Parkinson's disease (PD) is an aging-related disease and the second most common neurodegenerative disease after Alzheimer's disease. The main symptoms of PD are movement disorders accompanied with ...deficiency of neurotransmitter dopamine (DA) in the striatum due to cell death of the nigrostriatal DA neurons. Two main histopathological hallmarks exist in PD: cytosolic inclusion bodies termed Lewy bodies that mainly consist of α-synuclein protein, the oligomers of which produced by misfolding are regarded to be neurotoxic, causing DA cell death; and black pigments termed neuromelanin (NM) that are contained in DA neurons and markedly decrease in PD. The synthesis of human NM is regarded to be similar to that of melanin in melanocytes; melanin synthesis in skin is via DOPAquinone (DQ) by tyrosinase, whereas NM synthesis in DA neurons is via DAquinone (DAQ) by tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC). DA in cytoplasm is highly reactive and is assumed to be oxidized spontaneously or by an unidentified tyrosinase to DAQ and then, synthesized to NM. Intracellular NM accumulation above a specific threshold has been reported to be associated with DA neuron death and PD phenotypes. This review reports recent progress in the biosynthesis and pathophysiology of NM in PD.
Objective To evaluate the implications of assisted reproductive technologies (ART) on neonatal birth weight. Design A retrospective study using analysis of covariance and multiple logistic regression ...analysis of the Japanese ART registry. Setting Japanese institutions providing ART treatment. Patient(s) A total of 25,777 singleton neonates reaching term gestation following ART during the years 2007–2008, with 11,374 achieved through fresh embryo transfers (fresh ET) and 14,403 achieved through frozen-thawed embryo transfers (FET). Intervention(s) None. Main Outcome Measure(s) Birth weight. Result(s) The mean birth weight after FET was significantly higher compared with fresh ET and all Japanese births (3,100.7 ± 387.2 g, 3,009.8 ± 376.8 g, and 3,059.6 ± 369.6 g, respectively). The risk for low birth weight in FET was significantly lower compared with fresh ET. In fresh ET, ovarian stimulations were associated with about twofold risk of low birth weight compared with natural cycle. Regarding to the duration of embryonic culture, the risks resulting from a shorter culturing time were significantly higher compared with a longer culturing time in fresh ET. Conclusion(s) The best method of embryo transfer for fetal growth was FET after extended culturing until blastocyst stage. However, further investigations should be performed to understand the safety of ART treatment.
Tyrosine hydroxylase (TH), which catalyzes the conversion of l-tyrosine to l-DOPA, is the rate-limiting enzyme in the biosynthesis of catecholamines. It is well known that both α-synuclein and 14-3-3 ...protein family members bind to the TH molecule and regulate phosphorylation of its N-terminus by kinases to control the catalytic activity. In this present study we investigated whether other proteins aside from these 2 proteins might also bind to TH molecules. Nano-LC-MS/MS analysis revealed that 5′-nucleotidase domain-containing protein 2 (NT5DC2), belonging to a family of haloacid dehalogenase-type (HAD) phosphatases, was detected in the immunoprecipitate of PC12D cell lysates that had been reacted with Dynabeads protein G-anti-TH antibody conjugate. Surprisingly, NT5DC2 had already been revealed by Genome-Wide Association Studies (GWAS) as a gene implicated in neuropsychiatric disorders such as schizophrenia, bipolar disorder, which are diseases related to the abnormality of dopamine activity in the brain, although the role that NT5DC2 plays in these diseases remains unknown. Therefore, we investigated the effect of NT5DC2 on the TH molecule. The down-regulation of NT5DC2 by siRNA increased the synthesis of catecholamines (dopamine, noradrenaline, and adrenaline) in PC12D cells. These increases might be attributed to the catalytic activity of TH and not to the intracellular stability of TH, because the intracellular content of TH assessed by Western blotting was not changed by the down-regulation of NT5DC2. Collectively, our results indicate that NT5DC2 inhibited the synthesis of dopamine by decreasing the enzymatic activity of TH.
