Evaluation of circulating microRNA profiles in blood as potential candidate biomarkers in a subacute ruminal acidosis cow model - a pilot study.

BACKGROUND: Subacute ruminal acidosis (SARA) is a metabolic disorder often observed in high-yielding dairy cows, that are fed diets high in concentrates. We hypothesized that circulating miRNAs in blood of cows could serve as potential candidate biomarkers to detect animals with metabolic dysbalances such as SARA. MicroRNAs (miRNAs) are a class of small non-coding RNAs, serving as regulators of a plethora of molecular processes. To test our hypothesis, we performed a pilot study with non-lactating Holstein-Friesian cows fed a forage diet (FD; 0% concentrate, n = 4) or a high-grain diet (HG; 65% concentrate, n = 4) to induce SARA. Comprehensive profiling of miRNA expression in plasma and leucocytes were performed by next generation sequencing (NGS). The success of our model to induce SARA was evaluated based on ruminal pH and was evidenced by increased time spent with a pH threshold of 5.8 for an average period of 320 min/d. RESULTS: A total of 520 and 730 miRNAs were found in plasma and leucocytes, respectively. From these, 498 miRNAs were shared by both plasma and leucocytes, with 22 miRNAs expressed exclusively in plasma and 232 miRNAs expressed exclusively in leucocytes. Differential expression analysis revealed 10 miRNAs that were up-regulated and 2 that were down-regulated in plasma of cows when fed the HG diet. A total of 63 circulating miRNAs were detected exclusively in the plasma of cows with SARA, indicating that these animals exhibited a higher number and diversity of circulating miRNAs. Considering the total read counts of miRNAs expressed when fed the HG diet, differentially expressed miRNAs ( log2 fold change) and known function, we have identified bta-miR-11982, bta-miR-1388-5p, bta-miR-12034, bta-miR-2285u, and bta-miR-30b-3p as potential candidates for SARA-biomarker in cows by NGS. These were further subjected to validation using small RNA RT-qPCR, confirming the promising role of bta-miR-30b-3p and bta-miR-2285. CONCLUSION: Our data demonstrate that dietary change impacts the release and expression of miRNAs in systemic circulation, which may modulate post-transcriptional gene expression in cows undergoing SARA. Particularly, bta-miR-30b-3p and bta-miR-2285 might serve as promising candidate biomarker predictive for SARA and should be further validated in larger cohorts.

Time trends, frequency, characteristics and prognosis of short-duration transient global amnesia.

BACKGROUND AND PURPOSE: Transient global amnesia (TGA) is characterized by a sudden onset of anterograde amnesia lasting up to 24 h. One major differential for TGA is transient epileptic amnesia, which typically lasts < 1 h. However, TGA can also be short in duration and little is known about the time trends, characteristics and prognosis of TGA cases lasting < 1 h. METHODS: We compared the clinical features of TGA ascertained in two independent cohort studies in Oxfordshire, UK [Oxford cohort 1977-1987 versus Oxford Vascular Study (OXVASC) 2002-2018] to determine the time trends of clinical features of TGA. Results were validated in another independent contemporary TGA cohort in Italy [Northern Umbria TGA registry (NU) 2002-2018]. We compared the risk factors, clinical features and long-term prognosis (major cardiovascular events, recurrent TGA and seizure/epilepsy) of patients presenting with episodes lasting < 1 h versus those lasting ≥ 1 h. RESULTS: Overall, 639 patients with TGA were included (114 Oxford cohort, 100 OXVASC, 425 NU). Compared with the original Oxford cohort, there were more cases with TGA lasting < 1 h in OXVASC [32 (32.0%) vs. 9 (8.8%)] and NU (11.8% vs. 8.8% in Oxford cohort). In both OXVASC and NU, patient age, vascular risk factors and clinical features were largely similar between those with TGA lasting < 1 h versus those lasting ≥ 1 h. Moreover, there was no difference in the long-term risk of seizure/epilepsy or major cardiovascular events between TGA lasting < 1 h versus TGA lasting ≥ 1 h. CONCLUSIONS: Short-duration TGA episodes (<1 h) were not uncommon and were more frequent than in earlier studies. The clinical features and long-term prognosis of short-duration TGA did not differ from more typical episodes lasting ≥ 1 h.

