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Abstract Time-varying metamaterials rely on large and fast changes of the linear permittivity. Beyond the linear terms, however, the effect of a non-perturbative modulation of the medium on harmonic generation remains largely unexplored. In this work, we study second harmonic generation at an optically pumped time-varying interface between air and a 310 nm Indium Tin Oxide film. We observe a modulation contrast at the second harmonic wavelength up to 93% for a pump intensity of 100 GW/cm2, leading to large frequency broadening and shift. We experimentally demonstrate that a significant contribution to the enhancement comes from the temporal modulation of the second order nonlinear susceptibility. Moreover, we show the frequency-modulated spectra resulting from single and double-slit time diffraction could be exploited for enhanced optical computing and sensing, enabling broadband time-varying effects on the harmonic signal and extending the application of Epsilon-Near-Zero materials to the visible range.

Abstract The KM3NeT/ARCA neutrino detector is currently under construction at 3500 m depth offshore Capo Passero, Sicily, in the Mediterranean Sea. The main science objectives are the detection of high-energy cosmic neutrinos and the discovery of their sources. Simulations were conducted for the full KM3NeT/ARCA detector, instrumenting a volume of 1 km $$^3$$ 3 , to estimate the sensitivity and discovery potential to point-like neutrino sources. This paper covers the reconstruction of track- and shower-like signatures, as well as the criteria employed for neutrino event selection. With an angular resolution below 0.1 $$^\circ $$ ∘ for tracks and under 2 $$^\circ $$ ∘ for showers, the sensitivity to point-like neutrino sources surpasses existing observed limits across the entire sky.

Abstract This review screened 296 articles on wearable sensors for home monitoring of people with Parkinson’s Disease within the PubMed Database, from January 2017 to May 2023. A three-level maturity framework was applied for classifying the aims of 59 studies included: demonstrating technical efficacy, diagnostic sensitivity, or clinical utility. As secondary analysis, user experience (usability and patient adherence) was evaluated. The evidences provided by the studies were categorized and stratified according to the level of maturity. Our results indicate that approximately 75% of articles investigated diagnostic sensitivity, i.e. correlation of sensor-data with clinical parameters. Evidence of clinical utility, defined as improvement on health outcomes or clinical decisions after the use of the wearables, was found only in nine papers. A third of the articles included reported evidence of user experience. Future research should focus more on clinical utility, to facilitate the translation of research results within the management of Parkinson’s Disease.

Abstract The measurement of the flux of muons produced in cosmic ray air showers is essential for the study of primary cosmic rays. Such measurements are important in extensive air shower detectors to assess the energy spectrum and the chemical composition of the cosmic ray flux, complementary to the information provided by fluorescence detectors. Detailed simulations of the cosmic ray air showers are carried out, using codes such as CORSIKA, to estimate the muon flux at sea level. These simulations are based on the choice of hadronic interaction models, for which improvements have been implemented in the post-LHC era. In this work, a deficit in simulations that use state-of-the-art QCD models with respect to the measurement deep underwater with the KM3NeT neutrino detectors is reported. The KM3NeT/ARCA and KM3NeT/ORCA neutrino telescopes are sensitive to TeV muons originating mostly from primary cosmic rays with energies around 10 TeV. The predictions of state-of-the-art QCD models show that the deficit with respect to the data is constant in zenith angle; no dependency on the water overburden is observed. The observed deficit at a depth of several kilometres is compatible with the deficit seen in the comparison of the simulations and measurements at sea level.

This retrospective cohort study assesses the effectiveness of straight-stem cementless versus cemented prostheses in hip replacement surgeries for elderly patients with femoral neck fractures. We analyzed 80 patients aged 70 and over who underwent surgery between 2018 and 2021. Clinical outcomes were evaluated using the Harris Hip Score, WOMAC Score, and Visual Analogue Scale, alongside radiological assessments through Brooker’s classification. Preoperative Dorr classification and five postoperative criteria (subsidence, cortical hypertrophy, pedestal sign, radiolucent lines, and stress shielding) were used to assess implant efficacy. The results demonstrated satisfactory mid-term outcomes for both groups, with slightly higher clinical scores observed in the cementless stem group. The Harris Hip Score (HHS) averaged 74.4 ± 6.7 in the cemented group and 79.2 ± 10.4 in the cementless group, with a statistically significant difference (p = 0.0146). The WOMAC Score showed an average of 30.1 ± 4.6 in the cemented group compared to 27.1 ± 6.9 in the cementless group, also indicating a statistically significant improvement (p = 0.0231). However, radiographic findings call for a re-evaluation of long-term stability. Our statistical analysis, which included power calculation and multivariate analysis to adjust for confounding variables, offers a comprehensive assessment of implant effectiveness. The findings contribute to the ongoing debate on the choice between cemented and cementless prostheses, indicating that both are viable options catering to different patient needs. Further research overcoming this study’s limitations is crucial for a deeper understanding of optimal treatment strategies in hip replacement surgery for the elderly.

Abstract While Free and Open Source (F/OSS) coding has traditionally been described as a separate commons linked to values of openness and sharing, recent research suggests an increasing integration of private corporations into F/OSS practices, blurring the boundaries between F/OSS and commodified coding. However, there is a dearth of empirical, and especially quantitative studies exploring this phenomenon. To address this gap, we model the power dynamics and infrastructural aspects of software production within GitHub, a central hub for F/OSS development, using a large-scale, directed network. Using various network statistics, we detect the ecosystem’s most impactful actors and find a nuanced picture of the influence of individuals, open source organizations, and private corporations in F/OSS practices. We find that the majority of public repositories on GitHub depend on a small core of specialized repositories and users. In accordance with expectations, individuals and open source organizations are more prevalent in this core of elite GitHub users, however, we also find a significant amount of private organizations with an indirect, yet consistent influence within GitHub. In addition, we find that directly influential individuals tend to facilitate sponsorship methods more often than indirectly or non-influential individuals. Our research highlights a hybridization of F/OSS and sheds light on the complex interplay between influence, power, and code production in the multi-language dependency ecosystem of GitHub.

Abstract The progression of Parkinson’s disease (PD) is heterogeneous across patients, affecting counseling and inflating the number of patients needed to test potential neuroprotective treatments. Moreover, disease subtypes might require different therapies. This work uses a data-driven approach to investigate how observed heterogeneity in PD can be explained by the existence of distinct PD progression subtypes. To derive stable PD progression subtypes in an unbiased manner, we analyzed multimodal longitudinal data from three large PD cohorts and performed extensive cross-cohort validation. A latent time joint mixed-effects model (LTJMM) was used to align patients on a common disease timescale. Progression subtypes were identified by variational deep embedding with recurrence (VaDER). In each cohort, we identified a fast-progressing and a slow-progressing subtype, reflected by different patterns of motor and non-motor symptoms progression, survival rates, treatment response, features extracted from DaTSCAN imaging and digital gait assessments, education, and Alzheimer’s disease pathology. Progression subtypes could be predicted with ROC-AUC up to 0.79 for individual patients when a one-year observation period was used for model training. Simulations demonstrated that enriching clinical trials with fast-progressing patients based on these predictions can reduce the required cohort size by 43%. Our results show that heterogeneity in PD can be explained by two distinct subtypes of PD progression that are stable across cohorts. These subtypes align with the brain-first vs. body-first concept, which potentially provides a biological explanation for subtype differences. Our predictive models will enable clinical trials with significantly lower sample sizes by enriching fast-progressing patients.

