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.

HUGO(TM) RAS System in urogynaecology: the first nerve sparing Sacral Colpopexy for Pelvic Organ Prolapse.

Background: Minimally invasive sacral colpopexy is considered the gold standard for surgical treatment of Pelvic Organ Prolapse (POP), combining high success rates with low recurrence risk in comparison to other techniques. This is the first case of robotic sacral colpopexy (RSCP) performed with the innovative Hugo™ RAS robotic system. Objectives: The aim of this article is to show the surgical steps of a nerve sparing RSCP performed with the new Hugo™ RAS robotic system (Medtronic), by also evaluating the feasibility of this technique using this novel Robotic System. Materials and Methods: A 50-year-old Caucasian woman with symptomatic pelvic organ prolapse (POP-Q): Aa: +2, Ba: +3, C: +4, D: +4, Bp: -2, Ap: -2 , TVL:10 GH: 3,5 BP:3 underwent RSCP as well as a subtotal hysterectomy with bilateral salpingo-oophorectomy, using the new surgical robot Hugo™ RAS in the Division of Urogynaecology and Pelvic Reconstructive Surgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. Main outcome measures: Intraoperative data, docking specifics, objective and subjective outcomes at three months follow up. Results: Surgical procedure was carried out without intra-operative complications, operative time (OT) was 150 minutes, docking time was 9 minutes. No system errors or faults in the robotic arms were registered. Urogynaecological examination at three months follow up showed a complete resolution of the prolapse. Conclusion: RSCP using the Hugo™ RAS system seems to be a feasible and effective approach according to results in terms of operative time, cosmetic results, postoperative pain and length of hospitalisation. Large number of case reports as well as longer follow up are mandatory to better define its benefits, advantages, and costs.

Overnight switch from rasagiline to safinamide in Parkinson's disease patients with motor fluctuations: a tolerability and safety study.

BACKGROUND AND PURPOSE: When switching between monoamine oxidase type B (MAO-B) inhibitors, a 15-day suspension period is a precautionary measure to avoid a serotonin syndrome and hypertensive crisis. However, this indication results in a major inconvenience for parkinsonian patients because of the worsening of their clinical condition. In routine clinical practice, neurologists often perform a substitution of these two drugs without solution of continuity (i.e. overnight), to avoid worsening of fluctuations and prolonged OFF periods. Therefore, a safety open label study was performed to investigate the possible risks of switching overnight from rasagiline to safinamide. METHODS: The study population included 20 advanced patients with Parkinson's disease on stable treatment with rasagiline and levodopa (alone or in combination with other anti-parkinsonian medication). The possible occurrence of serotonin syndrome and hypertension was monitored through a strict clinical observation and a 24-h Holter recording (ABPM) performed twice, whilst subjects were on rasagiline and immediately after switching to safinamide. RESULTS: No cases of serotonin syndrome or hypertensive crisis occurred during the study. Changes that were not significant occurred in the primary end-point: 24-h mean blood pressure (BP) had a mild +4.4% increase in the ABPM2 versus ABPM1 (P = 0.17), 24-h systolic and diastolic BP values were slightly higher at ABPM2 compared to ABPM1 (respectively +3.3%, P = 0.13; and 5.4%, P = 0.08) and 24-h systolic BP variability was unchanged between the two ABPM evaluations (from 8.6 ± 2.9 to 8.9 ± 1.8; P = 0.27). CONCLUSION: The results of the present study confirm that the overnight switch from rasagiline to safinamide is safe and well tolerated by patients.

Laparoscopic sacral hysteropexy for pelvic organ prolapse in a patient affected by marfan syndrome: a case report.

BACKGROUND: Marfan Syndrome (MS) is a dominantly inherited connective tissue disorder with consequences on the strength and resilience of connective tissues that may predispose to Pelvic Organ Prolapse (POP). Literature lacks studies investigating POP surgery in patients affected by MS that might help surgical management decisions. OBJECTIVE: The objective of this paper is to describe the surgical procedure of laparoscopic sacral hysteropexy (LSHP) in a 37 years old woman affected by MS with symptomatic POP. MATERIALS AND METHODS AND MAIN OUTCOME MEASURES: We performed a nerve-sparing laparoscopic sacral hysteropexy without complications and looked for anatomical and subjective outcomes. The patient completed The Female Sexual Distress Scale (FSDS), Pelvic Floor Disability Index (PFDI-20), and Wexner questionnaires preoperatively and postoperatively. RESULTS: The patient stated a complete resolution of all POP related symptoms and there was a total correction of the descensus. Furthermore, no perioperative and postoperative complications were noted. CONCLUSIONS: LSHP could be an effective and safe procedure for the treatment of POP in women affected by MS and this case report is the first to describe a reconstructive procedure in this category of patients. WHAT IS NEW?: The literature lacks studies investigating POP surgery in women with MS, that might help surgeons, thus we present this case to describe surgical and functional outcomes in this patient category, underlying the higher risk of complications and relapses related to the weakness of connective tissue. This case report may represent the basis of future studies to confirm the safety, efficacy and feasibility of LSHP and sacral colpopexy in patients with MS.