Subgroup comparison according to clinical phenotype and serostatus in autoimmune encephalitis: a multicenter retrospective study.

BACKGROUND AND PURPOSE: Autoimmune encephalitides (AE) include a spectrum of neurological disorders whose diagnosis revolves around the detection of neuronal antibodies (Abs). Consensus-based diagnostic criteria (AE-DC) allow clinic-serological subgrouping of AE, with unclear prognostic implications. The impact of AE-DC on patients' management was studied, focusing on the subgroup of Ab-negative-AE. METHODS: This was a retrospective multicenter study on patients fulfilling AE-DC. All patients underwent Ab testing with commercial cell-based assays (CBAs) and, when available, in-house assays (immunohistochemistry, live/fixed CBAs, neuronal cultures) that contributed to defining final categories. Patients were classified as Ab-positive-AE [N-methyl-d-aspartate-receptor encephalitis (NMDAR-E), Ab-positive limbic encephalitis (LE), definite-AE] or Ab-negative-AE (Ab-negative-LE, probable-AE, possible-AE). RESULTS: Commercial CBAs detected neuronal Abs in 70/118 (59.3%) patients. Testing 37/48 Ab-negative cases, in-house assays identified Abs in 11 patients (29.7%). A hundred and eighteen patients fulfilled the AE-DC, 81 (68.6%) with Ab-positive-AE (Ab-positive-LE, 40; NMDAR-E, 32; definite-AE, nine) and 37 (31.4%) with Ab-negative-AE (Ab-negative-LE, 17; probable/possible-AE, 20). Clinical phenotypes were similar in Ab-positive-LE versus Ab-negative-LE. Twenty-four/118 (20.3%) patients had tumors, and 19/118 (16.1%) relapsed, regardless of being Ab-positive or Ab-negative. Ab-positive-AE patients were treated earlier than Ab-negative-AE patients (P = 0.045), responded more frequently to treatments (92.3% vs. 65.6%, P < 0.001) and received second-line therapies more often (33.3% vs. 10.8%, P = 0.01). Delays in first-line therapy initiation were associated with poor response (P = 0.022; odds ratio 1.02; confidence interval 1.00-1.04). CONCLUSIONS: In-house diagnostics improved Ab detection allowing better patient management but was available in a patient subgroup only, implying possible Ab-positive-AE underestimation. Notwithstanding this limitation, our findings suggest that Ab-negative-AE and Ab-positive-AE patients share similar oncological profiles, warranting appropriate tumor screening. Ab-negative-AE patients risk worse responses due to delayed and less aggressive treatments.

Characterization of microRNA in the follicular fluid of patients undergoing assisted reproductive technology.

Female fertility plays a decisive role in the reproduction of mammals, with related issues that include oocyte or embryo quality, establishment of pregnancy, and the physiology of the tissues that contribute to reproduction and metabolic disorders associated with reproductive failure. Although reproductive failure may be attributed to various factors in different species, female infertility is largely controlled by a number of molecular signals that can be regulated in a cycle- and tissue-dependent manner.

Is primary meningococcal arthritis in children more frequent than we expect? Two pediatric case reports revealed by molecular test.

BACKGROUND: Primary meningococcal arthritis is a rare infectious disease that occurs in less than 3% of meningococcal infections and is characterized by arthritis without meningitis, fever, rash, or hemodynamic instability Barahona [Case Rep Orthop 4696014:2017 ]. There are no validated clinical criteria that can be used for the diagnosis. We present two pediatric cases of atypical presentation of meningococcal disease revealed by molecular tests. CASE PRESENTATION: The clinical presentation of the two children (6- and 9-years-old) was characterized by signs of arthritis. By Real Time Polymerase Chain Reaction (RT-PCR), we identified N. meningitidis serogroup Y in the joint fluid in both cases. After specific antimicrobial treatment, the clinical conditions of the two patients quickly improved during hospitalization. CONCLUSIONS: We believe that the incidence of meningococcal arthritis could be underestimated in those settings where the use of RT-PCR is limited. Clearer data on the incidence of meningococcal disease would help to design specific treatments and the best possible national vaccine strategies [Fiji Sci Rep 23:39784, 2016, J Infect 67:385-90, 2013].