Abstract Background The anatomic variants of the intercostobrachial nerve (ICBN) represent a potential risk of injuries during surgical procedure such as axillary lymph node dissection and sentinel lymph node biopsy in breast cancer and melanoma patients. The aim of this systematic review and meta-analysis was to investigate the different origins and branching patterns of the intercostobrachial nerve also providing an analysis of the prevalence, through the analysis of the literature available up to September 2023. Materials and methods The protocol for this study was registered on PROSPERO (ID: CRD42023447932), an international prospective database for reviews. The PRISMA guideline was respected throughout the meta-analysis. A systematic literature search was performed using PubMed, Scopus and Web of Science. A search was performed in grey literature through google. Results We included a total of 23 articles (1,883 patients). The prevalence of the ICBN in the axillae was 98.94%. No significant differences in prevalence were observed during the analysis of geographic subgroups or by study type (cadaveric dissections and in intraoperative dissections). Only five studies of the 23 studies reported prevalence of less than 100%. Overall, the PPE was 99.2% with 95% Cis of 98.5% and 99.7%. As expected from the near constant variance estimates, the heterogeneity was low, I2 = 44.3% (95% CI 8.9%−65.9%), Q = 39.48, p = .012. When disaggregated by evaluation type, the difference in PPEs between evaluation types was negligible. For cadaveric dissection, the PPE was 99.7% (95% CI 99.1%–100.0%) compared to 99.0% (95% CI 98.1%–99.7%). Conclusions The prevalence of ICBN variants was very high. The dissection of the ICBN during axillary lymph-node harvesting, increases the risk of sensory disturbance. The preservation of the ICBN does not modify the oncological radicality in axillary dissection for patients with cutaneous metastatic melanoma or breast cancer. Therefore, we recommend to operate on these patients in high volume center to reduce post-procedural pain and paresthesia associated with a lack of ICBN variants recognition.

BackgroundGrowing evidence reveals the important role of clinical psychological factors in chronic-immune diseases. The aim of this study was to investigate Health-Related Quality of Life (HR-QoL), depression, anxiety, and alexithymia in patients with severe hypersensitivity reactions such as Severe Allergic Asthma (SAA) and Hymenoptera Venom Anaphylaxis (HVA).MethodsThe Short-Form Health Survey-36 (SF-36), the Beck Depression Inventory Questionnaire (BDI-II), the Hamilton Anxiety Rating Scale (HAM-A) and the Toronto Alexithymia Scale (TAS-20) were used to assess HR-QoL and clinical psychological features of patients with SAA and HVA.ResultsOverall, 78 patients were recruited. Patients with SAA (n = 35) reported lower scores for physical functioning [65 (58–75) vs. 90 (85–95); p =

Digital health, encompassing the use of digital technologies in healthcare, and telemedicine, facilitating healthcare delivery across long distances, have witnessed widespread applications across various healthcare domains. The COVID-19 pandemic accelerated the adoption of digital solutions in healthcare, overcoming barriers to access and fostering transitions to new care models. However, healthcare professionals often lack digital health competencies, necessitating targeted training initiatives. This study presents a project initiated by the Order of Physicians and Dentists of Rome, promoting a comprehensive training program in digital health for healthcare professionals. This investigation aims to describe the project, report demographic characteristics of participants, and analyze survey results on participants’ perceptions of the training program. The Erasmus+ project, titled ‘Training of Physician Trainers in Telemedicine, eHealth, and Digital Medicine,’ facilitated the digital transition of the healthcare sector through international training. The project involved structured courses, job-shadowing, and support activities in Malta and Madrid. A survey, developed using the Delphi methodology, assessed participants’ views on telemedicine. Thirty participants, selected based on merit, engaged in the project. Survey responses highlighted a strong impact on participants’ understanding of digital health concepts and increased confidence in utilizing digital tools. Notably, 85% acknowledged significant skill acquisition in healthcare digitalization. The project addressed a critical training gap among healthcare professionals, emphasizing the need for ongoing education in digital health. Despite existing recommendations, formal digital health education remains limited. The study underscores the importance of educational efforts to foster a digitalized healthcare model.

Abstract High refractive index dielectric nanoantennas strongly modify the decay rate via the Purcell effect through the design of radiative channels. Due to their dielectric nature, the field is mainly confined inside the nanostructure and in the gap, which is hard to probe with scanning probe techniques. Here we use single-molecule fluorescence lifetime imaging microscopy (smFLIM) to map the decay rate enhancement in dielectric GaP nanoantenna dimers with a median localization precision of 14 nm. We measure, in the gap of the nanoantenna, decay rates that are almost 30 times larger than on a glass substrate. By comparing experimental results with numerical simulations we show that this large enhancement is essentially radiative, contrary to the case of plasmonic nanoantennas, and therefore has great potential for applications such as quantum optics and biosensing.

The study focuses on analysing the high-level carrier lifetime ( $\tau _{\mathrm {HL}}$ ) in 4H silicon carbide (4H-SiC) PiN diodes under varying temperatures and proton implantation doses. The objective is to identify an empirical law applicable in technology computer-aided design (TCAD) modelling for SiC devices, describing the dependence of carrier lifetime on temperature to gain insights into how irradiation dose may influence the $\tau _{\mathrm {HL}}$ . We electrically characterize diodes of different diameters subjected to different proton irradiation doses and examine the variations in current-voltage (I-V) and ideality factor (n) curves under various irradiation conditions. The effects of proton irradiation on the epitaxial layer are analysed through capacitance-voltage (C-V) measurements. We correlate the observed effects on I-V, n, and C-V curves to the hypothesis of formation of acceptor-type defects related to carbon vacancies, specifically the Z $_{\mathrm {1/2}}$ defects generated during the irradiation process. The impact of irradiation on carrier lifetime is investigated by measuring $\tau _{\mathrm {HL}}$ using the open circuit voltage decay (OCVD) technique at different temperatures on diodes exposed to various H+ irradiation doses with constant ion energy. This investigation reveals the presence of a proportional relationship between 1/ $\tau _{\mathrm {HL}}$ and the dose of irradiated protons: the proportionality coefficient, referred to as the damage coefficient (K $_{\mathrm {T}}$ ), exhibits an Arrhenius-type dependence on temperature. OCVD-measured lifetime on the various diodes demonstrates a power-law dependence of lifetime on temperature. The exponent of this dependence varies with the irradiation dose, notably showing an increase in temperature dependence at the highest H+ ion dose. This suggests a threshold-like dependence on H+ irradiation dose in the $\tau _{\mathrm {HL}}$ -temperature relationship.

Lower-limb gait training (GT) exoskeletons have been successfully used in rehabilitation programs to overcome the burden of locomotor impairment. However, providing suitable net interaction torques to assist patient movements is still a challenge. Previous transparent operation approaches have been tested in treadmill-based GT exoskeletons to improve user-robot interaction. However, it is not yet clear how a transparent lower-limb GT system affects user’s gait kinematics during overground walking, which unlike treadmill-based systems, requires active participation of the subjects to maintain stability. In this study, we implemented a transparent operation strategy on the ExoRoboWalker, an overground GT exoskeleton, to investigate its effect on the user’s gait. The approach employs a feedback zero-torque controller with feedforward compensation for the exoskeleton’s dynamics and actuators’ impedance. We analyzed the data of five healthy subjects walking overground with the exoskeleton in transparent mode (ExoTransp) and non-transparent mode (ExoOff) and walking without exoskeleton (NoExo). The transparent controller reduced the user-robot interaction torque and improved the user’s gait kinematics relative to ExoOff. No significant difference in stride length is observed between ExoTransp and NoExo (p = 0.129). However, the subjects showed a significant difference in cadence between ExoTransp (50.9± 1.1 steps/min) and NoExo (93.7 ± 8.7 steps/min) (p = 0.015), but not between ExoTransp and ExoOff (p = 0.644). Results suggest that subjects wearing the exoskeleton adjust their gait as in an attention-demanding task changing the spatiotemporal gait characteristics likely to improve gait balance.

