The proximity between styloid process and internal carotid artery as a possible risk factor for dissection: a case-control study.

PURPOSE: The anatomical proximity of the styloid process (SP) to the ipsilateral internal carotid artery (ICA) has been recently recognized as a possible risk factor for carotid artery dissection (CAD). We aimed to verify this hypothesis by comparing the minimum distance between SP and ICA in young adult patients (< 55 years) with and without CAD. METHODS: Thirty-one CAD patients (cases) were compared with 41 sex-matched patients without dissection, group one of control (G1), and with 16 sex-matched patients with vertebral artery dissection (VAD), group two of control (G2). Two independent observers measured, on CT angiography images, the minimum distance on the axial plane between the SP and ICA in cases and controls. They evaluated both the intercentric and the marginal distance. Differences between groups were estimated by Student t-test. RESULTS: SP-ICA intercentric distance ipsilateral to dissection was significantly shorter compared to that of the contralateral side of cases (p < 0.001), to those of left and right side of G1 patients (p < 0.001 for both), and to those of left and right side of G2 patients (p < 0.001 for both). SP-ICA marginal distance of cases was significantly shorter compared to those of left and right side of G1 patients (p < 0.001 for both) and to those of left and right side of G2 patients (p < 0.001 for both). CONCLUSION: A short SP-ICA distance appears to be a risk factor for CAD as it likely induces a continuous microtraumatism of the vessel wall during normal head and neck movements.

Eating psychopathology in ballet dancers: a meta-analysis of observational studies.

OBJECTIVE: To assess whether ballet dancers have higher eating psychopathology mean scores than the general population. METHODS: Meta-analysis of cross-sectional observational studies comparing the scores of one or more of the validated eating psychopathological scales between ballet dancers and any control groups. RESULTS: Twelve studies were included in the metanalysis. Ballet dancers had a significantly higher EAT score (12 studies retrieved, SMD 0.82 [95% CI 0.44-1.19], p < 0.00001, I2 = 84)]; subgroup analysis suggested a possible role of control subjects' choice in explaining heterogeneity. Scores on the EDI subscales of Drive for Thinness, Bulimia, and Body dissatisfaction were available from four studies; Drive for Thinness was higher in ballet dancers (SMD 0.62 [0.01, 1.22]), as well as the Bulimia scale (SMD 0.38 [0.02, 0.73], p = 0.04) and the Body Dissatisfaction scale (SMD 0.34 [0.15, 0.53]). Data on Perfectionism, Interpersonal problems, Ineffectiveness, and Maturity fears, were available from three studies. Higher scores in Perfectionism (SMD 0.68 [0.24, 1.12] p = 0.02), Interpersonal problems (SMD 0.24 [0.02, 0.47], in Inefficacy, (SMD 2.18 [1.31, 3.06]) were found for ballet dancers; on the other hand, Maturity fears scores were not significantly different between ballet dancers and controls (IV-MD = 0.15 [- 0.07, 0.36]). Seven studies reported tests not performed elsewhere. DISCUSSION: Ballet dancers show a higher level of restriction and drive for thinness than controls, and they may be, therefore, at higher risk for the development of eating disorders. Available studies do not allow the discrimination of dysfunctional eating attitudes and behaviors from adaptive responses. LEVEL OF EVIDENCE: Level I (evidence obtained from systematic reviews and meta-analyses).

SARS-CoV-2 infection in patients with autoimmune rheumatic diseases in northeast Italy: A cross-sectional study on 916 patients.

