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The organ-specific microbiome plays a crucial role in tissue homeostasis, among other things by inducing regulatory T cells (Treg). This applies also to the skin and in this setting short chain fatty acids (SCFA) are relevant. It was demonstrated that topical application of SCFA controls the inflammatory response in the psoriasis-like imiquimod (IMQ)-induced murine skin inflammation model. Since SCFA signal via HCA2, a G-protein coupled receptor, and HCA2 expression is reduced in human lesional psoriatic skin, we studied the effect of HCA2 in this model. HCA2 knock-out (HCA2-KO) mice reacted to IMQ with stronger inflammation, presumably due to an impaired function of Treg. Surprisingly, injection of Treg from HCA2-KO mice even enhanced the IMQ reaction, suggesting that in the absence of HCA2 Treg switch from a suppressive into a proinflammatory type. HCA2-KO mice differed in the composition of the skin microbiome from wild type mice. Co-housing reversed the exaggerated response to IMQ and prevented the alteration of Treg, implying that the microbiome dictates the outcome of the inflammatory reaction. The switch of Treg into a proinflammatory type in HCA2-KO mice could be a downstream phenomenon. This opens the opportunity to reduce the inflammatory tendency in psoriasis by altering the skin microbiome.

Objectives(a) Assessing mental disorders, psychological distress, psychological wellbeing in patients with systemic sclerosis (SSc); (b) identifying psychological features independently contributing to the status of having the diagnosis of SSc.MethodsTwo hundred SSc outpatients were compared with 100 healthy subjects. Mental disorders were assessed via the Mini International Neuropsychiatric Interview (MINI). Self-reported rating scales were administered: Health Assessment Questionnaire Disability Index (HAQ-DI), Symptom Checklist-90-Revised (SCL-90-R), Psychological Well Being scales (PWB). General linear models allowed to verify which psychological feature would individually make unique contributions to overall status of having the diagnosis of SSc.ResultsMajor depressive episode/disorder, panic disorder were more prevalent among patients with SSc (p

IntroductionBulimic episodes experienced by patients with Binge Eating Disorder (BED) might be sustained by an enhanced behavioral propensity to approach food stimuli.MethodsTo test this hypothesis, automatic approach avoidance tendencies toward high-calorie foods (HCF), low-calorie foods (LCF), and neutral objects were assessed in a group of 23 patients with BED, and their performance was compared to the one of 17 patients with obesity without BED and a group of 32 normal weight participants. All participants performed a mobile approach-avoidance task in which they were required to approach and avoid different stimuli by respectively pulling their phone toward themselves or pushing it away. Reaction times were analyzed.ResultsResults showed a significant three-way interaction between group, type of movement and stimulus. Post-hoc analyses revealed that all the groups displayed an approach bias toward HCF. Patients with BED and healthy controls also displayed an approach bias toward LCF, a bias that was absent in obese individuals without BED. Moreover, patients with BED were faster in approaching food stimuli, both HCF and LCF, compared to healthy controls.DiscussionThese behavioral tendencies are quite consistent with the real-life attitudes of both BED patients and patients with obesity and might contribute to the maintenance of unhealthy eating habits such as binging in patients with BED and high-calorie diets in patients with obesity.

The organ-specific microbiome plays a crucial role in tissue homeostasis, among other things by inducing regulatory T cells (Treg). This applies also to the skin and in this setting short chain fatty acids (SCFA) are relevant. It was demonstrated that topical application of SCFA controls the inflammatory response in the psoriasis-like imiquimod (IMQ)-induced murine skin inflammation model. Since SCFA signal via HCA2, a G-protein coupled receptor, and HCA2 expression is reduced in human lesional psoriatic skin, we studied the effect of HCA2 in this model. HCA2 knockout (HCA2-KO) mice reacted to IMQ with stronger inflammation, presumably due to an impaired function of Treg. Surprisingly, injection of Treg from HCA2-KO mice even enhanced the IMQ reaction, suggesting that in the absence of HCA2 Treg switch from a suppressive into a proinflammatory type. HCA2-KO mice differed in the composition of the skin microbiome from wild type mice. Co-housing reversed the exaggerated response to IMQ and prevented the alteration of Treg, implying that the microbiome dictates the outcome of the inflammatory reaction. The switch of Treg into a proinflammatory type in HCA2-KO mice could be a downstream phenomenon. This opens the opportunity to reduce the inflammatory tendency in psoriasis by altering the skin microbiome. [ABSTRACT FROM AUTHOR]

BackgroundGNAO1-related disorders (GNAO1-RD) encompass a diverse spectrum of neurodevelopmental and movement disorders arising from variants in the GNAO1 gene. Dyskinetic crises, marked by sudden and intense exacerbations of abnormal involuntary movements, present a significant challenge in GNAO1-RD.ObjectivesThis study aimed to establish a standardized framework for understanding dyskinetic crises, addressing crucial aspects such as definition, triggers, diagnostic criteria, complications, and management strategies.MethodsA Delphi consensus process was conducted involving international experts in GNAO1-RD. The panel of thirteen experts participated in three voting rounds, discussing 90 statements generated through a literature review and clinical expertise.ResultsConsensus was achieved on 31 statements, defining dyskinetic crises as abrupt, paroxysmal episodes involving distinct abnormal movements in multiple body regions, triggered by emotional stress or infections. Dyskinetic crises may lead to functional impairment and complications, emphasizing the need for prompt recognition. While individualized pharmacological recommendations were not provided, benzodiazepines and clonidine were suggested for acute crisis management. Chronic treatment options included tetrabenazine, benzodiazepines, gabapentin, and clonidine. Deep brain stimulation should be considered early in the treatment of refractory or prolonged dyskinetic crisis.ConclusionThis consensus provides a foundation for understanding and managing dyskinetic crises in GNAO1-RD for clinicians, caregivers, and researchers. The study emphasizes the importance of targeted parental and caregiver education, which enables early recognition and intervention, thereby potentially minimizing both short- and long-term complications. Future research should concentrate on differentiating dyskinetic crises from other neurological events and investigating potential risk factors that influence their occurrence and nature. The proposed standardized framework improves clinical management, stakeholder communication, and future GNAO1-RD research.

IntroductionProbiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. From this definition, accurate enumeration of probiotic products is a necessity. Nonetheless, this definition does not specify the methods for assessing such viability. Colony forming units is the de facto gold standard for enumerating viable in probiotic products. The notion of microbial viability has been anchored in the concept of cultivability, which refers to a cell’s capacity to replicate and form colonies on agar media. However, there is a growing consensus that the term “viability” should not be exclusively tied to the ability to cultivate cells. For example, bacterial cells can exist in a Viable But Non-Culturable (VBNC) state, characterized by the maintenance of characteristics such as membrane integrity, enzymatic activity, pH gradients, and elevated levels of rRNA, despite losing the ability to form colonies.MethodsHerein we present the results of a collaborative inter-laboratory ring test for cytometric bacterial quantification. Specifically, membrane integrity fluorescence flow cytometry (FFC) method and the newer impedance flow cytometry (IFC) method have been used. Both methods interrogate single cells in solution for the presence of intact membranes. FFC exploits fluorochromes that reflect the presence or absence of an intact membrane. IFC probes membrane integrity in a label-free approach by detecting membrane-induced hindrances to the propagation of electricity.ResultsA performance ring-test and comparison design on the FFC method showed that the method is robust against the exchange of equipment, procedures, materials, and operators. After initial method optimization with assessments of rehydration medium, wake-up duration, and phase shift gating on the individual strains, the IFC method showed good agreement with the FFC results. Specifically, we tested 6 distinct species of probiotic bacteria (3 Lactobacillus and 3 Bifidobacterium strains) finding good agreement between FFC and IFC results in terms of total and live cells.DiscussionTogether, these results demonstrate that flow cytometry is a reliable, precise, and user-friendly culture-independent method for bacterial enumeration.

In the present study, the adaptive behavior of a concrete beam with integrated fluidic actuators was numerically investigated through three-dimensional (3D) non-linear finite element (FE) analysis. The employed numerical approach for the mechanical behavior of concrete is based on the microplane theory, implemented in the in-house software MAcroscopic Space Analysis (MASA). Different cases were analyzed and the results compared with experimental tests available in the literature. First, a reference concrete beam without actuators was numerically analyzed in order to calibrate and validate the employed non-linear microplane material model. Thereafter, the validated model was used for the non-linear analysis of the concrete beam with integrated fluidic actuators, with respect to different load cases. The obtained results confirm the capability of the model to reproduce the deformational behavior of the beam for all analyzed cases. A fundamental aspect is the realistic modeling of the actuators and related applied pressure. The use of a non-linear material model allows to realistically capture the possible cracking and consequent failure of the beam. It is worth mentioning that a full model validation should be extended to the long-term behavior of actuated structural elements. In future perspective, the well-established numerical framework for concrete, based on coupled 3D hygro-thermo-mechanical model, can be used to 1) investigate the performance of adaptive structural components, with respect to more complex loading conditions, e.g., cyclic; 2) perform durability analysis under exposure to different combinations of mechanical and/or environmental loading conditions.

Inflammation-dependent changes in gene expression programs in innate immune cells, such as macrophages, involve extensive reprogramming of metabolism. This reprogramming is essential for the production of metabolites required for chromatin modifications, such as acetyl-CoA, and regulate their usage and availability impacting the macrophage epigenome. One of the most transcriptionally induced proinflammatory mediator is nitric oxide (NO), which has been shown to inhibit key metabolic enzymes involved in the production of these metabolites. Recent evidence indicates that NO inhibits mitochondrial enzymes such as pyruvate dehydrogenase (PDH) in macrophages induced by inflammatory stimulus. PDH is involved in the production of acetyl-CoA, which is essential for chromatin modifications in the nucleus, such as histone acetylation. In addition, acetyl-CoA levels in inflamed macrophages are regulated by ATP citrate lyase (ACLY) and citrate transporter SLC25A1. Interestingly, acetyl-CoA producing enzymes, such as PDH and ACLY, have also been reported to be present in the nucleus and to support the local generation of cofactors such as acetyl-CoA. Here, we will discuss the mechanisms involved in the regulation of acetyl-CoA production by metabolic enzymes, their inhibition by prolonged exposure to inflammation stimuli, their involvement in dynamic inflammatory expression changes and how these emerging findings could have significant implications for the design of novel therapeutic approaches.

Background: Bradykinesia has been reported in patients with dystonia. Despite this, the pathophysiological mechanisms of bradykinesia in dystonia remain largely unknown.Methods: We here performed a comprehensive literature search and reviewed clinical and experimental studies on bradykinesia in patients with dystonia.Results: Many studies have documented the presence of bradykinesia in patients with idiopathic and inherited isolated dystonia, regardless of the presence of parkinsonism. In addition, bradykinesia has been observed as a side effect in dystonic patients who have undergone deep brain stimulation, in those with functional dystonia as well as in those with combined dystonia, e.g., dystonia-parkinsonism. These clinical and experimental findings support the hypothesis that dysfunction in a brain network involving the basal ganglia, primary sensorimotor cortex, and cerebellum may play a key role in the pathophysiology of both bradykinesia and dystonia.Conclusion: Bradykinesia is frequently observed in dystonia. We may gain insights into the pathophysiological underpinnings of two distinct movement disorders by investigating this issue. Furthermore, a deeper understanding of bradykinesia in dystonia may have terminological implications in this field.

BackgroundTuberous sclerosis complex (TSC) is a rare multisystemic disorder. This genetically determined disease is characterized by highly variable clinical expression, including epilepsy as a common feature. Seizures can also occur as a manifestation of symptomatic hypoglycemia. The latter could be caused by an insulinoma, whose association to TSC has already been debated. In TSC-associated tumors, dysregulation of the mTOR pathway is believed to be present, leading to significant impacts on cellular metabolism, growht, and proliferation. To date, the association between TSC and insulinoma has been reported in 11 adults. Here, we present the first case of a pediatric patient with TSC diagnosed with an insulinoma and review the existing literature on this topic.Case presentationA 11-year-old female with TSC presented with seizures unresponsive to standard therapy. Further investigation revealed that these seizures were caused by hypoglycemia. Subsequent evaluation led to the diagnosis of a pancreatic insulinoma, which was surgically removed. Following the procedure, the patient was free from seizures.ConclusionsIn individuals with TSC, the recurrence of epileptiform episodes throughout their lifetime, especially if previously well controlled with antiepileptic therapy, should raise suspicion for hypoglycemic events. These events may potentially be associated with the presence of an insulinoma. Further research and increased awareness are necessary to gain a better understanding of the association between TSC and insulinomas, and to guide clinical management strategies.

Due to its excellent properties, poly(ethylene terephthalate) (PET) is one of the most produced and consumed polymers. Among plastics, it represents the main contributor to environmental pollution. Following the circular economy model, the chemical upcycling of PET reduces the amount of waste generated and transforms it into high-value products. The depolymerization of poly(ethylene terephthalate) into oligomers or monomers leads to forming a library of reactive molecules involved in different polymerization processes to obtain compounds with improved properties. Herein, several β-hydroxy amines were synthesized and used for the chemical recycling of water bottle waste by an environmental benefit aminolysis process to get very useful new terephthalamide diol monomers. The recycled diol monomers were subsequently exploited to synthesize poly(urethane acrylates) (PUAs) UV-curable coatings, and their chemical, thermal and mechanical characterizations were performed. The results show the great potential of the developed synthesis protocols to obtain PUAs with final properties that can be modulated to meet the requirements of different applications.

