Reliability and minimal detectable change of the Short Physical Performance Battery in older adults with mild cognitive impairment.

OBJECTIVES: Reliability of the Short Physical Performance Battery (SPPB) are rarely examined among older adults with mild cognitive impairment (MCI). This study aimed to investigate the test-retest reliability and minimal detectable change (MDC) of the SPPB in older adults with MCI. METHODS: Participants included 100 older adults with MCI. The SPPB was assessed with the first 2 assessments separated by a 20-min interval and the third separated by a 1-week interval. The intraclass correlation coefficient (ICC) and MDC values were estimated. RESULTS: The intraday ICC was 0.73 for the SPPB score, 0.90 for the 4-m walk time (4mwt), and 0.95 for the 5-times chair stand time (5cst); the corresponding interday ICC values were 0.76, 0.89, and 0.91, respectively. The MDC values ranged from 1.1 to 1.2 for the SPPB score, from 0.77 to 0.80 s for the 4mwt, and from 1.32 to 1.77 for the 5cst. CONCLUSIONS: The SPPB had satisfactory reliability among older adults with MCI. The test-retest reliability of the SPPB is sufficient (>0.7) for group comparisons. Moreover, the test-retest reliability for the 4mwt and 5cst subscale performances is acceptable (> 0.9) for individual-level measurements over time.

A novel c-Kit/phospho-prohibitin axis enhances ovarian cancer stemness and chemoresistance via Notch3-PBX1 and ß-catenin-ABCG2 signaling.

BACKGROUND: The underlying mechanism involved in ovarian cancer stemness and chemoresistance remains largely unknown. Here, we explored whether the regulation of c-Kit and plasma membrane prohibitin (PHB) affects ovarian cancer stemness and chemotherapy resistance. METHODS: Mass spectrum analysis and an in vitro kinase assay were conducted to examine the phosphorylation of PHB at tyrosine 259 by c-Kit. The in vitro effects of c-Kit on membrane raft-PHB in ovarian cancer were determined using tissue microarray (TMA)-based immunofluorescence, western blotting, immunoprecipitation, colony and spheroid formation, cell migration and cell viability assays. In vivo tumor initiation and carboplatin treatment were conducted in nude mice. RESULTS: We found that c-Kit and PHB colocalized in the raft domain and were positively correlated in human ovarian serous carcinoma. c-Kit interacted with PHB and facilitated the phosphorylation of PHB at tyrosine 259 (phospho-PHBY259) in the membrane raft to enhance ovarian cancer cell motility. The generation of SKOV3GL-G4, a metastatic phenotype of SKOV3 green fluorescent protein and luciferase (GL) ovarian cancer cells, in xenograft murine ascites showed a correlation between metastatic potential and stem cell characteristics, as indicated by the expression of c-Kit, Notch3, Oct4, Nanog and SOX2. Further study revealed that after activation by c-Kit, raft-phospho-PHBY259 interacted with Notch3 to stabilize Notch3 and increase the downstream target PBX1. Downregulation of raft-phospho-PHBY259 increased the protein degradation of Notch3 through a lysosomal pathway and inhibited the ß-catenin-ABCG2 signaling pathway. Moreover, raft-phospho-PHBY259 played an important role in ovarian cancer stemness and tumorigenicity as well as resistance to platinum drug treatment in vitro and in vivo. CONCLUSIONS: These findings thus reveal a hitherto unreported interrelationship between c-Kit and PHB as well as the effects of raft-phospho-PHBY259 on ovarian cancer stemness and tumorigenicity mediated by the Notch3 and ß-catenin signaling pathways. Targeting the c-Kit/raft-phospho-PHBY259 axis may provide a new therapeutic strategy for treating patients with ovarian cancer.

Utilizing Cerebral Perfusion Scan and Diffusion-tensor MR Imaging to Evaluate the Effect of Hyperbaric Oxygen Therapy in Carbon Monoxide-induced Delayed Neuropsychiatric Seqeulae- A Case Report and Literature Review.

