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Introduction Nocturnal stridor, a life-threatening condition linked to respiratory failure and sudden death during sleep, is a serious issue in patients with multiple system atrophy (MSA). However, little is known about polysomnographic findings and clinical features of MSA patients with nocturnal stridor. Hence, we investigated video-polysomnography (VPSG) findings and clinical features associated with nocturnal stridor in patients with MSA. Methods We retrospectively analyzed the clinical data of patients with MSA (n = 49) who underwent overnight VPSG for the evaluation of sleep-disordered breathing. The presence of nocturnal stridor was confirmed based on overnight VPSG findings. Clinical data, including VPSG findings and clinical features, were compared between MSA patients with and without nocturnal stridor. Results Nocturnal stridor was present in 31 (63.3%) patients with MSA. Patients with stridor showed significantly higher apnea-hypopnea, respiratory disturbance, and oxygen desaturation indices than those without stridor (P = 0.024, P = 0.049, and P = 0.006, respectively). Patients with stridor had more severe axial motor features, more impaired activities of daily living, and longer disease duration than those without stridor (P = 0.012, P = 0.036, and P = 0.003, respectively). However, there were no significant between-group differences in sex, age at disease onset, MSA subtype, parkinsonian features, cerebellar ataxia, residual urine volume, or systolic and diastolic blood pressure change. Conclusions MSA with nocturnal stridor is related to higher apnea indices in conjunction with higher O2 desaturation index, more severe axial motor features, more impaired activities of daily living, and longer disease duration.

Background Alpha-synuclein (α-Syn) immunostaining in the enteric nervous system (ENS) has been investigated to determine the role of diagnostic biomarker of Parkinson's disease (PD). However, determining factors for alpha-synuclein (α-Syn) deposition in the ENS of humans are still unclear. We aimed to investigate a possible association between SNCA variants and the presence of α-Syn immunostaining in the ENS in patients with PD and healthy individuals. Methods The study subjects consisted of 38 patients with PD and 46 healthy individuals. α-Syn immunohistochemistry was performed for gastric and colonic mucosal tissues of patients with PD and controls. Mucosal biopsy tissues of the ENS were obtained using standard biopsy forceps by endoscopic gastroduodenoscopy or colonoscopy. Two variants within the SNCA gene (the single nucleotide polymorphism [SNP] rs11931074 and the microsatellite REP1) were genotyped. Results In patients with PD, the rs11931074 (G allele) was significantly associated with the presence of α-Syn immunostaining in the ENS (OR = 5.96, 95% CI = 1.70–20.97, P = 0.01). In an interaction analysis, SNP rs11931074–PD status interaction was significantly associated with positive α-Syn immunostaining in the ENS (OR = 7.33, 95% CI = 1.58–33.88, P = 0.01). Longer SNCA REP1 alleles were not associated with positive α-Syn immunostaining in the ENS. Conclusion This exploratory study demonstrated that α-Syn deposition in the ENS may be associated with SNCA variants in patients with PD.

Metabolomics is a powerful tool for the investigation of interactions between diet, nutrients, and human metabolism. Ecklonia cava is an edible brown alga that is abundantly found in Korea and Japan and contains unique polyphenols referred to as phlorotannins. However, there are few metabolomics studies related to the effects of polyphenols in humans. In this study, we performed a mass spectrometry-based metabolomics analysis of urine samples from participants with a body mass index (BMI) higher than 25 kg/m2 and lower than 30 kg/m2 to investigate the effects of the intake of seapolynol isolated from E. cava. Metabolomic profiling showed that the levels of riboflavin, urocanic acid, 5-hydroxy-6-methoxyindole glucuronide, and guanidino valeric acid were significantly increased in the seapolynol intake group compared with the placebo group. A correlation analysis was performed to identify the association between the metabolites’ levels and clinical characteristics related to body fat. Among the metabolites whose concentrations changed in the seapolynol intake group, riboflavin was associated with BMI, body weight, fat mass, and percent body fat. These findings suggest that the decreased body fat induced by the intake of seapolynol is related to an increase in the antioxidant effect of riboflavin.

Introduction While metals have been implicated in the pathophysiology of Parkinson's disease (PD), the clinical evidence is scarce. Further, the contribution of metals for the risk or clinical presentation of PD remains to be explored. Methods To investigate the associations between the level of metals in blood serum and PD risk or clinical presentation, including sex-related differences, we studied 325 PD patients and age- and sex-matched 304 controls. We collected clinical data of the PD patients, including age at onset, PD duration, levodopa-equivalent dose (LED), Hoehn and Yahr stage (H-Y stage), presence of motor fluctuation, levodopa-induced dyskinesia (LID), freezing of gait, hallucination, and Mini-Mental State Examination (MMSE) score. Iron, copper, and zinc levels in serum were assayed by inductively coupled plasma mass spectrometry. Statistical analyses were performed to determine the sex-related differences in metal levels. Results Among the three metal elements tested, serum copper levels showed significant correlations with PD risk or clinical presentation. Higher copper levels were associated with a decreased PD risk. Higher copper or lower iron levels were associated with the risk of LID in women. Serum copper levels were negatively correlated with MMSE scores in PD patients. Conclusions This clinical study suggests significant associations between serum metal levels and PD risk or essential clinical features, demonstrating the possible roles of metals in PD pathogenesis or symptom development.

Appropriate nutrient intake is essential for maintaining health and resisting disease. The current study investigated the association between household income quintile and nutrient intake using data from KNHANES 2019. A total of 5088 South Korean adults were analyzed. The estimated average requirement cut-point method, extended to handle participants with intakes higher than the tolerable upper level, was utilized to determine the need for dietary modification. The suitability of overall vitamin, overall mineral, and individual nutrient intake was evaluated by logistic regression analysis. Subgroup analysis was performed on overall mineral intake suitability. None of the individual nutrients had an intake ratio of over 70%, with the ratio being under 30% for some nutrients. The intake of iron, phosphorus, vitamin B9, and vitamin C had a significant upward trend as household income rose. A subgroup analysis revealed sex differences in the trends of overall mineral intake. The results revealed that some nutrients are not consumed appropriately in the Korean population. Furthermore, they suggest that household income is significantly associated with the intake of overall minerals and several individual nutrients. These results suggest that nutritional assistance is required for certain vulnerable groups, and provide supplementary data for appropriate interventions or further research.

Introduction Parkinson's disease (PD) is a debilitating, neurodegenerative condition frequently complicated by psychiatric symptoms. Patients with PD may be at higher risk for suicide than the general population, but previous estimates are limited and conflicting. The aim of this study is to estimate the suicide rate based on the clinical case registry and to identify risk factors for suicide among patients diagnosed with PD. Methods The target sample consisted of 4362 patients diagnosed with PD who were evaluated at a general hospital in Seoul, South Korea, from 1996 to 2012. The standardized mortality ratio for suicide among PD patients was estimated. In order to identify the clinical correlates of suicide, case-control study was conducted based on retrospective chart review. The 29 suicide cases (age: 62.3 ± 13.7 years; females: 34.5%) were matched with 116 non-suicide controls (age: 63.5 ± 9.2 years; females 56.9%) by the year of initial PD evaluation. Results The SMR for suicide in PD patients was 1.99 (95% CI 1.33–2.85). Mean duration from time of initial diagnosis to suicide among cases was 6.1 ± 3.5 years. Case-control analysis revealed that male, initial extremity of motor symptom onset, history of depressive disorder, delusion, any psychiatric disorder, and higher L-dopa dosage were significantly associated with suicide among PD patients. Other PD-related variables such as UPDRS motor score were not significantly associated with death by suicide. Conclusion Suicide risk in PD patients is approximately 2 times higher than that in the general population. Psychiatric disorders, and also L-dopa medication need further attention with respect to suicide.

