Liensinine and neferine exert neuroprotective effects via the autophagy pathway in transgenic Caenorhabditis elegans.

BACKGROUND: Liensinine and neferine are the main bisbenzylisoquinoline alkaloids obtained from the seeds of Nelumbo nucifera, which commonly used as edible food and traditional medicine in Asia. It was reported that liensinine and neferine could inhibit the activities of acetylcholinesterase and cross the blood-brain barriers, suggesting their therapeutic potential for the management of Alzheimer's disease. METHODS: Here, we employed SH-SY5Y human neuroblastoma cells stably transfected with the human Swedish amyloid precursor protein (APP) mutation APP695 (APP695swe SH-SY5Y) as an in vitro model and transgenic Caenorhabditis elegans as an in vivo model to investigate the neuroprotective effects and underlying mechanism of liensinine and neferine. RESULTS: We found that liensinine and neferine could significantly improve the viability and reduce ROS levels in APP695swe SH-SY5Y cells, inhibit ß-amyloid and tau-induced toxicity, and enhance stress resistance in nematodes. Moreover, liensinine and neferine had obviously neuroprotective effects by assaying chemotaxis, 5-hydroxytryptamine sensitivity and the integrity of injured neurons in nematodes. Preliminary mechanism studies revealed that liensinine and neferine could upregulate the expression of autophagy related genes (lgg-1, unc-51, pha-4, atg-9 and ced-9) and reduce the accumulation of ß-amyloid induced autophagosomes, which suggested autophagy pathway played a key role in neuroprotective effects of these two alkaloids. CONCLUSIONS: Altogether, our findings provided a certain working foundation for the use of liensinine and neferine to treat Alzheimer's disease based on neuroprotective effects.

Phenotypic Heterogeneity in Patients with Mutations in the Mitochondrial Complex I Assembly Gene NDUFAF5.

BACKGROUND: Rare mutations in NADH:ubiquinone oxidoreductase complex assembly factor 5 (NDUFAF5) are linked to Leigh syndrome. OBJECTIVE: We aimed to describe clinical characteristics and functional findings in a patient cohort with NDUFAF5 mutations. METHODS: Patients with biallelic NDUFAF5 mutations were recruited from multi-centers in Taiwan. Clinical, laboratory, radiological, and follow-up features were recorded and mitochondrial assays were performed in patients' skin fibroblasts. RESULTS: Nine patients from seven unrelated pedigrees were enrolled, eight homozygous for c.836 T > G (p.Met279Arg) in NDUFAF5 and one compound heterozygous for p.Met279Arg. Onset age had a bimodal distribution. The early-onset group (age <3 years) presented with psychomotor delay, seizure, respiratory failure, and hyponatremia. The late-onset group (age ≥5 years) presented with normal development, but slowly progressive dystonia. Combing 25 previously described patients, the p.Met279Arg variant was exclusively identified in Chinese ancestry. Compared with other groups, patients with late-onset homozygous p.Met279Arg were older at onset (P = 0.008), had less developmental delay (P = 0.01), less hyponatremia (P = 0.01), and better prognosis with preserved ambulatory function into early adulthood (P = 0.01). Bilateral basal ganglia necrosis was a common radiological feature, but brainstem and spinal cord involvement was more common with early-onset patients (P = 0.02). A modifier gene analysis showed higher concomitant mutation burden in early-versus late-onset p.Met279Arg homozygous cases (P = 0.04), consistent with more impaired mitochondrial function in fibroblasts from an early-onset case than a late-onset patient. CONCLUSIONS: The p.Met279Arg variant is a common mutation in our population with phenotypic heterogeneity and divergent prognosis based on age at onset. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Prediction of adverse health outcomes using an electronic frailty index among nonfrail and prefrail community elders.