Impact of a supportive care service for cancer outpatients: management and reduction of hospitalizations. Preliminary results of an integrated model of care.

PURPOSE: Supportive care in oncology is a primary need for every oncology department nowadays. In 2012, in our institution, a dedicated supportive care service (SCS) was created in order to deal with any need our on-treatment patients might have (e.g. tumour-related or treatment-related symptoms). We hypothesized that this service had a positive impact on the number of unplanned hospitalizations; to confirm our hypothesis, we decided to review admission data in 2011 and 2012. METHODS: Using our internal software, we compared admission data in 2011 (that is, the year before the dedicated service was created) and 2012 (when such service began, that is April of that year). We also made an evaluation of the costs of these hospitalizations. RESULTS: Despite an increase of the number of patients treated in our day hospital (+6.5 %), the number of unplanned hospital admissions decreased by 3.2 % (from 17.3 to 14.1 %). The number of patients accessing to emergency room went from 66 to 61 % (a reduction of 5 %). The costs of these hospitalizations were reduced by 2.2 %. CONCLUSIONS: The introduction of the dedicated SCS in our oncology department caused a net reduction by 3.2 % of the number of unplanned hospitalizations of on-treatment cancer patients.

Work related stress and blood glucose levels.

AIM: The aim of the study is to evaluate work-related subjective stress in a group of workers on a major Italian company in the field of healthcare through the administration of a valid "questionnaire-tool indicator" (HSE Indicator Tool), and to analyze any correlation between stress levels taken from questionnaire scores and blood glucose values. MATERIAL AND METHODS: We studied a final sample consisting of 241 subjects with different tasks. The HSE questionnaire - made up of 35 items (divided into 7 organizational dimensions) with 5 possible answers - has been distributed to all the subjects in occasion of the health surveillance examinations provided by law. The questionnaire was then analyzed using its specific software to process the results related to the 7 dimensions. These results were compared using the Pearson correlation and multiple linear regression with the blood glucose values obtained from each subject. RESULTS: From the analysis of the data the following areas resulted critical, in other words linked to an intermediate (yellow area) or high (red area) condition of stress: sustain from managers, sustain from colleagues, quality of relationships and professional changes. A significant positive correlation (p <0.05) between the mean values of all critical areas and the concentrations of glucose values have been highlighted with the correlation index of Pearson. Multiple linear regression confirmed these findings, showing that the critical dimensions resulting from the questionnaire were the significant variables that can increase the levels of blood glucose. CONCLUSION: The preliminary results indicate that perceived work stress can be statistically associated with increased levels of blood glucose.

Risk of jugular compression blocks in workers exposed to prolonged upright posture.

BACKGROUND: The working posture affects the peripheral venous circulation, although the current literature does not report any correlation between working posture and the abnormalities of the jugular veins flow. The purpose of this preliminary research is to study, in female workers, the prevalence of Venous Compressive Syndrome (VCS) caused by total block of the internal jugular veins flow, so-called "White Compression". Due to complete compression by postural, muscular, fascial, anatomical or bone anomalies, White Compression is not visible by EchoColorDoppler (ECD) and its flow can only be detected by the rotational movements of the head or by Valsalva's maneuver. METHODS: We studied a sample of female workers with ECD (n=128), in supine and upright position divided into subgroups according to the obliged posture maintained during working hours: group A, seated work (n = 61; 47.7%); group B, standing work (n = 41; 32.0%); group C, mixed (both standing and seated work) (n = 26; 20.3%). The total sample (n = 128) had the mean age of 46 ± 10 years (minimum 18 and maximum 67 years) and mean Body Mass Index (BMI) of 23 ± 4 kg/m2 (min 16 kg/m2 and a maximum of 42 kg/m2). RESULTS: Group A and group C did not show any White Compression in orthostatic and clinostatic position. The 9.75% (p = 0.0125) of Group B had a White Compression in orthostatic position: two female workers on the left side (4.9%) and two female workers on the right side (4.9%). CONCLUSIONS: We conclude that there is a risk of jugular compression blocks in female workers exposed to prolonged upright posture. Yet there is no longitudinal study that identifies the White Compressions as etiology of a chronic neurodegenerative disease. The authors hope that some wider studies can confirm the prevalence of these compressions in standing posture and their patho-physiological consequences.

Work-related stress in healthcare workers.