Acute liver failure (ALF) is characterized by loss of liver function in response to sustained augmentation of the acute-phase response (APR) in the liver, which can progress even to death. Although the inflammatory interleukin-6 (IL-6)–axis is a crucial factor that drives the hepatic APR by releasing diverse acute-phase proteins (APPs), therapeutic strategies to block the IL-6–STAT3-mediated APR are not well developed. Here, we show that the nuclear receptor retinoic acid-related orphan receptor α (RORα) limits APR-mediated liver injury by inhibiting the hepatic IL-6–STAT3 signaling pathway. Administration of JC1-40, an RORα activator, diminished diethylnitrosamine-induced acute liver injury and repressed transcriptional expression of APPs such as CXCL1 and LCN2 in mice. IL-6-mediated activation of STAT3 was repressed after RORα activation by either adenoviral infusion of RORα or JC1-40 treatment in primary hepatocytes. Activation of RORα decreased transcriptional expression of IL-6 receptor α, an upstream activator of STAT3, both in vitro and in vivo. This may be one mechanism underlying the RORα-mediated inhibition of STAT3. Taken together, our results suggest that RORα is a regulator of the hepatic IL-6–STAT3 signaling pathway and may be a new therapeutic target for treating APR-associated inflammatory ALF.

The aim of this study was to examine the correlation between the tongue coating thickness (TCT) and ultraviolet (UV) fluorescence and propose a new method for the estimation of TCT using a computerized tongue image acquisition system (CTIS). In this prospective and observational single-center study, we acquired tongue images under visible light and near-UV light for 60 patients with functional dyspepsia. Tongue images were acquired twice within a 30-minute interval to assess the reliability of CTIS. Then, the tongue coating was scraped and weighed to derive the wet weight of the tongue coating (WWTC). The percentage of the tongue coating area was calculated from the tongue images acquired under visible light. Mean color values (mCVs) for the UV fluorescence of the dorsal surface of the tongue were also computed. The reliabilities of the derived mCVs and percentage of the tongue coating area were acceptable (intraclass correlation coefficients, 0.907–0.947). The mCVs were more strongly correlated with WWTC than with the area, with mCV of modified lightness showing the strongest association (r = 0.785, P

Background The severity of parkinsonism and response to levodopa vary in patients with multiple system atrophy (MSA) because of the heterogeneity of nigrostriatal neuropathology. Objective To investigate the difference in clinical features between MSA patients with predominantly pre-synaptic nigrostriatal dysfunction and those with trans-synaptic nigrostriatal dysfunction. Methods We retrospectively analyzed clinical data of 61 patients with MSA who underwent both [18F]FP-CIT-PET and [18F]FDG-PET within 3 months of clinical evaluation, and who had ≤3 years of disease duration. Tracer uptake of the striatum on [18F]FP-CIT-PET and glucose metabolism of the striatum on [18F]FDG-PET were analyzed using eight striatal subregional volumes-of-interest templates. The patients were classified into two subgroups according to the predominant pre-synaptic tracer uptake loss of the posterior putamen on [18F]FP-CIT-PET (MSA-SNpc, n = 21) and trans-synaptic dopaminergic dysfunction reflected by both [18F]FP-CIT-PET and [18F]FDG-PET (MSA-STR, n = 40). Results Parkinsonian features were significantly more severe in the MSA-STR group than in the MSA-SNpc group (P = .005) and cerebellar ataxia was significantly more severe in the MSA-SNpc group (P = .036). The cerebellar type of MSA was significantly more common in the MSA-SNpc group (P = .001). There was no difference in age at onset, disease duration at the time of study, or Mini-Mental Status Examination scores between the groups. Conclusions Patients with MSA showed distinct clinical features depending on whether the pattern of nigrostriatal dysfunction was predominantly pre-synaptic or trans-synaptic.

Retinoic acid-related orphan receptor α (RORα) is considered a key regulator of polarization in liver macrophages that is closely related to nonalcoholic steatohepatitis (NASH) pathogenesis. However, hepatic microenvironments that support the function of RORα as a polarity regulator were largely unknown. Here, we identified maresin 1 (MaR1), a docosahexaenoic acid (DHA) metabolite with a function of specialized proresolving mediator, as an endogenous ligand of RORα. MaR1 enhanced the expression and transcriptional activity of RORα and thereby increased the M2 polarity of liver macrophages. Administration of MaR1 protected mice from high-fat diet-induced NASH in a RORα-dependent manner. Surprisingly, RORα increased the level of MaR1 through transcriptional induction of 12-lipoxygenase (12-LOX), a key enzyme in MaR1 biosynthesis. Furthermore, we demonstrated that modulation of 12-LOX activity enhanced the protective function of DHA against NASH. Together, these results suggest that the MaR1/RORα/12-LOX autoregulatory circuit could offer potential therapeutic strategies for curing NASH.

This study evaluated the use of low-dose chest computed tomography (LDCT) for detecting bone fragility. LDCT-measured vertebral bone attenuation by volumetric methods showed good correlation with bone mineral density (BMD) measured by dual-energy x-ray absorptiometry (DXA, and good diagnostic performance for identifying osteoporosis and compression fractures. The results of this study suggest the feasibility of obtaining comprehensive information on bone health in subjects undergoing LDCT. Osteoporosis is a prevalent but underdiagnosed disease that increases fracture risk. This study evaluated the utility of vertebral attenuation derived from low-dose chest computed tomography (LDCT) compared to dual-energy x-ray absorptiometry (DXA) for detecting bone fragility. A total of 232 subjects (78 men and 154 women) aged above 50 years who underwent both LDCT and DXA within 30 days were evaluated. LDCT-measured bone attenuation in Hounsfield units (HU) of four vertebrae (T4, T7, T10, and L1) was evaluated using volumetric methods for correlation with DXA-measured bone mineral density (BMD) and for the diagnosis of compression fractures, osteoporosis, and low BMD (osteoporosis or osteopenia) in men and women, with DXA measurements as the reference standard. The average attenuation of the four vertebrae showed strong correlation with DXA-measured BMD of the lumbar spine (r = 0.726, p

Background and Purpose Pain is common in post-stroke patients and has been shown to be associated with depression, fatigue, and decreased quality of life (QOL). However, studies examining different types of post-stroke pain are scarce. We investigated differences in the related factors and their QOL impacts between musculoskeletal pain (MSP) and central post-stroke pain (CPSP). Methods We assessed 364 consecutive stroke patients who were admitted to Asan Medical Center and contacted 12 months after stroke onset. We categorized pain and paresthesia as MSP, CPSP, combined pain, or other pain. Post-stroke depression (Beck Depression Inventory), fatigue (Fatigue Severity Scale), sleep disturbance (Verran Snyder-Halpern scale), social support (ENRICHED Social Support Instrument), and QOL (Medical Outcome Study 36-Item Short Form) were assessed. Results Of the 364 patients analyzed, 135 (37.1%) had pain, 78 (21.4%) had MSP, 22 (6.0%) had CPSP, 16 (4.4%) had combined pain, and 19 (5.2%) had other pain. In multivariate analyses, CPSP was related to modified Rankin scale (P=.004), sensory dysfunction (P

Ethnopharmacological relevance Yukmijihwang-tang (YMJ) is a typical herbal formula to treat Yin-deficiency (YD) syndrome by enriching the fluid-humor of the body. YMJ has been used to treat dry mouth symptoms for hundreds of years in traditional East Asian medicine. Xerostomia, a subjective oral dryness, is common in the elderly and results in impaired quality of life. Many conventional treatments for xerostomia provide only temporary symptom relief, and have side effects. The aim of this study is to investigate the efficacy and safety of YMJ for the treatment of xerostomia in the elderly. Methods This study was designed as a randomized, placebo-controlled, double-blinded, two center trial. Ninety-six subjects aged 60–80 years who had experienced xerostomia for at least 3 months and presented with score>40 on the visual analog scale (VAS) for subjective oral dryness were recruited and randomly allocated to YMJ and placebo groups. YMJ or placebo was administered to each group for 8 weeks (3 g of YMJ or placebo, three times per day). The primary outcome was change of VAS for xerostomia from 0 to 8 weeks. Results VAS for xerostomia was decreased by 22.04±22.76 in the YMJ group and 23.58±23.04 in the placebo group. YMJ had no effect on xerostomia. However, participants with BMIs lower than 29.37 kg/m2 showed improvement of xerostomia after 8 weeks of treatment with YMJ compared to placebo. In addition, YMJ improved oral moisture, which is associated with subjective oral dryness in the YMJ group, and the relationship between VAS for xerostomia and YD was significant. Conclusion A trend was observed in which YMJ improved oral moisture status and subjective oral dryness in elderly subjects with lower BMI and greater tendency toward YD.

