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The relationship with bike infrastructure is missing in the current examination of user perception, which places a great deal of emphasis on visual aesthetic quality or surveys. Italy is experiencing the great development of cycling infrastructures, and the related plans, in line with sustainability objectives, have the task of examining users in various aspects. The purpose of this study is to examine users’ criteria based on perceptions of the landscape in the presence of cycling infrastructures and to analyze the current infrastructures and understand their alignment with sustainable plans. One of the multiple-criteria decision analysis (MCDA) methods based on fuzzy comprehensive evaluation (FCE) was utilized, and it entails identifying the factors that constitute an index and assessing the priority of these factors in relation to other components. The findings demonstrate that the primary variables are distinct aspects of the landscape that are objective. We discovered that these components perform better for urban than metropolitan sectors in this study, as we divided the scenarios into metropolitan and general (urban, suburban, and coastal urban) scenarios.

The analysis of gross primary production (GPP) is crucial to better understand CO2 exchanges between terrestrial ecosystems and the atmosphere, while the quantification of water-use efficiency (WUE) allows for the estimation of the compensation between carbon gained and water lost by the ecosystem. Understanding these dynamics is essential to better comprehend the responses of environments to ongoing climatic changes. The objective of the present study was to analyze, through AMERIFLUX and LBA network measurements, the variability of GPP and WUE in four distinct tropical biomes in Brazil: Pantanal, Amazonia, Caatinga and Cerrado (savanna). Furthermore, data measured by eddy covariance systems were used to assess remotely sensed GPP products (MOD17). We found a distinct seasonality of meteorological variables and energy fluxes with different latent heat controls regarding available energy in each site. Remotely sensed GPP was satisfactorily related with observed data, despite weak correlations in interannual estimates and consistent overestimations and underestimations during certain months. WUE was strongly dependent on water availability, with values of 0.95 gC kg−1 H2O (5.79 gC kg−1 H2O) in the wetter (drier) sites. These values reveal new thresholds that had not been previously reported in the literature. Our findings have crucial implications for ecosystem management and the design of climate policies regarding the conservation of tropical biomes, since WUE is expected to change in the ongoing climate change scenario that indicates an increase in frequency and severity of dry periods.

This study investigates the rain-initiated mixing and variability in the concentration of selected trace gases in the atmosphere over the central Amazon rain forest. It builds on comprehensive data from the Amazon Tall Tower Observatory (ATTO), spanning from 2013 to 2020 and comprising the greenhouse gases (GHG) carbon dioxide (CO2) and methane (CH4), the reactive trace gases carbon monoxide (CO), ozone (O3), nitric oxide (NO), and nitrogen dioxide NO2 (NO2) as well as selected volatile organic compounds (VOC). Based on more than 1000 analyzed rainfall incidents, the study resolves the trace gas concentration patterns before, during, and after the rain events, along with its vertical concentration gradients across the forest canopy. The assessment of the rainfall events was conducted independently for daytime and nighttime periods, which allows us to elucidate the influence of solar radiation. The concentrations of CO2, CO, and CH4 clearly declined during rainfall, which can be attributed to the downdraft-related entrainment of pristine air from higher altitudes into the boundary layer, a reduction of the photosynthetic activity under increased cloud cover, as well as changes in the surface fluxes. Notably, CO showed a faster reduction than CO2, and the vertical gradient of CO2 and CO is steeper than for CH4. Conversely, the O3 concentration increased across all measurement heights in the course of the rain-related downdrafts. Following the O3 enhancement by up to a factor of two, NO and VOC concentrations decreased, whereas NO2 increased. The temporal and vertical variability of the trace gases is intricately linked to the diverse sink and source processes, surface fluxes, and free troposphere transport. Within the canopy, several interactions unfold among soil, atmosphere, and plants, shaping the overall dynamics. Also, the concentration of biogenic VOC (BVOC) clearly varied with rainfall, driven by factors such as light, temperature, physical transport, and soil processes. Our results disentangle the patterns in trace gas concentration in the course of the sudden and vigorous atmospheric mixing during rainfall events. By selectively uncovering processes that are not clearly detectable under undisturbed conditions, our results contribute to a better understanding of the trace gas life cycle and its interplay with meteorology, cloud dynamics, and rainfall in the Amazon and beyond. [ABSTRACT FROM AUTHOR]

Given the increasing occurrence of landslides on the East Coast Northeast of Brazil (ECNEB), it is essential to understand its conditions and triggering factors because meteorological anomalies triggered by a landslide will threaten life and property in the region. In this sense, this research aimed to diagnose the meteorological conditions that triggered landslides in the ECNEB in May 2017, evaluate the terrain’s intrinsic conditions using elevation, slope, and susceptibility parameters and determine critical precipitation thresholds for the city with the highest number of landslide risk areas in the region. A dynamic downscaling experiment was carried out using the Regional Climate Model (RegCM) to verify the ability of this model to represent rainfall over the ECNEB. The results from the intrinsic factors showed that the ECNEB is highly susceptible to landslides with various high-risk sectors for landslides to the population. The extreme rainfall event was associated with the convergence of humidity at low levels over the ocean, which contributed to landslides in the ECNEB, mainly in the State of Pernambuco, where 67 landslides were registered. The RegCM numerical simulation underestimated the high daily rainfall signal seen on the Tropical Rainfall Measuring Mission satellite. It is suggested that sensitivity tests can be performed using other physical parameters to find the best model configuration for the ECNEB. This work recommends that exploring the relationship between precipitation and landslides will provide objective criteria for assessing risk areas by contributing to the predictability of disasters in this region.

Although seasonally dry tropical forests are considered invaluable to a greater understanding of global carbon fluxes, they remain as one of the ecosystems with the fewest observations. In this context, ecological and ecosystem models can be used as alternative methods to answer questions related to the interactions between the biosphere and the atmosphere in dry forests. The objective of this study was to calibrate the simple tropical ecosystem model (SITE) and evaluate its performance in characterizing the annual and seasonal behavior of the energy and carbon fluxes in a preserved fragment of the Caatinga biome. The SITE model exhibited reasonable applicability to simulate variations in CO2 and energy fluxes (r > 0.7). Results showed that the calibrated set of vegetation parameters adequately simulated gross primary productivity (GPP) and net ecosystem CO2 exchange (NEE). The SITE model was also able to accurately retrieve the time at which daily GPP and NEE peaked. The model was able to simulate the partition of the available energy into sensible and latent heat fluxes and soil heat flux when the calibrated parameters were used. Therefore, changes in the dynamics of dry forests should be taken into consideration in the modeling of ecosystem carbon balances.

