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Abstract Large bone defects are a significant health problem today with various origins, including extensive trauma, tumours, or congenital musculoskeletal disorders. Tissue engineering, and in particular bone tissue engineering, aims to respond to this demand. As such, we propose a specific model based on Elastin-Like Recombinamers-based click-chemistry hydrogels given their high biocompatibility and their potent on bone regeneration effect conferred by different bioactive sequences. In this work we demonstrate, using biochemistry, histology, histomorphometry and imaging techniques, the biocompatibility of our matrix and its potent effect on bone regeneration in a model of bone parietal lesion in female New Zealand rabbits.

Abstract Reconstructing rainfall variability and moisture sources is a critical aspect to understand past and future hydroclimate dynamics. Here, we use changes in the deuterium content of land-plant leaf waxes from two marine sediment cores located off Chile to reconstruct changes in rainfall amount and variation in moisture sources over the last ~50 ka. The records indicate increased moisture in central Chile during precession maxima, but an obliquity modulation is evident in southern Chile. While the southern westerly winds are the dominant factor of precipitation in southern Chile by bringing moisture and perturbations from the extratropics, the subtropics represent an additional moisture source during precession maxima due to a stronger subtropical jet increasing moisture transport from the tropics to the mid-latitudes. These findings imply that a combination of orbital modulation of moisture sources and rainfall amount explains the last glacial moisture maximum and early Holocene moisture minimum in south-central Chile.

Abstract Background Marinesco-Sjögren syndrome (MSS) is an autosomal recessive neuromuscular disorder that arises in early childhood and is characterized by congenital cataracts, myopathy associated with muscle weakness, and degeneration of Purkinje neurons leading to ataxia. About 60% of MSS patients have loss-of-function mutations in the SIL1 gene. Sil1 is an endoplasmic reticulum (ER) protein required for the release of ADP from the master chaperone Bip, which in turn will release the folded proteins. The expression of non-functional Sil1 leads to the accumulation of unfolded proteins in the ER and this triggers the unfolded protein response (UPR). A dysfunctional UPR could be a key element in the pathogenesis of MSS, although our knowledge of the molecular pathology of MSS is still incomplete. Methods RNA-Seq transcriptomics was analysed using the String database and the Ingenuity Pathway Analysis platform. Fluorescence confocal microscopy was used to study the remodelling of the extracellular matrix (ECM). Transmission electron microscopy (TEM) was used to reveal the morphology of the ECM in vitro and in mouse tendon. Results Our transcriptomic analysis, performed on patient-derived fibroblasts, revealed 664 differentially expressed (DE) transcripts. Enrichment analysis of DE genes confirmed that the patient fibroblasts have a membrane trafficking issue. Furthermore, this analysis indicated that the extracellular space/ECM and the cell adhesion machinery, which together account for around 300 transcripts, could be affected in MSS. Functional assays showed that patient fibroblasts have a reduced capacity of ECM remodelling, reduced motility, and slower spreading during adhesion to Petri dishes. TEM micrographs of negative-stained ECM samples from these fibroblasts show differences of filaments in terms of morphology and size. Finally, structural analysis of the myotendinous junction of the soleus muscle and surrounding regions of the Achilles tendon revealed a disorganization of collagen fibres in the mouse model of MSS (woozy). Conclusions ECM alterations can affect the proper functioning of several organs, including those damaged in MSS such as the central nervous system, skeletal muscle, bone and lens. On this basis, we propose that aberrant ECM is a key pathological feature of MSS and may help explain most of its clinical manifestations.

Battista Guarini’s letters had a great fortune in print between the Nineties of the Sixteenth and the first decade of the Seventeenth century. Then comes a period of oblivion, ending in the Thirties of the Eighteenth century, when the letters were included into the draft edition of all Guarini’s Works, made by the printer Giovanni Alberto Tumermani. Although the three volumes of letters (edited by Apostolo Zeno in cooperation with Lodovico Antonio Muratori) were never published, the contribution of the studies made in preparation for printing is still relevant today. Specifically, Zeno found and transcribed letters, whose originals are lost; moreover, he copied twice the annotations that Giovan Niccolò Panizzari, a Guarini’s friend, had written at the first edition of the printed letters (Venezia, Ciotti, 1593). These annotations provide important information about the transition from letter-document to letter-work and about the author will. In this article I want to reconstruct the authorial intervention in Ciotti’s first edition and provide the Panizzari’s annotations scholar edition.

Abstract Many of the most sensitive physics experiments searching for rare events, like neutrinoless double beta ( $$0\nu \beta \beta $$ 0 ν β β ) decay, coherent elastic neutrino nucleus scattering and dark matter interactions, rely on cryogenic macro-calorimeters operating at the mK-scale. Located underground at the Gran Sasso National Laboratory (LNGS), in central Italy, CUORE (Cryogenic Underground Observatory for Rare Events) is one of the leading experiments for the search of $$0\nu \beta \beta $$ 0 ν β β decay, implementing the low-temperature calorimetric technology. We present a novel multi-device analysis to correlate environmental phenomena with the low-frequency noise of low-temperature calorimeters. Indeed, the correlation of marine and seismic data with data from a couple of CUORE detectors indicates that cryogenic detectors are sensitive not only to intense vibrations generated by earthquakes, but also to the much fainter vibrations induced by marine microseisms in the Mediterranean Sea due to the motion of sea waves. Proving that cryogenic macro-calorimeters are sensitive to such environmental sources of noise opens the possibility of studying their impact on the detectors physics-case sensitivity. Moreover, this study could pave the road for technology developments dedicated to the mitigation of the noise induced by marine microseisms, from which the entire community of cryogenic calorimeters can benefit.