BACKGROUND: Whether patients with autoimmune rheumatic diseases (ARD) have a higher risk for SARS-CoV-2 infection (COVID-19) and how SARS-CoV-2 pandemic impacts on adherence to therapy has not been fully elucidated. We assessed the rate and clinical presentation of COVID-19, and adherence to therapy in a large cohort of patients with ARD followed-up in a tertiary University-Hospital in Northeast Italy. METHODS: Between April 9th and April 25th, 2020, after SARS-CoV-2 infection peak, a telephone survey investigating the impact of COVID-19 on patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), ANCA-associated vasculitis (AAV), and idiopathic inflammatory myopathies (IIM) was administered. Demographics, disease activity status, therapy, occupational exposure, and adherence to social distancing advise were also collected. RESULTS: 916 patients (397 SLE, 182 AAV, 176 SSc, 111 RA, 50 IIM) completed the survey. 148 patients developed at least one symptom compatible with COVID-19 (cough 96, sore throat 64, fever 64, arthromyalgias 59, diarrhea 26, conjunctivitis 18, ageusia/hyposmia, 18). Among the 916 patients, 65 (7.1%) underwent SARS-CoV-2 nasopharyngeal swab (18 symptomatic and 47 asymptomatic), 2 (0.21%) tested positive, a proportion similar to that observed in the general population of the Veneto region. No deaths occurred. 31 patients (3.4%) withdrew ≥1 medication, mainly immunosuppressants or biologics. Adoption of social distancing was observed by 860 patients (93.9%), including 335 (36.6%) who adopted it before official lockdown. CONCLUSIONS: COVID-19 incidence seems to be similar in our cohort compared to the general population. Adherence to therapy and to social distancing advise was high.

Repeated AAV-mediated gene transfer by serotype switching enables long-lasting therapeutic levels of hUgt1a1 enzyme in a mouse model of Crigler-Najjar Syndrome Type I.

Adeno-associated virus (AAV) -mediated gene therapy is a promising strategy to treat liver-based monogenic diseases. However, two major obstacles limit its success: first, vector dilution in actively dividing cells, such as hepatocytes in neonates/children, due to the non-integrating nature of the vector; second, development of an immune response against the transgene and/or viral vector. Crigler-Najjar Syndrome Type I is a rare monogenic disease with neonatal onset, caused by mutations in the liver-specific UGT1 gene, with toxic accumulation of unconjugated bilirubin in plasma, tissues and brain. To establish an effective and long lasting cure, we applied AAV-mediated liver gene therapy to a relevant mouse model of the disease. Repeated gene transfer to adults by AAV-serotype switching, upon neonatal administration, resulted in lifelong correction of total bilirubin (TB) levels in both genders. In contrast, vector loss over time was observed after a single neonatal administration. Adult administration resulted in lifelong TB levels correction in male, but not female Ugt1-/- mice. Our findings demonstrate that neonatal AAV-mediated gene transfer to the liver supports a second transfer of the therapeutic vector, by preventing the induction of an immune response and supporting the possibility to improve AAV-therapeutic efficacy by repeated administration.

Early social isolation differentially affects the glucocorticoid receptor system and alcohol-seeking behavior in male and female Marchigian Sardinian alcohol-preferring rats.

Adverse early life experiences during postnatal development can evoke long-lasting neurobiological changes in stress systems, thereby affecting subsequent behaviors including propensity to develop alcohol use disorder. Here, we exposed genetically selected male and female Marchigian Sardinian alcohol-preferring (msP) and Wistar rats to mild, repeated social deprivation from postnatal day 14 (PND14) to PND21 and investigated the effect of the early social isolation (ESI) on the glucocorticoid receptor (GR) system and on the propensity to drink and seek alcohol in adulthood. We found that ESI resulted in higher levels of GR gene and protein expression in the prefrontal cortex (PFC) in male but not female msP rats. In female Wistars, ESI resulted in significant downregulation of Nr3c1 mRNA levels and lower GR protein levels. In male and female msP rats, plasma corticosterone levels on PND35 were similar and unaffected by ESI. Wistar females exhibited higher levels of corticosterone compared with males, independently from ESI. In alcohol self-administration experiments we found that the pharmacological stressor yohimbine (0.0, 0.312, 0.625, and 1.25 mg/kg) increased alcohol self-administration in both rat lines, regardless of ESI. After extinction, 0.625 mg/kg yohimbine significantly reinstated alcohol seeking in female rats only. ESI enhanced reinstatement in female msP rats. Overall, the present results indicate that repeated social deprivation during the third week of postnatal life affects GR expression in a strain- and sex-dependent manner: such effect may contribute, at least partially, to the heightened sensitivity of female msP rats to the effects of yohimbine-induced alcohol seeking.

Psilocybin prevents reinstatement of alcohol seeking by disrupting the reconsolidation of alcohol-related memories.

