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Parkinson's disease is the second most common age-related neurodegenerative disorder, typified by the progressive loss of substantia nigra pars compacta dopamine neurons and the consequent decrease in the neurotransmitter dopamine. Patients exhibit a range of clinical symptoms, with the most common affecting motor function and including resting tremor, rigidity, akinesia, bradykinesia and postural instability. Current pharmacological interventions are palliative and largely aimed at increasing dopamine levels through increased production and/or inhibition of metabolism of this key neurotransmitter. The gold standard for treatment of both familial and sporadic Parkinson's disease is the peripheral administration of the dopamine precursor, levodopa. However, many patients gradually develop levodopa-induced dyskinesias and motor fluctuations. In addition, dopamine enhancement therapies are most useful when a portion of the nigrostriatal pathway is intact. Consequently, as the number of substantia nigra dopamine neurons and striatal projections decrease, these treatments become less efficacious. Current translational research is focused on the development of novel disease-modifying therapies, including those utilizing gene therapeutic approaches. Herein we present an overview of current gene therapy clinical trials for Parkinson's disease. Employing either recombinant adeno-associated virus type 2 (rAAV2) or lentivirus vectors, these clinical trials are focused on three overarching approaches: augmentation of dopamine levels via increased neurotransmitter production; modulation of the neuronal phenotype; and neuroprotection. The first two therapies discussed in this article focus on increasing dopamine production via direct delivery of genes involved in neurotransmitter synthesis (amino acid decarboxylase, tyrosine hydroxylase and GTP [guanosine triphosphate] cyclohydrolase 1). In an attempt to bypass the degenerating nigrostriatal pathway, a third clinical trial utilizes rAAV2 to deliver glutamic acid decarboxylase to the subthalamic nucleus, converting a subset of excitatory neurons to GABA-producing cells. In contrast, the final clinical trial is aimed at protecting the degenerating nigrostriatum by striatal delivery of rAAV2 harbouring the neuroprotective gene, neurturin. Based on preclinical studies, this gene therapeutic approach is posited to slow disease progression by enhancing neuronal survival. In addition, we discuss the outcome of each clinical trial and discuss the potential rationale for the marginal yet incremental clinical advancements that have thus far been realized for Parkinson's disease gene therapy. [ABSTRACT FROM AUTHOR]

Introduction: Frailty is a risk factor for adverse outcomes after injury. Herein, we compared three frailty scales: the Canadian Study of Health and Aging clinical frailty scale, the rib fracture frailty index (RFFI) and the modified frailty index-5, to assess which scale is most applicable in predicting risk for negative outcomes in older patients with rib fractures., Methods: Patients ≥65 admitted for rib fractures were retrospectively scored for frailty using the RFFI, Canadian Study of Health and Aging clinical frailty scale, and modified frailty index-5. Outcomes examined were in-hospital mortality, pneumonia, in-hospital intubation, hospital length of stay, and discharge to skilled nursing facilities. Areas under the curve, sensitivity, specificity, negative predictive value, and positive predictive value were determined for each frailty scale with each outcome. Agreement was determined using Fleiss' Kappa. P <0.05 was considered significant., Results: Three hundred forty-one patients were included. All three scales demonstrated similar predictive abilities for the measured outcomes. RFFI predicted mortality and pneumonia 70% of the time. All three scales predicted discharge to skilled nursing facilities 60% of the time. The concordance for all three frailty scales was 241/341 (70.7%). Fleiss Kappa was 0.40 [0.34-0.46] (P < 0.001), indicating a fair to moderate agreement. The predictive ability of all three scales was higher in patients 65-74 y old than in patients ≥75., Conclusions: Overall, no scale appeared to significantly outperform the others by areas under the curve estimation. Interrater reliability was higher in the 65 to 74-y-old population compared to the 75 and older population., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Visual rating of the cingulate island sign (CIS) on [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) positron emission tomography (PET) has a high specificity for dementia with Lewy bodies (DLB) in selected cohorts such as DLB versus Alzheimer's disease (AD). In a mixed memory clinical population this study aimed to uncover the prevalence of CIS, the diagnostic accuracy for DLB, and the relationship between CIS and disease severity., Methods: CIS on [ 18 F]FDG-PET was retrospectively assessed with the visual CIS rating scale (CISRs) in 1000 patients with a syndrome diagnosis of mild cognitive impairment (MCI) or dementia with no restrictions in etiological diagnosis., Results: In this cohort 24.3 % had a CISRs score ≥1 and 3.5 % had a CISRs score = 4. The prevalence of a CISRs score ≥1 was highest in DLB (74.0 %, n = 57). A CISRs score ≥1 was present in at least 9 % in other diagnostic groups. The prevalence of CIS across disease severities showed no statistically significant difference (p = 0.23). To differentiate DLB from non-DLB the optimal cut-off was a CISRs score ≥1 (balanced accuracy = 77.1 %) in MCI/mild dementia and a CISRs score ≥2 (balanced accuracy = 80.6 %) in moderate/severe dementia. The positive predictive value of a CISRs score = 4 for DLB was 57.7 % in MCI/mild dementia and 33.3 % in moderate/severe dementia., Conclusion: The CISRs is useful in differentiating DLB from other etiologies in a mixed memory clinical population. Balanced accuracy and positive predictive value may vary across disease severities in the population studied., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a disabling disorder, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available. We used rigorous criteria to recruit PI-ME/CFS participants with matched controls to conduct deep phenotyping. Among the many physical and cognitive complaints, one defining feature of PI-ME/CFS was an alteration of effort preference, rather than physical or central fatigue, due to dysfunction of integrative brain regions potentially associated with central catechol pathway dysregulation, with consequences on autonomic functioning and physical conditioning. Immune profiling suggested chronic antigenic stimulation with increase in naïve and decrease in switched memory B-cells. Alterations in gene expression profiles of peripheral blood mononuclear cells and metabolic pathways were consistent with cellular phenotypic studies and demonstrated differences according to sex. Together these clinical abnormalities and biomarker differences provide unique insight into the underlying pathophysiology of PI-ME/CFS, which may guide future intervention., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Hepatic resection (HR) is an excellent option for patients with hepatocellular carcinoma (HCC). For patients meeting the Milan criteria, a liver transplant (LT) is also a viable option for patients with HCC, especially those with end-stage liver disease. With increasing rates of LTs amongst the elderly, we sought to determine long-term outcomes in patients who underwent HR compared to LTs in this patient population., Methods: We queried the national cancer database for elderly patients (≥70 years) diagnosed with HCC between 2004 and 2020. The primary outcome was overall survival (OS) computed using the Kaplan-Meier method and Cox proportional hazard regression. One-to-one propensity score matching was conducted on the basis of clinicodemographic features to account for baseline differences between patients undergoing each procedure., Results: Of the 5090 patients included, 4674 (91.8%) and 416 (8.2%) patients underwent HR and LT, respectively. Compared with HR patients, patients receiving LT had better OS (p < 0.001) and greater median survival time (65.6 months HR vs. 97.9 months LT, p < 0.001). On multivariable analysis, a LT was independently associated with improved survival (adjusted hazard ratio: 0.61, 95% confidence interval: 0.50-0.76, p < 0.001)., Conclusions: LT is associated with improved survival for well-selected elderly patients with HCC. Age alone should not be used as the sole parameter for the candidacy of LT in elderly patients., (© 2023 Wiley Periodicals LLC.)

