Geriatric Patients Living with HIV/AIDS (GEPPO) is a new prospective observational multicentre cohort consisting of all the HIV-positive geriatric patients being treated at 10 clinics in Italy, and ...HIV-negative controls attending a single geriatric clinic. The aim of this analysis of the GEPPO cohort was to compare prevalence and risk factors of individual non-communicable diseases (NCD), multi-morbidity (MM) and polypharmacy (PP) amongst HIV positive and HIV negative controls at enrolment into the GEPPO cohort.
This cross-sectional study was conducted between June 2015 and May 2016. The duration of HIV infection was subdivided into three intervals: < 10, 10-20 and > 20 years. The NCD diagnoses were based on guidelines defined criteria, including cardiovascular disease, hypertension, type 2 diabetes, chronic kidney disease, dyslipidaemia, chronic obstructive pulmonary disease. MM was classified as the presence of two or more co-morbidities. The medications prescribed for the treatment of comorbidities were collected in both HIV positive and HIV negative group from patient files and were categorized using the Anatomical Therapeutic Chemical (ATC) classification. PP was defined as the presence of five or more drug components other than anti-retroviral agents.
The study involved a total of 1573 patient: 1258 HIV positive and 315 HIV negative). The prevalence of individual comorbidities was similar in the two groups with the exception of dyslipidaemia, which was more frequent in the HIV-positive patients (p < 0.01). When the HIV-positive group was stratified based on the duration of HIV infection, most of the co-morbidities were significantly more frequent than in control patients, except for hypertension and cardiovascular disease, while COPD was more prevalent in the control group. MM and PP were both more prevalent in the HIV-positive group, respectively 64% and 37%.
MM and PP burden in geriatric HIV positive patients are related to longer duration of HIV-infection rather than older age per se.
Microplastics contamination is reported for the first time on Mytilus chilensis from Ushuaia Bay, one of the most remote areas of South America. Our results demonstrate the occurrence of ...microplastics in all samples, with an average of 8.6 ± 3.53 items per individual. Fibers and fragments were the most abundant, with a percentage of 77.91 and 17.44%, respectively. The average length of the fibers was 742.3 ± 702.1 μm, while the average cross-sectional area of fragments was 1944.80 ± 960.94 μm2. The polymers identified were polyamides, semi-synthetic cellulosic materials, and PVC copolymers. The number of microplastics per individual was greater than those reported in even more populated regions. Probably, the modifications included in the technique led to optimize the extraction of MPs, reflecting the detection of a greater number of particles. M. chilensis could play a role in an extensive evaluation of MPs in the Ushuaia Bay, providing information on the interaction of MPs and biota.
•This study constitutes the first record of microplastics on marine organisms from the Beagle Channel.•The frequency of occurrence of microplastics in our study was 100%.•Fibers and fragments were the most common type of microplastics.•The mean concentration of microplastics was 8.6 ± 3.53 particles/ind.•The number of microplastics per individual was greater than those reported to more populated places.
Software programming is an acquired evolutionary skill originating from consolidated cognitive functions (i.e., attentive, logical, coordination, mathematic calculation, and language comprehension), ...but the underlying neurophysiological processes are still not completely known. In the present study, we investigated and compared the brain activities supporting realistic programming, text and code reading tasks, analyzing Electroencephalographic (EEG) signals acquired from 11 experienced programmers. Multichannel spectral analysis and a phase-based effective connectivity study were carried out. Our results highlighted that both realistic programming and reading tasks are supported by modulations of the Theta fronto-parietal network, in which parietal areas behave as sources of information, while frontal areas behave as receivers. Nevertheless, during realistic programming, both an increase in Theta power and changes in network topology emerged, suggesting a task-related adaptation of the supporting network system. This reorganization mainly regarded the parietal area, which assumes a prominent role, increasing its hub functioning and its connectivity in the network in terms of centrality and degree.
Elite controllers are able to control viral replication without antiretroviral therapy. Exceptional elite controllers do not show disease progression for more than 25 years. Different mechanisms have ...been proposed and several elements of both innate and adaptive immunity are implicated. Vaccines are immune stimulating agents that can promote HIV-RNA transcription; transient plasma HIV-RNA detectability has been described within 7-14 days after different vaccinations. The most reliable mechanism involved in virosuppressed people living with HIV is a generalized inflammatory response that activates bystander cells harboring latent HIV. So far no data about viral load increase in elite controllers after SARS-CoV-2 vaccination are reported in literature.