BACKGROUND: For most psychiatric conditions, including alcohol use disorder (AUD), FDA-approved pharmacological treatments are limited and their efficacy is restricted to only certain subgroups of patients. Scientific interest in the potential of psychedelic drugs has dramatically increased because of clinical preliminary evidence of efficacy in treating various psychiatric disorders. One of the most promising compounds belonging to this class of molecules is psilocybin. Here, to elucidate the therapeutic potential and treatment modalities of this drug, we investigated the effect of psilocybin on alcohol drinking and seeking in genetically selected Marchigian Sardinian alcohol-preferring (msP) rats, a well validated animal model of AUD characterized by excessive drinking and seeking. METHODS: Using male and female msP rats, we tested the effect of psilocybin on home cage voluntary alcohol consumption. We also tested the effect of the drug on the alcohol deprivation effect (ADE) model of relapse and on cue-induced reinstatement of alcohol seeking after a period of abstinence. Finally, we evaluated if psilocybin may disrupt the reconsolidation process of alcohol-related memory. RESULTS: Psilocybin did not reduce alcohol consumption, nor it prevented increased alcohol drinking after a period of forced abstinence and cue-induced reinstatement of alcohol-seeking. Noteworthy, in a memory retrieval-reconsolidation paradigm, psilocybin markedly attenuated resumption of alcohol seeking. CONCLUSIONS: Altogether these data suggest that, despite psilocybin does not affect alcohol drinking and relapse, it may be highly effective if used to block the reconsolidation process of alcohol-related memories. This opens to the possibility of using this psychedelic drug in clinical settings in which AUD patients undergo procedures to recall the memory of alcohol and are then treated with psilocybin during the memory reconsolidation phase.

Dendritic cell functional improvement in a preclinical model of lentiviral-mediated gene therapy for Wiskott-Aldrich syndrome.

Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency caused by the defective expression of the WAS protein (WASP) in hematopoietic cells. It has been shown that dendritic cells (DCs) are functionally impaired in WAS patients and was(-/-) mice. We have previously demonstrated the efficacy and safety of a murine model of WAS gene therapy (GT), using stem cells transduced with a lentiviral vector (LV). The aim of this study was to investigate whether GT can correct DC defects in was(-/-) mice. As DCs expressing WASP were detected in the secondary lymphoid organs of the treated mice, we tested the in vitro and in vivo function of bone marrow-derived DCs (BMDCs). The BMDCs showed efficient in vitro uptake of latex beads and Salmonella typhimurium. When BMDCs from the treated mice (GT BMDCs) and the was(-/-) mice were injected into wild-type hosts, we found a higher number of cells that had migrated to the draining lymph nodes compared with mice injected with was(-/-) BMDCs. Finally, we found that ovalbumin (OVA)-pulsed GT BMDCs or vaccination of GT mice with anti-DEC205 OVA fusion protein can efficiently induce antigen-specific T-cell activation in vivo. These findings show that WAS GT significantly improves DC function, thus adding new evidence of the preclinical efficacy of LV-mediated WAS GT.

Extraction of information on elder motor ability from clinical and biomechanical data through data mining.

This study aimed at evaluating the additional knowledge provided by a biomechanical test coupled with clinical tests for motor ability assessment. A database including clinical test scores and sit-to-stand test variables obtained from 110 medically stable elderly subjects was submitted to data mining by searching for association rules. The presence of rules revealed some redundancies due to sample homogeneity, as mainly observed in the joint analysis of a questionnaire for daily activities assessment (Nottingham test) and the sit-to-stand, and due to similar evaluated information, as resulted from the joint analysis of a balance and gait scale (Tinetti test) and the sit-to-stand. Conversely, when no association rules were found, the tests carried unrelated information. The associations mined while analysing these clinical tests encouraged the integration of biomechanical tests, increasing significantly its clinical applicability and reducing the information redundancy. The information extracted also allowed to highlight rules typical of elderly persons that may serve as a knowledge-based tool for the detection of possible deviation from normality.

Genetic vaccination for the immunotherapy of B-cell malignancies.

