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BACKGROUND Variants in GBA are the most common genetic risk factor for Parkinson's disease (PD). The impact of different variants on the PD clinical spectrum is still unclear. OBJECTIVES We determined the frequency of GBA-related PD in Italy and correlated GBA variants with motor and nonmotor features and their occurrence over time. METHODS Sanger sequencing of the whole GBA gene was performed. Variants were classified as mild, severe, complex, and risk. β-glucocerebrosidase activity was measured. The Kaplan-Meier method and Cox proportional hazard regression models were performed. RESULTS Among 874 patients with PD, 36 variants were detected in 14.3%, including 20.4% early onset. Patients with GBA-PD had earlier and more frequent occurrence of several nonmotor symptoms. Patients with severe and complex GBA-PD had the highest burden of symptoms and a higher risk of hallucinations and cognitive impairment. Complex GBA-PD had the lowest β-glucocerebrosidase activity. CONCLUSIONS GBA-PD is highly prevalent in Italy. Different types of mutations underlie distinct phenotypic profiles. © 2020 International Parkinson and Movement Disorder Society.

Objectives To report the results of a national survey aimed at quantifying the current level of diffusion of Levodopa/carbidopa intestinal gel (LCIG) in Italy. Methods Sixty Parkinson's Disease (PD) specialists in Italy were invited to complete a survey covering issues on clinical and practical aspects of LCIG therapy. Results Clinical features of 905 patients were collected retrospectively. The majority of centres reported the use of a multidisciplinary team, biochemistry testing, neurophysiological and neuropsychological tests before and after treatment, in addition to caregivers' training and patient's follow as outpatients. Most centres (60%) used internal guidelines for patient selection. The overall rate of adverse events was 55.1%. Weight loss, chronic polyneuropathy and stoma infection were the most frequently reported. 40% of centres used replacement therapy with Vitamin B12 and Folic acid from the start of LCIG and continued this for the duration of treatment. The rate of discontinuation was of 25.7% overall, with 9.5% of cases occurring in the first year. The main causes of withdrawal were device-related complications, disease progression (comorbidity, severe dementia) and caregiver and/or patient dissatisfaction. Conclusions In Italy LCIG infusion is managed in a uniform manner at a clinical, practical and organizational level even though the selection criteria are not standardized through the country. The high percentage of patients remaining on treatment in the short- and long-term follow-up confirms effectiveness of treatment, careful follow-up, and appropriate patient and caregivers training.

Background: Knowledge on anaemia management in non-dialysis chronic kidney disease (ND-CKD) patients regularly followed in renal clinics is scarce although being essential to identifying areas of therapeutic improvement. Methods: We prospectively evaluated anaemia management in two visits, performed 6 months apart, in 755 prevalent ND-CKD stage 3b-5 patients followed in 19 nephrology clinics from ≥6 months. Anaemia was defined as severe (Hb

Patients with chronic inflammatory demyelinating polyneuropathy (CIDP) received immune globulin intravenous, 10% caprylate/chromatography purified (IGIV-C, Gamunex; n = 59) or placebo (n = 58) every 3 weeks for up to 24 weeks (first period) in a randomized, double-blind, parallel-group, response-conditional, crossover study. Motor and sensory nerves were assessed at baseline and endpoint/week 24. A nonsignificant trend toward improvement in the proximal amplitude of the most severely affected motor nerve was observed with IGIV-C (0.69 +/- 1.86 mV) versus placebo (0.47 +/- 2.29 mV), and a greater improvement of 1.08 +/- 2.15 mV with IGIV-C versus 0.46 +/- 2.03 mV with placebo (P = 0.089) was observed with exclusion of data from Erb's point stimulation. Greater improvements from baseline favoring IGIV-C were observed for 127/142 electrophysiologic parameters. The averaged motor amplitudes from all motor nerves significantly improved with IGIV-C versus placebo [treatment difference, 0.62 mV; 95% confidence interval (CI), 0.05, 1.20; P = 0.035], and conduction block decreased significantly (treatment difference, -5.54%; 95% CI, -10.43, -0.64; P = 0.027), particularly in the lower limbs. Overall, the data suggest that IGIV-C improves electrophysiologic parameters in CIDP.