Abstract Purpose Parosteal Osteosarcoma is a well-differentiated, low-grade bone sarcoma. It most commonly occurs in the third decade of life, usually in the distal femur. This study aims to perform a literature review about the types of reconstructions reported and to analyze the results of an updated technique of resection using custom-made 3D-printed cutting guides. Methods We perform a systematic literature review about parosteal osteosarcoma, evaluating treatments, margins, local recurrence, complications, and functional results when available. We also report a case treated in our Center with a revisited technique introducing custom-made 3D-printed cutting guides. Results We analyzed 12 studies with a total of 151 patients. The distal femur was the most frequently reported site (81.5%). After distal femur resection, reconstruction was performed with graft in most cases (48%), followed by prosthetic reconstruction (40%). Margins were wide in 85.5% of cases. The total incidence of local recurrence was 11%. Functional results were excellent in all cases, with a mean MSTS score of 86%. In our case, with the help of the jigs, the surgical technique was relatively easy, graft fusion excellent and fast, margins wide, and functional results excellent. Conclusions In the literature, the most commonly used type of reconstruction after resection is biological with graft. Indeed, despite the increasing number of prosthetic reconstructions, the historical diaphysometaphyseal hemiresection and graft is still indicated in parosteal osteosarcoma of the distal femur. New technologies, such as the jigs we used, allow significant advantages during the procedure: reduce the resection and graft preparation time, allow a better match between components, and help to obtain safer margins, sparing as much bone as possible.

Background: The COVID-19 pandemic has impacted nursing theatre staff, departmental activity, and delivery of services to patients. This work-based project aimed to investigate the challenges of nursing leadership in an elective orthopaedic department at current times. Methods: The study collected qualitative data exploring theatre staff’s expectations from leadership, offering insight on how the pandemic has influenced the way of working and exploring how the future in this unit may look. The answers from 20 practitioners to an anonymised open-ended survey were examined using thematic analysis. Results: The participants described a leader as a good communicator who focuses on empowering others and supporting the team, identified by the majority as a senior team member. From the findings, three topics were identified: immediate changes, delayed changes, and pre-existing conditions. The answers painted a reality that is complex and multifaceted, where numerous variables play a part in the physical and mental health of each candidate, impacting their performance as well as their work/life balance. Overall, the strongest subjects recurring in the findings were the need for nursing leadership to focus on supporting staff with training opportunities, to actively plan for a reduction in staffing shortages, and to be constantly mindful of staff well-being. Conclusions: This study pointed out that the need for constant communication with their staff, building honest relationships, and being a reliable leader, focused on empowering others and supporting the team were important factors for the nursing management during the COVID-19 pandemic and post-COVID-19 era.

Wilson’s disease (WD) is a biallelic disease-causing variant in the ATP7B gene on chromosome 13q14.3 that results in copper accumulation in many organs, particularly the liver and brain. The phenotypic spectrum is wide and symptoms at onset can be heterogeneous. We describe two Sicilian siblings, a young man and his elder sister, both compound heterozygous for the variants c.1286-2A>G and c.2668G>A (p.Val890Met) in the ATB7B gene. The male patient presented with liver cirrhosis, which quickly progressed to end-stage liver disease (Child–Pugh score = C10), while his sister had moderate steatotic liver disease (SLD). Our findings highlight that SLD may not always be related to obesity in overweight patients, especially when there are other potential risk factors such as a family history of chronic liver disease, or the persistence of high transaminase despite the adoption of adequate dietary and pharmacological intervention. Screening for conditions such as WD could identify patients at risk of developing SLD and avoid delays in diagnosis. Phenotypic variability in WD is considerable; therefore, further studies are needed to identify which WD patients have a greater risk of developing SLD and determine factors that can predict the severity of the disease.

Purpose: Primary bone tumors of the fibula are rare. Distal fibular resection has a significant impact on ankle biomechanics and gait, possibly leading to complications such as ankle instability, valgus deformity, and degenerative changes. Question: Is there a need for reconstructive surgery after distal fibular resection, and what reconstructive procedures are available? Materials and methods: The review is registered with the PROSPERO International Register of Systematic Reviews. Inclusion criteria consisted of all levels of evidence, human studies, patients of all ages and genders, publication in English, and resection of the distal portion of the fibula due to tumor pathology. The reviewers defined four different categories of interest by method of treatment. Additional articles of interest during full-text review were also added. Results: The initial search resulted with a total of 2958 records. After screening, a total of 50 articles were included in the study. Articles were divided into ‘No reconstruction’, ‘Soft tissue reconstruction’, ‘Bone and soft tissue reconstruction’, and ‘Arthrodesis, arthroplasty or other reconstruction options’ groups. Conclusion: Limb salvage surgery should be followed by reconstruction in order to avoid complications. Soft tissue reconstructions should always be considered to stabilize the joint after fibular resection. Bone reconstruction with reversed vascularized fibula is the preferred technique in young patients and in cases of bone defects more than 3 cm, while arthrodesis should be considered in adult patients. Whenever possible for oncologic reason, if a residual peroneal malleolus could be preserved, we prefer augmentation with a sliding ipsilateral fibular graft.

