Gender differences in microRNA expression in levodopa-naive PD patients.

Gender is an important factor influencing epidemiological and clinical features of Parkinson's disease (PD). We aimed to evaluate gender differences in the expression of a panel of miRNAs (miR-34a-5p, miR-146a, miR-155, miR-29a, miR-106a) possibly involved in the pathophysiology or progression of disease. Serum samples were obtained from 104 PD patients (58 men and 46 women) never treated with levodopa. We measured levels of miRNAs using quantitative PCR. Correlations between miRNA expression and clinical data were assessed using the Spearman's correlation test. We used STRING to evaluate co-expression relationship among target genes. MiR-34a-5p was significantly upregulated in PD male patients compared to PD female patients (fc: 1.62; p < 0.0001). No correlation was found with age, BMI, and disease severity, assessed by UPDRS III scale, in male and female patients. MiR-146a-5p was significantly upregulated in female as compared to male patients (fc: 3.44; p < 0.0001) and a significant correlation was also observed between disease duration and mir-146a-5p. No differences were found in the expression of miR-29a, miR-106a-5p and miR-155 between genders. Predicted target genes for miR-34a-5p and miR-146-5p and protein interactions in biological processes were reported. Our study supports the hypothesis that there are gender-specific differences in serum miRNAs expression in PD patients. Follow-up of this cohort is needed to understand if these differences may affect disease progression and response to treatment.

Abitudini, stili di vita e socialità: una cluster analysis di studenti universitari italiani.

The analysis of health determinants in the student population can be useful in raising awareness on safe living conditions in new generations. The selection of specific biomedical markers, like advanced glycation end products (AGEs), and the analysis of social behaviors can support lifestyle choices evaluation. A questionnaire, containing an anamnestic section, a physical activity evaluation section, and a sociological section, was administered to a total of 110 students from two Italian universities, selected from the Faculty of Science of Movement and from the Faculty of Medicine. In addition, all subjects recruited in this study underwent to an AGEs accumulation assessment through skin autofluorescence. A non-hierarchical cluster analysis was performed on the collected data allowed the identification of two group of students: group 1 mainly consisted of male subjects from the Faculty of Science of Movement, characterized by an active lifestyle and a rather detached affective family condition; group 2 largely consisted of female subjects from the Faculty of Medicine, more sedentary and with stable relationships. The data analysis confirmed the correlation between low AGEs levels and healthy lifestyles, but at the same time underlined divergences between students from different Faculties.

Early outcome of anatomical lung resection for non-small cell lung cancer in the elderly.

OBJECTIVE: Surgery is the mainstay of early-stage lung cancer treatment. However, since life expectancy is constantly increasing, we wanted to investigate whether this principle also applies to elderly (≥70-year-old) patients. PATIENTS AND METHODS: We analyzed a prospectively maintained database on anatomical lung resections at our institute. Patients were divided in two groups: <70 years and ≥70 years (elderly). Outcome indicators were postoperative cardiopulmonary complications rate and 30-day readmission rate. Baseline and surgical characteristics were compared by mean of t-test, Mann-Whitney U test, chi2 and Fisher exact tests. Propensity score matching was performed to account for differences between groups in the outcome's analysis. RESULTS: We selected 241 patients with lung cancer (2017-2021) who underwent anatomical lung resections. Median age was 70.5 (IQR: 64-76). 133 patients (54%) aged 70 and above. Patients and surgical characteristics (comorbidities, lung function, performance status, type and extension of lung resection and surgical approach) were similar among groups, except for atrial fibrillation (p=0.01) and previous cancer history (p<0.0001) which were more frequent in the elderly group. Non-elderly patients were more frequently active smokers (p<0.0001). Cardiopulmonary complications rate was 23%, 30-day readmission rate was 12.6%. We did not observe any significant difference in all the short-term outcome indicators between the elderly and the younger counterpart. Particularly, complications rate (p=0.91) and 30-day readmission (p=0.84) did not differ between groups. CONCLUSIONS: In our series, short-term outcomes are not compromised in elderly patients. The evolution in surgical strategy and expertise contribute to offer surgical resection with curative intent for lung cancer to a large spectrum of patients.

May chronic cough in chronic obstructive pulmonary disease be a contraindication of Percutaneous Endoscopic Gastrostomy placement: a case report.

