Anxiety,depression,and quality of life in Parkinson's disease:the implications of multidisciplinary treatment

Anxiety and depression in Parkinson's disease(PD) reduce well-being of the patients.Emotional alterations influence motor skills and cognitive performance;moreover,they contribute significantly and independently to worsen rehabilitative treatment response.We investigated anxiety,depression,and quality of life in PD patients subjected to multidisciplinary rehabilitative training.The self-controlled study included 100 PD patients(49 males and 51 females with the mean age of 64.66 years) admitted to 60 days hospitalization rehabilitative program,between January 2017 and December 2018.Motor,cognitive,linguistic abilities,and functional independence were evaluated at admission(T0 baseline visit) and 60 days after(T1) the multidisciplinary rehabilitation including motor exercises,speech therapies,and cognitive intervention.The multidisciplinary rehabilitation improved functional status in PD patients and exerted its positive effects on mood,motor abilities,autonomy in the activities of daily life,perception of quality of life,cognitive performance and speech skills.Non-motor symptoms may worsen severe disability and reduce quality of life.They are often poorly recognized and inadequately treated.Nonetheless,multidisciplinary rehabilitative training represents an optimal strategy to improve disease management.The study was approved by Istituito di Ricovero e Cura a Carattere Scientifico(IRCCS) Centro Neurolesi "Bonino-Pulejo" Ethical Committee(approval No.6/2016) in June 2016.     

Hyperhomocysteinemia and the MTHFR C677T polymorphism promote steatosis and fibrosis in chronic hepatitis C patients

The factors and mechanisms implicated in the development of hepatitis C virus (HCV)-related steatosis are unknown. Hyperhomocysteinemia causes steatosis, and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism induces hyperhomocysteinemia. We investigated the role of these factors in the development of HCV-related steatosis and in the progression of chronic hepatitis C (CHC). One hundred sixteen CHC patients were evaluated for HAI, fibrosis and steatosis grades, body mass index, HCV genotypes, HCV RNA levels, homocysteinemia, and the MTHFR C677T polymorphism. Hyperhomocysteinemia was associated with the TT genotype of MTHFR (r = 0.367; P = .001). Median values of homocysteine in the CC, CT, and TT genotypes of the MTHFR gene were 9.3, 12.2, and 18.6 micromol/L, respectively (P = .006). Steatosis correlated with the MTHFR polymorphism, homocysteinemia, HAI and fibrosis. Steatosis above 20% was significantly associated with fibrosis. Prevalence and high grade (>20%) of steatosis were 41% and 11% in CC, 61% and 49% in CT, and 79% and 64% in TT, respectively (P = .01). Relative risk of developing high levels of steatosis was 20 times higher for TT genotypes than CC genotypes. According to multivariate analysis, steatosis was independently associated with hyperhomocysteinemia (OR = 7.1), HAI (OR = 3.8), liver fibrosis (OR = 4.0), and HCV genotype 3 (OR = 4.6). On univariate analysis, fibrosis was associated with age, steatosis, MTHFR, homocysteinemia and HAI; however, on multivariate analysis, liver fibrosis was independently associated with age (P = .03), HAI (P = .0001), and steatosis (P = .007). In conclusion, a genetic background such as the MTHFR C677T polymorphism responsible for hyperhomocysteinemia plays a role in the development of higher degree of steatosis, which in turn accelerates the progression of liver fibrosis in CHC.     

Endothelial nitric oxide synthase gene influences the risk of pre-eclampsia, the recurrence of negative pregnancy events, and the maternal-fetal flow

OBJECTIVES: Pre-eclampsia is associated with vascular endothelial dysfunction, adverse pregnancy outcome and cardiovascular disease in later life. An inadequate nitric oxide availability related to polymorphisms in the endothelial nitric oxide synthase gene (eNOS) might predispose to the disease. METHODS: We investigated the role of eNOS T-786C, G894T and 4a4b polymorphisms in predisposing to both pre-eclampsia and the recurrence of negative pregnancy events, per se and in the presence of angiotensin-converting enzyme (ACE) DD genotype, and investigated their influence on maternal-fetal flow in 106 non-thrombophilic women with a history of pre-eclampsia, compared with 106 women with a history of normal pregnancy. RESULTS: No association between eNOS polymorphisms and predisposition to pre-eclampsia was found; nevertheless, the contemporary presence of eNOS 894TT and -786CC genotypes represented a susceptibility factor to the disease. In 48 out of 106 women, documented complications (pre-eclampsia and fetal growth restriction) were present in the current pregnancy. The eNOS 894TT genotype influenced the risk of recurrence of negative events (odds ratio = 5.45), particularly in contemporary women homozygous for both eNOS 894TT and ACE DD genotypes (odds ratio = 11.4). Throughout the pregnancy, a progressive alteration of maternal-fetal flow indices was found in women carrying the eNOS 894TT genotype, and this effect was strengthened in women with the contemporary presence of the ACE DD genotype. CONCLUSIONS: An original finding is the increased risk of pre-eclampsia and recurrence of pregnancy negative events, probably by modulating the maternal-fetal flow, in women homozygous for the eNOS 894T allele previously analyzed for the ACE I/D polymorphism.     