IntroductionThis paper describes the creation and preliminary results of a patient-driven registry for the collection of patient-reported outcomes (PROs) and patient-reported experiences (PREs) in Behçet’s disease (BD).MethodsThe project was coordinated by the University of Siena and the Italian patient advocacy organization SIMBA (Associazione Italiana Sindrome e Malattia di Behçet), in the context of the AIDA (AutoInflammatory Diseases Alliance) Network programme. Quality of life, fatigue, socioeconomic impact of the disease and therapeutic adherence were selected as core domains to include in the registry.ResultsRespondents were reached via SIMBA communication channels in 167 cases (83.5%) and the AIDA Network affiliated clinical centers in 33 cases (16.5%). The median value of the Behçet’s Disease Quality of Life (BDQoL) score was 14 (IQR 11, range 0–30), indicating a medium quality of life, and the median Global Fatigue Index (GFI) was 38.7 (IQR 10.9, range 1–50), expressing a significant level of fatigue. The mean Beliefs about Medicines Questionnaire (BMQ) necessity-concern differential was 0.9 ± 1.1 (range – 1.8–4), showing that the registry participants prioritized necessity belief over concerns to a limited extent. As for the socioeconomic impact of BD, in 104 out of 187 cases (55.6%), patients had to pay from their own pocket for medical exams required to reach the diagnosis. The low family socioeconomic status (p

Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a rare neurological disorder characterized by a wide spectrum of symptoms: epilepsy, movement disorders and neurocognitive impairment. The gold standard treatment for GLUT1DS are ketogenic dietary therapies (KDTs), specifically classical ketogenic diet (CKD). Despite the benefits, CKD often represents a challenge for patients and their families since meal preparation is extremely demanding and deviates a lot from normal diet. To assure an optimal compliance to CKD a psychological support for parents and patients with GLUT1DS is highly recommended. Specifically, a psychoeducational intervention that ameliorates the knowledge about the illness and its therapy improves treatment' s adherence and efficacy. The aim of this case report is to investigate the effectiveness of a psychoeducational program, partially implemented through telepsychology, based on the theoretical model of Cognitive Behavioral Play Therapy (CBPT) to support KDT knowledge and adherence in a patient with GLUT1DS who presented a worsening of her clinical picture due to a sparse knowledge of KDTs principles which determined a low adherence. Thus, with this case report we propose a model of intervention with psychoeducation in a patient with a complex chronic disease.

De novo CLTC mutations underlie a spectrum of early-onset neurodevelopmental phenotypes having developmental delay/intellectual disability (ID), epilepsy, and movement disorders (MD) as major clinical features. CLTC encodes the widely expressed heavy polypeptide of clathrin, a major component of the coated vesicles mediating endocytosis, intracellular trafficking, and synaptic vesicle recycling. The underlying pathogenic mechanism is largely unknown. Here, we assessed the functional impact of the recurrent c.2669C > T (p.P890L) substitution, which is associated with a relatively mild ID/MD phenotype. Primary fibroblasts endogenously expressing the mutated protein show reduced transferrin uptake compared to fibroblast lines obtained from three unrelated healthy donors, suggesting defective clathrin-mediated endocytosis. In vitro studies also reveal a block in cell cycle transition from G0/G1 to the S phase in patient’s cells compared to control cells. To demonstrate the causative role of the p.P890L substitution, the pathogenic missense change was introduced at the orthologous position of the Caenorhabditis elegans gene, chc-1 (p.P892L), via CRISPR/Cas9. The resulting homozygous gene-edited strain displays resistance to aldicarb and hypersensitivity to PTZ, indicating defective release of acetylcholine and GABA by ventral cord motor neurons. Consistently, mutant animals show synaptic vesicle depletion at the sublateral nerve cords, and slightly defective dopamine signaling, highlighting a generalized deficit in synaptic transmission. This defective release of neurotransmitters is associated with their secondary accumulation at the presynaptic membrane. Automated analysis of C. elegans locomotion indicates that chc-1 mutants move slower than their isogenic controls and display defective synaptic plasticity. Phenotypic profiling of chc-1 (+/P892L) heterozygous animals and transgenic overexpression experiments document a mild dominant-negative behavior for the mutant allele. Finally, a more severe phenotype resembling that of chc-1 null mutants is observed in animals harboring the c.3146 T > C substitution (p.L1049P), homologs of the pathogenic c.3140 T > C (p.L1047P) change associated with a severe epileptic phenotype. Overall, our findings provide novel insights into disease mechanisms and genotype–phenotype correlations of CLTC-related disorders.

BackgroundAlthough children with neurodevelopmental disability (NDD) present with several deficits, they partially share developmental impairments in prelinguistic intersubjective and socio-communicative skills, which are not easily assessed by conventional tests during the first years of life.AimThe current paper presents a new procedure to assess the prelinguistic intersubjective and socio-communicative skills of NDD children aged 0–36 months. A specific observation form template, called the Observation of Prelinguistic Intersubjective and Socio-Communicative Skills (OPISCoS) form, has been designed to systematically detect infant skills during daily routines (e.g., mealtime, playtime, desk activities). The OPISCoS form helps speech therapists to provide parents support to better perceive and understand early communicative signals from their children, avoiding the risk of excessive or reduced social stimulation.MethodsThe OPISCoS form is composed of three sections, namely, “Pragmatics and Communication,” “Decoding,” and “Expression,” which are useful to delineate the communication abilities of children with NDD and are not tapped by traditional batteries. Vignettes from clinical practice illustrate and provide exemplifications for using the OPISCoS form with NDD infants and their parents.ResultsThe OPISCoS form was reported for two children and showed potential in detecting disrupted communicative behaviors and planning specific early interventions. Further, we observed an improvement not only in children's communicative abilities improve but also in their interactions with parents. From a clinical point of view, the OPISCoS form (1) offers an observational perspective of prelinguistic intersubjective and socio-communicative skills in infants with NDD and (2) may be useful to practitioners to enhance parents’ sensitivity to their infants’ communicative behavior.ConclusionThe OPISCoS form was developed in clinical practice and is based on a very preliminary description of a new observational procedure as integration for the assessment of NDD children. The OPISCoS form appears to be a useful tool for the clinical assessment of prelinguistic intersubjective and socio-communicative skills in NDD infants as well as for promoting the quality of early parenting.

Ending poverty in all its forms everywhere is the number one Sustainable Development Goal of the UN 2030 Agenda. To monitor the progress toward such an ambitious target, reliable, up-to-date and fine-grained measurements of socioeconomic indicators are necessary. When it comes to socioeconomic development, novel digital traces can provide a complementary data source to overcome the limits of traditional data collection methods, which are often not regularly updated and lack adequate spatial resolution. In this study, we collect publicly available and anonymous advertising audience estimates from Facebook to predict socioeconomic conditions of urban residents, at a fine spatial granularity, in four large urban areas: Atlanta (USA), Bogotá (Colombia), Santiago (Chile), and Casablanca (Morocco). We find that behavioral attributes inferred from the Facebook marketing platform can accurately map the socioeconomic status of residential areas within cities, and that predictive performance is comparable in both high and low-resource settings. Our work provides additional evidence of the value of social advertising media data to measure human development and it also shows the limitations in generalizing the use of these data to make predictions across countries.