Neuropathy can severely affect patients' quality of life (QoL), causing disability and decreased motor efficiency while modifying their perception of the external environment. We performed a large, multi-perspective, and multi-measurement assessment using validated clinical measurements of disability and QoL. With regard to general disability, more than 10% of patients needed assistance to walk. With regard to arm disability, about 10% of patients had severe disability defined as impairment in carrying out simple tasks. General disability was similar both in polyneuropathic and multi-neuropathic groups, but arm disability appeared more severe in multi-neuropathic patients. QoL profiles were highly deteriorated in our sample with respect to the Italian normative sample. All age brackets were highly impaired except for older patients for whom the QoL picture was only mildly impaired with respect to Italian norms. We believe that our study provides reliable data on QoL in patients with neuropathies and that it may represent a quantitative step forward in understanding the disability of patients with neuropathy.

Altered martial indices before orthopedic surgery are associated with higher rates of complications and greatly affect the patient&rsquo, s functional ability. Oral supplements can optimize the preoperative martial status, with clinical efficacy and the patient&rsquo, s tolerability being highly dependent on the pharmaceutical formula. Patients undergoing elective hip/knee arthroplasty were randomized to be supplemented with a 30-day oral therapy of sucrosomial ferric pyrophosphate plus L-ascorbic acid. The tolerability was 2.7% among treated patients. Adjustments for confounding factors, such as iron absorption influencers, showed a relevant response limited to older patients (&ge, 65 years old), whose uncharacterized Hb loss was averted upon treatment with iron formula. Older patients with no support lost &minus, 2.8 &plusmn, 5.1%, while the intervention group gained +0.7 &plusmn, 4.6% of circulating hemoglobin from baseline (p = 0.019). Gastrointestinal diseases, medications, and possible dietary factors could affect the efficacy of iron supplements. Future opportunities may consider to couple ferric pyrophosphate with other nutrients, to pay attention in avoiding absorption disruptors, or to implement interventions to obtain an earlier martial status optimization at the population level.

(1) Background: It is recommended that an athlete, in order to ensure correct nutrition and performance, should consume between 1.2 and 2.0 g/kg/day of protein, while the daily recommended protein intake for a non-athlete is 0.8and 0.9 mg/kg/day. It is unclear if athletes living in Mediterranean countries are able to meet protein requirements without supplementation, since Mediterranean diet de-emphasizes meat and meat products. (2) Methods: 166 athletes (125 males) enrolled between 2017 and 2019 were required to keep a dietary journal for three consecutive days (2 workdays and 1 weekend day). Athletes had to be &gt, 18 years old, train in a particular sport activity more than 3 h a week and compete at least at an amateur level. Journal data were collected and then translated into macro-nutrient content (grams of protein, carbohydrates, and lipids) by a nutritionist. (3) Results: The protein intake reported by this specific population vary slightly from the Academy of Nutrition and Dietetics (AND), Dietitians of Canada (DC), and the American College of Sports Medicine (ACSM) joint statement recommendation level. Average protein levels without protein supplementation fell within the protein guidelines. Counterintuitively, the intake among those who supplemented their diet with protein was higher compared with those who did not, even when excluding the contribution of supplements. Although the majority of subjects participating in the study were able to meet protein intake recommended for athletes without protein supplementation, 27% of athletes were below the guideline range. (4) Conclusions: these data suggest that athletes&rsquo, nutrition should be more often evaluated by a nutritionist and that they will benefit from increasing their nutritional knowledge in order to make better food choices, resorting to protein supplementation only when effectively needed.