Introduction: The role of angioembolization (AE) in patients with benign liver diseases is an area of active research. This study aims to assess any difference in liver resection outcomes in patients with benign tumors dependent on utilization of preoperative AE., Methods: A retrospective cohort study of patients undergoing elective liver resections for benign liver tumors was performed using the National Surgical Quality Improvement Program database (2014-2019). Only tumors of 5 cm in size or more were included in the analysis. We categorized the patients based on preoperative AE (AE + versus AE -). The primary outcome measured included bleeding complications within 72 h. The secondary outcomes were to determine predictors of bleeding., Results: After propensity score matching, there were 103 patients in both groups. There was no difference in intraoperative or postoperative blood transfusions within 72 h of surgery (14.6% versus 12.6%; P = 0.68), reoperation (1.9% versus 1.9%; P = 1), or mortality (1.0% versus 0.0%; P = 1) between the two groups. Multivariate regression analysis revealed an open surgical approach (odds ratio [OR]: 4.59 confidence interval [CI]: 2.94-7.16), use of Pringle maneuver (OR: 1.7, CI: 1.26-2.310), preoperative anemia (OR: 2.79, CI: 2.05-3.80), and preoperative hypoalbuminemia (OR: 1.53 [1.14-2.05]) were associated with the need for intraoperative or postoperative blood transfusions within 72 h of surgery., Conclusions: Preoperative AE was not associated with reducing intraoperative or postoperative bleeding complications or blood transfusions within 72 h after surgery., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: The cingulate island sign (CIS) is a metabolic pattern on [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) positron emission tomography (PET) associated with dementia with Lewy bodies (DLB). The aim of this study was to validate the visual CIS rating scale (CISRs) for the diagnosis of DLB and to explore the clinical correlates., Methods: This single-center study included 166 DLB patients and 161 patients with Alzheimer's disease (AD). The CIS on [ 18 F]FDG-PET scans was rated using the CISRs independently by three blinded raters., Results: The optimal cut-off to differentiate DLB from AD was a CISRs score ≥ 1 (sensitivity = 66%, specificity = 84%) whereas a CISRs score ≥ 2 (sensitivity = 58%, specificity = 92%) was optimal to differentiate amyloid positive DLB (n = 43 (82.7%)) and AD. To identify DLB with abnormal (n = 53 (72.6%)) versus normal (n = 20 (27.4%)) dopamine transporter imaging, a CISRs cut-off of 4 had a specificity of 95%. DLB with a CISRs score of 4 performed significantly better in tests on free verbal recall and picture based cued recall, but worse on processing speed compared to DLB with a CISRs score of 0., Conclusion: This study confirms the CISRs as a valid marker for the diagnosis of DLB with a high specificity and a lower, but acceptable, sensitivity. Concomitant AD pathology does not influence diagnostic accuracy of the CISRs. In DLB patients, presence of CIS is associated with relative preserved memory function and impaired processing speed., Competing Interests: Declaration of Competing Interest All authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: In patients with rib fractures, adverse outcomes are associated with number of rib fractures; however, studies suggest an association with frailty. We assessed whether frailty, measured using the Canadian Study of Health and Aging clinical frailty scale, was associated with adverse outcomes in this population., Methods: Patients ≥50 years admitted for rib fractures from July 2015 to June 2020 were retrospectively scored for frailty. Demographics, comorbidities, injury information, hospital course, and complications were collected. Univariate analyses were performed to assess significant differences between the fit, prefrail, and frail groups. The association between number of rib fractures and frailty with outcomes was determined., Results: Controlling for age, sex, Injury Severity Score, preadmission anticoagulant, injury mechanism, and comorbidities and nonchest Abbreviated Injury Scores showing significant differences, the number of rib fractures was associated with developing pneumonia (odds ratio = 1.197 [1.076-1.332]; P = .001), hospital length of stay (odds ratio = 1.066 [1.033-1.100], P < .001), mortality (odds ratio = 1.157 [1.048-1.278], P = .004), and discharge to long-term acute care facilities (odds ratio = 1.295 [1.084-1.546], P = .004). Frailty was associated with hospital length of stay (odds ratio = 1.659 [1.059-2.598], P = .027) and discharge to skilled nursing facilities (odds ratio = 5.282 [1.567-17.802], P = .007)., Conclusion: In our population, the number of rib fractures was associated with respiratory complications and mortality. Frailty was associated with longer hospitalization and discharge to higher level of care., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: In patients with systemic lupus erythematosus (SLE), fatigue is a debilitating symptom with poorly understood pathophysiology. Cardiorespiratory dysfunction has been hypothesised as a contributor to SLE-fatigue. The purpose of this exploratory study was to examine changes in cardiorespiratory function, following an exercise training programme in women with SLE, together with patient reported outcomes and other pathophysiological measures that may underlie SLE-fatigue., Methods: Sixteen women with SLE and fatigue (Fatigue Severity Scale (FSS) ≥3) were enrolled in a supervised aerobic exercise training programme of vigorous intensity. The primary outcome was time to reach anaerobic threshold (AT-Time) during a cardiopulmonary exercise test (CPET). Secondary outcomes included changes in the 10-minute walk test (10MWT), FSS scores and the Patient Reported Outcomes Measurement Information System (PROMIS-57) survey. Mitochondrial function was assessed by the oxygen consumption rate (OCR)/extracellular acidification rate (ECAR) metabolic potential ratio., Results: Following 12 weeks of exercise training, AT-Time increased by 93±82 (mean±SD) s (p<0.001), 10MWT increased by 84±66 m (p<0.001) and peak oxygen uptake (VO 2 ) increased by 1.4±2.0 mL/kg/min (p=0.013). There were improvements in FSS score (-1.4±1.0, p<0.0001) and in most of the PROMIS-57 domains. The decrease in FSS scores correlated with an increase in the OCR/ECAR ratio (Pearson's correlation r=-0.59, p=0.03). A subset of subjects (9/15) had significant reduction in their Interferon Stimulated Genes (ISG) (p=0.007) accompanied by a significant increase in the OCR/ECAR ratio (p=0.013)., Conclusions: Cardiorespiratory function was improved in concomitance with reductions in fatigue following a 12-week aerobic exercise programme. The reduction in fatigue scores correlated with improvements in mitochondrial function., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Fatigue is a persistent and debilitating symptom following cancer treatments such as chemotherapy. Recent clinical studies have suggested a common single-nucleotide polymorphism of brain-derived neurotrophic factor (BDNF), Val66Met (rs6265), may be related to the severity of fatigue following cancer treatment. In this study, we tested transgenic mice homozygous for the human Val66Met BDNF gene and wild-type controls. We injected three doses of 5-fluorouracil (5FU) as a model of chemotherapy treatment, and we used changes in voluntary wheel running activity (VWRA) as a measure of fatigue-like behavior. Prior to 5FU injection, we found that during the baseline wheel-running period, the Val66Met mice lost more weight than WT controls. We next administered 5FU and saw a robust fatigue-like phenotype that lasted about 2 weeks. During the first week, the fatigue-like phenotype was less severe in the Val66Met mice and unrelated to the age of the mice. In contrast, during the second week after 5FU treatment, the fatigue-like phenotype was unrelated to the BDNF genotype but was more severe in middle aged mice compared to young mice. We conclude that the BDNF polymorphism may play a direct, protective role against chemotherapy-induced fatigue., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wolff, Allen, Feng and Saligan.)