Vaccination protocols based on targeting of the idiotype expressed on malignant B cells have so far provided encouraging results in clinical trials. The essential requirement to induce an immune response is the inclusion of carriers to overcome T-cell tolerance. Chemical cross-linking of idiotypic protein is so far the method of choice to induce protective responses in human studies. Meanwhile, a flurry of alternative strategies to simplify vaccine production is being tested in murine model. Thanks to the advance in antibody engineering the two relevant antigenic domains of the lymphoma immunoglobulin can be assembled into an appropriate format, genetically linked to molecules that act as immunological adjuvants and directly delivered as plasmid DNA. Upon immunization, rejection of tumor cells may depend on cellular or humoral mechanisms, whose relative importance has not been entirely estimated. We have recently analyzed the specificity of anti-idiotypic antibodies induced by DNA vaccination and characterised the elements contributing to optimal anti-idiotypic responses.

Human ballistic arm abduction movements: effects of L-dopa treatment in Parkinson's disease.

In patients with Parkinson's disease who had never previously been treated with any antiparkinsonism drug, we studied the effects of L-dopa on ballistic arm abduction movement in a step-tracking task. L-Dopa treatment increased the mean velocity of the initial movement towards the target without loss of accuracy and with improved motor performance under open-loop conditions. Performance also improved in motor tasks with expected perturbation. EMG patterns of arm abduction movements showed abnormal features in untreated patients and improved after L-dopa treatment.

Covalent bonding of heparin to a vinyl copolymer for biomedical applications.

In order to prepare polymer surfaces of vinyl type, provided with long-term haemocompatibility, a commercial ethylene-vinyl alcohol copolymer (EVAL) was covalently heparinized, employing two different bifunctional reagents (adipoil chloride and hexamethylene diisocyanate). The amount and activity of the heparin bonded to the polymer films were evaluated as a function of the concentration of the heparin solutions employed. Also, the influence exerted by the presence of various hydrophilic 'spacing arms' of different molecular weights, either neutral or provided with electrical charge, was investigated. By in vitro measurements of activated partial thromboplastin time it was seen that all the heparinized samples possessed a high degree of haemocompatibility. For the sake of comparison, heparin was also bonded ionically to EVAL functionalized by introduction of quaternary ammonium groups bonded covalently (by adipoil chloride) to the hydroxyl groups of the polymer. It was seen that the covalent immobilization system provides the polymer surfaces with a superior haemocompatibility.

Foot pain and disability in older persons: an epidemiologic survey.

OBJECTIVE: To investigate the prevalence of foot pain in older people and its association with pathological conditions of the feet and with disability in basic and instrumental activities of daily living. DESIGN: Cross-sectional survey of a community-dwelling older population. PARTICIPANTS: A total of 459 subjects, 73% of the population aged 65 years and older living in Dicomano, Florence, Italy. MEASUREMENTS: A standardized medical examination was performed by a geriatrician to collect information on the presence of pain, specific problems of the feet, gait, and several indicators of physical health status. Disability in basic and instrumental activities of daily living was evaluated by self-report. RESULTS: The prevalence of foot pain was very high, especially in subjects affected by calluses or corns, hallux deformities, hammer toes, pes planus, and edema and among those who complained of difficulty in looking after the basic needs of the feet. Patients with foot pain needed a greater number of steps and longer time to walk the same distance. Foot pain was associated with a higher prevalence of disability in instrumental activities of daily living, particularly those related to standing and ambulation capacities, but it was not related to higher prevalence of disability in basic activities of daily living. CONCLUSIONS: Foot pain is associated with specific conditions of the feet and disability in instrumental activities of daily living. Adequate assessment and treatment of foot problems may prevent foot pain and potentially reduce risk of disability. This hypothesis needs to be tested in longitudinal studies and specific intervention trials.

Flunarizine-induced parkinsonism in the elderly.

Twenty-seven patients (19 women and 8 men, ages 63 to 88 years; mean, 74 years) displayed mild to moderate parkinsonism and altered ballistic motor performances during long-term flunarizine treatment. One month after, flunarizine withdrawal, 20 patients showed clear-cut improvements in both clinical features and ballistic motor performances; a complete recovery within 6 months was observed in all these patients but one, who still showed very mild slowness of movement. On the other hand, seven patients showed little clinical improvement and still maintained markedly altered ballistic motor performances 1 month after drug withdrawal. At the 2-month follow-up assessments, either they did not improve further or they deteriorated; they were successfully treated with L-dopa and, despite the ameliorations, after 12 to 24 months they still have definite parkinsonian syndrome. The authors conclude that (1) flunarizine, even at the recommended dose (10 mg daily), can induce reversible parkinsonism, at least in subjects older than 60; (2) the persistence of a marked symptomatology 2 months after flunarizine withdrawal should lead to starting treatment with antiparkinsonism drugs; (3) the study of ballistic movements is proposed as a useful tool for objective quantification and early detection of bradykinesia.