BACKGROUND: Percutaneous Endoscopic Gastrostomy (PEG) can involve some complications, despite the good safety of its track record. The Buried Bumper Syndrome (BBS) is a rare, late and dangerous complication that consists in the erosion of the internal bumper through the gastric wall. Case presentation We report the development of BBS in a man with chronic obstructive pulmonary disease (COPD) who had a persistent chronic cough which was prevalently but not solely in the morning and required placement of a PEG tube for continuous infusion of Levodopa/carbidopa intestinal gel for advanced Parkinson's disease. CONCLUSION: We believe that COPD with chronic cough while not representing an absolute contraindication to PEG placement, may potentially cause BBS and therefore an appropriate regimen of tube care by expert personnel is mandatory in this setting.

Uniportal VATS for pectus excavatum: the Southern Switzerland experience.

OBJECTIVE: The Nuss procedure is a minimally invasive approach used to treat the pectus excavatum. One to three curved metal bars are inserted behind the sternum in order to push it into a normal position. A bilateral thoracoscopy, with 3 or 4 incisions on each side, has been reported as a safe method to repair the chest. The aim of this observational cohort study is to evaluate the safety and efficacy of the modified uniportal thoracoscopic Nuss procedure. PATIENTS AND METHODS: A retrospective review on 248 consecutive patients treated in Southern Switzerland in the last 5 years for chest deformity was performed. Conservative treatment with vacuum bel or dinamic compression was performed in 235 cases. Thirteen patients with pectus excavatum were surgically treated with a modified single-incision thoracoscopic approach and introduction of a single retrosternal Nuss Bar. Demographics, clinical characteristics, surgical data and results were analyzed and discussed. RESULTS: The male/female ratio was 11/2, with mean age of 20.75 (±5.05) years. The Haller index was 3.65±0.5. The operative duration was 68. 2±13.3 min and hospitalization stay ranged from 2 to 10 days. There was no instance of intraoperative cardiac perforation or macrovascular injury. No pleural effusion or infection was reported. The overall complication rate after a postoperative follow-up of 24.6±3 months was 7.6%, without mortality, major bleeding, infectious complications, displacement or recurrence. Patients satisfaction and postoperative pain were also analyzed. CONCLUSIONS: The modified single-incision thoracoscopic Nuss procedure is both safe and effective for pectus excavatum correction with non-recurrence after two years.

Predictors of fatigue severity in early, de novo Parkinson disease patients: A 1-year longitudinal study.

INTRODUCTION: Fatigue is one of the most common and disabling nonmotor symptom in Parkinson's disease (PD). The aim of the present study was to investigate the 1-year course of fatigue in a consecutive sample of de novo drug-naïve patients with PD, and at systematically searching for baseline motor and nonmotor predictors associated with fatigue severity over time. METHODS: Fifty-five consecutive de novo PD patients (age: 64.71 ± 7.74 years) underwent a comprehensive examination, including Parkinson Fatigue Scale, Epworth Sleepiness Scale, Parkinson's Disease Sleep Scale, Beck Depression Inventory, Parkinson's Anxiety Scale, Apathy Evaluation Scale, and an extensive neuropsychological evaluation. Bivariate and multiple regression analyses were performed to identify baseline predictors independently related to fatigue severity at 1-year follow-up. RESULTS: Prevalence rate of fatigue (defined by PFS cut-off) increased from 22% at baseline to 38% at 1-year follow-up. A similar increase in prevalence was observed for excessive daytime sleepiness, and apathy. Among patients with fatigue at baseline, 91% had fatigue at follow-up too (i.e., persistent fatigue). Multivariate regression analysis identified fatigue (p < 0.01), daytime sleepiness (p < 0.01), and emotional apathy (p < 0.01) as the main baseline variables significantly predicting fatigue severity at 1-year follow-up. CONCLUSION: In early PD, fatigue increases and persists over time, and its severity is related to higher baseline levels of fatigue, excessive daytime sleepiness, and emotional apathy. These results warrant to monitor fatigue since the early stage of disease, and suggest that treating excessive daytime sleepiness and emotional apathy might prevent its worsening.

Fatigue in Parkinson's disease: Italian validation of the Parkinson Fatigue Scale and the Fatigue Severity Scale using a Rasch analysis approach.