BACKGROUND: Early recognition of older people at risk of undesirable clinical outcomes is vital in preventing future disabling conditions. Here, we report the prognostic performance of an electronic frailty index (eFI) in comparison with traditional tools among nonfrail and prefrail community-dwelling older adults. The study is to investigate the predictive utility of a deficit-accumulation eFI in community elders without overt frailty. METHODS: Participants aged 65-80 years with a Clinical Frailty Scale of 1-3 points were recruited and followed for 2 years. The eFI score and Fried's frailty scale were determined by using a semiautomated platform of self-reported questionnaires and objective measurements which yielded cumulative deficits and physical phenotypes from 80 items of risk variables. Kaplan-Meier method and Cox proportional hazards regression were used to analyze the severity of frailty in relation to adverse outcomes of falls, emergency room (ER) visits and hospitalizations during 2 years' follow-up. RESULTS: A total of 427 older adults were evaluated and dichotomized by the median FI score. Two hundred and sixty (60.9%) and 167 (39.1%) elders were stratified into the low- (eFI ≤ 0.075) and the high-risk (eFI > 0.075) groups, respectively. During the follow-up, 77 (47.0%) individuals developed adverse events in the high-risk group, compared with 79 (30.5%) in the low-risk group (x2, p = 0.0006). In multivariable models adjusted for age and sex, the increased risk of all three events combined in the high- vs. low-risk group remained significant (adjusted hazard ratio (aHR) = 3.08, 95% confidence interval (CI): 1.87-5.07). For individual adverse event, the aHRs were 2.20 (CI: 1.44-3.36) for falls; 1.67 (CI: 1.03-2.70) for ER visits; and 2.84 (CI: 1.73-4.67) for hospitalizations. Compared with the traditional tools, the eFI stratification (high- vs. low-risk) showed better predictive performance than either CFS rating (managing well vs. fit to very fit; not discriminative in hospitalizations) or Fried's scale (prefrail to frail vs. nonfrail; not discriminative in ER visits). CONCLUSION: The eFI system is a useful frailty tool which effectively predicts the risk of adverse healthcare outcomes in nonfrail and/or prefrail older adults over a period of 2 years.

Blood neurofilament light chain as a surrogate marker for dystonia.

BACKGROUND AND PURPOSE: Dystonia is a heterogeneous movement disorder, and it remains unclear whether neurodegeneration is involved. Neurofilament light chain (NfL) is a biosignature of neurodegeneration. We aimed to investigate whether plasma NfL levels were elevated and associated with disease severity in patients with dystonia. METHOD: We enrolled 231 unrelated dystonia patients (isolated dystonia n = 203; combined dystonia n = 28) and 54 healthy controls from movement disorder clinics. Clinical severity was evaluated using the Fahn Marsden Dystonia Rating Scale, the Unified Dystonia Rating Scale, and the Global Dystonia Rating Scale. Blood NfL levels were measured by single-molecule array. RESULTS: Plasma NfL levels were significantly higher in those with generalized dystonia compared to those with focal dystonia (20.1 ± 8.8 vs. 11.7 ± 7.2 pg/mL; p = 0.01) or controls (p < 0.01), while the level was comparable between the focal dystonia group and controls (p = 0.08). Furthermore, the dystonia combined with parkinsonism group had higher NfL levels than the isolated dystonia group (17.4 ± 6.2 vs. 13.5 ± 7.5 pg/mL; p = 0.04). Notably, whole-exome sequencing was performed in 79 patients and two patients were identified as having likely pathogenic variants: one had a heterozygous c.122G>A (p.R41H) variant in THAP1 (DYT6) and the other carried a c.1825G>A (p.D609N) substitution in ATP1A3 (DYT12). No significant correlation was found between plasma NfL levels and dystonia rating scores. CONCLUSION: Plasma NfL levels are elevated in patients with generalized dystonia and dystonia combined with parkinsonism, suggesting that neurodegeneration is involved in the disease process of this subgroup of patients.

Impact of a targeted temperature management quality improvement project on survival and neurologic outcomes in cardiac arrest patients.