Background: Thymosin β4 (Tβ4) is the most abundant member of the β-thymosins and plays an important role in the control of actin polymerization in eukaryotic cells. While its effects in multiple organs and diseases are being widely investigated, the safety profile has been established in animals and humans, currently, little is known about its influence on Alzheimer's disease (AD) and the possible mechanisms. Thus, we aimed to evaluate the effects and mechanisms of Tβ4 on glial polarization and cognitive performance in APP/PS1 transgenic mice., Methods: Behavior tests were conducted to assess the learning and memory, anxiety and depression in APP/PS1 mice. Thioflavin S staining, Nissl staining, immunohistochemistry/immunofluorescence, ELISA, qRT-PCR, and immunoblotting were performed to explore Aβ accumulation, phenotypic polarization of glial cells, neuronal loss and function, and TLR4/NF-κB axis in APP/PS1 mice., Results: We demonstrated that Tβ4 protein level elevated in all APP/PS1 mice. Over-expression of Tβ4 alone alleviated AD-like phenotypes of APP/PS1 mice, showed less brain Aβ accumulation and more Insulin-degrading enzyme (IDE), reversed phenotypic polarization of microglia and astrocyte to a healthy state, improved neuronal function and cognitive behavior performance, and accidentally displayed antidepressant-like effect. Besides, Tβ4 could downregulate both TLR4/MyD88/NF-κB p65 and p52-dependent inflammatory pathways in the APP/PS1 mice. While combination drug of TLR4 antagonist TAK242 or NF-κB p65 inhibitor PDTC exerted no further effects., Conclusions: These results suggest that Tβ4 may exert its function by regulating both classical and non-canonical NF-κB signaling and is restoring its function as a potential therapeutic target against AD.

Fatigue is a persistent and debilitating symptom following radiation therapy for prostate cancer. However, it is not well-understood how radiation targeted to a small region of the body can lead to broad changes in behavior. In this study, we used targeted pelvic irradiation of healthy male mice to test whether inflammatory signaling mediates changes in voluntary physical activity levels. First, we tested the relationship between radiation dose, blood cell counts, and fatigue-like behavior measured as voluntary wheel-running activity. Next, we used oral minocycline treatments to reduce inflammation and found that minocycline reduces, but does not eliminate, the fatigue-like behavioral changes induced by radiation. We also used a strain of mice lacking the MyD88 adaptor protein and found that these mice also showed less fatigue-like behavior than the wild-type controls. Finally, using serum and brain tissue samples, we determined changes in inflammatory signaling induced by irradiation in wild-type, minocycline treated, and MyD88 knockout mice. We found that irradiation increased serum levels of IL-6, a change that was partially reversed in mice treated with minocycline or lacking MyD88. Overall, our results suggest that inflammation plays a causal role in radiation-induced fatigue and that IL-6 may be an important mediator., Competing Interests: There are no conflicts of interest to report.

Background: Androgen deprivation therapy (ADT) is a cornerstone treatment for prostate cancer. Despite the clinical benefits, ADT is associated with multiple adverse effects including fatigue. The goal of the study was to examine metabolomic changes to better understand cancer-related fatigue specific to ADT treatment., Methods: A total of 160 plasma samples collected from participants with (+ADT, n = 58) or without neoadjuvant ADT (-ADT, n = 102) prior to radiation therapy for treatment of non-metastatic localized prostate cancer were included in the study. Fatigue and sleep-related impairment were measured using the Patient Reported Outcomes Measurement Information System. Plasma metabolites were identified and measured using untargeted ultrahigh-performance liquid chromatography/mass spectrometry metabolomics analyses. Partial least square discriminant analysis was used to identify discriminant metabolite features, and the diagnostic performance of selected classifiers was quantified using AUROC curve analysis. Pathway enrichment analysis was performed using metabolite sets enrichment analyses., Findings: Steroid hormone biosynthesis pathways, including androstenedione metabolism as well as androgen and estrogen metabolism, were overrepresented by metabolites that significantly discriminated samples in the +ADT from the -ADT group. Additional overrepresented metabolic pathways included amino acid metabolism, glutathione metabolism, and carnitine synthesis. Of the metabolites that were significantly different between the groups, steroid hormone biosynthesis metabolites were most significantly correlated with fatigue severity. Sleep-related impairment was strongly correlated with fatigue severity and inversely correlated with ADT-induced reduction in androsterone sulfate., Conclusions: Patients with non-metastatic prostate cancer receiving neoadjuvant ADT prior to radiation therapy reported relatively more severe fatigue. Increased fatigue in this population may be attributable to sleep-related impairment associated with alterations in steroid hormone biosynthesis. Findings in this study provide a basis for further research of changes in sleep patterns and their role in this specific subcategory of cancer-related fatigue caused by the treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Feng, Barb, Allen, Regan and Saligan.)

