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This study endeavored to overcome the physiological barriers hindering optimal bioavailability in ophthalmic therapeutics by devising drug delivery platforms that allow therapeutically effective drug concentrations in ocular tissues for prolonged times. Thermosensitive drug delivery platforms were formulated by blending poloxamers (F68 and F127) with low-molecular-weight hyaluronic acid (HA) in various concentrations and loaded with hydrocortisone (HC). Among the formulations examined, only three were deemed suitable based on their desirable gelling properties at a temperature close to the eye’s surface conditions while also ensuring minimal gelation time for swift ocular application. Rheological analyses unveiled the ability of the formulations to develop gels at suitable temperatures, elucidating the gel-like characteristics around the physiological temperature essential for sustained drug release. The differential scanning calorimetry findings elucidated intricate hydrogel–water interactions, indicating that HA affects the water–polymer interactions within the gel by increasing the platform hydrophilicity. Also, in vitro drug release studies demonstrated significant hydrocortisone release within 8 h, governed by an anomalous transport mechanism, prompting further investigation for optimized release kinetics. The produced platforms offer promising prospects for efficacious ocular drug delivery, addressing pivotal challenges in ocular therapeutics and heralding future advancements in the domain.

This study aims to analyze the dynamics of change in settlement models from the Roman, late antique, and Byzantine periods, focusing on how these transformations influenced the formation of Islamic societies in the rural landscapes of western Sicily. The study is centered around the territory of Corleone in the Sicani Mountains (central-western Sicily). This region, strategically located between the significant cities of Palermo on the Tyrrhenian Sea and Agrigento on the Strait of Sicily, has been pivotal in the communication network spanning from the Roman era to the Middle Ages and beyond. The area has been subject to extensive surveys and excavations, revealing diverse dynamics of continuity, resilience, and innovation in settlement patterns from the Roman to the Islamic periods. Beyond presenting the results of archaeological fieldwork, this study employs GIS-based spatial and statistical analyses and utilizes a range of topographic (elevation, slope, aspect, topographic position index (TPI), and distance to water sources) and ecological factors (vegetation series). These analyses aim to assess the evolving relationships and site positioning within the territory over time. Combining archaeological data with topographic and ecological landscape analysis, this integrated approach elucidates the complex transition dynamics from the Roman settlement system to the Islamic age’s landscape formation in western Sicily’s rural areas. The study thereby contributes to a deeper understanding of the intricate interplay between historical developments and environmental factors in shaping rural settlement patterns.

Background: Heart failure is an epidemiologically relevant disease because of the aging population and widespread lifestyles that promote it. In addition to the acute event, it is possible for the disease to become chronic with periodic flare-ups. It is essential to study pathology from a diagnostic and prognostic point of view and to identify parameters for effective monitoring. In addition, heart failure is associated with multiple comorbidities, including cognitive impairment, which is monitored clinically but not through specific biomarkers in these patients. The purpose of this review is to gather the most recent scientific evidence on a few possible biomarkers previously identified for monitoring heart failure and associated cognitive impairment. Methods: We surveyed studies inherent to a set of previously identified markers, evaluating English-language articles from the past five years conducted in adult heart failure patient populations. We used the databases PubMed, Web of Sciences, and Cochrane Library for search studies, and we considered articles published in journals with an impact factor greater than five in the publication year. Results: Among the biomarkers evaluated, a concordant indication for serial measurements for heart failure monitoring emerged only for interleukin-6. For the other markers, there is still little evidence available, which is interesting but sometimes conflicting. Interesting studies have also emerged for biomarkers of cognitive decline assessed in patients with heart failure, confirming the hypotheses of the increasingly studied heart-brain correlation. Conclusion: Certainly, further studies in large populations are needed to identify effective biomarkers for monitoring heart failure and associated cognitive impairment.