Iron is a fundamental element in human history, from the dawn of civilization to contemporary days. The ancients used the metal to shape tools, to forge weapons, and even as a dietary supplement. This last indication has been handed down until today, when martial therapy is considered fundamental to correct deficiency states of anemia. The improvement of the martial status is mainly targeted with dietary supplements that often couple diverse co-factors, but other methods are available, such as parenteral preparations, dietary interventions, or real-world approaches. The oral absorption of this metal occurs in the duodenum and is highly dependent upon its oxidation state, with many absorption influencers possibly interfering with the intestinal uptake. Bone marrow and spleen represent the initial and ultimate step of iron metabolism, respectively, and the most part of body iron circulates bound to specific proteins and mainly serves to synthesize hemoglobin for new red blood cells. Whatever the martial status is, today’s knowledge about iron biochemistry allows us to embrace exceedingly personalized interventions, which however owe their success to the mythical and historical events that always accompanied this metal.

Mutations in the gene encoding the mitochondrial carrier protein SLC25A46 are known to cause optic atrophy associated with peripheral neuropathy and congenital pontocerebellar hypoplasia. We found novel biallelic SLC25A46 mutations (p.H137R, p.A401Sfs*17) in a patient with Parkinson's disease and optic atrophy. Screening of six unrelated patients with parkinsonism and optic atrophy allowed us to identify two additional mutations (p.A176V, p.K256R) in a second patient. All identified variants are predicted likely pathogenic and affect very conserved protein residues. These findings suggest for the first time a possible link between Parkinson's Disease and SLC25A46 mutations. Replication in additional studies is needed to conclusively prove this link.

Background: There is a growing awareness that nutritional habits may influence risk of several inflammatory and immune-mediated disorders, including autoimmune diseases, through various mechanisms. The aim of the present study was to investigate dietary habits and their relationship with redox homeostasis in the setting of thyroid autoimmunity. Materials and Methods: Two hundred subjects (173 females and 27 males; median age, 37 years) were enrolled. None were under any pharmacological treatment. Exclusion criteria were any infectious/inflammatory/autoimmune comorbidity, kidney failure, diabetes, and cancer. In each subject, serum thyrotropin (TSH), free thyroxine, antithyroid antibodies, and circulating oxidative stress markers were measured. A questionnaire on dietary habits, evaluating the intake frequencies of food groups and adherence to the Mediterranean diet, was submitted to each participant. Results: Among the 200 recruited subjects, 81 (71 females and 10 males) were diagnosed with euthyroid Hashimoto's thyroiditis (HT); the remaining 119 (102 females and 17 males) served as controls. In questionnaires, HT subjects reported higher intake frequencies of animal foods (meat, p = 0.0001; fish, p = 0.0001; dairy products, p = 0.004) compared with controls, who reported higher intake frequencies of plant foods (legumes, p = 0.001; fruits and vegetables, p = 0.030; nuts, p = 0.0005). The number of subjects who preferentially consumed poultry instead of red/processed meat was lower in HT subjects than in controls (p = 0.0141). In logistic regression analysis, meat consumption was associated with increased odds ratio of developing thyroid autoimmunity, while the Mediterranean diet traits were protective. In HT subjects, serum advanced glycation end products (markers of oxidative stress) were significantly higher (p = 0.0001) than in controls, while the activity of glutathione peroxidase and thioredoxin reductase, as well as total plasma antioxidant activity, were lower (p = 0.020, p = 0.023, and p = 0.002, respectively), indicating a condition of oxidative stress. Stepwise regression models demonstrated a significant dependence of oxidative stress parameters on consumption of animal foods, mainly meat. Conclusions: The present study suggests a protective effect of low intake of animal foods toward thyroid autoimmunity and a positive influence of such nutritional patterns on redox balance and potentially on oxidative stress-related disorders.