PURPOSE: Detection of regional cerebral blood flow (rCBF) and/or brain magnetic resonance imaging (MRI) has been used to investigate functional defect of brain caused by carbon monoxide (CO) poisoning. In this report, we attempted to demonstrate the correlation of changes in brain singlephoton emission computed tomography (SPECT) and diffusion-tensor MR image (DTI) with functional improvement of severe delayed neuropsychiatric sequelae (DNS) after CO intoxication during the treatment of hyperbaric oxygen therapy (HBOT). CASE REPORT: The patient had normal activities of daily life after he recovered from acute CO poisoning. One month later, he presented symptoms of declined cognitive functioning, aphasia, apraxia, dysphagia, muscle rigidity, urine and fecal incontinence. After one course of HBOT, these symptoms improved significantly and the patient could regain most of his previous functioning. The patient's improvement was evidenced by increased rCBF in Brodmann areas 7, 8, 11 and 40, as well as higher mean fractional anisotropy (FA) value of DTI. CONCLUSION: Although the efficacy of HBOT in DNS patients is still needed to be evaluated in large clinical study, these data suggest that HBOT may be the choice to improve DNS efficiently and shorten the duration of suffering with favorable outcome.

Immediate single-tooth replacement with acellular dermal matrix allogeneic bone and ossifying collagen scaffold: A case series.

The pursuit of predictable implant success in the aesthetic zone continues as technology develops. Creating stable marginal bone and an optimal peri-implant mucosal environment is the foundation for a long-term healthy and aesthetic implant treatment outcome. Tissue stability is dependent on multiple factors, including the regenerative materials used to create the peri-implant supporting tissues and maintain the tissue volume. The present study aims to describe a technique that combines a flapless approach to extract hopeless teeth in the aesthetic zone and implant insertion using an acellular dermal matrix placed to contain the coronal aspect of an innovative ossifying collagen scaffold designed to promote neoformation of vital native bone. This technique combines a minimally invasive approach with the application of a novel biomaterial that offers stable augmentation of the gingival thickness as well as bone fill in the facial gap, the space between the implant and the buccal plate, to ensure predictable aesthetic results. A collection of cases are presented to demonstrate the surgical technique and the situation over a follow-up period of 22 months. Pre- and post-treatment CBCT imaging were utilised to quantify the stability or changes noted in the alveolar bone, and pre-and post-treatment intraoral scanning were used for the same purpose in the peri-implant phenotype. This case series presents stable and aesthetic clinical outcomes evaluated through digital assessment.

A comparison of test-retest reliability of four cognitive screening tools in people with dementia.

PURPOSE: This study aimed to compare the test-retest reliability and minimal detectable change (MDC) of the Mini-Mental State Examination (MMSE), the Short Portable Mental Status Questionnaire (SPMSQ), the Montreal Cognitive Assessment (MoCA), and the Saint Louis University Status Examination (SLUMS) in a single sample of people with dementia. METHODS: Sixty people with dementia were assessed twice two weeks apart, and the test-retest reliability was examined using the intraclass correlation coefficient (ICC) for four screening tools. The MDC95 value was calculated based on the standard error of measurement to estimate the random measurement error. RESULTS: The ICC values for screening tools were 0.86-0.90. The MDC95 values (MDC95%) were 5.0 (17.2%), 2.74 (27%), 4.71(20%), and 6.26 (24%) for the MMSE, SPMSQ, MoCA, and SLUMS, respectively. CONCLUSIONS: Overall, the four screening tools were similar in test-retest reliability which imply that the MMSE, MoCA, SPMSQ, and SLUMS were reliable in monitoring cognitive function in people with dementia. The results of the direct comparisons of test-retest reliability of the four screening tools provide useful information for both clinicians and researchers to select an appropriate cognitive screening tool.Implications for RehabilitationThe MMSE, MoCA, SPMSQ, and SLUMS are equally reliable and thus they could be used to monitor the cognitive function in people with dementia.The MDC values are useful in determining whether a real change has occurred between repeated assessments for people with dementia.

Capsid proteins of foot-and-mouth disease virus interact with TLR2 and CD14 to induce cytokine production.