BACKGROUND: Targeted temperature management (TTM) is recommended for postresuscitation care of patients with sudden cardiac arrest (SCA) and its implementation remains challenging. This study aimed to evaluate the newly designed Quality Improvement Project (QIP) to improve the quality of TTM and outcomes of patients with SCA. METHODS: Patients who experienced out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA) with return of spontaneous circulation (ROSC) and were treated in our hospital between January 2017 and December 2019 were enrolled retrospectively. All included patients received QIP intervention initiated as follows: (1) Protocols and standard operating procedures were created for TTM; (2) shared decision-making was documented; (3) job training instruction was created; and 4) lean medical management was implemented. RESULTS: Among 248 included patients, the postintervention group (n = 104) had shorter duration of ROSC to TTM than the preintervention group (n = 144) (356 vs 540 minutes, p = 0.042); better survival rate (39.4% vs 27.1%, p = 0.04), and neurologic performance (25.0% vs 17.4%, p < 0.001). After propensity score matching (PSM), patients who received TTM (n = 48 ) had better neurologic performance than those without TTM (n = 48) (25.1% vs 18.8%, p < 0.001). OHCA (odds ratio [OR] = 2.705, 95% CI: 1.657-4.416), age >60 (OR = 2.154, 95% CI: 1.428-3.244), female (OR = 1.404, 95% CI: 1.005-1.962), and diabetes mellitus (OR = 1.429, 95% CI: 1.019-2.005) were negative predictors of survival; while TTM (OR = 0.431, 95% CI: 0.266-0.699) and bystander cardiopulmonary resuscitation (CPR) (OR=0.589, 95% CI: 0.35-0.99) were positive predictors. Age >60 (OR= 2.292, 95% CI: 1.58-3.323) and OHCA (OR= 2.928, 95% CI: 1.858-4.616) were negative predictors of favorable neurologic outcomes; while bystander CPR (OR=0.572, 95% CI: 0.355-0.922) and TTM (OR=0.457, 95% CI: 0.296-0.705) were positive predictors. CONCLUSION: A new QIP with defined protocols, documented shared decision-making, and medical management guidelines improves TTM execution, duration from ROSC to TTM , survival, and neurologic outcomes of cardiac arrest patients.

Multimorbidity and prior falls correlate with risk of 30-day hospital readmission in aged 80+: A prospective cohort study.

BACKGROUND/PURPOSE: Thirty-day hospital readmission rate significantly raised with advanced age. The performance of existing predictive models for readmission risk remained uncertain in the oldest population. We aimed to examine the effect of geriatric conditions and multimorbidity on readmission risk among older adults aged 80 and over. METHODS: This prospective cohort study enrolled patients aged 80 and older discharged from a geriatric ward at a tertiary hospital, with phone follow-up for 12 months. Demographics, multimorbidity, and geriatric conditions were assessed before hospital discharge. Logistic regression models were conducted to analyse risk factors for 30-day readmission. RESULTS: Patients readmitted had higher Charlson comorbidity index scores, and were more likely to have falls, frailty, and longer hospital stay, compared to those without 30-day readmission. Multivariate analysis revealed that higher Charlson comorbidity index score was associated with readmission risk. Older patients with a fall history within 12 months had a near 4-fold increase in readmission risk. Severe frailty status before index admission was associated with a higher 30-day readmission risk. Functional status at discharge was not associated with readmission risk. CONCLUSION: In addition to multimorbidity, history of falls and frailty were associated with higher hospital readmission risk in the oldest.

Genetic analysis of IMPDH2 gene in Taiwanese patients with isolated or combined dystonia.

The inosine monophosphate dehydrogenase gene (IMPDH2) was recently reported as a novel gene associated with autosomal dominantly inherited dystonia. We investigated 245 Taiwanese patients with molecularly unassigned isolated or combined dystonia without features of neurodevelopmental disorders and found none had pathogenic variants. Our findings suggest that IMPDH2 may not play a major role in dystonia.

Validation of clinical frailty scale in Chinese translation.

BACKGROUND: Identification of frailty is crucial to guide patient care for the elderly. The Clinical Frailty Scale (CFS) is a reliable, synthesis and clinical judgment-based tool. However, a validated Chinese version of CFS (CFS-C) is lacking. The aim of this study is to describe the translation process of CFS into traditional Chinese and to evaluate its reliability and validity in a geriatric study population in Taiwan. METHODS: This cross-sectional study recruited 221 geriatric outpatients aged 65 years or older at a medical center in Taipei, Taiwan. The Chinese version of CFS was produced following Brislin's translation model. Weighted kappa for agreement and Kendall's tau for correlation were used to assess inter-rater reliability (a subgroup of 52 outpatients) between geriatricians and one research assistant, and validity tests (221 outpatients) by comparing CFS-C with Fried frailty phenotype and Frailty Index based on Comprehensive Geriatric Assessment (FI-CGA). Correlation between CFS-C and other geriatric conditions were also assessed. RESULTS: The inter-rater reliability revealed moderate agreement (weighted kappa = 0.60) and strong correlation (Kendall's tau = 0.67). For criterion validity, CFS-C categorisation showed fair agreement (weighted kappa = 0.37) and significant correlation (Kendall's tau = 0.46) with Fried frailty phenotype, and higher agreement (weighted kappa = 0.51) and correlation (Kendall's tau = 0.63) with FI-CGA categorisation. CFS-C was significantly correlated with various geriatric assessments, including functional disability, physical performance, hand grip, comorbidity, cognition, depression, and nutrition status. No significant correlation was found between CFS-C and appendicular muscle mass. CONCLUSIONS: The CFS-C demonstrated acceptable validity and reliability in Chinese older adults in Taiwan. Development of CFS-C enhanced consistency and accuracy of frailty assessment, both in research and clinical practice.