Research focusing on energy, water vapor, and CO2 exchanges over the Caatinga Biome is recent. Consequently, there exist research gaps on this topic that limit our ability to understand and project interannual and long-term variations in the CO2 cycle of this environment. Thus, the objective of this study was to evaluate the behavior of the energy and CO2 balances of the Caatinga Biome under extreme rainfall conditions (extreme drought and intense rainfall) using simulations of the SITE model (Simple Tropical Ecosystem Model). Meteorological data from the years 2009 (heavy rainfall) and 2012 (extreme drought) obtained from an INMET automatic station were used. Relationships between monthly GPP and NEE values and rainfall were also analyzed. Although the SITE model had been previously calibrated for the region, adjustments to the calibration were necessary for our study due to the extreme climatic values of the selected years. The results highlight the impact of rainfall on energy and mass exchanges over the Caatinga, particularly evident in the partitioning of the energy balance and the CO2 balance. In 2009 (during heavy rainfall), the fraction of Rn converted into LE was nearly 6% higher compared to the values observed in 2012 (during extreme drought). Regarding CO2, it was found that the Caatinga behaved as a sink, even under extreme drought conditions (2012), with annual average values of −1.86 µmol m−2 s−1 (2009) and −0.81 µmol m−2 s−1 (2012). Relationships between monthly GPP and NEE values and rainfall were also investigated, revealing an asymptotic relationship between the components of CO2 balance and rainfall. It was evident that both the monthly values of GPP and NEE tend to stabilize when monthly rainfall volumes exceed 200 mm. [ABSTRACT FROM AUTHOR]

The relationship with bike infrastructure is missing in the current examination of user perception, which places a great deal of emphasis on visual aesthetic quality or surveys. Italy is experiencing the great development of cycling infrastructures, and the related plans, in line with sustainability objectives, have the task of examining users in various aspects. The purpose of this study is to examine users' criteria based on perceptions of the landscape in the presence of cycling infrastructures and to analyze the current infrastructures and understand their alignment with sustainable plans. One of the multiple-criteria decision analysis (MCDA) methods based on fuzzy comprehensive evaluation (FCE) was utilized, and it entails identifying the factors that constitute an index and assessing the priority of these factors in relation to other components. The findings demonstrate that the primary variables are distinct aspects of the landscape that are objective. We discovered that these components perform better for urban than metropolitan sectors in this study, as we divided the scenarios into metropolitan and general (urban, suburban, and coastal urban) scenarios. [ABSTRACT FROM AUTHOR]

The analysis of gross primary production (GPP) is crucial to better understand CO2 exchanges between terrestrial ecosystems and the atmosphere, while the quantification of water-use efficiency (WUE) allows for the estimation of the compensation between carbon gained and water lost by the ecosystem. Understanding these dynamics is essential to better comprehend the responses of environments to ongoing climatic changes. The objective of the present study was to analyze, through AMERIFLUX and LBA network measurements, the variability of GPP and WUE in four distinct tropical biomes in Brazil: Pantanal, Amazonia, Caatinga and Cerrado (savanna). Furthermore, data measured by eddy covariance systems were used to assess remotely sensed GPP products (MOD17). We found a distinct seasonality of meteorological variables and energy fluxes with different latent heat controls regarding available energy in each site. Remotely sensed GPP was satisfactorily related with observed data, despite weak correlations in interannual estimates and consistent overestimations and underestimations during certain months. WUE was strongly dependent on water availability, with values of 0.95 gC kg−1 H2O (5.79 gC kg−1 H2O) in the wetter (drier) sites. These values reveal new thresholds that had not been previously reported in the literature. Our findings have crucial implications for ecosystem management and the design of climate policies regarding the conservation of tropical biomes, since WUE is expected to change in the ongoing climate change scenario that indicates an increase in frequency and severity of dry periods. [ABSTRACT FROM AUTHOR]

Com o objetivo de avaliar a ocorrência da infecção por Toxoplasma gondii, em ovinos das regiões periurbana e urbana do município de Curitiba, Paraná, Região Sul do Brasil, foram coletadas amostras de sangue de 167 ovinos, de três rebanhos. O teste de ELISA foi utilizado para detectar anticorpos anti-Toxoplasma gondii. Dos 167 soros ovinos, 43 (25,75%) apresentaram anticorpos anti-T. gondii. O parasito está difundido entre os ovinos das duas regiões estudadas.This study evaluated occurrence of the Toxoplasma gondii infection in ovine from urban and periurban areas of Curitiba, State of Paraná, Southern of Brazil. Blood samples from 167 sheep from three farms were collected. ELISA assay was used to detect IgG anti-Toxoplasma gondii antibodies. Of 167 ovine samples, 43 (25.75%) were positive. The parasite is widespread among sheep from urban and periurban areas of Curitiba.

Studying the dynamics of gross primary production (GPP) in seasonally dry tropical forests is of fundamental importance to understand the carbon dioxide (CO2) balance in this ecosystem, helping mitigate its potential impacts at the regional and global levels. Thus, the objective of this work was to evaluate the accuracy of GPP estimated via remote sensing in the Caatinga biome. A set of observed data retrieved from micrometeorological towers equipped with eddy covariance systems were used to validate remote sensing data. The set was measured in a preserved Caatinga fragment. Remotely sensed GPP data was retrieved from the MOD17A2 version 6.0 product of the Moderate Resolution Imaging Spectroradiometer (MODIS) sensor onboard the Terra satellite. The validation of MOD17A2 GPP estimates was carried out through the comparison with micrometeorological data measured in situ. In the Caatinga site the comparison between the two GPP data types showed a moderate correlation with Pearson's correlation coefficient (r) = 0.65 and coefficient of determination (R2) = 0.43 and the product performed better in representing GPP in the Caatinga during the dry season. Results showed that although the MOD17A2 product represents the annual behaviour of GPP, the algorithm could be improved in order to provide GPP information that is more similar to surface measured data over these land covers. [ABSTRACT FROM AUTHOR]

This research aims to provide a brief evaluation of remotely sensed estimates in representing gross primary production (GPP) over pasture in the Northeast Region of Brazil. We used GPP data measured in situ during a micrometeorological experiment performed in a pasture area located in the NEB region using the eddy covariance technique. Remotely sensed GPP was obtained through the MOD17A2H product of the Moderate Resolution Imaging Spectroradiometer (MODIS) sensor on board the Terra satellite. We concluded that the MOD17A2H product moderately represents surface-measured GPP in the studied site, highlighting the need for improvements in the quality of the remotely sensed GPP estimates over this type of ecosystem. [ABSTRACT FROM AUTHOR]