Background: The COVID-19 pandemic and its impact on hospitals' activity and organization has imposed a vast change in standard neurosurgical oncology practice to accommodate for shifting resources. Aims: This investigation aims to analyse the nationwide capability in reorganizing the surgical neuro-oncological activity during the COVID-19 pandemic to evaluate whether COVID-19-pandemic influenced the surgical management in these patients. Method: A web-based dataset model organized by the Italian Neurosurgical Society (SINCh) was sent to all the Italian neurosurgical departments in May 2021, requesting to report the types and numbers of surgical procedures performed in the pre-pandemic period (from March 9th 2019 to March 9th 2020) compared to the pandemic period (from March 10th 2020 to March 10th 2021). Results: This multicentre investigation included the surgical activity of 35 Italian Neurosurgical Departments in a pre-pandemic year versus a pandemic year. During the COVID period, 699 fewer neuro-oncological patients were operated on than in the pre-COVID period. We noted a slight increase in urgency and a more severe decrease in elective and benign pathology. None of these differences was statistically significant. Surgically treated patients who tested positive for SARS-CoV-2 were 36, of which 11 died. Death was found to be COVID-related only in 2 cases. Conclusion: The reorganization of the Italian Neurosurgical Departments was able to guarantee a redistribution of the CNS tumors during the inter-pandemic periods, demonstrating that patients even in the pandemic era could be treated without compromising the efficacy and safety of the surgical procedure.

Introduction: Health care is not free of ineffective, unsafe or inefficient diagnostic and therapeutic practices. To address this, different scientific societies and health authorities have proposed ‘do not do’ recommendations (DNDRs). Our goal was the selection by consensus of a set of DNDRs for paediatric intensive care in Spain. Material and method: The research was carried out in 2 phases: first, gathering potential DNDRs; second, selecting the most important ones, using the Delphi method, based on the prevalence of the practice to be modified, the severity of its potential risks and the ease with which it could be modified. Proposals and evaluations were both made by members of working groups of the Sociedad Española de Cuidados Intensivos Pediátricos (SECIP, Spanish Society of Paediatric Intensive Care), coordinated by email. The initial set of DNDRs was reduced based on the coefficient of variation (

In this contribution, new data concerning the distribution of native vascular flora in Italy are presented. It includes new records, confirmations, and status changes to the Italian administrative regions. Nomenclatural and distribution updates, published elsewhere, and corrigenda are provided as Suppl. material 1.

Abstract Background Branchio-oto-renal syndrome (BOR) is an autosomal dominant disorder characterized by deafness, branchiogenic malformations and renal abnormalities. Pathogenic variants in EYA1, SIX1 and SIX5 genes cause almost half of cases; copy number variants (CNV) and complex genomic rearrangements have been revealed in about 20% of patients, but they are not routinely and commonly included in the diagnostic work-up. Case presentation We report two unrelated patients with BOR syndrome clinical features, negative sequencing for BOR genes and the identification of a 2.65 Mb 8q13.2–13.3 microdeletion. Conclusions We highlight the value of CNV analyses in high level of suspicion for BOR syndrome but negative sequencing for BOR genes and we propose an innovative diagnostic flow-chart to increase current detection rate. Our report confirms a mechanism of non-allelic homologous recombination as causing this recurrent 8q13.2–13.3 microdeletion. Moreover, considering the role of PRDM14 and NCOA2 genes, both involved in regulation of fertility and deleted in our patients, we suggest the necessity of a longer follow-up to monitor fertility issues or additional clinical findings.

The aim of the study was to assess the quality, accuracy and benefit of navigated 2D and 3D ultrasound for intra-axial tumor surgery in a prospective study. Patients intended for gross total resection were consecutively enrolled. Intraoperatively, a 2D and 3D iUS-based resection was performed. During surgery, the image quality, clinical benefit and navigation accuracy were recorded based on a standardized protocol using Likert’s scales. A total of 16 consecutive patients were included. Mean ratings of image quality in 2D iUS were significantly higher than in 3D iUS (p < 0.001). There was no relevant decrease in rating during the surgery in 2D and 3D iUS (p > 0.46). The benefit was rated 2.2 in 2D iUS and 2.6 in 3D iUS (p = 0.08). The benefit remained stable in 2D, while there was a slight decrease in the benefit in 3D after complete tumor resection (p = 0.09). The accuracy was similar in both (mean 2.2 p = 0.88). Seven patients had a small tumor remnant in intraoperative MRT (mean 0.98 cm3) that was not appreciated with iUS. Crucially, 3D iUS allows for an accurate intraoperative update of imaging with slightly lower image quality than 2D iUS. Our preliminary data suggest that the benefit and accuracy of 2D and 3D iUS navigation do not undergo significant variations during tumor resection.