IntroductionPhysical activity (PA) promotes significant physical and psychosocial benefits for breast cancer survivors. While evidence exists regarding recommendations for the frequency, duration and intensity of exercise that optimise PA benefits for cancer survivors, the role of the environment in achieving optimal outcomes has yet to be determined. This paper presents a protocol for a clinical trial to evaluate the feasibility of a 3-month nature-based walking programme for breast cancer survivors. Secondary outcomes assessed include the impact of the intervention on fitness, quality of life outcomes, and biomarkers of ageing and inflammation.Methods and analysisThe trial is a 12-week single-arm pilot study. Twenty female breast cancer survivors will engage in a supervised moderate intensity walking intervention in small groups in a nature reserve for 50 minutes three times per week. Data will be collected at baseline and end of study, and include assessment of inflammatory cytokines and anti-inflammatory myokines (TNF-α, IL-1ß, IL-6, CRP, TGF-ß, IL-10, IL-13), as well as ageing (DNA methylation, ageing genes) biomarkers; surveys (Patient-Reported Outcomes Measurement Information System-29, Functional Assessment of Cancer Therapy-General, Post-Traumatic Growth Inventory); and fitness assessments (6 min Walk Test, Grip-Strength, One Repetition-Maximum Leg Press). Participants will also complete weekly surveys assessing social support and participate in an exit interview. This is an important first step for future research on the influence of exercise environment on cancer survivor PA outcomes.Ethics and disseminationThis study was approved by the Cedars Sinai Medical Center Institutional Review Board (IIT2020-20). Findings will be disseminated through academic manuscripts, conferences, and community presentations.Trial registration numberNCT04896580.

Olive oil is the most used vegetable oil for human consumption and its production represents an important economic sector, especially in Mediterranean countries. Olive trees are grown in more than 40 countries around the world on over 10 million hectares. The milling industry generates large quantities of liquid and solid residues, the disposal of which requires sophisticated and rather expensive procedures, given the polluting characteristics of the processing products. Since a considerable measure of olive-derived biomass is generated each year, it could be used as a potential source of bioactive compounds. This work evaluates the possibility of recovering natural antioxidants from by-products of the olive oil mill, through the optimization of extraction processes with green approaches. In the present work, through HPLC-PDA analysis with a validated method, it was possible to characterize a chemical profile of the extracts obtained through an optimized (DoE) and green approach. The waste products of the olive oil companies represent the samples considered in this work, and are derived from the pomace and the washing water of 2-phases, 2.5-phases, and 3-phase extra virgin olive oil (EVO) production plants. The optimized extraction methodology, starting from the 2.5-phase olive pomace, proved to be satisfactory in terms of efficiency by evaluating the effect of parameters such as extraction time and process temperature. The application of this methodology to other types of pomace and agro-industrial by-products has highlighted excellent results in terms of extraction yield, demonstrating the validity of this procedure as also suitable for other solid residues coming from the olive oil mill. Regarding the treatment in vegetation water, the developed protocol allowed the chromatographic profile of the analytes extracted from this matrix to be evaluated, leading to satisfactory results in terms of quantitative yields. Samples of these extracts are also subjected to biological tests in order to evaluate their antioxidant and enzyme inhibition activities.

Background and purpose: Classic Kaposi sarcoma (CKS) is a rare vascular disease mainly found in populations of Mediterranean origin. The pathogenesis involves Human Herpes Virus 8 (HHV8) and genetic mutations such as SNP309 in the MDM2 gene. The recently discovered BPTF mutation in cells of CKS patients demonstrated higher latency-associated nuclear antigen (LANA) staining and altered vital transcriptomics, implicating a potential role in tumorigenesis. This review explores the genetic underpinnings and treatments for CKS. Material and methods: A comprehensive literature search was conducted from 2004 to 2024, yielding 70 relevant papers. Ongoing clinical trials investigating novel treatments such as talimogene and abemaciclib were included in the search and presented in the results. Results: Clinical diagnosis and treatment can be challenging as the number of studies on CKS and treatment modalities is limited. Treatment strategies vary by disease stage, with local therapies like surgical intervention and radiation therapy recommended for early stages, while systemic therapies are considered in cases of systemic disease. Interpretation: While advancements in CKS treatment offer hope, further studies on immunotherapy are warranted to broaden the therapeutic options, such as anti-bromodomain or BPTF-targeted therapy.

Most acquired and inherited cardiomyopathies are characterized by regional left ventricular involvement and nonischemic myocardial scars, often with a disease-specific pattern. Irrespective of the etiology and pathophysiological mechanisms, myocardial disorders are invariably associated with cardiac fibrosis, which contributes to dysfunction and electrical instability. Accordingly, cardiac magnetic resonance plays a central role in the diagnostic work-up and prognostic risk stratification of cardiomyopathies, particularly with the increasing correlation between genetic background and specific disease phenotype. Starting from pattern and distribution of myocardial fibrosis at cardiac magnetic resonance, we provide a practical regional atlas of nonischemic myocardial scar to guide the diagnostic approach to nonischemic cardiomyopathies.

Proceedings

Despite steady progress in the development and promotion of the circular economy as a model, an overwhelming proportion of technological devices discarded by the Global North still finds its way to the Global South, where technology-related environmental health problems start from the predation of resources and continue all the way to recycling and disposal. We reviewed literature on TCEs in sub-Saharan Africa (SSA), focussing on: the sources and levels of environmental pollution; the extent of human exposure to these substances; their role in the aetiology of human diseases; their effects on the environment. Our review shows that even minor and often neglected technology-critical elements (TCEs), like rare earth elements (REEs) and platinum group elements (PGEs), reveal the environmental damage and detrimental health effects caused by the massive mining of raw materials, exacerbated by improper disposal of e-waste (from dumping to improper recycling and open burning). We draw attention of local research on knowledge gaps such as workable safer methods for TCE recovery from end-of-life products, secondary materials and e-waste, environmental bioremediation and human detoxification. The technical and political shortcomings in the management of TCEs in SSA is all the more alarming against the background of unfavourable determinants of health and a resulting higher susceptibility to diseases, especially among children who work in mines and e-waste recycling sites or who reside in dumping sites.This paper demonstrates, for the first time, that the role of unjust North-South dynamics is evident even in the environmental levels of minor trace elements and that the premise underlying attempts to solve the problem of e-waste dumped in Africa through recycling and disposal technology is in fact misleading. The influx of foreign electrical and electronic equipments should be controlled and limited by clearly defining what is a ‘useful’ second-hand device and what is e-waste; risks arising from device components or processing by-products should be managed differently, and scientific uncertainty and One Health thinking should be incorporated in risk assessment.

