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Nowadays, we face a profound fragmentation of knowledge, which is addressed in distinctive ways, conforming to the specifics of each field of knowledge and having a specific lexicon and ways to interpret reality. To better understand and communicate the complexity of the reality of motor and sports sciences in Italy, it is necessary to study its ontology based on a holistic and comprehensive approach such as System Thinking (ST). So, this preliminary review aimed to verify the coherence of terminology used by Italian academics (who study methodologies related to teaching) and practical communities (who live the reality of daily teaching) in motor and sports sciences, specifically regarding the didactic of physical and sports education. For this purpose, according to Design Based Research (DBR), a first investigation of the interpretative semantics of the discipline's specific terms was accomplished with the support of multiple sources of information such as documents, databases, and brainstorming performed by experts (representing the guiding team and stakeholders from all considered communities). Moreover, the frequency of some terms and keywords considered in European (ERC) and Italian (CUN) legislation was assessed to contextualize better the impact of common practice community keywords on the scientific and regulatory community. Successively, the studies that analyzed the terms from 2000 to 2020 in the leading scientific search engines (SCOPUS and Web of Science) were also investigated. Results indicate that in the CUN and ERC areas, there is a total absence of the most relevant lemma to the community of practice. Furthermore, significant terms such as play, sports education, psychomotricity, and gymnastics are less considered or unconsidered in the specific scientific and didactic fields. Possible solutions for a specific semantic model to reduce the gap are finally hypothesized and presented.

Abstract Background Although second-generation antipsychotics (SGAs) have proven to be effective therapeutic options for patients with schizophrenia, there is a notable lack of evidence on patients’ subjective perspectives regarding their well-being, quality of life, and satisfaction with these medications. This study aimed to evaluate the treatment satisfaction and effectiveness of lurasidone on quality of life and functioning in adult patients with schizophrenia in real-world Italian clinical practice. Methods This was a multicentre, national, non-interventional, single-arm, 3-month prospective study. Patients who were naive to lurasidone treatment and whose treating physician had decided to start them on this medication were enrolled and evaluated over a 3-month period. Eligible patients were adults (≥ 18 years of age) with a primary diagnosis of schizophrenia who were being treated with lurasidone (for the first time [i.e., they were lurasidone naive]) as part of routine clinical practice. Efficacy endpoints were changes in patient/caregiver treatment satisfaction (seven-point Likert scale from the Treatment Satisfaction Questionnaire for Medication), patient quality of life and functioning (QLS), investigator-rated global assessment of functioning (CGI-S, IAQ) after 6 weeks and 3 months of lurasidone, and number of relapses and hospitalizations. Results Sixty-one patients were enrolled and 59 completed the study. The median dosage of lurasidone at baseline was 37.00 mg/day. The median duration of titration was 86.0 days (Min 28; Max 115 days); the median number of dosage changes was 1.0. At the end of 3-month observation period, the median dose of lurasidone was 74.00 mg/day. QoL and Functioning Score showed a trend of improvement over time, reaching a mean change from baseline of 9.8 at the end of the study. According to the CGI-S, the percentage of patients who were “markedly or severely ill” showed a continuous decrease from baseline to 3 months, from 62.29% to 8.20%. Patient satisfaction increased over time, with 80.32% of patients reporting that they were somewhat, fairly, or very satisfied (including 63.93% who were completely or very satisfied) at the end of the study. No relapses/hospitalizations for psychiatric reasons were reported. Lurasidone was well tolerated with no safety concerns or discontinuations due to AEs. Conclusions Lurasidone represents a valid option for the treatment of schizophrenia and positively affects subjective well-being, quality of life and satisfaction. Trial registration NCT06527885 retrospectively registered (01/08/2024).

