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Background Acute kidney injury (AKI) is a worldwide public health problem and is often treated by non-nephrologists. The objective of this study was to evaluate the knowledge of non-nephrologists, undergraduate medical students and health professionals regarding AKI.Methods An unsupervised and closed-response electronic questionnaire was sent to sixth-year medical students and non-nephrologist health professionals working in the city of São Paulo, Brazil.Results A total of 424 responses were returned from 650 invitations (40.1% males, 39.2% physicians, 34.0% senior medical students or resident physicians, 16.3% nurses and 10.6% pharmacists). The knowledge of medical students and health professionals about the prevalence and lethality of AKI in hospitals ranged from 40.8% to 59.2%. The most recognized susceptibilities and risk factors for AKI were sepsis/septic shock (95.0%) and diabetes mellitus (91.3%); the less-recognized susceptibilities and risk factors were exposure to gadolinium-based contrast (23.3%) and chronic liver disease (55.7%). The study participants’ rate of knowledge regarding the diagnosis of AKI was 50.9–73.6%, and their rate of knowledge regarding the criteria of increased serum creatinine and reduced urine volume was 52.6%. The most-recognized nephrotoxic medications were vancomycin (82.3%) and diclofenac (80.4%), and the least-recognized were acyclovir (34.0%) and cotrimoxazole (30.4%). The indications for emergency renal replacement therapy that were recognized by the study respondents were metabolic acidosis (82.3%), uremic syndrome (81.6%), hyperkalemia unresponsive to clinical treatment (78.1%) and acute pulmonary edema (71.6%).Conclusion The study showed knowledge gaps that can impact patient care and can be used to guide professional training programs.

Selected case studies of precipitating ice clouds at Dome C (Antarctic Plateau) were used to test a new approach for the estimation of ice cloud reflectivity at 24 GHz (12.37 mm wavelength) using ground-based far infrared spectral measurements from the REFIR-PAD Fourier transform spectroradiometer and backscattering/depolarization lidar profiles. The resulting reflectivity was evaluated with the direct reflectivity measurements provided by a co-located micro rain radar (MRR) operating at 24 GHz, that was able to detect falling crystals with large particle size, typically above 600 µm. To obtain the 24 GHz reflectivity, we used the particle effective diameter and the cloud optical depth retrieved from the far infrared spectral radiances provided by REFIR-PAD and the tropospheric co-located backscattering lidar to calculate the modal radius and the intercept of the particle size distribution. These parameters spanned in the wide ranges between 570–2400 µm and 10−2–104 cm−5, respectively. The retrieved effective sizes and optical depths mostly varied in the ranges 70–250 µm and 0.1–5, respectively. From these parameters, the theoretical reflectivity at 24 GHz was obtained by integrating the size distribution over different cross sections for various habit crystals provided by Eriksson et al. (2018) databases. From the comparison with the radar reflectivity measurements, we found that the hexagonal column-like habits, the columnar crystal aggregates, and the 5/6 branches bullet rosettes showed the best agreement with the MRR observations. The dispersion coefficient of the crystal particle size distribution was assumed in the range 0–2 according to the temperature dependence found in previous studies. The retrieved values of the intercept and slope were found in good agreement with these studies. The presence of the inferred habits was confirmed by the crystal images taken by the ICE-CAMERA, operating in proximity of REFIR-PAD and the MRR. In particular, the occurrence of hexagonal column-like ice crystals was confirmed by the presence of 22∘ solar halos, detected by the HALO-CAMERA. The average crystal lengths obtained from the retrieved size distribution were also compared to those estimated from the ICE-CAMERA images. The agreement between the two results confirmed that the retrieved parameters of the particle size distributions correctly reproduced the observations.