Artemether: a new therapeutic strategy in experimental rheumatoid arthritis

The current research was designed to determine the effect of artemether in treatment of experimental rheumatoid arthritis. Collagen-induced arthritis was induced in Lewis rats. The intramusculary administration of artemether (ART) and intraperitoneally injection of methotrexate (MTX) were started on day 25 postimmunization and continued until final assessment on day 35. During this period, clinical examination was taken intermittently. The anticollagen type II antibody (CII Ab) and nitric oxide synthesis were measured. The paws and kness were then removed for histopathology and radiography assay.The biocompatibility of ART and MTX were assessed using fibrosarcoma cell line. Data showed that i.m. injection of ART to arthritic rats induced a significant reduction in paw edema. This beneficial effect was associated with a significant decrease in anti-CII antibody response compared with untreated rats. Histopathological assessment showed a reduced inflammatory cell infiltrate in joints of treated rats; tissue edema, and bone erosion in the paws were markedly reduced following ART therapy. Furthermore, our radiography results paralleled our histological findings. Cytotoxicity analysis of ART showed greater tolerability compared with MTX. Treatment with ART significantly diminished NO formation in treated rats compared with nontreated controls. Our data shed light on the therapeutic efficacy of artemether in experimental rheumatoid arthritis compared with a choice drug (methotrexate), and it may be offered as a second-line drug in treatment of rheumatoid arthritis.     

Potential effectiveness of stored cord blood (non-frozen) for emergency use

Bone marrow has been used for a number of years to assist patients who have accidentally received potentially lethal levels of irradiation. The intent of the transplant is to replace the victim's own bone marrow that has been injured from the irradiation or to act as temporary support to allow the patient's own marrow to recover. Following the Chernobyl disaster, some victims received bone marrow that was HLA matched or partially matched. However, donor marrows were difficult to obtain in adequate numbers; as a substitute for bone marrow, frozen fetal liver cells were used as a source of hematopoietic stem cells. The use of fetal livers, however, was unsuccessful. Human umbilical cord blood, currently considered an excellent source of hematopoietic stem cells, was not used at Chernobyl. For several years, we have been able experimentally to keep SJL/J mice alive with the use of human umbilical cord blood after the animals received lethal levels of irradiation. This finding suggests that under certain conditions human cord blood does not have to be HLA matched to facilitate rescue from irradiation. In addition, there are reports of unmatched HLA cord blood being used successfully for marrow transplantation. If human cord blood does not have to be matched for HLA, there may be emergency cataclysmic circumstances where the availability of umbilical cord blood may be of considerable value. To simulate a clinical situation such as a nuclear accident, in which human cord blood might serve as a source of stem cells for marrow transplantation, we attempted to rescue immunocompetent mice after 900 cGY of irradiation with the use of (nonfrozen) human cord blood stored in a blood bank. The blood was stored under routine conditions (3–6 °C) for 5 and 7 days in special bags that allow transmission of oxygen. Following lethal levels of irradiation, the cord blood was administered to the animals and a significant survival rate was obtained.     

Left atrial remodelling in patients undergoing transcatheter aortic valve implantation: a speckle-tracking prospective, longitudinal study

Aortic stenosis (AS) results in several left ventricular (LV) disturbances as well as progressive left atrial (LA) enlargement and dysfunction. Transcatheter aortic valve implantation (TAVI) reverses LV remodelling and improves overall systolic function but its effect on LA function remains undetermined. The aim of this prospective, longitudinal study was to investigate the effects of TAVI on LA structure and function. We studied thirty-two patients with severe symptomatic AS who underwent TAVI, using standard and 2-dimensional speckle-tracking echocardiography before, at 40-day and at 3-month follow-up. Following TAVI, mean transvalvular gradient decreased (p < 0.001). Both LA area index and LA volume index decreased at 40-day follow-up (16.2 ± 6.4 vs. 12.5 ± 2.9 cm²/m², and 47.3 ± 12.0 vs. 42.8 ± 12.5 mL/m², respectively, p < 0.05) and values remained unchanged at 3 months. The reduction of LA size was accompanied by a significant increase in global peak atrial longitudinal strain (14.4 ± 3.9 vs. 19.1 ± 4.7 %, p < 0.001) and in global peak atrial contraction strain (8.4 ± 2.5 vs. 11.0 ± 4.1 %, p < 0.05) at 3-month follow-up. LA stiffness measurements significantly decreased 3 months after TAVI (0.93 ± 0.59 vs. 0.65 ± 0.37, respectively, p < 0.001). Trans-aortic mean gradient change and pre-procedural LA volume were identified as predictors of global peak atrial longitudinal strain increase (β = ?0.41, β = ?0.35, respectively, p < 0.0001) while pre-procedural LA volume and trans-aortic mean gradient change as predictor of LA volume index reduction 3 months after TAVI (β = ?0.37, β = ?0.28, respectively, p < 0.0001). TAVI is associated with significant recovery of LA structure and function suggesting a reverse cavity remodelling. Such functional recovery is primarily determined by the severity of pre-procedural valve stenosis.