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Abstract Background 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. Case presentation 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. Conclusions 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.

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.

Purpose: Trichinellosis, a foodborne zoonosis due to nematodes of the genus Trichinella, usually occurs in form of outbreaks following the consumption of untreated meat. Sport hunted wildlife is an increasing source of human cases at the global scale, though North Italy has been rarely involved. We report here a wildlife derived trichinellosis outbreak which spread throughout an entire alpine valley. Methods & Materials: We retrospectively included 96 outpatients referred to the Infectious Diseases Hospital “Amedeo di Savoia”, Torino, North Italy between December 20th, 2019 and January 15th, 2020 after consuming raw sausages from a wild boar of unknown age hunted nearby the village of Chiomonte, in the Susa Valley, 63 Km away from Torino, on November 5th, 2019. Clinical, demographic and laboratory characteristics were recorded at the time of presentation. IgG serology for Trichinella was performed by immunoblot (Trichinella E/S IgG kit, Effegiemme, Milan, Italy). Results: In our cohort we found that 47% of patients were symptomatic, with an uncertain median time from consumption of raw sausage to symptoms and a median time from symptoms to presentation at clinic and serology testing of 14 (IQR 11.75) days. Peripheral blood eosinophilia >500/cmm and CK alterations were found in 26% and 24% of our cohort, respectively. IgG serology was resulted positive in 48/96 (50.0%) of the patients, allowing a diagnosis of confirmed Trichinella spp. infection, later identified as britovi. Only two patients required hospitalization, and no patient suffered serious consequences. Conclusion: We describe in this report the main features of the largest trichinellosis outbreak ever registered in Piedmont region. No major characteristics in clinical, laboratory or serological data were highlighted. Most likely, patients were infected after eating meat products from a single animal, given the very low prevalence of the infection in wild boars in the area. No autochthonous human case has ever been detected in Torino province, and a single wild boar has tested positive for Trichinella since official active surveillance was implemented in 2013. This outbreak should raise attention on the preventive key role of epidemiological veterinary surveillance, and the need to optimize sampling procedures and targeted health education

Sterile inflammation after myocardial infarction is classically credited to myeloid cells interacting with dead cell debris in the infarct zone1,2. Here we show that cardiomyocytes are the dominant initiators of a previously undescribed type I interferon response in the infarct borderzone. Using spatial transcriptomics analysis in mice and humans, we find that myocardial infarction induces colonies of interferon-induced cells (IFNICs) expressing interferon-stimulated genes decorating the borderzone, where cardiomyocytes experience mechanical stress, nuclear rupture and escape of chromosomal DNA. Cardiomyocyte-selective deletion of Irf3 abrogated IFNIC colonies, whereas mice lacking Irf3 in fibroblasts, macrophages, neutrophils or endothelial cells, Ccr2-deficient mice or plasmacytoid-dendritic-cell-depleted mice did not. Interferons blunted the protective matricellular programs and contractile function of borderzone fibroblasts, and increased vulnerability to pathological remodelling. In mice that died after myocardial infarction, IFNIC colonies were immediately adjacent to sites of ventricular rupture, while mice lacking IFNICs were protected from rupture and exhibited improved survival3. Together, these results reveal a pathological borderzone niche characterized by a cardiomyocyte-initiated innate immune response. We suggest that selective inhibition of IRF3 activation in non-immune cells could limit ischaemic cardiomyopathy while avoiding broad immunosuppression.

Abstract Background 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. Methods This cross-sectional study was conducted between June 2015 and May 2016. The duration of HIV infection was subdivided into three intervals: 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. Results 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

Nico Orengo hasn’t been only a novelist and a poet, but also a book reviewer for «La Stampa» and its book insert «Tuttolibri». This paper aims to demonstrate how Orengo has managed with “books of others” not only in the newspapers but also through his interviews for Rai radio programs, in which he has dealt with classics, bestsellers, and publishing for three decades. Moreover, this article attempts to map Orengo’s activity as a writer for Rai during the Seventies, a period of his life still little studied.

Children/adolescents with cancer can develop adverse effects impacting gross motor function. There is a lack of gross motor function assessment tools that have been validated for this population. The aim of this multicenter cross-sectional study was to preliminary validate the 88-item Gross Motor Function Measure (GMFM-88) for use in children/adolescents with cancer, exploring internal consistency and floor/ceiling effect. Inclusion criteria regarded children/adolescents diagnosed with cancer on treatment or

