The present study determined whether treatment during childhood with topiramate (TPM), a new generation antiepileptic drug, results in altered aortic reactivity in adult male and female rats. We also ...sought to understand the role of endothelium-derived contractile factors in TPM-induced vascular dysfunction. Male and female Wistar rats were treated with TPM (41 mg/kg/day) or water (TPM vehicle) by gavage during childhood (postnatal day, 16–28). In adulthood, thoracic aorta reactivity to phenylephrine (phenyl), as well as aortic thickness and expression of cyclooxygenases (COX-1 and COX-2), NOX2, and p47phox were evaluated. The aortic response to phenyl was increased in male and female rats from the TPM group when compared with the control group. In TPM male rats, the hyperreactivity to phenyl was abrogated by the inhibition of NADPH oxidase and COX-2, while in female rats, responses were restored only by inhibition of COX-2. In addition, TPM male rats presented aortic hypertrophy and increased expression of NOX-2 and p47phox, while TPM female rats showed increased COX-2 aortic expression. Taken together, for the first-time, the present study provides evidence that treatment with TPM during childhood causes vascular dysfunction in adulthood, and that the mechanism underlying the vascular effects of TPM is sex-specific.
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This paper adds to the series of systematic rapid living reviews, started in April 2020, to provide the rehabilitation community with updates on the latest scientific literature on rehabilitation ...needs due to the COVID-19 pandemic. The aim of this study was to present the results of a systematic search performed on papers published from May 1
to May 31
, 2020.
An extensive search on the main medical literature databases for articles published (including Epub), in English, from May 1
to May 31
, 2020 was performed, according to the methodology already described in the previous 2 rapid reviews, with 2 important improvements: first, we made the search string more comprehensive; second, we relied on accredited terminologies to describe the study designs and report the rehabilitation settings.
Fifty-eight out of 618 articles were finally included for qualitative analysis. The number of primary studies has increased, with respect to the previous months, although still around 60% papers are just expert opinions. Six papers report on the prevalence and /or characteristics of emerging disability after COVID-19, 12 on rehabilitation approaches to COVID-19 patients, up to 25 on the organization of rehabilitation services after COVID-19, 13 papers on the impact of COVID-19 on health conditions of rehabilitative interest and only 2 on late complications due to COVID-19 that may be of rehabilitative interest.
Nowadays, all patients with disability, regardless of COVID-19 infection, are suffering because of restrictions imposed to rehabilitation service delivery. Neurological involvement is often present during acute and postacute stage, conveying the risk of a long-lasting disability. Accordingly, careful neurological monitoring should be granted. Although new therapies are under development, the main gap in the available scientific literature is the lack of high-quality primary studies, so experimental studies on the effects of rehabilitation are still warranted.
This paper adds to the series of systematic rapid living reviews, started in April 2020, to provide the rehabilitation community with updates on the latest scientific literature on rehabilitation ...needs due to COVID-19 pandemic. The aim of this paper is to present the results of a systematic scientific literature search performed on papers published from April 1st to April 30th, 2020.
A systematic search was performed on PubMed, Embase, Scopus, CINAHL, PEDro, Web of Science and the main international guideline databases for articles published (including Epub), in English, from April 1st to April 30th, 2020. Papers were included if they reported on one of the following: 1) prevalence and features of the emerging disability after COVID-19; 2) rehabilitation strategies applied for COVID-19 patients, regardless of setting or stage; 3) information about rehabilitation services after COVID-19; 4) impact on diseases of rehabilitative interest; 5) complications of rehabilitative interest.
Out of 445 articles retrieved for the time frame, 50 were finally included for qualitative analysis. They consist of seven guidelines, one scoping review, one randomized controlled trial, four descriptive studies (qualitative), one case series, one case report, and 35 expert opinions.
This systematic rapid living review showed an increasing evidence on rehabilitation needs due to COVID-19 outbreak during April 2020. The main novelties include: 1) the first appearance of epidemiological data on the likely high incidence of neurological complications/disabling sequelae in patients hospitalized for COVID-19; 2) rapid guidelines on the management of chronically disabled patients in the COVID-19 era; 3) advices to provide COVID-19 patients with early respiratory rehabilitation in the acute phase, and with telemonitoring and telerehabilitation in the post-acute phase. Although the overall quality of studies has increased, prospective cohort studies on disability course in COVID-19 pandemic and experimental studies on the effects of rehabilitation are still warranted.