The mechanism of recognition of the foot-and-mouth disease virus (FMDV) by host innate immune cells is not well-understood. In this study, we first found that binary ethylenimine inactivated-FMDV (BEI-FMDV) with structurally intact capsid activated TLR2, but not other TLRs, and this specific activation was blocked by anti-TLR2 Abs or knockout of TLR2. BEI-FMDV activated NF-κB to induce cytokines, notably interferon-ß and IL-6, in a TLR2 and MyD88-dependent manner. Coexpression of TLR6 and CD14 showed additive effects on BEI-FMDV/TLR2-mediated activation of NF-κB. Further studies demonstrated that recombinant capsid proteins rVP1 and rVP3 of FMDV but not rVP0 bound directly with CD14 and TLR2. The rVP1- and rVP3-mediated activation of TLR2 and NF-κB were enhanced by the coexpression of TLR1 or TLR6. Immunoprecipitation of either rVP1 or rVP3 with mouse macrophage cell extracts revealed that rVP1 or rVP3 associated with TLR2, CD14 and TLR6 suggesting that rVP1 and rVP3 interact with CD14, TLR2/TLR1, and TLR2/TLR6 heterodimer. Additional study confirmed that rVP1 and rVP3 interacted with the swine TLR2 signaling pathway to induce IL-6 in swine macrophages. Our results identify VP1 and VP3 of FMDV as novel TLR agonists whose recognition by CD14, TLR2/TLR1, and TLR2/TLR6 of host innate immune cells is critical for the induction of cytokine production.

Tc-99m TRODAT-1 SPECT is a Potential Biomarker for Restless Leg Syndrome in Patients with End-Stage.

Rationales: Restless leg syndrome (RLS) is a common complication in patients with end-stage renal disease (ESRD). However, there is a lack of biomarkers linking uremic RLS to dopaminergic neurons. Previous studies demonstrated that Tc-99m TRODAT-1 SPECT was a biomarker for RLS but the correlation between the physiologic parameter was lacking. METHODS: Overall, 32 patients were enrolled in the study and divided into the following 3 groups: (1) control (n = 13), (2) ESRD without RLS (n = 8) and (3) ESRD with RLS (n = 11). All patients had a clinical diagnosis of RLS and received Tc-99m TRODAT-1 SPECT. A subgroup analysis was performed to compare differences between the control and ESRD with RLS groups. Tc-99m TRODAT-1 SPECT was performed and activities in the striatum and occipital areas were measured using manually delineated regions of interest (ROIs) by an experienced nuclear medicine radiologist who was blinded to clinical data. RESULTS: The total ratio of Tc-99m TRODAT SPECT was lower in the ESRD with RLS group (p = 0.046). The uptake ratio of TRODAT negatively correlated with serum parathyroid hormone (r = -0.577, p = 0.015) and ferritin (r = -0.464, p = 0.039) concentrations. However, the uptake positively correlated with the hemoglobin concentration (r = 0.531, p = 0.011). The sensitivity and specificity of the total TRODAT ratio for predicting RLS in the overall population were 95.0% and 67.7%, respectively, at a cutoff value of 0.980 (area under the curve of receiver operating characteristic curve was 0.767, p = 0.024). CONCLUSION: In patients with ESRD and RLS, Tc-99m TRODAT might be a potential biomarker. Dysregulated hemoglobin, serum parathyroid hormone and serum ferritin concentrations might influence the uptake of the TRODAT ratio.

Test-retest reliability and minimal detectable change of the Cognitive Abilities Screening Instrument in patients with dementia.

BACKGROUND: The Cognitive Abilities Screening Instrument (CASI) is widely used to assess global cognitive function in patients with dementia. It contains nine cognitive domains, namely long-term memory, short-term memory, attention, mental manipulation, orientation, abstraction and judgment, language, visual construction, and list-generating fluency. However, test-retest reliability and minimal detectable change (MDC) of the CASI are largely unknown in patients with dementia, which limits its utility and the explanation of a score change. PURPOSE: The purpose of this study was to examine test-retest reliability and calculate MDC of the CASI in patients with dementia. METHODS: Fifty-two patients with dementia completed the CASI twice with a two-week interval. The frequencies of the scores in the Clinical Dementia Rating (0.5, 1, and ≥ 2) were 38.5, 36.5, and 25.0, respectively. Test-retest reliability was examined using intraclass correlation coefficient (ICC) for the total score and nine domains of the CASI. The MDC was calculated based on standard error of measurement. RESULTS: The ICC value of the CASI total score was 0.97 while the ICC value for the nine domains were 0.65-0.92. The MDC values (MDC%) were 11.6 (12.9%), 2.8 (23.2%), 4.5 (41.2%), 3.4 (42.1%), 4.9 (49.2%), 5.3 (29.2%), 3.4 (28.8%), 2.2 (22.3%), 3.2 (32.1%), and 3.1 (30.7%) for CASI total score, long-term memory, short-term memory, attention, mental manipulation, orientation, abstraction and judgment, language, visual construction, and list-generating fluency, respectively. CONCLUSION: Our results revealed that the CASI has sufficient test-retest reliability. The MDC values are useful in determining a real change (i.e., improvement or deterioration) between two assessments of an individual patient. However, four domains (i.e., short-term memory, attention, mental manipulation, and list-generating fluency) demonstrated lower ICC values and substantial random measurement errors. Clinicians and researchers should be cautious while using these four domains to explain score changes between repeated assessments of patients with dementia.