Abstract Adverse life events (e.g., severe accidents, violence/abuse, organic disorders) can elicit traumatic responses characterized by intrusive thoughts, hyperarousal, and avoidance—highlighting the need for sound assessment tools. Also, these traumatic components could heighten anxiety and depression symptoms. This study aims included to: (1) assessing the psychometric properties of the Post-Traumatic Symptom Questionnaire (PTSQ) and delineating clinical cut-offs; (2) investigating how distinct trauma components contribute to anxiety and depression symptoms. Involving 761 participants who experienced a traumatic event, Part I tested the PTSQ psychometric properties, defining clinical cut-offs. Part II tested the impact of traumatic components on anxiety and depression symptoms, using a multiple multivariate latent regression model. PTSQ exhibited exemplary fit indices and robust psychometric properties. Clinically relevant cut-offs were identified. The differential contributions of intrusion, avoidance, and hyperarousal to anxiety and depression symptoms were evaluated, elucidating the strength and nature of these relationships. This study reaffirms the PTSQ as a psychometrically sound and reliable instrument. It underscores the effects of intrusion, avoidance, and hyperarousal on anxiety and depression symptoms in individuals with traumatic experiences. These insights advocate for evidence-based interventions aimed at alleviating the psychological suffering associated with trauma components, fostering adaptation and supporting psychological health.

Abstract Coronavirus disease 2019 (COVID-19) has been associated with brain functional, structural, and cognitive changes that persist months after infection. Most studies of the neurologic outcomes related to COVID-19 focus on severe infection and aging populations. Here, we investigated the neural activities underlying COVID-19 related outcomes in a case-control study of mildly infected youth enrolled in a longitudinal study in Lombardy, Italy, a global hotspot of COVID-19. All participants (13 cases, 27 controls, mean age 24 years) completed resting-state functional (fMRI), structural MRI, cognitive assessments (CANTAB spatial working memory) at baseline (pre-COVID) and follow-up (post-COVID). Using graph theory eigenvector centrality (EC) and data-driven statistical methods, we examined differences in ECdelta (i.e., the difference in EC values pre- and post-COVID-19) and Volumetricdelta (i.e., the difference in cortical volume of cortical and subcortical areas pre- and post-COVID) between COVID-19 cases and controls. We found that ECdelta significantly between COVID-19 and healthy participants in five brain regions; right intracalcarine cortex, right lingual gyrus, left hippocampus, left amygdala, left frontal orbital cortex. The left hippocampus showed a significant decrease in Volumetricdelta between groups (p = 0.041). The reduced ECdelta in the left amygdala associated with COVID-19 status mediated the association between COVID-19 and disrupted spatial working memory. Our results show persistent structural, functional and cognitive brain changes in key brain areas associated with olfaction and cognition. These results may guide treatment efforts to assess the longevity, reversibility and impact of the observed brain and cognitive changes following COVID-19.

Musculoskeletal disorders are common among older adults, affecting mobility and quality of life. Effective rehabilitation is essential, but the implementation of programs faces challenges. Traditional methods often necessitate in-person assessments, which can be difficult for older adults with mobility limitations. Telerehabilitation offers a solution, bringing therapy closer to patients. However, the accurate remote monitoring of health and performance remains a challenge. This study addresses this gap by developing and validating the System for Tracking and Evaluating Performance (STEP). STEP is a hardware-software system that automates physical performance tests, eliminating the need for constant expert supervision. The system focuses on three standard tests: the Six-Minute Walking Test (6MWT), the Ten-Meter Walking Test (10MWT), and the 30-s Sit-to-Stand Test (30STS). Validation compared results from the STEP app with in-person assessments by physicians for patients undergoing rehabilitation after knee or hip arthroplasty. The study found strong positive correlations between the app’s results and the physicians’ assessments for all tests. These findings demonstrate the STEP system’s potential as a reliable tool for remote physical performance assessment. Further research is needed to explore its integration into clinical practice and cost-effectiveness in reducing the need for operator assistance in monitoring patients with physical limitations.