Abstract The antimicrobial peptide SET-M33 is under study for the development of a new antibiotic against major Gram-negative pathogens. Here we report the toxicological evaluation of SET-M33 administered intravenously to rats and dogs. Dose range finding experiments determined the doses to use in toxicokinetic evaluation, clinical biochemistry analysis, necroscopy and in neurological and respiratory measurements. Clinical laboratory investigations in dogs and rats showed a dose-related increase in creatinine and urea levels, indicating that the kidneys are the target organ. This was also confirmed by necroscopy studies of animal tissues, where signs of degeneration and regeneration were found in kidney when SET-M33 was administered at the highest doses in the two animal species. Neurological toxicity measurements by the Irwin method and respiratory function evaluation in rats did not reveal any toxic effect even at the highest dose. Finally, repeated administration of SET-M33 by short infusion in dogs revealed a no-observed-adverse-effect-level of 0.5 mg/kg/day.

Abstract Predictive factors for response to regorafenib in recurrent glioblastoma, IDH-wildtype, are scarcely recognized. The objective of this study was to identify molecular predictive factors for response to regorafenib using a clinically available platform. We analyzed a prospective cohort of 30 patients harboring recurrent glioblastoma, IDH-wildtype, and treated with regorafenib. Next-generation sequencing (NGS) analysis was performed on DNA extracted from paraffin-embedded tissues using a clinically available platform. Moreover, MGMT methylation and EGFRvIII expression analyses were performed. Six-month progression-free survival (PFS) was 30% and median overall survival (OS) was 7.5 months, in line with literature data. NGS analysis revealed a mutation in the EGFR pathway in 18% of cases and a mutation in the mitogen-activated protein-kinase (MAPK) pathway in 18% of cases. In the remaining cases, no mutations were detected. Patients carrying MAPK pathway mutation had a poor response to regorafenib treatment, with a significantly shorter PFS and a nonsignificantly shorter OS compared to EGFR-mutated patients (for PFS, 2.5 vs 4.5 months, p = 0.0061; for OS, 7 vs 9 months, p = 0.1076). Multivariate analysis confirmed that MAPK pathway mutations independently predicted a shorter PFS after regorafenib treatment (p = 0.0188). The negative prognostic role of MAPK pathway alteration was reinforced when we combined EGFR-mutated with EGFRvIII-positive cases. Recurrent glioblastoma tumors with an alteration in MAPK pathway could belong to the mesenchymal subtype and respond poorly to regorafenib treatment, while EGFR-altered cases have a better response to regorafenib. We thus provide a molecular selection criterion easy to implement in the clinical practice.

Glucocorticoids, such as dexamethasone, are used as anti-inflammatory and immunosuppressive drugs, however patients may exhibit resistance or side effects. Here the authors propose that a dexamethasone related neutrophil-specific DNA methylation index can be used as a marker of glucocorticoid exposure and response and as a prognostic factor in brain tumor survival.

Here, the authors report that α-synuclein phase-separates into liquid condensates with positively charged polypeptides such as Tau. The condensates undergo different maturation processes, including the formation of α-synuclein/Tau amyloid hetero-aggregates inside the condensates.

Tools such as pens, forks, and scissors play an important role in many daily-life activities, an importance underscored by the presence in visual cortex of a set of tool-selective brain regions. This review synthesizes decades of neuroimaging research that investigated the representational spaces in the visual ventral stream for objects, such as tools, that are specifically characterized by action-related properties. Overall, results reveal a dissociation between representational spaces in ventral and lateral occipito-temporal cortex (OTC). While lateral OTC encodes both visual (shape) and action-related properties of objects, distinguishing between objects acting as end-effectors (e.g., tools, hands) versus similar noneffector manipulable objects (e.g., a glass), ventral OTC primarily represents objects' visual features such as their surface properties (e.g., material and texture). These areas act in concert with regions outside of OTC to support object interaction and tool use. The parallel investigation of the dimensions underlying object representations in artificial neural networks reveals both the possibilities and the difficulties in capturing the action-related dimensions that distinguish tools from other objects. Although artificial neural networks offer promise as models of visual cortex computations, challenges persist in replicating the action-related dimensions that go beyond mere visual features. Taken together, we propose that regions in OTC support the representation of tools based on a behaviorally relevant action code and suggest future paths to generate a computational model of this object space. [ABSTRACT FROM AUTHOR]