Natural product myricetin is a pan-KDM4 inhibitor which with poly lactic-co-glycolic acid formulation effectively targets castration-resistant prostate cancer.

BACKGROUND: Castration-resistant prostate cancer (CRPC) with sustained androgen receptor (AR) signaling remains a critical clinical challenge, despite androgen depletion therapy. The Jumonji C-containing histone lysine demethylase family 4 (KDM4) members, KDM4A‒KDM4C, serve as critical coactivators of AR to promote tumor growth in prostate cancer and are candidate therapeutic targets to overcome AR mutations/alterations-mediated resistance in CRPC. METHODS: In this study, using a structure-based approach, we identified a natural product, myricetin, able to block the demethylation of histone 3 lysine 9 trimethylation by KDM4 members and evaluated its effects on CRPC. A structure-based screening was employed to search for a natural product that inhibited KDM4B. Inhibition kinetics of myricetin was determined. The cytotoxic effect of myricetin on various prostate cancer cells was evaluated. The combined effect of myricetin with enzalutamide, a second-generation AR inhibitor toward C4-2B, a CRPC cell line, was assessed. To improve bioavailability, myricetin encapsulated by poly lactic-co-glycolic acid (PLGA), the US food and drug administration (FDA)-approved material as drug carriers, was synthesized and its antitumor activity alone or with enzalutamide was evaluated using in vivo C4-2B xenografts. RESULTS: Myricetin was identified as a potent α-ketoglutarate-type inhibitor that blocks the demethylation activity by KDM4s and significantly reduced the proliferation of both androgen-dependent (LNCaP) and androgen-independent CRPC (CWR22Rv1 and C4-2B). A synergistic cytotoxic effect toward C4-2B was detected for the combination of myricetin and enzalutamide. PLGA-myricetin, enzalutamide, and the combined treatment showed significantly greater antitumor activity than that of the control group in the C4-2B xenograft model. Tumor growth was significantly lower for the combination treatment than for enzalutamide or myricetin treatment alone. CONCLUSIONS: These results suggest that myricetin is a pan-KDM4 inhibitor and exhibited potent cell cytotoxicity toward CRPC cells. Importantly, the combination of PLGA-encapsulated myricetin with enzalutamide is potentially effective for CRPC.

A Clinical and Integrated Genetic Study of Isolated and Combined Dystonia in Taiwan.

Dystonia is a clinically and genetically heterogeneous movement disorder. However, genetic causes of dystonia remain largely unknown in Asian subjects. To address this, we applied an integrated two-step approach that included gene dosage analysis and a next-generation sequencing panel containing 72 known genes causative for dystonia and related movement disorders to 318 Taiwanese patients with isolated or combined dystonia. Whole-genome sequencing was performed for one multiplex family with no known causative variant. The panel confirmed the genetic diagnosis in 40 probands (12.6%). A genetic diagnosis was more likely with juvenile onset compared with adult onset (24.2% vs 10.8%; P = 0.03) and those with combined features, especially with myoclonus, compared with isolated dystonia (35.3% vs 10.5%; P = 0.004). The most common causative genes were SGCE followed by GCH1, TH, CACNA1B, PRRT2, MR1, CIZ1, PLA2G6, and PRKN. Genetic causes were identified from single cases in TOR1A, TUBB4A, THAP1, ATP1A3, ANO3, GNAL, KMT2B, SLC6A3, ADCY5, CYP27A1, PANK2, C19orf12, and SPG11. The whole-genome sequencing analysis identified a novel intragenic deletion in OPHN1 in a multiplex family with X-linked dystonia and intellectual delay. Our findings delineate the genetic architecture and clinical spectrum of dystonia-causing pathogenic variants in an Asian population.