Aims: Evaluate effectiveness and safety of multiple HyperArc courses and patterns of progression in patients affected by BMs with intracranial progression. Methods: 56 patients were treated for 702 BMs with 197 (range 2–8) HyperArc courses in case of exclusive intracranial progression. Primary end-point was the overall survival (OS), secondary end-points were intracranial progression-free survival (iPFS), toxicity, local control (LC), neurological death (ND), and whole-brain RT (WBRT)-free survival. Site of progression was evaluated against isodoses levels (0, 1, 2, 3, 5, 7, 8, 10, 13, 15, 20, and 24 Gy.). Results: The 1-year OS was 70 %, and the median was 20.8 months (17–36). At the univariate analysis (UVA) biological equivalent dose (BED) > 51.3 Gy and non-melanoma histology significantly correlated with OS. The median time to iPFS was 4.9 months, and the 1-year iPFS was 15 %. Globally, 538 new BMs occurred after the first HA cycle in patients with extracranial disease controlled. 96.4 % of them occurred within the isodoses range 0–7 Gy as follows: 26.6 % (0 Gy), 16.5 % (1 Gy), 16.5 % (2 Gy), 20.1 % (3 Gy), 13.1 % (5 Gy), 3.4 % (7 Gy) (p = 0.00). Radionecrosis occurred in 2 metastases (0.28 %). No clinical toxicity of grade 3 or higher occurred during follow-up. One- and 2-year LC was 90 % and 79 %, respectively. At the UVA BED > 70 Gy and non-melanoma histology were significant predictors of higher LC. The 2-year WBRT-free survival was 70 %. After a median follow-up of 17.4 months, 12 patients deceased by ND. Conclusion: Intracranical relapses can be safely and effectively treated with repeated HyperArc, with the aim to postpone or avoid WBRT. Diffuse dose by volumetric RT might reduce microscopic disease also at relatively low levels, potentially acting as a virtual CTV. Neurological death is not the most common cause of death in this population, which highlights the impact of extracranial disease on overall survival.

Abstract Background John M. Opitz, a towering figure in both stature and scientific achievement, left an indelible mark on the fields of genetics, pediatrics, and embryology. Born in 1935 in Hamburg to a Jewish family, Opitz’s early life was marked by adversities. Despite these challenges, he pursued a remarkable career, immigrating to the United States at 15 years and becoming a renowned scientist in institutions like Iowa State University and the University of Wisconsin, where he made groundbreaking contributions to clinical genetics. Main body A testament to his compassionate nature, Opitz dedicated himself to understanding and treating rare genetic disorders, earning him eponymous recognition in several medical conditions. His impact extended beyond academia, as evidenced by his collaborative efforts with Sicilian universities to advance clinical genetics in Italy. Opitz’s teaching style emphasized simplicity, empathy, and meticulous clinical examination, leaving an indelible mark on students and colleagues. Conclusion John M. Opitz’s towering intellect, compassionate demeanor, and profound impact on medicine and genetics made him a figure of enduring significance. His legacy lives on through the countless lives he touched, the knowledge he transmitted, and the enduring friendships he forged. In remembering John Opitz, we honor not only a man, but also a myth—a symbol of resilience, humanity, and scientific excellence.

The best treatment of unicameral bone cyst and aneurismatic bone cyst (ABC) is debated in the literature. For simple bone cysts, multiple treatments were proposed from observation only to open curettage. The historical treatment with intraosseous injection of methylprednisolone acetate into the bone cysts nowadays is reduced due to the morbidity of multiple injections and the risk of multiple pathologic fractures until the healing. Different types of treatments for ABC are reported, including surgery, percutaneous treatments, and medical treatments; however, there is currently no consensus on the best approach. The association of curettage, bone graft, and elastic stable intramedullary nail (ESIN) had a success rate of over 85%. Decompressing the cyst wall is more critical for increasing the healing rate than the type of graft used to fill the cavity. In ABC, sclerotherapy offers the advantages of lower invasiveness and morbidity, associated with better functional scores and faster return to full weight-bearing. Moreover, they can be used in challenging locations. Selective arterial embolization is a complex procedure and often requires association with other treatments. Further studies are needed to confirm the effectiveness of denosumab and its side effects on skeletally immature patients. Curettage with adjuvants and autogenous bone grafting still shows promising results and can be used in larger, aggressive defects or superficial lesions. For simple bone cysts, the combination of curettage, bone graft, and ESIN showed the best results. Sclerotherapy for ABC also shows promising results.

