerative mitral stenosis (MS) among patients has increased. Percutaneous mitral valvuloplasty (PMV) has emerged as a well-established option for mitral rheumatic stenosis with specific characteristics. However, a blank therapeutic space must be filled with the treatment options for degenerative or rheumatic mitral stenosis in patients with many comorbidities and contraindication for valvuloplasty. We here present a comprehensive overview of the current possibilities, despite their scarce success. That is the reason why we propose a case series to facilitate a better understanding of our innovative technique in this challenging clinical context.

NANOGrav Data Hints at Primordial Black Holes as Dark Matter.

The NANOGrav Collaboration has recently published strong evidence for a stochastic common-spectrum process that may be interpreted as a stochastic gravitational wave background. We show that such a signal can be explained by second-order gravitational waves produced during the formation of primordial black holes from the collapse of sizeable scalar perturbations generated during inflation. This possibility has two predictions: (i) the primordial black holes may comprise the totality of the dark matter with the dominant contribution to their mass function falling in the range (10^{-15}÷10^{-11})M_{⊙} and (ii) the gravitational wave stochastic background will be seen as well by the Laser Interferometer Space Antenna experiment.

GW190521 Mass Gap Event and the Primordial Black Hole Scenario.

The LIGO/Virgo Collaboration has recently observed GW190521, the first binary black hole merger with at least the primary component mass in the mass gap predicted by the pair-instability supernova theory. This observation disfavors the standard stellar-origin formation scenario for the heavier black hole, motivating alternative hypotheses. We show that GW190521 cannot be explained within the primordial black hole (PBH) scenario if PBHs do not accrete during their cosmological evolution, since this would require an abundance which is already in tension with current constraints. On the other hand, GW190521 may have a primordial origin if PBHs accrete efficiently before the reionization epoch.

Public health and clinical approach to proactive management of frailty in multidimensional arena.

Background: Demographic changes have forced communities and people themselves to reshape ageing concepts and approaches and try to develop actions towards active and healthy ageing. In this context, the European Commission launched different private-public partnerships to develop new solutions and answers on questions related to this topic. The European Innovation Partnership on Active and Healthy Ageing, including topic related action groups as well reference sites committed towards a common action to facilitate active and healthy ageing, has contributed key elements for interventions, scaled up best practices and evaluated impact of their action to drive innovation across many regions in Europe over the past years. Methods: This paper describes action taken by A3 action group in the European Innovation Partnership on Active and Healthy Ageing. This paper gives an overview of how the partnership combined the view on frailty coming from public health as well as the clinical management. Results: Within different European regions, to tackle frailty, EIPonAHA partners have conceptualized functional decline and frailty, making use of good practice models working well on community programs. The A3 Group of EIPonAHA has worked alongside a process of innovation, targeting all ageing citizens with the clear goal of involving communities in the preventive approach. Conclusion: Engagement needs of older people with a focus on functionally rather than disease management as primary objective is considered as an overarching concept, also embracing adherence, compliance, empowerment, health literacy, shared decision-making, and activation. Furthermore, training of staff working with ageing people across all sectors needs to be implemented and evaluated in future studies.

Primordial Black Hole Dark Matter: LISA Serendipity.

There has recently been renewed interest in the possibility that the dark matter in the Universe consists of primordial black holes (PBHs). Current observational constraints leave only a few PBH mass ranges for this possibility. One of them is around 10^{-12} M_{⊙}. If PBHs with this mass are formed due to an enhanced scalar-perturbation amplitude, their formation is inevitably accompanied by the generation of gravitational waves (GWs) with frequency peaked in the mHz range, precisely around the maximum sensitivity of the LISA mission. We show that, if these primordial black holes are the dark matter, LISA will be able to detect the associated GW power spectrum. Although the GW source signal is intrinsically non-Gaussian, the signal measured by LISA is a sum of the signal from a large number of independent sources suppressing the non-Gaussianity at detection to an unobservable level. We also discuss the effect of the GW propagation in the perturbed Universe. PBH dark matter generically leads to a detectable, purely isotropic, Gaussian and unpolarized GW signal, a prediction that is testable with LISA.

Candidate genes in panic disorder: meta-analyses of 23 common variants in major anxiogenic pathways.