The intestinal microbiota is an important environmental factor implicated in CRC development. Intriguingly, modulation of DNA methylation by gut microbiota has been reported in preclinical models, although the relationship between tumor-infiltrating bacteria and CIMP status is currently unexplored. In this study, we investigated tumor-associated bacteria in 203 CRC tumor cases and validated the findings using The Cancer Genome Atlas datasets. We assessed the abundance of Bacteroides fragilis, Escherichia coli, Fusobacterium nucleatum, and Klebsiella pneumoniae through qPCR analysis and observed enrichment of all four bacterial species in CRC samples. Notably, except for E. coli, all exhibited significant enrichment in cases of CIMP. This enrichment was primarily driven by a subset of cases distinguished by high levels of these bacteria, which we labeled as “Superhigh”. The bacterial Superhigh status showed a significant association with CIMP (odds ratio 3.1, p-value = 0.013) and with MLH1 methylation (odds ratio 4.2, p-value = 0.0025). In TCGA CRC cases (393 tumor and 45 adj. normal), bacterial taxa information was extracted from non-human whole exome sequencing reads, and the bacterial Superhigh status was similarly associated with CIMP (odds ratio 2.9, p

ABSTRACT Objective: Although 18F-sodium fluoride (18F-NaF) uptake is frequently observed in extraosseous metastases of medullary thyroid carcinoma (MTC) with calcification, it can also occur in metastatic sites without visible calcium deposition, leading to the hypothesis that visually undetectable calcium accumulation may be responsible for this uptake. The aim of this study was to indirectly support this hypothesis by analyzing the correlation between the degree of 18F-NaF uptake and radiodensity in extraosseous MTC metastases, since calcium deposition can increase attenuation even when not visually detectable. Subjects and methods: Extraosseous metastatic lesions of 15 patients with MTC were evaluated using 18F-NaF positron-emission tomography (PET)/computed tomography (CT) and segmented by levels of standardized uptake value (SUV). The correlation between mean SUV and mean Hounsfield unit (HU) values was assessed for the entire group of segments and for two subgroups with different mean HU values. Results: Very high correlations were observed between mean SUV and mean HU values for both the entire group of segments and the subgroup with a mean HU value greater than 130 (p = 0.92 and p = 0.95, respectively; p < 0.01). High correlation (p = 0.71) was also observed in the subgroup with mean HU values ranging from 20 to 130 (p < 0.01). Conclusion: The findings of the present study suggest that there is an association between 18F-NaF uptake and calcium deposition in extraosseous metastases of MTC, supporting the hypothesis that visually undetectable calcium accumulation may be responsible for 18F-NaF uptake in regions without visible calcium deposition.

Summary: Background: The COVID-19 pandemic heightened risks for individuals with hematological malignancies due to compromised immune systems, leading to more severe outcomes and increased mortality. While interventions like vaccines, targeted antivirals, and monoclonal antibodies have been effective for the general population, their benefits for these patients may not be as pronounced. Methods: The EPICOVIDEHA registry (National Clinical Trials Identifier, NCT04733729) gathers COVID-19 data from hematological malignancy patients since the pandemic's start worldwide. It spans various global locations, allowing comprehensive analysis over the first three years (2020–2022). Findings: The EPICOVIDEHA registry collected data from January 2020 to December 2022, involving 8767 COVID-19 cases in hematological malignancy patients from 152 centers across 41 countries, with 42% being female. Over this period, there was a significant reduction in critical infections and an overall decrease in mortality from 29% to 4%. However, hospitalization, particularly in the ICU, remained associated with higher mortality rates. Factors contributing to increased mortality included age, multiple comorbidities, active malignancy at COVID-19 onset, pulmonary symptoms, and hospitalization. On the positive side, vaccination with one to two doses or three or more doses, as well as encountering COVID-19 in 2022, were associated with improved survival. Interpretation: Patients with hematological malignancies still face elevated risks, despite reductions in critical infections and overall mortality rates over time. Hospitalization, especially in ICUs, remains a significant concern. The study underscores the importance of vaccination and the timing of COVID-19 exposure in 2022 for enhanced survival in this patient group. Ongoing monitoring and targeted interventions are essential to support this vulnerable population, emphasizing the critical role of timely diagnosis and prompt treatment in preventing severe COVID-19 cases. Funding: Not applicable.

Objectives: Elderly patients with hematologic malignancies face the highest risk of severe COVID-19 outcomes. The infection's impact on different age groups remains unstudied in detail. Methods: We analyzed elderly patients (age groups: 65-70, 71-75, 76-80, and >80 years old) with hematologic malignancies included in the EPICOVIDEHA registry between January 2020 and July 2022. Univariable and multivariable Cox regression models were conducted to identify factors influencing death in COVID-19 patients with hematological malignancy. Results: The study included data from 3,603 elderly patients (aged 65 or older) with hematological malignancy, with a majority being male (58.1%) and a significant proportion having comorbidities. The patients were divided into four age groups, and the analysis assessed COVID-19 outcomes, vaccination status, and other variables in relation to age and pandemic waves. The 90-day survival rate for patients with COVID-19 was 71.2%, with significant differences between groups. The pandemic waves had varying impacts, with the first wave affecting patients over 80 years old, the second being more severe in 65-70, and the third being the least severe in all age groups. Factors contributing to 90-day mortality included age, comorbidities, lymphopenia, active malignancy, acute leukemia, less than three vaccine doses, severe COVID-19, and using only corticosteroids as treatment. Conclusion: These data underscore the heterogeneity of elderly hematological patients, highlight the different impacts of COVID-19 waves and the pivotal importance of vaccination, and may help in planning future healthcare efforts.

Malaria, an infectious disease with a tremendous impact on human health is caused by Plasmodium parasites, and transmitted by Anopheles mosquitoes. New approaches to control the disease involve transmission blocking strategies aiming to target the parasite in the mosquito. Here, we investigated the putative inhibitory activity of essential oils and their components on the early mosquito stages of the parasite. We employed an in vitro assay of gametocyte-to-ookinete development of the rodent model parasite Plasmodium berghei combined with high content screening. 60 essential oils with known composition were tested. The results revealed that fifteen EOs had inhibitory activity. Furthermore, a machine learning approach was used to identify the putative inhibitory components. Five of the most important chemical components indicated by the machine learning-based models were actually confirmed by the experimental approach. This combined approach was used for the first time to identify the potential transmission blocking activity of essential oils and single components at the zygote and ookinete stages.

Abstract Background Forced migration leaves deep marks on the psychological well-being of migrants, with post-traumatic stress disorder (PTSD) and other psychological conditions being prevalent among them. While research has clarified the extent to which pre-migration trauma is a predictor of mental health outcomes, the role of post-migration stressors in the settlement environment are yet to be fully characterized. Methods We monitored mental health of a cohort of 100 asylum-seekers during their 14-day COVID-19-related quarantine in reception facilities in Rome, Italy, through the administration of six questionnaires (a demographic survey, the WHO-5 well-being index, the Primary Care PTSD Screen for Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5), the Harvard Trauma Questionnaire, the Trauma and Loss Spectrum—Self Report, and the LiMEs—Italian version). Through the combination of statistical analysis and supervised learning, we studied the impact of the first contact with the reception system on asylum-seekers’ mental health and sought for possible risk and shielding factors for PTSD. Results We find that sheltering in refugee centers has a positive impact on migrants’ mental health; asylum-seekers with PTSD reported more traumatic events and personality characteristics related to loss and trauma; life events are predictors of PTSD in asylum-seekers. Conclusions We identify past traumatic experiences as predictors of PTSD, and establish the positive role the immediate post-migration environment can play on migrants’ psychological well-being. We recommend for host countries to implement reception models that provide effective protection and integration of asylum-seekers, similar to those in the Italian system.

Geoscientific models are facing increasing challenges to exploit growing datasets coming from remote sensing. Universal differential equations (UDEs), aided by differentiable programming, provide a new scientific modelling paradigm enabling both complex functional inversions to potentially discover new physical laws and data assimilation from heterogeneous and sparse observations. We demonstrate an application of UDEs as a proof of concept to learn the creep component of ice flow, i.e. a nonlinear diffusivity differential equation, of a glacier evolution model. By combining a mechanistic model based on a two-dimensional shallow-ice approximation partial differential equation with an embedded neural network, i.e. a UDE, we can learn parts of an equation as nonlinear functions that then can be translated into mathematical expressions. We implemented this modelling framework as ODINN.jl, a package in the Julia programming language, providing high performance, source-to-source automatic differentiation (AD) and seamless integration with tools and global datasets from the Open Global Glacier Model in Python. We demonstrate this concept for 17 different glaciers around the world, for which we successfully recover a prescribed artificial law describing ice creep variability by solving ∼ 500 000 ordinary differential equations in parallel. Furthermore, we investigate which are the best tools in the scientific machine learning ecosystem in Julia to differentiate and optimize large nonlinear diffusivity UDEs. This study represents a proof of concept for a new modelling framework aiming at discovering empirical laws for large-scale glacier processes, such as the variability in ice creep and basal sliding for ice flow, and new hybrid surface mass balance models.