Insulin and insulin-like growth factor contribute to normal brain function. Recent experimental and clinical studies showed that type 2 diabetes mellitus (T2DM) and Parkinson's disease (PD) or Alzheimer's disease (AD) share several dysregulated pathways.We aimed to investigate whether genome-wide significant loci of T2DM are associated with the risk of PD and AD as well as the severity of cognitive impairment.Study subjects were 500 PD patients, 400 AD patients, and 500 unrelated controls. We selected 32 genetic variants from 11 genes (CDC123, CDKAL1, CDKN2B, FTO, GLIS3, HHEX, IGF2BP2, KCNJ11, KCNQ1, SLC30A8, and TCF7L2) and intergenic regions based on results of recent genome-wide association studies (GWAS) in T2DM. These variants were reported to be T2DM-susceptibility loci and have been replicated in other independent studies. All association analyses were performed using logistic regression models, adjusting for age and sex.KCNQ1 SNP rs163182 showed the strongest association with AD, but it was not significant after Bonferroni correction (OR = 1.30, 95% CI = 1.07-1.59, Pcorrected = 0.32). In PD patients, CDC123 SNP rs11257655 showed modest association with MMSE score26, and CDKN2B SNPs (rs2383208, rs10965250, and rs10811661) showed modest association with MoCA score26, which were not significant after Bonferroni correction. Other genetic variants had no association with the risk of PD or AD and the severity of cognitive impairment.Our results suggest that genome-wide significant loci of T2DM play no major role in the risk and cognitive impairment of PD and AD.

This study was undertaken to describe the clinical and imaging characteristics of patients with chorea associated with nonketotic hyperglycemia (C-NKH) in comparison with patients with chorea associated with uremia (C-URE). We retrospectively analyzed the clinical data of consecutive 10 C-NKH and five C-URE patients who were treated between January 1, 2001 and January 31, 2013. Women were more frequently affected by C-NKH (70% vs. 30%) and C-URE (80% vs. 20%) compared with men. The C-NKH patients demonstrated T1–hyperintense and inhomogeneous lesions in the basal ganglia, whereas C-URE patients demonstrated T2-hyperintense and homogeneous lesions in the basal ganglia. The mean time for chorea resolution after treatment was significantly shorter in C-NKH patients than in C-URE patients (4.4 ± 2.6 d vs. 73.8 ± 14.2 d, respectively; P = 0.005). The clinical and imaging features are remarkably different between C-NKH and C-URE patients, suggesting distinct pathogenic mechanisms. © 2015 International Parkinson and Movement Disorder Society

Drug-induced parkinsonism (DIP) is the common cause of parkinsonism. It is difficult to make a differentiation between DIP and Parkinson's disease (PD) because there are no notable differences in the clinical characteristics between the two entities. In this study, we examined the relationship between the characteristics of [(18)F] fluorinated-N-3-fluoropropyl-2-β-carboxymethoxy-3-β-(4-iodophenyl)nortropane (FP-CIT) positron emission tomography (PET) images and clinical features in DIP patients. We retrospectively studied 76 patients with DIP who underwent [(18)F] FP-CIT PET. We also enrolled 16 healthy controls who underwent it. We compared the clinical characteristics between the DIP patients with normal [(18)F] FP-CIT PET scans and those with abnormal ones. Symmetric parkinsonism was more frequent in the patients with normal [(18)F] FP-CIT PET scans as compared with those with abnormal ones. Interval from drug intake to onset of parkinsonism was longer in the patients with abnormal [(18)F] FP-CIT PET scans as compared with those with normal ones. A semi-quantitative analysis showed that specific to non-specific binding ratios in the putamen was lower in the patients with abnormal [(18)F] FP-CIT PET scans as compared with those with normal ones and the age-matched control group. Our results suggest that symmetric parkinsonism was more prevalent, and the duration of drug exposure before the onset of parkinsonism was shorter in the patients with normal [(18)F] FP-CIT PET scans as compared with those with abnormal ones.

Tongue diagnosis is a significant procedure to examine the physiological and pathological changes of the human body in oriental medicine. However, the conventional method of tongue diagnosis including direct observation of tongue has limitations because of various external factors and subjective factors. Therefore, the current study investigated the usefulness of the tongue diagnosis system (TDS) as a diagnostic tool for evaluating tongue coating thickness (TCT) by assessing the agreement between the TDS and a gold standard established by assessors using the conventional method.The present study was designed as a prospective clinical trial including 60 patients with functional dyspepsia. The TDS was used to capture tongue images twice within a 30-min interval to assess its reproducibility. Tongue coating percentage was measured by the TDS, and TCT was classified as either no coating, thin coating, or thick coating according to the existing diagnostic criteria. After both TDS examinations, the weight of tongue coating was quantitatively measured, and the correlation between the actual quantity of tongue coating and the percentage of the coating measured by the TDS was analyzed using Pearson׳s correlation. After collecting tongue images in all 60 patients, tongue coating was evaluated using a conventional method by 5 well-trained assessors to establish the gold standard for evaluating TCT, which allowed us to assess the diagnostic agreement between the TDS and the gold standard. After 2 weeks, TCT evaluation was repeated by the same assessors using the same images but in a random order.The agreement between the TDS and the gold standard for evaluating TCT was almost perfect (weighted kappa, 0.840), as was the reproducibility of the TDS (weighted kappa, 0.851). The percentage of tongue coating measured by the TDS was significantly correlated with the weight of tongue coating (r=0.442, p0.001). The levels of intra-rater reliability ranged from substantial to almost perfect (range of weighted kappa, 0.777-0.923). The inter-rater reliability of 5 assessors was moderate (weighted kappa, 0.563).The present study demonstrated that the TDS can be used as a diagnostic tool for the objective and standardized evaluation of TCT in actual clinical practice.

This report seeks to inform National Social Life, Health, and Aging Project (NSHAP) data users of the prevalence and predictors of missing data in the in-person interview (CAPI) and leave-behind questionnaire (LBQ) in Wave 2 of NSHAP, and methods to handle missingness.Missingness is quantified at the unit and item levels separately for CAPI and LBQ data, and at the item level is assessed within domains of conceptually related variables. Logistic and negative binomial regression analyses are used to model predictors of unit- and item-level nonresponse, respectively.Unit-level nonresponse on the CAPI was 10.6% of those who responded at Wave 1, and LBQ nonresponse was 11.37% of those who completed the Wave 2 CAPI component. CAPI item-level missingness was less than 1% of items for most domains but 7.1% in the Employment and Finances domain. LBQ item-level missingness was 5% across domains but 8.3% in the Attitudes domain. Missingness was predicted by characteristics of the sample and features of the study design.Multiple imputation is recommended to handle unit- and item-level missingness and can be readily and flexibly conducted with multiple imputation by chained equations, inverse probability weighting, and in some instances, full-information maximum-likelihood methods.