Magnetic resonance imaging volumetric analysis for diabetic striatopathy with two episodes of hemichorea-hemiballism syndrome: A case report.

RATIONALE: Diabetic striatopathy (DS) is an uncommon movement disorder among diabetic patients characterized by clinical hemichorea-hemiballism with neuroimage change of the striatum. Here, we report a case of DS with relapsed hemichorea-hemiballism attacks even during euglycemic period, and the MRI changes by volumetric analysis. PATIENT CONCERNS: A 69-year-old diabetic female suffered from a relapsed episode of hemichorea-hemiballism during her euglycemic period after the treatment of hyperglycemia. DIAGNOSES: To investigate the serial MRI changes in a case with diabetic striatopathy who had clinical hemichorea-hemiballism syndrome. INTERVENTIONS: Semi-quantitative volumetric analyses from T1 images of these brain MRIs were obtained during the disease course. OUTCOMES: Besides, the negative finding of the first brain MRI during her first hospital admission, three afterward MRI examinations disclosed a waxing-and-waning mode of volume change from high-signal T1 images in left striatum. The clinical symptoms paralleled with the neuroimage changes in striatum. The MR signal volume changes were valuable for the clinical course of the hemichorea-hemiballism caused by diabetic striatopathy LESSONS:: Serial MR images for the diabetic striatopathy presented as a key pathognomonic relationship with the clinical hemichorea-hemiballism syndrome, assessed by our simplied volumetric analysis. Clinical involuntary movements may relapse and persist even with euglycemic condition as our case.

Inhibition of JNK and prothymosin-alpha sensitizes hepatocellular carcinoma cells to cisplatin.

Cisplatin is a potent chemotherapeutic drug widely used for the treatment of human cancer. However, its efficacy against hepatocellular carcinoma (HCC) is poor for reasons that remain unclear. We show here that prothymosin-alpha (PTMA) is overexpressed in HCC cell lines. Silencing PTMA using short-hairpin RNA sensitizes HCC cells to cisplatin, while ectopic expression of PTMA induces cell resistance to the drug. Cisplatin inhibits both the JNK pathway and PTMA in a dose-dependent manner. Treatment with a JNK inhibitor also reduces PTMA protein stability and sensitizes HCC cells to cisplatin. Notably, the effects of PTMA silencing and JNK inhibition can be reversed by ectopic expression of PTMA. We show that PTMA silencing induces translocation of proapoptotic Bax to mitochondria and enhances cisplatin-induced cytochrome c release and caspase-9 activation. Conversely, ectopic expression of PTMA reverses these effects. Our results indicate that PTMA is positively regulated by JNK and protects HCC cells against cisplatin-induced cell death. The JNK/PTMA axis may thus represent a novel target for chemotherapy against HCC.

Reversible Changes of Brain Perfusion SPECT for Carbon Monoxide Poisoning-Induced Severe Akinetic Mutism.