BackgroundFace-to-face visual contact is a key component of the early parent-child interaction, therefore a visual impairment condition of the parent or the child represents a risk factor for dyadic patterns' development.AimsThe study presents a critical single case of a blind father and a 18-month-old visually impaired child. The study aims to explore changes in the relational functioning of this dyad during an early family-centered intervention.Methods and proceduresTen parent-child sessions were videotaped and micro-analytically coded. Data were analyzed through a State Space Grid crossing child's social cues and types of father verbalizations.Outcomes and resultsFindings showed a stable increase in the amount of child social cues over time. Moreover, the dyad exhibited progressive changes in dyadic regulation, stability, and organization. The return time to the “active interaction” region of interest decreased progressively. A reduction was observed also for the time spent by the dyad in the region “no vocal contact.”Conclusions and implicationsThis critical single case highlighted the benefits of parental engagement in early interventions for the dyadic regulation in parent-child interaction.

BackgroundHigh levels of mental health problems have been consistently reported among neonatal healthcare professionals. While studies suggest that personality, coping strategies and safety culture might contribute to the psychological wellbeing of healthcare professionals, they have not been systematically investigated in low-risk (i.e., neonatal wards; NWs) and high-risk (i.e., neonatal intensive care units; NICUs) neonatal contexts. The current study investigated potential predictors of professionals' emotional distress and whether they differ according to the work setting (i.e., NICUs vs. NWs).MethodsHealthcare professionals (N = 314) from 7 level-3 (i.e., NICUs) and 6 level-2 (i.e., NWs) neonatal units in Tuscany were included. Emotional distress (i.e., anxiety, depression, psychosomatic, post-traumatic stress symptoms and emotional exhaustion), Behavioral Inhibition System (BIS) and Behavioral Approach System (BAS) sensitivity, coping strategies and safety culture were assessed through well-validated, self-reported questionnaires.ResultsGreater BIS/BAS sensitivity, avoidance coping strategies and a sub-dimension of safety culture (i.e., stress recognition) were significantly associated with greater risk of emotional distress, whereas job satisfaction emerged as a protective factor. Three specific profiles of professionals in term of personality, coping and safety culture were identified and further predicted emotional distress. Neonatal wards and NICUs personnel presented different associations between personality, coping and safety culture.ConclusionThese findings highlighted significant modifiable contributors of neonatal mental healthcare professionals' wellbeing. Institutional initiatives that target these factors and, particularly, job satisfaction may promote professionals' emotional wellbeing and thus improve caring processes.

Over the last years, a constantly increasing number of genetic diseases associated with epilepsy and movement disorders have been recognized. An emerging group of conditions in this field is represented by genetic disorders affecting G-protein-coupled receptors (GPCRs)–cAMP signaling. This group of postsynaptic disorders includes genes encoding for proteins highly expressed in the central nervous system and involved in GPCR signal transduction and cAMP production (e.g., GNAO1, GNB1, ADCY5, GNAL, PDE2A, PDE10A, and HPCA genes). While the clinical phenotype associated with ADCY5 and GNAL is characterized by movement disorder in the absence of epilepsy, GNAO1, GNB1, PDE2A, PDE10A, and HPCA have a broader clinical phenotype, encompassing movement disorder, epilepsy, and neurodevelopmental disorders. We aimed to provide a comprehensive phenotypical characterization of genetic disorders affecting the cAMP signaling pathway, presenting with both movement disorders and epilepsy. Thus, we reviewed clinical features and genetic data of 203 patients from the literature with GNAO1, GNB1, PDE2A, PDE10A, and HPCA deficiencies. Furthermore, we delineated genotype–phenotype correlation in GNAO1 and GNB1 deficiency. This group of disorders presents with a highly recognizable clinical phenotype combining distinctive motor, epileptic, and neurodevelopmental features. A severe hyperkinetic movement disorder with potential life-threatening exacerbations and high susceptibility to a wide range of triggers is the clinical signature of the whole group of disorders. The existence of a distinctive clinical phenotype prompting diagnostic suspicion and early detection has relevant implications for clinical and therapeutic management. Studies are ongoing to clarify the pathophysiology of these rare postsynaptic disorders and start to design disease-specific treatments.

AimsTo perform a cost-effectiveness analysis (CEA) comparing personalised dosimetry with standard dosimetry in the context of selective internal radiation therapy (SIRT) with TheraSphere for the management of adult patients with locally advanced hepatocellular carcinoma (HCC) from the Italian Healthcare Service perspective.Materials and methodsA partition survival model was developed to project costs and the quality-adjusted life years (QALYs) over a lifetime horizon. Clinical inputs were retrieved from a published randomised controlled trial. Health resource utilisation inputs were extracted from the questionnaires administered to clinicians in three oncology centres in Italy, respectively. Cost parameters were based on Italian official tariffs.ResultsOver a lifetime horizon, the model estimated the average QALYs of 1.292 and 0.578, respectively, for patients undergoing personalised and standard dosimetry approaches. The estimated mean costs per patient were €23,487 and €19,877, respectively. The incremental cost-utility ratio (ICUR) of personalised versus standard dosimetry approaches was €5,056/QALY.ConclusionsPersonalised dosimetry may be considered a cost-effective option compared to standard dosimetry for patients undergoing SIRT for HCC in Italy. These findings provide evidence for clinicians and payers on the value of personalised dosimetry as a treatment option for patients with HCC.

BackgroundThe COVID-19 pandemic is a collective trauma that may expose susceptible individuals to high levels of stress. Pregnant women represent a high-risk population, considering that pregnancy is a period of heightened neuroplasticity and susceptibility to stress through epigenetic mechanisms. Previous studies showed that the methylation status of the BDNF gene is linked with prenatal stress exposure. The goals of this study were (a) to assess the association between pandemic-related stress and postnatal anxiety and (b) to investigate the potential role of maternal BDNF methylation as a significant mediator of this association.MethodsIn the present study, we report data on the association among pandemic-related stress during pregnancy, maternal BDNF methylation, and postnatal anxiety symptoms. Pandemic-related stress and postnatal anxiety were assessed through self-report instruments. BDNF methylation was estimated in 11 CpG sites in DNA from mothers’ buccal cells. Complete data were available from 108 mothers.ResultsResults showed that pandemic-related stress was associated with an increased risk of postnatal anxiety, r = 0.20, p < 0.05. CpG-specific BDNF methylation was significantly associated with both prenatal pandemic-related stress, r = 0.21, p < 0.05, and postnatal maternal anxious symptoms, r = 0.25, p = 0.01. Moreover, a complete mediation by the BDNF CpG6 methylation emerged between pandemic-related stress during pregnancy and postnatal maternal anxiety, ACME = 0.66, p < 0.05.ConclusionThese findings suggest that BDNF epigenetic regulation by pandemic-related stress might contribute to increase the risk of anxiety in mothers. Policymakers should prioritize the promotion of health and wellbeing in pregnant women and mothers during the present healthcare emergency.