BACKGROUND: In the assessment of work-related stress it is crucial to find the factors that generate and increase it in order to identify categories of individuals at risk, to plan interventions for prevention, elimination or reduction of risk. The aim of the study is to assess the subjective stress in 68 workers of a large Italian company dealing with human health, through the use of a questionnaire-indicating tool, elaborated by the Italian National Institute for insurance against accidents at work (INAIL) and developed by the Health and Safety Executive (HSE). METHODS: We studied a final sample of 68 individuals (34 drivers/rescuers and 34 video display unit (VDU) operators). The questionnaire consists of 35 items (divided into six areas) with five possible answers each, that cover working conditions considered potential causes of stress. RESULTS: The drivers/rescuers had a better performance than the VDU operators, especially in the areas "demand", "relationships" and "role". We compared men and women in the two groups, finding that, in VDU operators, women had a better performance than men in all areas, except "role" and "changes", in which the overall scores were the same in men and women. In the drivers/rescuers women showed more critical scores in the items "relationships" and "change". CONCLUSION: The results show that: the questionnaire-indicating tool is useful, with a demonstrated effectiveness for the occupational physician during the visits and proven validity; additional future efforts should focus on understanding the psycho-social, organizational and individual problems related to stress and the consequent implementation of preventive measures.

How autistic women are aware of their body and take care of their health? Focus on menstruation cycles and gynecological care.

Objective: The combination of femininity and inequality is an increasingly studied in the field of social medicine, even more if the girls or women in question experience conditions of disability or neurodivergence. The onset of menstruation, menarche, constitutes a significant and transformative event in women's lives comprising a true and proper watershed in mental and reproductive health and sexual welfare. The onset of menstruation has a profound effect not just for girls but, in the case of disabled girls, for the whole family. In this scoping review, we have researched the literature in studies which consider the issue of menstruation and autism. The works in scientific literature have been selected which, in the last 5 years, investigated the issue of menstrua-tion for autistic girls and/or women. Results: Selected studies, although few in number, have all equally evidenced the total lack of in-depth understanding of this theme, notwithstanding the fact that females, girls and women with autism would benefit from specialized services if these existed. Families, girls and women involved, moreover, although not experiencing menstruation per se in a negative light, note a deterioration in their condition particularly in respect of sensorial perception and the intensification of anxious depressive instances. This work highlights the need to deepen the aspects concerning the period in autistic girls/women, up to now the question appears to have been little studied, investigated in an uneven way. We propose a social medical program to improve sexual-affective knowledge and body awareness in autistic people.

Overall survival for sorafenib plus interleukin-2 compared with sorafenib alone in metastatic renal cell carcinoma (mRCC): final results of the ROSORC trial.

BACKGROUND: The ROSORC trial, a randomised, phase II trial comparing sorafenib plus interleukin (IL-2) versus sorafenib alone as first-line treatment of metastatic renal cell carcinoma (mRCC) failed to demonstrate differences in progression-free survival (PFS). Updated overall survival (OS) results are reported. PATIENTS AND METHODS: In this study, 128 patients were randomised to receive sorafenib 400 mg twice daily plus subcutaneous IL-2 4.5 million international units (MIU) five times per week for 6 weeks every 8 weeks (arm A) or sorafenib alone (arm B). OS was estimated with the Kaplan-Meier method and compared with the two-sided log-rank test. RESULTS: After a median follow-up of 58 months (interquartile range: 28-63 months), the median OS was 38 and 33 months in arms A and B, respectively (P = 0.667). The 5-year OS was 26.3% [95% confidence interval (CI) 15.9-43.5) and 23.1% (95% CI 13.2-40.5) for the combination- and single-agent arm, respectively. Most of the patients who were refractory to first-line treatment were subsequently treated with different targeted agents; they had a median survival greater than expected. CONCLUSIONS: This outcome suggests a synergistic effect of the subsequent therapies following sorafenib failure. CLINICALTRIALSGOV IDENTIFIER: NCT00609401.

Reproductive and post-reproductive life history of wild-caught Drosophila melanogaster under laboratory conditions.