The Senhance ® assisted laparoscopy in urogynaecology: case report of sacral colpopexy with subtotal hysterectomy with bilateral salpingo-oophorectomy for pelvic organ prolapse *: * Video Article, to see the video use this link: https://qrco.de/bbdi3G.

The aim of this case report was to evaluate the feasibility, efficacy, and safety of nerve-sparing laparoscopic sacrocolpopexy (SCP) performed with a minimally invasive approach by using 2.9-mm Senhance ® surgical robotic system (Senhance ® , TRANSENTERIX Inc., USA). A 60-year-old Caucasian woman with symptomatic pelvic organ prolapse-Q (POP-Q) Aa: 2, Ba: 3, C: +4, Bp:2, Ap: 2, TVL:10 underwent subtotal hysterectomy with bilateral salpingo-oophorectomy, with nerve-sparing SCP performed using the Senhance surgical robotic system.. The urogynaecological assessment on the day of discharge and at the 3 month follow-up showed surgical anatomic success (<2 POP-Q stage). The patient was fully satisfied with the cosmetic result. This is the first case of SCP performed with this innovative system. SCP using "Senhance ®" is a feasible and effective approach with good results in terms of operative time, cosmesis, postoperative pain and length of hospitalisation.

Laparoscopic sacrocolpopexy plus ventral rectopexy as combined treatment for multicompartment pelvic organ prolapse.

BACKGROUND: Pelvic organ prolapse (POP) is a dynamic disorder that affects the entire pelvic diaphragm. POP may often involve multiple organs. Abdominal sacrocolpopexy is considered the gold standard to treat female anterior and apical prolapse. Abdominal ventral mesh rectopexy has gained increasing acceptance as an effective treatment for rectal prolapse. The aim of the present study was to assess the safety, feasibility and 1-year outcomes of laparoscopic sacrocolpopexy plus ventral rectopexy as a combined treatment of multicompartment POP. METHODS: All female patients at our institution with anterior and apical prolapse with symptoms of obstructed defecation were examined by an urogynecologist and a colorectal surgeon, and were judged suitable for the study. Patients with Pelvic Organ Prolapse Quantification (POP-Q) system stage III and IV and concomitant rectal prolapse were treated by laparoscopic sacrocolpopexy plus ventral rectopexy. After surgery, 1- and 12-month follow-up was performed and the data were retrospectively analyzed. Patients' symptoms were evaluated using the Female Sexual Distress Scale (FSDS), Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ-12), and Wexner-Agachan constipation score. RESULTS: A total of 98 patients underwent surgery. No intraoperative or postoperative morbidity occurred. At the time of follow-up, all women expressed great satisfaction with the surgical treatment: all the patients had at most POP-Q Stage 1 and 78.8% had a Patient Global Impression of Improvement (PGI-I) score < 3. Significant improvement of symptoms related to POP and to obstructed defecation syndrome, as shown by the FSDS, PISQ-12, and Wexner-Agachan constipation score, was observed in all patients at follow-up CONCLUSIONS: Laparoscopic sacrocolpopexy with ventral rectopexy is a feasible and safe procedure for the combined surgical management of anterior, apical, and posterior prolapse, and provides excellent objective and subjective outcomes.

Early-morning OFF and levodopa dose failures in patients with Parkinson's disease attending a routine clinical appointment using Time-to-ON Questionnaire.

BACKGROUND AND PURPOSE: In patients with Parkinson's disease (PD) with motor fluctuations, total daily OFF time is comprised of both end-of-dose time and the time taken to turn ON with medication. However, little is known about the impact of delays in ON time. METHODS: This was a single-visit pilot study of fluctuating patients with PD attending a routine appointment. During a single visit, adult patients with idiopathic PD who were treated with levodopa for at least 1 year completed a questionnaire evaluating the time waiting for ON and the symptoms experienced while waiting to turn ON. Patients then completed a 5-day home time-to-ON diary, where they documented how long it took to turn ON following their first morning dose of levodopa in 5-min increments. RESULTS: A total of 151 consecutive patients completed the study survey, of whom 97 (64.2%) experienced motor fluctuations. Of the patients experiencing motor fluctuations, 54 (56%) reported delays in ON time (latency >30 min) following their first morning dose of levodopa. Half (51%) reported that they had experienced delayed ON at least once in the previous week and 21% reported having delayed ON during all seven mornings of the previous week. In addition, 10% of patients reported having dose failures on four or more mornings during the previous week. The most common symptoms experienced while waiting for ON were slowness (94.8%), fatigue (87.6%), reduced dexterity (82.5%), problems in walking (66.0%) and problems with balance (59.8%). CONCLUSION: Early-morning OFF problems such as delays in time to ON and dose failures are common in levodopa-treated patients with PD.