To evaluate the contribution of non-synonymous-coding variants of known familial and genome-wide association studies (GWAS)-linked genes for Parkinson's disease (PD) to PD risk in the East Asian population, we sequenced all the coding exons of 39 PD-related disease genes and evaluated the accumulation of rare non-synonymous-coding variants in 375 early-onset PD cases and 399 controls. We also genotyped 782 non-synonymous-coding variants of these genes in 710 late-onset PD cases and 9046 population controls. Significant enrichment of LRRK2 variants was observed in both early- and late-onset PD (odds ratio = 1.58; 95% confidence interval = 1.29-1.93; P = 8.05 × 10(-6)). Moderate enrichment was also observed in FGF20, MCCC1, GBA and ITGA8. Half of the rare variants anticipated to cause loss of function of these genes were present in healthy controls. Overall, non-synonymous-coding variants of known familial and GWAS-linked genes appear to make a limited contribution to PD risk, suggesting that clinical sequencing of these genes will provide limited information for risk prediction and molecular diagnosis.

Background: Early detection of recurrence of head and neck squamous cell carcinoma (HNSCC), which is often obscured by surgical or radiotherapy-induced tissue distortion, is essential for proper patient management. Methods: A total of 143 consecutive patients with previously untreated HNSCC were evaluated by whole-body fluorine 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and regular clinical follow-up after curative treatment. The 18F-FDG PET/CT was performed ∼3–6 and 12 months after treatment and findings suspicious for recurrence or SPC were confirmed using histopathology. Results: The sensitivities of 3–6- and 12-month PET/CT scans at patient level were 96% and 93%, respectively, and those of regular clinical follow-up were 11% and 19%, respectively (McNemar test, P

This study was performed to determine whether pure cancellous bone graft and Kirschner (K-) wire fixation were sufficient to achieve bony union and restore alignment in scaphoid nonunion. A total of 65 patients who underwent cancellous bone graft and K-wire fixation were included in this study. The series included 61 men and four women with a mean age of 34 years (15 to 72) and mean delay to surgery of 28.7 months (3 to 240). The patients were divided into an unstable group (A) and stable group (B) depending on the pre-operative radiographs. Unstable nonunion was defined as a lateral intrascaphoid angle > 45°, or a radiolunate angle > 10°. There were 34 cases in group A and 31 cases in group B. Bony union was achieved in 30 patients (88.2%) in group A, and in 26 (83.9%) in group B (p = 0.439). Comparison of the post-operative radiographs between the two groups showed no significant differences in lateral intrascaphoid angle (p = 0.657) and scaphoid length (p = 0.670) and height (p = 0.193). The radiolunate angle was significantly different (p = 0.020) but the mean value in both groups was < 10°. Comparison of the dorsiflexion and palmar flexion of movement of the wrist and the mean Mayo wrist score at the final clinical visit in each group showed no significant difference (p = 0.190, p = 0.587 and p = 0.265, respectively). Cancellous bone graft and K-wire fixation were effective in the treatment of stable and unstable scaphoid nonunion. Cite this article: Bone Joint J 2013;95-B:809–14.

Objectives Due to relatively high 18F-fluorodeoxyglucose accumulation in the tonsillar region, the detection of occult tonsillar cancers by 18F-fluorodeoxyglucose positron emission tomography/computerised tomography remains controversial. Therefore, we assessed the usefulness of quantitative tonsil 18F-fluorodeoxyglucose uptake in identifying occult tonsillar squamous cell carcinoma. Design A case–control study of retrospective cohorts. Setting University Teaching Hospital. Main outcome measures We assessed all patients diagnosed with tonsillar cancers or cervical lymph node metastasis of unknown primary tumours between 2005 and 2010 who underwent 18F-fluorodeoxyglucose positron emission tomography/computerised tomography. The subjects were grouped into A (apparent early pT-stage tonsillar squamous cell carcinoma; n = 27), B (occult tonsillar squamous cell carcinoma, primary tumours were found by surgery; n = 21), C (cervical metastasis of unknown primary tumour, primary tumours were not found by surgery and for follow-up; n = 16) and D (33 healthy controls). Tonsillar maximum standardised uptake values were bilaterally measured and compared between groups. Results The sensitivity and specificity of qualitative assessment of 18F-fluorodeoxyglucose positron emission tomography/computerised tomography for detection of occult tonsillar cancers were 67% and 69%, respectively. Mean maximum standardised uptake values of tonsils with cancer were 11.19 ± 5.46 in group A and 8.12 ± 4.52 in group B, which were significantly higher than that of group C (4.62 ± 1.76) or group D (4.57 ± 1.62) (P

This study was implemented to evaluate the effect of individualized acupuncture treatment (AT) on functional dyspepsia (FD).A randomized, waitlist-controlled, two-center trial was performed. Seventy-six patients with FD were enrolled in the trial with partially individualized AT in a more realistic clinical setting performed twice a week for 15 minutes a session over 4 weeks. The participants were randomly allocated to a group receiving 8 sessions of AT for 4 weeks or a waitlist control group. After 4 consecutive weeks, the AT group was followed up without AT and the control group received the identical AT. The proportion of responders with adequate symptom relief, Nepean Dyspepsia Index (NDI), FD-related quality of life, Beck Depression Inventory, State-Trait Anxiety Inventory, Acupuncture Belief Scale, and acupuncture credibility test were assessed.After the first 4 weeks, the proportion of responders significantly improved (59% in AT group [n = 37] versus 3% in control group [n = 39]; p 0.001). The difference was no longer significant at 8 weeks, at which point the waitlist control group showed similar improvement after receiving AT (68% in the AT group versus 79% in the control group). Total NDI scores were significantly reduced in the AT group compared with the waitlist group (p = 0.03). Among NDI items, discomfort (p = 0.01), burning (p = 0.02), fullness after eating (p = 0.02), and burping (p = 0.02) were significantly improved in the AT group compared with the control group. No significant differences were observed between groups in other secondary variables.Individualized AT adequately relieves symptoms in patients with FD, and this effect may persist up to 8 weeks.

Objective Despite the widespread use of deep brain stimulation (DBS) for patients with Parkinson's disease (PD), long-term outcomes remain unclear. We aimed to analyze the mortality of advanced PD patients who received DBS surgery. Methods We assessed the survival rate of 158 consecutive advanced PD patients who underwent DBS surgery between April 2002 and May 2014. Kaplan-Meier survival curves were constructed using death as the endpoint. Cox proportional hazards regression models were used to assess the association of clinical risk factors with survival. Results Twenty-seven (17.1%) PD patients (13 men and 14 women) died during the mean follow-up period of 5.3 ± 3.1 years. The survival rate was 97% at 3 years and 85% at 5 years after DBS surgery. Pneumonia (n = 7) was the most common specific cause of death. Orthostatic hypotension was more frequent in deceased patients than in survivors (P = 0.026). In a step-wise Cox regression analysis, male sex (hazard ratio (HR) = 3.00; 95% confidence interval (CI) = 1.35–6.65; P = 0.007), visual hallucination (HR = 3.95; 95% CI = 1.60–9.78; P = 0.003), and nursing home admission (HR = 2.81; 95% CI = 1.30–6.09; P = 0.009) predicted poor survival. Conclusion The poor survival of advanced PD patients who underwent DBS surgery was associated with male sex, orthostatic hypotension, visual hallucination, and nursing home admission.