Investigating DYT1 in a Taiwanese dystonia cohort.

BACKGROUND/PURPOSE: A heterozygous three-nucleotide (GAG) in-frame deletion in the TOR1A gene causes the rare disease, dystonia (DYT1), which typically presents as focal limb dystonia during adolescence, then spreads to other limbs. This study investigated the frequency and clinical features of DYT1 in a Taiwanese dystonia cohort. METHODS: We performed targeted next generation sequencing in 318 patients with primary dystonia. We identified one DYT1 family with various types of dystonia, and we described the clinical presentations observed in this family during a 30-year follow-up. We compared the clinical characteristics to those reported in previous studies on DYT1 from 2000 to 2020. RESULTS: Among 318 patients, we identified only one DYT1 patient (0.3%) with an autosomal dominant family history of dystonia. The proband was a 43-year-old man that experienced progressive onset of focal lower limb dystonia from age 11 years. The disease spread caudal-rostrally to the upper limbs and cervical muscles. Prominent cervical dystonia was noted during follow-up, which was an atypical presentation of DYT1. Clinical assessments of other family members showed intrafamily variability. The proband's father and an affected sibling demonstrated only mild right-hand writer's cramp. A systematic review of previously reported DTY1 cases showed that Asian patients had a higher frequency of cervical dystonia (44.8%) than groups of Ashkenazi Jews (35%) and Non-Jewish Caucasians (30.5%) (P = 0.04). CONCLUSION: Our findings revealed that DYT1 is rare in a Taiwanese dystonia cohort. The presentation of marked cervical dystonia could be the main feature of Asian patients with DYT1.

Restoration of dysnatremia and acute kidney injury benefits outcomes of acute geriatric inpatients.

Dysnatremia and dyskalemia are common problems in acutely hospitalized elderly patients. These disorders are associated with an increased risk of mortality and functional complications that often occur concomitantly with acute kidney injury in addition to multiple comorbidities. In a single-center prospective observational study, we recruited 401 acute geriatric inpatients. In-hospital outcomes included all-cause mortality, length of stay, and changes in functional status as determined by the Activities of Daily Living (ADL) scale, Eastern Cooperative Oncology Group (ECOG) performance, and Clinical Frailty Scale (CFS). The prevalence of dysnatremia alone, dyskalemia alone, and dysnatremia plus dyskalemia during initial hospitalization were 28.4%, 14.7% and 32.4%, respectively. Patients with electrolyte imbalance exhibited higher mortality rates and longer hospital stays than those without electrolyte imbalance. Those with initial dysnatremia, or dysnatremia plus dyskalemia were associated with worse ADL scores, ECOG performance and CFS scores at discharge. Subgroup analyses showed that resolution of dysnatremia was related to reduced mortality risk and improved CFS score, whereas recovery of renal function was associated with decreased mortality and better ECOG and CFS ratings. Our data suggest that restoration of initial dysnatremia and acute kidney injury during acute geriatric care may benefit in-hospital survival and functional status at discharge.

Mutations in the PKM2 exon-10 region are associated with reduced allostery and increased nuclear translocation.

PKM2 is a key metabolic enzyme central to glucose metabolism and energy expenditure. Multiple stimuli regulate PKM2's activity through allosteric modulation and post-translational modifications. Furthermore, PKM2 can partner with KDM8, an oncogenic demethylase and enter the nucleus to serve as a HIF1α co-activator. Yet, the mechanistic basis of the exon-10 region in allosteric regulation and nuclear translocation remains unclear. Here, we determined the crystal structures and kinetic coupling constants of exon-10 tumor-related mutants (H391Y and R399E), showing altered structural plasticity and reduced allostery. Immunoprecipitation analysis revealed increased interaction with KDM8 for H391Y, R399E, and G415R. We also found a higher degree of HIF1α-mediated transactivation activity, particularly in the presence of KDM8. Furthermore, overexpression of PKM2 mutants significantly elevated cell growth and migration. Together, PKM2 exon-10 mutations lead to structure-allostery alterations and increased nuclear functions mediated by KDM8 in breast cancer cells. Targeting the PKM2-KDM8 complex may provide a potential therapeutic intervention.

KDM4B is a coactivator of c-Jun and involved in gastric carcinogenesis.

