Search

Apolipoprotein A-I (ApoA-I) is elevated in the plasma of a subgroup of trauma patients with systemic hyperfibrinolysis. We hypothesize that apoA-I inhibits platelet activation and clot formation. The effects of apoA-I on human platelet activation and clot formation were assessed by whole blood thrombelastography (TEG), platelet aggregometry, P-selectin surface expression, microfluidic adhesion, and Akt phosphorylation. Mouse models of carotid artery thrombosis and pulmonary embolism were used to assess the effects of apoA-I in vivo. The ApoA-1 receptor was investigated with transgenic mice knockouts (KO) for the scavenger receptor class B member 1 (SR-BI). Compared to controls, exogenous human apoA-I inhibited arachidonic acid and collagen-mediated human and mouse platelet aggregation, decreased P-selectin surface expression and Akt activation, resulting in diminished clot strength and increased clot lysis by TEG. ApoA-I also decreased platelet aggregate size formed on a collagen surface under flow. In vivo, apoA-I delayed vessel occlusion in an arterial thrombosis model and conferred a survival advantage in a pulmonary embolism model. SR-BI KO mice significantly reduced apoA-I inhibition of platelet aggregation versus wild-type platelets. Exogenous human apoA-I inhibits platelet activation, decreases clot strength and stability, and protects mice from arterial and venous thrombosis via the SR-BI receptor.

The Effects of the Metaverse on People. Social and Political Risks of a Platform in the Making. The metaverse is configured as the final frontier of digital spaces: a land of opportunities (social, economic, technological, recreational). A space that is beginning to take shape thanks to the technological evolution of VR, AR, XR devices, artificial intelligence, IoT and the increasingly pervasive spread of digital services. It is a frontier imagined as an environment capable of uniting the physical and digital worlds in a technological (and cultural) convergence that can guarantee full interoperability between different platforms and devices. In this paper, we want to try to investigate the critical aspects of such an ecosystem which, beyond the enthusiasm of the pioneers, already presents a number of risks that could turn this promised land into a real hell. The dangers linked to the art world and NFT, the enormous amount of data in the hands of an oligarchy composed of the tech giants, the possible addictions, social tensions and forms of control that already animate the current digital world, could, in fact, have an enormous impact on society as a whole. An analysis of this media ecosystem, of the imaginary connected to it, of its history and of the logics that animate it, can help us face the risks and better govern our unbridled race towards this new frontier.

Measurement(s) Standardized Mortality Ratio Technology Type(s) Public database

The intercalated disc (ICD) is a membrane structure of the cardiac muscle involved in normal heart function. Here the authors report that knockdown of the ICD-bound transmembrane protein 65 results in impaired ICD structure, abnormal cardiac electrophysiology and cardiomyopathy in mice.

BackgroundCOVID-19 may result in persistent symptoms in the post-acute phase, including cognitive and neurological ones. The aim of this study is to investigate the cognitive and neurological features of patients with a confirmed diagnosis of COVID-19 evaluated in the post-acute phase through a direct neuropsychological evaluation.MethodsIndividuals recovering from COVID-19 were assessed in an out-patient practice with a complete neurological evaluation and neuropsychological tests (Mini-Mental State Examination; Rey Auditory Verbal Test, Multiple Feature Target Cancellation Test, Trial Making Test, Digit Span Forward and Backward, and Frontal Assessment Battery). Pre- and post-COVID-19 global and mental health status was assessed along with the history of the acute phase of infection. Post-COVID-19 cognitive status was modeled by combining persistent self-reported COVID-related cognitive symptoms and pathologic neuropsychological tests.ResultsA total of 406 individuals (average age 54.5 ± 15.1 years, 45.1% women) were assessed on average at 97.8 ± 48.0 days since symptom onset. Persistent self-reported neurological symptoms were found in the areas of sleep (32%), attention (31%), and memory (22%). The MMSE mean score was 28.6. In total, 84 subjects (20.7%) achieved pathologic neuropsychological test results. A high prevalence of failed tests was found in digit span backward (18.7%), trail making (26.6%), and frontal assessment battery (10.9%). Cognitive status was associated with a number of factors including cardiovascular disease history, persistent fatigue, female sex, age, anxiety, and mental health stress.ConclusionCOVID-19 is capable of eliciting persistent measurable neurocognitive alterations particularly relevant in the areas of attention and working memory. These neurocognitive disorders have been associated with some potentially treatable factors and others that may stratify risk at an early stage.