The emergence and spread of drug-recalcitrant Plasmodium falciparum parasites threaten to reverse the gains made in the fight against malaria. Urgent measures need to be taken to curb this impending challenge. The higher plant-derived sesquiterpene, quinoline alkaloids, and naphthoquinone natural product classes of compounds have previously served as phenomenal chemical scaffolds from which integral antimalarial drugs were developed. Historical successes serve as an inspiration for the continued investigation of plant-derived natural products compounds in search of novel molecular templates from which new antimalarial drugs could be developed. The aim of this study was to identify potential chemical scaffolds for malaria drug discovery following analysis of historical data on phytochemicals screened in vitro against P. falciparum. To identify these novel scaffolds, we queried an in-house manually curated database of plant-derived natural product compounds and their in vitro biological data. Natural products were assigned to different structural classes using NPClassifier. To identify the most promising chemical scaffolds, we then correlated natural compound class with bioactivity and other data, namely (i) potency, (ii) resistance index, (iii) selectivity index and (iv) physicochemical properties. We used an unbiased scoring system to rank the different natural product classes based on the assessment of their bioactivity data. From this analysis we identified the top-ranked natural product pathway as the alkaloids. The top three ranked super classes identified were (i) pseudoalkaloids, (ii) naphthalenes and (iii) tyrosine alkaloids and the top five ranked classes (i) quassinoids (of super class triterpenoids), (ii) steroidal alkaloids (of super class pseudoalkaloids) (iii) cycloeudesmane sesquiterpenoids (of super class triterpenoids) (iv) isoquinoline alkaloids (of super class tyrosine alkaloids) and (v) naphthoquinones (of super class naphthalenes). Launched chemical space of these identified classes of compounds was, by and large, distinct from that of legacy antimalarial drugs. Our study was able to identify chemical scaffolds with acceptable biological properties that are structurally different from current and previously used antimalarial drugs. These molecules have the potential to be developed into new antimalarial drugs.

The antimalarial drug-resistance conundrum which threatens to reverse the great strides taken to curb the malaria scourge warrants an urgent need to find novel chemical scaffolds to serve as templates for the development of new antimalarial drugs. Plants represent a viable alternative source for the discovery of unique potential antiplasmodial chemical scaffolds. To expedite the discovery of new antiplasmodial compounds from plants, the aim of this study was to use phylogenetic analysis to identify higher plant orders and families that can be rationally prioritised for antimalarial drug discovery. We queried the PubMed database for publications documenting antiplasmodial properties of natural compounds isolated from higher plants. Thereafter, we manually collated compounds reported along with plant species of origin and relevant pharmacological data. We systematically assigned antiplasmodial-associated plant species into recognised families and orders, and then computed the resistance index, selectivity index and physicochemical properties of the compounds from each taxonomic group. Correlating the generated phylogenetic trees and the biological data of each clade allowed for the identification of 3 hot plant orders and families. The top 3 ranked plant orders were the (i) Caryophyllales, (ii) Buxales, and (iii) Chloranthales. The top 3 ranked plant families were the (i) Ancistrocladaceae, (ii) Simaroubaceae, and (iii) Buxaceae. The highly active natural compounds (IC50 ≤ 1 µM) isolated from these plant orders and families are structurally unique to the legacy antimalarial drugs. Our study was able to identify the most prolific taxa at order and family rank that we propose be prioritised in the search for potent, safe and drug-like antimalarial molecules.