This study aimed to compare lymphatic absorption of conjugated linoleic acids (CLAs) in the triacylglycerol (TAG) or free fatty acid (FFA) form and to examine the antiobesity effects of different doses of CLAs in the TAG form in animals. Conjugated linoleic TAGs (containing 70.3 wt% CLAs; CLA-TAG) were prepared through lipase-catalyzed esterification of glycerol with commercial CLA mixtures (CLA-FFA). Lymphatic absorption of CLA-TAG and CLA-FFA was compared in a rat model of lymphatic cannulation. Greater amounts of cis-9,trans-11 and trans-10,cis-12 CLAs were detected in the collected lymph from a lipid emulsion containing CLA-TAG. This result suggests that CLA-TAG has greater capacity for lymphatic absorption than does CLA-FFA. The antiobesity efficacy of CLA-TAG at different doses was examined in mice with diet-induced obesity. A high-fat diet (HFD) for 12 weeks caused a significant increase in body weight and epididymal and retroperitoneal fat weights, which were significantly decreased by 2% dietary supplementation (w/w) with CLA-TAG. CLA-TAG at 2% significantly attenuated the HFD-induced upregulation of serum TAG, but led to hepatomegaly and exacerbated HFD-induced hypercholesterolemia. CLA-TAG at 1% significantly attenuated upregulation of retroperitoneal fat weight and significantly increased liver weight, which was decreased by the HFD. Nonetheless, the liver weight in group "HFD +1% CLA-TAG" was not significantly different from that of normal diet controls. CLA-TAG at 1% significantly reduced serum TAG levels and did not exacerbate HFD-induced hypercholesterolemia. Thus, 1% dietary supplementation with CLA-TAG reduces retroperitoneal fat weight without apparent hepatomegaly, a known side-effect of CLAs in mouse models of obesity.

Objectives Specific guidelines for initial dosing of warfarin in ischaemic stroke patients have not been developed. Therefore, we have developed an age- and weight-adjusted warfarin initiation nomogram (AW-WIN) for ischaemic stroke patients and then evaluated the efficacy and safety of AW-WIN compared with physician-determined warfarin dosing (PDWD). Methods The age- and weight-adjusted warfarin initiation nomogram was administered to 104 acute ischaemic stroke patients between January 2008 and February 2009. A historical control group (PDWD) of 96 patients was selected from comparable patients who were discharged with warfarin during the previous year. Time-to-therapeutic international normalized ratios (INRs) and the incidence of excessive anticoagulation were compared in the AW-WIN and PDWD groups. Results The general characteristics, risk factors, and stroke mechanism of the AW-WIN and PDWD groups did not differ significantly. The mean time to INR ≥ 2.0 was significantly shorter in the AW-WIN than in the PDWD group (4.9 ± 0.7 vs. 6.2 ± 0.8 days, P = 0.0008). After adjustment for potential confounding variables, the AW-WIN group reached target INR faster than the PDWD group (hazard ratio, 1.76; 95% confidence interval, 1.26–2.45; P = 0.001). The time-to-therapeutic INR ≥1.7 was shorter (P = 0.0002), the proportion of patients with therapeutic INR (2–3) at 5 days was higher (P = 0.002), and the rate of excessive anticoagulation of ≥3.5 INR during hospitalization was lower (P = 0.024) in the AW-WIN than in the PDWD group. Conclusions AW-WIN reduces the time to target INR and the risk of excessive anticoagulation. AW-WIN may be an efficient and safe method of anticoagulation during the acute phase of ischaemic stroke.

We reviewed the outcome of distal chevron metatarsal osteotomy without tendon transfer in 19 consecutive patients (19 feet) with a hallux varus deformity following surgery for hallux valgus. All patients underwent distal chevron metatarsal osteotomy with medial displacement and a medial closing wedge osteotomy along with a medial capsular release. The mean hallux valgus angle improved from −11.6° pre-operatively to 4.7° postoperatively, the mean first-second intermetatarsal angle improved from −0.3° to 3.3° and the distal metatarsal articular angle from 9.5° to 2.3° and the first metatarsophalangeal joints became congruent post-operatively in all 19 feet. The mean relative length ratio of the metatarsus decreased from 1.01 to 0.99 and the mean American Orthopaedic Foot and Ankle Society score improved from 77 to 95 points. In two patients the hallux varus recurred. One was symptom-free but the other remained symptomatic after a repeat distal chevron osteotomy. There were no other complications. We consider that distal chevron metatarsal osteotomy with a medial wedge osteotomy and medial capsular release is a useful procedure for the correction of hallux varus after surgery for hallux valgus.

Despite its proven effect, anticoagulation is not recommended to the acute ischaemic stroke due to the risk of bleeding complications. The purpose of this study is development of individualized warfarin initiation program for acute or subacute stroke patients.Among stroke patients who regularly visited out-patient clinics, we included patients who have continuously taken the same dose of warfarin as the prothrombin time remained at target International Nomarlized Ratio (INR). We assessed potential variables that affect the maintenance dose of warfarin. Using these variables, we developed an individualized warfarin initiation program.The median warfarin maintenance dose (interquartile range) in the 321 included patients was 4 (3-5) mg per day. Age (adjusted R(2) = 0.221, P0.001) and body weight (added to age, adjusted R(2) = 0.238, P = 0.008) were significant predicting factors of the dose. We classified the maintenance doses into high (HG), standard, and low group (LG) based on the distribution of maintenance doses. Decision tree analysis categorized younger (or=55 years old) and heavier (or=55 kg) patients into HG, and very old (or=80 years old) or low body weight (55 kg among those56 years old) patients into LG. We recommend 7 mg of warfarin as a standard initial dose, but 10 mg was recommended for HG patients and 5 mg for LG.We expect that this individualized program may reduce the time to target INR without excessive anticoagulation. Further prospective studies are needed to reveal the efficacy and safety of applying this program for acute stroke patients.

Background: It is unknown whether the development of cerebral microbleeds (MBs), small areas of signal loss on T2*-weighted gradient-echo imaging (GRE), follows a slow or a rapid process. We hypothesized that MBs may develop rapidly after certain critical events, such as strokes, and investigated the frequency, location, and factors associated with the formation of new MBs after acute ischemic stroke. Methods: We retrospectively examined 237 consecutive acute ischemic stroke patients who underwent MRI within 24 hours and follow-up MRI during the week after symptom onset. We defined new MBs as MBs that newly appeared on follow-up GRE outside the infarcted area. We examined the association of new MBs with demographics, risk factors, laboratory data, baseline MBs, and small vessel disease (SVD; leukoaraiosis and lacunar infarctions). Results: Seventy-five patients (31.6%) had baseline MBs, and 30 (12.7%) developed new MBs. Multiple logistic regression analysis indicated that the presence of baseline MBs (odds ratio [OR] 5.72, 95% confidence interval [CI] 2.12–15.42, p = 0.001) and severe SVD (OR 2.94, 95% CI 1.12–7.77, p = 0.03) independently predicted the development of new MBs. Of the 56 new MBs, 29 (51.8%) appeared in the lobar location, 17 (30.4%) appeared in the deep location, and 10 (17.9%) appeared in the infratentorial location. Conclusions: This study suggests that new microbleeds (MBs) can develop rapidly after acute ischemic stroke. Baseline MBs and severe small vessel disease are predictors for the development of new MBs. Further studies will be needed to investigate the clinical implications and mechanisms of these findings.