Background: Progressive supranuclear palsy (PSP) is a rare rapidly progressive, neurodegenerative disease characterized by falls and ocular movement disturbances. The use of health-related quality of life (HR-QoL) measures allows assessing changes in health status induced by therapeutic interventions or disease progress in neurodegenerative diseases. The PSP-QoL is a 45-item, self-administered questionnaire designed to evaluate HR-QoL in PSP. Methods and Results: Here, the PSP-QoL was translated into Italian and validated in 190 PSP (96 women and 94 men; mean age ± standard deviation, 72 ± 6.5; mean disease duration, 4.2 ± 2.3) patients diagnosed according to the Movement Disorder Society criteria and recruited in 16 third level movement disorders centers participating in the Neurecanet project. The mean PSP-QoL total score was 77.8 ± 37 (physical subscore, 46.5 ± 18.7; mental subscore, 33.6 ± 19.2). The internal consistency was high (Cronbach’s alpha = 0.954); corrected item-total correlation was > 0.40 for the majority of items. The significant and moderate correlation of the PSP-QoL with other HR-QoL measures as well as with motor and disability assessments indicated adequate convergent validity of the scale. Gender and geographic location presented a significant impact on the PSP-QoL in our sample with women and patients from the South of Italy scoring higher than their counterparts. Conclusion: In conclusion, the Italian version of the PSP-QoL is an easy, reliable and valid tool for assessment of HR-QoL in PSP.

Progressive supranuclear palsy (PSP) is a rare, rapidly progressive, neurodegenerative disease characterized by falls and ocular movement disturbances. Caring for a partner or relative who suffers from PSP entails a strenuous and demanding task, usually lasting for years that affects carers’ everyday life routines and emotional and social well-being. The 26-item Parkinsonism Carers QoL (PQoL Carer) is a self-administered, concise instrument evaluating the quality of life of caregivers of patients with atypical parkinsonism (both PSP and multiple system atrophy). Here, the PQoL Carer was translated into Italian and validated in 162 carers of PSP patients (54.3% women; mean age (standard deviation), 62.4 (15.4)) diagnosed according to the Movement Disorder Society criteria and recruited in 16 third-level movement disorders centers participating in the Neurecanet project. The mean PQoL total score was 40.66 ± 19.46. The internal consistency was excellent (Cronbach’s alpha = 0.941); corrected item-total correlation was > 0.40 for all the items. A correlation with other health-related quality of life measures as well as with behavioral assessments was shown suggesting adequate convergent validity of the scale. PQoL also correlated with patients’ severity of disease. The discriminant validity of the scale was evidenced by its capacity to differentiate between carers with varying levels of self-reported health (p < 0.001). In conclusion, the Italian version of the PQoL Carer is an easy, consistent, and valid tool for the assessment of the quality of life in carers of PSP patients.

Over the past few years, the contribution of oxysterols to the onset and development of some of the major neurodegenerative diseases (such as Alzheimer's and Parkinson's diseases) has been scientifically asserted, being mainly related to altered brain cholesterol homeostasis. To counteract oxysterol induced inflammation at neuronal level, one possible intervention approach is the administration of some nutrients and/or plant secondary metabolites. On the other hand, the pleiotropic beneficial effects of physical activity seem to play an important role on prevention and counteraction of neurodegenerative diseases, through the modulation of oxysterol homeostasis and the prevention of demyelination. The present review provides a picture of the promising role of nutraceuticals and physical activity on oxysterol-mediated neurodegeneration, pointing out also the different in vitro and in vivo aspects that need to be further investigated for a better understanding of the association of these three counterparts and their overall effect on people at increased risk for neurodegenerative diseases.

Preclinical and clinical studies suggest that many food molecules could interact with drug transporters and metabolizing enzymes through different mechanisms, which are predictive of what would be observed clinically. Given the recent incorporation of dietary modifications or supplements in traditional medicine, an increase in potential food-drug interactions has also appeared. The objective of this article is to review data regarding the influence of food on drug efficacy. Data from Google Scholar, PubMed, and Scopus databases was reviewed for publications on pharmaceutical, pharmacokinetic, and pharmacodynamic mechanisms. The following online resources were used to integrate functional and bioinformatic results: FooDB, Phenol-Explorer, Dr. Duke's Phytochemical and Ethnobotanical Databases, DrugBank, UniProt, and IUPHAR/BPS Guide to Pharmacology. A wide range of food compounds were shown to interact with proteins involved in drug pharmacokinetic/pharmacodynamic profiles, starting from drug oral bioavailability to enteric/hepatic transport and metabolism, blood transport, and systemic transport/metabolism. Knowledge of any food components that may interfere with drug efficacy is essential, and would provide a link for obtaining a holistic view for cancer, cardiovascular, musculoskeletal, or neurological therapies. However, preclinical interaction may be irrelevant to clinical interaction, and health professionals should be aware of the limitations if they intend to optimize the therapeutic effects of drugs.