In recent decades, the Arctic Ocean has undergone changes associated with enhanced poleward inflow of Atlantic and Pacific waters and increased heat flux exchange with the atmosphere in seasonally ice-free regions. The associated changes in upper-ocean heat content can alter the exchange of energy at the ocean–ice interface. Yet, the role of ocean heat content in modulating Arctic sea ice variability at sub-seasonal timescales is still poorly documented. We analyze ocean heat transports and surface heat fluxes between 1980–2021 using two eddy-permitting global ocean reanalyses, C-GLORSv5 and ORAS5, to assess the surface energy budget of the Arctic Ocean and its regional seas. We then assess the role of upper-ocean heat content, computed in the surface mixed layer (Qml) and in the 0–300 m layer (Q300), as a sub-seasonal precursor of sea ice variability by means of lag correlations. Our results reveal that in the Pacific Arctic regions, sea ice variability in autumn is linked with Qml anomalies leading by 1 to 3 months, and this relationship has strengthened in the Laptev and East Siberian seas during 2001–2021 relative to 1980–2000, primarily due to reduced surface heat loss since the mid-2000s. Q300 anomalies act as a precursor for wintertime sea ice variability in the Barents and Kara seas, with considerable strengthening and expansion of this link from 1980–2000 and 2001–2021 in both reanalyses. Our results highlight the role played by upper-ocean heat content in modulating the interannual variability of Arctic sea ice at sub-seasonal timescales. Heat stored in the ocean has important implications for the predictability of sea ice, calling for improvements in forecast initialization and a focus upon regional predictions in the Arctic region.

Ralstonia spp. are low-virulent environmental Gram-negative bacteria that can cause serious nosocomial infections in immunocompromised patients. We report the characteristics of a cluster of R. insidiosa bacteremia cases occurring in our oncology day ward in Milan, Italy, between January and March 2022. A case was defined as a cancer patient attending our day ward and whose blood culture (performed because of bacteremia symptoms) led to the isolation of Ralstonia insidiosa. An epidemiological investigation was conducted in order to seek the possible source of infection. Seven adult patients received curative or palliative treatment via infusion through a Port-a-Cath (PAC). All developed symptoms within 24 h of the infusion (three during the infusion itself). Ralstonia insidiosa was isolated in the blood drawn from the PAC in all patients. All of the isolates were susceptible to carbapenems, fluoroquinolones, and piperacillin/tazobactam but resistant to aminoglycosides and cephalosporins. Systemic and/or lock antibiotic therapy led to stable symptom resolution and negative blood cultures in five patients, whereas bacteremia recurred in two patients. An epidemiological investigation suggested that extrinsic contamination of antiseptic solutions was the possible cause of the R. insidiosa infections. Although R. insidiosa is not considered a virulent pathogen, clinicians, microbiologists, and infection control teams should be aware about its potential to cause outbreaks of nosocomial bloodstream infections, especially in immunocompromised patients bearing central venous catheters.

Abstract Background Point-of-care ultrasound (POCUS) is becoming increasingly crucial in the Pediatric Emergency Department for objective patient examination. However, despite its growing interest and wide-ranging applications, POCUS remains relatively unexplored in general pediatric training and education. Many physicians still find it challenging to comprehend and implement. Methods A theoretical-practical POCUS course for pediatric residents was conducted at the University of Catania, Italy. The course’s effectiveness and practical impact on residents was assessed through a pre-post training survey. The first part of the questionnaire focused on the self-perceived time needed to learn how to recognize the following conditions using POCUS: (i) Pleural effusion (ii) Lung consolidation (iii) Pneumothorax (PNX) (iv) Cardiac contractility (v) Pericardial effusion (vi) Perisplenic effusion (vii) Morison’s pouch effusion (viii) Douglas’ pouch effusion (ix) Filling and collapsibility of the inferior vena cava. In the second part, we compared the potential role of POCUS in (i) Reducing the use of ionizing radiation in children (ii) Increasing the sense of security in diagnosis and treatment decisions making and (iii) Increasing the residents’ confidence level with POCUS after the course on a 1-to-10 rating scale. Results Seventy-two residents participated in the study. The statistical analysis showed significant pre-post differences in almost all the items considered, except for “cardiac contractility” and “PNX”. Furthermore, the perceived potential role of POCUS in reducing ionizing radiation usage and the sense of security in diagnosis and treatment decisions showed statistically significant differences (p

Giant cell tumor of bone (GCTB) is characterized by uncertain biological behavior due to its local aggressiveness and metastasizing potential. In this study, we conducted a meta-analysis of the contemporary literature to evaluate all management strategies for GCTB metastases. A combination of the terms “lung metastases”, “giant cell tumor”, “bone”, “treatment”, and “oncologic outcomes” returned 133 patients meeting our inclusion criteria: 64 males and 69 females, with a median age of 28 years (7–63), at the onset of primary GCTB. Lung metastases typically occur at a mean interval of 26 months (range: 0–143 months) after treatment of the primary site, commonly presenting as multiple and bilateral lesions. Various treatment approaches, including surgery, chemotherapy, radiotherapy, and drug administration, were employed, while 35 patients underwent routine monitoring only. Upon a mean follow-up of about 7 years (range: 1–32 years), 90% of patients were found to be alive, while 10% had died. Death occurred in 25% of patients who had chemotherapy, whereas 96% of those not treated or treated with Denosumab alone were alive at a mean follow-up of 6 years (range: 1–19 years). Given the typically favorable prognosis of lung metastases in patients with GCTB, additional interventions beyond a histological diagnosis confirmation may not be needed. Denosumab, by reducing the progression of the disease, can play a pivotal role in averting or delaying lung failure.