The utilization of molecular genetics approaches in examination of panic disorder (PD) has implicated several variants as potential susceptibility factors for panicogenesis. However, the identification of robust PD susceptibility genes has been complicated by phenotypic diversity, underpowered association studies and ancestry-specific effects. In the present study, we performed a succinct review of case-control association studies published prior to April 2015. Meta-analyses were performed for candidate gene variants examined in at least three studies using the Cochrane Mantel-Haenszel fixed-effect model. Secondary analyses were also performed to assess the influences of sex, agoraphobia co-morbidity and ancestry-specific effects on panicogenesis. Meta-analyses were performed on 23 variants in 20 PD candidate genes. Significant associations after correction for multiple testing were observed for three variants, TMEM132D rs7370927 (T allele: odds ratio (OR)=1.27, 95% confidence interval (CI): 1.15-1.40, P=2.49 × 10(-6)), rs11060369 (CC genotype: OR=0.65, 95% CI: 0.53-0.79, P=1.81 × 10(-5)) and COMT rs4680 (Val (G) allele: OR=1.27, 95% CI: 1.14-1.42, P=2.49 × 10(-5)) in studies with samples of European ancestry. Nominal associations that did not survive correction for multiple testing were observed for NPSR1 rs324891 (T allele: OR=1.22, 95% CI: 1.07-1.38, P=0.002), TPH1 rs1800532 (AA genotype: OR=1.46, 95% CI: 1.14-1.89, P=0.003) and HTR2A rs6313 (T allele: OR=1.19, 95% CI: 1.07-1.33, P=0.002) in studies with samples of European ancestry and for MAOA-uVNTR in female PD (low-active alleles: OR=1.21, 95% CI: 1.07-1.38, P=0.004). No significant associations were observed in the secondary analyses considering sex, agoraphobia co-morbidity and studies with samples of Asian ancestry. Although these findings highlight a few associations, PD likely involves genetic variation in a multitude of biological pathways that is diverse among populations. Future studies must incorporate larger sample sizes and genome-wide approaches to further quantify the observed genetic variation among populations and subphenotypes of PD.

Effects of concurrent aerobic and strength training on breast cancer survivors: a pilot study.

OBJECTIVES: The aim of the study was to evaluate the effects of a combined aerobic and strength program on physiological and psychological parameters in female breast cancer survivors. STUDY DESIGN: Randomised controlled trial. METHODS: 20 patients (age: 45.6 ± 2.7 yrs) surgically treated for breast cancer that had completed all cancer therapies at least 6 months before and with no contraindications to physical activity, were recruited and randomly assigned to an intervention group (n = 10) and a control group (n = 10). Intervention group patients attend to a 24-week combined aerobic and strength training program. Physiological (i.e. VO2max, bioelectrical impedance test, maximal strength of principal muscular groups) and psychological (i.e. functional assessment of chronic illness therapy-fatigue: FACIT-F) parameters were assessed at baseline and after 24 weeks. RESULTS: After 24 weeks the intervention group showed significant improvement in VO2max (38.8%), strength of upper and lower limbs (ranging from 13 to 60%) and decrease in fat mass percentage (-6.3%). The FACIT-F showed significant increase in all of the three scores that can be derived (FACIT-F Trial outcome: 13%; FACT-G total score: 18%; FACIT-F total score: 15%) showing patient's quality of life (QOL) improvement. No significant change in all the parameters was found for the control group. CONCLUSION: These results show the positive effects of a combined aerobic and strength training program on breast cancer survivors and underline the importance of the early inclusion of structured physical activity in the rehabilitation protocol.

Age of onset in obsessive-compulsive disorder: admixture analysis with a large sample.

BACKGROUND: Research into age of onset in obsessive-compulsive disorder (OCD) has indicated significant differences between patients with early and late onset of the disorder. However, multiple criteria have been used arbitrarily for differentiating between early- and late-onset OCD, rendering inconsistent results that are difficult to interpret. METHOD: In the current study, admixture analysis was conducted in a sample of 377 OC patients to determine the number of underlying populations of age of onset and associated demographic and clinical characteristics. Various measures of anxiety, depression, co-morbidity, autism, OCD, tics and attention deficit hyperactivity disorder (ADHD) symptoms were administered. RESULTS: A bimodal age of onset was established and the best-fitting cut-off score between early and late age of onset was 20 years (early age of onset ≤19 years). Patients with early age of onset were more likely to be single. Early age of onset patients demonstrated higher levels of OCD severity and increased symptoms on all OCD dimensions along with increased ADHD symptoms and higher rates of bipolar disorder. CONCLUSIONS: It is suggested that 20 years is the recommended cut-off age for the determination of early versus late age of onset in OCD. Early age of onset is associated with a generally graver OCD clinical picture and increased ADHD symptoms and bipolar disorder rates, which may be related to greater functional implications of the disorder. We propose that age of onset could be an important marker for the subtyping of OCD.

Association of ethnicity with antipsychotic dosage using STRUCTURE analysis.