KDM4/JMJD2 Jumonji C-containing histone lysine demethylases (KDM4A-D) constitute an important class of epigenetic modulators in the transcriptional activation of cellular processes and genome stability. Interleukin-8 (IL-8) is overexpressed in gastric cancer, but the mechanisms and particularly the role of the epigenetic regulation of IL-8, are unclear. Here, we report that KDM4B, but not KDM4A/4C, upregulated IL-8 production in the absence or presence of Helicobacter pylori. Moreover, KDM4B physically interacts with c-Jun on IL-8, MMP1, and ITGAV promoters via its demethylation activity. The depletion of KDM4B leads to the decreased expression of integrin αV, which is exploited by H. pylori carrying the type IV secretion system, reducing IL-8 production and cell migration. Elevated KDM4B expression is significantly associated with the abundance of p-c-Jun in gastric cancer and is linked to a poor clinical outcome. Together, our results suggest that KDM4B is a key regulator of JNK/c-Jun-induced processes and is a valuable therapeutic target.

Helicobacter pylori cholesterol glucosylation modulates autophagy for increasing intracellular survival in macrophages.

Cholesterol-α-glucosyltransferase (CGT) encoded by the type 1 capsular polysaccharide biosynthesis protein J (capJ) gene of Helicobacter pylori converts cellular cholesterol into cholesteryl glucosides. H. pylori infection induces autophagy that may increase bacterial survival in epithelial cells. However, the role of H. pylori CGT that exploits lipid rafts in interfering with autophagy for bacterial survival in macrophages has not been investigated. Here, we show that wild-type H. pylori carrying CGT modulates cholesterol to trigger autophagy and restrain autophagosome fusion with lysosomes, permitting a significantly higher bacterial burden in macrophages than that in a capJ-knockout (∆CapJ) mutant. Knockdown of autophagy-related protein 12 impairs autophagosome maturation and decreases the survival of internalised H. pylori in macrophages. These results demonstrate that CGT plays a crucial role in the manipulation of the autophagy process to impair macrophage clearance of H. pylori.

Identification of a Chlorophyll Dephytylase Involved in Chlorophyll Turnover in Arabidopsis.

Chlorophyll turns over in green organs during photosystem repair and is salvaged via de- and rephytylation, but the enzyme involved in dephytylation is unknown. We have identified an Arabidopsis thaliana thylakoid protein with a putative hydrolase domain that can dephytylate chlorophyll in vitro and in vivo. The corresponding locus, CHLOROPHYLL DEPHYTYLASE1 (CLD1), was identified by mapping a semidominant, heat-sensitive, missense allele (cld1-1). CLD1 is conserved in oxygenic photosynthetic organisms, sharing structural similarity with pheophytinase, which functions in chlorophyll breakdown during leaf senescence. Unlike pheophytinase, CLD1 is predominantly expressed in green organs and can dephytylate chlorophyll in vitro. The specific activity is significantly higher for the mutant protein encoded by cld1-1 than the wild-type enzyme, consistent with the semidominant nature of the cld1-1 mutation. Supraoptimal CLD1 activities in cld1-1 mutants and transgenic seedlings led to the proportional accumulation of chlorophyllides derived from chlorophyll dephytylation after heat shock, which resulted in light-dependent cotyledon bleaching. Reducing CLD1 expression diminished thermotolerance and the photochemical efficiency of photosystem II under prolonged moderate heat stress. Taken together, our results suggest that CLD1 is the long-sought enzyme for removing the phytol chain from chlorophyll during its turnover at steady state within the chloroplast.

Thrombolytic therapy is an only determinant factor for stroke evolution in large anterior choroidal artery infarcts.