Long-term effects of vaginal erbium laser in the treatment of genitourinary syndrome of menopause.

OBJECTIVES: To evaluate the long-term efficacy of a second generation of vaginal laser treatment, the vaginal erbium laser, as a non-ablative photothermal therapy for the management of genitourinary syndrome of menopause. METHODS: The study was performed using an erbium laser crystal yttrium-aluminum-garnet (XS Fotona Smooth™, Fotona, Ljubljana, Slovenia) with a wavelength of 2940 nm. Postmenopausal women (n = 205) were treated with three laser applications at 30-day intervals. Symptoms were assessed before and after treatment throughout 24 months, using the subjective visual analog scale (VAS) and the objective vaginal health index score (VHIS). In addition, postmenopausal women suffering from stress urinary incontinence were evaluated with the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF). RESULTS: Vaginal erbium laser treatment induced a significant (p < 0.01) decrease in VAS for both vaginal dryness and dyspareunia, as well an increase in VHIS (p < 0.01) up to the 12th month after the last laser treatment. The values returned to levels similar to the baseline after 18 and 24 months. In addition, vaginal erbium laser treatment improved mild-moderate stress urinary incontinence in 114 postmenopausal women. Less than 3% of patients discontinued treatment due to adverse events. CONCLUSIONS: These results suggest that vaginal erbium laser may be effective and safe for the treatment of genitourinary syndrome of menopause.

A non-invasive prevention program model for the assessment of osteoporosis in the early postmenopausal period: a pilot study on FRAX(®) and QUS tools advantages.

OBJECTIVE: The study analyses the performances of FRAX algorithm and quantitative ultrasound (QUS) tool in relationship to the dual-energy X-ray absorptiometry (DXA) categorization to identify patients at risk of osteoporosis during menopause and to reach new thresholds for recommending the first DXA examination. DESIGN: Retrospective cohort study. PATIENTS AND MEASUREMENTS: Two hundred eighty-two postmenopausal patients filled out a questionnaire which determined their FRAX index and performed a bone evaluation by QUS of the calcaneus to determine their stiffness index (SI). Thereafter, they underwent assessments by the gold-standard DXA bone examination. RESULTS: Statistically significant correlations were observed between FRAX (calculated without BMD) and both QUS and DXA diagnosis. FRAX mean indices of risk corresponding to the diagnosis of osteoporosis by QUS and DXA were similar. Receiver operating characteristic (ROC) curve analysis showed that both FRAX and QUS tests were sufficiently accurate in predicting the alteration of bone mineral composition. The ROC curves of QUS allowed us to identify, in our population, SI cutoff for normal patients (SI > 90.5) and for patients having osteoporosis (SI < 78.5). We selected a cutoff screening value from FRAX ROC curve for major clinical fracture (2.94). The following diagnostic algorithm demonstrated that the use of FRAX test alone has a sensitivity of 85.3 % and a specificity of 33.8 % while the use of QUS exam alone showed a sensitivity of 81.3 % and a specificity of 45.1 %. When considering the capacity of QUS exam in combination with FRAX test, the final algorithm showed a sensitivity of 69.4 % and a specificity of 57.7 %. CONCLUSIONS: The use of QUS test with adjusted cutoffs offers a similar performance to the FRAX test alone in terms of sensitivity. The combined use of the tests reduces the sensibility but increases the specificity and adds clinical information related to the bone status of the patient.

Symptom relief in Parkinson disease by safinamide: Biochemical and clinical evidence of efficacy beyond MAO-B inhibition.

In an open pilot study, doses of safinamide (100, 150, and 200 mg once a day, higher than previously tested) were administered to 13 parkinsonian patients along with a stable dose of dopamine (DA) agonist, causing a significant progressive improvement in motor performance as evaluated by the Unified Parkinson Disease Rating Scale (UPDRS) part III over an 8-week period (4.2 points; P < 0.001). In association with levodopa, the same doses of safinamide in another group of patients (N = 11) induced a significant decrease in motor fluctuations (UPDRS part IV, 2.1 points; P < 0.001), accompanied by a dose-proportional increase of the levodopa AUC, up to 77% from baseline. Because MAO-B was fully inhibited (95%) at all doses tested, we suggest that these biochemical and symptomatic dose-dependent effects must be related to additional mechanisms of action, such as inhibition of glutamate release, increased dopamine release, or inhibition of dopamine re-uptake. These hypotheses are under investigation and will pursue confirmation in controlled clinical trials.