Several studies have examined whether ethnicity as an independent factor can influence the individual's dosage of antipsychotics. However, there has been inconsistency in the results of these studies, particularly between white and non-white populations. This retrospective study tests the hypothesis of different dosing of antipsychotics in white Europeans vs. non-white Europeans considering both the self-reported ethnicity and the geographical ancestry calculated using 196 DNA markers.We collected self-reported ethnicity and DNA samples from 209 schizophrenia patients. We tested the association between self-reported and genetically-determined ethnicity with the chlorpromazine equivalent dose of each antipsychotic prescribed at the time of the assessment.We did not find any significant difference between self-reported white European -ethnicity and chlorpromazine equivalent doses (p=0.972). Furthermore, when we considered the geographical ancestry determined by the 196 SNPs, we could not find any correlation between the European ancestry and chlorpromazine equivalent dose.Our preliminary analysis shows that there is no evidence that different ethnic groups receive different dose of antipsychotics.

Possible association of nicotinic acetylcholine receptor gene (CHRNA4 and CHRNB2) polymorphisms with nicotine dependence in Japanese males: an exploratory study.

INTRODUCTION: Smoking is a leading global cause of avoidable mortality. It has been reported that the nicotinic acetylcholine receptor (CHRNA4 and CHRNB2) genes might be associated with smoking behavior in several ethnic populations. However, no study between the 2 genes and nicotine dependence (ND) using a Japanese population has been reported. METHODS: We examined the association between ND and 5 single nucleotide polymorphisms (SNPs) within the CHRNA4 and 3 SNPs within the CHRNB2 using a well characterized sample of 558 Japanese healthy male workers with a relatively homogeneous background. The Fagerström test for nicotine dependence (FTND) was used to quantify the degree of ND. Additionally, we explored the effect of gene-gene interactions of the 2 genes on ND. RESULTS: We found CHRNB2 rs4845652 genotypes to be associated with FTND scores under an additive genetic model: rs4845652 T-allele carriers had lower ND levels (p=0.038; when adjusted for smoking duration: p=0.052). Furthermore, we demonstrated a possible gene-gene interaction of CHRNA4 and CHRNB2 on ND in a dose-dependent manner: those smokers with CHRNA4 rs1044397 GG or GA genotypes along with CHRNB2 rs4845652 CC genotype are likely to demonstrate higher ND scores. DISCUSSION: These findings suggest that CHRNB2 rs4845652 T-allele carriers may be associated with lower levels of ND, and that certain allelic combinations of CHRNA4 and CHRNB2 might be correlated with higher ND levels. This preliminary study has certain limitations (issues such as sample size/power and multiple testing) that need to be taken into account, and the present work thus has an experimental nature.

Gene expression profiling of phytoplasma-infected Madagascar periwinkle leaves using differential display.

Phytoplasmas are small (0.2-0.8 µm), wall-less, pleiomorphic prokaryotes responsible of numerous economically important plant diseases. They are characterized by a very small genome and are obligate parasites of phloem tissues and some insects that act as vectors of infection. To investigate molecular mechanisms involved in pathogenesis, the differential display technique was here applied to identify plant genes whose transcription was significantly altered in leaves of Madagascar periwinkle (Catharanthus roseus (L.) G.Don) infected by 'Candidatus Phytoplasma pyri'. We detected, reamplified, cloned, and sequenced 16 putative differentially expressed cDNA fragments. Northern blot analysis revealed that seven of the 16 genes identified were up-regulated following phytoplasma infection, while three genes were down-regulated. The remaining six genes did not show significant changes in the level of expression. Identified genes are mainly involved in plant defence/stress responses, protein metabolism and transport, transcriptional regulation, vesicle trafficking, and carbohydrate metabolism. The possible role played by these genes in the phytoplasma infection is discussed.

Go for it! Exercising makes you happy and strong.

Despite it is generally recognized the beneficial role of physical activity, large portion of the population is physically inactive. Very alarmingly, the well-known gender gap in physical activity is constantly increasing. Several barriers obstacle women to perform physical activity although exercising would be of paramount importance for their health in particular during pregnancy and menopause. In addition to physical health benefits, physical activity may influence well-being and resilience, greatly impacting on quality of life. Here we explore the relationship between physical activity resilience and well-being in a group of 1107 female residents in the Metropolitan area of Naples.

Digital Innovation in Healthcare: A Device with A Method for Monitoring, Managing and Preventing the Risk of Chronic Polypathological Patients.