Non-prosthetic peri-implant fractures (NPPIFs) are often reported mixed with periprosthetic fractures (PPFs), but they are different entities. Due to the increase in the age of the world’s population and to the intensification of surgeries for fractures, nowadays, peri-implant fractures are a very frequent entity in clinical practice, with an increasing trend expected in the future. A clear exclusive classification of NPPIFs is not reported in the literature. The aim of this study is to provide a valid comprehensive classification for all the NPPIFs. X-rays of all the peri-implant cases treated in our unit in a 3-year period were retrospectively collected. Five orthopedic surgeons reviewed 30 X-rays of NPPIFs, providing a code according to the classification proposed. After a 3-month interval, they reviewed the same X-rays. Eighteen femoral, eight humeral, and four forearm peri-implant fractures were collected and showed to the raters. Inter- and intra-observer reliability was calculated using a k-statistic, showing a moderate agreement between observers (κ = 0.73) and a substantial agreement between the observations of the same viewer (κ = 0.82). The literature lacks a comprehensive classification for peri-implant fractures that considers all the bones and all the types of implants. The proposed classification is meant to be an instrument for orthopedic surgeons to categorize these types of fractures and seems to be simple, easy to comprehend, and reproducible. This new classification can provide the orthopedic surgeon a reliable method to clearly catalogue different fractures according to the site and the implants; the physicians can use it, through a code, in clinical practice to describe an NPPIF without the need of images. Further studies may be necessary to confirm the validity and eventually to improve the suggested classification.

Although the postmortem interval estimation still represents one of the main goals of forensic medicine, there are still several limitations that weigh on the methods most used for its determination: for this reason, even today, precisely estimating the postmortem interval remains one of the most important challenges in the forensic pathology field. To try to overcome these limitations, in recent years, numerous studies have been conducted on the potential use of the mRNA degradation time for reaching a more precise post mortem interval (PMI) estimation. An evidence-based systematic review of the literature has been conducted to evaluate the state of the art of the knowledge focusing on the potential correlation between mRNA degradation and PMI estimation. The research has been performed using the electronic databases PubMed and Scopus. The analysis conducted made it possible to confirm the potential applicability of mRNA for reaching a more precise PMI estimation. The analysis of the results highlighted the usefulness of some mRNAs, such as β-actin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA, especially in short time frames, within a few hours or days of death. The matrices on which these analyses were conducted were also analyzed, resulting in less exposure to the external environment, including the heart, brain, and dental pulp. The major limitations were also reported, including the short time intervals analyzed in most of the articles, the lack of mathematical models, and the failure to report the error rate between the mRNA degradation time and PMI. Given the still small number of published articles, the lack of globally recognized standardized methods, and the numerous techniques used to evaluate the mRNA degradation times, numerous and larger studies are still necessary to reach more solid and shared evidence.

Cestodes use own lipid-binding proteins to capture and transport hydrophobic ligands, including lipids that they cannot synthesise as fatty acids and cholesterol. In E. granulosus s.l., one of these lipoproteins is antigen B (EgAgB), codified by a multigenic and polymorphic family that gives rise to five gene products (EgAgB8/1-5 subunits) assembled as a 230 kDa macromolecule. EgAgB has a diagnostic value for cystic echinococcosis, but its putative role in the immunobiology of this infection is still poorly understood. Accumulating research suggests that EgAgB has immunomodulatory properties, but previous studies employed denatured antigen preparations that might exert different effects than the native form, thereby limiting data interpretation. This work analysed the modulatory actions on macrophages of native EgAgB (nEgAgB) and the recombinant form of EgAg8/1, which is the most abundant subunit in the larva and was expressed in insect S2 cells (rEgAgB8/1). Both EgAgB preparations were purified to homogeneity by immunoaffinity chromatography using a novel nanobody anti-EgAgB8/1. nEgAgB and rEgAgB8/1 exhibited differences in size and lipid composition. The rEgAgB8/1 generates mildly larger lipoproteins with a less diverse lipid composition than nEgAgB. Assays using human and murine macrophages showed that both nEgAgB and rEgAgB8/1 interfered with in vitro LPS-driven macrophage activation, decreasing cytokine (IL-1β, IL-6, IL-12p40, IFN-β) secretion and ·NO generation. Furthermore, nEgAgB and rEgAgB8/1 modulated in vivo LPS-induced cytokine production (IL-6, IL-10) and activation of large (measured as MHC-II level) and small (measured as CD86 and CD40 levels) macrophages in the peritoneum, although rEgAgB8/1 effects were less robust. Overall, this work reinforced the notion that EgAgB is an immunomodulatory component of E. granulosus s.l. Although nEgAgB lipid’s effects cannot be ruled out, our data suggest that the EgAgB8/1 subunit contributes to EgAgB´s ability to regulate the inflammatory activation of macrophages.

Increased risk of neurodegenerative diseases has been envisaged for air pollution exposure. On the other hand, environmental risk factors, including air pollution, have been suggested for Amyotrophic Lateral Sclerosis (ALS) pathomechanism. Therefore, the neurotoxicity of ultrafine particulate matter (PM0.1) (PM < 0.1 μm size) and its sub-20 nm nanoparticle fraction (NP20) has been investigated in motor neuronal-like cells and primary cortical neurons, mainly affected in ALS. The present data showed that PM0.1 and NP20 exposure induced endoplasmic reticulum (ER) stress, as occurred in cortex and spinal cord of ALS mice carrying G93A mutation in SOD1 gene. Furthermore, NSC-34 motor neuronal-like cells exposed to PM0.1 and NP20 shared the same proteomic profile on some apoptotic factors with motor neurons treated with the L-BMAA, a neurotoxin inducing Amyotrophic Lateral Sclerosis/Parkinson–Dementia Complex (ALS/PDC). Of note ER stress induced by PM0.1 and NP20 in motor neurons was associated to pathological changes in ER morphology and dramatic reduction of organellar Ca2+ level through the dysregulation of the Ca2+-pumps SERCA2 and SERCA3, the Ca2+-sensor STIM1, and the Ca2+-release channels RyR3 and IP3R3. Furthermore, the mechanism deputed to ER Ca2+ refilling (e.g. the so called store operated calcium entry-SOCE) and the relative currents ICRAC were also altered by PM0.1 and NP20 exposure. Additionally, these carbonaceous particles caused the exacerbation of L-BMAA-induced ER stress and Caspase-9 activation. In conclusion, this study shows that PM0.1 and NP20 induced the aberrant expression of ER proteins leading to dysmorphic ER, organellar Ca2+ dysfunction, ER stress and neurotoxicity, providing putative correlations with the neurodegenerative process occurring in ALS.

Opportunistic sensors are increasingly used for rainfall measurement. However, their raw data are collected by a variety of systems that are often not primarily intended for rainfall monitoring, resulting in a plethora of different data formats and a lack of common standards. This hinders the sharing of opportunistic sensing (OS) data, their automated processing, and, at the end, their practical usage and integration into standard observation systems. This paper summarises the experiences of the more than 100 members of the OpenSense Cost Action involved in the OS of rainfall. We review the current practice of collecting and storing precipitation OS data and corresponding metadata, and propose new common guidelines describing the requirements on data and metadata collection, harmonising naming conventions, and defining human-readable and machine readable file formats for data and metadata storage. We focus on three sensors identified by the OpenSense community as prominent representatives of the OS of precipitation: Commercial microwave links (CML): fixed point-to-point radio links mainly used as backhauling connections in telecommunication networks Satellite microwave links (SML): radio links between geostationary Earth orbit (GEO) satellites and ground user terminals. Personal weather stations (PWS): non-professional meteorological sensors owned by citizens. The conventions presented in this paper are primarily designed for storing, handling, and sharing historical time series and do not consider specific requirements for using OS data in real time for operational purposes. The conventions are already now accepted by the ever growing OpenSense community and represent an important step towards automated processing of OS raw data and community development of joint OS software packages.

Proximal humerus fractures account for about 5% of fragility fractures. These involve a significant burden of disability and a reduced quality of life. This study aims to compare functional results and surgical outcomes (closed reduction and internal fixation with the internal closure system of the proximal humerus) and the conservative management of proximal humerus fractures by 2-, 3-, 4-parts, in patients older than 55 years. Between January 2017 and April 2019, 65 patients with 2, 3 or 4-part fractures were retrospectively analyzed: 29 patients (5 males and 24 females) with an average age of 70.8 ± 9.9 years treated non-surgically (conservative group (CG)) and 36 patients (11 males and 25 females) with an average age of 66.2 ± 7.1 years treated surgically with plate fixation (operating group (OG)). Using different evaluation scores, we compared the OG and the CG. Through the DASH score we have seen how at 12 months there is a satisfactory result in patients with conservative treatment (p = 0.0019). Constant-Murley scale shows no difference between the two treatments (p = 0.2300). BARTHEL scale and SST score did not give statistically satisfactory results. Also, after one year of follow-up, patients treated with conservative therapy had a higher improvement in their Range of Motion (ROM) values than patients treated with surgical treatment. The results in terms of pain in NPRS at 3, 6, 12 months are better for conservative groups (p = 0,0000). Our findings suggest that conservative treatment in proximal humeral fractures, particularly in multi-fragmented fractures in patients over 55 years of age, designs an excellent alternative to the surgical option.