Abstract Background In response to the imperative need for standardized support for adolescent Gender Dysphoria (GD), the Italian Academy of Pediatrics, in collaboration with the Italian Society of Pediatrics, the Italian Society for Pediatric Endocrinology and Diabetes, Italian Society of Adolescent Medicine and Italian Society of Child and Adolescent Neuropsychiatry is drafting a position paper. The purpose of this paper is to convey the author's opinion on the topic, offering foundational information on potential aspects of gender-affirming care and emphasizing the care and protection of children and adolescents with GD. Main body Recognizing that adolescents may choose interventions based on their unique needs and goals and understanding that every individual within this group has a distinct trajectory, it is crucial to ensure that each one is welcomed and supported. The approach to managing individuals with GD is a multi-stage process involving a multidisciplinary team throughout all phases. Decisions regarding treatment should be reached collaboratively by healthcare professionals and the family, while considering the unique needs and circumstances of the individual and be guided by scientific evidence rather than biases or ideologies. Politicians and high court judges should address discrimination based on gender identity in legislation and support service development that aligns with the needs of young people. It is essential to establish accredited multidisciplinary centers equipped with the requisite skills and experience to effectively manage adolescents with GD, thereby ensuring the delivery of high-quality care. Conclusion Maintaining an evidence-based approach is essential to safeguard the well-being of transgender and gender diverse adolescents.

Objectives: To retrospectively describe the patterns of use of dalbavancin for treating infections in diabetic patients in Italian and Spanish standard clinical practice. Methods: DALBADIA [NCT04959799] was a multicentre, observational, retrospective cohort study, conducted in Italy and Spain. The study enrolled 97 adults with type 1 or 2 diabetes mellitus, treated with dalbavancin as per standard clinical practice for a Gram-positive bacterial infection or the Gram-positive component of a mixed infection. Results: Dalbavancin was used to treat cellulitis (18/92 patients, 19.6%), followed by prosthetic joint infection (14 patients, 15.2%), endocarditis (13 patients, 14.1%), and primary bacteraemia (10 patients, 10.9%); 78/92 (84.8%) patients had Gram-positive infections only, and 14 (15.2%) had mixed infections. The most frequently isolated microorganisms were Staphylococcus aureus in 43 (55.8% of the patients with microbial isolation), 25.6% of which methicillin-resistant; Staphylococcus epidermidis in 13 (16.9%), 53.8% of which methicillin-resistant; Enterococcus faecalis in 11 (14.3%). The main reason for the dalbavancin choice was the intent to simplify the antibiotic regimen (81.5% of cases). A multidisciplinary team participated in the treatment choice process for 53 (57.6%) patients. Dalbavancin was given as first-line antibiotic in 34 (37.0%) patients and administered as one infusion in 32 (34.8%), and as two infusions in 39 (42.4%). In total, 57/62 (91.9%) eligible patients with available assessment were judged clinically cured or improved at the end of observation. Conclusion: In clinical practice, dalbavancin was used in diabetic patients to treat ABSSSIs and other difficult-to-treat infections with a favourable safety profile and a high rate of positive clinical responses.

BackgroundDengue is the most prevalent arboviral infection causing an estimated 50-60 million cases of febrile illness globally per year, exacting considerable disease burden. Few instruments exist to assess the patient illness experience, with most based on healthcare provider assessment, lacking standardization in timepoints and symptom assessment. This study aimed to evaluate the content validity of the novel 'Dengue Virus Daily Diary (DENV-DD)', designed to measure symptom intensity and disease burden within outpatient infant to adult populations.MethodsThe Dengue Illness Index Report Card was used as a foundation to create the DENV-DD, consisting of patient- and observer-reported outcome (PRO/ObsRO) instruments. In two South American dengue-endemic communities, qualitative combined concept elicitation and cognitive debriefing interviews were conducted among individuals and caregivers of children with symptomatic laboratory-confirmed dengue. Interviews were conducted across two rounds allowing DENV-DD modifications. A small-scale quantitative assessment of the DENV-DD was also conducted with data from an independent Dengue Human Infection Model (DHIM) to generate early evidence of feasibility of DENV-DD completion, instrument performance and insight into the sign/symptom trajectory over the course of illness.ResultsForty-eight participants were interviewed (20 adults, 20 older children/adolescents with their caregivers, 8 caregivers of younger children). A wide spectrum of signs/symptoms lasting 3-15 days were reported with fever, headache, body ache/pain, loss of appetite, and body weakness each reported by > 70% participants. DENV-DD instructions, items and response scales were understood, and items were considered relevant across ages. DHIM data supported feasibility of DENV-DD completion.ConclusionsFindings demonstrate content validity of the DENV-DD (PRO/ObsRO instruments) in dengue-endemic populations. Psychometric and cultural validity studies are ongoing to support use of the DENV-DD in clinical studies.

Gonadal and gonosomal mosaicism describe phenomena in which a seemingly healthy individual carries a genetic variant in a subset of their gonadal tissue or gonadal and somatic tissue(s), respectively, with risk of transmitting the variant to their offspring. In families with one or more affected offspring, occurrence of the same apparently de novo variants can be an indicator of mosaicism in either parent. Panel-based deep sequencing has the capacity to detect low-level mosaic variants with coverage exceeding the typical limit of detection provided by current, readily available sequencing techniques. In this study, we report three families with more than one affected offspring with either confirmed or apparent parental gonosomal or gonadal mosaicism for PIK3CD pathogenic variants. Data from targeted deep sequencing was suggestive of low-level maternal gonosomal mosaicism in Family 1. Through this approach we did not detect pathogenic variants in PIK3CD from parental samples in Family 2 and Family 3. We conclude that mosaicism was likely confined to the maternal gonads in Family 2. Subsequent long-read genome sequencing in Family 3 showed that the paternal chromosome harbored the pathogenic variant in PIK3CD in both affected children, consistent with paternal gonadal mosaicism. Detection of parental mosaic variants enables accurate risk assessment, informs reproductive decision-making, and provides helpful context to inform clinical management in families with PIK3CD pathogenic variants.