BackgroundThis paper aimed to evaluate the frequency of observation of genetically determined developmental encephalopathies with epilepsy and movement disorders in a specialistic center, the distribution of etiologies and presenting clinical hallmarks, and the mean times for the achievement of molecular genetic diagnosis.Patients and MethodsRetrospective data about clinical phenotypes, etiology, and diagnostic pathways were collected in all the genetically confirmed patients with developmental encephalopathies with epilepsy and movement disorders referred to our institution between 2010 and 2020. The cohort was divided into two groups according to the predominant movement disorder type: 1) Group A: patients with hyperkinetic movement disorders; 2) Group B: patients with hypokinetic movement disorders. Both groups were analyzed in terms of developmental, epileptic, and movement disorder phenotypes.ResultsThe cohort included 69 patients (Group A = 53; Group B = 16). The etiological spectrum was heterogeneous with a predominance of Rett and Angelman syndrome in Group A and neurodegenerative disorders in Group B. A moderate/severe intellectual disability was assessed in 58/69 patients (mean age at the first signs of developmental impairment = 1,87 ± 1,72 years). Group A included patients with an earlier onset of epileptic seizures (2,63 ± 3,15 vs. 4,45 ± 5,55 years of group B) and a predominant generalized motor semiology of seizures at the onset. Focal seizures were the main initial epileptic manifestations in Group B. Seizures were noticed earlier than movement disorders in Group A while the opposite occurred in Group B. A higher increase in molecular genetic diagnosis was obtained in the last five years. Mean diagnostic delay was longer in Group B than in Group A (12,26 ± 13,32 vs. 5.66 ± 6.41 years). Chorea as an initial movement disorder was associated with a significantly longer diagnostic delay and a higher age at etiological diagnosis.ConclusionsThis study suggested: (a) a higher frequency of genetic defects involving neurotransmission, neuronal excitability, or neural development in patients with hyperkinetic movement disorders; (b) a higher frequency of neurodegenerative courses and a longer diagnostic delay in patients with hypokinetic movement disorders.

Sportsman’s hernia is a painful syndrome in the inguinal area occurring in patients who play sports at an amatorial or professional level. Pain arises during sport, and sometimes persists after activity, representing an obstacle to sport resumption. A laparoscopic/endoscopic approach is proposed by many authors for treatment of the inguinal wall defect. Aim of this study is to assess the open technique in terms of safety and effectiveness, in order to obtain the benefit of an open treatment in an outpatient management. From October 2017 to July 2019, 34 patients underwent surgery for groin pain syndrome. All cases exhibited a bulging of the inguinal posterior wall. 14 patients were treated with Lichtenstein technique with transversalis fascia plication and placement of a polypropylene mesh fixed with fibrin glue. In 20 cases, a polypropylene mesh was placed in the preperitoneal space. The procedure was performed in day surgery facilities. Early or late postoperative complications did not occur in both groups. All patients returned to sport, in 32 cases with complete pain relief, whereas 2 patients experienced mild residual pain. The average value of return to sport was 34.11 ± 8.44 days. The average value of return to play was 53.82 ± 11.69 days. With regard to postoperative pain, no substantial differences between the two techniques were detected, and good results in terms of the resumption of sport were ensured in both groups. Surgical treatment for sportsman’s hernia should be considered only after the failure of conservative treatment. The open technique is safe and allows a rapid postoperative recovery.

Bullous pemphigoid (BP) represents the most common autoimmune bullous disease and is characterized by IgG autoantibodies targeting collagen XVII (BP180). BP has reportedly been occurred in association with other inflammatory skin diseases. Here, we describe the unusual occurrence of BP in a female patient with a concomitant history of generalized morphea (localized scleroderma, LoS) and cutaneous and genital lichen sclerosus (LiS). The occurrence of BP was associated with elevated serum levels of anti-BP180 IgG autoantibodies, which decreased upon clinical remission. Autoimmune bullous diseases and sclerosing dermatitis are immunologically distinct entities, whose association has been rarely described. In this study, we provide a literature review on cases of BP developed in patients with either LoS or LiS. Further, we discussed immunological mechanisms which may have favored the emergence of BP in our patient.

Background: In women with rheumatic diseases (RDs) menstruation-related disorders have never been investigated. The aim of this study was to evaluate gynecological symptoms/disorders in fertile age women with RDs.Materials and methods: All patients (n = 200) filled up a self-administered questionnaire on their gynecological history, menstrual cycle pattern, menstrual-related symptoms, and quality of life (QoL). The RD group was then compared to a control group of 305 age-matched fertile age women.Results: Among patients with RDs, 58% had arthritis, 40% connective tissue diseases (CTDs), and 1.5% systemic vasculitis. No differences were observed between CTDs and arthritis, except for a family history of HMB which was more common among women with CTDs (p < .01). When compared to controls, women with RDs reported more frequent heavy menstrual bleeding (HMB) during adolescence (51.7 and 25.4%, respectively; p = .0001) and adult life (37.7 and 25.9%, respectively; p = .0065). Also, dysmenorrhea in adolescence was significantly more common among cases (55.6 and 45.4%, respectively; p = .0338). Gynecological pain (dysmenorrhea, non-menstrual pelvic pain, dyspareunia, dysuria, and dyschezia) in patients with RDs was more frequent than in controls (p = .0001, .0001, .0001, .0001, .0002, respectively). Considering women who reported moderate and severe symptoms in RDs, dysmenorrhea and dyspareunia remain significantly more frequent in women with RDs than in controls (p = .0001; p = .0022; respectively). QoL scores were significantly reduced in women with RDs, either in physical (p = .0001) and mental domains (p = .0014) of short-form 12.Conclusion: Women affected by RDs frequently presented menstruation-related disorders; thus, female patients with RDs should be questioned about gynecological symptoms and referred to the gynecologist for an accurate evaluation.

The COVID-19 pandemic is a collective trauma that is threatening citizens' mental health resulting in increased emotional stress, reduced social support, and heightened risk for affective symptoms. The present study aimed to investigate the effects of antenatal pandemic-related emotional stress and perceived social support on the symptoms of depression and anxiety of mothers who were pregnant during the initial COVID-19 outbreak in northern Italy. A sample of 281 mothers was enrolled at eight maternity units in the first hotspot region of the COVID-19 outbreak in northern Italy. Participants filled out online questionnaires assessing the direct or indirect exposure to the SARS-CoV-2 virus, pandemic-related stress, perceived social support, as well as symptoms of depression and anxiety. Depressive and anxious symptomatology was above clinical concern, respectively, in 26 and 32% of the respondents. Mothers who reported no exposure to SARS-CoV-2 during pregnancy and those who reported at least one direct or indirect exposure did not differ in terms of affective symptoms. Continuous scores and risk for severe depression and anxiety were positively associated with prenatal pandemic-related emotional stress and negatively linked with perceived social support during pregnancy. Women who become mothers during the COVID-19 emergency may be at high risk for affective problems. Dedicated preventive programs are needed to provide adequate preventive support and care for maternal mental health during and after the COVID-19 pandemic.