The acute and sublethal chronic effects of sodium dodecyl sulphate (SDS) on the survival, metabolism, and growth of juveniles of Centropomus parallelus were investigated at three different salinities. Results of 96h LC50 test showed that juveniles of C. parallelus were very sensitive to SDS in comparison to other species investigated. For each group of exposure to nominal concentrations of SDS (0.10 and 0.25mg/L) and the control group (0.0mg/L), at the different salinities (5, 20, and 30) there were significant differences in the specific growth rate, oxygen consumption, and ammonia excretion rates, O:N atomic ratio at the different exposure periods (15 and 30 days). There were also interactions between factors for the parameters investigated. The present results show a pronounced effect of SDS, mainly at the highest concentration and salinity, as well as after a long time of exposure. [Copyright &y& Elsevier]

Given the increasing occurrence of landslides on the East Coast Northeast of Brazil (ECNEB), it is essential to understand its conditions and triggering factors because meteorological anomalies triggered by a landslide will threaten life and property in the region. In this sense, this research aimed to diagnose the meteorological conditions that triggered landslides in the ECNEB in May 2017, evaluate the terrain's intrinsic conditions using elevation, slope, and susceptibility parameters and determine critical precipitation thresholds for the city with the highest number of landslide risk areas in the region. A dynamic downscaling experiment was carried out using the Regional Climate Model (RegCM) to verify the ability of this model to represent rainfall over the ECNEB. The results from the intrinsic factors showed that the ECNEB is highly susceptible to landslides with various high-risk sectors for landslides to the population. The extreme rainfall event was associated with the convergence of humidity at low levels over the ocean, which contributed to landslides in the ECNEB, mainly in the State of Pernambuco, where 67 landslides were registered. The RegCM numerical simulation underestimated the high daily rainfall signal seen on the Tropical Rainfall Measuring Mission satellite. It is suggested that sensitivity tests can be performed using other physical parameters to find the best model configuration for the ECNEB. This work recommends that exploring the relationship between precipitation and landslides will provide objective criteria for assessing risk areas by contributing to the predictability of disasters in this region. [ABSTRACT FROM AUTHOR]

Although seasonally dry tropical forests are considered invaluable to a greater understanding of global carbon fluxes, they remain as one of the ecosystems with the fewest observations. In this context, ecological and ecosystem models can be used as alternative methods to answer questions related to the interactions between the biosphere and the atmosphere in dry forests. The objective of this study was to calibrate the simple tropical ecosystem model (SITE) and evaluate its performance in characterizing the annual and seasonal behavior of the energy and carbon fluxes in a preserved fragment of the Caatinga biome. The SITE model exhibited reasonable applicability to simulate variations in CO2 and energy fluxes (r > 0.7). Results showed that the calibrated set of vegetation parameters adequately simulated gross primary productivity (GPP) and net ecosystem CO2 exchange (NEE). The SITE model was also able to accurately retrieve the time at which daily GPP and NEE peaked. The model was able to simulate the partition of the available energy into sensible and latent heat fluxes and soil heat flux when the calibrated parameters were used. Therefore, changes in the dynamics of dry forests should be taken into consideration in the modeling of ecosystem carbon balances. [ABSTRACT FROM AUTHOR]

Discrimination between axonotmesis and neurotmesis is crucial in traumatic nerve injury. We present the case of a 43-year-old woman which presented hypoesthesia in the fourth and fifth right fingers, started after surgery for Dupuytren syndrome. At ultrasound study, the ulnar digital sensory branch was identified. Before the division into the two terminal branches, a neuroma was observed, while neurotmesis was excluded. This case shows the utility of ultrasonography in peripheral nervous system examination and the possibility of visualization of very small nerves and their terminal branches. [ABSTRACT FROM AUTHOR]

7-methyl-2-phenylimidazo[1,2-b]pyridazin-3-carboxylic acid (DM1) and 6-methoxy-2-phenylimidazo[1,2-b]pyridazin-3-carboxylic acid (DM2) have been shown to act as human (h) Cav3.1 voltage-gated calcium channel blockers with promising in vivo anti-absence activity, positioning them as potential antiepileptic drugs. The primary aim of this work was to develop cost-effective and environmentally friendly synthetic procedures for preparing 2-phenylimidazo[1,2-b]pyridazine derivatives. After optimizing the synthesis of this compound class using efficient and green techniques such as microwaves and ultrasound irradiation, we further evaluated the antiepileptic effects of DM1 and DM2 in two animal models: CD-1 ICR mice after pentylenetetrazol administration and DBA/2 mice with seizures induced by audiogenic stimuli. Their neuroprotective effect against oxidative stress were assessed using C6 rat brain glioma cells. DM1 and DM2 exhibited potent anti-seizure effects in both animal models and demonstrated significant in vitro neuroprotective activity by reducing reactive oxygen species release. To lay the groundwork for the future rational optimization of this promising class of compounds, the molecular bases of DM1 and DM2 activity were investigated by modelling their interaction with hCav3.1 channels. The calculated binding modes of DM1 and DM2 to hCav3.1 channels partially mirrored that of the selective Cav3.1 blocker Z944, paving the way for future lead optimization., (© 2024 Wiley‐VCH GmbH.)

Background and Objectives: The incidence of ischemic stroke in young adults has increased substantially. There are limited data in the literature concerning the short-term clinical outcome in young adults with acute stroke after revascularization treatment. Due to the lack of available data on gender differences short-term clinical outcome, we designed the present study., Materials and Methods: We collected data from 127 patients aged 50 years or younger consecutively admitted to the Stroke-Unit of "Cardarelli" Hospital in Naples between August 2017 and September 2022 due to ischemic stroke. All of them underwent thrombolysis and/or endovascular treatment., Results and Conclusions: Smoking, hypertension, and dyslipidemia emerged as the most prevalent risk factors. A gender-based analysis revealed that the history of stroke was the only statistically significant factor more frequently observed in the female group. The leading stroke etiology was "cardioembolism," succeeded by strokes of "other determined origin", "undetermined etiology," "large-artery atherosclerosis," and "small-artery occlusion." Concerning reperfusion therapy, intravenous thrombolysis ranked as the most utilized treatment, followed by "bridging" therapy (combining intravenous thrombolytic therapy with thrombectomy) and primary mechanical thrombectomy. Notably, the average NIHSS scores 7 days post-revascularization were lower among females compared to males, constituting a statistically significant distinction. Nevertheless, no statistically significant correlation surfaced between gender and treatment type in NIHSS mean values at admission, 2 hours, 24 hours post-revascularization, or 7 days post-revascularization. This suggests that the observed disparity in mean NIHSS score between male and female groups after 7 days may potentially stem from other factors, such as endogenous estrogens., Competing Interests: Declarations Ethical approval None. Conflict of interest None. Informed consent None., (© 2024. Fondazione Società Italiana di Neurologia.)