Computed tomography (CT), magnetic resonance imaging (MRI), and radiography expose patients to electromagnetic fields (EMFs) and ionizing radiation. As an alternative, Electrical Impedance Tomography (EIT) offers a less EMF-influenced method for imaging by measuring superficial skin currents to provide a map of the body’s conductivity. EIT allows for functional monitoring of anatomical regions using low electromagnetic fields and minimal exposure times. This paper investigates the application of EIT for the morphological and functional assessment of tissues. Using the Finite Element Method (FEM) (Comsol 5.2), both two-dimensional and three-dimensional models and simulations of physiological and pathological tissues were developed to replicate EIT operations. The primary objective is to detect carcinoma by analysing the electrical impedance response to externally applied excitations. An eight-electrode tomograph was utilised for this purpose, specifically targeting epithelial tissue. The study allowed the characterisation of tomographs of any size and, therefore, the possibility to verify both their geometric profile and the ideal value of the excitation current to be delivered per second of the type of tissue to be analysed. Simulations were conducted to observe electrical impedance variations within a homogeneously modelled tissue and a carcinoma characterized by regular geometry. The outcomes demonstrated the potential of EIT as a viable technique for carcinoma detection, emphasizing its utility in medical diagnostics with reduced EMF exposure.

Abstract Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative condition leading to progressive muscle weakness, atrophy, and ultimately death. Traditional ALS clinical evaluations often depend on subjective metrics, making accurate disease detection and monitoring disease trajectory challenging. To address these limitations, we developed the nQiALS toolkit, a machine learning-powered system that leverages smartphone typing dynamics to detect and track motor impairment in people with ALS. The study included 63 ALS patients and 30 age- and sex-matched healthy controls. We introduce the three core components of this toolkit: the nQiALS-Detection, which differentiated ALS from healthy typing patterns with an AUC of 0.89; the nQiALS-Progression, which separated slow and fast progression at specific thresholds with AUCs ranging between 0.65 and 0.8; and the nQiALS-Fine Motor, which identified subtle progression in fine motor dysfunction, suggesting earlier prediction than the state-of-the-art assessment. Together, these tools represent an innovative approach to ALS assessment, offering a complementary, objective metric to traditional clinical methods and which may reshape our understanding and monitoring of ALS progression.

Background: Surgical debridement and split thickness graft is the most common treatment for acute burn patients that require surgery. However, there is a relevant minority that will require more complex reconstructive options. Microsurgery has evolved as a valuable tool in the acute setting allowing early closure of complex wounds in order to avoid infection, maintain function and even for limb salvage in one stage reconstruction. We present our experience in the management of severely acute burned patients with free flaps, flap survival rate and complications in Chile’s National Health service. Method: We performed a retrospective analysis of all major burn patients admitted in our unit who received a microsurgical flap in the period between april 2019 and march 2023. Data was collected on patient sex, age, mechanism of injury, total burned surface area (TBSA), location of the defect, days to reconstruction, flaps used, operatory time, flap survival and complications. Results: In the study period we had 925 admissions. A total of 36 patients had 42 free flaps (5,1%). All but two patients were male (95 %), mean age 46 years (range 20–––76 years). Total body surface area burned averaged 14 % (range 1–64 %). The majority of injuries were caused by high voltage electricity (59 %) and fire (33 %). 59 % compromised lower limbs and 31 % upper limbs. In 81 % of the cases anterolateral thigh flaps were used. Mean time to reconstruction was 39 days(range 1–64 days), we had 9 complications (21 %) and only one flap was lost (2,9%). Discussion: The introduction of free flaps in the burn reconstruction field was first described in sequelae management. In the acute phase it has also proven to be safe and feasible with a surgical indication of 1,5% to 2% of the admissions in different series. In our unit, 5,1% of our admissions required it, with a low flap loss rate. The increased confidence for its use in the acutely burned setting allowed us to achieve complex coverage while maintaining surgical risk and an internationally acceptable rate of losses and complications. Free flaps cpnstitute an active approach in the classical treatment of this pathology pushing the boundaries in the local environment.

Abstract Aim This study aims to validate a Perceived Social Support Scale for University Students (EPSSEU) during periods of social restrictions, by focusing on family and university support. Subject and methods This cross-sectional study was conducted with undergraduate students from a public higher education institution. The college students who participated in the study—1353 at baseline and 378 after 6 months—answered a virtual questionnaire containing questions on: sociodemographic and lifestyle data, items proposed for the EPSSEU, Satisfaction with Social Support Scale (ESSS), and Depression, Anxiety and Stress Scale (DASS-21). Exploratory factor analysis, Cronbach’s alpha reliability analysis, as well as discriminant, convergent, and known-group validations were performed. Results The results showed two factors support from: i) the university and ii) friends and family— which explained 61.82% of the variance in the data. The EPSSEU showed good reliability (Cronbach’s alpha = 0.796) as well as validity, with higher scores among individuals without depression, anxiety, or stress. Conclusion The EPSSEU shows adequate psychometric qualities and may be a useful instrument for assessing university students’ social support in pandemics, social distancing, and remote teaching contexts.

