Health-related lifestyles among Italian university students: A cross-sectional study.

OBJECTIVES: to investigate lifestyle, health-related behaviours, and nutritional knowledge among a sample of Italian university students and to identify social determinants of - and barriers to - healthier lifestyles. DESIGN: cross-sectional observational study. SETTING AND PARTICIPANTS: students attending degree courses in health professions in a single university in Northern Italy (No. 1,495) were invited to participate in a structured web survey. MAIN OUTCOME MEASURES: a comprehensive, validated questionnaire was used. Questions regarded nutritional knowledge and habits, smoking habit, physical activity, self-efficacy, and barriers to change. Anthropometric and sociodemographic information was collected. Descriptive statistics were used to summarize results. With single and multiple regression models, differences between subgroups and ranked predictors of students' attitudes towards healthy behaviours were analysed. Statistical significance was set at p<0.05. RESULTS: a total of 554 subjects completed the survey (participation rate: 42%; completion rate: 88%). Students showed good nutritional knowledge (73%), but some deficiencies related to low fruit/high sweets consumption, and a lack of basic macronutrients information. Only 30% of the students led a very active lifestyle and physical inactivity was greatest among overweight/obese students. Sedentary lifestyle and unhealthy diet were mainly associated with modifiable risk factors, e.g., being overweight and smoking. CONCLUSIONS: this study provides evidence that health profession students have good knowledge, but their health-related lifestyle is a concern, especially given the role of prescribers that they will play. Structured programmes need to be developed to address the modifiable risk factors associated with detrimental behaviours manifest already during the university years.

Impairments of Photoreceptor Outer Segments Renewal and Phototransduction Due to a Peripherin Rare Haplotype Variant: Insights from Molecular Modeling.

BACKGROUND: Retinitis pigmentosa punctata albescens (RPA) is a particular form of retinitis pigmentosa characterized by childhood onset night blindness and areas of peripheral retinal atrophy. We investigated the genetic cause of RPA in a family consisting of two affected Egyptian brothers with healthy consanguineous parents. METHODS: Mutational analysis of four RPA causative genes was realized by Sanger sequencing on both probands, and detected variants were subsequently genotyped in their parents. Afterwards, found variants were deeply, statistically, and in silico characterized to determine their possible effects and association with RPA. RESULTS: Both brothers carry three missense PRPH2 variants in a homozygous condition (c.910C > A, c.929G > A, and c.1013A > C) and two promoter variants in RHO (c.-26A > G) and RLBP1 (c.-70G > A) genes, respectively. Haplotype analyses highlighted a PRPH2 rare haplotype variant (GAG), determining a possible alteration of PRPH2 binding with melanoregulin and other outer segment proteins, followed by photoreceptor outer segment instability. Furthermore, an altered balance of transcription factor binding sites, due to the presence of RHO and RLBP1 promoter variants, might determine a comprehensive downregulation of both genes, possibly altering the PRPH2 shared visual-related pathway. CONCLUSIONS: Despite several limitations, the study might be a relevant step towards detection of novel scenarios in RPA etiopathogenesis.

Adaptive Modelling of Mutated FMO3 Enzyme Could Unveil Unexplored Scenarios Linking Variant Haplotypes to TMAU Phenotypes.

BACKGROUND: Trimethylaminuria (TMAU) is a rare genetic disease characterized by the accumulation of trimethylamine (TMA) and its subsequent excretion trough main body fluids, determining the characteristic fish odour in affected patients. We realized an experimental study to investigate the role of several coding variants in the causative gene FMO3, that were only considered as polymorphic or benign, even if the available literature on them did not functionally explain their ineffectiveness on the encoded enzyme. METHODS: Mutational analysis of 26 TMAU patients was realized by Sanger sequencing. Detected variants were, subsequently, deeply statistically and in silico characterized to determine their possible effects on the enzyme activity. To achieve this goal, a docking prediction for TMA/FMO3 and an unbinding pathway study were performed. Finally, a TMAO/TMA urine quantification by 1H-NMR spectroscopy was performed to support modelling results. RESULTS: The FMO3 screening of all patients highlighted the presence of 17 variants distributed in 26 different haplotypes. Both non-sense and missense considered variants might impair the enzymatic kinetics of FMO3, probably reducing the interaction time between the protein catalytic site and TMA, or losing the wild-type binding site. CONCLUSIONS: Even if further functional assays will confirm our predictive results, considering the possible role of FMO3 variants with still uncertain effects, might be a relevant step towards the detection of novel scenarios in TMAU etiopathogenesis.