A small series of arylsulfonamide derivatives was designed and synthesized to study linear and cyclic inhibitors targeting human Carbonic Anhydrases (hCAs EC 4.2.1.1) as essential enzymes regulating (patho)-physiological processes. Particularly, the synthesis of these ten compounds was inspired to the well-known arylsulfonamides having flexible or constrained linkers able to maintain the two crucial moieties, anchoring zinc group and hydrophobic tail, in the optimized orientation within CA cavities of tumor-expressed isoforms hCA IX and hCA XII. The synthesized imine derivatives and related cyclic 1,3-thiazin-4-ones were screened in a stopped-flow carbon dioxide hydrase assay and proved to be effective inhibitors against hCA IX and hCA XII isoforms with K i values ranging of 3.7-215.7 nM and 5.7-415.0 nM, respectively. Molecular docking studies of both series of arylsulfonamides were conducted to propose their binding mode within hCA IX and hCA XII active sites thus highlighting their distinct ability to occupy the two catalytic cavities. Moreover, the 4-[(3-cyanophenyl)methylidene]aminobenzene-1-sulfonamide 7 proved to reduce the cell viability of breast carcinoma (MCF-7) and colon rectal carcinoma (HCT-116) human cell lines under the fixed doses of 10 μM. These results encouraged us to continue our efforts in developing potent and efficient arylsulfonamides targeting hCA IX and hCA XII isoforms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Today, plastic pollution is a widespread problem in all ecosystems and has a particularly severe impact on marine ecosystems and external fertilisers such as the mussel Mytilus galloprovincialis. The present study aims to assess the toxicological reproductive health effects in this organism following exposure to two concentrations of polystyrene microplastics (PS-MPs) (0.5 and 1 μg/L), representative of conditions in the Mediterranean Sea. After exposure, the electrophoretic pattern of protamine-like (PL) proteins, the major basic protein component of Mytilus galloprovincialis sperm chromatin, was analysed. Compared to the unexposed condition, differences were observed by SDS-PAGE and an increased ability of PL to bind and protect DNA from oxidative damage was then measured, particularly for PL from mussels exposed to 1 μg/L PS-MPs. At this dose of PS-MPs, a reduced release of all PLs from the sperm nuclei was also observed, whereas the digestion by micrococcal nuclease did not show any significant differences between the exposed and the unexposed conditions. Finally, the possibility of poly(ADP)-ribosylation of the PLs was investigated. PL-II showed an increase in poly(ADP)-ribosylation after PS-MPs exposure, which may account for the difference in the ability of the PLs to bind DNA. In conclusion, while all the results might suggest a molecular mechanism of gametic plasticity occurring upon exposure of mussels to PS-MPs 1 μg/L, they also indicate that this dose of exposure could be extremely detrimental to the reproductive health of Mytilus galloprovincialis because it could prevent the release of basic nuclear proteins from the sperm DNA at fertilisation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The phenomenon of suicide risk (SR) represents a psychiatric, social and environmental emergency. The acute psychiatric ward as the Italian Service for Psychiatric Diagnosis and Care (SPDC) represents the place where SR is high due to the acute and serious conditions of people hospitalized. The objective of this study was to evaluate the characteristics of subjects admitted to a SPDC over a 6-year period for SR represented by: suicidal ideation, attempted and failed suicide., Methods: With a retrospective single-center observational design, we collected hospitalizations from 01/01/2017 to 31/12/2022 in the SPDC of AUSL-Modena for SR, analyzed the modality of SR and compared the demographic and clinical variables of subjects with SR with those hospitalized for other clinical reasons in the same period. Data were statistically analyzed., Results: In the 6-year of study period, we collected 2,930 hospitalizations in the SPDC of AUSL- Modena and among them, 68% (n = 528) were carried out due to SR, which represented the second leading cause of hospitalization (18%), in particular among females (Pearson Chi2 = 17.41, p < 0.001). Individuals with SR were more frequently voluntary admitted (Pearson Chi2 = 215.41, p < 0.001) for a shorter period (7.36 ± 8.16 vs 11.66 ± 15.93, t = 6.03, t-test, p < 0.001) and less frequently repeated the hospitalization during the study period for the same reason (Pearson Chi2 = 6.0, p = 0.014). The most frequent psychiatric disorders associated with SR were depressive, personality and adjustment disorders, which represented the most common factor associated with SR (68%), followed by family/relationship problems (12%) and alcohol/substance abuse (8%). We highlighted three kinds of suicidal risk: suicidal ideation (40%), often associated with personality disorders and substance use disorders, drug ingestion (30%) concomitant with conflicting family relationships and use of violent means (30%) associated with depressive disorders (Pearson Chi2 = 42.83, p = 0.002)., Conclusions: Our study provides a real-world setting evaluation of subjects hospitalized for SR and, in accordance with literature, suggests that suicidal behavior is the product of many clinical and social factors' interaction, that occurred in a crucial moment of life in vulnerable individuals. The identification of subjects at SR represents the first step of preventive multi-professional interventions., Competing Interests: Declarations Ethics approval and consent to participate The study was approved by the Ethics Committee of the North Emilia Area Vasta (Prot. 306/2022/AOU) with subsequent amendment for extension of the period examined (Prot. 10826/2023) and authorized by the AUSL- Modena (Prot. no. 688; 27/4/2023). Consent for publication is not applicable. If the informed consent is waived, we would require full name of committee that waived the informed consent. As the study was conducted retrospectively, it was not possible to obtain written informed consent from the enrolled subjects, in accordance with the European GDPR 679/2016 and General Authorization n. 9/2016, extended by Provision n. 424/2018. Data access was granted to the study manager and collaborators, who were bound by confidentiality and data processing obligations under applicable regulations. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Cannabidiolic (CBDA) and cannabigerolic (CBGA) acids are naturally occurring compounds from Cannabis sativa plant, previously identified by us as dual PPARα/γ agonists. Since the development of multitarget-directed ligands (MTDL) represents a valuable strategy to alleviate and slow down the progression of multifactorial diseases, we evaluated the potential ability of CBDA and CBGA to also inhibit enzymes involved in the modulation of the cholinergic tone and/or β-amyloid production. A multidisciplinary approach based on computational and biochemical studies was pursued on selected enzymes, followed by behavioral and electrophysiological experiments in an AD mouse model. The β-arrestin assay on GPR109A and qPCR on TRPM7 were also carried out. CBDA and CBGA are effective on both acetyl- and butyryl-cholinesterases (AChE/BuChE), as well as on β-secretase-1 (BACE-1) enzymes in a low micromolar range, and they also prevent aggregation of β-amyloid fibrils. Computational studies provided a rationale for the competitive (AChE) vs. noncompetitive (BuChE) inhibitory profile of the two ligands. The repeated treatment with CBDA and CBGA (10 mg/kg, i.p.) improved the cognitive deficit induced by the β-amyloid peptide. A recovery of the long-term potentiation in the hippocampus was observed, where the treatment with CBGA and CBDA also restored the physiological expression level of TRPM7, a receptor channel involved in neurodegenerative diseases. We also showed that these compounds do not stimulate GPR109A in β-arrestin assay. Collectively, these data broaden the pharmacological profile of CBDA and CBGA and suggest their potential use as novel anti-AD MTDLs., (© 2024 The Author(s). Phytotherapy Research published by John Wiley & Sons Ltd.)