Objectives: The aim of this study was to validate a novel iPad-based rapid hearing loss screening tool (SHOEBOX QuickTest) in individuals with cognitive impairment.Design: Cross-sectional validation study.Setting: Bruyère Research Institute, Ottawa, Canada.Subjects and Methods: Twenty-five individuals with mild cognitive impairment (MCI) and mild dementia from the Bruyère Memory Program were included in this study. The study consisted of two components: (1) SHOEBOX QuickTest hearing screener and (2) a conventional hearing test (pure tone audiometry).Measurements: Hearing was assessed at 1,000, 2,000, and 4,000 Hz separately for each ear. The agreement between hearing ability groupings (good vs. reduced) from conventional hearing test and SHOEBOX QuickTest was determined. Specifically, accuracy, sensitivity, specificity, as well as alignment between conventional thresholds and hearing threshold ranges.Results: An overall accuracy of 84% was observed for SHOEBOX QuickTest, and a sensitivity and specificity of 100 and 66.7%, respectively. 72% ([95% CI], 60.0–84.1%) of conventional audiometry thresholds were within the pre-established 10 dB SHOEBOX QuickTest.Conclusion: SHOEBOX QuickTest is a valid hearing loss screening tool for individuals with cognitive impairment. Implementing this iPad-based screening tool in memory clinics could not only aid in the timely diagnosis of hearing loss, but also assist physicians in providing a better assessment of cognitive impairment by ruling out hearing loss as a confounding variable.

Previous studies have clearly demonstrated that the addition of lentisk oil (LO) to streptococcal cultures makes it possible to differentiate Streptococcus spp. into three categories with Streptococcus mitis and Streptococcus intermedius sensitive, Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus mutans partially sensitive, and Streptococcus salivarius insensitive to the product. We have investigated here whether the winterization of LO, an easy and cheap procedure that removes some of the fatty substances contained within, resulted in a better antimicrobial effect on human pathogens affecting the pharyngeal mucosa and middle ear such as S. pyogenes, S. pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae, without affecting, or minimally affecting, S. salivarius strains, oral probiotics commonly used to reduce oral and middle ear infection recurrence, especially in children. Our results not only demonstrated a stronger antimicrobial action of winterized LO (WLO) on S. pyogenes, compared to what was seen with LO, but also demonstrated a strong antimicrobial action vs. S. pneumoniae and M. catarrhalis and a very limited effect on S. salivarius (strains K12 and M18). Moreover, WLO demonstrated a co-acting action when tested along with the antibiotics amoxicillin (A) and amoxicillin clavulanate (AC), effects clearly visible also on H. influenzae. Our results also showed that at least part of the antimicrobial effect observed was due to the presence of anacardic acids (AAs). Finally, WLO, when tested with human peripheral blood mononuclear cells (h-PBMCs), reduced the release of IL-6 and TNF-α and, in the case of cells stimulated by LPS, the release of IFN-γ. In conclusion, our study highlights an enhanced antimicrobial role for LO when winterized, suggests a co-acting effect of this when given with antibiotics, identifies AAs as possible active ingredients, and proposes a possible anti-inflammatory role for it.

The ongoing outbreak of the Coronavirus Disease 2019 (COVID-19) and the ensuing preventative lock-down and shelter-in-place policies enacted around the world have caused unanticipated disruptions in the delivery of educational content and accessibility services to children, youth and adults with disabilities. The rapid move to online and remote learning, socialization, and therapeutic activities have surfaced some of the inadequacies of existing systems and infrastructures as well as opportunities for creating novel and accessible solutions. We conducted semi-structured remote interviews with nine special education teachers, therapists, community advocates, and individuals with disabilities to capture their perspectives on delivering services and supporting children and adults with disabilities and their families during the pandemic. Participants shared reflections on their experience and those who they serve during the initial phases of the COVID-19 crisis and the challenges and insights that this experience surfaced. Findings include a need to better support families in facilitating remote learning experiences for their children, developing tactile modes of engagement to complement online interactions, and the impact of a lack of contingency plans specifically to support people with disabilities and their families during crizes. The participants also described the lack of clarity about the future as one of the most difficult aspects of the pandemic. We conclude with a discussion of these findings and directions for future research.

New advances in directing the neuronal differentiation of human embryonic and induced pluripotent stem cells (hPSCs, abbreviation intended to convey both categories of pluripotent stem cells) have promoted the development of culture systems capable of modeling early neurogenesis and neural specification at some of their critical milestones. The hPSC-derived neural rosette can be considered the in vitro counterpart of the developing neural tube, since both structures share a virtually equivalent architecture and related functional properties. Epigenetic stimulation methods can modulate the identity of the rosette neural progenitors in order to generate authentic neuronal subtypes, as well as a full spectrum of neural crest derivatives. The intrinsic capacity of induced pluripotent cell-derived neural tissue to self-organize has become fully apparent with the emergence of innovative in vitro systems that are able to shape the neuronal differentiation of hPSCs into organized tissues that develop in three dimensions. However, significant hurdles remain that must be completely solved in order to facilitate the use of hPSCs in modeling (e.g., late-onset disorders) or in building therapeutic strategies for cell replacement. In this direction, new procedures have been established to promote the maturation and functionality of hPSC-derived neurons. Meanwhile, new methods to accelerate the aging of in vitro differentiating cells are still in development. hPSC-based technology has matured enough to offer a significant and reliable model system for early and late neurogenesis that could be extremely informative for the study of the physiological and pathological events that occur during this process. Thus, full exploitation of this cellular system can provide a better understanding of the physiological events that shape human brain structures, as well as a solid platform to investigate the pathological mechanisms at the root of human diseases. [ABSTRACT FROM AUTHOR]

White matter (WM) abnormalities and ventricular enlargement in brain MRI are well-known features in infantile-onset Pompe disease (IOPD) in the era of enzyme replacement therapy (ERT). In this multicentric observational retrospective study, we report a small cohort of IOPD subjects under ERT treatment (n = 5, median age at MRI = 7.4 years, median period of treatment = 85 months) that showed the classic features of extensive supratentorial WM abnormalities but also unusual findings such as early infratentorial WM abnormalities and late supratentorial U-fiber involvement. Given the recent implementation of ERT and the rarity of the disease, a complete spectrum of presentation and understanding of progressive pathology in the brain of IOPD subjects in treatment remains underacknowledged. The availability of long-term follow-up of IOPD subjects under ERT treatment allows a better insight into the evolution of brain abnormalities in such disease.

Although many models for service life predictions have been developed, their application to existing bridges is still not at a satisfactory level. The here presented coupled three-dimensional chemo-hygro-thermo-mechanical (CHTM) model can realistically simulate both corrosion phases: initiation and propagation. The focus of this research is the transport processes in cracked and uncracked concrete before reinforcement depassivation. Realistic environmental conditions with the surface water and chloride contents variable in time are simulated based on the meteorological data for a mountain region in Croatia where case studies bridges are located. Application of the large quantities of de-icing salts in combination with the poorly designed and executed details resulted in a high chloride content in concrete of the superstructure of both bridges: at the reinforcement level, chloride content in cracked concrete elements exceeds the threshold value up to 10 times. Numerical results match well with the chloride content measured on the bridges after 11 and 14 years of service. Accounting for the realistic environmental conditions (wetting–drying cycles, application of de-icing salts only in the winter season, etc.) in the numerical simulations results in the continuous transport processes in concrete and higher chloride content in deeper concrete layers as opposed to the finite element models with the constant boundary conditions.