Introduction
Safinamide is a recent antiparkinsonian drug that modulates both dopaminergic and glutamatergic systems with positive effects on motor and nonmotor symptoms of Parkinson’s disease (PD). ...Here, we aimed to describe the efficacy and safety of safinamide in the Italian PD patients in real-life conditions.
Methods
We performed a sub-analysis of the Italian cohort of the SYNAPSES study, a multi-country, multi-center, retrospective-prospective cohort observational study, designed to investigate the use of safinamide in routine clinical practice. Patients received for the first time a treatment with safinamide and were followed up for 12 months. The analysis was conducted on the overall population and in subgroups of interest: i) patients > 75 years, ii) patients with relevant comorbidities and iii) patients affected by psychiatric symptoms.
Results
Italy enrolled 616/1610 patients in 52 centers, accounting for 38% of the entire SYNAPSES cohort. Of the patients enrolled, 86.0% were evaluable at 12 months, with 23.3% being > 75 years, 42.4% with psychiatric conditions and 67.7% with relevant comorbidities.
Safinamide was effective on motor symptoms and fluctuations as measured through the Unified PD rating scale III and IV scores, and on the total score, without safety issues in none of the subgroups considered.
Conclusion
The SYNAPSES data related to Italian patients confirms the good safety profile of safinamide even in special groups of patients. Motor fluctuations and motor impairment improved at the follow-up suggesting the significant role of safinamide in managing motor symptoms in PD patients.
The study aimed to evaluate if maternal exposure to fluoxetine (FLX) during pregnancy and lactation would result in altered aortic reactivity in adult offspring. We also sought to understand the role ...of endothelium derived relaxing factors in aortic response. Wistar rats (75–80 days old), whose progenitors had received FLX (5 mg/kg, FLX offspring) or tap water (control offspring) during pregnancy and lactation were anesthetized, after which the aorta was removed and cut into two rings, one with (Endo+) and the other without (Endo-) endothelium. Concentration-effect curves for acetylcholine (ACh), sodium nitroprusside (SNP), and phenylephrine (Phe) were performed. The vasodilation to ACh and SNP was similar between control and FLX groups in both male and female offspring. In male rats, the response to Phe was similar between the FLX and control groups on Endo+ and Endo- rings. The response to Phe was reduced on Endo+ rings from female FLX when compared with the control group. The endothelium removal, as well as L-NAME, indomethacin, and tranylcypromine incubation corrected the reduced Phe-induced contraction in the aorta from the female FLX group. On the other hand, catalase, NS-398, and L-NIL did not interfere with the vasoconstriction. The aortic level of nitric oxide (NO) was higher in the female FLX than the control group. Although endothelial NO synthase isoform and cyclooxygenase (COX)-1 expressions were similar between the groups, there was a notable increment in neuronal NO synthase expression in the aorta of FLX-exposed female rats, suggesting an important role of this enzyme in the higher levels of NO. Our results show that developmental exposure to FLX causes sex-specific alteration in aortic function through a mechanism involving endothelial factors, probably NO and COX-1 products.
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The harmonization of staff education is a key element for ensuring the highest standard of rehabilitation care across Europe. With this aim, the European Union of Medical Specialists (UEMS) has ...created a Common Training Framework, which consists of a common set of knowledge, skills and competencies for postgraduate medical training. As a body linked to the Physical and Rehabilitation (PRM) Section of the UEMS, the European PRM Board is committed to promoting the harmonization of PRM physicians qualifications. The European PRM Board accomplishes this mission, not only by determining the theoretical knowledge necessary for the practice of the PRM specialty, and the core competencies (training outcomes) to be achieved at the end of training, but also by ascertaining that a standard level of education is achieved and maintained by PRM physicians, through a medically driven system of certification. This paper provides an overview of the methodology and outcomes of the European PRM Board examination, while showing how the approach to PRM education should be considered as a reference point by scientific societies, higher education institutions, health policymakers, patients associations, and all the other bodies caring for high-quality rehabilitation provision to disabled people, at the national and European level.