Background: Metabolomics is the newest -omics methodology and allows for a functional snapshot of the biochemical activity and cellular state. The goal of this study is to characterize metabolomic profiles associated with cancer-related fatigue, a debilitating symptom commonly reported by oncology patients., Methods: Untargeted ultrahigh performance liquid chromatography/mass spectrometry metabolomics approach was used to identify metabolites in plasma samples collected from a total of 197 participants with or without cancer. Partial least squares-discriminant analysis (PLS-DA) was used to identify discriminant metabolite features, and diagnostic performance of selected classifiers was quantified using area under the receiver operating characteristics (AUROC) curve analysis. Pathway enrichment analysis was performed using Fisher's exact test and the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway database., Findings: The global metabolomics approach yielded a total of 1120 compounds of known identity. Significant metabolic pathways unique to fatigued cancer versus control groups included sphingolipid metabolism, histidine metabolism, and cysteine and methionine metabolism. Significant pathways unique to non-fatigued cancer versus control groups included inositol phosphate metabolism, primary bile acid biosynthesis, ascorbate and aldarate metabolism, starch and sucrose metabolism, and pentose and glucuronate interconversions. Pathways shared between the two comparisons included caffeine metabolism, tyrosine metabolism, steroid hormone biosynthesis, sulfur metabolism, and phenylalanine metabolism., Conclusions: We found significant metabolomic profile differences associated with cancer-related fatigue. By comparing metabolic signatures unique to fatigued cancer patients with metabolites associated with, but not unique to, fatigued cancer individuals (overlap pathways) and metabolites associated with cancer but not fatigue, we provided a broad view of the metabolic phenotype of cancer-related fatigue., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Cancer-related fatigue is an extremely common and debilitating psychiatric symptom that affects up to 80% of cancer patients. Despite its negative impact on the patient's quality of life, there is no well-established biomarker or mechanisms associated with this debilitating condition. The functional brain-derived neurotrophic factor (BDNF) Val66Met single nucleotide polymorphism (SNP) has been associated with a variety of psychiatric illnesses. We hypothesized that Val66Met may influence the risk for developing cancer-related fatigue. BDNF Val66Met was analyzed by polymerase chain reaction in 180 patients with confirmed cancer diagnoses. Fatigue was measured using the Functional Assessment of Cancer Therapy-Fatigue (FACIT-Fatigue) questionnaire. Depression was measured using the Hamilton Depression Scale (HAM-D). Data were transformed when necessary and regression models were constructed to access the association between genotype and symptom severity. Participants carrying the Met allele reported significantly less fatigue compared to the Val/Val genotype group. The presence of the Met allele did not influence depression levels. The results suggest that the BDNF Val66Met polymorphism confers protective advantage against cancer-related fatigue; whereas having the Val/Val genotype may be a genetic risk factor. Findings from this study not only provide clues to the neural basis of cancer-related fatigue, but also allow for symptom severity prediction and patient education with the goal to improve symptom management.

Fatigue and cognitive deficits are often co-occurring symptoms reported by patients after radiation therapy for prostate cancer. In this study, we induced fatigue-like behavior in mice using targeted pelvic irradiation to mimic the clinical treatment regimen and assess cognitive behavioral changes. We observed that pelvic irradiation produced a robust fatigue phenotype, a reduced rate of spontaneous alternation in a Y-maze test, and no behavioral change in an open field test. We found that reversal learning for fatigued mice was slower with respect to time, but not with respect to effort put into the test, suggesting that fatigue may impact the ability or motivation to work at a cognitive task without impairing cognitive capabilities. In addition, we found that mice undergoing pelvic irradiation show lower whole-brain levels of mature BDNF, and that whole-brain proBDNF levels also correlate with spontaneous alternation in a Y-maze test. These results suggest that changes in BDNF levels could be both a cause and an effect of fatigue-related changes in behavior., Competing Interests: The authors have declared that no competing interests exist.

Following the publication of the article, the authors realized that they have overlooked acknowledging the assistance they received from the Murine Phenotyping Core at NHLBI. Therefore, the Acknowledgements section of the Declarations should also have stated the following: 'We would like to thank the Murine Phenotyping Core at NHLBI for all their help with the mouse experiments, including Dr Danielle Springer, Audrey Noguchi, Michele Allen, Heather Potts and Morteza Peiravi.' The authors regret their oversight in failing to include this information in the Acknowledgements section of their paper. [the original article was published in International Journal of Molecular Medicine 45: 485‑496, 2020; DOI: 10.3892/ijmm.2019.4435].

Cancer-related fatigue (CRF) is commonly reported by patients both during and after receiving treatment for cancer. Current CRF diagnoses rely on self-report questionnaires which are subject to report and recall biases. Objective measurements using a handheld dynamometer, or handgrip device, have been shown in recent studies to correlate significantly with subjective self-reported fatigue scores. However, variations of both the handgrip fatigue test and fatigue index calculations exist in the literature. The lack of standardized methods limits the utilization of the handgrip fatigue test in the clinical and research settings. In this study, we provide detailed methods for administering the physical fatigue test and calculating the fatigue index. These methods should supplement existing self-reported fatigue questionnaires and help clinicians assess fatigue symptom severity in an objective and quantitative manner.