Chronic lipid overnutrition has been demonstrated to promote cardiac dysfunction resulting from metabolic derangement, inflammation, and fibrosis. Oleoylethanolamide (OEA), an endogenous peroxisome proliferator activating receptor (PPAR)-α agonist, has been extensively studied for its metabolic properties. The aim of this study was to determine if OEA has beneficial effects on high-fat diet (HFD)-induced cardiac disruption in obese mice, focusing on the underlying pathological mechanisms. OEA treatment restores the metabolic pattern, improving serum glycaemic and lipid profile. OEA also reduces heart weight and serum creatine kinase-myocardial band (CK-MB), a marker of cardiac damage. Accordingly, OEA modulates cardiac metabolism, increasing insulin signaling and reducing lipid accumulation. OEA increases AMPK and AKT phosphorylation, converging in the rise of AS160 activation and glucose transporter (GLUT)4 protein level. Moreover, OEA reduces the transcription of the cardiac fatty acid transporter CD36 and fatty acid synthase and increases PPAR-α mRNA levels. Adiponectin and meteorite-like protein transcription levels were significantly reduced by OEA in HFD mice, as well as those of inflammatory cytokines and pro-fibrotic markers. An increased autophagic process was also shown, contributing to OEA's cardioprotective effects. Metabolomic analyses of cardiac tissue revealed the modulation of different lipids, including triglycerides, glycerophospholipids and sphingomyelins by OEA treatment. In vitro experiments on HL-1 cardiomyocytes showed OEA's capability in reducing inflammation and fibrosis following palmitate challenge, demonstrating a direct activity of OEA on cardiac cells, mainly mediated by PPAR-α activation. Our results indicate OEA as a potential therapeutic to restrain cardiac damage associated with metabolic disorders., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Aims/hypothesis: The diagnosis of type 2 diabetes is increasing in young people worldwide. This study evaluated the frequency and clinical characteristics of young people presenting with type 2 diabetes from the multinational SWEET e.V Registry 2012-2021, including the first years of the COVID-19 pandemic., Methods: This is a longitudinal observational study based on the SWEET Registry, which collects demographic and clinical data on children and adolescents with diabetes from centres worldwide, with the diagnosis and classification of diabetes provided locally by each centre according to International Society for Paediatric and Adolescent Diabetes definitions. By July 2022, the SWEET Registry included 96,931 individuals from 130 centres with a total of 1,154,555 visits. Data were analysed by region: Europe (EU), Australia and New Zealand (AU/NZ), South America (SA), North America (NA) and Asia/Middle East and Africa (AS/AF). Trends in proportions for the two-year periods, calculated as cases with type 2 diabetes diagnoses over all cases with diabetes diagnoses, were estimated using logistic regression models adjusted for age at onset and sex., Results: Overall, there were 2819 of 58,170 new cases (4.8%) with type 2 diabetes: 614 in EU, 293 in AU/NZ, 79 in SA, 1211 in NA and 622 in AS/AF. The proportion of type 2 diabetes increased from 3.2% to 6.0% from 2012/2013 to 2020/2021, a relative rate of increase of 9% per two-year period (95% CI 5.9, 12.3; p<0.001). In the two-year period of the COVID-19 pandemic, type 2 diabetes continued to follow the observed trend, with a proportion of 6.0% in 2020-2021 compared with 5.4% in 2018-2019. High variability in the proportion of type 2 diabetes was observed across regions, with the lowest values observed in EU and the highest in NA. A significant increase in the proportion of type 2 diabetes was observed in EU, AU/NZ and NA. The median HbA 1c was not uniform and was highest in AS/AF (85 mmol/mol [9.9%]; IQR 55-111 [7.2-12.3%]) and lowest in EU (63 mmol/mol [7.9%]; IQR 48-99 [6.5-11.2%]), and the difference between EU and NA (median value 73 mmol/mol [8.8%]; IQR 50-105 [6.7-11.8%]) was statistically significant (p=0.047). There was also a difference in BMI SD score by region: the lowest median BMI SD score was 2.2 (IQR 1.4-2.7) in AS/AF and the highest was 3.1 (IQR 2.5-3.6) in AU/NZ., Conclusions/interpretation: The multinational SWEET data from the years 2012 to 2021 inclusive support recent findings of a worldwide increase in type 2 diabetes in young people, albeit with regional differences. This increase highlights the need for ongoing preventive measures and available advanced treatment modalities worldwide., (© 2024. The Author(s).)

The efficacy of Hylotelephium telephium (L.) H. Ohba (better known with its botanical synonym Sedum telephium L.) fresh leaf juice in the treatment of Herpes labialis wounds has been reported in traditional medicine in particular in Central regions of Italy; however, scientific insights are missing and the mechanism of action is not well understood. Aim of this study was to investigate the biological properties of S. telephium that underlie its ability to heal herpetic lesions. S. telephium fresh leaf juice (STJ) was analysed to obtain phytochemical information and tested in vitro to evaluate its antiviral activity against HSV-1 in Vero cells, then, according to computational predictions, immunomodulatory properties of STJ in human lympho-monocytes (PBMC), as well as its effect on cell viability in human keratinocytes (HaCaT cells), were also evaluated. Our results, at least in part, may explain the improvement of herpetic lesions empirically observed in patients treated with STJ: such improvement was not related to direct anti-viral effect of the juice but to its experimentally confirmed activity as cell viability booster and immunomodulatory agent.