INTRODUCTION: The Fatigue Severity Scale (FSS-9) and the Parkinson Fatigue Scale (PFS-16) are commonly used for assessing fatigue in Parkinson's disease (PD). Here we validated the Italian version of these scales, assessed their psychometric properties by Rasch analysis, and computed their optimal cut-off scores using clinical diagnosis of PD-related fatigue as the gold standard. METHODS: PD patients (n = 167) completed the Italian versions of FSS-9 and PFS-16. Each item of PFS-16 was scored both on a 5-point (PFS-16polytomous) and on a 2-point scale (PFS-16dichotomous). RESULTS: All scales showed an adequate overall Rasch model fit, high reliability, and good discriminant, convergent, and concurrent validity, but were less accurate in measuring very high and very low fatigue levels. No evidence of differential item functioning with respect to age, sex, and severity of parkinsonian symptoms was found. Some items of FSS-9 (item 1), PFS-16polytomous (items 1 and 13), and PFS-16dichotomous (items 1, 8, and 13) showed misfit, possibly due to their content concerning sleep and motivation disorders. When FSS-9 and PFS-16polytomous' responses were rescored on a 3-point scale, the discriminability across response categories improved. The optimal cut-off score in detecting clinically-diagnosed fatigue (observed in 20% of the sample) was 3.09 for PFS-16polytomous, 8.00 for PFS-16dichotomous, and 4.67 for FSS-9. CONCLUSIONS: The Italian version of PFS-16 and FSS-9 showed sound psychometric properties and can be confidently used to quantify fatigue symptoms in PD, although clinical diagnosis of fatigue should rely on validated criteria. The PFS-16polytomous exhibited advantages with respect to PFS-16dichotomous.

Physical and physiological demands and hormonal responses in basketball small-sided games with different tactical tasks and training regimes.

OBJECTIVES: To evaluate external and internal training load (TL) and hormonal responses in basketball 3-versus-3 small-sided games (SSGs). DESIGN: Randomized repeated-measures study. METHODS: Twelve male basketball players participated to four 3-versus-3 SSGs characterized by different tactical tasks (offensive; defensive) and training regimes (long-intermittent: three 4-min bouts with 2' rest in between; short-intermittent: six 2-min bouts with 1' rest in between). Variables measured were: PlayerLoad (PL); percentage of maximal heart rate (%HRmax); Edwards' TL. Before and after the SSGs, saliva samples were collected to measure cortisol (C) and testosterone (T). Two-way (task; regime) repeated-measures ANOVA was performed for PL and %HRmax; C concentrations were analysed with a three-way (task; regime; time: pre/post) repeated-measures ANOVA; non-parametric analyses were performed for Edwards' TL and T. RESULTS: PL was moderately higher in offensive task (148.0±16.8 AU) compared to defensive (137.1±15.5 AU), and short regime (147.0±18.2 AU) compared to long (137.9±14.6 AU). %HRmax was moderately higher in offensive task (91.1±4.1%) compared to defensive: (88.7±5.4%), while it did not differ between regimes (long: 90.0±5.6%) (short: 89.8±4.2%); additionally, an interaction (task*regime) effect was found (ES: strong). Edwards' TL was moderately higher in offense-long SSG (56.6+2.4 AU) compared to defense-short (52.4+4.4 AU). C increased after the SSGs (ES: strong). T decreased after offense-short (ES: moderate) and increased after defense-long (ES: moderate) SSGs. CONCLUSIONS: Tactical tasks and training regimes influence external and internal demands of basketball SSGs. Steroid hormones respond in SSGs.

Motor, behavioural, and cognitive correlates of fatigue in early, de novo Parkinson disease patients.