Background Chemoprevention represents the possibility to prevent, stop or reverse the cancerogenetic process. In this context the interest towards natural extracts and botanical drugs has constantly grown due to their phytochemical content. Castanea sativa Mill. (CSM) extracts showed to exert positive effect in the prevention/counteraction of chronic/degenerative diseases, therefore, we evaluated the potential chemopreventive effect of CSM bark extract. Methods Flow cytometry (FCM) analyses of Jurkat cells treated with CSM bark extract (0–500 μg·mL−1) for 24–72 h allowed evaluating its cytotoxicity and ability to induce apoptosis through the intrinsic or extrinsic pathways. Moreover, to evaluate CSM bark extract selectivity towards cancer cells, its cytotoxic and pro-apoptotic effect was also evaluated in human peripheral blood lymphocytes (PBL). Results CSM bark extract induced apoptosis in Jurkat cells in a dose- and time- dependent manner activating the extrinsic pathways as evidenced by the increase of activated caspase-8 positive cells. Moreover, IC50 calculated after 24 h treatment resulted 304 and 128 μg·mL−1 in PBL and Jurkat cells respectively. Conclusions Our data suggest that CSM bark extract might be considered an interesting potential anti-cancer agent, since it induces apoptosis in cancer cells without appreciable cytotoxic effects on non-transformed cells. Electronic supplementary material The online version of this article (doi:10.1186/s12906-017-1756-6) contains supplementary material, which is available to authorized users.

Cereals and legumes are key components of a healthy and balanced diet. Accordingly, many national nutritional guidelines emphasize their health promoting properties by placing them at the base of nutritional food pyramids. This concept is further validated by the observed correlation between a lower risk and occurrence of chronic diseases and the adherence to dietary patterns, like the Mediterranean diet, in which cereal grains, legumes and derived products represent a staple food. In the search for a dietary approach to control/prevent chronic degenerative diseases, protein derived bioactive peptides may represent one such source of health-enhancing components. These peptides may already be present in foods as natural components or may derive from hydrolysis by chemical or enzymatic treatments (digestion, hydrolysis or fermentation). Many reports are present in the literature regarding the bioactivity of peptides in vitro and a wide range of activities has been described, including antimicrobial properties, blood pressure-lowering (ACE inhibitory) effects, cholesterol-lowering ability, antithrombotic and antioxidant activities, enhancement of mineral absorption/bioavailability, cyto- or immunomodulatory effects, and opioid-like activities. However it is difficult to translate these observed effects to human. In fact, the active peptide may be degraded during digestion, or may not be absorbed or reach the target tissues at a concentration necessary to exert its function. This review will focus on bioactive peptides identified in cereals and legumes, from an agronomical and biochemical point of view, including considerations about requirements for the design of appropriate clinical trials necessary for the assessment of their nutraceutical effect in vivo.

Knowledge about mineral bone disorder (MBD) management in non-dialysis chronic kidney disease (ND-CKD) patients is scarce, although essential to identifying areas for therapeutic improvement. We prospectively evaluated current management of CKD-MBD in two visits, performed 6 months apart, in 727 prevalent ND-CKD stage 3b–5 patients from 19 nephrology clinics. Therapeutic inertia was defined as lack of treatment despite hyperphosphatemia and/or hypocalcemia, and/or hyperparathyroidism. The primary endpoint was the prevalence of achieved target for CKD-MBD parameters and related treatments (phosphate binders, vitamin D and calcium supplements). The secondary endpoint was the assessment of prevalence and clinical correlates of therapeutic inertia. Over 65 % of patients did not reach parathormone (PTH) targets, while 15 and 19 % did not reach phosphate and calcium targets, respectively. The proportion of untreated patients decreased from stage 3b to 5 (at baseline, from 60 to 16 %, respectively). From baseline to the 6-month visit, the achievement of targets remained stable. Low protein diet was prescribed in 26 % of patients, phosphate binders in 17.3 % (calcium-based binders 15.5 %, aluminium binders 1.8 %), and vitamin D in 50.5 %. The overall prevalence of therapeutic inertia at the 6-month visit was 34.0 % (for hyperphosphatemia, 54.3 %). Compared to CKD stage 3, the likelihood of therapeutic inertia was 40 and 68 % lower at stage 4 and 5, respectively. PTH, calcium and phosphate targets were not reached in a significant proportion of patients. One-third of patients with at least one MBD parameter not-at-target remained untreated. Therapeutic inertia regarding CKD-MBD treatment may be a major barrier to optimizing the prevention and cure of CKD-MBD.