The life history of the fruit fly (Drosophila melanogaster) is well understood, but fitness components are rarely measured by following single individuals over their lifetime, thereby limiting insights into lifetime reproductive success, reproductive senescence and post-reproductive lifespan. Moreover, most studies have examined long-established laboratory strains rather than freshly caught individuals and may thus be confounded by adaptation to laboratory culture, inbreeding or mutation accumulation. Here, we have followed the life histories of individual females from three recently caught, non-laboratory-adapted wild populations of D. melanogaster. Populations varied in a number of life-history traits, including ovariole number, fecundity, hatchability and lifespan. To describe individual patterns of age-specific fecundity, we developed a new model that allowed us to distinguish four phases during a female's life: a phase of reproductive maturation, followed by a period of linear and then exponential decline in fecundity and, finally, a post-ovipository period. Individual females exhibited clear-cut fecundity peaks, which contrasts with previous analyses, and post-peak levels of fecundity declined independently of how long females lived. Notably, females had a pronounced post-reproductive lifespan, which on average made up 40% of total lifespan. Post-reproductive lifespan did not differ among populations and was not correlated with reproductive fitness components, supporting the hypothesis that this period is a highly variable, random 'add-on' at the end of reproductive life rather than a correlate of selection on reproductive fitness. Most life-history traits were positively correlated, a pattern that might be due to genotype by environment interactions when wild flies are brought into a novel laboratory environment but that is unlikely explained by inbreeding or positive mutational covariance caused by mutation accumulation.

[Legal medical considerations on a case of erectile dysfunction]. / Considerazioni medicolegali su un caso di disfunzione erettile.

The primary obstruction of the bladder neck is a condition which is diagnosed in many young people with symptoms of lower urinary tract, such as obstructive symptoms (difficulty in the initial phase of urination and urinary retention) and irritative symptoms (pollakiuria, dysuria and nocturia). These tests are needed for the diagnosis: uroflowmetry, urodynamics, rx urethrocystography. For the treatment are used alpha-blockers or surgery. The main diagnostic test is the urodynamic study. Even though the alpha-blockers are effective and safe drugs, sometimes the treatment is surgical. The gold standard is the transurethral incision of the prostate or bladder neck (TUIP), a technique with good results, but with some complications, including retrograde ejaculation, that is the most dangerous, and erectile dysfunction, that occurs in a lower percentage of patients. In this work was studied, in terms of forensic medicine, the case of a patient who is 35 years old and reported erectile dysfunction after an intervention of transurethral incision of the prostate or bladder neck. Although there is a limited possibility, documented in the literature, of erectile dysfunction as a result of TUIP, there is no sufficient evidence to confer the responsibility of patient's organic nature impotence to the health professional civil conduct which is directly related to the transurethral incision of the bladder neck, considering the presence of a lumbo-sacral disc disease in the patient, documented by CT two years before the surgery.

Malpractice claims in interventional radiology: frequency, characteristics and protective measures.

PURPOSE: The use of interventional radiology procedures has considerably increased in recent years, as has the number of related medicolegal litigations. This study aimed to highlight the problems underlying malpractice claims in interventional radiology and to assess the importance of the informed consent process. MATERIALS AND METHODS: The authors examined all insurance claims relating to presumed errors in interventional radiology filed by radiologists over a period of 14 years after isolating them from the insurance database of all radiologists registered with the Italian Society of Medical Radiology (SIRM) between 1 January1993 and 31 December 2006. RESULTS: In the period considered, 98 malpractice claims were filed against radiologists who had performed interventional radiology procedures. In 21 cases (21.4%), the event had caused the patient's death. In >80% of cases, the event occurred in a public facility. The risk of a malpractice claim for a radiologist practising interventional procedures is 47 per 1,000, which corresponds to one malpractice claim for each 231 years of activity. DISCUSSION: Interventional radiology, a discipline with a biological risk profile similar to that of surgery, exposes practitioners to a high risk of medicolegal litigation both because of problems intrinsic to the techniques used and because of the need to operate on severely ill patients with compromised clinical status. CONCLUSIONS: Litigation prevention largely depends on both reducing the rate of medical error and providing the patient with correct and coherent information. Adopting good radiological practices, scrupulous review of procedures and efficiency of the instruments used and audit of organisational and management processes are all factors that can help reduce the likelihood of error. Improving communication techniques while safeguarding the patient's right to autonomy also implies adopting clear and rigorous processes for obtaining the patient's informed consent to the medical procedure.