ABSTRACT The urban plan of Palermo (Sicily, Italy) has evolved throughout Punic, Roman, Byzantine, Arab, and Norman ages until it stabilized within the borders that correspond to the current historic center. During the 2012 to 2013 excavation campaign, new remains of the Arab settlement, directly implanted above the structures of the Roman age, were found. The materials investigated in this study derived from the so-called Survey No 3, which consists of a rock cavity of subcylindrical shape covered with calcarenite blocks: it was probably used to dispose of garbage during the Arabic age and its content, derived from daily activities, included grape seeds, scales and bones of fish, small animal bones, and charcoals. Radiocarbon dating confirmed the medieval origin of this site. The composition of the bacterial community was characterized through a culture-dependent and a culture-independent approach. Culturable bacteria were isolated under aerobic and anaerobic conditions and the total bacterial community was characterized through metagenomic sequencing. Bacterial isolates were tested for the production of compounds with antibiotic activity: a Streptomyces strain, whose genome was sequenced, was of particular interest because of its inhibitory activity, which was due to the Type I polyketide aureothin. Moreover, all strains were tested for the production of secreted proteases, with those belonging to the genus Nocardioides having the most active enzymes. Finally, protocols commonly used for ancient DNA studies were applied to evaluate the antiquity of isolated bacterial strains. Altogether these results show how paleomicrobiology might represent an innovative and unexplored source of novel biodiversity and new biotechnological tools. IMPORTANCE One of the goals of paleomicrobiology is the characterization of the microbial community present in archaeological sites. These analyses can usually provide valuable information about past events, such as occurrence of human and animal infectious diseases, ancient human activities, and environmental changes. However, in this work, investigations about the composition of the bacterial community of an ancient soil sample (harvested in Palermo, Italy) were carried out aiming to screen ancient culturable strains with biotechnological potential, such as the ability to produce bioactive molecules and secreted hydrolytic enzymes. Besides showing the biotechnological relevance of paleomicrobiology, this work reports a case of germination of putatively ancient bacterial spores recovered from soil rather than extreme environments. Moreover, in the case of spore-forming species, these results raise questions about the accuracy of techniques usually applied to estimate antiquity of DNA, as they could lead to its underestimation.

We present Lightcurve Anomaly Identification and Similarity Search ( LAISS ), an automated pipeline to detect anomalous astrophysical transients in real-time data streams. We deploy our anomaly detection model on the nightly Zwicky Transient Facility (ZTF) Alert Stream via the ANTARES broker, identifying a manageable ∼1–5 candidates per night for expert vetting and coordinating follow-up observations. Our method leverages statistical light-curve and contextual host galaxy features within a random forest classifier, tagging transients of rare classes ( spectroscopic anomalies), of uncommon host galaxy environments ( contextual anomalies), and of peculiar or interaction-powered phenomena ( behavioral anomalies). Moreover, we demonstrate the power of a low-latency (∼ms) approximate similarity search method to find transient analogs with similar light-curve evolution and host galaxy environments. We use analogs for data-driven discovery, characterization, (re)classification, and imputation in retrospective and real-time searches. To date, we have identified ∼50 previously known and previously missed rare transients from real-time and retrospective searches, including but not limited to superluminous supernovae (SLSNe), tidal disruption events, SNe IIn, SNe IIb, SNe I-CSM, SNe Ia-91bg-like, SNe Ib, SNe Ic, SNe Ic-BL, and M31 novae. Lastly, we report the discovery of 325 total transients, all observed between 2018 and 2021 and absent from public catalogs (∼1% of all ZTF Astronomical Transient reports to the Transient Name Server through 2021). These methods enable a systematic approach to finding the “needle in the haystack” in large-volume data streams. Because of its integration with the ANTARES broker, LAISS is built to detect exciting transients in Rubin data.

Post-Mortem Microbiology (PMM) aims to detect infections that could be a cause of stillbirth. A newborn having no sign of life after delivery is defined as stillbirth. Different infections could cause a chain of events leading to stillbirth but the relationships between maternal infection and stillbirth are often not very clear; as a matter of fact, the positive serologic tests do not prove causality. Screening, prevention, and treatment of maternal infections are important to reduce the stillbirth risk. The identification of an infectious agent that causes stillbirth through PMM is a shared aim by microbiologists, pathologists and surgeons, and it is also the common goal in clinical and forensic autopsies. The aim of this paper is a review the major infections that lead to stillbirths.