•Nano-LC-MS/MS revealed that NT5DC2 binds to tyrosine hydroxylase in PC12D cells.•Down-regulation of NT5DC2 by siRNA increased the synthesis of catecholamines.•NT5DC2 had already been revealed as a gene implicated in neuropsychiatric disorders.
Dietary content during pregnancy is important because it is necessary for the growth of the fetus. With the assumption that the nutritional status of the fetus can be monitored by measuring amino ...acid concentrations in the amniotic fluid, we investigated whether the habitual dietary intake of pregnant women affected the composition of the amniotic fluid and the significance of performing amniotic fluid analysis. The subjects were 34 mothers who delivered full-term babies by cesarean section. Three biological samples were collected from the mothers: blood, cord blood, and amniotic fluid. At the same time, the mothers’ prenatal nutritional intake information was also recorded. When the amino acid contents of the samples were compared with the mothers’ nutrient intake, many amino acids in the amniotic fluid were positively correlated with lipid intake, but not with protein intake. There was a negative correlation between lipid intake and carbohydrate intake, and the amino acid contents of the amniotic fluid were also negatively correlated with carbohydrate intake. The results of this study were consistent with those found in animal models, suggesting that the analysis of amniotic fluid may be a useful method to investigate the effects of habitual diet during human pregnancy on the fetus.
Background
The prognosis of patients with cholangiocarcinoma is unsatisfactory. Therefore, evaluation of prognostic factors and establishment of new therapeutic strategies are needed to improve their ...long-term survival. The aim of this study was to identify useful prognostic factors for patients with intrahepatic, hilar, and distal cholangiocarcinoma.
Materials and Methods
Records of 127 patients with cholangiocarcinoma (21 with intrahepatic cholangiocarcinoma, 50 with hilar cholangiocarcinoma, and 56 with distal cholangiocarcinoma) who underwent surgical resection were reviewed retrospectively. Relationships between survival and clinicopathological factors including patient demographics and tumor characteristics were evaluated using univariate and multivariate analysis.
Results
For all 127 patients, overall 1-, 3-, 5-year survival rates were 80, 51, and 40%, respectively. Univariate analysis revealed that adjuvant chemotherapy (
P
= .049), tumor differentiation (
P
= .014), lymph node metastasis (
P
< .001), surgical margin status (
P
< .001), UICC pT factor (
P
< .001), and UICC stage (
P
< .001) were associated significantly with survival. UICC pT factor (
P
= .007), adjuvant chemotherapy (
P
= .009), surgical margin status (
P
= .012), and lymph node metastasis (
P
= .014) remained independently associated with long-term survival by multivariate analysis. The 5-year survival rates of patients with or without positive surgical margins were 13 and 49%, respectively. The 5-year survival rates of patients treated with or without adjuvant chemotherapy were 47 and 36%, respectively.
Conclusions
R0 resection and adjuvant chemotherapy may be mandatory to achieve long-term survival for patients with cholangiocarcinoma.
Purpose
Previous evidence regarding the impact of exercise interventions on chemotherapy-induced peripheral neuropathy often focuses on lower-extremity functions, such as muscle strength and balance ...ability, while their effects on upper extremities remain unknown. We aimed to evaluate the efficacy of combined hand exercise intervention on upper-extremity function, symptoms, and quality-of-life in patients with chemotherapy-induced peripheral neuropathy (CIPN).
Methods
After screening 341 patients, 42 were randomly assigned to either the intervention (n = 21) or control (n = 21) group. Participants were evaluated at baseline (T0) and after one (T1) and two (T2) chemotherapy cycles. The primary outcome was upper-extremity function measured using the Michigan Hand Outcomes Questionnaire (MHQ) at T2. The intention-to-treat and as-treated populations were compared using a mixed-effect model.