Human papilloma virus (HPV) infection and its progression still represent a great medical challenge worldwide. Clinical evidence has demonstrated the beneficial effects of polyhexamethylene biguanide (PHMB) on HPV clinical manifestations; however, evidence of the effect of this molecule on HPV viral load is still lacking. In this in vitro study, 13 ThinPrep Papanicolaou (Pap) tests were treated with a PHMB solution (0.10 g/100 mL) for 2 h. We observed no cytological changes but a significant reduction in the viral load of high-risk (HR) HPV after PHMB treatment, also revealing a dose-dependent antiviral effect. In addition, by stratifying the obtained results according to HR-HPV genotype, we observed a significant reduction in the viral load of HPV 16, P2 (56, 59, 66), 31, and P3 (35, 39, 68) and a strong decrease in the viral load of HPV 45, 52, and P1 (33, 58). Overall, 85% of the analyzed cervical cell samples exhibited an improvement in HPV viral load after PHMB exposure, while only 15% remain unchanged. For the first time, the data from this pilot study support the activity of PHMB on a specific phase of the HPV viral lifecycle, the one regarding the newly generated virions, reducing viral load and thus blocking the infection of other cervical cells.

Identifying mutations in cancer-associated genes to guide patient treatments is essential for precision medicine. Circulating tumor DNA (ctDNA) offers valuable insights for early cancer detection, treatment assessment, and surveillance. However, a key issue in ctDNA analysis from the bloodstream is the choice of a technique with adequate sensitivity to identify low frequent molecular changes. Next-generation sequencing (NGS) technology, evolving from parallel to long-read capabilities, enhances ctDNA mutation analysis. In the present review, we describe different NGS approaches for identifying ctDNA mutation, discussing challenges to standardized methodologies, cost, specificity, clinical context, and bioinformatics expertise for optimal NGS application.

Abstract The influence of deep and regional geological structures is becoming increasingly important in superhot geothermal systems due to their proximity to the transition between brittleness and ductility. In the Los Humeros geothermal field in Mexico, where subsurface fluids reach temperatures of over 350 °C, the surface structures resulting from the collapse of calderas have so far only been interpreted at the local scale. The aim of this work is to place the recent tectonic and volcano-tectonic geomorphologic evolution and structures in the Los Humeros volcanic area in a regional context. NE- and NW-striking dominant structures resulting from a morpho-structural analysis on a regional scale are confirmed by negative and positive anomalies, respectively, after Butterworth filtering of gravity field data with different wavelengths over a local area of about 1000 km2. By analyzing the slip and dilation trends of the observed directions, we show the relevance of the regional context for reservoir exploration. The magnitudes of the principal stresses we estimate indicate a trans-tensional fault regime, a combination of strike-slip and normal faulting. The structures derived from the gravity and morpho-structural analyses, which are parallel to the maximum horizontal stress, have the highest potential for tensile and shear failure. Therefore, the corresponding negative gravity anomalies could be related to fracture porosity. Consequently, we hypothesize that these structures near the transition between brittleness and ductility control fluid flow in the Los Humeros geothermal field.

Abstract Introduction The objective was to characterize real-world outcomes of drug–drug interactions (DDIs) between antiretrovirals (ARVs) and other drugs, including over-the-counter medications (OTC), and treatment outcomes in clinical practice. Methods www.clinicalcasesDDIs.com is an open-access website for healthcare providers to consult and briefly describe real-world clinical cases on DDI with ARVs. We reviewed all the clinical cases reported to the website between March 2019 and May 2023. Results A total of 139 cases were reported, mostly involving ritonavir or cobicistat (boosters; 74 cases), unboosted integrase inhibitors (InSTI; 29 cases), and non-nucleoside reverse transcriptase inhibitors (NNRTI; 23 cases). Central nervous system drugs (29 cases) and cardiovascular drugs (19 cases) were the most frequently described co-medications. Notably, OTC medications were implicated in 27 cases, including mineral supplements (11 cases), herbals (8 cases), weight loss drugs (4 cases), anabolic steroids (3 cases), and recreational drugs (1 case). OTC acted as the perpetrator drug in 21 cases, leading to loss of ARV efficacy in 17 instances (mineral supplements in 10 cases, weight loss drugs in 4 cases, herbals in 3 cases). Additionally, toxicity was reported in 4 out of 6 cases where OTC was considered the victim drug of the DDI (anabolic steroids in 3 cases, MDMA in 1 case). Conclusions Frequent unwanted outcomes resulting from DDIs between ARVs and OTC medications underscore the importance of integrating non-prescription drugs into medication reconciliation. The real-world data available through www.clinicalcasesDDIs.com serves as a valuable resource for assessing the clinical relevance of DDIs.