Combined androgen deprivation therapy (ADT) and radiation therapy (RT) is the standard of care treatment for non‑metastatic prostate cancer (NMPC). Despite the efficacy, treatment‑related symptoms including fatigue greatly reduce the quality of life of cancer patients. The goal of the study is to examine the influence of combined ADT/RT on fatigue and understand its underlying mechanisms. A total of 64 participants with NMPC were enrolled. Fatigue was assessed using the Functional Assessment of Cancer Therapy‑Fatigue. Mitochondrial function parameters were measured as oxygen consumption from peripheral blood mononuclear cells (PBMCs) extracted from participants' whole blood. An ADT/RT‑induced fatigue mouse model was developed, with fatigue measured as a reduction in voluntary wheel‑running activity (VWRA) in 54 mice. Mitochondrial function was assessed in the ADT/RT mouse brains using western blot analysis of glucose transporter 4 (GLUT4) and transcription factor A, mitochondrial (TFAM). The results demonstrated that fatigue in the ADT group was exacerbated during RT compared with the non‑ADT group. This effect was specific to fatigue, as depressive symptoms were unaffected. PBMCs of fatigued subjects exhibited decreased ATP coupling efficiency compared to non‑fatigued subjects, indicative of mitochondrial dysfunction. The ADT/RT mice demonstrated the synergistic effect of ADT and RT in decreasing VWRA. Brain tissues of ADT/RT mice exhibited decreased levels of GLUT4 and TFAM suggesting that impaired neuronal metabolic homeostasis may contribute to fatigue pathogenesis. In conclusion, these findings suggest that fatigue induced by ADT/RT may be attributable to mitochondrial dysfunction both peripherally and in the central nervous system (CNS). The synergistic effect of ADT/RT is behaviorally reproducible in a mouse model and its mechanism may be related to bioenergetics in the CNS.

Background: Cancer-related fatigue (CRF) is a debilitating symptom frequently reported by patients during and after treatment for cancer. CRF is a multidimensional experience and is often solely assessed by self-report measures. The goal of the study is to examine the physical and cognitive aspects of self-reported CRF using a cognitive function test and a physical fatigue index in order to provide objective measures that can characterize the CRF phenotype., Methods: A total of 59 subjects with nonmetastatic prostate cancer receiving external beam radiation therapy were included in the study. Fatigue was measured using the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) questionnaire. Cognitive characteristics of CRF was measured using the Stroop Color-Word Interference computerized test and the motor aspect of fatigue was measured using the static fatigue test using a handgrip dynamometer., Findings: Functional Assessment of Cancer Therapy-Fatigue scores significantly correlated with the Stroop Interference score, but not performance accuracy in all test conditions. Fatigued subjects exhibited a more rapid decline to 50% of maximal strength and increased static fatigue index in the handgrip test, whereas maximal grip strength was not affected., Conclusions: The results suggest that CRF exhibits both cognitive and physical characteristics. Subjective fatigue was associated with increased time required to overcome cognitive interference, but not cognitive performance accuracy. Fatigued patients exhibited decreased physical endurance and the ability to sustain maximal strength over time. These objective measures may serve as valuable tools for clinicians to detect cognitive and physical impairment associated with CRF., (Published 2019. This article is a U.S. Government work and is in the public domain in the USA. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: Cancer-related fatigue is one of the most debilitating side effects of cancer and cancer therapy. We aimed to investigate co-occurring symptoms associated with persistent fatigue in men receiving external beam radiation therapy (EBRT) for nonmetastatic prostate cancer., Methods: A sample of 47 men with prostate cancer scheduled to receive radiotherapy (RT) were followed at baseline and 1 year after RT. Clinical and demographic data were obtained from chart review. Symptom measurements included urinary dysfunction (American Urological Association symptoms score), fatigue (Functional Assessment of Cancer Therapy - Fatigue questionnaire), sleep disturbance (Patient-Reported Outcomes Measurement Information System - Sleep Disturbance form), pain (physical well-being domain pain item of the Functional Assessment of Cancer Therapy - General), and depressive symptoms (Hamilton Depression Rating Scale). Paired t tests, correlations, general linear models, and logistic regressions were used to determine associations between fatigue and other symptom scores., Results: At 1 year after RT, 34% of subjects continued to experience fatigue. Urinary dysfunction was the best clinical predictor of persistent fatigue. Pain and depressive symptoms further improved the predictive power of the model. A multivariate linear regression model containing all these three clinical variables (urinary dysfunction, pain, and depressive symptoms) explained 74% of total variance associated with persistent fatigue after RT., Conclusions: Persistent fatigue at 1 year after EBRT in prostate cancer survivors is likely related to a cluster of symptoms elicited by chronic inflammation. Therapies that target each of these symptoms will likely reduce fatigue in this patient population., (© 2019 S. Karger AG, Basel.)

Background: Prostate cancer survivors commonly experience late-onset lower urinary tract symptoms following radiotherapy. We aimed to compare lower urinary tract symptoms in patients treated with stereotactic body radiotherapy (SBRT) to those treated with a combination of lower dose SBRT and supplemental intensity-modulated radiotherapy (SBRT + IMRT)., Methods: Subjects with localized prostate carcinoma scheduled to receive SBRT or a combination of SBRT and IMRT were enrolled and followed for up to 2 years after treatment completion. Participants treated with SBRT received 35-36.25 Gy in 5 fractions, while those treated with SBRT + IMRT received 19.5 Gy of SBRT in 3 fractions followed by 45-50.4 Gy of IMRT in 25-28 fractions. Urinary symptoms were measured using the American Urological Association (AUA) Symptom Score., Results: Two hundred patients received SBRT (52% intermediate risk, 37.5% low risk according to D'Amico classification) and 145 patients received SBRT + IMRT (61.4% high risk, 35.2% intermediate risk). Both groups experienced a transient spike in urinary symptoms 1 month after treatment. More severe late urinary flare (increase in AUA scores ≥ 5 points from baseline to 1 year after treatment completion and an AUA score ≥ 15 at 1 year after treatment) was experienced by patients who received SBRT compared to those treated with SBRT + IMRT., Conclusion: Participants who received SBRT and supplemental IMRT experienced less severe late urinary flare 1 year after treatment compared to those who received higher dose SBRT alone. This information can be used by clinicians to provide patients with anticipatory counseling to mitigate any psychological burden that comes with unanticipated late urinary toxicities.