INTRODUCTION: Fatigue is one of the most common and disabling non-motor symptoms in Parkinson's disease (PD). The objective of this study was to determine prevalence and motor, behavioural, and cognitive correlates of distressing fatigue in early, de novo PD patients. METHODS: Eighty-one consecutive de novo PD patients (64% men; mean age 65.73 ± 8.26 years) underwent a comprehensive examination, including Parkinson's disease Fatigue Scale (PFS), Epworth Sleepiness Scale (ESS), Parkinson's Disease Sleep Scale (PDSS), Beck Depression Inventory (BDI), Parkinson's Anxiety Scale (PAS), and Apathy Evaluation Scale (AES). Moreover, all patients underwent a detailed neuropsychological evaluation exploring attention and working memory, executive functions, memory, visuospatial abilities and language. Score of patients with or without distressing fatigue (defined as a PFS score ≥ 8) were compared by Student's t-test or Pearson's chi-square test. Logistic regression analyses were performed to search for motor and non-motor features independently associated with presence of distressing fatigue. RESULTS: Twelve (15%) patients presented distressing fatigue. Logistic regression identified sleepiness (p = 0.04), "episodic anxiety" subscale of PAS (p = 0.005), and "cognitive apathy" subscale of AES (p = 0.017) as the main factors associated with distressing fatigue. No significant association was found between diagnosis of Mild Cognitive Impairment and distressing fatigue (p = 0.745). CONCLUSION: In a sample of consecutive de novo PD patients, distressing fatigue is associated with episodic anxiety, cognitive apathy and sleepiness, but not with cognitive impairment. Our findings suggest possible shared pathogenic mechanisms underlying these non-motor symptoms and foster development of early combined therapeutic approaches.

Determinants of the effectiveness of fast break actions in elite and sub-elite Italian men's basketball games.

The aim of this study was to examine the determinants of successful and unsuccessful fast-break (FB) actions in elite and sub-elite basketball games. Fifteen 1st-division (elite) and fifteen 3rd-division (sub-elite) Italian men's championship games were analysed across two seasons (2012/2013 and 2013/2014). A binary logistic regression analysis was performed, and the fast-break outcome (successful vs. unsuccessful) was adopted as the dependent variable separately in both elite and sub-elite games. FB execution (initiation, advance and completion phases), typology (primary and secondary break) and the number of players involved (equal number or superiority) were used as independent variables. The results showed that the rate of success of FB actions was 63.5% and 59.7% in elite and sub-elite games, respectively. Moreover, successful FBs were more likely to be completed in the lane in relation to unsuccessful ones in both elite and sub-elite games (p<0.05). Finally, descriptive statistics showed that both elite and sub-elite teams executed FBs similarly. This study highlighted that completion zone was the only predictor of a successful fast break in basketball, while the typology and number of players involved did not predict fast break effectiveness. Moreover, elite and sub-elite teams executed fast break actions similarly. These findings might be useful for basketball coaches to optimize the training of FB actions.

Session-RPE for quantifying the load of different youth basketball training sessions.

The aim of the study was to evaluate youth basketball training, verifying the reliability of the session-RPE method in relation to session duration (< and ≥ 80 minutes) and workout typology (reduced and high warm-up, conditioning, technical, tactical, game portions within a single session) categories. Six male youth basketball players (age, 16.5±0.5 years; height, 195.5±6.75 cm; body mass, 93.9±10.9 kg; and body mass index, 23.6±2.8 kg.m-2) were monitored (HR, type and duration of workouts) during 15 (66 individual) training sessions (80±26 minutes). Edwards' HR method was used as a reference measure of internal training load (ITL); the CR-10 RPE scale was administered 30 minutes after the end of each session. The results obtained showed that all comparisons between different session durations and workout portions revealed effects in term of Edwards' ITLs except for warm-up portions. Moderate to strong relationships between Edwards' and session- RPE methods emerged for all sessions (r = .85, P < .001), player's sessions (r range = .79 - .95, P < .001), session durations (< 80 minutes: r = .67, P < .001; ≥ 80 minutes: r = .75, P < .001), and workout portions (r range = .78 - .89, P range = .002 - < .001). The findings indicated that coaches of youth basketball players can successfully use session-RPE to monitor the ITL, regardless of session durations and workout portions.

Performance profile of NCAA Division I men's basketball games and training sessions.