Pulmonary arterial hypertension (PAH) is a chronic, progressive disease characterized by an increase in blood pressure in the lungs' arteries. It can occur in a variety of species, including humans, dogs, cats, and horses. To date, PAH has a high mortality rate in both veterinary and human medicine, often due to complications such as heart failure. The complex pathological mechanisms of PAH involve multiple cellular signalling pathways at various levels. IL-6 is a powerful pleiotropic cytokine that regulates several phases of immune response, inflammation, and tissue remodelling. The hypothesis of this study was that the use of an IL-6 antagonist in PAH could interrupt or mitigate the cascade of events that leads to the progression of the disease and the worsening of clinical outcome, as well as tissue remodelling. In this study, we used two pharmacological protocols with an IL-6 receptor antagonist in a monocrotaline-induced PAH model in rats. Our results showed that the use of an IL-6 receptor antagonist had a significant protective effect, ameliorating both haemodynamic parameters, lung and cardiac function, tissue remodelling, and the inflammation associated with PAH. The results of this study suggest that the inhibition IL-6 could be a useful pharmacological strategy in PAH, in both human and veterinary medicine.

ABSTRACT We performed whole-genome sequencing with bait enrichment techniques to analyze Andes virus (ANDV), a cause of human hantavirus pulmonary syndrome. We used cryopreserved lung tissues from a naturally infected long-tailed colilargo, including early, intermediate, and late cell culture, passages of an ANDV isolate from that animal, and lung tissues from golden hamsters experimentally exposed to that ANDV isolate. The resulting complete genome sequences were subjected to detailed comparative genomic analysis against American orthohantaviruses. We identified four amino acid substitutions related to cell culture adaptation that resulted in attenuation of ANDV in the typically lethal golden hamster animal model of hantavirus pulmonary syndrome. Changes in the ANDV nucleocapsid protein, glycoprotein, and small nonstructural protein open reading frames correlated with mutations typical for ANDV strains associated with increased virulence in the small-animal model. Finally, we identified three amino acid substitutions, two in the small nonstructural protein and one in the glycoprotein, that were only present in the clade of viruses associated with efficient person-to-person transmission. Our results indicate that there are single-nucleotide polymorphisms that could be used to predict strain-specific ANDV virulence and/or transmissibility. IMPORTANCE Several orthohantaviruses cause the zoonotic disease hantavirus pulmonary syndrome (HPS) in the Americas. Among them, HPS caused by Andes virus (ANDV) is of great public health concern because it is associated with the highest case fatality rate (up to 50%). ANDV is also the only orthohantavirus associated with relatively robust evidence of person-to-person transmission. This work reveals nucleotide changes in the ANDV genome that are associated with virulence attenuation in an animal model and increased transmissibility in humans. These findings may pave the way to early severity predictions in future ANDV-caused HPS outbreaks.