Cancer-related fatigue (CRF) is a common burden in cancer patients and little is known about its underlying mechanism. The primary aim of this study was to identify gene signatures predictive of post-radiotherapy fatigue in prostate cancer patients. We employed Fisher Linear Discriminant Analysis (LDA) to identify predictive genes using whole genome microarray data from 36 men with prostate cancer. Ingenuity Pathway Analysis was used to determine functional networks of the predictive genes. Functional validation was performed using a T lymphocyte cell line, Jurkat E6.1. Cells were pretreated with metabotropic glutamate receptor 5 (mGluR5) agonist (DHPG), antagonist (MPEP), or control (PBS) for 20 min before irradiation at 8 Gy in a Mark-1 γ-irradiator. NF-κB activation was assessed using a NF-κB/Jurkat/GFP Transcriptional Reporter Cell Line. LDA achieved 83.3% accuracy in predicting post-radiotherapy fatigue. "Glutamate receptor signaling" was the most significant (p = 0.0002) pathway among the predictive genes. Functional validation using Jurkat cells revealed clustering of mGluR5 receptors as well as increased regulated on activation, normal T cell expressed and secreted (RANTES) production post irradiation in cells pretreated with DHPG, whereas inhibition of mGluR5 activity with MPEP decreased RANTES concentration after irradiation. DHPG pretreatment amplified irradiation-induced NF-κB activation suggesting a role of mGluR5 in modulating T cell activation after irradiation. These results suggest that mGluR5 signaling in T cells may play a key role in the development of chronic inflammation resulting in fatigue and contribute to individual differences in immune responses to radiation. Moreover, modulating mGluR5 provides a novel therapeutic option to treat CRF.

Fatigue is a common and debilitating condition that affects most cancer patients. To date, fatigue remains poorly characterized with no diagnostic test to objectively measure the severity of this condition. Here we describe an optimized method for assessing mitochondrial function of PBMCs collected from fatigued cancer patients. Using a compact extracellular flux system and sequential injection of respiratory inhibitors, we examined PBMC mitochondrial functional status by measuring basal mitochondrial respiration, spare respiratory capacity, and energy phenotype, which describes the preferred energy pathway to respond to stress. Fresh PBMCs are readily available in the clinical setting using standard phlebotomy. The entire assay described in this protocol can be completed in less than 4 hours without the involvement of complex biochemical techniques. Additionally, we describe a normalization method that is necessary for obtaining reproducible data. The simple procedure and normalization methods presented allow for repeated sample collection from the same patient and generation of reproducible data that can be compared between time points to evaluate potential treatment effects.

Purpose: Cancer-related fatigue is a common complaint during cancer treatment and is often associated with cognitive impairment. This study examined cognitive deficits that were associated with fatigue symptoms during external-beam radiation therapy (EBRT) in men with localized prostate cancer., Methods: A total of 36 participants were enrolled and followed up at baseline, 24 h, 7 days, 14 days after EBRT initiation, at midpoint, and at completion of EBRT. Fatigue was measured by self-report using the Functional Assessment of Cancer Therapy - Fatigue (FACT-F), and cognitive impairment by the Computer Assessment of Mild Cognitive Impairment (CAMCI®)., Results: Subjects with increased fatigue during EBRT reported a significant decline in cognitive function and had difficulties with CAMCI®'s route finding and item recall tasks during EBRT. Increased fatigue during EBRT was associated with perceived cognitive difficulties in executive function and recognition memory, but not with attention or verbal memory., Conclusions: Our results suggest that there might be specific cognitive domains that are associated with increased fatigue during EBRT. These findings will provide important information for targeting specific cognitive domains using pharmacotherapy or behavioral interventions. CAMCI® is a valuable tool for psycho social providers to detect subtle cognitive impairment in fatigued cancer patients in a clinical setting., (© 2018 S. Karger AG, Basel.)

Fatigue is one of the most common and debilitating side effects of cancer and cancer treatment, and yet its etiology remains elusive. The goal of this study is to understand the role of chronic inflammation in fatigue following repeated stress from radiotherapy. Fatigue and non-fatigue categories were assessed using ≥ 3-point change in Functional Assessment of Cancer Therapy-Fatigue questionnaire (FACT-F) administered to participants at baseline/before radiotherapy and one year post-radiotherapy. Whole genome microarray and cytokine multiplex panel were used to examine fatigue-related transcriptome and serum cytokine changes, respectively. The study included 86 subjects (discovery phase n = 40, validation phase n = 46). The sample in the discovery phase included men with prostate cancer scheduled to receive external-beam radiotherapy. A panel of 48 cytokines were measured and the significantly changed cytokine found in the discovery phase was validated using sera from a separate cohort of men two years after completing radiotherapy for prostate cancer at a different institution. Effects of the significantly changed cytokine on cell viability was quantified using the MTT assay. During the discovery phase, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and TRAIL decoy receptor, TNFRSF10C (TRAIL-R3), were significantly upregulated in fatigued (≥3-point decrease from baseline to 1yr-post radiotherapy) subjects (n = 15). In the validation phase, TRAIL correlated with fatigue scores 2yrs post-radiotherapy. TRAIL caused selective cytotoxicity in neuronal cells, but not in microglial and muscle cells, in vitro. Late-onset inflammation directed by TRAIL may play a role in fatigue pathogenesis post-repeated stress from irradiation., (Published by Elsevier Ltd.)

Background: Fatigue is one of the most debilitating adverse effects of cancer therapy. Identifying biomarkers early during cancer therapy may help us understand the biologic underpinnings of the persistence of fatigue following therapy., Objective: We aimed to identify early biomarkers of fatigue by examining correlations of levels of cytokines during external beam radiation therapy (EBRT) with persistence of fatigue 1 year following treatment completion in men with nonmetastatic prostate cancer (NM-PC)., Methods: A sample of 34 men with nonmetastatic prostate cancer scheduled to receive EBRT were followed up at baseline (T1), midpoint of EBRT (T2), and 1 year following EBRT (T3). Demographic and clinical data were obtained by chart review. The Functional Assessment of Cancer Therapy-Fatigue was administered to measure fatigue levels. Plasma cytokine levels were determined at T1 and T2 using the Bio-Rad Bio-Plex Cytokine Assay Kits., Results: Significant correlations were observed between levels of interleukin 2 (IL-3), IL-8, IL-9, IL-10, IL-16, interferon γ-induced protein 10, interferon α2, interferon γ, and stromal cell-derived factor 1α at T2 with worsening of fatigue from T1 to T3., Conclusions: Immunological changes prior to chronic fatigue development may reflect the long-term response to radiation therapy-induced damage., Implications for Practice: Early biomarkers for chronic fatigue related to cancer therapy will help advance our understanding of the etiology of this distressing symptom and will help nurses identify patients at risk of developing chronic fatigue after cancer treatment. This information will also aid in patient education, as well as symptom management.