Beta-globin cluster haplotypes in normal individuals and beta(0)39-thalassemia carriers from Sardinia, Italy.

Seven polymorphic sites in the beta-globin cluster in association with specific thalassemia mutations were analyzed in a sample from Sardinia, Italy. In order to verify previous works carried out on normal samples (beta(A)/beta(A)) and family studies on beta-thalassemia homozygotes individuals, the haplotype frequencies in both normal individuals (beta(A)/beta(A)) and beta(0)39-thalassemia carriers (beta(A)/beta0) were studied. In our work chromosomes carrying beta(0)39 mutation are characterized by a prevalence of haplotype II (- + + - + + +) (52%) relative to haplotype I (+- - - - + +) (29%), in contrast, among chromosomes with beta(A) the frequency of haplotype I is much greater than that of haplotype II. These data confirm what was found by other authors. Nevertheless, our results disagree with those of previous studies of Sardinians, both in frequencies values and in the numbers of haplotypes identified. Population analysis performed with samples carrying the beta-thalassemic mutation highlighted the peculiarity of Sardinians with respect to other Mediterranean populations. The Corsican population is most similar to the Sardinian population, confirming previous analyses performed with both classical markers and mitochondrial and genomic DNA.

Inhibition of p38 mitogen activated protein kinase controls airway inflammation in cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) airways are characterised by chronic inflammation, increased interleukin (IL)-8 secretion, and neutrophil activation which are considered the principal factors of morbidity and mortality in CF patients. Optimising management of this chronic inflammatory response is therefore a key issue of basic and clinical CF research. Several reports have addressed ways to manage CF airways inflammation, and an attractive therapeutic strategy may be the inhibition of the p38-mitogen activated protein kinase (p38-MAP-k) pathway. METHODS: A new ex vivo model was used to study the mucosal inflammatory response to environmental airways stimuli. Nasal biopsy tissues from CF patients and controls were cultured ex vivo for 20 minutes, 4 hours, and 24 hours in the presence of lipopolysaccharide (LPS) from Pseudomonas aeruginosa (PA) with and without the p38-MAP-k inhibitor SB203580. Quantitative mRNA assessment, immunohistochemistry, and Western blots were used to detect the expression and modulation of inflammatory markers. RESULTS: PA-LPS challenge induced a time dependent mucosal inflammation indicated by rapid epithelial activation, IL-8 release, COX-2 upregulation, and neutrophil migration to the upper mucosal layers. Some of these LPS induced changes (IL-8 release and neutrophil migration) were specific to CF tissues. SB203580 significantly controlled all LPS induced mucosal changes in CF tissues. CONCLUSION: These findings provide a rationale and proof of principle for the potential use of p38-MAP-k inhibitors to control inflammation in patients with CF.

Primary cervical dystonia and scoliosis: a multicenter case-control study.

OBJECTIVE: To study the distribution of prior scoliosis among patients with primary adult-onset cervical dystonia (CD) and matched control subjects. METHODS: Case and control subjects were selected among consecutive outpatients attending four Italian centers. Control outpatients were matched for age (+/-5 years), sex, and referral center. Information on prior scoliosis, other spine diseases, and family history of dystonia was obtained by a standardized questionnaire and supported by medical records. Conditional logistic regression models were used to adjust simultaneously for age, disease duration, and education level and to determine the independent association of exposure variables with the outcome. RESULTS: Prior scoliosis developing in middle or late childhood or at around the puberty occurred more frequently among 72 case patients than among 144 neurologic control subjects. No subject reported conditions considered to be responsible for secondary scoliosis. The association of scoliosis and CD was not confounded by age, duration of disease, education level, other spine diseases, or family history of dystonia (adjusted odds ratio [OR] 6.8; 95% CI 1.5 to 29.5; p = 0.011). The OR of family history of dystonia (18.7; 95% CI 2.4 to 147.5; p = 0.005) fell to 11.7 (95% CI 1.3 to 103; p = 0.03) after controlling for scoliosis. CONCLUSIONS: Prior scoliosis may increase the risk of developing CD. The observed decrease in the magnitude of the association between family history of dystonia and CD after controlling for scoliosis suggests a link between the two conditions.