Background: In the United States, a disproportionate number of persons with HIV (PWH) and opioid use disorder (OUD) are involved in the justice system. Medications for OUD (MOUD) can reduce convictions and incarceration time in persons with OUD. Extended-release naltrexone (XR-NTX) has been shown to reduce craving of opioids, recurrence of use, and overdose and help achieve or maintain HIV viral suppression in PWH with OUD involved with the justice system. Objectives: This retrospective study aimed to describe factors associated with reincarceration and to evaluate if XR-NTX was associated with reduced reincarceration among PWH and OUD who were released to the community from incarceration. Methods: Data from participants released to the community from incarceration from a completed randomized controlled trial was analyzed using a generalized linear model to estimate odds ratios associated with reincarceration and a Kaplan-Meier survival analysis to determine time to reincarceration and non-reincarcerated individuals were compared. Results: Of the 77 participants, 41 (53.2%) were reincarcerated during the 12-month study period. The mean time to reincarceration was 190 days (SD=108.3). Compared with participants who remained in the community, reincarcerated participants were more likely to have major depressive disorder at study baseline, increased opioid cravings, longer mean lifetime incarceration, and a higher physical quality of life score. XR-NTX was not significantly associated statistically with reincarceration in this analysis. Conclusion: Reducing reincarceration is a public health priority, given the high proportion of PWH and OUD in the U.S. justice system as well as high degrees of persons returning to the community and having care interrupted due to reincarceration. This analysis determined that potentially identifying depression in recently released individuals could improve HIV outcomes, decrease recurrence of opioid use, and reduce reincarceration.

Objective(s)'Getting to Zero' (GTZ) initiatives aim to eliminate new HIV infections over a projected time frame. Increased preexposure prophylaxis (PrEP) uptake among populations with the highest HIV incidence, such as young Black MSM, is necessary to accomplish this aim. Agent-based network models (ABNMs) can help guide policymakers on strategies to increase PrEP uptake.DesignEffective PrEP implementation requires a model that incorporates the dynamics of interventions and dynamic feedbacks across multiple levels including virus, host, behavior, networks, and population. ABNMs are a powerful tool to incorporate these processes.MethodsAn ABNM, designed for and parameterized using data for young Black MSM in Illinois, was used to compare the impact of PrEP initiation and retention interventions on HIV incidence after 10 years, consistent with GTZ timelines. Initiation interventions selected individuals in serodiscordant partnerships, or in critical sexual network positions, and compared with a controlled setting where PrEP initiators were randomly selected. Retention interventions increased the mean duration of PrEP use. A combination intervention modeled concurrent increases in PrEP initiation and retention.ResultsSelecting HIV-negative individuals for PrEP initiation in serodiscordant partnerships resulted in the largest HIV incidence declines, relative to other interventions. For a given PrEP uptake level, distributing effort between increasing PrEP initiation and retention in combination was approximately as effective as increasing only one exclusively.ConclusionSimulation results indicate that expanded PrEP interventions alone may not accomplish GTZ goals within a decade, and integrated scale-up of PrEP, antiretroviral therapy, and other interventions might be necessary.

The genus Stephanostomum consists of digenean trematodes found in many marine teleosts. In this study, Stephanostomum cesticillus (Molin, 1858) Looss, 1899 metacercariae were identified in European hake (Merluccius merluccius, Linnaeus, 1758) caught in the Tyrrhenian Sea. The metacercariae were found encapsulated in the muscle, close to the spine and gills. Out of 131 specimens, 111 (P = 84.7%, mI = 25.1 mA = 21.3) were infected by digenean trematode metacercariae. Morphological and histological evaluations were carried out. The members of this genus are characterised by a double crown of spines close to the oral sucker. For identification of the parasite, molecular analysis was performed via 28S and 18S ribosomal DNA (rDNA) genes. Partial rDNA sequences of Stephanostomum highly matched to S. cesticillus for the percentage of similar identity from the nucleotide database of BLAST. The present survey reports the presence of S. cesticillus metacercariae in M. merluccius for the first time. Our results improve current knowledge on hake parasites to better understand the distribution of S. cesticillus in M. merluccius caught in the Mediterranean Sea and shed light on the life cycle of the parasite adding other possible hosts.