Context: Cancer-related fatigue (CRF) persists months after treatment completion. Although a CRF biomarker has not yet been identified, validated self-report questionnaires are used to define and phenotype CRF in the discovery of potential biomarkers., Objectives: The purposes of this study are to identify CRF subjects using three well-known CRF phenotyping approaches using validated self-report questionnaires and to compare the biologic profiles that are associated with each CRF phenotype., Methods: Fatigue in men with nonmetastatic prostate cancer receiving external beam radiation therapy was measured at baseline (T1), midpoint (T2), end point (T3), and one-year post-external beam radiation therapy (T4) using the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) and Patient Reported Outcomes Measurement Information System-Fatigue. Chronic fatigue (CF) and nonfatigue subjects were grouped based on three commonly used phenotyping approaches: 1) T4 FACT-F <43; 2) T1-T4 decline in FACT-F score ≥3 points; 3) T4 Patient Reported Outcomes Measurement Information System-Fatigue T-score >50. Differential gene expressions using whole-genome microarray analysis were compared in each of the phenotyping criterion., Results: The study enrolled 43 men, where 34%-38% had CF based on the three phenotyping approaches. Distinct gene expression patterns were observed between CF and nonfatigue subjects in each of the three CRF phenotyping approaches: 1) Approach 1 had the largest number of differentially expressed genes and 2) Approaches 2 and 3 had 40 and 21 differentially expressed genes between the fatigue groups, respectively., Conclusion: The variation in genetic profiles for CRF suggests that phenotypic profiling for CRF should be carefully considered because it directly influences biomarker discovery investigations., (Published by Elsevier Inc.)

Objectives: The relationship between obesity (Body Mass Index ->30 kg/m(2)) and quality of life (QoL) following prostate cancer (PCa) radiation therapy (RT) is unknown. Excess abdominal fat may compromise the precise delivery of radiation, putting surrounding organs at risk for greater radiation exposure. Stereotactic body radiation therapy (SBRT) utilizes a real-time tracking system that provides updated prostate position information and allows for correction of the therapeutic beam during treatment with high accuracy. In this study, we evaluate the impact of obesity on patient reported outcomes following SBRT for prostate cancer., Materials and Methods: Between February 2008 and April 2012, 88 obese and 178 non-obese patients with PCa were treated with SBRT at Georgetown University Hospital, Washington, DC. Health-related quality of life (HRQol) was assessed via the expanded prostate cancer index composite (EPIC)-26 at baseline, 6, 12, 18, and 24 months after 5-fraction delivery of 35-36.25 Gy with the CyberKnife. Patients who received androgen deprivation therapy (ADT) were excluded from this analysis due to its known negative impact on HRQoL., Results: Pretreatment characteristics of obese and non-obese patient groups were similar except that obese patients had lower total testosterone levels. Urinary and bowel function and bother scores between the two patient cohorts were comparable at baseline and subsequent follow-ups. Sexual function and bother were also similar at baseline between both groups. Bother was defined by displeasure patients may experience from functional decline. At 24 months post-SBRT, obese men experienced borderline clinically significant decrease in sexual function and greater sexual bother compared to non-obese patients. Fatigue was significantly higher in obese patients compared to non-obese patients at 18 months post-SBRT., Conclusions: Prostate SBRT affects obese and non-obese patients similarly in total HRQoL scores and majority of its domains. Obesity has been associated with cancer recurrence; therefore longer follow-up is required to determine the impact of obesity on cancer control.

Amyloid-like protein aggregation is associated with neurodegeneration and other pathologies. The nature of the toxic aggregate species and their mechanism of action remain elusive. Here, we analyzed the compartment specificity of aggregate toxicity using artificial β-sheet proteins, as well as fragments of mutant huntingtin and TAR DNA binding protein-43 (TDP-43). Aggregation in the cytoplasm interfered with nucleocytoplasmic protein and RNA transport. In contrast, the same proteins did not inhibit transport when forming inclusions in the nucleus at or around the nucleolus. Protein aggregation in the cytoplasm, but not the nucleus, caused the sequestration and mislocalization of proteins containing disordered and low-complexity sequences, including multiple factors of the nuclear import and export machinery. Thus, impairment of nucleocytoplasmic transport may contribute to the cellular pathology of various aggregate deposition diseases., (Copyright © 2016, American Association for the Advancement of Science.)

Lycopene biosynthesis by Blakeslea trispora was greatly enhanced in a stirred-tank reactor when a nonsynchronous inoculation process, in which the (+) mating type was inoculated after the (-) mating type has been grown for a certain period of time, was applied. The lycopene concentration with nonsynchronous inoculation in a 24-h inoculation interval was 33 % higher than that with synchronous inoculation. The optimum inoculation ratio was 1:2 (+/-) at the 36 and 48 h inoculum age of mating types (+) and (-), respectively. Fermentation time for the individual strains and mated conditions showed that the (+) mating type grows faster than the (-) mating type. Morphological observation showed that the mycelium ratio of B. trispora (-) in mating culture with nonsynchronous inoculation was higher than that with synchronous inoculation. The results indicated that nonsynchronous inoculation process increased the dominance of B. trispora (-) in joint cultivation and hence stimulated lycopene biosynthesis.

Correlative microscopy allows imaging of the same feature over multiple length scales, combining light microscopy with high resolution information provided by electron microscopy. We demonstrate two procedures for coordinate transformation based correlative microscopy of vitrified biological samples applicable to different imaging modes. The first procedure aims at navigating cryo-electron tomography to cellular regions identified by fluorescent labels. The second procedure, allowing navigation of focused ion beam milling to fluorescently labeled molecules, is based on the introduction of an intermediate scanning electron microscopy imaging step to overcome the large difference between cryo-light microscopy and focused ion beam imaging modes. These methods make it possible to image fluorescently labeled macromolecular complexes in their natural environments by cryo-electron tomography, while minimizing exposure to the electron beam during the search for features of interest., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The zygomycete fungus Blakeslea trispora is usually used as a natural source of lycopene and β-carotene. In this study, the B. trispora (-) strain, a major mating type for lycopene production, was treated with N(+) ion implantation and N-methyl-N'-nitro-N-nitrosoguanidine (NTG), and further isolated on the screening plates supplemented with lovastatin and crude extracts of trisporic acid (CTA). After several rounds of screening, four mutants with higher yield of lycopene and biomass were isolated. Among these mutants, I5 obtained with N(+) ion implantation showed a maximum lycopene yield (28.8 mg/g), which was 64 % higher than the parent strain (17.5 mg/g) in the production of lycopene. The results indicated that N(+) ion implantation is more suitable for B. trispora (-) than NTG treatment, and the addition of lovastatin promoted the generation of positive mutant and CTA amplified the color differences between colonies.