Background: Anti-GQ1b antibody has been found in Miller Fisher syndrome (MFS), Guillain-Barre syndrome (GBS) with ophthalmoplegia, Bickerstaff brainstem encephalitis (BBE), and acute ophthalmoplegia without ataxia (AO). The aim of this study was to determine the clinical features of AO associated with anti-GQ1b antibody. Methods: We retrospectively collected 34 patients with anti-GQ1b antibody syndrome. Of these patients, 31 patients had ophthalmoplegia. The patients with ophthalmoplegia were classified into MFS (n = 13), AO (n = 11), GBS with ophthalmoplegia (n = 6), and BBE (n = 1). We analyzed clinical features and patterns of external and internal ophthalmoplegia of AO, and neuro-ophthalmologic findings were compared with those of other anti-GQ1b syndromes with ophthalmoplegia. Results: AO was observed in 11 (32.4%) of the 34 patients with anti-GQ1b antibody. External ophthalmoparesis was present in all the patients and included mixed horizontal-vertical (n = 7), pure horizontal (n = 3), and pure vertical gaze palsy (n = 1). Binocular involvement was common, but unilateral ophthalmoparesis was also observed in 27.3%. Other findings included ptosis (n = 5, 45.5%) and internal ophthalmoplegia (n = 6, 54.5%). Other anti-GQ1b antibody syndromes had prominent neurologic signs including ataxia, weakness, and facial palsy in addition to ophthalmoplegia. The patterns of neuro-ophthalmologic findings did not differ between AO and other anti-GQ1b antibody syndromes with ophthalmoplegia. Conclusions: Acute ophthalmoplegia (AO) commonly occurs in anti-GQ1b antibody syndrome and manifests as various combinations of external and internal ophthalmoplegia. Internal ophthalmoplegia is fairly common and unilateral involvement may occur in AO.

Low-grade fibromyxoid sarcoma is a recently recognised soft tissue neoplasm. It is rare and has a tendency to arise from deep soft tissue of the lower extremities. An origin from the colon has not been reported in the medical literature. We report the low-grade fibromyxoid sarcoma originating from the colon in a 43-year-old male patient, treated by right hemicolectomy and nephrectomy.

An early sign of cognitive decline in older adults is often a disruption in social function, but our understanding of this association is limited. We aimed to determine whether those screening positive for early stages of cognitive impairment have differences across multiple dimensions of social function and whether associations differ by gender. United States nationally representative cohort (2010), the National Social life, Health, and Aging Project (NSHAP). Community-dwelling adults aged 62–90 years (N = 3,310) with a response rate of 76.9 %. Cognition was measured using a survey adaptation of the Montreal Cognitive Assessment categorized into three groups: normal, mild cognitive impairment (MCI), and dementia. We measured three domains of social relationships, each comprised of two scales: network structure (size and density), social resources (social support and social strain), and social engagement (community involvement and socializing). We used multiple linear regression to characterize the relationship of each social relationship measure to cognition. Individuals screened as at risk for MCI and early dementia had smaller network sizes by 0.3 and 0.6 individuals (p

Gastric and colonic alpha-synuclein immunoreactivity has been reported in patients with Parkinson's disease (PD). However, enteric alpha-synuclein also has been reported in healthy individuals.We aimed to investigate the utility of alpha-synuclein immunoreactivity from gastric and colonic mucosal tissues obtained by routine endoscopy to detect PD, and to correlate the pathological burden of alpha-synuclein with motor and nonmotor features of PD.We recruited 104 study subjects, consisting of 38 patients with PD, 13 patients with probable multiple system atrophy (MSA), and 53 healthy controls. Gastric and colonic mucosal tissues obtained by endoscopic gastroduodenoscopy and colonoscopy were assessed using alpha-synuclein immunohistochemistry. Detailed motor and nonmotor features of PD were correlated with enteric alpha-synuclein immunoreactivity.No difference was seen in the enteric α-SYN immunoreactivity among patients with PD (31.6% for stomach and 10.4% for colon), patients with MSA (40.0% for stomach and 8.0% for colon), and healthy controls (33.3% for stomach and 18.5% for colon). The frequency of positive alpha-synuclein immunoreactivity was higher in gastric biopsy tissues than in colonic biopsy tissues in all of the study groups (P 0.05). No significant correlation was found between the presence of alpha-synuclein immunoreactivity and the motor and nonmotor features of PD.The presence of alpha-synuclein immunoreactivity in gastric and colonic mucosa was detected in a similar manner in patients with PD, patients with MSA, and controls, thus suggesting a limited role of enteric mucosal alpha-synuclein as a diagnostic biomarker for PD. Future studies are warranted to detect pathological alpha-synuclein strains.

The availability of social and financial resources has profound implications for health and well-being in later life. Older adults often share resources with others who live with them, sometimes in households including relatives or friends. We examine differences in social support, social connections, money, and the household environment across types of living arrangements, develop hypotheses from two theoretical perspectives, one focusing on obligations toward kin, and one focused on social exchange within households, and test them using data from the National Social Life, Health, and Aging Project. We find that availability of resources is not consistently associated with the presence of grandchildren and other young relatives, but often differs with presence of other adults. These findings suggest that a single type of resource tells us little about the distribution of the resources of older adults, and call on us to examine multiple resources simultaneously.

For ideal non-thrombogenicity under normal physiologic conditions, we propose endothelialization. Endothelialization means that synthetic biomaterials are seeded by endothelial cells to mimic natural blood vessels. In our study, we synthesized amphiphilic polyurethane (PU)/poly(ethyleneglycol)diacrylate (PEGDA) interpenetrating polymer networks (IPNs) with different levels of surface energy to investigate the effect of adhesion and the growth of human umbilical vein endothelial cells (HUVECs). Collagen with cell-binding molecules was adsorbed on the surface of PU/PEGDA IPNs to enhance the adhesion of HUVECs. The morphology of collagens adsorbed on the IPN surfaces depends highly on the surface energy of the IPNs. As the surface becomes hydrophilic, there is greater aggregation of the adsorbed collagens on the IPN surface. The HUVECs successfully adhere to the collagen-immobilized IPN surface. The morphology of the endothelial cells (ECs) that adhere to IPN 2k-C and IPN 2k after 1 day and after 3 days incubation shows that ECs were successfully spread. The adhesion and the proliferation of ECs increase on non-treated IPN surfaces as the hydrophobicity of the IPNs increases. The surface energy of IPN 2k-C is suitable for the adhesion and proliferation of ECs. Therefore, platelet adhesion is significantly reduced on the EC-hybridized surface of IPNs.

We investigated the role of mortalin (HSPA9) and its interaction with other mitochondria-related genes (parkin, PINK1, DJ1, and COQ2) as a risk factor for Parkinson's disease (PD) and Alzheimer's disease (AD) in 500 PD, 400 AD, and 500 control subjects. The HSPA9 variants identified by direct sequencing or its interaction with other genes assessed by genetic risk scores did not show a significant association with PD or AD risk. Our findings did not provide a strong evidence for the role of HAPA9 and its interaction with other mitochondria-related genes as a genetic risk factor for PD or AD.

Objectives This article describes new longitudinal data on older adults' egocentric social networks collected by the National Social Life, Health, and Aging Project (NSHAP). We describe a novel survey technique that was used to record specific personnel changes that occurred within respondents' networks during the 5-year study period, and we make recommendations regarding usage of the resulting data. Method Descriptive statistics are presented for measures of network size, composition, and structure at both waves, respondent-level summary measures of change in these characteristics between waves, as well as measures that distinguish between changes associated with losses of Wave 1 network members, additions of new ones, and changes in relationships with network members who were present at both waves. Results The NSHAP network change module was successful in providing reliable information about specific changes that occurred within respondents' confidant networks. Most respondents lost at least one confidant from W1 and added at least one new confidant between waves as well. Network growth was more common than network shrinkage. Both lost and new ties were weaker than ties that persisted throughout the study period. Discussion These data provide new insight into the dynamic nature of networks in later life, revealing norms of network turnover, expansion, and weakening. Data limitations are discussed.