We report the case of a 65-year-old woman of European ancestry, diagnosed with HIV-1/HCV co-infection more than 25 years ago. Since then, HIV-RNA remained undetectable and she never received ARV therapy. In 2021 she was vaccinated with mRNA-BNT162b2 vaccine (Pfizer-BioNTech®). She was administered with three doses in June, July and October 2021, respectively. The last available viral load was undetectable in March 2021. We observed an increase of VL at 32 cp/ml and 124 cp/mL, two and seven months after the second vaccine dose, respectively. During monthly follow-up, HIV-RNA gradually and spontaneously dropped becoming undetectable without ARV intervention. COVID-19 serology was positive with IgG 535 BAU/mL, showing response to vaccination. We measured total HIV-DNA at different time-points and we found it detectable both at the time of the higher plasma HIV-RNA (30 cp/10^6 PBMCs) and when it was undetectable (13 cp/10^6 PBMCs), in reduction.
This case is the first report, to our knowledge, describing a rebound of plasma HIV-RNA in an elite controller after three doses of mRNA-BNT162b2 vaccine for SARS-CoV-2. Concomitantly with a spontaneous reduction of plasma HIV-RNA ten months after the third dose of mRNA-BNT162b2 vaccine (Pfizer-BioNTech®) without antiretroviral therapy intervention, we observed a reduction of total HIV-DNA in peripheral mononuclear cells. The potential role of vaccinations in altering HIV reservoir, even in elite controllers when plasma HIV-RNA is undetectable, could be a valuable aspect to take into account for the future HIV eradication interventions.
Combination antiretroviral treatment is associated with clear benefits in HIV-positive subjects, and is also effective in the central nervous system (CNS), meaning HIV-associated dementia is now an ...uncommon event. Nevertheless, a significant number of patients show symptoms of neurocognitive impairment which may negatively affect their quality of life. Although several risk factors for HIV-associated neurocognitive disorders have been identified, there is no clear recommendation for their prevention and management. In this review, the penetration of drugs into the cerebrospinal fluid/CNS is discussed as well as the viral and clinical consequences associated with higher/lower compartmental exposure. We also review the potential interventions according to the currently identified underlying mechanisms, including persistent CNS immune activation, legacy effects, low-level viral replication and escape, co-morbidities, and antiretroviral-associated direct and indirect 'neurotoxicity'. Adjunctive therapies and interventions (including neuro-rehabilitation) are then briefly discussed. The treatment of HIV infection in the CNS is a complex area of therapeutics requiring multidisciplinary interventions and further study.
•Two and three months of social isolation lead to cognitive deficits in a CFC paradigm in 5xFAD+ and wild-type animals.•Two and three months of social isolation lead to increased plaques in the ...hippocampus of 5xFAD + mice.•Three months of isolation increased hippocampal BACE1 expression in 5xFAD + and wild-type animals.•These effects cannot be prevented by exercise or exercise and an enriched environment during 3 months of isolation.
Research has demonstrated that stress can exacerbate AD pathology in transgenic mouse models of AD. The purpose of the present studies was to extend this work by determining whether a social stressor, isolation stress, would increase the number of Aβ plaques in 5xFAD + transgenic mice in comparison to group-housed controls, and accelerate the onset of cognitive deficits in contextual fear-conditioning. Additionally, we aimed to determine whether the pathological impact of isolation stress could be prevented through exposure to exercise alone or to exercise and an enriched environment throughout the isolation period. Two-month-old 5xFAD + and 5xFAD- animals were isolated or group-housed for two and three months. An additional subset of 5xFAD + mice were housed in isolation, housed in isolation with an exercise wheel, or housed in isolation with an exercise wheel and an enriched environment. Both two and three months of isolation stress significantly increased the number of plaques in the hippocampus of 5xFAD + mice, and three months of isolation increased hippocampal BACE1 expression. Isolated animals also displayed a significant cognitive deficit in contextual fear-conditioning, independent of genotype. Furthermore, neither exercise nor an enriched environment were able to prevent these isolation-induced effects. Understanding how stress impacts the onset and progression of AD is critical, as many individuals endure significant stress over their lifespan, including prolonged social isolation, a societal trend likely to worsen with time.