Supernova (SN) 1987A is one of the best candidates to exploit the capabilities of the freshly launched XRISM satellite. This celestial object offers the unique opportunity to study the evolution of an SN into a young supernova remnant. To date, the X-ray emission has been dominated by the shocked circumstellar medium, with no shocked ejecta firmly detected. However, recent studies provide compelling evidence that in the forthcoming years, the X-ray emission from SN 1987A will increasingly stem from the ejecta. Our aim is to assess the proficiency of the XRISM-Resolve high-resolution spectrometer in pinpointing signatures of the shocked ejecta in SN 1987A. Taking advantage of a self-consistent state-of-the-art magneto-hydrodynamic simulation that describes the evolution from SN 1987A to its remnant, we synthesized the XRISM-Resolve spectrum of SN 1987A, as it would be collected in the allocated observation during the performance verification phase, which is foreseen for 2024. Our predictions clearly show the leading role of shocked ejecta in shaping the profile of the emission lines. The Doppler broadening associated with the bulk motion along the line of sight of the rapidly expanding ejecta is shown to increase the line widths well above the values observed so far. The quantitative comparison between our synthetic spectra and the XRISM spectra will enable us to establish a strong connection between the broadened line emission and the freshly shocked ejecta. This, in turn, will allow us to retrieve the ejecta dynamics and chemical composition from the X-ray emission.

Abstract Background The Order of Physicians and Dentists of the Province of Rome aims at focusing on the satisfaction of healthcare personnel as an essential factor for the quality of medical care in the health sector. The aim of this study is to assess and prioritize the factors that can be linked to a higher or lower degree of job satisfaction in Primary Care Pediatricians (PCPs). Methods This study is a cross sectional survey. A questionnaire was administered to all primary care pediatricians registered to the Order, exploring in particular the work activity organization, the level of satisfaction in their professional life, and the level of perceived health. A pilot activity was conducted to validate the questionnaire. Fisher exact test and ordinal logistic regression (ologit) models were used for the univariate and multivariate analysis. Results The highest level of job dissatisfaction, in both men and women, was found to be in the practice type without any form of association; among women, it reached an even higher level for those who had their own practice at a distance of 20–40 km from their home. Women, compared to men, maintained a lower level of job satisfaction also while working in Pediatric Primary Care Units (PPCUs). In PPCUs, for the same distance, females showed a more similar pattern to males. Men working in PPCUs, regardless of distance, declared a higher degree of job satisfaction. Both men and women, working as a group pediatrician or in PPCUs, did not show a significant difference in the level of job satisfaction. Conclusions The study contributes to a deeper understanding of the factors that may influence levels of career satisfaction in female and male PCPs. Therefore, research and interventions regarding job satisfaction should foster an organizational network connection among PCPs for their job and individual well-being, from a perspective of enhancing patient care. A major effort to improve work-life balance and career satisfaction among women is important, suggesting that interventions for improving job satisfaction could benefit from a gender-specific approach.

Abstract The Pandora Software Development Kit and algorithm libraries provide pattern-recognition logic essential to the reconstruction of particle interactions in liquid argon time projection chamber detectors. Pandora is the primary event reconstruction software used at ProtoDUNE-SP, a prototype for the Deep Underground Neutrino Experiment far detector. ProtoDUNE-SP, located at CERN, is exposed to a charged-particle test beam. This paper gives an overview of the Pandora reconstruction algorithms and how they have been tailored for use at ProtoDUNE-SP. In complex events with numerous cosmic-ray and beam background particles, the simulated reconstruction and identification efficiency for triggered test-beam particles is above 80% for the majority of particle type and beam momentum combinations. Specifically, simulated 1 GeV/c charged pions and protons are correctly reconstructed and identified with efficiencies of 86.1 $$\pm 0.6$$ ± 0.6 % and 84.1 $$\pm 0.6$$ ± 0.6 %, respectively. The efficiencies measured for test-beam data are shown to be within 5% of those predicted by the simulation.

Abstract Background Attachment theory represents a reference model for understanding better how pre-existing personality factors can influence the coping with some chronic conditions. The onset of a chronic disease can represent a "threat" to the relationships between the subject and parental figures according to the type of bond that already exists. The aim of our study was to explore attachment styles in a sample of hemodialysis patients, hypothesizing that a secure attachment bond can constitute a protective factor for the quality of life and mental health in this type of patients. Design We used a cross-sectional design. Methods Fifty hemodialysis patients were given the following tests: Attachment Style Questionnaire (ASQ) to assess attachment styles, Parental Bonding Instrument (PBI) to assess parental bonding, Short Form Health Survey-36 (SF-36) for perceived quality of life and Middlesex Hospital Questionnaire (MHQ) to detect key psychological symptoms and relevant traits. Results The results showed that secure attachment style correlated with good general health (r = 0.339; p

Background: The treatment of displaced intra-articular calcaneal fractures (DIACF) is debated. This study compares open reduction and internal fixation (ORIF) with minimally invasive osteosynthesis (MIOS). Methods: We conducted a retrospective study on 70 patients with DIACF treated between January 2018 and September 2022, divided into ORIF (n = 50) and MIOS (n = 20) groups. Functional outcomes were assessed using the Maryland Foot Score (MFS) and the Creighton-Nebraska Health Foundation Assessment Scale (CNHFAS). Radiographic outcomes, complication rates, and reintervention rates were evaluated. A chi-square analysis examined the correlation between Sanders classification and treatment choice. Results: The chi-square analysis indicated no significant correlation between the complexity of the fracture and the type of treatment chosen (χ2 = 0.175, p = 0.916). Additionally, the Cochran–Armitage test for trend showed no significant trend in the choice of treatment based on fracture complexity (statistic = 0.048, p = 0.826). A Kaplan–Meier analysis showed a longer time to reintervention for MIOS (p = 0.029). Complication rates were similar, with specific complications varying between groups. Quality-of-life outcomes were comparable. Conclusions: ORIF is preferable for high-demand patients due to better anatomical outcomes, while MIOS suits high-risk patients by reducing reinterventions and complications. Further randomized trials are needed to confirm these findings.

Kounis Syndrome (KS) is a clinical entity triggered by allergic or hypersensitivity reactions capable of inducing acute coronary events. Several causes can induce KS, including drugs and insect stings. Here, a rare case of post mortem assessment of fatal KS related to fluorescein retinal angiography has been reported. An 80-year-old man in follow-up for a retinal vein thrombosis underwent a retinal fluoroangiography. Approximately 30 min later, the patient complained of sweating and dizziness, and suddenly lost consciousness due to a cardiac arrest. Despite the immediate cardiopulmonary resuscitation, he died. The autopsy revealed foamy yellowish edema in the respiratory tract and coronary atherosclerosis with eccentric plaques partially obstructing the lumen. The routine histology highlighted lung emphysema and myocyte break-up with foci of contraction band necrosis at the myocardial tissue. Biochemistry showed increased serum tryptase, troponin, and p-BNP. Activated and degranulated (tryptase) mast cells were detected, using immunohistochemistry, in the larynx, lungs, spleen, and heart. Acute myocardial ischemia due to allergic coronary vasospasm related to fluorescein hypersensitivity has been assessed as cause of death. KS-related deaths are considered rare events, and the post mortem assessment of KS quite difficult. The integration of several investigations (gross and microscopic examination, biochemistry, immunohistochemistry) can provide useful findings to support the diagnosis, helping to reduce the unrecognized cases as much as possible.