O aquecimento global é atribuído ao aumento das emissões de gases de efeito estufa (GEE), como dióxido de carbono (CO2), metano (CH4) e óxido nitroso (N2O). As mudanças no uso da terra têm impactos significativos nas emissões de GEE, sendo responsáveis por aproximadamente 44% das emissões do país em 2019. Essa é uma revisão que aborda as principais rotas de formação dos GEE no solo com foco na influência das mudanças do uso da terra nas emissões de GEE. Constata-se que as emissões de CO2 pelo solo estão relacionadas à respiração de raízes, microrganismos e decomposição da matéria orgânica (MO) do solo, assim mudanças no uso da terra podem alterar as características do solo, favorecendo a intensificação das emissões de CO2. As emissões de CH4 pelo solo ocorrem em condições de anaerobiose por microrganismos metanogênicos, no entanto as mudanças no uso da terra, como a conversão de florestas em pastagens, podem aumentar as emissões de CH4 devido a uma maior concentração de microrganismos metanogênicos no solo. Já o N2O é produzido no solo durante o processo de nitrificação e desnitrificação por microrganismos, e a fertilização nitrogenada em áreas agrícolas pode aumentar as emissões de N2O, especialmente quando associada à umidade e disponibilidade de carbono orgânico no solo. Destaca-se a importância de compreender as dinâmicas de formação e emissão de GEE decorrentes das mudanças de uso da terra, pois estratégias eficientes de manejo podem reduzir essas emissões e contribuir para o cumprimento das metas do Brasil em relação à redução de GEE estabelecidas em acordos internacionais.

BackgroundTelerehabilitation (TR) offers a valuable opportunity to improve access to care and has shown results comparable to onsite rehabilitation (SR) across different conditions. The present study aimed to explore the efficacy of TR and SR in improving clinically meaningful outcomes in people with multiple sclerosis (pwMS).Materials and methodsSubjects enrolled in the study were assigned to one of two treatment arms: a 6-week TR intervention or a 6-week onsite rehabilitation (SR) intervention. Pre-and post-intervention evaluation included assessment of global wellbeing using the Multiple Sclerosis Quality of Life-54 scale (QoL), fatigue using the Fatigue Severity Status scale (FSS), cognitive status using the Symbol Digit Modalities Test (SDMT), and balance dysfunction using the Berg Balance Scale (BBS). Group-level and single-subject improvements were considered as outcome measures, with QoL as the primary endpoint. To determine significant group changes over time for the entire pwMS cohort, a paired t-test was applied to the overall QoL score, focusing on both physical and mental composites. An independent sample t-test was used to assess differences in baseline and follow-up performance, as well as changes over time between the intervention groups (TR and SR). This same analysis was repeated for the other clinical domains (FSS, BBS, and SDMT). The minimal clinically important difference (MCID) according to treatment group (TR vs. SR) was explored using logistic regression. Additionally, a multiple linear regression model was applied to evaluate the impact of baseline clinical-demographic features on the observed post-intervention modifications.ResultsA total of 51 subjects completed the study (37 women, mean age 46.3 ± 9.8, median Expanded Disability Status Scale 3.5, min. 2, max. 6.5). The entire sample benefited from the rehabilitation treatment, with significant improvements observed at both the group and individual levels across all measured domains for both intervention groups (TR vs. SR). Quality of life improved significantly (p = 0.005), as did fatigue and balance (both p < 0.001), and cognition (p = 0.003).ConclusionsBoth SR and TR approaches effectively improved the perception of fatigue, cognitive performance, balance, and quality of life in a population of MS patients with moderate disability.

This perspective discusses how to best define “e-cigarette use” among youth in a way that is relevant to individual and human health. Commonly-used definitions of youth e-cigarette use have been adapted from measures validated for tobacco cigarette smoking among adults, but may not carry the same meaning for a different product (with a much lower risk profile and very different patterns of use) and a different population (whose use is more often transient and experimental, rather than frequent and persistent). We discuss strengths and weaknesses of different definitions, and recommend improvements in defining youth e-cigarette use. We find that current literature employs a range of definitions of e-cigarette use, from lifetime use (“even a puff”) to daily use. More lenient measures capture more potentially at-risk youth, but much of this is transient experimentation that has negligible risks in and itself, if not persistent. More stringent measures such as daily use are more relevant to individual and public health. Future research should examine possible improvements to definitions which include intensity of use (e.g., number of puffs per day) and persistence/duration of use, either via self-report or technology-assisted data capture.

Transgender and gender-diverse (TGD) individuals face an elevated risk of cancer in comparison with the general population. This increased risk is primarily attributed to an imbalanced exposure to modifiable risk factors and a limited adherence to cancer screening programmes, stemming from historical social and economic marginalisation. Consequently, these factors contribute to poorer clinical outcomes in terms of cancer diagnosis and mortality. A focal point of interest is the potential carcinogenic effect of gender-affirming hormone therapy (GAHT). It is crucial to recognise that GAHT serves as an essential, life-saving treatment for TGD individuals. Therefore, if a demonstrated direct correlation between GAHT and elevated cancer risk emerges, essential shared decision-making discussions should occur between oncology practitioners and patients. This narrative review aims to collect and discuss evidence regarding potential correlations between GAHT and the most prevalent tumours known to be influenced by sex hormones. The objective is to comprehend how these potential carcinogenic effects impact health and inform health interventions for TGD individuals. Unfortunately, the scarcity of epidemiological data on cancer incidence in the TGD population persists due to the absence of sexual orientation and gender identity data collection in cancer centres. Consequently, in most cases, establishing a positive or negative correlation between GAHT and cancer risk remains speculative. There is an urgent need for concerted efforts from researchers and clinicians worldwide to overcome barriers and enhance cancer prevention and care in this specific population.