This study aimed to analyse live and stoppage time phases, their ratio, and action played on half and full court in college basketball games. Differences were assessed for the entire games and between halves. Moreover, differences of the live/stoppage time ratio were analysed between games and game-based conditioning drills. Ten games as well as fifteen defensive, fourteen offensive and six scrimmage-type drills of the same division I men's college team (13 players) were analysed using time-motion analysis technique. Live and stoppage time were classified in five classes of duration: 1-20, 21-40, 41-60, 61-80, >80 seconds. Half court actions started and finished in the same half court. Full court actions were classified as transfer (TR) phases when at least 3 teammates crossed the mid-court line. TR phases were then classified in 5 classes of frequency: 1TR, 2TR, 3TR, 4TR, and >4TR. The results revealed no statistically significant differences between games or between halves for the considered parameters. The only significant difference was observed for live/stoppage time ratio between halves (p<0.001). Furthermore, a significant difference of the live/stoppage ratio was found between games and game-based drills (p<0.01). Post-hoc analysis demonstrated significant differences of scrimmage-type drills in comparison to games, and defensive and offensive drills (p<0.05), whereas no differences emerged for the other pairwise comparisons. The absence of differences between games in the analysed parameters might be important to characterize the model of performance in division I men's college games. Furthermore, these results encourage coaches to use game-based conditioning drills to replicate the LT/ST ratio documented during games.

Continuous intra jejunal infusion of levodopa-carbidopa intestinal gel by jejunal extension tube placement through percutaneous endoscopic gastrostomy for patients with advanced Parkinson's disease: a preliminary study.

OBJECTIVE: Levodopa is the gold standard in the pharmacological treatment of Parkinson's disease (PD) and its oral administration is associated with the development of disabling motor and non-motor complications in advanced disease. Levodopa is rapidly metabolized and has a short plasma half-life thus requiring frequent, repeated dosing. Impaired gastric emptying is common in PD, and likely contributes to the unpredictable motor responses observed with orally-dosed levodopa. A new therapeutic protocol for patients with advanced PD include a carbidopa/levodopa combination using continuous, modulated enteral administration achieved inserting a Jejunal Extension Tube Placement through Percutaneous Endoscopic Gastrostomy (PEG-J). The aim of this work is to assess efficacy and safety of levodopa-carbidopa intestinal gel (LCIG) delivered continuously through an intrajejunal percutaneous tube (PEG-J). PATIENTS AND METHODS: We enrolled 11 adults with advanced PD and preserved sensitivity to L-dopa. For pre-procedural endoscopic evaluation each patient underwent a diagnostic esophagogastroduodenoscopy (EGD) 7 days before PEG-J placement to evaluate the presence of gastric anatomical or wall anomalies and the presence of oesophageal or gastric varices. Treatment with LCIG, consisting of a water-based suspension containing micronized levodopa (20 mg/mL) and carbidopa (5 mg/mL) in methylcellulose (Duodopa®), was administered by continuous jejunal infusion for 12h/day using a portable pump (CADD-Legacy) by PEG-J. Clinical evaluations were performed at baseline (T0) before LCIG initiation, and after 3 (T3) and 6 (T6) months of therapy. The efficacy and safety outcomes were assessed by using the Unified Parkinson's Disease Rating Scale (UPDRS) parts II, III and IV. RESULTS: Mean age of patients was 71.18 ± 5.4 SD at LCIG initiation. Out of the 11 patients, 2 (18%) dropped-out LCIG at T3. Patients showed statistically significant (p < 0.05) higher performances in activities of daily living and a statistically significant (p < 0.001) lower incidence and severity of motor fluctuations, as rating by UPDRS part IV, compared to their best oral therapy. During observational period, 5 patients experienced adverse events. Success rate for PEG-J placement was 100%. CONCLUSIONS: Our work shows that continuous intrajejunal infusion of LCIG ensures a reduction in motor Fluctuations compared to oral administration of levodopa-carbidopa in advanced PD. Based on our results and on the evidence emerging in the literature, this therapeutic approach should be the gold standard for therapy in these patients.

Increased CD1D polymorphism: identification of two novel alleles, CD1D*03 and *04, in individuals from Morocco.

Two novel CD1D alleles were identified in unrelated individuals from Morocco. They differ each from the common CD1D*01 allele by one nucleotide substitution in exon 2 resulting in one amino acid change in the G-ALPHA1-LIKE domain. According to the IMGT unique numbering for G domain, CD1D*03 has one nucleotide transition c136 > t in codon 46, with an arginine-to-cysteine amino acid change (R46 > C) in the D-STRAND, whereas CD1D*04 has one transition c98 > t in codon 33, with a threonine-to-methionine amino acid change (T33 > M) in the C-STRAND. This suggests that CD1D is more polymorphic than previously assumed.