Refractory acute myeloid leukaemia is very difficult to treat and represents an unmet clinical need. In recent years, new drugs and combinations of drugs have been tested in this category, with encouraging results. However, all treated patients relapsed and died from the disease. The only curative option is allogeneic transplantation through a graft from a healthy donor immune system. Using myeloablative conditioning regimens, the median overall survival regimens is 19%. Several so-called sequential induction chemotherapies followed by allogeneic transplantation conditioned by reduced intensity regimens have been developed, improving the overall survival to 25–57%. In the allogeneic transplantation field, continuous improvements in practices, particularly regarding graft versus host disease prevention, infection prevention, and treatment, have allowed us to observe improvements in survival rates. This is true mainly for patients in complete remission before transplantation and less so for refractory patients. However, full myeloablative regimens are toxic and carry a high risk of treatment-related mortality. In this review, we describe the results obtained with the different modalities used in more recent retrospective and prospective studies. Based on these findings, we speculate how allogeneic stem cell transplantation could be modified to maximise its therapeutic effect on refractory acute myeloid leukaemia.

The concept of gray-zone lymphoma (GZL) has been progressively refined since its introduction in the literature in 1998. For several years, it was applied to a rather broad spectrum of conditions, posing the problem of the differential diagnosis between any type of Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma, with special reference to primary mediastinal forms (PMBL). Officially recognised as a provisional entity in the 4th and revised 4th editions of the WHO Classification of Tumour of Haematopoietic and Lymphoid Tissues with the term “B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and classic Hodgkin lymphoma”, it was limited to tumours showing either morphologic features reminiscent of classic HL (CHL) but carrying a complete B-cell phenotype or conversely provided with a PMBL morphology yet revealing CHL phenotypic characteristics. The definition of GZL has been further revised in the recently published International Lymphoma Classification and 5th edition of the WHO Classification of Haematolymphoid Tumours, which have limited it to mediastinal neoplasms (MGZL) based on emerging molecular evidence. The aim of this review is to critically discuss the issue of MGZL, as well as in light of the suboptimal response to current therapies.

Abstract The ICARUS collaboration employed the 760-ton T600 detector in a successful 3-year physics run at the underground LNGS laboratory, performing a sensitive search for LSND-like anomalous $$\nu _e$$ ν e appearance in the CERN Neutrino to Gran Sasso beam, which contributed to the constraints on the allowed neutrino oscillation parameters to a narrow region around 1 eV $$^2$$ 2 . After a significant overhaul at CERN, the T600 detector has been installed at Fermilab. In 2020 the cryogenic commissioning began with detector cool down, liquid argon filling and recirculation. ICARUS then started its operations collecting the first neutrino events from the booster neutrino beam (BNB) and the Neutrinos at the Main Injector (NuMI) beam off-axis, which were used to test the ICARUS event selection, reconstruction and analysis algorithms. ICARUS successfully completed its commissioning phase in June 2022. The first goal of the ICARUS data taking will be a study to either confirm or refute the claim by Neutrino-4 short-baseline reactor experiment. ICARUS will also perform measurement of neutrino cross sections with the NuMI beam and several Beyond Standard Model searches. After the first year of operations, ICARUS will search for evidence of sterile neutrinos jointly with the Short-Baseline Near Detector, within the Short-Baseline Neutrino program. In this paper, the main activities carried out during the overhauling and installation phases are highlighted. Preliminary technical results from the ICARUS commissioning data with the BNB and NuMI beams are presented both in terms of performance of all ICARUS subsystems and of capability to select and reconstruct neutrino events.

Abstract Esmethadone (REL-1017) is the opioid-inactive dextro-isomer of methadone and a low-affinity, low-potency uncompetitive NMDA receptor antagonist. In a Phase 2, randomized, double-blind, placebo-controlled trial, esmethadone showed rapid, robust, and sustained antidepressant effects. Two studies were conducted to evaluate the abuse potential of esmethadone. Each study utilized a randomized, double-blind, active-, and placebo-controlled crossover design to assess esmethadone compared with oxycodone (Oxycodone Study) or ketamine (Ketamine Study) in healthy recreational drug users. Esmethadone 25 mg (proposed therapeutic daily dose), 75 mg (loading dose), and 150 mg (Maximum Tolerated Dose) were evaluated in each study. Positive controls were oral oxycodone 40 mg and intravenous ketamine 0.5 mg/kg infused over 40 min. The Ketamine study included oral dextromethorphan 300 mg as an exploratory comparator. The primary endpoint was maximum effect (Emax) for Drug Liking, assessed using a bipolar 100-point visual analog scale (VAS). A total of 47 and 51 participants completed the Oxycodone Study and the Ketamine Study, respectively (Completer Population). In both studies, esmethadone doses ranging from therapeutic (25 mg) to 6 times therapeutic (150 mg) had a meaningful and statistically significantly (p

Allogeneic stem cell transplantation remains the only therapy for congenital, severe haemoglobinopathies that is able to reverse the pathological phenotype. In the severe form of thalassemia, regular transfusions are needed early in life. This population of patients could benefit from allo-SCT. However, the great efficacy of transplantation must be counterbalanced by the mortality and morbidity related to the procedure. In this short review, we reviewed the most recent data in the field of transplantation in transfusion-dependent thalassemia (TDT), highlighting the factors that have a major impact on outcomes.

Abstract This article reports the first observation of the Moon and the Sun shadows in the sky distribution of cosmic-ray induced muons measured by the KM3NeT/ORCA detector. The analysed data-taking period spans from February 2020 to November 2021, when the detector had 6 Detection Units deployed at the bottom of the Mediterranean Sea, each composed of 18 Digital Optical Modules. The shadows induced by the Moon and the Sun were detected at their nominal position with a statistical significance of 4.2 $$\sigma $$ σ and 6.2 $$\sigma $$ σ , and an angular resolution of $$\sigma _{res}=0.49^\circ $$ σ res = 0 . 49 ∘ and $$\sigma _{res}=0.66^\circ $$ σ res = 0 . 66 ∘ , respectively, consistent with the prediction of $$0.53^\circ $$ 0 . 53 ∘ from simulations. This early result confirms the effectiveness of the detector calibration, in time, position and orientation and the accuracy of the event direction reconstruction. This also demonstrates the performance and the competitiveness of the detector in terms of pointing accuracy and angular resolution.

Abstract In the era of precision measurements of the neutrino oscillation parameters, upcoming neutrino experiments will also be sensitive to physics beyond the Standard Model. KM3NeT/ORCA is a neutrino detector optimised for measuring atmospheric neutrinos from a few GeV to around 100 GeV. In this paper, the sensitivity of the KM3NeT/ORCA detector to neutrino decay has been explored. A three-flavour neutrino oscillation scenario, where the third neutrino mass state ν 3 decays into an invisible state, e.g. a sterile neutrino, is considered. We find that KM3NeT/ORCA would be sensitive to invisible neutrino decays with 1/α 3 = τ 3 /m 3 < 180 ps/eV at 90% confidence level, assuming true normal ordering. Finally, the impact of neutrino decay on the precision of KM3NeT/ORCA measurements for θ 23, Δ m 31 2 $$ \Delta {m}_{31}^2 $$ and mass ordering have been studied. No significant effect of neutrino decay on the sensitivity to these measurements has been found.

BackgroundDeep phenotyping of Parkinson’s disease (PD) is essential to investigate this fastest-growing neurodegenerative disorder. Since 2015, over 800 individuals with PD and atypical parkinsonism along with more than 800 control subjects have been recruited in the frame of the observational, monocentric, nation-wide, longitudinal-prospective Luxembourg Parkinson’s study.ObjectiveTo profile the baseline dataset and to explore risk factors, comorbidities and clinical profiles associated with PD, atypical parkinsonism and controls.MethodsEpidemiological and clinical characteristics of all 1,648 participants divided in disease and control groups were investigated. Then, a cross-sectional group comparison was performed between the three largest groups: PD, progressive supranuclear palsy (PSP) and controls. Subsequently, multiple linear and logistic regression models were fitted adjusting for confounders.ResultsThe mean (SD) age at onset (AAO) of PD was 62.3 (11.8) years with 15% early onset (AAO 50 years, 2.80 (2.62) years, 62.7% and 53.3 (19.5). The highest frequency of hyposmia was detected in PD followed by PSP and controls (72.9%; 53.2%; 14.7%), challenging the use of hyposmia as discriminating feature in PD vs. PSP. Alcohol abstinence was significantly higher in PD than controls (17.6 vs. 12.9%, p = 0.003).ConclusionLuxembourg Parkinson’s study constitutes a valuable resource to strengthen the understanding of complex traits in the aforementioned neurodegenerative disorders. It corroborated several previously observed clinical profiles, and provided insight on frequency of hyposmia in PSP and dietary habits, such as alcohol abstinence in PD.Clinical trial registration: clinicaltrials.gov, NCT05266872.