[Medico legal considerations on prosthesis surgery of the erectile dysfunction in a La Peyronie disease case]. / Considerazioni medico legali sulla chirurgia protesica della disfunzione erettile in un caso di malattia di La Peyronie.

Peyronie's disease is characterized by the presence of an inelastic fibrous plaque of the penile tunica albuginea affecting 3-10% of the male population. The fibrous scar causes the curvature of the erect penis, which prevents the penetration. In the stabilization phase the plaque can cause a variable degree of erectile dysfunction (20-54%). In the treatment of the chronic disease, surgery is the gold standard and in case of concomitant erectile dysfunction the placement of a penile prosthesis is indicated. This surgery is loaded with an increase of the variables which can affect the outcome, such as individual clinical features and functionality of the device. The present case concerns a patient suffering from erectile dysfunction associated with Peyronie's disease who underwent surgery for implantation of hydraulic three-component penile prosthesis. After surgery a malfunction of the prosthesis was detected, which required unloading measures under sedation and a surgical revision of the scrotal pump. The latter was followed by the displacement of the prosthesis' cylinder and by a new surgical treatment for the reintegration of the prosthesis and the repair of the left corpus cavernosum. After two months a wrong positioning of the two cylinders inserted into the corpora cavernosa, with the left cranial extreme positioned 2 cm below the contralateral, was detected. In this case the failure of surgical treatment highlights a negligent behavior and the responsibility of the doctors by failing to examine adequately the variables, both clinical and not clinical, that might affect the outcome of the intervention.

Parents-children co-regulation as therapeutic variable and target in autism spectrum disorders. From observation of drive to need of cooperative parent-mediated therapy.

Abstract: Autism spectrum disorders (ASDs) belong to the category of neurodevelopmental disorders. ASD emerges in early childhood and involves deficits in communication, language, behavioural inflexibility and fixity, and sensorial neurodivergent perception. ASDs have a biological pathogenesis related to genetic and epigenetic factors. Additionally, research has shown that starting from childhood, autistic persons could find emotional regulation challenging during communication with caregivers. The importance of emotional co-regulation has always been under-lined in psychology, starting with Freud who introduced the concept of the Compassionate Other. Emotional difficulties are grasped immediately and almost instinctively by parents, who try to modulate their approach to the child's needs from the very beginning. This paper seeks to highlight the importance of emotional co-regulation as a wake-up call-in developmental trajectories that present peculiarities or anomalies. It also emphasizes the significance of emotional co-regulation as a useful tool for intervening in the dysfun-ctionality of such trajectories. This intervention aims to directly involve parents in treatment, as seen in Cooperative parent-mediated therapy. This approach is crucial for facilitating the evolution of the cognitive framework while utilizing this target. This article aims to review the most recent literature on co-regulation after explaining the theoretical framework that gave rise to this concept. It's now well established the importance of adopting a develop-mental approach that starts from the bodily dimension as the basis for the relationship with caregivers, pairs, and unfamiliar people. It is from this basis that starts the affective, emotional, and cognitive construction of the internal and external world of the child. This scoping review takes into account the most recent evidence on co-regulation and autism, emphasizing the importance of this process in diagnostic and therapeutic settings.

Case Report: A child with NFKB1 haploinsufficiency explaining the linkage between immunodeficiency and short stature.

We report the case of a patient with common variable immunodeficiency (CVID) presenting with short stature and treated with recombinant human growth hormone (rhGH). Whole exome sequencing revealed a novel single-nucleotide duplication in the NFKB1 gene (c.904dup, p.Ser302fs), leading to a frameshift and thus causing NFKB1 haploinsufficiency. The variant was considered pathogenic and was later found in the patient's mother, also affected by CVID. This is the first reported case of a patient with CVID due to NFKB1 mutation presenting with short stature. We analyzed the interconnection between NFKB1 and GH - IGF-1 pathways and we hypothesized a common ground for both CVID and short stature in our patient.

Levetiracetam versus carbamazepine in patients with late poststroke seizures: a multicenter prospective randomized open-label study (EpIC Project).