This paper introduces scales on shared activity and relationship quality for married and partnered older adults using multiple indicators from the second wave of National Social Life, Health, and Aging Project.We assessed the reliability of the scales using Cronbach's alpha and the item-total correlation. We conducted exploratory factor analysis to explore the structure of the items and compared the distribution of each scale means by age group and gender.We found that the relational quality scale has a 2-factor structure, including a positive and negative dimension. The shared activity scale has a 1-factor structure. We found that partnered men show both higher positive and higher negative relationship quality than do partnered women, suggesting that more older men than women experience ambivalent feelings toward their spouse or partner and more women than men have relationships of indifferent quality, with relatively low costs and relatively low benefits.The separate conceptualization of shared activity and relationship quality provides one way to examine the dynamic nature of marital quality in later life such as the extent to which shared activities among couples promote or detract from relationships' quality. Analyses for individuals and for dyads are discussed.

Despite the importance of airway surface liquid pH in the lung's defenses against infection, the mechanism of airway HCO3− secretion remains unclear. Our aim was to assess the contribution of apical and basolateral Cl−/HCO3− exchangers to Cl− and HCO3− transport in the Calu-3 cell line, derived from human airway submucosal glands. Changes in intracellular pH (pHi) were measured following substitution of Cl− with gluconate. Apical Cl− substitution led to an alkalinization in forskolin-stimulated cells, indicative of Cl−/HCO3− exchange. This was unaffected by the anion exchange inhibitor DIDS but inhibited by the CFTR blocker CFTRinh-172, suggesting that the HCO3− influx might occur via CFTR, rather than a solute carrier family 26 (SLC26) exchanger, as recently proposed. The anion selectivity of the recovery process more closely resembled that of CFTR than an SLC26 exchanger, and quantitative RT-PCR showed only low levels of SLC26 exchanger transcripts relative to CFTR and anion exchanger 2 (AE2). For pHi to rise to observed values (∼7.8) through HCO3− entry via CFTR, the apical membrane potential must reverse to at least +20 mV following Cl− substitution; this was confirmed by perforated-patch recordings. Substitution of basolateral Cl− evoked a DIDS-sensitive alkalinization, attributed to Cl−/HCO3− exchange via AE2. This appeared to be abolished in forskolin-stimulated cells but was unmasked by blocking apical efflux of HCO3− via CFTR. We conclude that Calu-3 cells secrete HCO3− predominantly via CFTR, and, contrary to previous reports, the basolateral anion exchanger AE2 remains active during stimulation, providing an important pathway for basolateral Cl− uptake.

Background The genetic factors that determine the heterogeneity of cognitive impairment in Alzheimer's disease (AD) patients have been rarely reported. We aimed to investigate the association between top hits of genome-wide association studies (GWAS) and specific cognitive domains in AD patients. Methods We investigated 86 single nucleotide polymorphisms (SNPs) selected from 12 genes ( ABCA7 , APOE , BIN1 , CD2AP , CD33 , CLU , CR1 , EPHA1 , LRAT , MS4A6A , PCDH11X , and PICALM ) based on results of the recent GWAS and genotyped in 211 AD cases. We also analyzed results of comprehensive neuropsychological evaluations in all cases. We performed multiple regression analyses. Results There were four significant associations between genotypes and phenotypes of AD patients: CR1 SNP rs11803956 correlated with Mini-Mental State Examination (MMSE) score (β=1.718, P corrected =0.002); ABCA7 SNP rs3752232 correlated with Rey Complex Figure Test (RCFT) copy score (β=−6.861, P corrected =0.013); APOE SNP rs2075650 correlated with the percentile of RCFT copy score (β=14.005, P corrected =0.021) and the percentile of total score in phonemic fluency (β=11.052, P corrected =0.035). Conclusion Our results suggest that CR1 , ABCA7 , and APOE correlate with specific aspects of cognitive impairments in AD patients.

Background and purpose The progression pattern of brain structural changes in patients with isolated cerebrovascular disease (CVD) remains unclear. To investigate the role of isolated CVD in cognitive impairment patients, patterns of cortical thinning and hippocampal atrophy in pure subcortical vascular mild cognitive impairment (svMCI) and pure subcortical vascular dementia (SVaD) patients were characterized. Methods Forty-five patients with svMCI and 46 patients with SVaD who were negative on Pittsburgh compound B (PiB) positron emission tomography imaging and 75 individuals with normal cognition (NC) were recruited. Results Compared with NC, patients with PiB(-) svMCI exhibited frontal, language and retrieval type memory dysfunctions, which in patients with PiB(-) SVaD were further impaired and accompanied by visuospatial and recognition memory dysfunctions. Compared with NC, patients with PiB(-) svMCI exhibited cortical thinning in the frontal, perisylvian, basal temporal and posterior cingulate regions. This atrophy was more prominent and extended further toward the lateral parietal and medial temporal regions in patients with PiB(-) SVaD. Compared with NC subjects, patients with PiB(-) svMCI exhibited hippocampal shape deformities in the lateral body, whilst patients with PiB(-) SVaD exhibited additional deformities within the lateral head and inferior body. Conclusions Our findings suggest that patients with CVD in the absence of Alzheimer's disease pathology can be demented, showing cognitive impairment in multiple domains, which is consistent with the topography of cortical thinning and hippocampal shape deformity.

Background Xerostomia, a subjective sense of dry mouth, is not generally regarded a disease despite its high prevalence among the elderly, and therefore continues to impair affected patients’ quality of life. In traditional Korean medicine, ‘Yin-Deficiency’ has been implicated in the pathogenesis of xerostomia among the elderly. Yukmijihwang-tang is a famous herbal prescription used to relieve ‘Yin-Deficiency’, and reportedly has antioxidant effects; therefore, it is postulated that Yukmijihwang-tang can be used to treat xerostomia in the elderly. However, to our knowledge, no clinical trial has been conducted on the effects of Yukmijihwang-tang on xerostomia. Thus, we designed a randomized clinical trial to investigate the effects and safety of Yukmijihwang-tang on xerostomia in the elderly. In addition, we will clarify the aforementioned assumption that ‘Yin-Deficiency’ is the major cause of xerostomia in the elderly by identifying a correlation between xerostomia and ‘Yin-Deficiency’. Methods/Design This randomized, double-blind, placebo-controlled trial will be carried out at two centers: Kyung Hee University Korean Medicine Hospital and Kyung Hee University Hospital at Gangdong. We will recruit 96 subjects aged 60-80 years who have experienced xerostomia for 3 months prior to participation. Subjects who present with score >40 on the visual analogue scale for xerostomia and unstimulated salivary flow rate under 0.3mL/min will be included and the randomization will be carried out by an independent statistician by using a random number creation program. The subjects and all researchers except the statistician will be blinded to the group assignment. Yukmijihwang-tang or placebo will be administered to each group for 8 weeks. The primary outcome is change in the scores for the visual analogue scale for xerostomia and the dry mouth symptom questionnaire from 0 to 8 weeks. Discussion It will be assessed whether Yukmijihwang-tang can be used as a new herbal treatment for xerostomia in the elderly by demonstrating its therapeutic effects in a well-designed clinical trial. Trial registration ClinicalTrials.gov Identifier:NCT01579877

Alzheimer's disease (AD) and Parkinson's disease (PD) have overlapping clinical and pathological features, suggesting a common pathway for these 2 neurodegenerative disorders. Here we investigated the association of both AD and PD GWAS top hits with PD susceptibility. We selected 25 single nucleotide polymorphisms (SNPs) in 9 genes (ABCA7, APOE, BST1, CLU, CR1, LRRK2, PARK16, PICALM, and SNCA) that were genotyped in 1036 PD case patients and 1208 controls. Case patients and controls were all ethnic Koreans. Logistic regression analysis was performed to calculate age- and sex-adjusted odds ratios. None of the AD-susceptibility loci (ABCA7, APOE, CLU, CR1, and PICALM) showed statistically significant association with PD susceptibility. In contrast, we replicated associations of SNCA, LRRK2, BST1, and PARK16 with PD susceptibility in Koreans. Of those, the SNCA SNP rs11931074 showed the most significant association with PD susceptibility (adjusted odds ratio = 1.48; 95% confidence interval = 1.31-1.67; p = 2.20E-10). In a logistic regression analysis with SNPs coded under an additive model, there was no significant genetic interaction between the LRRK2 and the PARK16 locus gene RAB7L1 in PD risk. Our results confirm the associations of SNCA, LRRK2, BST1, and PARK16 with PD susceptibility and fail to show significant associations of AD genome-wide association study (GWAS) top hits with PD susceptibility in a Korean population.