Ao se ter em mente as mudanças realizadas nas instituições escolares brasileiras após as recentes reformas nas diretrizes de ensino, deve-se buscar compreender qual o projeto que embasa tais mudanças. Sendo assim, este trabalho objetiva elaborar uma análise crítica das premissas ideológicas que fazem da escola e da vida dos estudantes um projeto laboral, cujo imperativo é a “felicidade”, ao invés da práxis cidadã que pressupõe os conflitos sociopolíticos. Realizou-se, portanto, uma revisão da literatura existente a respeito dos fatores teóricos e práticos que caracterizam o Projeto de Vida como uma disciplina a ser ofertada na grade curricular no Ensino Médio brasileiro. Tal literatura foi encontrada em portais especializados no compartilhamento de artigos, periódicos e matérias a respeito do tema proposto, como Pepsic e Google Acadêmico. O neoliberalismo deve ser visto não apenas como um modelo econômico, mas como uma forma de construção de subjetividade. Deste modo, entende-se que, por meio da prática de autoafirmação e competitividade proposta pela disciplina Projeto de Vida, o mesmo se faz valer dentro do modelo educacional brasileiro.

M-mode ultrasonography has been used in the assessment of diaphragm kinetics. The sonographic diaphragmatic parameters can provide valuable information in the assessment and follow-up of patients with diaphragmatic dysfunction, during ventilation, and can potentially help to understand post-operative pulmonary dysfunction or weaning failure from ventilation. We conducted a systematic review of literature concerning the clinical applications of diaphragmatic ultrasound in children. The morphological and functional evaluation of the diaphragm by ultrasound technique is becoming an increasingly widespread practice in intensive, medical and surgery category. Our systematic review shows how diaphragmatic ultrasonography finds indication in different areas. It requires a standardization of parameters and normal measurement values.

The use of nature-based solutions (NbS) to address the risks posed by hydro-meteorological hazards have not yet become part of the mainstream policy response, and one of the main reasons cited for this, is the lack of evidence that they can effectively reduce disaster risk. This paper addresses this issue, by providing model-based evidence from five European case studies which demonstrate the effectiveness of five different NbS in reducing the magnitude of the hazard and thus risk, in present-day and possible future climates. In OAL-Austria, the hazard is a deep-seated landslide, and the NbS analysed is afforestation. Modelling results show that in today's climate and a landcover scenario of mature forest, a reduction in landslide velocity of 27.6 % could be achieved. In OAL-Germany, the hazard is river flooding and the NbS analysed is managed grazing with removal of woody vegetation. Modelling results show that the NbS could potentially reduce maximum flood water depth in the near-future (2031–2060) and far-future (2070–2099), by 0.036 m and 0.155 m, respectively. In OAL-Greece, the hazard is river flooding, and the NbS is upscaled natural storage reservoirs. Modelling results show that in a possible future climate the upscaled NbS show most potential in reducing the total flooded area by up to 1.26 km2. In OAL-Ireland, the hazard is surface and river flooding, and the NbS is green roofs. Results from a modelled upscaling analysis under two different climate scenarios show that both maximum flood water depth, and total flooded area were able to be reduced. In OAL-UK, the hazard is shallow landslides, and the NbS is high-density planting of two different tree species. Modelling results under two different climate scenarios show that both tree species were able to improve slope stability, and that this increased over time as the NbS matured. The significance of these results is discussed within the context of the performance of the NbS over time, to different magnitude events, impact with stakeholders in engendering wider support for the adoption of the NbS in the OALs, and the uncertainty in the modelling analyses.

The non-breeding distribution and ecology of many migratory songbirds are often poorly studied, but very relevant for their conservation in a changing climate. The Snow Bunting is the most northerly breeding passerine worldwide, and winters in temperate/temperate-cold areas. Characterised by specialisation for cold climate and strong migratory connectivity, it underwent a recent range contraction and is declining because of rising winter temperatures. Investigating its migration and wintering distribution and ecology is relevant to understand the possible impacts of climate change. We used citizen science records to describe and model the species distribution during migration and winter in Italy, and evaluated its cultural relevance. Snow Buntings occur in Italy in November-mid April, mostly clustered in northern and, particularly, north-eastern regions (coasts and plateaus in mountain regions); all the observations involving >12 individuals occurred at a single site in the Lessinia plateau. The elevation pattern of observations (both during winter and migration) showed a bimodal distribution (mostly at the sea level and in middle-elevation mountains, peaking around 1500 m asl). Species Distribution Models showed that the most suitable areas largely coincide with the areas from where most observations occurred, and were similar during winter and migration. Such areas are characterised by relatively cold and dry climates, and by flat or gentle sloping terrain largely occupied by open or semi-open habitats (grassland, pastures, sandy habitats). Snow Buntings had a much higher occurrence rates in social media/networks than other bunting species, indicating that nature recreationists have a particular preference for this species, which can be used as a flagship species. The species will likely suffer from ongoing climate variation, and preserving suitable open landscapes, with grassland-dominated habitats, is key to the maintenance of suitable stop-over and wintering sites. At the same time, this would also benefit many declining breeding species.