[The relationship between physical exercise and gut microbiota in the human being: a systematic review]. / Relazione tra esercizio fisico e microbiota intestinale nell'essere umano: revisione sistematica.

BACKGROUND: the relationship between physical exercise and gut microbiota has opened new therapeutic frontiers for many inflammatory diseases. However, there is still a lot of uncertainty about how to administer exercise. OBJECTIVES: to review the literature to bridge this gap and examine the relationship between cardiorespiratory fitness (CRF) and microbiota. DESIGN: systematic review. SETTING AND PARTICIPANTS: studies involving humans who undergoing exercise programmes of any lengths, intensities, and types were included. The research was carried out through PubMed, Scopus, and Web of Science. MAIN OUTCOME MEASURES: the primary outcome was change in gut microbiota composition (α and ß-diversity), while the secondary outcome was the CRF level. RESULTS: the 15 studies included (all with PEDro scale <=5) used aerobic training alone or combined with resistance exercises. In general, exercise has shown positive effects on the microbiota, influencing the faecal count of some bacterial phyla (in particular Bacteroidetes, Firmicutes, and Proteobacteria), with a weak tendency towards proportionality in relation to training duration and intensity. However, the evidence supporting the exercise effects on the gut microbiota and the relationship with CRF are of low quality. CONCLUSIONS: despite the weak evidence in favour of the effects of the practice of physical exercise on the intestinal microbiota, there are still many aspects that need to be explored. In particular, future studies shall have higher quality and methodological rigour, standardize the methods for outcome assessment, and determine type and thresholds of interventions intensity and duration.

A novel RLBP1 gene geographical area-related mutation present in a young patient with retinitis punctata albescens.

BACKGROUND: Autosomal recessive forms of retinitis punctata albescens (RPA) have been described. RPA is characterized by progressive retinal degeneration due to alteration in visual cycle and consequent deposit of photopigments in retinal pigment epithelium. Five loci have been linked to RPA onset. Among these, the retinaldehyde-binding protein 1 gene, RLBP1, is the most frequently involved and several founder mutations were reported. We report results of a genetic molecular investigation performed on a large Sicilian family in which appears a young woman with RPA. RESULTS: The proband is in homozygous condition for a novel RLBP1 single-pair deletion, and her healthy parents, both heterozygous, are not consanguineous. Thenovelc.398delC (p.P133Qfs*258) involves the exon 6 and leads to a premature stop codon, resulting in a truncated protein entirely missing of CRAL-TRIO lipid-binding domain. Pedigree analysis showed other non-consanguineous relatives heterozygous for the same mutation in the family. Extension of mutation research in the native town of the proband revealed its presence also in healthy subjects, in a heterozygous condition. CONCLUSIONS: A novel RLBP1 truncating mutation was detected in a young girl affected by RPA. Although her parents are not consanguineous, the mutation was observed in a homozygous condition. Being them native of the same small Sicilian town of Fiumedinisi, the hypothesis of a geographical area-related mutation was assessed and confirmed.

[Evaluating quality and safety in long term care: results from the experimentation of the Smart Star model]. / La valutazione della qualità e sicurezza assistenziale nelle RSA: risultati della sperimentazione del modello Smart Star.