The study analyses differences in the perceived age, cuteness and mental abilities of robots displayed as 3D models in a VR setting, manipulating anthropomorphic variables such as height, head dimension, and limb length. Participants (N = 122) were randomly assigned to one of four experimental conditions where they interacted with a robot with a different combination of physical dimensions. The interactions took place in a CAVE – an immersive VR room, which allowed participants to directly perceive the dimensions of the robot. In the CAVE we collected from participants impressions about the robot using Likert scales and numeric input. After the interaction, they had to fill in a post-test questionnaire measuring their tendency to anthropomorphism, literacy about Artificial Intelligence, and sensitivity to cute stimuli. Results show that changes in the physical appearance of the robots affect the perception of their age. A small robot with an increased head-to-body ratio is also perceived to be cuter, and the tendency towards anthropomorphism is related to higher perceived levels of experience in the robot. Results thus may be considered relevant when developing robots for specific functions, such as serving adults or children activities, studies, or work. [ABSTRACT FROM AUTHOR]

Background: Transphyseal hematogenous osteomyelitis (THO) is a common infectious condition, being present in 25% of patients with hematogenous osteomyelitis. A large proportion of pediatric hematogenous osteomyelitis infections can spread through the growth cartilage and therefore may be potentially responsible for growth disorders, leading to limb-length discrepancy or angular deformities. The purpose of the present study was to identify both the prevalence of complications caused by transphyseal osteomyelitis and factors influencing their occurrence. Methods: The records for all patients who had been treated for THO over a 17-year period at the University Hospitals of Geneva and the Gesù Bambino Hospital in Rome were retrospectively analyzed. Clinical, biological, and bacteriological data were analyzed. Magnetic resonance imaging (MRI) scans were reviewed for all patients to assess the cross-sectional area of growth plate involvement. Restart of growth of the affected physeal cartilage was subsequently monitored by means of iterative radiographic examination. Results: From a cohort of 594 patients with hematogenous osteomyelitis, 89 patients (15.0%) were found to have THO. The median age was 84 months (range, 1 to 167 months), with a bimodal distribution and peaks at 30 and 150 months; 59.6% (53) of the 89 patients were male. The lower limbs were most often affected, with the distal tibia and fibula accounting for 47.2% of all cases. Methicillin-sensitive Staphylococcus aureus and Kingella kingae were the most frequently identified pathogens, accounting for 61.8% of the cases. Virulence factors, such as Panton-Valentine leukocidin (PVL), toxic shock syndrome toxin (TSST), and accessory gene regulator (Agr), were recorded in 12.4% of MSSA strains. Transphyseal lesions affected a median of 7.6% (range, 0.79% to 58.2%) of the physeal surface. Complications affecting further growth were noted in 13% of patients with THO. Thrombocytopenia, leukocytosis, and the presence of virulence factors significantly influenced the occurrence of complications. Conclusions: THO affects all age categories of the pediatric population. In the present study, growth disturbance occurred in 13% of cases. The presence of deep thrombocytopenia, leukocytosis, and virulence factors, such as Agr, TSST, and PVL, seems to strongly influence the occurrence of such complications. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Aerosol vertical stratification significantly influences the Earth's radiative balance and particulate-matter-related air quality. Continuous vertically resolved observations remain scarce compared to surface-level and column-integrated measurements. This work presents and makes available a novel, long-term (2016–2022) aerosol dataset derived from continuous (24/7) vertical profile observations from three selected stations (Aosta, Rome, Messina) of the Italian Automated Lidar-Ceilometer (ALC) Network (ALICENET). Using original retrieval methodologies, we derive over 600,000 quality-assured profiles of aerosol properties at the 15 min temporal and 15 metre vertical resolutions. These properties include the particulate matter mass concentration (PM), aerosol extinction and optical depth (AOD), i.e., air quality legislated quantities or essential climate variables. Through original ALICENET algorithms, we also derive long-term aerosol vertical layering data, including the mixed aerosol layer (MAL) and elevated aerosol layers (EALs) heights. Based on this new dataset, we obtain an unprecedented, fine spatiotemporal characterisation of the aerosol vertical distributions in Italy across different geographical settings (Alpine, urban, and coastal) and temporal scales (from sub-hourly to seasonal). Our analysis reveals distinct aerosol daily and annual cycles within the mixed layer and above, reflecting the interplay between site-specific environmental conditions and atmospheric circulations in the Mediterranean region. In the lower troposphere, mixing processes efficiently dilute particles in the major urban area of Rome, while mesoscale circulations act either as removal mechanisms (reducing the PM by up to 35% in Rome) or transport pathways (increasing the loads by up to 50% in Aosta). The MAL exhibits pronounced diurnal variability, reaching maximum (summer) heights of >2 km in Rome, while remaining below 1.4 km and 1 km in the Alpine and coastal sites, respectively. The vertical build-up of the AOD shows marked latitudinal and seasonal variability, with 80% (30%) of the total AOD residing in the first 500 m in Aosta-winter (Messina-summer). The seasonal frequency of the EALs reached 40% of the time (Messina-summer), mainly in the 1.5–4.0 km altitude range. An average (wet) PM > 40 μg m−3 is associated with the EALs over Rome and Messina. Notably, 10–40% of the EAL-affected days were also associated with increased PM within the MAL, suggesting the entrainment of the EALs in the mixing layer and thus their impact on the surface air quality. We also integrated ALC observations with relevant, state-of-the-art model reanalysis datasets (ERA5 and CAMS) to support our understanding of the aerosol patterns, related sources, and transport dynamics. This further allowed measurement vs. model intercomparisons and relevant examination of discrepancies. A good agreement (within 10–35%) was found between the ALICENET MAL and the ERA5 boundary layer height. The CAMS PM10 values at the surface level well matched relevant in situ observations, while a statistically significant negative bias of 5–15 μg m−3 in the first 2–3 km altitude was found with respect to the ALC PM profiles across all the sites and seasons. [ABSTRACT FROM AUTHOR]