Flexibility of anticipatory postural adjustments revealed by self-paced and reaction-time arm movements.

In standing humans, it is not certain whether anticipatory postural adjustments associated with rapid, voluntary elbow flexion movements (focal movements) originate as a selection from preset synergies or as the result of specific planning of motor commands. We studied these muscle recruitment patterns when the same focal movement was made under behavioral conditions of a self-paced task (SPT) and a reaction-time task (RTT). While standing still, eight normal subjects performed focal movements under the SPT and RTT behavioral conditions and under three different biomechanical conditions: (1) unloaded-upright, (2) loaded-upright (holding a 3800-g metal bar), and (3) unloaded-forward leaning. Anticipatory postural adjustments were quantified using the latency and duration of electromyographic (EMG) data and the center of pressure (COP) displacement data. Postural-kinematic [joint and body center of gravity (COG) motion] data were used to quantify the anticipatory postural program's effectiveness at preventing postural movement. Focal movement kinematics and associated EMG activity differed due to biomechanical but not behavioral (SPT vs. RTT) conditions. The maximum and net displacement of the body COG measurements did not differ between the behavioral conditions. The amplitude, timing, and net movements of lower extremity joints were influenced by the behavioral conditions. However, the behavioral conditions significantly affected the phasing (including order of activation) and duration of anticipatory postural EMG activity and the phasing of COP displacements under certain biomechanical conditions. These findings support the theory that anticipatory postural adjustments are planned in detail.

Remote effects of cortical dysgenesis on the primary motor cortex: evidence from the silent period following transcranial magnetic stimulation.

OBJECTIVE: In cortical dysgenesis (CD), animal studies suggested abnormal cortico-cortical connections. Cerebral areas projecting to the primary motor cortex (M1) modulate the cortical silent period (CSP) following transcranial magnetic stimulation (TMS). Therefore, we used the CSP to investigate remote effects of CD on the M1. METHODS: A detailed investigation, including single-pulse TMS and electrical nerve stimulation, was performed in 3 consecutive adults with focal CD located outside the M1 and in 18 controls. Two patients with unilateral CD were epileptic and treated with anti-epileptic drugs. One patient with focal CD on both sides had no history of seizures. Neurological examination was normal in all patients. Recordings were made from both first dorsal interosseous muscles. RESULTS: In CD patients, the CSP was significantly lengthened contralaterally to the affected hemispheres. In treated patients with unilateral CD, the interside difference of the CSP duration was also significantly increased. In contrast, excitability threshold, peripheral and corticospinal motor conduction studies, and peripheral as well as ipsilateral silent periods were not significantly modified. CONCLUSIONS: Our findings indicate that focal CD outside the M1 may produce CSP modifications, which are likely due to changes of afferent control.

Cortical silent period in two patients with meningioma and preoperative seizures: a pre- and postsurgical follow-up study.

OBJECTIVES: Prolongation of the cortical silent period (CSP) following transcranial magnetic stimulation has been reported in patients with partial epilepsy involving the primary motor cortex (M1). This study aimed to investigate the relationship between the expected intraindividual variations in risk factors for seizures and CSP duration. METHODS: We studied a 59-year-old woman with a rolandic meningioma and simple motor partial seizures and a 71-year-old woman with a parietal/occipital meningioma and complex partial seizures. Both patients had seizure as their initial symptom with complete postsurgical remission. Repeated pre- and postoperative CSP recordings were made from both first dorsal interosseous muscles. We compared the results to those obtained in 13 normals. RESULTS: In the patient with simple motor partial seizures, the CSP was significantly prolonged in preoperative recordings and 3 weeks after surgery. This CSP lengthening partly subsided 3 months after surgery. Finally, the CSP was normal 6, 8, and 18 months after surgery. In the patient with complex partial seizures, no CSP change was observed. CONCLUSIONS: In our patient with a rolandic meningioma, CSP prolongation was observed when the risk of seizure relapse was supposed to be higher (preoperative and early postoperative periods). This supports the view that CSP changes reflect compensatory mechanisms in M1 epilepsy.