The Smart Star model is a rating system to evaluate the quality of care in nursing homes for the elderly; it uses a five star rating score. We tested the model in a sample of 16 nursing homes in Italy. The Smart Star model showed to be effective in the multidimensional evaluation of the performance of nursing homes. One of the major strengths of the model consisted in its flexibility of application, that suggested its possible adaptation for different areas of healthcare.

CCM3/SERPINI1 bidirectional promoter variants in patients with cerebral cavernous malformations: a molecular and functional study.

BACKGROUND: Cerebral cavernous malformations (CCMs) are vascular anomalies of the nervous system mostly located in the brain presenting sporadically or familial. Causes of familial forms are mutations in CCM1 (Krit1), CCM2 (MGC4607) and CCM3 (PDCD10) genes. Sporadic forms with no affected relative most often have only one lesion and no germ line mutations. However, a number of sporadic cases with multiple lesions have been reported and are indeed genetic cases with a de novo mutation or a mutation inherited from an asymptomatic parent. METHODS: Here, we performed an analysis of regulatory region of CCM genes in 60 sporadic patients, negative for mutations in coding region and intron-exon boundaries and large deletion/duplications in CCM genes by direct sequencing and MLPA. Among 5 variants identified in 851-bp region shared by CCM3 and SERPINI1 genes and acting as asymmetric bidirectional promoter, two polymorphisms c.-639 T > C/rs9853967 and c.-591 T > C/rs11714980 were selected. A case-control study was performed to analyze their possible relationships with sporadic CCMs. Promoter haplotypes activities on CCM3/SERPINI1 genes expression were tested by dual-luciferase assay. RESULTS: No variants were identified in CCM1 and CCM2 regulatory regions. In CCM3/SERPINI1 asymmetric bidirectional promoter 5 variants, 2 of them unknown and 3 corresponding to polymorphisms c.-639 T > C/rs9853967, c.-591 T > C/rs11714980 and c.-359G > A/rs9834676 were detected. While rs9853967 and rs11714980 polymorphisms fall in a critical regulatory fragment outside the minimal promoter in intergenic region, other variants had no effects on transcription factor binding according to RegRNA tool. Case-control study performed on 60 patients and 350 healthy controls showed frequencies of the mutated alleles significantly higher in the control group than in patients. Furthermore, the functional assay showed a significant reduction of CCM3 expression for C-C haplotype even more than for T-C and C-T haplotypes. In SERPINI1 direction, the reduction was not statistically significant. CONCLUSIONS: Our data indicated that rs9853967 and rs11714980 polymorphisms could be associated with a protective role in CCM disease.

[Second victims in healthcare: the stages of recovery following an adverse event]. / Le seconde vittime in sanità: le fasi di recupero dopo un evento avverso.

A second victim has been defined as "a healthcare worker involved in an unanticipated adverse patient event, medical error and/or a patient related-injury who becomes victimized in the sense that the worker is traumatized by the event". The aim of the present research study was to assess the "second victim" phenomenon in Italy. Fifty interviews were conducted with different health care professionals previously involved in medical errors. All study participants clearly remembered the event. Support obtained by second victims was poor and inefficient. Healthcare workers become second victims every day and, considering that human resources are the most important resource of healthcare organizations, it is fundamental to implement valid programs to support and train these workers about the phenomenon.

[Evaluating the quality of care in nursing homes: comparison of three International models]. / La valutazione della qualità nelle residenze sanitarie assistenziali: tre modelli internazionali a confronto.