BackgroundTemporary intravascular shunts (TIVS) may allow quick revascularization and distal reperfusion, reducing the ischemic time (IT) when an arterial injury occurs. Furthermore, TIVS temporarily restore peripheral perfusion during the treatment of concomitant life-threatening injuries or when patients require evacuation to a higher level of care. Notwithstanding, there are still disputes regarding the use of TIVS, in view of the paucity of evidence in terms of potential benefits and with regard to the anticoagulation during the procedure. The present study aimed to assess TIVS impact, safety, and timing on limb salvage in complex civilian vascular traumas.Patients and methodsData were retrieved from the prospective database of our department, which included all patients hospitalized with a vascular injury of the extremities between January 2006 and December 2022. Patients undergoing TIVS during vascular injury management were included in group A, and those who could not postpone immediate care for TIVS insertion were included in group B (control group). Data concerning the times required for extremity revascularization or other surgical procedures such as orthopedic interventions and the time of limb ischemia were compared between the two groups. A comparison of the postoperative course between the two groups was also performed.ResultsA total of 53 patients were included: group A (TIVS insertion, n = 31) and group B (control, n = 22). Revascularization time significantly differed (p = 0.002) between the two groups, which is lower in group A (4.17 ± 2.37 h vs. 5.81 ± 1.26 h). TIVS positively affected the probability of limb salvage (p = 0.02). At multivariate analysis, the factors independently associated with limb salvage were TIVS usage, the necessity of hyperbaric oxygen therapy, and the total IT. In group A, there were three deaths and one major amputation, and in group B, there were two deaths and four major amputations.ConclusionsThe use of TIVS minimizes revascularization time and improves limb salvage probability. A multidisciplinary approach is recommended, and correct surgical timing is key to ensure the best outcome.

BackgroundPrimary care providers (PCPs) play an essential role in obesity care as they represent the first contact for patients seeking weight loss interventions.ObjectiveThis study explored the knowledge, experiences, and perceptions of PCPs in the Lazio Region of Italy in the management of obesity.Design and subjectsWe conducted an anonymous survey delivered from March to July 2022 via the newsletter of Rome Provincial Order of Physicians and Dentists and at the annual meeting of the regional section of the Italian Obesity Society.ApproachThe survey consisted of 24 closed-ended questions grouped into 5 sections: sociodemographic and work information; assessment of obesity; management of obesity; connections with regional Centres for Obesity Management; attitudes towards obesity.Key resultsA total of 92 PCPs accessed the survey. Of those, 2.2% were excluded because they did not see any patients with obesity. A total of 68 PCPs (75.6%) had complete questionnaires and were included in this analysis. All participants reported asking their patients about their eating habits, lifestyle, and clinical complications at the first assessment. Body weight and blood pressure were measured by 98.5% of participants and 82% calculate body mass index (BMI), while a small proportion of PCPs analysed body composition and fat distribution. Over 80% prescribed laboratory tests and ECG. Approximately 40% of PCPs did not refer patients for nutritional counselling, and most prescribed a low-calorie diet. Sixty-three percent referred patients to an endocrinologist, 48.5% to a psychotherapist, and a minority to specialists for obesity complications. Twenty-three percent prescribed anti-obesity medications and 46.5% referred patients for bariatric surgery only in severe cases. Ninety-one percent stated that obesity is “a complex and multifactorial disease” and 7.4% considered obesity to be secondary to other conditions.ConclusionsDespite most PCPs adopt a correct approach to manage patients with obesity, many aspects could be improved to ensure optimal and multidisciplinary management.

Sinorhizobium meliloti is a model alpha-proteobacterium for investigating microbe-host interactions, in particular nitrogen-fixing rhizobium-legume symbioses. Successful infection requires complex coordination between compatible host and endosymbiont, including bacterial production of succinoglycan, also known as exopolysaccharide-I (EPS-I). In S. meliloti EPS-I production is controlled by the conserved ExoS-ChvI two-component system. Periplasmic ExoR associates with the ExoS histidine kinase and negatively regulates ChvI-dependent expression of exo genes, necessary for EPS-I synthesis. We show that two extracytoplasmic proteins, LppA (a lipoprotein) and JspA (a lipoprotein and a metalloprotease), jointly influence EPS-I synthesis by modulating the ExoR-ExoS-ChvI pathway and expression of genes in the ChvI regulon. Deletions of jspA and lppA led to lower EPS-I production and competitive disadvantage during host colonization, for both S. meliloti with Medicago sativa and S. medicae with M. truncatula. Overexpression of jspA reduced steady-state levels of ExoR, suggesting that the JspA protease participates in ExoR degradation. This reduction in ExoR levels is dependent on LppA and can be replicated with ExoR, JspA, and LppA expressed exogenously in Caulobacter crescentus and Escherichia coli. Akin to signaling pathways that sense extracytoplasmic stress in other bacteria, JspA and LppA may monitor periplasmic conditions during interaction with the plant host to adjust accordingly expression of genes that contribute to efficient symbiosis. The molecular mechanisms underlying host colonization in our model system may have parallels in related alpha-proteobacteria.

Introdução: Feohifomicose é uma infecção fúngica causada por diversos fungos do gênero Dematiaceous, com pigmento enegrecido, principalmente dos gêneros Wangiella, Alternaria e Exophiala. Encontrados em solo com ampla distribuição pelo mundo, podendo infectar imunossuprimidos, sendo oportunistas e imunocompetentes, sendo neste últimos menor a prevalência. A maioria dos casos identificados estão associados a pacientes imunossuprimidos, submetidos a transplantes de órgãos ou a malignidade. Lesões cutâneas e nódulos subcutâneos são as formas de apresentação mais comuns. A maioria das infecções é superficial e precedida de trauma local. Os sintomas variam de acordo com o acometimento e geralmente incluem lesões cutâneas, abscessos, úlceras e nódulos. Objetivos: Reportaremos um caso, diagnosticado como feohifomicose cutânea em região dorsal de membro inferior direito, em paciente imunocompetente, atendida no ambulatório do serviço de infectologia do Hospital Heliópolis-SP. Realizada coleta de dados, revisão de prontuário e pesquisa bibliográfica sobre feohifomicose. O relato foi feito mediante obtenção de Termo de Consentimento Livre e Esclarecido em que o paciente autoriza utilização de dados clínicos. Discussão: Paciente, 51 anos, natural de Bom Jesus da Lapa, procedente de São Paulo há 12 anos, relata surgimento de lesão em dorso de pé direito, em julho de 2022 após viagem para Bahia. Lesão medindo 5 mm, hipercrômica, dolorosa ao toque. Realizado diagnóstico de feohifomicose através de biópsia de lesão, com cloração de Grocott positivo, juntamente com Ácido Periódico de Schiff positivo para hifas e esporos. Surgimento de lesão semelhante em região retroauricular esquerda. Iniciado tratamento com Itraconazol, com melhora progressiva de sintomas. O exame histopatológico se torna necessário para o diagnóstico. Este seria um dos raros casos relatados sobre feohifomicose em pacientes imunocompetentes, descritos em literatura.