Malignant pleural mesothelioma (MPM) represents a significant clinical challenge due to limited therapeutic options and poor prognosis. Beyond mere survivorship, setting up an effective framework to improve functioning and quality of life is an urgent need in the comprehensive management of MPM patients. Therefore, this study aims to review the current understanding of MPM sequelae and the effectiveness of rehabilitative interventions in the holistic approach to MPM. A narrative review was conducted to summarize MPM sequelae and their impact on functioning, disability, and quality of life, focusing on rehabilitation interventions in MPM management and highlighting gaps in knowledge and areas for further investigation. Our findings showed that MPM patients experience debilitating symptoms, including fatigue, dyspnea, pain, and reduced exercise tolerance, decreasing quality of life. Supportive and rehabilitative interventions, including pulmonary rehabilitation, physical exercise improvement, psychological support, pain management, and nutritional supplementation, seem promising approaches in relieving symptoms and improving quality of life but require further research. These programs emphasize the pivotal synergy among patient-tailored plans, multidisciplinary team involvement, and disease-specific focus. Despite advancements in therapeutic management, MPM remains a challenging disease with limited effective interventions that should be adapted to disease progressions. Rehabilitative strategies are essential to mitigate symptoms and improve the quality of life in MPM patients. Further research is needed to establish evidence-based guidelines for rehabilitative interventions tailored to the unique needs of MPM patients.

Abstract In recent decades, the food system has been faced with the significant problem of increasing food waste. Therefore, the feed industry, supported by scientific research, is attempting to valorise the use of discarded biomass as co-products for the livestock sector, in line with EU objectives. In parallel, the search for functional products that can ensure animal health and performances is a common fundamental goal for both animal husbandry and feeding. In this context, camelina cake (CAMC), cardoon cake (CC) and cardoon meal (CM), due valuable nutritional profile, represent prospective alternatives. Therefore, the aim of this work was to investigate the antioxidant activity of CAMC, CC and CM following in vitro digestion using 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), Ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) assays. Total phenolic content (TPC) and angiotensin converting enzyme (ACE) inhibitory activity, actively involved in modulating antioxidant properties, were also studied. Further, a peptidomic analysis was adopted to substantiate the presence of bioactive peptides after in vitro digestion. The results obtained confirmed an interesting nutritional profile of CAMC, CC and CM and relevant antioxidant and ACE inhibitory activities. In particular, considering antioxidant profile, CM and CC revealed a significantly higher (10969.80 ± 18.93 mg TE/100 g and 10451.40 ± 149.17 mg TE/100 g, respectively; p

Background and aimsENHANCE was a phase 3 study that evaluated efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor-δ (PPAR) agonist, versus placebo in patients with primary biliary cholangitis with inadequate response or intolerance to ursodeoxycholic acid (UDCA).Approach and resultsPatients were randomized 1:1:1 to oral seladelpar 5 mg (n=89), 10 mg (n=89), placebo (n=87) daily (with UDCA, as appropriate). Primary end point was a composite biochemical response [alkaline phosphatase (ALP) < 1.67×upper limit of normal (ULN), ≥15% ALP decrease from baseline, and total bilirubin ≤ ULN] at month 12. Key secondary end points were ALP normalization at month 12 and change in pruritus numerical rating scale (NRS) at month 6 in patients with baseline score ≥4. Aminotransferases were assessed. ENHANCE was terminated early following an erroneous safety signal in a concurrent, NASH trial. While blinded, primary and secondary efficacy end points were amended to month 3. Significantly more patients receiving seladelpar met the primary end point (seladelpar 5 mg: 57.1%, 10 mg: 78.2%) versus placebo (12.5%) ( p < 0.0001). ALP normalization occurred in 5.4% ( p =0.08) and 27.3% ( p < 0.0001) of patients receiving 5 and 10 mg seladelpar, respectively, versus 0% receiving placebo. Seladelpar 10 mg significantly reduced mean pruritus NRS versus placebo [10 mg: -3.14 ( p =0.02); placebo: -1.55]. Alanine aminotransferase decreased significantly with seladelpar versus placebo [5 mg: 23.4% ( p =0.0008); 10 mg: 16.7% ( p =0.03); placebo: 4%]. There were no serious treatment-related adverse events.ConclusionsPatients with primary biliary cholangitis (PBC) with inadequate response or intolerance to UDCA who were treated with seladelpar 10 mg had significant improvements in liver biochemistry and pruritus. Seladelpar appeared safe and well tolerated.