Introduction: Video-based clinical rating plays an important role in assessing dystonia and monitoring the effect of treatment in dyskinetic cerebral palsy (CP). However, evaluation by clinicians is time-consuming, and the quality of rating is dependent on experience. The aim of the current study is to provide a proof-of-concept for a machine learning approach to automatically assess scoring of dystonia using 2D stick figures extracted from videos. Model performance was compared to human performance.Methods: A total of 187 video sequences of 34 individuals with dyskinetic CP (8–23 years, all non-ambulatory) were filmed at rest during lying and supported sitting. Videos were scored by three raters according to the Dyskinesia Impairment Scale (DIS) for arm and leg dystonia (normalized scores ranging from 0–1). Coordinates in pixels of the left and right wrist, elbow, shoulder, hip, knee and ankle were extracted using DeepLabCut, an open source toolbox that builds on a pose estimation algorithm. Within a subset, tracking accuracy was assessed for a pretrained human model and for models trained with an increasing number of manually labeled frames. The mean absolute error (MAE) between DeepLabCut’s prediction of the position of body points and manual labels was calculated. Subsequently, movement and position features were calculated from extracted body point coordinates. These features were fed into a Random Forest Regressor to train a model to predict the clinical scores. The model performance trained with data from one rater evaluated by MAEs (model-rater) was compared to inter-rater accuracy.Results: A tracking accuracy of 4.5 pixels (approximately 1.5 cm) could be achieved by adding 15–20 manually labeled frames per video. The MAEs for the trained models ranged from 0.21 ± 0.15 for arm dystonia to 0.14 ± 0.10 for leg dystonia (normalized DIS scores). The inter-rater MAEs were 0.21 ± 0.22 and 0.16 ± 0.20, respectively.Conclusion: This proof-of-concept study shows the potential of using stick figures extracted from common videos in a machine learning approach to automatically assess dystonia. Sufficient tracking accuracy can be reached by manually adding labels within 15–20 frames per video. With a relatively small data set, it is possible to train a model that can automatically assess dystonia with a performance comparable to human scoring.

In recent years, significant scientific progress has been made in the therapy of non-small cell lung cancer (NSCLC), which has made possible a better knowledge of this pathology and above all the realization of new personalized therapies. The main therapeutic revolution in advanced NSCLC is immuno-oncology, a new therapeutic strategy that aims to awaken the immune system to fight cancer cells.

Aim: To explore the attitudes of healthcare workers towards COVID‐19 vaccines. Design: A qualitative descriptive design was used. Methods: Five focus groups were conducted between October and November 2021, with a total of 30 nurses from different contexts in Northern Italy. Thematic analysis was used to analyse the transcripts. Results: Three main themes were identified: 'favourable', 'unsure' and 'contrary to' COVID‐19 vaccines. The favourable position was underpinned by trust in science, research and vaccination; protection for themselves, their families, patients and the population; duty as professionals; necessity to set an example for others. Participants who were unsure had doubts about the composition, safety and efficacy of the vaccine and were sometimes afraid that media provided incomplete information. The main reason why nurses were against was the feeling that being forced to vaccinate perceived as blackmail. Favourable or unsure nurses struggled to deal with those who were against and developed a series of emotions that ranged from respect and attempt to rationalize, to frustration and defeat. Conclusions: Identifying the areas of hesitation is essential to understand what affects the choices of acceptance, delay or refusal of vaccination. The issues that emerged regarding proper communication within the vaccination campaign highlights the key importance of adequate vaccination strategies. Implication for the Profession and/or Patient Care: Understanding attitudes towards vaccine and related motivations among healthcare workers could help develop more specific and targeted vaccination campaigns that can ensure proper vaccination coverage rates and avoid hesitancy or refusal. Impact: Healthcare workers experiences of COVID‐19 vaccines, their views and know how they feel during COVID‐19 vaccinations.Healthcare workers had three different positions in COVID‐19 vaccination.This research will guide and target future vaccination campaigns. Reporting Method: The study is reported using the Standards for Reporting Qualitative Research (SRQR). Patient or Public Contribution: No Patient or Public Contribution. [ABSTRACT FROM AUTHOR]