Used since decades to produce pectin, citrus processing waste poor in lignin and rich in hemicellulose obtained from lemon and orange juice industrial manufacturing is ideally suited also as microcrystalline cellulose and nanocellulose raw material. The study merges the outcomes of chemistry and bioeconomy research between 2007 and early 2024 with technology and economic insight, to reach five conclusions that will hopefully inform practice-oriented work of researchers and bioeconomy company's managers interested in the sustainable manufacturing of these important biomaterials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Direct oral anticoagulants (DOACs) are widely used for treatment and secondary prophylaxis of venous thromboembolism (VTE) and represent the gold standard for VTE secondary prophylaxis, with low-intensity DOACs administration becoming increasingly used worldwide in such scenario. Albeit widespread DOACs usage there are few literature data regarding their efficacy and safety in major thrombophilia carriers and almost no data is available for low intensity apixaban and rivaroxaban as secondary VTE prophylaxis in such patients. The aim of our study is to evaluate and confront the efficacy and safety of low-dose DOACs for VTE secondary prophylaxis, in major thrombophilia carriers vs patients at high risk of VTE recurrence for other reasons. We retrospectively evaluated patients who required long-term anticoagulant secondary prophylaxis to prevent recurrent VTE, treated with apixaban 2.5 mg BID or rivaroxaban 10 mg daily and that were screened for thrombophilia. The examined patients were 339. Baseline characteristics such as sex, age, obesity rate, smoking, number of previous VTEs and comorbidities (such as cardiovascular diseases, diabetes, mild CKD) were equally distributed in either group. The median low-dose DOACs administration time was 19.20 months (IQR 12.17-35.67). During low-dose DOACs treatment, 13 (3.8%) VTE recurrences were observed; 14 bleeding events were registered (4,1%), with no major bleeding (MB), 6 clinically relevant non major bleeding (CRNMB) (1.8%) and 8 minor bleeding (2.3%). No statistically significant difference in the rate of VTE recurrence and/or bleeding events emerged between major thrombophilia carriers and non-major thrombophilia carriers. In multivariate analysis increased risk of VTE recurrence was found for patients with cardiovascular comorbidities (HR 4.00 - p = 0.034) and for patients with more than one previous VTE episode (HR 5.14 - p = 0.034). Our data suggest that low-dose DOACs may be effective and safe in secondary VTE prophylaxis for carriers of major thrombophilia with no increase in VTE recurrence and/or bleeding risk., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To develop and validate a questionnaire to evaluate missed nursing care (MNC) in a home care setting., Design: A new instrument was developed and tested performing a preliminary analysis of a multicenter cross-sectional study in Italy. Reporting was performed according to COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) guidelines., Sample: Eight hundred out of a total of 2549 home care nurses enrolled in AIDOMUS-IT were considered for the validation of the Missed Nursing Care in Home Care (MNC&#95;HC)., Measurements: The MNC&#95;HC instrument was developed by a panel of experts and underwent content and face validation. Exploratory (EFA) and confirmatory factor analyses (CFA) were conducted., Results: EFA revealed a one-factor solution, explaining 56% of the total variance for MNC&#95;HC. CFA confirmed excellent structural validity, with a one-factor model showing an exceptional fit (χ 2 (27) = 141.39, p < .001, RMSEA = 0.04, SRMR = 0.04, CFI = 0.99, TLI = 0.99, factor loadings > 0.5). MNC&#95;HC also demonstrated high reliability (Cronbach's α = 0.92). The activity with the highest rate of missed care was the documentation of nursing care (77%), while activities related to nursing techniques (e.g., injections, dressings, etc.) were reported to be missed less (33.63%)., Conclusions: MNC&#95;HC is a quick-filling, valid, reliable, and psychometrically sound instrument for measuring MNC in home care useful for future research., (© 2024 The Author(s). Public Health Nursing published by Wiley Periodicals LLC.)

Most patients with Primary Mediastinal B-Cell Lymphoma (PMBCL) are cured by rituximab and doxorubicin-based immunochemotherapy, with or without radiotherapy. In cases with relapsed and refractory (RR) disease the prognosis was historically poor. Recently, immune checkpoint-based strategies have been shown to be highly effective in patients with RR-PMBCL. We report the case of a 23-year-old woman who, due to recurring episodes of symptomatic chemotherapy-induced sinus bradycardia, was unable to receive the planned six courses of immunochemotherapy, mediastinal radiotherapy, and autologous transplantation, leading to the early initiation of a chemo-free strategy. The patient maintains a continuous complete remission at a four-year follow-up after only two cycles of immunochemotherapy followed by nivolumab plus brentuximab vedotin (BV) and pembrolizumab consolidation. Beyond describing an underreported complication of anticancer treatments, the favorable clinical outcome suggests that in PMBCL, a minimal load of chemotherapy, integrated by early PD-1 blockade, with or without BV, may be sufficient to achieve long-term disease control and cure at least in some patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Tactile acuity is a somatosensory measure of the extent to which humans can discern tactile stimuli. It is influenced by how peripheral signals are processed centrally. In the oral cavity, Occlusal Tactile Acuity (OTA) is the ability to perceive minimal thicknesses between antagonist teeth. The aim of the current study was to assess the association between psychological traits and OTA of otherwise healthy individuals., Methods: Sixty-three volunteers (32 males; mean age ± SD: 24.6 ± 2.7 years) participated in this study. Somatosensory amplification, anxiety, depression, physical symptoms and pain catastrophizing were scored using questionnaires, and subgroups of severity were created per variable based on cut-offs. OTA was measured using 9 aluminium foils with thickness (ranging from 8 to 72 μm) and one sham test (without foil). Each thickness was tested 10 times in random order, the participants were instructed to report whether they felt the foil between their molars and the mean percentage of correct answers was computed. A linear mixed model was used with OTA as a dependent variable and psychological domain as an independent variable., Results: Significantly different OTA was observed among the anxiety subgroups (p = .003), supporting a decreased perception of thicknesses 24 and 32 μm (p = .018 and p < .001, respectively) in participants with moderate/severe anxiety compared to those with no/mild anxiety. Significantly different OTA was also observed among the pain catastrophizing subgroups (p = .008), showing decreased perception of thicknesses 32 and 40 μm (p < .001 and p = .007, respectively) in severe catastrophizing levels, compared to no/mild catastrophizing levels. No significant differences were observed for the other variables., Conclusions: Healthy adults with increased anxiety or pain catastrophizing levels show decreased interdental acuity as compared to participants with minor or no psychological impairment., (© 2024 The Author(s). Journal of Oral Rehabilitation published by John Wiley & Sons Ltd.)