New digital technologies can have a huge impact on the traditional healthcare sector, both from a clinical and economic perspective. Doctors and health specialists will increasingly need technology to improve the services they provide to their patients. Here a novel patented device for automatic processing of clinical data of chronic poly-pathological patients is presented. The invention consists of a reconfigurable equipment that allows the assessment of clinical risk severity indexes that can be customized for polypathological patients and which acts both as a decision support system for specialist doctors in the diagnosis and treatment phases, and as a monitoring system in the clinical environment.

Association study of tardive dyskinesia and five DRD4 polymorphisms in schizophrenia patients.

Tardive dyskinesia (TD) is a side effect of chronic antipsychotic medication exposure. Abnormalities in dopaminergic activity in the nigro-striatal system have been most often suggested to be involved because the agents that cause TD share in common potent antagonism of dopamine D(2) receptors (DRD2). Thus, a number of studies have focused on the association of dopamine system gene polymorphisms and TD, with the most consistent findings being an association between TD and the Ser9Gly polymorphism of the DRD3 gene and the TaqIA site 3' of the DRD2 gene. The DRD4 gene codes for the third member of the D(2)-like dopamine receptor family, and the variable number tandem-repeat polymorphism in exon 3 of DRD4 has been associated with TD. However, other polymorphisms have not been thoroughly examined. In this study, we investigated five polymorphisms spanning the DRD4 gene and their association with TD in our European Caucasian sample (N=171). Although the exon 3 variable number tandem repeat was not associated with TD, haplotypes consisting of four tag polymorphisms were associated with TD in males. This study suggests that DRD4 may be involved in TD in the Caucasian population, although further replication studies are needed.

Smart Healthy Age-Friendly Environments - Policy Recommendations of the Thematic Network SHAFE.

The European Commission (DG SANTE) launched a call for proposals in November 2017 on strategic initiatives for a Joint Statement in 2018. Ten proposals were voted until December 7th in the European Union Health Policy Platform[1]; the proposal under the theme Smart Healthy Age-Friendly Environments (SHAFE)[2] was the most voted and was confirmed by the European Commission in March 2018. In this context, since March 2018, Cáritas Coimbra and AFEdemy Ltd are thus coordinating one of the three Thematic Networks for 2018, SHAFE, in close cooperation with main partners, such as the European Innovation Partnership on Active and Healthy Ageing (EIP-AHA), the European Innovation Partnership on Smart Cities and Communities (EIP-SCC), the Reference Sites Collaborative Network, the European Covenant on Demographic Change, Eurocities, the European Health Telematics Association (EHTEL), the European Connected Health Alliance (ECHAlliance), the European Construction, Built Environment and Energy Efficient Building Technology Platform (ECTP) and the European Centre for Social Welfare Policy and Research. SHAFE aims to facilitate the creation of healthy and friendly environments for all ages through the use of new technologies, towards the production of a comprehensive and participatory Joint Statement. This document was presented to the European Commission on 12 November 2018, with five main areas of recommendations to the EC, Member States and other local, regional and national organisations and is open for endorsement and implementation from this date onwards.

Public Prevention Plans to Manage Climate Change and Respiratory Allergic Diseases. Innovative Models Used in Campania Region (Italy): The Twinning Aria Implementation and the Allergy Safe Tree Decalogue.

In recent years, climate change has been influenced by air pollution, and this destructive combination has justifiably sounded an alarm for nations and many institutional bodies worldwide. Official reports state that the emission of greenhouse gases produced by human activity are growing, and consequently also the average temperature. The World Health Organization (WHO) believes that health effects expected in the future due to climate change will be dramatic, and has invited international groups to investigate potential remedies. A task force has been established by the Italian Society of Allergology, Asthma and Clinical Immunology (SIAAIC), with the aim to actively work on correlation between pollution and climate change. The Task Force provided prevention tools to suggest city leaders how to improve the health conditions of allergic people in public urban parks. The "Allergy Safe Tree Decalogue" suggests the preparation and maintenance of public low allergy-impact greenery. Through the Twinning ARIA project, the Division for the Promotion and Enhancement of Health Innovation Programs of Campania Region (Italy), sought to promote the implementation of the project in the regional Health System. The main objective will be to investigate the current use and usefulness of mobile phone Apps in the management of allergic respiratory disease, through Mobile Airways Sentinel networK (MASK), the Phase 3 of the ARIA initiative, based on the freely available MASK App (the Allergy Diary, Android and iOS platforms). The effects of these prevention activities will be registered and compared with monitoring efforts thanks to the Aerobiology Units, located throughout the Campania area. A joint effort between researchers and public administrations for the implementation of prevention plans coherently with the two models proposed in a specific area, i.e. the Decalogue for public administrations and the MASK Allergy Diary app for individual patients suffering from allergy, will be implemented as a pilot.