Most of the stars in the Universe are M spectral class dwarfs, which are known to be the source of bright and frequent stellar flares. In this paper, we propose new approaches to discover M-dwarf flares in ground-based photometric surveys. We employ two approaches: a modification of a traditional method of parametric fit search and a machine learning algorithm based on active anomaly detection. The algorithms are applied to Zwicky Transient Facility (ZTF) data release 8, which includes the data from the ZTF high-cadence survey, allowing us to reveal flares lasting from minutes to hours. We analyse over 35 million ZTF light curves and visually scrutinize 1168 candidates suggested by the algorithms to filter out artefacts, occultations of a star by an asteroid, and other types of known variable objects. The result of this analysis is the largest catalogue of ZTF flaring stars to date, representing 134 flares with amplitudes ranging from −0.2 to −4.6 mag, including repeated flares. Using Pan-STARRS DR2 colours, we assign a spectral subclass to each object in the sample. For 13 flares with well-sampled light curves and available geometric distances from Gaia DR3, we estimate the bolometric energy. This research shows that the proposed methods combined with the ZTF's cadence strategy are suitable for identifying M-dwarf flares and other fast transients, allowing for the extraction of significant astrophysical information from their light curves. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a neurodegenerative disorder of the central nervous system characterized by a variety of symptoms such as fatigue, spasticity, tremors, and cognitive disorders. Individuals with MS may employ different coping strategies to manage these symptoms, which in turn can significantly impact their quality of life (QoL). This review aims to analyze these coping strategies and their impact on QoL. Furthermore, it seeks to identify the key factors that influence the choice and effectiveness of these coping strategies, providing insights into which strategies are most beneficial for enhancing QoL in people with MS. Methods: Systematic searches were performed in Scopus, PubMed, Web of Science, and Scopus databases. This systematic review has been registered in OSF with the number DOI 10.17605/OSF.IO/QY37X. Results: A total of 1192 studies were identified. After reading the full text of the selected studies and applying predefined inclusion criteria, 19 studies were included based on their pertinence and relevance to the topic. The results revealed that emotional variables, demographic factors, personality traits, and family support significantly influence the choice of coping strategies used to manage the symptoms of MS. Problem-solving and task-oriented coping were prevalent among MS patients and associated with better QoL outcomes. Emotional-focused and avoidance strategies were generally linked to poorer QoL, though avoidance provided temporary relief in certain contexts. Social support, emotional health, and cognitive reframing were crucial in enhancing QoL. Conclusions: The findings underscore the importance of tailored psychoeducational and therapeutic interventions focusing on emotional health, social support, and adaptive coping strategies. These interventions can significantly improve the long-term outcomes for individuals with MS. Future research should explore the dynamic interactions between coping strategies and QoL over time, providing a comprehensive understanding of how to best support MS patients in managing their disease. [ABSTRACT FROM AUTHOR]