Abstract Background The observation of gait abnormalities, parkinsonism and vascular lesions in elderly patients is often reported as vascular parkinsonism (VP). However the status of striatal ...dopamine transporter (DAT) and the effects of brain vascular lesions on motor features and levodopa responsiveness are poorly defined. Methods We recorded clinical features, chronic response to levodopa and vascular risk factors in a cross-sectional cohort of consecutive elderly patients with possible Parkinson's disease (PD) or VP recruited in 20 centers in Italy. Results We included a total of 158 patients. Onset of motor symptoms was asymmetric in 93 (59%) and symmetric in 65 patients (41%). Symmetric motor onset was associated with greater disease severity. Chronic levodopa response was positive in 75 (47.8%) and negative in 82 patients (52.2%). A negative response to levodopa was associated with greater frequency of symmetric onset of motor symptoms, worst disease severity, absence of dyskinesia and greater number of vascular risk factors. Frontal lobe showed largest vascular load. Striatal DAT was normal in 48 (30.4%) and abnormal in 110 (69.6%) patients. Patients with normal DAT binding showed higher vascular load at MRI. Significant predictive factors of worst disease severity and negative response to levodopa were hypertension, vascular lesions in basal ganglia/periventricular regions, and normal DAT uptake. Conclusions Multiple cerebral vascular lesions modify clinical presentation and severity in patients with parkinsonism and this is underlined by specific risk factors primarily hypertension. Striatal DAT assessment is helpful in identifying patients where therapy benefit is less likely.
This study sought to investigate whether pulse pressure (PP) is associated with endothelium-dependent vasodilation in a group of never-treated hypertensives.
Pulse pressure represents a ...well-established independent predictor for cardiovascular morbidity and mortality. Forearm endothelial dysfunction, defined as impaired vasodilating response to acetylcholine (ACh), may be associated with several cardiovascular risk factors. Recently, the prognostic value of coronary and forearm endothelial dysfunction has been demonstrated.
All patients underwent measurement of blood pressure (BP) both clinically and in an ambulatory setting. Endothelium-dependent and -independent vasodilation was investigated by strain-gauge plethysmography in 262 hypertensive patients (age 30 to 55 years) during intra-arterial infusion of increasing doses of ACh and sodium nitroprusside.
We observed that systolic BP rather than diastolic BP significantly induces the PP increase. Linear regression analysis revealed a significant inverse correlation between ACh-stimulated forearm blood flow (FBF) and age, body mass index, clinic and monitored systolic BP, and clinic and monitored PP. However, stepwise multivariate analysis showed that monitored PP was the strongest independent predictor of ACh-stimulated FBF, accounting for 33.6% of the variation. After adjustment for other covariates, ACh-stimulated FBF decreases by 8.7% for each mm Hg increment in monitored PP.
Our data indicate that monitored PP is inversely correlated with ACh-stimulated vasodilation. It is possible to hypothesize that elevation in PP reduces FBF by increasing oxidative stress and reducing production of nitric oxide caused by reduced shear stress. In addition, the present findings demonstrate the accuracy of ambulatory BP as a prognostic predictor of hypertension-associated endothelial dysfunction.
OBJECTIVES (1) To evaluate the predictive value of a detailed clinical screening of aspiration in patients withneurological diseases, both with and without symptoms of dysphagia taking ...videofluoroscopy as the gold standard; (2) to assess the existence of risk factors for silent aspiration, measuring the cost-benefit ratio of radiological examination. METHODS 93 consecutive patients meeting the diagnostic criteria for a neurological disease with a risk of swallowing dysfunctions (cerebrovascular accidents, brain injury, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, myotonic dystrophy, and abiotrophic diseases) underwent a detailed clinical assessment using a 25 item form to check for symptoms of dysphagia and impairment of the oropharyngeal swallowing mechanism. The 3 oz water swallow test was also performed to assess the aspiration risk. Sensitivity, specificity, positive predictive, and negative predictive values (NPV) of dysphagia, history of cough on swallowing, and 3 oz test positivity, versus videofluoroscopy documented aspiration, taken as the gold standard, were measured in all the patients and in subgroups with different neurological disorders. RESULTS Non-specific complaints of dysphagia showed a very poor predictive value, whereas the symptom “cough on swallowing” proved to be the most reliable in predicting the risk of aspiration, with 74% sensitivity and specificity, 71% positive predictive, and 77% negative predictive value. The standardised 3-oz test had a higher predictive potential than the clinical signs, but had low sensitivity. The association of cough on swallowing with the 3 oz test gave a positive predictive of 84%, and an negative predictive value of 78%. In cases where the clinical tests failed to detect any impairment, videofluoroscopy documented only a low risk (20%) for mild aspiration. CONCLUSIONS The association of two clinical items (such as history of cough on swallowing and 3 oz test positivity) provides a useful screening tool, the cost:benefit ratio of which seems very competitive in comparison with videofluoroscopy in aspiration risk evaluation.
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