Understanding the mechanisms of multidrug resistance (MDR) could improve clinical drug efficacy. Multidrug resistance is associated with ATP binding cassette (ABC) transporters, but the factors that ...regulate their expression at clinically relevant drug concentrations are poorly understood. We report that a single-step selection with low doses of anti-cancer agents, similar to concentrations reported in vivo, induces MDR that is mediated exclusively by ABCG2. We selected breast, ovarian and colon cancer cells (MCF-7, IGROV-1 and S-1) after exposure to 14 or 21 nM doxorubicin for only 10 days. We found that these cells overexpress ABCG2 at the mRNA and protein levels. RNA interference analysis confirmed that ABCG2 confers drug resistance. Furthermore, ABCG2 upregulation was facilitated by histone hyperacetylation due to weaker histone deacetylase 1-promoter association, indicating that these epigenetic changes elicit changes in ABCG2 gene expression. These studies indicate that the MDR phenotype arises following low-dose, single-step exposure to doxorubicin, and further suggest that ABCG2 may mediate early stages of MDR development. This is the first report to our knowledge of single-step, low-dose selection leading to overexpression of ABCG2 by epigenetic changes in multiple cancer cell lines.
Recent records of lithodid crabs in deeper waters off the Antarctic continental slope raised the question of the return of crabs to Antarctic waters, following their extinction in the lower Miocene ...~15 million years ago. Antarctic cooling may be responsible for the impoverishment of the marine high Antarctic decapod fauna, presently comprising only five benthic shrimp species. Effects of polar conditions on marine life, including lowered metabolic rates and short seasonal food availability, are discussed as main evolutionary driving forces shaping Antarctic diversity. In particular, planktotrophic larval stages should be vulnerable to the mismatch of prolonged development and short periods of food availability, selecting against complex life cycles. We hypothesize that larval lecithotrophy and cold tolerance, as recently observed in Subantarctic lithodids, represent, together with other adaptations in the adults, key features among the life-history adaptations of lithodids, potentially enabling them to conquer polar ecosystems. The return of benthic top predators to high Antarctic waters under conditions of climate change would considerably alter the benthic communities.
The rate of accumulation of atazanavir and ritonavir within cells is still debated due to methodological limitations. Our aim was to measure peripheral blood mononuclear cell (PBMC) concentrations of ...atazanavir and ritonavir and investigate whether single-nucleotide polymorphisms of OATP, ABCB1, CYP3A4 and PXR genes are involved in intracellular drug penetration.
HIV-positive patients administered 300 mg of atazanavir/100 mg of ritonavir were enrolled. Blood sampling was performed at the end of the dosing interval (Ctrough). PBMC-associated and plasma atazanavir and ritonavir concentrations were measured by validated HPLC coupled with a single mass detector (HPLC-MS) and HPLC-photodiode array (PDA) methods, respectively. Cell count and mean cellular volume were determined using a Coulter counter. Genotyping was conducted using real-time PCR.
Thirty-five patients were enrolled. Median atazanavir and ritonavir intracellular concentrations were 1844 and 716 ng/mL, respectively. Median plasma concentrations were 645 ng/mL for atazanavir and 75 ng/mL for ritonavir, while median intracellular/plasma concentration ratios were 2.4 and 9.2, respectively. Median ritonavir intracellular concentrations were higher for OATP1B1 521 T→C TC or CC carriers and for PXR 44477 A→G AG or GG carriers. Atazanavir intracellular/plasma concentration ratios were higher in patients GG for the ABCB1 2677 G→T single-nucleotide polymorphism (SNP) compared with GT and TT groups.
Our study showed a higher intracellular ritonavir accumulation than previously reported. Ritonavir intracellular concentrations were associated with OATP1B1 521 and PXR 44477 SNPs while intracellular atazanavir exposure was associated with the ABCB1 2677 SNP. Further clinical studies are necessary in order to confirm these data.
PDF