The aim of this observational descriptive study was to identify the main international models evaluating the quality of nursing homes for non self-sufficient elderly persons, and to apply them in the Italian health system. Firstly, a bibliographic search of institutional websites and Pubmed-Medline was performed to identify the main international models. Secondly, three variables were chosen to evaluate the level of implementability of the models: (1) frequency of use of quality indicators in the international models; (2) degree of constructability of the models in two Italian nursing homes; (3) perceived relevance of the indicators used by the chosen models, by nursing home workers. Thirdly, the chosen models were evaluated. Three international models were identified, respectively used in USA, Canada and Australia. About 80% of the indicators used by the three models were constructable in the two Italian nursing homes that were evaluated. The two nursing homes were "promoted" according to the Canadian model, "better than sufficient" according to the Australian model, but "failed" when US model indicators were applied. The poorest performances in the two Italian nursing homes, with respect to international quality standards, were related to indicators of incontinence, physical restraints (1,1% for USA and 13% for Canada and Australia, versus 55% in one of the nursing homes and 30% in the second home), diagnosis of depressive symptoms, and antipneumococcical vaccination (0% in the two nursing homes, in comparison with the 93,8% in the USA). A low level of performance in prevention and safety matters was identified, while performance was higher for aspects warranted by law. The survey also revealed thatnursing home workers' perceptions of the utility of specific indicators were often based on habit rather than on the actual relevance of care indicators. The development of a model of quality of care that offers a multidimensional evaluation of the level of performance of Italian nursing homes is needed.

[Defensive Medicine: Defensive Medicine: Overview of the literature]. / Overview della letteratura scientifica sul tema medicina difensiva.

A literature review was performed on the subject of defensive medicine, in order to gather information and evidence for identifying a shared definition of this phenomenon, identify its causes, quantify its frequency and its economic impact.Results show that defensive medicine is primarily the result of medical professionals adapting to the pressure of litigation risks, and whose behaviour is motivated by fear of malpractice claims rather than by the patient's health. Defensive medicine seems to have become a diffuse phenomenon, afflicting all diagnostic-therapeutic areas and some disciplines to a greater degree, and leading to a large waste of human, organizational and economic resources.

[Second victims of medical errors: a systematic review of the literature]. / Le seconde vittime in Sanità: una revisione sistematica di letteratura.

"Second victims" are health care providers who remain traumatized and suffer at the psycho-physical level after being involved in a patient adverse event. A systematic review of the literature was conducted to: a) estimate the prevalence of second victims among healthcare workers, b) describe personal and work outcomes of second victims, c) identify coping strategies used by second victims to face their problems, and d) describe current support strategies. Findings reveal that the prevalence of "second victims" of medical errors is high, ranging in four studies from 10.4% to 43.3%. Medical errors have a negative impact on healthcare providers involved, leading to physical, cognitive and behavioural symptoms including the practice of defensive medicine. Managers of health organizations need to be aware of the "second victim" phenomenon and ensure adequate support is given to healthcare providers involved. The best strategy seems to be the creation of networks of support at both the individual and organizational levels. More research is needed to evaluate the efficacy of support structures for second victims and to quantify the extent of the practice of defensive medicine following medical error.

Effectiveness of a combined lifestyle intervention for older people in long-term care: A randomized controlled trial.

PURPOSE: Lifestyle medicine interventions combining physical, nutritional, and psychological components have been found effective in general older population. However, evidence from the long-term care (LTC) is scarce. METHODS: We conducted a pragmatic, two-arm, parallel group, superiority randomized controlled trial. Residents living in a LTC facility for one or more years, able to discern and to express informed consent, and requiring nursing care were considered eligible. The three-months intervention combined bi-weekly physical exercise groups, a healthy diet, and weekly psychological wellbeing sessions. Patients of the control group were subjected to routine care. At the end of the study participants were assessed using Barthel Index, Katz Activities of Daily Living, and Tinetti scales. RESULTS: A total of 54 patients with a mean age of 84 years took part to the study. Physical exercise and psychological wellbeing sessions were mostly attended by all the subjects of the intervention group. Both groups took less calories than planned in the diets; in addition, the intervention group showed a lower energy and carbohydrates intake than the control group. At the end of the study, the intervention group showed a significant improvement in the total scores of all the scales. CONCLUSIONS: This intervention was effective in improving functionality in older people living in the LTC setting. Results were achieved in a short timeframe, likely due to synergistic interactions between components. However, a further exploration of underlying factors is needed, to better understand the barriers that hampered a complete intervention delivery in this context.