By virtue of their ability to bind different growth factors, morphogens and extracellular matrix proteins, heparan sulfate proteoglycans (HSPGs) play a determinant role in cancer cell differentiation and migration. Despite a strong conceptual basis and promising preclinical results, clinical trials have failed to demonstrate any significant advantage of administering heparin to oncology patients. We exploited our anti-heparan sulfate branched peptide NT4 to test the opposite approach, namely, targeting HSPGs to interfere with their functions, instead of using heparin as a soluble competitor in human cell lines from pancreas adenocarcinoma, colon adenocarcinoma, rhabdomyosarcoma and two different breast cancers. We found that the anti-heparan sulfate peptide NT4 is more effective than heparin for inhibiting cancer cell adhesion, directional migration, colony formation and even cell growth, suggesting that targeting cell membrane HSPGs may be a more effective anti-metastatic strategy than using soluble heparin. Analysis of NT4 effects on cancer cell directional migration, associated to cellular distribution of HSPGs and cadherins in different migrating cancer cell lines, provided further indications on the molecular basis of HSPG functions, which may explain the efficiency of the HSPG targeting peptide. [ABSTRACT FROM AUTHOR]

Objective: To present a list of key points for good Temporomandibular Disorders (TMDs) clinical practice on behalf of the International Network for Orofacial Pain and Related Disorders Methodology (INfORM) group of the International Association for Dental, Oral and Craniofacial Research (IADR). Methods: An open working group discussion was held at the IADR General Session in New Orleans (March 2024), where members of the INfORM group finalized the proposal of a list of 10 key points. Results: The key points covered knowledge on the etiology, diagnosis, and treatment. They represent a summary of the current standard of care for management of TMD patients. They are in line with the current need to assist general dental practitioners advance their understanding and prevent inappropriate treatment. Conclusions: The key points can be viewed as a guiding template for other national and international associations to prepare guidelines and recommendations on management of TMDs adapted to the different cultural, social, educational, and healthcare requirements. [ABSTRACT FROM AUTHOR]