The Gulf of Milazzo (north-eastern Sicily) has been recognized as Italian Site of National Interest (SNI; areas characterized by high level of contamination with potential effects on human health) in 2005 because of its high level of pollution. In this study we measured the concentration of polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides (OCPs), and polyBrominated diphenyl ether (PBDE) in seawater and sediments sampled from the Gulf of Milazzo in order to assess (i) the environmental status of contamination, and (ii) cancer and non-cancer human health risk potentially due to dermal absorption from contaminated seawater and/or ingestion of contaminated fish. Particularly, POPs content in pelagic and demersal fish of different size classes (small, medium, and large) were estimated, starting from the measured seawater and sediments concentrations, using the KABAM model. In particular, Monte Carlo simulation techniques were applied to address uncertainty in assessment of the risk and to provide quantitative estimates of probability of exposition. Ingestion of contaminated pelagic and demersal fish was the dominant pathway of exposition with high probability of significant cancer risk (Ingestion Cancer Risk >10–4) and significant non-cancer risk (Hazard Index >1). No human health risks emerged to be associated to dermal adsorption from contaminated seawater. Benzo(a)pyrene show the highest Ingestion Cancer Risk with respect to the other PAHs, while the highest Hazard Index for non-cancerogenic molecules was estimated for the PBDE47 congener.

Heavy metals and PAHs were measured in animal foodstuffs from Augusta-Melilli-Priolo area in order to evaluate the potential human health risk associated to their consumption. All heavy metals were detected in seafood products while most of them were 1 for baby, children and teenagers, indicating a non-carcinogenic risk for these age categories by seafood ingestion. The CRAs overcame 1*10−5 for almost age categories (except “baby”) and for elderly, by seafood and beef ingestions respectively. Moreover, the MOE for PAHs showed a certain cancer risk for “baby” related to cow milk ingestion.

Diet is advocated as a key factor influencing gut microbiota. Several studies have focused on the effect of different carbohydrates, mainly fiber, on gut microbiota. However, what remains to be elucidated is the impact of a key component of diet that is widely debated upon: dietary fats. This review highlights the importance of understanding the source, quality, and type of fats that could differentially modify the intestinal microbiome. Fats from plant-based sources such as nuts, or vegetable oils have shown positive alterations in gut microbiota biodiversity both in in vivo and in vitro studies. Nuts and other plant-based fat sources, dietary patterns (e.g., Mediterranean diet) rich in polyunsaturated and monounsaturated fats and, in some cases, polyphenols, and other phytochemicals, have been associated with increased bacterial diversity, as well beneficial butyrate-producing bacteria imparting a positive metabolic influence. It is with this interest, this narrative review brings together evidences on different plant-based fat sources, dietary patterns rich in vegetable fats, and associated changes in gut microbiota.

CAPN1 encodes calpain-1, a large subunit of μ-calpain, a calcium-activated cysteine protease widely present in the central nervous system. Mutations in CAPN1 have recently been identified in a complicated form of Hereditary Spastic Paraplegia (HSP) with a combination of cerebellar ataxia and corticomotor tract disorder (SPG76). Therefore, CAPN1 is now considered one of those genes that clinically manifest with a spectrum of disorders ranging from spasticity to cerebellar ataxia and represent a link between Spinocerebellar Ataxia and HSP, two groups of diseases previously considered separate but sharing pathophysiological pathways. We here describe clinical and molecular findings of two Italian adult siblings affected with a pure form of HSP and harboring the novel homozygote c.959delA variant (p.Tyr320Leufs*73) in the CAPN1 gene. Although the reason why mutations in CAPN1 may cause heterogeneous clinical pictures remains speculative, our findings confirm that the spectrum of the CAPN1-linked phenotypes includes pure HSP with onset during the third decade of life. Further studies are warrantied in order to clarify the mechanism underlying the differences in CAPN1 mutation clinical expression.

Use of videogames (VGs) is almost ubiquitous in preadolescents’ and adolescents’ everyday life. One of the most intriguing research topics about positive effects of VG use is about the domain of visuospatial competencies. Previous research show that training with videogames enables children and adolescents to improve their scores in visuospatial tests (such as mental rotation of shapes and cubes), and that such training could overcome gender differences in these domains. Our study aimed at (1) verifying the positive effects of videogame use in the visuospatial domain both for male and female adolescents and preadolescents and (2) verifying whether the visualization style (2D or isometric 3D) of the VG has an influence about the positive effects of gaming. Six measures of visuospatial competency were administered to 318 preadolescents (mean of age = 13.94 years, range 10–18) prior and after a 3-day training with 2D and 3D Tetris. Results indicate that (1) gaming on the whole has slight positive effects both for males and females in enhancing visuospatial competencies, at least in the short term, and (2) it seems that participants who used the videogame with 2D graphics obtained greater improvements in the mental rotation domain while the participants who used the videogame with 3D graphics obtained greater improvements in the spatial visualization domain. However, a general learning effect between T1 and T2 was measured, which was found regardless of Experimental condition, indicating that the effect of training with videogames can be less relevant than expected.

In Alzheimer’s disease (AD), both cholesterol and glucose dysmetabolism precede the onset of memory deficit and contribute to the disease’s progression. It is indeed now believed that oxidized cholesterol in the form of oxysterols and altered glucose uptake are the main triggers in AD affecting production and clearance of Aβ, and tau phosphorylation. However, only a few studies highlight the relationship between them, suggesting the importance of further extensive studies on this topic. Recently, a molecular link was demonstrated between cholesterol oxidative metabolism and glucose uptake in the brain. In particular, 27-hydroxycholesterol, a key linker between hypercholesterolemia and the increased AD risk, is considered a biomarker for reduced glucose metabolism. In fact, its excess increases the activity of the renin-angiotensin system in the brain, thus reducing insulin-mediated glucose uptake, which has a major impact on brain functioning. Despite this important evidence regarding the role of 27-hydroxycholesterol in regulating glucose uptake by neurons, the involvement of other cholesterol oxidation products that have been clearly demonstrated to be key players in AD cannot be ruled out. This review highlights the current understanding of the potential role of cholesterol and glucose dysmetabolism in AD progression, and the bidirectional crosstalk between these two phenomena.