BACKGROUND: Early-life environmental exposures during critical windows (CWs) of development can impact life course health. Exposure to neuroactive metals such as manganese (Mn) during prenatal and early postnatal CWs may disrupt typical brain development, leading to persistent behavioral changes. Males and females may be differentially vulnerable to Mn, presenting distinctive CWs to Mn exposure. METHODS: We used magnetic resonance imaging to investigate sex-specific associations between early-life Mn uptake and intrinsic functional connectivity in adolescence. A total of 71 participants (15-23 years old; 53% female) from the Public Health Impact of Manganese Exposure study completed a resting-state functional magnetic resonance imaging scan. We estimated dentine Mn concentrations at prenatal, postnatal, and early childhood periods using laser ablation-inductively coupled plasma-mass spectrometry. We performed seed-based correlation analyses to investigate the moderating effect of sex on the associations between Mn and intrinsic functional connectivity adjusting for age and socioeconomic status. RESULTS: We identified significant sex-specific associations between dentine Mn at all time points and intrinsic functional connectivity in brain regions involved in cognitive and motor function: 1) prenatal: dorsal striatum, occipital/frontal lobes, and middle frontal gyrus; 2) postnatal: right putamen and cerebellum; and 3) early childhood: putamen and occipital, frontal, and temporal lobes. Network associations differed depending on exposure timing, suggesting that different brain networks may present distinctive CWs to Mn. CONCLUSIONS: These findings suggest that the developing brain is vulnerable to Mn exposure, with effects lasting through late adolescence, and that females and males are not equally vulnerable to these effects. Future studies should investigate cognitive and motor outcomes related to these associations.

For several years, the application of versatile Lagrangian puff models like CALPUFF has been widely acknowledged as a standard practice in numerous countries globally for forecasting odour exposure levels in the vicinity of industrial facilities. In this case study, the CALPUFF model was adopted to assess the odour impact related to a rendering plant located in Italy. For the implementation of the emission scenario, data obtained from olfactometric monitoring conducted at the plant were taken into account. The modelling study was divided into two parts. Firstly, the odour impact resulting from the current emission condition of the plant was evaluated, distinguishing between different macro-areas of the plant: production department, cooking vats, and wastewater treatment plant. Secondly, simulations of predictive impact scenarios were conducted, assuming the introduction of odour emission containment systems for the macro-areas identified as the major contributors to impact. In particular, from the simulations, it emerged that the production department contributes negligibly to the odour impacts on the surrounding area. The cooking tanks revealed odour concentrations, at the 98th percentile on an annual basis, near the closest residential areas to the plant, reaching the odour perception threshold (1 ouE/m3). The contribution of the water treatment plant proved to be significant, with concentrations estimated on some sensitive receptors around the odour nuisance threshold (5 ouE/m3). For this reason, it was hypothesized to introduce cooling systems that facilitate the condensation of vapours emitted from the cooking vats before the release into the atmosphere. In this way, based on the simulation results, receptor concentrations lower than 1 ouE/m3 would be achieved. Regarding the wastewater treatment plant, various predictive scenarios were hypothesized, assuming the covering of one or more tanks and the conveyance of air streams to be treated. The results of the different scenarios highlighted that the configuration ensuring the greatest reduction in impacts, among those analyzed, involves covering three tanks. This way, the odour impact could be reduced by approximately 80% compared to the current scenario. However, the solution that appears to be of greater interest seemed to be the closure of only one tank: in this way, by intervening on a single emission source, receptor concentrations could be reduced by an average of 60%.

The present paper intends to discuss recent developments in detection and quantification of odorous compounds in real industrial gaseous emissions. In this work, the chemical characterization of industrial odours is carried out using an Agilent gas chromatograph (mod. 8890) coupled with three different detectors to obtain a more complete chemical characterization: a Mass Spectrometer (Agilent 5977B MSD), a Flame Ionization detector (FID, Agilent) and a Pulsed Flame Photometric Detector (PFPD, OI Analytical mod. 5833). This system (GC-MS/FID/PFPD) offers different significant advantages if compared with the classical analytical techniques currently adopted in the chemical characterisation of industrial odour mixtures. Applied to industrial case studies, it enables the selective detection and quantification of Volatile Organic Sulphur Compounds (VOSCs), even present in traces (ppb level) in complex gaseous mixtures, facilitating the identification of molecules responsible of odour harassment. This instrumentation represents a crucial development in enhancing the understanding of the chemical composition of odorous mixtures, demonstrating cost-effectiveness and time efficiency.