Predisposing and protective factors influencing suicide ideation, attempt, and death in patients accessing substance use treatment: a systematic review and meta-analysis protocol.

BACKGROUND: The lifetime risk of suicide in patients with substance use disorder is five to ten times the risk in the general population. Critically, up to 19% of patients continue to think about and attempt suicide even after accessing treatment. Therefore, suicidality represents a significant clinical concern in patients struggling with substance use that warrants careful investigation of the factors involved. While most previous research has relied on limited cross-sectional designs, a growing number of prospective studies are improving our understanding of the factors involved. However, a systematic study of these factors has not yet been conducted. METHODS: The primary objective of this review and possible meta-analysis will be to identify key risk and protective factors for suicide ideation, attempt, and death in patients accessing substance use treatment, guided by current models of suicide. Secondary and tertiary objectives will be to obtain pooled effect sizes for the factors identified and to disaggregate factors for suicidality before and after treatment, and for suicidal thought versus action. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we will conduct an electronic search of the literature using the databases Embase, Medline, PsycINFO, and Web of Science. Two authors will independently screen studies based on pre-specified inclusion and exclusion criteria, extract relevant data, and assess study quality. Observational and randomized-controlled studies will be included, whereas case-studies and reviews will be excluded. We will extract data on risk and protective factors associated with suicide ideation, attempt (odds or risk ratios), and death (hazard ratio). Given sufficient data (> 5 studies), we will calculate pooled effects using comprehensive meta-analysis. DISCUSSION: This systematic review will contribute to our knowledge of risk and protective factors for suicidality in patients before and after treatment. Understanding these factors will help define areas of research for further investigation to ultimately inform risk assessment and prevention strategies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (reference number: CRD42018076260).

An Approach to Prevent Frailty in Community Dwelling Older Adults: a pilot study performed in Campania region in the framework of the PERSSILAA project.

We developed and tested an innovative physical training method in older adults that embeds the gym program into everyday life in the most conservative way possible. Physical training was included in the activities of local parishes where older women from Southern Italy spend most of their free time and was delivered by trained physical therapists with the support of an ICT tool known as CoCo. 113 older women (aged 72.0 [69.0-75.0] years) noncompliant to conventional exercise programs participated to the study. 57 of them underwent the final anthropometric assessment and 50 the final physical tests. In study completers handgrip strength and physical performance evaluated with the chair-stand, the two minutes step and the chair-sit and -reach tests significantly improved. Quality of life as evaluated with the EuroQol-5dimension (EQ-5D) questionnaire improved as well. In conclusion, a training program designed to minimally impact on life habits of older people is effective in improving fitness in patients noncompliant to other to physical exercise programs.

Innovative Approaches to Active and Healthy Ageing: Campania Experience to Improve the Adoption of Innovative Good Practices.

The demographic projections on the European population predict that people aged over 60 will increase by about two million/year in the next decades. Since 2012, the Campania Reference Site of the European Innovation Partnership on Active and Healthy Ageing supports the innovation of the Regional Health System, to face up demographic changes and sustainability. Campania Reference Site provides the opportunity to connect loco-regional stakeholders in social and health care services (universities, healthcare providers, social services, local communities and municipalities), with international organizations, in order to adopt and scale up innovative solutions and approaches. This paper describes the building process of Campania Reference Site and the main results achieved, that have been allowing it to become a hub for open innovation in the field of active and healthy aging at regional, national and international level.

Health tourism: an opportunity for sustainable development.

In February 2017, the "Programma Mattone Internazionale Salute" (ProMis), that is the Italian Program for Internationalization of Regional Health Systems of the Ministry of Health (MoH), presented the first version of its Position Paper on Health Tourism, which embeds a first shared approach to the recommendations expressed by the European Committee of Regions (CoR) on "Age-Friendly" tourism. The CoR stresses the importance of local and regional authorities in the coordination of multi-sectoral policies such as healthcare, social assistance, transport, urban planning and rural development in relation to the promotion of mobility, security, accessibility of services, including health care and social services. "Age-friendly" tourism is an example of an innovative tourist offer that strives to meet the health needs of the entire "traveling" population, with an integrated and cross-sector approach that involves various organizations operating in sectors such as healthcare, accessibility and transport. The aim of the workshop was to explore the interest of the stakeholders to participate in a systemic action in the field of "health" tourism, and to identify priority implementation areas that offer opportunities to take advantage of validated, innovative experiences that strengthen the accessibility to health and social services in regional, national and international contexts. This effort provides the opportunity to take advantage of aligning the European Structural and Investment Funds (ESIF) to the development of tourism, coherently with the needs and resources of local and regional health authorities.