Objective: The objective of this study was to describe reported adverse events (AEs) associated with elexacaftor/tezacaftor/ivacaftor (ETI) in a pediatric sample with cystic fibrosis (CF) aged 6-18 years, with at least one F508del variant, followed at multiple Italian CF centers., Study Design: This was a retrospective, multicenter, observational study. All children receiving ETI therapy from October 2019 to December 2023 were included. We assessed the prevalence and type of any reported potential drug-related AEs, regardless of discontinuation necessity. Persistent AEs were defined as those continuing at the end of the observation period., Results: Among 608 patients on ETI, 109 (17.9%) reported at least 1 AE. The majority (n = 85, 77.9%) were temporary, with a median duration of 11 days (range 1-441 days). Only 7 (1.1%) patients permanently discontinued treatment, suggesting good overall safety of ETI. The most common AEs leading to discontinuation were transaminase elevations (temporary 14.1%, persistent 25.9%) and urticaria (temporary 41.2%, persistent 7.4%). Creatinine phosphokinase elevation was uncommon. No significant differences in AEs were observed based on sex, age groups (6-11 vs 12-18 years), or genotype. Pre-existing CF-related liver disease was associated with an increased risk of transaminase elevations. We identified significant variability in the percentage of reported AEs (ANOVA P value .026)., Conclusions: This real-world study highlights significant variability in reported AEs. Our findings suggest that ETI is a safe and well-tolerated therapy in children and adolescents with CF. However, further long-term safety and effectiveness investigations are warranted., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The aim of this study was to adapt the National Aeronautics and Space Administration Task Load Index (NASA-TLX) to the home care setting and translate and validate it in Italian. An online questionnaire containing the Italian version of the NASA-TLX adapted to the home care setting was administered to home care nurses to measure workload. Content Validity Index, Exploratory, and Confirmatory Factor Analyses were used to measure the psychometric characteristics of the modified NASA-TLX. The modified Italian version of NASA-TLX&#95;HC-IT showed good psychometric characteristics in measuring the workload of home care nurses, with excellent fit indices. The reliability, calculated with Cronbach's alpha, was 0.73, indicating adequate reliability. A negative correlation between workload and job satisfaction among home care nurses, as well as a positive association between high workload and intention to leave the workplace, was verified. The modified Italian version of the NASA-TLX&#95;HC-IT was confirmed to be a valid and reliable instrument to measure workload in home care nursing. Furthermore, the correlation between workload and the intention to leave the workplace among home care nurses was an important result that community nursing managers should consider preventing the shortage of home care nurses., (© 2024 The Author(s). Public Health Nursing published by Wiley Periodicals LLC.)

Introduction: Stroke negatively impacts both patients and their families, who must face multiple changes after the onset of the disease. Family caregivers must face new problems with a possible sense of inadequacy, stress and burden. Our retrospective study aimed to assess the burden of caregivers during the rehabilitation process of patients with Stroke., Material and Method: This study included patients with a diagnosis of stroke and their caregiver, who attended the Day Hospital of the IRCCS Neurolesi Center "Bonino-Pulejo", Messina, Italy, between January 2018 and October 2019, using electronic recovery system data. The final sample consisted of 30 patients and their caregivers., Results: Significant improvements were observed in patients' cognitive and mood scores, reflecting the efficacy of rehabilitation therapies. Additionally, a correlation emerged between patients' reported anxiety levels and caregivers' reported depression levels, highlighting a dynamic interaction between the emotional states of the two groups., Conclusion: The study highlights the intricate interplay between caregiver characteristics, patient outcomes, and family dynamics in the context of caregiving. Targeted interventions aimed at improving family resilience and coping mechanisms are crucial to optimizing the well-being of both caregivers and patients., (© 2024. The Author(s).)

Background: Alternating hemiplegia of childhood (AHC) is a rare disorder with both neurologic and cardiac manifestations. The ATP1A3-D801N variant is associated with a pathologically short QT interval and risk of ventricular arrhythmia following bradycardia; however, the mechanism of this remains unknown. We investigated the relationship between heart rate (HR), QT, and QTc, hypothesizing that individuals with ATP1A3-D801N have abnormal, impaired shortening of QT and QTc at lower HR leading to arrhythmia predisposition., Methods: We performed a retrospective observational study of individuals who underwent clinical evaluation, Holter monitoring, and genetic testing for AHC at Duke University Hospitals. We also compiled a group of healthy individuals as a control cohort. A larger, worldwide cohort of individuals with ATP1A3 -related phenotypes was compiled to investigate sinus node dysfunction. Linear regression analysis was then performed., Results: The cohort consisted of 44 individuals with ATP1A3 -related phenotypes with 81 Holter recordings (52.27% female; mean age at first Holter 8.04 years, range 0.58 - 33 years), compared to 36 healthy individuals with 57 Holter recordings (52.78% female; mean age at first Holter 9.84 years, range 0.08 - 38 years). Individuals with ATP1A3-D801N had reduced prolongation of QT at lower HR, manifest as a significantly lower slope for HR vs QT compared to healthy (P<0.0001). This resulted in a significantly higher slope of the relationship for HR vs QTc compared to healthy (P<0.0001). Individuals with ATP1A3 -related phenotypes and baseline QTc <350 milliseconds (ms) had increased shortening of QT and QTc at lower HR compared to those with normal QTc (P=0.003; P=0.001). Among worldwide cases, 3 out of 131 individuals with ATP1A3 -related phenotypes required device implantation and/or had sinus pauses >4 seconds., Conclusions: Individuals with the ATP1A3-D801N variant exhibit paradoxical shortening of QT and QTc at lower HR, which contributes to an increased risk of arrhythmias during bradycardia. This is exacerbated by an underlying risk of sinus node dysfunction., Clinical Perspective: What is Known:Individuals with ATP1A3-D801N have a short baseline QTc.Two individuals with AHC experienced ventricular fibrillation following bradycardia.What the Study Adds:The QT and QTc shorten to a greater extent at lower heart rate in individuals with ATP1A3-D801N than in healthy individuals. Individuals with ATP1A3 -related phenotypes and QTc <350ms show greater impairment of QT and QTc dynamics than those with normal QTc. There is low prevalence of device implantation and significant sinus pauses in individuals with ATP1A3 -related phenotypes, with a relatively greater prevalence in those with ATP1A3-D801N.

We developed a flow cytometry (FC) assay enabling the rapid and accurate identification of bacterial and viral infections using whole blood samples. The streamlined flow cytometry assay is designed to be user-friendly, making it accessible even for operators with limited experience in FC techniques. The key components of the assay focus on the expression levels of specific surface markers-CD64 on polymorphonuclear neutrophils (PMN) as a marker for bacterial infection, and CD169 on monocytes (MO) for viral infection. The strong performance indicated by an area under the receiver operating characteristic (ROC) curve of 0.94 for both PMN CD64 positive predictive value (PPV) 97.96% and negative predictive value (NPV) 76.67%, and MO CD169 PPV 82.6% and NPV 86.9%, highlight the assay's robustness in differentiating between bacterial and viral infections accurately. The FC assay includes the assessment of immune system status through HLA-DR and IL-1R2 modulation in MO, providing a useful insight into the patients' immune response. The significant increase in the frequency of MO exhibiting reduced HLA-DR expression and elevated IL-1R2 levels in infected patients (compared to healthy controls) underscores the potential of these markers as indicators of infection severity. Although the overall correlation between HLA-DR and IL-1R2 expression levels was not significant across all patients, there was a trend in patients with more severe disease suggesting that these markers may have the potential to assist in stratifying patient risk. The present FC assay has the potential to become routine in the clinical microbiology laboratory community and to be helpful in guiding clinical decision making.