Dynamic olfactometry involves human examiners for quantifying odour. Examiners directly inhale, although diluted, the increasingly concentrated odorous samples and, during the analysis, they are thus exposed to substances potentially dangerous to human health. EN 13725 still does not propose a protocol for assessing the risk related to such activities. In the scientific literature, only few studies have addressed this issue, with discrepant approaches based on a deterministic risk assessment. However, the risk assessment needs the definition of exposure parameters that are strictly linked to their specific working time and the activity of the olfactometric laboratory, in terms of hours worked, number and type of samples analysed. Therefore, a deterministic risk assessment method remains limited to the experience of a single laboratory. Despite the importance of the topic, many aspects of the subject still remain unexplored. This paper aims to highlight the critical aspects of deterministic approaches available in the scientific literature (mainly due to the variability of exposure parameters connected with the specific working activity of every single panellist and each olfactometric laboratory and the necessity of conducting risk assessment within 30 h permitted by EN 13725) and evaluate the possible new solutions to conduct risk assessment for olfactometric workers.

Accuracy in the characterisation of odour-emitting sources is particularly significant for the implementation of a truly representative odour impact study. The selection of sampling techniques to measure odour concentrations, along with an accurate method to assess Odour Emission Rate, is closely linked to the type of source under investigation. The distinction between active and passive sources is not always obvious, such as in the case of biological oxidation tanks. This kind of emissive source, commonly classified as a passive source, is characterised by convective flow that is generally not intense. Indeed, the flushing of a known airflow within a dynamic hood, such as a wind tunnel system, necessary to simulate the wind action on the surface of the tank, may not be the driving force of the system. The aim of the present study is to evaluate the emissive contributions of biological oxidation tanks, focusing on the phenomenon of aeration and the effect of wind on the liquid surface of an oxidation basin. Using different sampling methodologies, through different field measurements, the Specific Odour Emission Rates, associated with each contribution, were measured and compared. The results indicate that the stripping phenomenon due to the convective flow generated by aeration can account for up to 96% of the odorous emission contribution.

The surge of atmospheric contaminants due to industrial and population expansion has led to increased public concern over olfactory annoyance, particularly in residential areas adjacent to agricultural, industrial, and waste management facilities. Characterizing passive area sources, which lack defined flows, in terms of odor emissions, represents a challenging task, exacerbated by the dual role of wind as both a dispersal agent and driving force for emission. Many sampling devices have been developed over the past decades. In particular, Flux Chambers have a mixed headspace and a non-directional flow, and Wind Tunnels have a directional flow that is predominantly parallel to the inspected surface. Besides the significant differences between the two devices, the issue is further complicated by the variety of designs proposed within the same family. Wind tunnel designs have evolved from large, portable hoods to compact versions to improve portability and fluid dynamic performances. In particular, Low-Speed Wind Tunnels have gained traction due to reduced dilution within the hoods. The aim of this study is to investigate the fluid dynamics and mass transfer of the current Italian regulatory LSWT, mentioned by the Italian legislation, with the purpose of highlighting its strengths and limitations. Fluid dynamic analysis on this device reveals non-homogenous airflow distribution within the hood, indicating the presence of a preferential channel in the central body of the wind tunnel. Mass transfer analysis demonstrates a concentration gradient along the outlet duct’s vertical direction, possibly affecting sample representativeness. Future developments may aim to achieve uniform flow and concentration distribution, ensuring accurate odor emission assessments from passive area sources.