The detection of Legionella in environmental samples, such as water, is crucial for public health monitoring and outbreak prevention. Although effective, traditional detection methods, including culture-based techniques and polymerase chain reaction, have limitations such as long processing times, trained operators, and the need for specialized laboratory equipment. Biosensing technologies offer a promising alternative due to their rapid, sensitive, cost-effectiveness, and on-site detection capabilities. To summarize the current advancements in biosensor development for detecting Legionella in environmental samples, we used 'Legionella' AND 'biosensors' NEAR 'environmental samples' OR 'water' as keywords searching through the most relevant biomedical databases for research articles. After removing duplicates and inadequate articles from the n.1268 records identified using the PRISMA methodology exclusion criteria, we selected n.65 full-text articles which suited the inclusion criteria. Different results between the studies describing the current biosensing techniques, including optical, electrochemical, magnetic, and mass-sensitive sensors were observed. For each biosensing technique, sensitivity, specificity, and detection limits were evaluated. Furthermore, the integration of nanomaterials, microfluidics, and portable devices in biosensor systems' design were discussed, highlighting their role in enhancing detection performance. The potential challenges and future directions in the field of Legionella biosensing were also addressed, providing insights into the feasibility of implementing these technologies in routine environmental monitoring. Undoubtedly, biosensors can play a crucial role in the early detection and management of Legionella infections and outbreaks, ultimately protecting public health and safety. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic and progressive neurological disease that affects the central nervous system, resulting in a wide spectrum of cognitive, emotional, and physical deficits. The progressive course of MS poses significant challenges to patients and has a profound impact on health-related quality of life (HRQoL). The style of coping adopted plays a critical role in determining how individuals with MS adapt to and face the challenges of the disease and their overall well-being. This paper aims to examine the impact of coping strategies on HRQoL in young adults un-/minimally impaired (<5 years, EDSS ≤ 2.5) by MS (age 18–35 years). This retrospective cross-sectional cohort study included 98 young adults (33 males and 65 females) with relapsing–remitting MS who underwent neurological assessment using the Expanded Disability Status Scale. Participants completed the Italian version of the Multiple Sclerosis QoL-54 (MSQoL-54), which provides a physical and mental health score, and the Coping Orientation to Problems Experienced Inventory (Brief-COPE). The results showed a significant relationship between COPE scores and physical and mental health. Subjects affected by MS who tend to use more frequent coping strategies such as active planning, personal growth, and acceptance showed a better overall well-being and quality of life. These findings are relevant to clinical practice given the need to understand the coping variable to improve HRQoL. Understanding these relationships is crucial for developing effective interventions to enhance the well-being of MS subjects. [ABSTRACT FROM AUTHOR]

The achievement of smart pharmaceuticals whose bioactivity can be spatiotemporally controlled by light stimuli is known as photopharmacology, an emerging area aimed at improving the therapeutic outcome and minimizing side effects. This is especially attractive for antibiotics, for which the inevitable development of multidrug resistance and the dwindling of new clinically approved drugs represent the main drawbacks. Here, we show that nitrosation of the fluoroquinolone norfloxacin (NF), a broad-spectrum antibiotic, leads to the nitrosated bioconjugate NF–NO, which is inactive at the typical minimum inhibitory concentration of NF. Irradiation of NF–NO with visible blue light triggers the simultaneous release of NF and nitric oxide (NO). The photouncaging process is accompanied by the revival of the typical fluorescence emission of NF, quenched in NF–NO, which acts as an optical reporter. This permits the real-time monitoring of the photouncaging process, even within bacteria cells where antibacterial activity is switched on exclusively upon light irradiation. The mechanism of photorelease seems to occur through a two-step hopping electron transfer mediated by the lowest triplet state of NF–NO and the phosphate buffer ions or aminoacids such as tyrosine. Considering the well-known role of NO as an "unconventional" antibacterial, the NF–NO conjugate may represent a potential bimodal antibacterial weapon activatable on demand with high spatio-temporal control. [ABSTRACT FROM AUTHOR]

Audit and Feedback (A&F) is a systematic process involving the collection of data, which are subsequently compared with the established reference standards and then subsequently disseminated to healthcare providers through feedback meetings. This allows continuous improvement to be ensured in the quality of care processes. Often, the parameters taken into account concern only the patient and the treatment processes, neglecting other variables. Quality of life in the workplace and coping skills are determining variables for the clinical performance of all healthcare professionals. For this reason, in this study, these variables were investigated and differences were highlighted in two different role categories and context: cardiovascular emergency and neurological rehabilitation. A psychological screening was carried out by sending the computerized Coping Orientation to Problems Experienced—Nuova Versione Italiana (COPE—NVI) and Professional Quality of Life Scale—5 (ProQoL) questionnaires to all healthcare workers involved. Ninety-five healthcare providers (mean ± SD age: 47 ± 10.4 years; 37.9% male) answered the questionnaire and were assigned into two groups (G1 and G2) based on the ward in which they worked. These were further divided into two subgroups (R1 and R2) based on their role. The obtained results show that avoidance strategies are used more by health professionals working in rehabilitation (G2) wards than in intensive-care units (G1). Moreover, in G1 nurses, physical therapists and speech therapists (R2) obtained higher scores in terms of turning to religion (TR) and compassion satisfaction (CS), while physicians and psychologists (R1) obtained higher scores on the burnout scale (BO). The TR score for R2 was found to be higher, even in G2. The response trend of the two groups in the different departments was analyzed and commented on.