Background and purpose Factors related to post- stroke anger proneness (PSAP) are poorly studied. The aim of the present study was to determine the frequency of, and the factors related to, PSAP in the acute stage of stroke. Serotonin transporter protein genes and monoamine oxidase A (MAO-A) gene polymorphisms were also examined. Methods A total of 508 patients with acute IS were screened for PSAP at admission after stroke, using the modified Spielberger Trait Anger Scale. Blood samples were collected from each participant for DNA extraction and genotyping. The promoter of serotonin transporter protein (5-HTTLPR), the variable number of tandem repeat polymorphisms within intron 2 (VNTR STin2), and the 30-bp functional VNTR polymorphism in the promoter region of the MAO-A gene (MAOA-uVNTR) were genotyped. Results Post- stroke anger proneness was present in 15.1% of patients at admission. The factors related to PSAP were diabetes mellitus (P

To investigate the characteristics and prevalence of poststroke depression (PSD) and poststroke emotional incontinence (PSEI) and the factors related to these conditions at admission and 3 months after stroke.We evaluated 508 consecutive patients with acute ischemic stroke for PSD and PSEI at admission and 3 months later. PSD was evaluated using the Beck Depression Inventory, and PSEI was evaluated using Kim's criteria. Blood samples were collected and genotyped for the promoter region of the serotonin transporter protein (5-HTTLPR) and the number of tandem repeats within intron 2 (STin2 VNTR). Perceived social support (the ENRICHD Social Support Inventory) was also measured.PSD and PSEI were present in 13.7% and 9.4% of patients, respectively, at admission and in 17.7% and 11.7%, respectively, at 3 months after stroke. Multivariate analyses showed that PSD at admission was associated with the NIH Stroke Scale score at admission (p0.001), whereas PSD at 3 months was associated with the presence of microbleeds (p0.01) and perceived low social support (p0.001). In contrast, only lesion location (p = 0.022) was associated with PSEI at admission, whereas modified Rankin Scale score (p = 0.019), STin2 VNTR (p = 0.040), and low social support (p = 0.042) were related to PSEI 3 months after stroke.Diverse factors such as neurologic dysfunction, lesion location, microbleeds, genetic traits, and social support are differently related to acute and subacute emotional disturbances. Strategies to prevent or manage these problems should consider these differences.

Using the 10-item Spielberger Trait Anger Scale, the authors interviewed 145 patients with stroke regarding inability to control anger or aggression (ICAA). Poststroke depression and emotional incontinence were also assessed. ICAA was present in 47 patients (32%) and was closely related to motor dysfunction, dysarthria, emotional incontinence, and lesions affecting frontal-lenticulocapsular-pontine base areas. ICAA seems to be one of the major behavioral symptoms in patients with stroke.

We reviewed the results of a selective à la carte soft-tissue release operation for recurrent or residual deformity after initial conservative treatment for idiopathic clubfoot by the Ponseti method. Recurrent or residual deformity occurred in 13 (19 feet) of 33 patients (48 feet; 40%). The mean age at surgery was 2.3 years (1.3 to 4) and the mean follow-up was 3.6 years (2 to 5.3). The mean Pirani score had improved from 2.8 to 1.1 points, and the clinical and radiological results were satisfactory in all patients. However, six of the 13 patients (9 of 19 feet) had required further surgery in the form of tibial derotation osteotomy, split anterior tibialis tendon transfer, split posterior tibialis transfer or a combination of these for recurrent deformity. We concluded that selective soft-tissue release can provide satisfactory early results after failure of initial treatment of clubfoot by the Ponseti method, but long-term follow-up to skeletal maturity will be necessary.

The hepatopulmonary syndrome occurs when an intrapulmonary shunt (IPS) causes hypoxemia in patients with cirrhosis. Because IPS has not been clearly defined in children, we investigated the prevalence, clinical characteristics, and outcomes of IPS in children undergoing liver transplantation (OLT). Of the 107 pediatric OLT recipients between December 1994 and March 2005, 18 (16.8%) had IPS, as evaluated by contrast-enhanced echocardiography (CEE) at 9 months to 16 years of age. The degree of IPS was classified into five grades according to the extent of microbubbles in the left ventricle, with significant IPS defined as grade II or higher. Baseline characteristics, including serum total bilirubin, albumin, aminotransferase, and prothrombin time, did not differ in patients with or without IPS. The patients with IPS had significantly lower Pao2 and Sao2, longer duration of mechanical ventilation and hospital stay, and higher postoperative morbidity and mortality than patients without IPS (P < .05 each), but there were no other significant differences between the groups. The six patients with significant IPS (one grade II, three grade III, and two grade IV) showed a significantly greater morbidity and mortality than patients with grade I IPS (P < .05). Most of the positive CEE findings of IPS regressed within 6 months after OLT. These findings indicated that IPS is not uncommon among children undergoing OLT, but is reversible. Because severe IPS may increase patient morbidity and mortality, early assessment of IPS status using CEE is essential for pediatric OLT candidates.

Periodic alternating nystagmus (PAN) is characterized by periodic reversal of horizontal jerky nystagmus with a null period of several seconds. Damage to the uvulonodulus or to their connections with the brainstem vestibular nuclei has been suggested as a mechanism of PAN.1,2 However, PAN has rarely been reported in circumscribed cerebellar lesion.3 We report a patient with isolated nodular infarction who developed PAN without fixation in association with perverted head-shaking nystagmus (HSN) and loss of tilt suppression of the postrotatory nystagmus. This is the first report of PAN in circumscribed cerebellar infarction, and provides further evidence that PAN occurs due to dysfunction of cerebellar nodulus. A 69-year-old man with a history of hypertension developed acute vertigo with nausea/vomiting and postural imbalance. On examination, we observed spontaneous horizontal nystagmus in the primary position which reversed its direction with a cycle of approximately 2 minutes and a transition period of several seconds by using video Frenzel goggles (SLMED, Seoul, Korea) (see the video on the Neurology Web site at www.neurology.org). The …

18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has been reported to be superior to computed tomography (CT)/magnetic resonance imaging (MRI) in the evaluation of head and neck cancers, but little is known about its usefulness in oropharyngeal squamous cell carcinoma (SCC). We therefore compared FDG PET and CT/MRI in the preoperative staging of previously untreated oropharyngeal SCC.Thirty-two consecutive patients with oropharyngeal SCC underwent FDG PET and CT/MRI before surgery. Each method was interpreted separately to assess primary tumor and cervical node status. Their sensitivity and specificity were compared relative to histopathologic analysis.Histopathology revealed metastases in 29 of 39 dissected neck sides and in 47 of 163 dissected cervical levels. FDG PET had higher sensitivities than CT/MRI for primary tumor detection (25/32 vs. 30/32, P=0.063) and for identification of cervical metastases on neck side (22/29 vs. 28/29, P0.05) and level-by-level (37/47 vs. 45/47, P0.05) bases. In contrast, the specificity of the two methods did not differ significantly (P0.5). FDG PET correctly interpreted the false-negative results of CT/MRI in 6 of 7 primary tumors and 8 of 10 cervical levels.The improved preoperative staging of FDG PET may help in planning treatment, but its accuracy is insufficient to replace pathologic staging based on neck dissection.