The sampling of odorous emissions is a fundamental step in correctly quantifying odour concentration. Its importance was strongly emphasized in the recent Italian legislation (MASE, 2023), which describes strict constraints for conducting olfactometric sampling. In particular, for point sources, it is necessary to assess the variability of the source to evaluate any spikes in emissivity and then sample consistently with the trend of this emissivity. Therefore, this study aims to conduct a field sampling campaign that meets the criteria mentioned in the Italian recent directive, combining olfactometric sampling with continuous monitoring of the source using portable PID instrumentation. The results obtained during this preliminary monitoring campaign highlight that the variability in VOC emissions is not strictly correlated with potential variability in terms of odour concentration. Indeed, despite the variations observed in continuous measuring at the source, the odour concentration measurements remained stable throughout the monitoring period. Chemical speciation of samples identified high concentrations of propene, varying in accordance with PID reading, while the odour potential was primarily due to lower concentrations of octene and nonene, which remained relatively constant. These results indicate that continuous monitoring emission variability does not necessarily translate into odour concentration variability.

Gaseous emissions which may be of odour impact and interest are not solely derived from industrial processes or agricultural fields, but also from natural sources. Natural odorous gaseous emissions are often present in geothermal areas. In these cases, the inventory and the measurement of the emitted gas flows are not trivial. This work presents the experience of an olfactometric survey conducted in a geothermal-interest area, specifically around Mt. Amiata, Tuscany, Italy. Dynamic olfactometry analyses showed odour concentrations in the order of millions of ouE/m3. While the main constituent of these natural gas emissions was CO2, the very high odour concentration data primarily resulted from the high portion of H2S in these emissions, with detected concentrations ranging from 1,000 to 10,000 ppmv. This not only indicates the presence of odour impact potential but also the high risk for people in the nearby area due to the high concentration of this gas. In parallel with the measurement of representative concentration data of these spot vents, a flexible and innovative approach was established for the measurement of emitted gas flow. The main breakthrough was obtained via the revamping of a balometer, a tool used for the measurement of indoor airflows, in the measurement of the gas flow of large spot vents (i.e. mine gates). Thanks to this stretchy approach, it was possible to estimate the OER of these emissions: the overall OER of all the inventory of the investigated spot vents in the area was impressive, and reached almost 10 million of ouE/s.

Background & Aims: Biochemical response to ursodeoxycholic acid (UDCA) therapy is associated with good prognosis in people living with primary biliary cholangitis (PBC). Biochemical response is typically assessed early in disease and it is not known what proportion of patients lose previously attained biochemical response, nor whether this impacts long-term liver transplant (LT)-free survival. Methods: We identified all UDCA-treated patients with PBC from the Canadian Network for Autoimmune Liver disease with biochemical measurements at 1 year, and evaluated their liver biochemistry over time. Inadequate biochemical response was defined as serum alkaline phosphatase ≥1.67x the upper limit of normal or abnormal serum total bilirubin at 1 year of UDCA therapy and all time points thereafter. Multistate Markov models were used to estimate transition rates between biochemical response states and from each state to LT or death. Results were validated in an external cohort (GLOBAL PBC registry). Results: A total of 823 patients from eight centers were included. Mean age at diagnosis was 53 years, 91% were female, 33% had inadequate biochemical response to UDCA at 1 year (n = 269). Patients who retained initial adequate response had lower rates of LT or death compared to patients who subsequently lost response (relative rate 0.102, 95% CI 0.047-0.223). Patients who regained adequate response had lower rates than patients who did not (0.016, 95% CI 0.001-0.568), and patients who lost response once more (0.010, 95% CI 0.001-0.340). Patients who regained adequate response for a third time also had lower rates than patients who did not (0.151, 95% CI 0.040-0.566). Analyses in the GLOBAL PBC registry (n = 2,237) validated these results. Conclusion: Loss of biochemical response at any time is associated with heightened risks of LT or death in people living with PBC. Achievement of biochemical response is an important goal throughout follow-up, regardless of biochemical response profile early in therapy. Impact and implications:: Early biochemical response to ursodeoxycholic acid is associated with good prognosis in patients with primary biliary cholangitis (PBC). Our work demonstrates that patients with PBC transition between biochemical response states over time, and that these transitions correspond with changes in risk of liver transplantation or death. Clinicians should re-evaluate risk and optimize treatment decisions for patients with PBC throughout follow-up, regardless of early biochemical response to therapy.