Investigating G-quadruplex structures in RPGR gene: Implications for understanding X-linked retinal degeneration.

Aims: This pilot study investigates the potential pathogenic role of G-quadruplex (G4) structures in RPGR-associated retinal degeneration, starting from a case of suspected X-linked form affected family. We hypothesize that the stabilization of these structures might alter DNA replication and transcription, inducing genetic instability and influencing gene expression. Main methods: We conducted whole genome amplification experiments and next-generation sequencing to detect the blockade of polymerase activity by G4 structures. Our specific focus was the RPGR gene, which hosts a high concentration of predicted G4-forming motifs and is implicated in most X-linked retinal degeneration cases. To understand the potential interference of G4 structures, we applied computational and 3D molecular modeling to visualize interferences in DNA replication and transcription regulation. Key findings: Our data confirmed the obstruction of DNA polymerase enzymes by G4 structures, particularly when stabilized by the compound pyridostatin. This obstruction was evident in the reduced amplification of RPGR gene regions and a shift in the start/end sites of putative G4 motifs. Moreover, the modeling indicated a potential disruption of critical promoter elements and RNA polymerase binding, which could drastically alter gene expression. Significance: Our findings suggest that G4 formation in the RPGR gene could lead to genetic instability and affect the expression of RPGR, contributing to retinal dystrophy. Moreover, this study underscores the broader implications of G4 structures in other genetic disorders. Improved understanding of G4 structures could reveal novel therapeutic targets to combat genetic disorders, promoting the advancement of personalized medicine and precision health.

Beneficial effects of a combined lifestyle intervention for older people in a long-term-care facility on redox balance and endothelial function.

Objective: It has recently been highlighted how a short healthy life-style program (LSP) can improve the functional outcomes of older people admitted to a Long-Term Care (LTC) facility. Although it is known that life-style medicine-based interventions can exert anti-aging effects through the modulation of oxidative stress and mitochondrial function, the mechanisms underlying the aforementioned effects have not been clarified, yet. For this reason, in this study, the outcomes were focused on the investigation of the possible mechanisms underlying the benefits of a short LSP in older people. This was achieved by examining circulating markers of oxidative stress and immunosenescence, such as Tymosin ß (Tß4), before and after LSP and the effects of plasma of older people undergone or not LSP on endothelial cells. Methods: Fifty-four older people were divided into two groups (n = 27 each): subjects undergoing LSP and subjects not undergoing LSP (control). The LSP consisted of a combination of caloric restriction, physical activity, and psychological intervention and lasted 3 months. Plasma samples were taken before (T0) and after LSP (T1) and were used to measure thiobarbituric acid reactive substances (TBARS), 8-hydroxy-2-deoxyguanosine (8OHdG), 8-Isoprostanes (IsoP), glutathione (GSH), superoxide dismutase (SOD) activity and Tß4. In addition, plasma was used to stimulate human vascular endothelial cells (HUVEC), which were examined for cell viability, mitochondrial membrane potential, reactive oxygen species (ROS) and mitochondrial ROS (MitoROS) release. Results: At T1, in LSP group we did not detect the increase of plasma TBARS and IsoP, which was observed in control. Also, plasma levels of 8OHdG were lower in LSP group vs control. In addition, LSP group only showed an increase of plasma GSH and SOD activity. Moreover, plasma levels of Tß4 were more preserved in LSP group. Finally, at T1, in HUVEC treated with plasma from LSP group only we found an increase of the mitochondrial membrane potential and a reduction of ROS and MitoROS release in comparison with T0. Conclusions: The results of this study showed that a short LSP in older persons exerts antiaging effects by modulating oxidative stress also at cellular levels. Implications of those findings could be related to both prognostic and therapeutic strategies, which could be pursued as antiaging methods.

The practice of defensive medicine among Jordanian physicians: A cross sectional study.