BACKGROUND: Strokes are the leading cause of epileptic seizures in adults and account for 50% of seizures in those over the age of 65 years. The use of antiepileptic drugs to prevent recurrent poststroke seizures is recommended. METHODS: One hundred and twenty-eight patients with poststroke seizures were randomly allocated to treatment with either levetiracetam (LEV) or sustained-release carbamazepine (CBZ) in a multicenter randomized open-label study. After a titration study phase (2 weeks), the optimal individual dose of trial medication was determined and treatment was continued for another 52 weeks. The primary endpoint was defined as the proportion of seizure-free patients; the secondary endpoints were: evaluation of time recurrence to the first seizure, EEG tracings, cognitive functions and side effects. RESULTS: Of 128 patients, 22 discontinued the trial prematurely; thus a total of 106 patients (52 treated with LEV and 54 treated with CBZ) were included in the analysis. The results of the study were as follows: no significant difference in number of seizure-free patients between LEV and CBZ (p = 0.08); time to the first recurrence tended to be longer among patients on LEV; there was no correlation between the therapeutic effect and the EEG findings in either treatment group; LEV caused significantly fewer (p = 0.02) side effects than CBZ; attention deficit, frontal executive functions and functional scales (Activities of Daily Living and Instrumental Activities of Daily Living indices) were significantly worse in the CBZ group. CONCLUSIONS: This trial suggests that LEV may be a valid alternative to CBZ in poststroke seizures, particularly in terms of efficacy and safety. In addition, our results show that LEV has significant advantages over CBZ on cognitive functions. This trial also indicates that LEV in monotherapy is a safe and effective therapeutic option in elderly patients who have suffered epileptic seizures following a stroke.

ADRIS: The new open-source accessible driving simulator for training and evaluation of driving abilities.

BACKGROUND AND OBJECTIVE: Independent living and transportation are crucial aspects for people living with a disability. After an injury, it is important to assess driving ability, in terms of physical and psychological conditions, and to test the effects of prescribed drugs. Within this framework, driving simulators are suitable tools for training driving skills; however, available tools are expensive or lack appropriate sets of behavioral measures to fully characterize the drivers' ability. METHODS: This work presents the first step toward the development of ADRIS, a new open-source, accessible, realistic virtual reality simulator for training and testing driving skills of people with sensory-motor disability. This includes a prototype based on an open-source simulator for autonomous driving research (CARLA), with the addition of customized features such as adaptable driving controllers, a virtual reality headset, and the possibility to collect behavioral and physiological data. Also, the new system allows to set different environmental conditions, to include and control the timing of potentially dangerous situations, and to set scenarios with various difficulty levels. RESULTS: Tests on 17 healthy participants demonstrated that the simulator is well tolerated in terms of discomfort, physical fatigue, and mental effort. Also, the system is easy to use and is capable of providing a realistic driving experience, allowing the extraction of reliable behavioral parameters. CONCLUSIONS: ADRIS combines a high-fidelity virtual world, with customizable features specifically designed for the training and testing of people living with a disability, thus making it usable in many contexts such as home training, rehabilitation, education, and research.

Case Report: Zellweger Syndrome and Humoral Immunodeficiency: The Relevance of Newborn Screening for Primary Immunodeficiency.

Background: Zellweger syndrome (ZS) is a congenital autosomal recessive disease within the spectrum of peroxisome biogenesis disorders, characterized by the impairment of peroxisome assembly. The presence of peroxisome enzyme deficiencies leads to complex developmental sequelae, progressive disabilities, and multiorgan damage, due to intracellular accumulation of very-long-chain fatty acids (VLCFAs). Case Presentation: We report the case of an infant affected by ZS in which agammaglobulinemia, detected through neonatal screening of congenital immunodeficiencies, appeared as a peculiar trait standing out among all the other classical characteristics of the syndrome. The exome analysis through next-generation sequencing (NGS), which had previously confirmed the diagnostic suspicion of ZS, was repeated, but no mutations causative of inborn error of immunity (humoral defect) were detected. Conclusion: In this case, no genetic variants accountable for the abovementioned agammaglobulinemia were detected. Given that the scientific literature reports the involvement of peroxisomes in the activation of Nuclear Factor κ-light-chain-enhancer of activated B cells (NF-κB) pathway, which is crucial for B-cell survival, with this work, we hypothesize the existence of a link between ZS and humoral immunodeficiencies. Further studies are required to confirm this hypothesis.