Although it is noted that interpersonal sensorimotor coordination can influence several high-level socio-cognitive processes, its impact on creative collaboration is nearly unexplored. Here, we investigated the effects of a form of sensorimotor coordination, that is, sensorimotor synchronization, on a subsequent creative collaboration task. 60 pairs (n total = 120 participants) formed by previously unacquainted individuals performed a tower-building task either jointly or alone, followed by a dyadic creativity task. Tower building time in the joint condition was recorded through a sensorized platform and creativity performance was evaluated by two independent raters based on the quantity and quality of generated ideas. We controlled for gender composition and for the disposition to cooperate and to adopt a creative, analytical style. Results showed that male-male couples were more creative after the joint-action condition, whereas female-female and mixed-gender couples were more creative after the solo condition. Regression analyses of tower building time on creativity performance revealed that building time was a significant predictor of creativity dimensions in male-male and in mixed-gender couples but did not predict creative performance in female-female couples. Overall, these findings suggest that the manipulation of sensorimotor coordination can influence performance in a subsequent creative collaboration task, with the nature, and magnitude of this effect depending on the gender composition of the dyads. These results have potential implications for the design of sensorimotor-based strategies to enhance dyadic creative performance in several contexts, especially for the organizational settings.

Glycogenosis VII (GSD VII) is a rare autosomal recessive glycogen storage disorder caused by mutations in the PFKM gene encoding the phosphofructokinase (PFK) enzyme. A classical form with exercise intolerance, contractures, and myoglobinuria, a severe multisystem infantile form, an hemolytic variant and a late-onset form usually presenting with muscle pain and mild fixed proximal weakness have been reported. We describe a 65-year-old man affected by muscle PFK deficiency who, since the age of 33, presented with exercise intolerance and myoglobinuria. Muscle biopsy showed a vacuolar myopathy with glycogen storage. The biochemical assay of PFK-M showed very low residual activity (6%). Genetic analysis of PFKM gene evidenced the presence of the heterozygote c.1817A>C (p.Asp543Ala) and c.488 G>A (p.Arg100Gln) pathogenic mutations. In his fifth decade, he started cyclosporine after liver transplantation for hepatocellular carcinoma and, then, amiodarone because of atrial fibrillation. In the following years, he developed a progressive and severe muscle weakness, mainly involving lower limbs, up to a loss of independent walking. Muscle MRI showed adipose substitution of both anterior and posterior thigh muscles with selective sparing of the medial compartment. Marked signs of adipose substitution were also documented in the legs with a selective replacement of gemelli and peroneus muscles. The temporal relationship between the patient's clinical worsening and chronic treatment with cyclosporine and amiodarone suggests an additive toxic damage by these two potentially myotoxic drugs determining such an unusually severe phenotype, also confirmed by muscle MRI findings.

The early phase of systemic sclerosis (SSc) presents edema as one of the main features: this is clinically evident in the digital swelling (puffy fingers) as well as in the edematous skin infiltration of the early active diffuse subset. Other organs could be affected by this same disease process, such as the lung (with the appearance of ground glass opacities) and the heart (with edematous changes on cardiac magnetic resonance imaging). The genesis of tissue edema is tightly linked to pathological changes in the endothelium: various reports demonstrated the effect of transforming growth factor β, vascular endothelial growth factor and hypoxia-reperfusion damage with reactive oxygen species generation in altering vascular permeability and extravasation, in particular in SSc. This condition has an alteration in the glycocalyx thickness, reducing the protection of the vessel wall and causing non-fibrotic interstitial edema, a marker of vascular leak. Moreover, changes in the junctional adhesion molecule family and other adhesion molecules, such as ICAM and VCAM, are associated with an increased myeloid cells' extravasation in the skin and increased myofibroblasts transformation with further vascular leak and cellular migration. This mini-review examines current knowledge on determinants of vascular leak in SSc, shedding light on the role of vascular protection. This could enhance further studies in the light of drug development for early treatment, suggesting that the control of vascular leakage should be considered in the same way that vasodilation and inflammation reduction, as potential therapeutic targets.

Diverse microorganisms are able to grow on food matrixes and along food industry infrastructures. This growth may give rise to biofilms. This review summarizes, on the one hand, the current knowledge regarding the main bacterial species responsible for initial colonization, maturation and dispersal of food industry biofilms, as well as their associated health issues in dairy products, ready-to-eat foods and other food matrixes. These human pathogens include Bacillus cereus (which secretes toxins that can cause diarrhea and vomiting symptoms), Escherichia coli (which may include enterotoxigenic and even enterohemorrhagic strains), Listeria monocytogenes (a ubiquitous species in soil and water that can lead to abortion in pregnant women and other serious complications in children and the elderly), Salmonella enterica (which, when contaminating a food pipeline biofilm, may induce massive outbreaks and even death in children and elderly), and Staphylococcus aureus (known for its numerous enteric toxins). On the other hand, this review describes the currently available biofilm prevention and disruption methods in food factories, including steel surface modifications (such as nanoparticles with different metal oxides, nanocomposites, antimicrobial polymers, hydrogels or liposomes), cell-signaling inhibition strategies (such as lactic and citric acids), chemical treatments (such as ozone, quaternary ammonium compounds, NaOCl and other sanitizers), enzymatic disruption strategies (such as cellulases, proteases, glycosidases and DNAses), non-thermal plasma treatments, the use of bacteriophages (such as P100), bacteriocins (such us nisin), biosurfactants (such as lichenysin or surfactin) and plant essential oils (such as citral- or carvacrol-containing oils).

Aim: Research has extensively examined the relationship between defense mechanisms (DM) and personality traits. However, no study to date has explored if specific defenses (alone or in combination) are able to predict dysfunctional variants of personality domains, as conceived in the alternative DSM-5 model for personality disorders. This study aimed to investigate the relationship between DMs and DSM-5 maladaptive personality domains among adults.Materials and Methods: Three hundred and twenty-eight adults aged between 18 and 64 years old completed measures on DMs and maladapive personality domains. Regression analyses were performed to determine which DMs predicted the maladaptive personality domains of negative affectivity, detachment, antagonism, disinhibition, and psychoticism.Results: According to psychoanalytic literature, results showed that immature defenses positively predicted maladaptive personality domain scores, whereas mature defenses were generally related with better personality functioning. Moreover, different defense patterns emerged as significant predictors of the maladaptive personality domains comprised in the alternative DSM-5 model for personality disorder.Discussion: Our findings support the view that defense patterns represent core components of personality and its disorders, and suggest that an increased use of immature defenses and a reduced use of mature defenses have a negative impact on the development of personality.

The receptor tyrosine kinase Ron and its ligand, Macrophage Stimulating Protein (MSP), mediate multiple processes involved in the control of cell proliferation, migration and protection from apoptosis. Dysregulated signaling of Ron, due to hyperactivation or loss of negative regulation, is involved in tumor progression and metastasis. Growing evidence indicates that Ron is abnormally expressed and activated in certain types of primary epithelial cancers (i.e. breast, colon, lung, pancreas, bladder and thyroid), where it critically contributes to the maintenance of tumorigenic and invasive phenotype. Furthermore, a positive association between aberrant Ron expression and aggressive biological indicators as well as a worse clinical outcome have been reported in breast, bladder and thyroid carcinomas. Different approaches have proved effective in targeting receptor activation/expression both in vitro and in animal models, leading to reversion of the tumorigenic phenotype. Altogether these results show that Ron is an attractive molecular target for clinical intervention.