Background/Objectives: In Italy, the prevalence of celiac disease (CeD) among children exceeds 1.5% and has steadily increased with a linear trend over the past 25 years. The clinical presentation is heterogenous and a change in onset symptoms has been described in recent years. The aim of the study is to describe the pattern of clinical presentation of CeD during the last 12 years in a single Italian center. Methods: We retrospectively enrolled all children diagnosed with CeD at Bambino Gesù Children Hospital, Rome between 1 March 2011 and 22 June 2023. To investigate the changes in pattern of clinical presentation, we divided the patient population into three groups of approximately 4 years each (respectively: 49, 48 and 48 months). Patients who previously received a CeD diagnosis in other centers were excluded. Results: Overall, 4478 patients were diagnosed with CeD at our center. 1082 were excluded, leaving 3396 available for analysis. We divided the study cohort into three groups: group 1 (n = 909), group 2 (n = 1103), and group 3 (n = 1384). Diagnoses of CeD increased by 17.5%. The trend of the non-classic form shows a significative increase (p = 0.000064), showing a high prevalence of bloating and abdominal pain and a significant reduction in celiac crisis (p < 0.0001). Conclusions: Annual diagnoses of CeD increased during the study period, and the clinical presentation has changed in recent years, showing an increase in the non-classic form and a reduction in more severe forms of celiac crisis. [ABSTRACT FROM AUTHOR]

Background: The introduction of a smartphone‐based ecological momentary assessment (EMA) approach has allowed achieving data on the frequency of different awake bruxism (AB) behaviours (i.e., teeth contact, teeth clenching, teeth grinding, and mandible bracing) reported by an individual in the natural environment. Study Objectives: The fluctuation of AB reports over time has a certain degree of variability that has never been investigated. Therefore, the aim of this investigation was to assess the long‐term fluctuation of AB behaviours in a population of young adults. Methods: A smartphone application was used to assess a real‐time report on five specific oral conditions related to AB in a sample of 77 young adults, aged 24.0 ± 0.8 years. Data were recorded over three periods of 7 days, with a three‐month interval for a total of 6 months. Results: The average frequency of the relaxed condition was 72.9%, 78.2%, and 80.8% at the end of the first, second, and third sessions, respectively. On average, teeth contact and mandible bracing were the most frequently reported conditions, with a mean prevalence of 12.9% and 7%, respectively, whilst the frequency of teeth clenching and teeth grinding was less than 3%. The ANOVA test showed an absence of significant differences (p < 0.05) between the three recording periods, and the frequency was in general only moderately variable from day‐to‐day (e.g., the coefficient of variation (CV) for the condition "relaxed jaw muscles" was 0.3). No gender differences were detected either. Conclusions: Findings suggest that in a population of healthy individuals, the frequency of AB behaviours over a six‐month monitoring period is quite constant. This investigation represents a standpoint for future comparisons on the study of natural fluctuations of AB behaviours as well as on AB frequency in populations with risk/associated factors and possible clinical consequences. [ABSTRACT FROM AUTHOR]