PURPOSE: This study aimed to characterize changes in regional cerebral blood flow (rCBF) in patients who experienced carbon monoxide (CO) poisoning and subsequently developed severe delayed neuropsychiatric sequelae (DNS) with akinetic mutism. We determined whether these changes were reversible in parallel with improvements in neuropsychological function in response to treatment, including hyperbaric oxygen therapy. METHODS: Patients who developed severe DNS with akinetic mutism after acute CO intoxication between 2007 and 2011 were enrolled. Tc-ECD brain SPECT findings were compared between the patients with severe akinetic mutism and age-matched control subjects to characterize the pattern of rCBF. Perfusion SPECT was correlated with clinical outcomes after treatment with statistical parametric mapping (SPM8); the height threshold was P < 0.01 at peak level, and the corrected false discovery rate was P < 0.05 at the cluster level. RESULTS: Seven patients with akinetic mutism were analyzed. All patients had neurological symptoms caused by acute CO exposure, and all recovered to nearly normal daily function after initial treatments. In all cases, after a "lucid interval," DNS progressed to akinetic mutism. The SPECT images acquired at the onset of akinetic mutism demonstrated variable hypoperfusion in frontal-temporal-parietal regions, with the greatest severity in the left temporal-parietal regions. In parallel, we performed functional neuropsychiatric tests. After treatment, the brain SPECT showed significantly fewer hypoperfusion regions, and neuropsychiatric tests showed dramatically improved function. CONCLUSIONS: Our findings demonstrated both cerebral cortical and subcortical injuries in patients with CO-induced akinetic mutism. Improvement in rCBF correlated well with functional recovery after treatment.

Identification of the ß-catenin/JNK/prothymosin-alpha axis as a novel target of sorafenib in hepatocellular carcinoma cells.

Sorafenib is a kinase inhibitor used as anticancer drug against various human tumors, including advanced hepatocellular carcinoma (HCC). ß-Catenin and prothymosin alpha (PTMA) are overexpressed in HCC and other tumors. Previous studies have shown that PTMA expression modulates the response of HCC cells to sorafenib. However, the underlying mechanism of PTMA activity in this context remains unclear. We show here that sorafenib inhibits both ß-catenin and PTMA in a dose-dependent manner. Silencing ß-catenin reduces PTMA level and sensitizes HCC cells to sorafenib. In contrast, ectopic expression of ß-catenin induces PTMA expression and cell resistance to the drug. Sorafenib inhibits PTMA expression at the transcriptional level by inhibiting the ß-catenin pathway. Nucleotide deletion analysis of the PTMA gene promoter reveals that a DNA segment lying 1,500-1,600 bp upstream of the PTMA transcription start site represents an AP-1-binding site that is critical for ß-catenin modulation of gene transcription in response to sorafenib. In addition, chemical inhibitors that target JNK abrogate ß-catenin/AP-1 binding to the endogenous PTMA gene and reduces PTMA transcription and protein expression. Silencing of ß-catenin or c-Fos induces similar effects on gene regulation and these are reversed by ectopic expression of ß-catenin. Mutations in the PTMA promoter at the predicted ß-catenin/AP-1 binding site partly abrogate sorafenib's effects on PTMA transcription. These results indicate that PTMA is induced by the oncoprotein ß-catenin and protects HCC cells against sorafenib-induced cell death. The ß-catenin/JNK/PTMA axis may thus represent a novel target for chemotherapy against HCC.

Oncogenic c-Myc and prothymosin-alpha protect hepatocellular carcinoma cells against sorafenib-induced apoptosis.

Prothymosin alpha (PTMA) is overexpressed in various human tumors, including hepatocellular carcinoma (HCC). The significance of PTMA overexpression and its underlying mechanism remain unclear. We show here that silencing PTMA sensitizes HCC cells to the kinase inhibitor sorafenib. In contrast, ectopic expression of PTMA induces cell resistance to the drug. While inhibitors targeting JNK, ERK or PI3K reduce PTMA expression, only ERK activation is suppressed by sorafenib. In addition, inhibition of ERK produces a dramatic decrease in both endogenous PTMA level and promoter activation. Ectopic expression of active MKK1/2 considerably induces PTMA expression. We also identify a sorafenib-responsive segment lying 1000-1500-bp upstream of the PTMA transcription start site and observe that it is controlled by c-Myc and ERK. Mutation in the PTMA promoter at the predicted c-Myc binding site and silencing of c-Myc both abrogate sorafenib's effect on PTMA transcription. We also find that silencing PTMA potentiates Bax translocation to mitochondria in response to sorafenib and this is associated with increased cytochrome c release from mitochondria and enhanced caspase-9 activation. These results indicate that PTMA is positively regulated by the oncoprotein c-Myc and protects HCC cells against sorafenib-induced cell death, thus identifying PTMA as a new target for chemotherapy against HCC.