Results
In the intention-to-treat analysis, the decline in activities of daily living of MHQ was significantly suppressed in the intervention group compared with that in the control group at T2 (difference: 7.23; 95% confidence interval: 0.35–14.10). Similarly, in the as-treated analysis, the decline in activities of daily living of MHQ was significantly suppressed in the intervention group compared with that in the control group at T2 (difference: 13.09; 95% confidence interval: 5.68–20.49). Pain also significantly improved in the intervention group compared with that in the control group at T2 (difference: 13.21; 95% confidence interval: − 22.91 to − 3.51).
Conclusion
The combined hand exercise intervention may improve upper-extremity function, such as by suppressing decline in ADL, and reduce pain in patients with CIPN.
Residual pancreatic endocrine function is important for maintaining metabolic status after pancreatectomy and is closely related to patient nutritional status and prognosis. In contrast to insulin ...secretion, the significance of glucagon secretion following pancreatectomy remains unclear. In this study, we assessed the changes in pancreatic glucagon secretion during pancreatectomy to determine their pathophysiological significance. We evaluated glucagon and insulin secretion using a liquid meal tolerance test before and after pancreatectomy in patients scheduled to undergo pancreaticoduodenectomy (PD) or distal pancreatectomy (DP). After pancreatectomy, fasting plasma glucagon levels were significantly decreased in both the PD (n = 10) and DP (n = 5) groups (PD: from 18.4 to 10.5 pg/mL, p = 0.037; DP: from 21.0 to 12.1 pg/mL, p = 0.043), whereas postprandial plasma glucagon levels were not changed. In the liquid meal tolerance test after pancreatectomy, 60-min plasma glucagon levels and the area under the curve (AUC) for 0–120 min of PD were significantly higher than those for DP (60-min plasma glucagon: PD 49.0 vs. DP 21.7 pg/mL, p = 0.040; AUC0–120min: PD 4,749 vs. DP 3,564 μg min/mL, p = 0.028). Postoperative plasma glucose, serum insulin, and serum C-peptide levels during the liquid meal tolerance test were not significantly different between the two groups. Although fasting plasma glucagon levels decreased, postprandial glucagon responses were maintained after both PD and DP. The difference in residual meal-stimulated glucagon response between PD and DP suggests that a relative excess of postprandial glucagon is involved in the postoperative nutritional status after PD through its impact on systemic metabolic status.
Virtual reality-based mirror therapy (VRMT) has recently attracted attention as a novel and promising approach for treating upper extremity dysfunction in patients with stroke. However, the clinical ...efficacy of VRMT has not been investigated.
This study aimed to conduct a meta-analysis to evaluate the effects of VRMT on upper extremity dysfunction in patients with stroke. We screened articles published between January 2010 and July 2022 in PubMed, Scopus, MEDLINE, and Cochrane Central Register of Controlled Trials. Our inclusion criteria focused on randomized controlled trials (RCTs) comparing VRMT groups with control groups (e.g., conventional mirror therapy, occupational therapy, physical therapy, or sham therapy). The outcome measures included the Fugl-Meyer assessment upper extremity test (FMA-UE), the box and block test (BBT), and the manual function test (MFT). Risk of bias was assessed using the Cochrane Collaboration risk-of-bias tool 2.0. We calculated the standardized mean differences (SMD) and 95% confidence intervals (95% CI). The experimental protocol was registered in the PROSPERO database (CRD42022345756).
This study included five RCTs with 148 stroke patients. The meta-analysis showed statistical differences in the results of FMA-UE SMD = 0.81, 95% CI (0.52, 1.10),
< 0.001, BBT SMD = 0.48, 95% CI (0.16, 0.80),
= 0.003, and MFT SMD = 0.72, 95% CI (0.05, 1.40),
= 0.04 between the VRMT and the control groups.
VRMT may play a beneficial role in improving upper extremity dysfunction after stroke, especially when combined with conventional rehabilitation. However, there were differences in the type of VRMT, stage of disease, and severity of upper extremity dysfunction. Multiple reports of high-quality RCTs are needed to clarify the effects of VRMT.
https://www.crd.york.ac.uk/prospero/, identifier CRD42022345756.
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