The betacoronavirus genus contains five of the seven human coronaviruses, making it a particularly critical area of research to prepare for future viral emergence. We utilized three human betacoronaviruses, one from each subgenus—HCoV-OC43 (embecovirus), SARS-CoV-2 (sarbecovirus), and MERS-CoV (merbecovirus)—, to study betacoronavirus interactions with the PKR-like ER kinase (PERK) pathway of the integrated stress response (ISR)/unfolded protein response (UPR). The PERK pathway becomes activated by an abundance of unfolded proteins within the endoplasmic reticulum (ER), leading to phosphorylation of eIF2α and translational attenuation. We demonstrate that MERS-CoV, HCoV-OC43, and SARS-CoV-2 all activate PERK and induce responses downstream of p-eIF2α, while only SARS-CoV-2 induces detectable p-eIF2α during infection. Using a small molecule inhibitor of eIF2α dephosphorylation, we provide evidence that MERS-CoV and HCoV-OC43 maximize viral replication through p-eIF2α dephosphorylation. Interestingly, genetic ablation of growth arrest and DNA damage-inducible protein (GADD34) expression, an inducible protein phosphatase 1 (PP1)-interacting partner targeting eIF2α for dephosphorylation, did not significantly alter HCoV-OC43 or SARS-CoV-2 replication, while siRNA knockdown of the constitutive PP1 partner, constitutive repressor of eIF2α phosphorylation (CReP), dramatically reduced HCoV-OC43 replication. Combining GADD34 knockout with CReP knockdown had the maximum impact on HCoV-OC43 replication, while SARS-CoV-2 replication was unaffected. Overall, we conclude that eIF2α dephosphorylation is critical for efficient protein production and replication during MERS-CoV and HCoV-OC43 infection. SARS-CoV-2, however, appears to be insensitive to p-eIF2α and, during infection, may even downregulate dephosphorylation to limit host translation. [ABSTRACT FROM AUTHOR]

BackgroundTwenty-five single nucleotide polymorphisms (SNPs) are associated with adult diffuse glioma risk. We hypothesized that the inclusion of these 25 SNPs with age at diagnosis and sex could estimate risk of glioma as well as identify glioma subtypes.MethodsCase-control design and multinomial logistic regression were used to develop models to estimate the risk of glioma development while accounting for histologic and molecular subtypes. Case-case design and logistic regression were used to develop models to predict isocitrate dehydrogenase (IDH) mutation status. A total of 1273 glioma cases and 443 controls from Mayo Clinic were used in the discovery set, and 852 glioma cases and 231 controls from UCSF were used in the validation set. All samples were genotyped using a custom Illumina OncoArray.ResultsPatients in the highest 5% of the risk score had more than a 14-fold increase in relative risk of developing an IDH mutant glioma. Large differences in lifetime absolute risk were observed at the extremes of the risk score percentile. For both IDH mutant 1p/19q non-codeleted glioma and IDH mutant 1p/19q codeleted glioma, the lifetime risk increased from almost null to 2.3% and almost null to 1.7%, respectively. The SNP-based model that predicted IDH mutation status had a validation concordance index of 0.85.ConclusionsThese results suggest that germline genotyping can provide new tools for the initial management of newly discovered brain lesions. Given the low lifetime risk of glioma, risk scores will not be useful for population screening; however, they may be useful in certain clinically defined high-risk groups.

Pre-exposure prophylaxis (PrEP) is an effective HIV prevention measure but identifying those most at risk to target for treatment is challenging. Here, the authors demonstrate that non-selective PrEP distribution outperforms targeted strategies when use is not consistent, and/or prevalence of untreated HIV is high.

BACKGROUND:Chronic lymphocytic leukemia (CLL) was the predominant leukemia in a recent study of Chornobyl cleanup workers from Ukraine exposed to radiation (UR-CLL). Radiation risks of CLL significantly increased with increasing bone marrow radiation doses. Current analysis aimed to clarify whether the increased risks were due to radiation or to genetic mutations in the Ukrainian population. METHODS:A detailed characterization of the genomic landscape was performed in a unique sample of 16 UR-CLL patients and age- and sex-matched unexposed general population Ukrainian-CLL (UN-CLL) and Western-CLL (W-CLL) patients (n = 28 and 100, respectively). RESULTS:Mutations in telomere-maintenance pathway genes POT1 and ATM were more frequent in UR-CLL compared to UN-CLL and W-CLL (both p