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (

Introduction: The molecular profile of colorectal cancer (CRC) plays a crucial role in understanding patient prognosis and treatment response. Within CRC, a distinct subgroup can be identified by the presence of the BRAF V600E mutation. This specific mutation, classified as Class I of BRAF mutations, is known to be associated with a poor prognosis and resistance to standard therapy. To determine the most effective treatment approach for this specific subgroup of CRC, we conducted a network meta-analysis (NMA) to compare various pharmacological interventions and evaluate their relative effectiveness in BRAF-mutated CRCs. Materials and methods: On July 31, 2023, we conducted a systematic search of PubMed, Cochrane Central Register of Controlled Trials, and Embase. The inclusion criteria were as follows: 1) reporting of outcomes in patients with BRAF-mutated CRC who underwent first-line chemotherapy; 2) reporting of survival information as hazard ratios (HR); and 3) publication in English. The data were combined using HRs for overall and progression-free survival (OS and PFS) using random-effects models. NMA was performed under the Bayesian framework, utilizing the GeMTC package. The relative rankings of the treatments were determined using SUCRA scores. Results: A total of 16 studies were included. When compared to standard chemotherapy (CT) doublets (such as FOLFOX or FOLFIRI), none of the comparison arms demonstrated a gain in OS. CT doublet + bevacizumab did not show significant superiority over either CT doublet alone or 5FU/capecitabine + bevacizumab. FOLFOXIRI and FOLFOXIRI + bevacizumab did not show superiority over any other treatment schedule that was compared. CT doublets + bevacizumab had the highest SUCRA score (0.87), followed by single-agent fluoropyrimidines + bevacizumab (0.61), and FOLFOXIRI (0.56). Regarding PFS, no regimen was found to be superior to the combination of CT doublet plus bevacizumab. However, FOLFOXIRI + bevacizumab + atezolizumab showed a tendency towards better results (HR = 0.26, 95 % CI 0.05–1.1). Conclusions: Our review suggests that a CT doublet with bevacizumab is the most favorable option for OS. However, a reasonable alternative could be a triplet CT without bevacizumab.

Abstract To compare baseline characteristics, initial response and 12-month efficacy and safety outcomes in eyes with branch and central retinal vein occlusion (BRVO and CRVO) treated with dexamethasone implants (DEX) or anti-vascular endothelial growth factor (anti-VEGF) we performed a multi-centre, retrospective and observational study using Fight Retinal Blindness! Registry. Of 725 eligible eyes, 10% received DEX initially with very frequent adjunctive anti-VEGF (BRVO-DEX 49%, CRVO-DEX 60%). The primary outcome of mean adjusted change in VA at 12 months with DEX and anti-VEGF initiated groups were not statistically significantly different (BRVO: DEX + 6.7, anti-VEGF + 10.6 letters; CRVO: DEX + 2.8, anti-VEGF + 6.8 letters). DEX initiated eyes had fewer injections and visits than anti-VEGF initiated eyes. The BRVO-DEX eyes had greater initial mean changes in VA and central subfield thickness (CST) and achieved inactivity sooner than BRVO-anti-VEGF eyes. The mean CST after the first three months was above 350 μm in all but the BRVO-anti-VEGF group, suggesting undertreatment. In routine care DEX is uncommonly used when available as initial treatment of BRVO and CRVO requiring supplemental anti-VEGF within the first year. The 12-month outcomes were similar, but DEX initiated eyes had fewer injections and visits but more episodes of raised IOP Vs those starting anti-VEGF.