BACKGROUND: Large anterior choroidal artery (AChA) infarcts are frequently associated with stroke evolution. This study aimed to investigate the major determinants for stroke evolution in patients with large AChA infarcts. METHODS: We studied 118 consecutive adult patients with acute large AChA infarcts. The diagnosis was confirmed as abnormal hyperintensities in 3 or more rostracaudal magnetic resonance imaging slices (5 mm thickness) using diffusion-weighted imaging within typical AChA vascular regions. Stroke evolution was defined as neurologic deterioration with an increase in National Institutes of Health Stroke Scale (NIHSS) score by at least 4 or an increase of NIHSS score in motor function by at least 2 in 7 days after stroke onset. RESULTS: Forty-seven (39.8%) patients developed stroke evolution. Thrombolytic therapy was inversely associated with the occurrence of stroke evolution (P = .004). Using multivariate analysis, thrombolytic therapy was the only protective determinant for stroke evolution (adjusted odds ratio, .08; 95% confidence interval, .01 to .67). Patients with large AChA infarcts receiving thrombolytic therapy had less unfavorable long-term functional outcome than those not receiving thrombolytic therapy (adjusted odds ratio, .11; 95% confidence interval, .02-.75). CONCLUSIONS: Thrombolytic therapy is an only determinant factor for stroke evolution in large AChA infarcts, which reduced the risk of stroke evolution and improved functional outcome.

Hemiballism in a patient with parietal lobe infarction.

A 60-year-old man with a history of atrial fibrillation had an acute onset of ballistic movements of the left limbs with sensory extinction (video on the Neurology® Web site at www.neurology.org). The patient was treated with risperidone and anticoagulant; symptoms subsided 3 days later. Brain MRI showed acute infarction of the right posterior parietal lobe (figure 1) and SPECT revealed hypoperfusion in the right frontoparietal areas (figure 2).

Kinetic study on the tyrosinase and melanin formation inhibitory activities of carthamus yellow isolated from Carthamus tinctorius L.

Carthamus yellow (CY) is the major component of the yellow pigments of Carthamus tinctorius L. CY has been extensively used as a natural color additive for food and cosmetics. Here, our results demonstrate that carthamus yellow reduced the activity of mushroom tyrosinase in a dose-dependent manner with a half maximal inhibitory concentration (IC(50)) value of approximately 1.01 ± 0.03 mg/mL. A kinetic study of carthamus yellow on tyrosinase exhibited a mode of competitive inhibition with a Ki of 0.607 mg/mL. Moreover, cell viability analysis indicated that carthamus yellow used at concentrations of 1.0-4.0 mg/mL had no cytotoxicity in B16F10 melanoma cells. Melanin content analysis showed that melanin production in B16F10 melanoma cells treated with 4 mg/mL carthamus yellow can decrease to 82.3 ± 0.4% of the levels of melanin production of untreated cells. Thus, carthamus yellow has the potential to become a useful skin-whitening agent in the future.

A community-based study of Helicobacter pylori therapy using the strategy of test, treat, retest, and re-treat initial treatment failures.

BACKGROUND: Although eradication of Helicobacter pylori infection can decrease the risk of gastric cancer, the optimal regimen for treating the general population remains unclear. We report the eradication rate (intention-to-treat and per protocol) of a community-based H. pylori therapy using the strategy of test, treat, retest, and re-treat initial treatment failures. MATERIALS AND METHODS: In 2004, a total of 2658 residents were recruited for 13C-urea breath testing. Participants with positive results for infection received a standard 7-day triple therapy (esomeprazole 40 mg once daily, amoxicillin 1 g twice daily, and clarithromycin 500 mg twice daily), and a 10-day re-treatment (esomeprazole 40 mg once daily, amoxicillin 1 g twice daily, and levofloxacin 500 mg once daily) if the follow-up tests remained positive. Both H. pylori status and side-effects were assessed 6 weeks after treatment. RESULTS: Among 886 valid reporters, eradication rates with initial therapy were 86.9% (95% confidence interval [CI]: 84.7-89.1%) and 88.7% (95%CI: 86.5-90.9%) by intention-to-treat and per protocol analysis, respectively. Re-treatment eradicated infection in 91.4% (95%CI: 86-96.8%) of 105 nonresponders. Adequate compliance was achieved in 798 (90.1%) of 886 subjects receiving the initial treatment and in all 105 re-treated subjects. Mild side-effects occurred in 24% of subjects. Overall intention-to-treat and per protocol eradication rates were 97.7% (95%CI: 96.7-98.7%) and 98.8% (95%CI: 98.5-99.3%), respectively, which were only affected by poor compliance (odds ratio, 3.3; 95%CI, 1.99-5.48; p < .0001). CONCLUSIONS: A comprehensive plan using drugs in which the resistance rate is low in a population combined with the strategy of test, treat, retest, and re-treat of needed can result in virtual eradication of H. pylori from a population. This provides a model for planning country- or region-wide eradication programs.