Post-traumatic headaches: a clinical overview.

Headache attributed to head and/or neck trauma or injury, the so-called post-traumatic headache (PTH), is the most common secondary headache disorder and one of the most controversial clinical entities in the headache field, due to its unclear pathophysiological mechanisms and the unsolved role of associated psychological and medico-legal aspects. PTH, as a significant cause of morbidity after traumatic brain injury, may occur as an isolated symptom or as one of a constellation of symptoms known as post-concussive syndrome. However, in many cases, PTH might also represent an accentuation of non-disabling, remote or infrequent pre-existing primary headaches rather than a new onset headache strictly related to the trauma. Recently, the International Classification of Headache Disorders attempted to classify PTH; however, many unsolved issues are still to be clarified. In this brief review, we will focus on PTH clinical aspects and diagnostic criteria.

Post-traumatic headaches: an epidemiological overview.

Post-traumatic headache (PTH) is the most common secondary headache disorder, corresponding to approximately 4 % of all symptomatic headaches. PTH, a cardinal feature of the post-concussive syndrome, usually shows a phenotype similar to migraine or tension-type headache. However, rare cases of PTH similar to trigeminal autonomic cephalalgias have been described. Many studies have investigated PTH prevalence and potential risk factors for its development and maintenance. In general population, the majority of PTH patients is female and has been involved in vehicle-related accidents. Generally, headache gradually disappears over few weeks or months; however, PTH could become persistent and very disabling in a minority of patients. This brief review will focus on PTH epidemiological aspects.

The role of BOLD-fMRI in elucidating migraine pathophysiology.

Migraine is a neurologic disorder characterized by disabling attacks of throbbing headache with specific features and associated symptoms. Despite the recent discoveries in basic neurosciences, migraine pathophysiology is not completely understood. Nevertheless, in the last decades, advances in functional magnetic resonance imaging (fMRI) have significantly provided new insights into migraine mechanisms. Blood oxygen level dependent (BOLD) fMRI technique is the most commonly used method to explore brain function and connectivity due to high temporal and spatial resolution. The purpose of this review is to present a synthesis of recent BOLD-fMRI studies which have allowed us to elucidate the complex process involved in migraine pathophysiology.

Regional gray matter atrophy in patients with Parkinson disease and freezing of gait.

BACKGROUND AND PURPOSE: FOG is a troublesome symptom of PD. Despite growing evidence suggesting that FOG in PD may be associated with cognitive dysfunction, the relationship between regional brain atrophy and FOG has been poorly investigated. MATERIALS AND METHODS: Optimized VBM was applied to 3T brain MR images of 24 patients with PD and 12 HC. Patients were classified as either FOG- or FOG+ (n = 12) based on their responses to a validated FOG Questionnaire and clinical observation. All patients with PD also underwent a detailed neuropsychological evaluation. RESULTS: The VBM analysis in patients with FOG+ showed a reduced GM volume in the left cuneus, precuneus, lingual gyrus, and posterior cingulate cortex compared with both patients with FOG- and HC. We did not detect any significant change of GM volume when comparing HC versus all patients with PD (FOG- and FOG+). FOG clinical severity was significantly correlated with GM loss in posterior cortical regions. Finally, patients with FOG+ scored lower on tests of frontal lobe function. CONCLUSIONS: Our findings provide the first evidence that the development of FOG in patients with PD is associated with posterior GM atrophy, which may play a role in the complex pathophysiology of this disabling symptom.

Interictal cortical reorganization in episodic migraine without aura: an event-related fMRI study during parametric trigeminal nociceptive stimulation.

The aim of our study was to explore the pain processing network in patients with migraine during trigeminal nociceptive stimulation. Sixteen patients with episodic migraine without aura and 16 healthy controls performed functional magnetic resonance imaging during thermal stimuli (at 41, 51 and 53°C). Patients with migraine showed a greater activation in the perigenual part of anterior cingulate cortex at 51°C and less activation in the bilateral somatosensory cortex at 53°C compared to healthy controls. There were no differences in experimental pain perception between groups. Our findings demonstrate a functional reorganization of cerebral areas known to be involved in pain processing in patients with migraine.