Sensitisation to Aspergillus fumigatus and Penicillium notatum in laboratory workers.

Four workers in medical research laboratories, located in a basement level of a University facility equipped with a humidified air conditioning system, complained of cough and/or asthma and/or rhinitis during their normal working activities. Since exposure to toxic compounds was very low (similar to that of the outdoor environment) only microbiological monitoring was performed. Aspergillus fumigatus and Penicillium notatum were found in some laboratories. Eight laboratory workers (including the 4 symptomatic subjects) out of 26 investigated were found to be atopic. Specific IgE sensitisation to Aspergillus fumigatus was found in the 8 atopic and in the 6 non-atopic workers, while Penicililum notatum was found in 7 atopic and 4 non-atopic subjects. History, physical examination and laboratory data excluded the presence of aspergillosis or allergic bronchial aspergillosis in the sensitised subjects. Our results suggest that evaluation of immune parameters, along with monitoring of the working environment, may reduce the risk of sensitisation and/or allergic symptoms in atopic laboratory workers.

Optimised procedure for the calibration of the force platform location.

An innovative optimised method, including an experiment and a mathematical model, for the calibration of the force platform location in the optoelectronic reference frame is proposed. The calibration experiment adopts a bearing-marker testing object contacting the platform and does not directly measure the platform location. The experiment is designed in order to avoid the main drawbacks possibly occurring in commonly adopted methods. The mathematical model of the experiment estimates the expected ground reaction. An optimisation algorithm identifies the optimal platform location as the one that best matches the measured outcome of the calibration experiment with the corresponding model estimate. The innovative calibration procedure has been assessed in terms of inter-tester reliability and compared with commonly used calibration procedures of platform location. These results evidenced how the introduction of such optimised procedure could improve the reliability of the calibrated platform location and, consequently, of the kinetic variables considered in posture and gait analysis.

Effects of low frequency electromagnetic fields on expression of lymphocyte subsets and production of cytokines of men and women employed in a museum.

The objective of this study was to analyse the immune response to electromagnetic fields (ELMFs) in seven men and eight women employed in a museum. The workers were exposed in a room to an ELMFs (range 0.2-3.6 microT and 40-120 V/m) induced by 50 Hz electricity for 20 h a week. Control groups consisted of 47 women and 39 men with a similar percentage of atopic subjects, age (range 30-51 years) and smoking habits of the workers included in the study. Levels of blood lead (Pb) and urinary trans-trans muconic acid, a metabolite of benzene (markers of exposure to traffic and smoking) of the control and exposed groups were similar. Lymphocyte subsets were determined in men and women using conjugated antibodies. Serum interleukin (IL) 4 and interferon gamma and their 'in vitro' production by peripheral mononuclear blood cells (PMBCs) stimulated by phytohemoglutinin (PHA), as well as blastogenesis of PMBCs induced by PHA, were determined in women only. ELMF-exposed women showed a significant reduction in the percentage of B and NK CD3(-)-CD25+ lymphocytes and a slight reduction of CD16(+)-56+ NK lymphocytes. They also showed significantly lower levels of interferon gamma in serum, or produced in the supernatants by PMBCs both spontaneously and stimulated by PHA, while they did not show significant changes in serum and 'in vitro' produced IL-4, or in blastogenesis of PMBCs. Men working in the museum showed, in relation to the controls, a statistically significant reduction in both number and percentage of CD16(+)- CD56+ and CD3(-)-CD25+ lymphocyte subsets. On the whole, this investigation demonstrates a reduction of blood NK lymphocytes and of the production of interferon gamma in workers exposed to low frequency ELMFs. Recent studies have shown that stress and poor lifestyle induce the reduction of blood cytotoxic activities possibly acting on nervous functions. This may suggest that ELMFs reduces blood NK lymphocytes by combined effects on the immune and nervous systems.