BACKGROUND: Defensive medicine (DM) is a deviation from medical practice that is induced primarily by a threat of liability. While the DM behavior is well studied in the developed countries, little is known in developing countries and never been evaluated in Jordan. OBJECTIVE: To evaluate the prevalence of DM practice in Jordan among physicians and to investigate reasons behind its practice and potential strategies to alleviate this practice. METHODS: In this Cross-sectional study, self-administered questionnaire was distributed to a sample of physicians in both public and private sectors in Jordan. The collection period was from Jan 2021 to June 2021. The prevalence of DM practice was estimated among the study sample. Frequency scores of different DM behaviors, reasons of DM behaviors, and effectiveness of strategies in changing DM behaviors were summarized as average frequency scores with standard deviations. Multivariable linear regression models were conducted to evaluate potential predictors of total assurance and avoidance behavior scores. RESULTS: A total of 175 Jordanian physicians completed the survey. The prevalence of adopting (or witnessing) DM behaviors among the study sample was 68% (n = 119). Diagnostic laboratory exams followed by prescribed medications were the most practiced behaviors in excessive rate during a typical working week. Unfavorable legislation for the physician was reported as the headmost reason for practicing DM, followed by pressure from the public and mass media opinion. Continuous update of knowledge, abilities, and performance and following specific protocols and/or appropriate clinical evidence and appropriate multidisciplinary and multi-professional communication were the most effective strategies that can mitigate DM behaviors. CONCLUSIONS: Defensive medicine practice is common among Jordanian physicians with concerns about increasing pattern in the future.

Longitudinal monitoring of SARS-CoV-2 viral load in self-collected saliva from health care workers during breakthrough infections to spare working days.

IMPORTANCE: Real-time quantitative PCR (RT-qPCR) on nasopharyngeal swabs (NPS) has been used as the standard method for detecting and monitoring SARS-CoV-2 infection during the pandemic. However, NPS collection often causes discomfort and poses a higher risk of transmission to health care workers (HCW). Furthermore, RT-qPCR only provides relative quantification and does not allow distinguishing those samples with residual, no longer active infection, whereas droplet digital PCR (ddPCR) allows for precise quantification of viral load, offering greater sensitivity and reproducibility. This study highlights the effectiveness of using self-collected saliva as a convenient and reliable sampling method. By utilizing ddPCR to measure the SARS-CoV-2 viral load in saliva samples, individuals with low or undetectable viral loads can be quickly identified. This approach is particularly advantageous for surveillance programs targeting HCW, as it enables the early identification and release of uninfected personnel, minimizing lost workdays. Additionally, analyzing viral load in saliva samples by ddPCR is valuable in determining virus shedding duration across different SARS-CoV-2 variants, informing transmission and disease control. Finally, testing saliva could overcome the detection of historic cases due to prolonged RNA swabbing past-infection and the unnecessary exclusion of those individuals from the workplace.

UPO Biobank: The Challenge of Integrating Biobanking into the Academic Environment to Support Translational Research.

Biobanks are driving motors of precision and personalized medicine by providing high-quality biological material/data through the standardization and harmonization of their collection, preservation, and distribution. UPO Biobank was established in 2020 as an institutional, disease, and population biobank within the University of Piemonte Orientale (UPO) for the promotion and support of high-quality, multidisciplinary studies. UPO Biobank collaborates with UPO researchers, sustaining academic translational research, and supports the Novara Cohort Study, a longitudinal cohort study involving the population in the Novara area that will collect data and biological specimens that will be available for epidemiological, public health, and biological studies on aging. UPO Biobank has been developed by implementing the quality standards for the field and the ethical and legal issues and normative about privacy protection, data collection, and sharing. As a member of the "Biobanking and Biomolecular Resources Research Infrastructure" (BBMRI) network, UPO Biobank aims to expand its activity worldwide and launch cooperation with new national and international partners and researchers. The objective of this manuscript is to report an institutional and operational experience through the description of the technical and procedural solutions and ethical and scientific implications associated with the establishment of this university research biobank.