OBJECTIVES: To assess the impact of a personalized diet, with or without addition of VSL#3 preparation, on biomarkers of inflammation, nutrition, oxidative stress and intestinal microbiota in 62 healthy persons aged 65-85 years. DESIGN: Open label, randomized, multicenter study. PRIMARY ENDPOINT: High-sensitivity C-reactive protein. SETTING: Community. INTERVENTIONS: Eight week web-based dietary advice (RISTOMED platform) alone or with supplementation of VSL#3 (2 capsules per day). The RISTOMED diet was optimized to reduce inflammation and oxidative stress. MEASUREMENTS: Blood and stool samples were collected on days 1 and 56. RESULTS: Diet alone reduced ESR (p = 0.02), plasma levels of cholesterol (p < 0.01) and glucose (p = 0.03). Addition of VSL#3 reduced ESR (p = 0.05) and improved folate (p = 0.007), vitamin B12 (p = 0.001) and homocysteine (p < 0.001) plasma levels. Neither intervention demonstrated any further effects on inflammation. Subgroup analysis showed 40 participants without signs of low-grade inflammation (hsCRP

Degeneration of peripheral motor axons is a common feature of several debilitating diseases including complicated forms of hereditary spastic paraplegia. One such form is caused by loss of the mitochondrial energy-dependent protease paraplegin. Paraplegin-deficient mice display a progressive degeneration in several axonal tracts, characterized by the accumulation of morphological abnormal mitochondria. We show that adenoassociated virus-mediated (AAV-mediated) intramuscular delivery of paraplegin halted the progression of neuropathological changes and rescued mitochondrial morphology in the peripheral nerves of paraplegin-deficient mice. One single injection before onset of symptoms improved the motor performance of paraplegin-deficient mice for up to 10 months, indicating that the peripheral neuropathy contributes to the clinical phenotype. This study provides a proof of principle that gene transfer may be an effective therapeutic option for patients with paraplegin deficiency and demonstrates that AAV vectors can be successfully employed for retrograde delivery of an intracellular protein to spinal motor neurons, opening new perspectives for several hereditary axonal neuropathies of the peripheral nerves.

Osteoid osteoma is a small benign tumor that requires treatment due to the intense pain it causes. Surgical therapy has been the ablative technique of choice after a failure of medical therapy. Recently, numerous less invasive, alternative procedures have been proposed: drill trepanation with or without ethanol injections, cryoablation, and thermoablation with laser or radiofrequency. The aim of this review is to retrospectively assess the effect of radiofrequency (RF) thermoablation in the treatment of primary non-spinal osteoid osteoma. From June 2001 to July 2003, we treated 106 patients affected by osteoid osteoma with RF thermoablation. Five patients with spinal osteoid osteoma and four with a previously treated osteoma were excluded from the study. In this paper, we assess the results obtained in a selected group of 97 primary non-spinal osteoid osteoma. The lesions were predominantly in the metaphysics of the femur. Central nidus calcifications were frequent and there was no prevalence for which side they occurred. Primary success was achieved in 82 patients (85%), while we obtained secondary success in 15 patients (15%). In two patients (2%), pain persisted between the two treatments and failed to be resolved, even after the second treatment; therefore, surgical excision was performed and complete resolution was obtained. No complications were reported. In conclusion, our results confirm that the treatment of choice for non-spinal osteoid osteoma is RF thermoablation, offering several advantages over ablative techniques.