IgG4-related disease is a rare fibroinflammatory condition. Prompt recognition is fundamental to initiate treatment and to prevent organ damage. Diagnostic and classification criteria are primarily intended for use by clinicians with established expertise in IgG4-related disease. Absence of disease awareness among primary care physicians and specialists without expertise in IgG4-related disease remains the main cause of diagnostic delay. We aimed to identify red flags that might increase the suspicion of IgG4-related disease in primary and secondary care settings. A task force of experts in IgG4-related disease from the European Reference Network for Rare Connective Tissue Diseases (ERN-ReCONNET), patient representatives, and primary care physicians derived potential red flags for IgG4-related disease through a systematic literature search and a level of agreement exercise. Five red flags reached 100% agreement among experts: swelling in one or more organ system; pancreatic and biliary tree involvement; increased serum IgG4; IgG4 + plasma cell tissue infiltration; and obliterative phlebitis. Red flags for IgG4-related disease are intended for use in primary and secondary care to improve referral to centres of expertise and prompt early diagnosis., Competing Interests: Declaration of interests GPG received funding from The European Commission within the contract SANTE/2018/B3/030-SI2·813822 to support collaboration with European Reference Network (ERN) ReCONNET as a methodologist in the systematic review on red flags for IgG4-related disease. FF received honoraria from GSK for lectures and plenary presentations at educational events. TA received travel grants from AbbVie and Neovil; declares study support from Janssen; and received honoraria from AbbVie, Amgen, AstraZeneca, GSK, and Neovil for lectures and plenary presentations at educational events. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Prolonged treatment with anti-CD20 antibodies can lead to hypogammaglobulinemia and increased infection risk in multiple sclerosis (MS). We investigated switch from anti-CD20 to cladribine as a strategy to prevent immunoglobulin reduction while preserving efficacy. We prospectively analysed serum IgG, IgM, neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) in 44 patients, 14 who were switched from anti-CD20 to cladribine and 30 continuing anti-CD20. Over 1 year, serum IgG, IgM, NfL and GFAP remained stable after switch and similar to patients continuing anti-CD20. More than 90 % of patients remained free of disease activity. Cladribine should be further explored as de-escalating agent from anti-CD20 in MS., Competing Interests: Declaration of competing interest The employer (Department of Neurology, Regional Hospital Lugano (EOC), Lugano, Switzerland) receives financial support from Abbvie, Biogen Idec, Lundbeck, Merck, Novartis Roche, Sanofi, Teva. The submitted work is not related to these agreements., (Copyright © 2024. Published by Elsevier B.V.)

Background and Objectives: Autism Spectrum Disorder (ASD) involves challenges in social communication and daily functioning. Emerging research highlights that virtual reality (VR) interventions can significantly improve social skills in adults with ASD by providing immersive, controlled practice environments. This systematic review will assess the effectiveness of VR-based interventions for improving social skills in adults with ASD. Materials and Methods: Studies were identified from an online search of PubMed, Web of Science, Cochrane Library, and Embase databases without any search time range. This review was registered on Open OSF ( n ) P4SM5. Results: Recent studies show that VR interventions significantly enhance job interview skills, social abilities, and practical tasks in adults with ASD, with improvements in confidence, social understanding, and everyday skills. VR has been shown to be user-friendly and effective in providing immersive, adaptable training experiences. Conclusions: The review highlights VR's promising role in improving social skills, job interview abilities, and daily functioning in adults with ASD. It emphasizes the need for broader studies, standardized interventions, and exploration of VR's integration with other therapies to enhance long-term effectiveness and address comorbidities like anxiety and depression.

Temporomandibular disorders (TMDs) are a common musculoskeletal condition, presenting treatment challenges due to their non-specific nature. Categorizing patients with TMDs into clusters based on neurobiological pain mechanisms could provide a promising approach to facilitate targeted treatments. This observational study (1) used a network analysis (NA) to explore the complexity of TMDs by investigating relationships among biopsychosocial variables, and (2) validated potential TMD subgroups based on mechanism-specific pain categories. One hundred and two patients with TMD were included. Biopsychosocial variables covered: general health, psychosocial features, TMD pain, and TMD characteristics. A NA evaluated the associations between variables and determined the role of each feature within the network. Hierarchical clustering was used to identify TMD subgroups. The NA revealed significant correlations primarily within the same feature domains, indicating a strong interplay between symptoms and psychological factors. Cluster analysis identified two subgroups driven by nociceptive and nociplastic pain mechanisms; the nociplastic group exhibited higher levels of anxiety, depression, pain catastrophization, central sensitization, pain duration, and more pain locations, along with poorer sleep quality, quality of life, and health status. In contrast, the nociceptive group exhibited restricted maximal mouth opening (MMO), heightened pain during TMJ palpation and mouth opening, and a greater positive response to manual therapy. Across all features, psychological factors, pain locations, and MMO primarily contributed to the separation of subgroups. By adopting a data-driven approach, these results support the significant role of considering the neurobiological basis of pain to improve patient classification. This knowledge may facilitate clinical reasoning and personalized treatments. PERSPECTIVE: This study used a network analysis to explore the complex biopsychosocial interactions present in people with TMDs, identifying important variables such as the Central Sensitization Inventory and pain-free maximal mouth opening. The findings distinguish potential nociceptive and nociplastic pain subgroups, offering important insights for targeted therapeutic strategies., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In addition to its critical role in neurogenesis, brain-derived neurotrophic factor (BDNF) modulates pain and depressive behaviors., Methods: In a translational perspective, we tested the anti-migraine activity of highly purified and characterized recombinant human BDNF (rhBDNF) in an animal model of cephalic pain based on the chronic and intermittent NTG administration (five total injections over nine days), used to mimic recurrence of attacks over a given period. To achieve this, we assessed the effects of two doses of rhBDNF (40 and 80 µg/kg) administered intranasally to adult male Sprague-Dawley rats, on trigeminal hyperalgesia (by orofacial formalin test), gene expression (by rt-PCR) of neuropeptides and inflammatory cytokines in specific areas of the brain related to migraine pain. Serum levels of CGRP, PACAP, and VIP (by ELISA) were also evaluated. The effects of rhBDNF were compared with those of sumatriptan (5 mg/kg i.p), administered 1 h before the last NTG administration., Results: Both doses of rhBDNF significantly reduced NTG-induced nocifensive behavior in Phase II of the orofacial formalin test. The anti-hyperalgesic effect of intranasal high-dose rhBDNF administration in the NTG-treated animals was associated with a significant modulation of mRNA levels of neuropeptides (CGRP, PACAP, VIP) and cytokines (IL-1beta, IL-10) in the trigeminal ganglion, medulla-pons, and hypothalamic area. Of note, the effects of rhBNDF treatment were comparable to those induced by the administration of sumatriptan. rhBDNF administration at both doses significantly reduced serum levels of PACAP, while the higher dose also significantly reduced serum levels of VIP., Conclusions: The findings suggest that intranasal rhBDNF has the potential to be a safe, non-invasive and effective therapeutic approach for the treatment of primary headache, particularly migraine., (© 2024. The Author(s).)