Introdução: O sarcoma de Kaposi (SK) é uma neoplasia endotelial associada ao Herpesvírus Humano 8, que comumente, se restringe a lesões cutâneas e de mucosa oral. O sarcoma em sua forma clínica clássica é uma patologia rara e com incidência de 0,02 por 100 mil habitantes, com ocorrência de uma mulher para cada 10 homens. Suas formas mais agressivas incluem lesões viscerais e sangramentos internos. É classificado nas variantes: clássica, endêmica, iatrogênica e epidêmica- raro em imunocompetentes. Objetivos: Contribuir com as discussões a respeito do Sarcoma de Kaposi com o caso disseminado de uma paciente idosa imunocompetente, que iniciou com placas eritematosas, infiltradas, violáceas prevalentes em membros inferiores e abdômen há um ano. Paciente internada m enfermaria do serviço de infectologia do Hospital Heliópolis-SP. O estudo foi feito mediante obtenção de Termo de Consentimento Livre e Esclarecido em que o paciente autoriza utilização de dados clínicos. Discussão: Mulher, 66 anos, natural de Santos (São Paulo), imunocompetente, com surgimento de pápulas eritematosas em membros inferiores há 1 ano, que evoluíram em 40 dias para placas infiltrativas, violáceas, pruriginosas, dolorosas, em todo corpo com predomínio em membros inferiores e abdome. O diagnóstico foi efetuado por imuno-histoquímica e anatomopatológico, com biópsia cutânea de membro inferior direito, apresentando compatibilidade com SK, positividade para CD31, ERG e HHV-8 e neoplasia em colágeno denso da derme com crescimento a cerca de estruturas pré-existentes. Estadiamento realizado com lesões compatíveis com Sarcoma de Kaposi em broncoscopia. Corticoides e antibióticos foram utilizados sem sucesso até iniciar a quimioterapia. Descartadas neoplasias por imagem e marcadores tumorais, juntamente com demais imunodeficiências primárias. Este seria um dos raros casos relatados sobre Sarcoma de Kaposi disseminado em paciente imunocompetente, descritos em literatura.

Introdução: A esquistossomose é um importante problema de saúde pública na África Subsaariana, Ásia e América do Sul. Mais de 200 milhões de pessoas em todo o mundo são afetadas e cerca de 600 milhões de pessoas com risco de infecção em 79 países endêmicos. No Brasil, 6 a 10 milhões de pessoas vivem com o Schistosoma mansoni. Em áreas endêmicas como estados de Minas Gerais e Bahia, a prevalência ultrapassa a 15%. A infecção esquistossomótica do sistema nervoso central é conhecida como neuroesquistossomose e pode afetar o cérebro ou a medula espinhal ocorrendo durante todas as fases da esquistossomose. Forma rara de esquistossomose, sendo assintomática ou resultar em complicações graves manifestando-se como síndromes neurológicas. Comumente associada à infestação por Schistosoma japonicum, mas também associados ao Schistosoma mansoni e ao Schistosoma haematobium. Objetivos: Apresentaremos um raro caso, com observação de um ano, dos sintomas de Neuroesquistossomose em sua forma encefálica como manifestação de uma síndrome tumoral cerebral, do ambulatório do serviço de infectologia do Hospital Heliópolis-SP. Realizada coleta de dados, revisão de prontuário e pesquisa bibliográfica sobre Neuroesquistossomose. O estudo foi feito mediante obtenção de Termo de Consentimento Livre e Esclarecido em que o paciente autoriza utilização de dados clínicos. Discussão: Paciente, masculino, 61 anos, nascido em Brejo Santo (Ceará), iniciou sintomas de parestesia em membro superior e inferior direitos, associados a síncopes e episódios convulsivos há 1 ano. Evolui com quadro de lentificação de fala com afasia, piora das crises convulsivas e distúrbio de marcha, de caráter progressivo. Diagnosticado com Neuroesquistossomose apresentando exame histopatológico positivo com ovos de Schistosoma mansoni em biópsia cerebral. Imagem com efeito de massa em ínsula esquerda, associada a edema cerebral, presente em tomografia de crânio, interpretada inicialmente como glioma. A progressão da doença deve apontar para a possibilidade de sequelas motoras irreversíveis, devendo-se iniciar uma ampla investigação com exames de imagem de rastreio e biópsia para o diagnóstico precoce. O exame histopatológico se torna necessário e primordial, a fim de tratar o doente e evitar a progressão da doença ao longo dos anos. Este seria um dos raros casos relatados sobre neuroesquistossomose, descritos em literatura.

Introdução: A tuberculose é uma doença infecciosa causada pela bactéria Mycobacterium tuberculosis. No Brasil, a cada ano, cerca de 70 mil pessoas são acometidas pela doença. Responsável por mais de 4,5 mil mortes no país. Dentre as causas extrapulmonares temos a doença granulomatosa da glândula paratireoide. Esse tipo de acometimento é surpreendentemente raro, em comparação aos demais acometimentos extrapulmonares, onde a tireoidite autoimune ou relacionada à infecção são observadas com incidência de aproximadamente 10% ao longo da vida. Evidenciado o aumento da função paratireoidiana devido à inflamação crônica associada, sendo uma causa de hiperparatireoidismo primário. Objetivos: Apresentaremos um relato de caso, diagnosticado como tuberculose de paratireoide, manifestando-se com disfunção tireoidiana e seus sintomas clínicos, encontrados em um paciente do ambulatório do serviço de infectologia do Hospital Heliópolis-SP. Realizada coleta de dados, revisão de prontuário e pesquisa bibliográfica sobre tuberculose extrapulmonar. O estudo foi feito mediante obtenção de Termo de Consentimento Livre e Esclarecido em que o paciente autoriza utilização de dados clínicos. Discussão: Paciente, feminino, 64 anos, natural de Mirangaba (Bahia), procedente de Santo André (São Paulo). Iniciou sintomas de hipertireoidismo com perda ponderal não intencional, pressão arterial resistente, palpitações, tremores e mudança do humor como ansiedade. Associada a fadiga e linfonodo em cadeia cervical palpável, evidenciada necrose caseosa em anatomopatológico. Fez-se tratamento cirúrgico, com ressecção de glândula paratireoide sendo a peça encaminhada para exame anatomopatológico e cultura. Diagnosticada com tuberculose de paratireoide, apresentando inflamação crônica granulomatosa com necrose caseosa e presença de baciloscopia positiva (bacilos evidenciados). A tuberculose extrapulmonar é menos frequente, sendo a paratireoide um acometimento raro. Deve-se iniciar uma ampla investigação com exclusão das demais etiologias e biópsia para o diagnóstico precoce. O exame histopatológico se torna necessário. Este seria um dos raros casos relatados sobre tuberculose em glândula paratireoide, descritos em literatura.

Introdução: A tuberculose é uma doença de distribuição global. De acordo com a OMS um terço da população mundial está infectada pelo Mycobacterium tuberculosis e em risco de desenvolver a doença, sendo que a forma extrapulmonar ocorre em cerca de 10% dos casos. 2 a 20% dos pacientes com tuberculose pulmonar desenvolvem a forma urogenital da doença, que incide principalmente em homens na 4ª e 5ª décadas de vida. Apresenta evolução insidiosa e diagnóstico tardio com sintomas apenas nas fases mais avançadas, o que leva a destruição dos órgãos urogenitais e insuficiência renal. Objetivos: Reportaremos um caso, diagnosticado como tuberculose vesical, em paciente imunocompetente, atendido no ambulatório do serviço de infectologia do Hospital Heliópolis-SP. Realizada coleta de dados, revisão de prontuário e pesquisa bibliográfica sobre tuberculose urogenital. Relato feito mediante obtenção de Termo de Consentimento Livre e Esclarecido em que o paciente autoriza utilização de dados clínicos. Discussão: Paciente, masculino, 53 anos, natural de Boa Vista do Tupim (BA), procedente de Arujá (SP), eletricista, casado; relata disúria, polaciúria, redução do fluxo urinário e dor em hipogástrio há quatro anos. Em 2014 realizou Ressecção Transuretral de próstata e em 2022 abordou novamente o canal uretral para retirada de nódulo de bexiga. Entretanto mantém as mesmas queixas. Chega ao Serviço de Infectologia do Hospital Heliópolis no dia 10/02/2023 encaminhado da Urologia com suspeita de tuberculose vesical, onde já havia iniciado tratamento empírico com Rifampicina, Isoniazida, Pirazinamida e Etambutol (RIPE), porém apresentou intolerância à medicação. Tabagista e presença de doença renal crônica. Inicialmente suspenso o esquema por ausência de evidência microbiólogica ou anatomopatológica. Retorna em 2 meses mantendo queixas. Traz resultado anatomopatológico de nódulo vesical retirado em 2022 com processo inflamatório e esboços granulomatosos, artefatos de necrose aderidos a mucosa vesical e pesquisa de BAAR e fungos negativos. Ademais, traz resultados que constam PCR para micobactéria positivo, BAAR urinário e demais pesquisas e sorologias negativas. Apresenta dilatação pielocalicial bilateral pelo USG e alteração de função renal. Confirmada hipótese de tuberculose urogenital e iniciado tratamento com RIPE com regressão dos sintomas. Sendo este, um dos raros casos sobre tuberculose vesical, relatados em literatura.