Abstract Background Long distance heavy goods vehicle (HGV) drivers exhibit higher than nationally representative rates of obesity, and obesity-related co-morbidities, and are underserved in terms of health promotion initiatives. The purpose of this study was to evaluate the effectiveness of the multicomponent ‘Structured Health Intervention For Truckers’ (SHIFT), compared to usual care, at 6- and 16–18-month follow-up. Methods We conducted a two-arm cluster RCT in transport sites throughout the Midlands, UK. Outcome measures were assessed at baseline, at 6- and 16–18-month follow-up. Clusters were randomised (1:1) following baseline measurements to either the SHIFT arm or usual practice control arm. The 6-month SHIFT programme included a group-based interactive 6-h education and behaviour change session, health coach support and equipment provision (Fitbit® and resistance bands/balls to facilitate a ‘cab workout’). The primary outcome was device-assessed physical activity (mean steps/day) at 6 months. Secondary outcomes included the following: device-assessed sitting, physical activity intensity and sleep; cardiometabolic health, diet, mental wellbeing and work-related psychosocial variables. Data were analysed using mixed-effect linear regression models using a complete-case population. Results Three hundred eighty-two HGV drivers (mean ± SD age: 48.4 ± 9.4 years, BMI: 30.4 ± 5.1 kg/m2, 99% male) were recruited across 25 clusters (sites) and randomised into either the SHIFT (12 clusters, n = 183) or control (13 clusters, n = 199) arms. At 6 months, 209 (55%) participants provided primary outcome data. Significant differences in mean daily steps were found between groups, in favour of the SHIFT arm (adjusted mean difference: 1008 steps/day, 95% CI: 145–1871, p = 0.022). Favourable differences were also seen in the SHIFT group, relative to the control group, in time spent sitting (− 24 mins/day, 95% CI: − 43 to − 6), and moderate-to-vigorous physical activity (6 mins/day, 95% CI: 0.3–11). Differences were not maintained at 16–18 months. No differences were observed between groups in the other secondary outcomes at either follow-up. Conclusions The SHIFT programme led to a potentially clinically meaningful difference in daily steps, between trial arms, at 6 months. Whilst the longer-term impact is unclear, the programme offers potential to be incorporated into driver training courses to promote activity in this at-risk, underserved and hard-to-reach essential occupational group. Trial registration ISRCTN10483894 (date registered: 01/03/2017)

Abstract Background Persons involved in the justice system are at high risk for HIV and drug overdose upon release to the community. This manuscript describes a randomized controlled trial of two evidence-based linkage interventions for provision of HIV prevention and treatment and substance use disorder (SUD) services in four high risk communities to assess which is more effective at addressing these needs upon reentry to the community from the justice system. Methods This is a 5-year hybrid type 1 effectiveness-implementation randomized controlled trial that compares two models (Patient Navigation [PN] or Mobile Health Unit [MHU] service delivery) of linking justice-involved individuals to the continuum of community-based HIV and SUD prevention and treatment service cascades of care. A total of 864 justice-involved individuals in four US communities with pre-arrest histories of opioid and/or stimulant use who are living with or at-risk of HIV will be randomized to receive either: (a) PN, wherein patient navigators will link study participants to community-based service providers; or (b) services delivered via an MHU, wherein study participants will be provided integrated HIV prevention/ treatment services and SUD services. The six-month post-release intervention will focus on access to pre-exposure prophylaxis (PrEP) for those without HIV and antiretroviral treatment (ART) for people living with HIV (PLH). Secondary outcomes will examine the continuum of PrEP and HIV care, including: HIV viral load, PrEP/ ART adherence; HIV risk behaviors; HCV testing and linkage to treatment; and sexually transmitted infection incidence and treatment. Additionally, opioid and other substance use disorder diagnoses, prescription, receipt, and retention on medication for opioid use disorder; opioid and stimulant use; and overdose will also be assessed. Primary implementation outcomes include feasibility, acceptability, sustainability, and costs required to implement and sustain the approaches as well as to scale-up in additional communities. Discussion Results from this project will help inform future methods of delivery of prevention, testing, and treatment of HIV, HCV, substance use disorders (particularly for opioids and stimulants), and sexually transmitted infections for justice-involved individuals in the community. Trial registration: Clincialtrials.gov NCT05286879 March 18, 2022.