Objective: To screen obesity-related protein biomarkers of young men using differential proteomic method and OffGel electrophoresis., Methods: Ten male obese volunteers with the age of 18 - 44 years were selected. The control group was matched with the ratio of 1:1 considering the factors of age and gender etc. Two milliliter venous blood was collected after 8 hours fasting. Albumin and IgG were removed from the plasma samples with highly specific immune-affinity method. Then the peptide-mixed samples were separated by pI with OffGel electrophoresis after solution digestion. Further separation and identification were performed by Nano HPLC-Chip-MS/MS system. The different proteins between the two groups were compared., Results: Overall, 332 and 301 proteins were identified in the obesity and control groups, respectively. There were 43 proteins with significant differences between the two groups, 17 of which were in the control group and 26 in the obesity group. Protein function annotation results showed that the level of adiponectin was lower while the level of C-reaction protein and three other phosphatases were higher in the obesity group compared with the control group., Conclusion: Adiponectin, C-reaction protein and three phosphatases were closely related to obesity of young men.

We have previously demonstrated that α-synuclein overexpression increases the membrane conductance of dopaminergic-like cells. Although α-synuclein is thought to play a central role in the pathogenesis of several neurodegenerative diseases including Parkinson's disease, multiple system atrophy, and diffuse Lewy body disease, the mechanism of action is not completely understood. In this study, we sought to determine whether multiple factors act together with α-synuclein to engender cell vulnerability through an augmentation of membrane conductance. In this article, we employed a cell model that mimics dopaminergic neurons coupled with α-synuclein overexpression and oxidative stressors. We demonstrate an enhancement of α-synuclein-induced toxicity in the presence of combined treatment with dopamine and paraquat, two molecules known to incite oxidative stress. In addition, we show that combined dopamine and paraquat treatment increases the expression of heme oxygenase-1, an antioxidant response protein. Finally, we demonstrate for the first time that combined treatment of dopaminergic cells with paraquat and dopamine enhances α-synuclein-induced leak channel properties resulting in increased membrane conductance. Importantly, these increases are most robust when both paraquat and dopamine are present suggesting the need for multiple oxidative insults to augment α-synuclein-induced disruption of membrane integrity.

Background: α-Synuclein aggregates in Lewy bodies and plays a central role in the pathogenesis of a group of neurodegenerative disorders, known as "Synucleinopathies", including Parkinson's disease. Parkin mutations result in loss of parkin E3-ubiquitin ligase activity and cause autosomal recessive early onset parkinsonism., Results: We tested how these two genes interact by examining the effects of parkin on post-translational modification of α-Synuclein in gene transfer animal models, using a lentiviral gene delivery system into the striatum of 2-month old male Sprague Dawley rats.Viral expression of wild type α-Synuclein caused accumulation of α-Synuclein and was associated with increased cell death and inflammation. α-Synuclein increased PLK2 levels and GSK-3β activity and increased the levels of phosphorylated α-Synuclein and Tau. Parkin co-expression reduced the levels of phosphorylated α-Synuclein and attenuated cell death and inflammation. Parkin reduced PLK2 levels and increased PP2A activation., Conclusions: These data suggest that parkin reduces α-Synuclein levels and alters the balance between phosphatase and kinase activities that affect the levels of phosphorylated α-Synuclein. These results indicate novel mechanisms for parkin protection against α-Synuclein-induced toxicity in PD.

This article evaluates Prussian blue (iron hexacyanoferrate) colloids as a heterogeneous photo-Fenton catalyst for the degradation of Rhodamine B. The emphasis is laid on the effects of alkali metal cations on the photo-Fenton process. The facts show that alkali cations strongly affect the degradation rate of organic species. The degradation rates of Rhodamine B, Malachite Green, and Methyl Orange in the presence of KCl, KNO(3), and K(2)SO(4), respectively, are faster than their degradation rates in the presence of the corresponding sodium salts. The average degradation rates of Rhodamine B in 0.2 M KCl, NaCl, RbCl, and CsCl solution, decline in sequence, and the rate in KCl solution is greater than that without any salt added deliberately. Thus, potassium ions accelerate the degradation rate, but sodium, rubidium, and cesium ions slow the rate. The order of the rates is R(K)>R>R(Na)>R(Rb)>R(Cs), which is consistent with that of the voltammetric oxidation currents of Prussian blue in the corresponding cation solutions. This phenomenon is attributed to the molecular recognition of the microstructure in Prussian blue nanoparticles to the alkali cations. The reaction mechanism of the photo-Fenton process has also been explored., (2010 Elsevier B.V. All rights reserved.)

alpha-Synuclein has been linked to the pathogenesis of Parkinson's disease and other synucleinopathies through its propensity to form toxic oligomers. The exact mechanism for oligomeric synuclein-directed cell vulnerability has not been fully elucidated, but one hypothesis portends the formation of synuclein-containing pores within cell membranes leading to leak channel-mediated calcium influx and subsequent cell death. Here we demonstrate synuclein-induced formation of sodium dodecyl sulfate-stable oligomers, intracellular synuclein-positive aggregates, alterations in membrane conductance reminiscent of leak channels and subsequent cytotoxicity in a dopaminergic-like cell line. Furthermore we demonstrate that the synuclein-induced membrane conductance changes are blocked by direct extracellular application of an anti-synuclein antibody. The work presented here confirms that synuclein overexpression leads to membrane conductance changes and demonstrates for the first time through antibody-blocking studies that synuclein plays a direct role in the formation of leak channels.

Objective: To evaluate the treatment of non-invasive aspergillosis of the maxillary sinus by using functional endoscopic sinus surgery (FESS) and the correlated factors that affect the treatment., Method: 41 cases of local, non-invasive aspergillosis of the maxillary sinus undergone FESS were studied., Result: The period of convalescence of double pathway (via ostium of maxillary sinus and canine fossa) was 4.7 weeks while single pathway (via ostium of maxillary sinus only) was 9.3 weeks. There was significant difference (P < 0.01). The period of convalescence of group using anti-fungal drugs to wash the operative cavity was 6.4 weeks while the group without using drugs was 6.7 weeks. There was no statistic significance (P > 0.05)., Conclusion: FESS is effective in treating of non-invasive aspergillosis of the maxillary sinus. The operation of double pathway is superior to that of single pathway. Whether to use antifungal drugs to wash the operative cavity has no obvious effect on the efficacy.