Human retinal secretome: A cross-link between mesenchymal and retinal cells.

In recent years, mesenchymal stem cells (MSC) have been considered the most effective source for regenerative medicine, especially due to released soluble paracrine bioactive components and extracellular vesicles. These factors, collectively called the secretome, play crucial roles in immunomodulation and in improving survival and regeneration capabilities of injured tissue. Recently, there has been a growing interest in the secretome released by retinal cytotypes, especially retinal pigment epithelium and Müller glia cells. The latter trophic factors represent the key to preserving morphofunctional integrity of the retina, regulating biological pathways involved in survival, function and responding to injury. Furthermore, these factors can play a pivotal role in onset and progression of retinal diseases after damage of cell secretory function. In this review, we delineated the importance of cross-talk between MSCs and retinal cells, focusing on common/induced secreted factors, during experimental therapy for retinal diseases. The cross-link between the MSC and retinal cell secretomes suggests that the MSC secretome can modulate the retinal cell secretome and vice versa. For example, the MSC secretome can protect retinal cells from degeneration by reducing oxidative stress, autophagy and programmed cell death. Conversely, the retinal cell secretome can influence the MSC secretome by inducing changes in MSC gene expression and phenotype.

Amplification of protease-activated receptors signaling in sporadic cerebral cavernous malformation endothelial cells.

In the central nervous system, thrombin-mediated activation of protease-activated receptors (PARs) results in neuroinflammation and increased vascular permeability. These events have been linked to cancer and neurodegeneration. Endothelial cells (ECs) isolated from sporadic cerebral cavernous malformation (CCM) specimens showed dysregulation of genes involved in "thrombin-mediated PAR-1 activation" signaling. CCM is a vascular disease involving brain capillaries. In CCM, ECs show defective cell junctions. Oxidative stress and neuroinflammation play a key role in disease onset and progression. In order to confirm the possible role of thrombin pathway in sporadic CCM pathogenesis, we evaluated PARs expression in CCM-ECs. We found that sporadic CCM-ECs overexpress PAR1, PAR3 and PAR4, together with other coagulation factor encoding genes. Moreover, we investigated about expression of the three familial CCM genes (KRIT1, CCM2 and PDCD10) in human cerebral microvascular ECs, following thrombin exposure, as well as protein level. Thrombin exposure affects EC viability and results in dysregulation of CCM gene expression and, then, in decreased protein level. Our results confirm amplification of PAR pathway in CCM suggesting, for the first time, the possible role of PAR1-mediated thrombin signaling in sporadic CCM. Thrombin-mediated PARs over activation results in increased blood-brain barrier permeability due to loss of cell junction integrity and, in this context, also the three familial CCM genes may be involved.

Expression of sarcoglycans in the human cerebral cortex: an immunohistochemical and molecular study.

The sarcoglycan (SG) complex (SGC) is a subcomplex within the dystrophin-glycoprotein complex (DGC) and is composed of several transmembrane proteins (α, ß, δ, γ, ε and ζ). The DGC supplies a transmembranous connection between the subsarcolemmal cytoskeleton networks and the basal lamina in order to protect the lipid bilayer and to provide a scaffold for signaling molecules in all muscle cells. In addition to its role in muscle tissue, dystrophin and some DGC components are expressed in neurons and glia. Very little is known about the SG subunits in the central nervous system (CNS) and some data suggested the presence of ε and ζ subunits only. In fact, mutations in the ε-SG gene cause myoclonus-dystonia, indicating its importance for brain function. To determine the presence and localization of SGC in the human cerebral cortex, we performed an investigation using immunofluorescence, immunoblotting and reverse transcriptase polymerase chain reaction. The results showed that all SG subunits are expressed in the human cerebral cortex, particularly in large neurons but also in astrocytes. These data suggest that the SG subcomplex may be involved in the organization of CNS synapses.