Association between vitiligo and risk of retinal detachment: a population-based cohort study in Taiwan.

BACKGROUND: Vitiligo is reportedly associated with several ocular abnormalities. However, the relationship between vitiligo and retinal detachment (RD) remains unclear. OBJECTIVES: To examine the risk of RD in patients with vitiligo. METHODS: A nationwide population-based cohort study was conducted using data from the Taiwan National Health Insurance Database from 2007 to 2018. A total of 21 132 patients with vitiligo were matched in a 1 : 4 ratio with people without vitiligo by age, sex and comorbidity propensity score. Cumulative incidence and Cox proportional hazard models were used to investigate the risk of RD in patients with vitiligo. Subgroup analysis was performed. RESULTS: The cohort with vitiligo had a significantly higher rate of RD than the cohort without vitiligo [adjusted hazard ratio (aHR) 1.44, 95% confidence interval (CI) 1.20-1.72; P < 0.001]. Patients with vitiligo who required treatments such as phototherapy, systemic corticosteroids or immunosuppressants exhibited an even greater risk of RD (aHR 1.57, 95% CI 1.16-2.14; P = 0.004). CONCLUSIONS: Our study revealed a 1.44-fold increased risk of RD in patients with vitiligo, with an even higher risk in patients receiving phototherapy, systemic corticosteroids or immunosuppressants. The risk remained consistently higher over a 10-year follow-up period.

A Network Comparison of Sexual Dysfunction, Psychological Factors, and Body Dissociation between Individuals with and without Sexual Trauma Histories.

Sexual dysfunction is associated with psychological symptoms, including depression and anxiety. Sexual dysfunctions are often attributed to dissociation symptoms in individuals who reported sexual trauma histories. This study utilized a network approach to analyze relationships between sexual and psychological symptoms and examine whether the identified network structures differed between individuals who reported a history of sexual trauma and those who did not. Sexual dysfunction, history of sexual trauma, internalizing symptoms, dissociation symptoms, sex-related shame, and negative body image were assessed in 1,937 United States college students (women = 69.5%). Nearly half (46.8%) of the participants reported a sexual trauma history in their lifetime. Using regularized partial correlation networks, the relationships between sexual and psychological symptoms were analyzed and compared between groups with and without trauma histories. Internalizing symptoms were positively correlated with sexual dysfunction regardless of the presence of sexual trauma history. Anxiety had a stronger influence in the trauma network than in the no-trauma network. Feeling separated from the body during sexual activity was a central symptom and was related to difficulties relaxing and enjoying sex only in the trauma network. Sex-related shame appeared to play a more important role in men compared to women. To improve clinical practice of assessing and treating sexual dysfunction, researchers and clinicians should consider core symptoms that connect different aspects of sexual and psychological functioning while being aware of the unique role of dissociation in the context of traumatic stress.

Psychometric Properties and Clinical Utility of CBCL and P-GBI Sleep Items in Children and Adolescents.

OBJECTIVE: Sleep is crucial to overall health, playing a complex role in a wide range of mental health concerns in children and adults. Nevertheless, clinicians may not routinely assess sleep problems due to lack of awareness or limitations such as cost or time. Scoring sleep-related items embedded on broader scales may help clinicians get more out of tools they are already using. The current study explores evidence of reliability, validity, and clinical utility of sleep-related items embedded on two caregiver-report tools: the Child Behavior Checklist (CBCL) and Parent General Behavior Inventory (P-GBI). METHOD: Youth aged 5-18 years and their parents were recruited from both an academic medical center (N = 759) and an urban community health center (N = 618). Caregivers completed the CBCL and P-GBI as part of a more comprehensive outpatient evaluation. Exploratory factor analyses, multi-group confirmatory factor analyses, and graded response models evaluated dimensionality, reliability, and invariance across samples. Correlations and receiver operating characteristic curve analyses probed associations with diagnostic and demographic variables. RESULTS: Two subscales emerged for each itemset. Across both samples, P-GBI sleep subscales were more reliable and consistent than CBCL sleep subscales, showed greater coverage of sleepiness and insomnia constructs, were better at discriminating individuals within a wider range of sleep complaints, and showed significant correlation with mood disorder diagnoses. CONCLUSIONS: The P-GBI sleep items provide a brief, reliable measure for assessing distinct dimensions of sleep complaints and detecting mood symptoms or diagnoses related to the youth's sleep functioning, making them a useful addition to clinical practice.

Association between chronic kidney disease and risk of bullous pemphigoid: a nationwide population-based cohort study.

BACKGROUND: Studies have shown that bullous pemphigoid (BP) occurs in patients with chronic kidney disease (CKD). However, the risk of developing BP in patients with CKD remains inconclusive. OBJECTIVE: To investigate whether CKD increases the risk of BP. METHODS: Participants were recruited from the National Health Insurance Database of Taiwan between 2007 and 2018. Overall, 637,664 newly diagnosed patients with CKD and 637,664 age-, sex-, and comorbidity-matched non-CKD participants were selected. A competing risk model was used to evaluate the risk of development of BP. RESULTS: After adjusting for age, sex, and comorbid diseases in the multivariate model, CKD was a significant risk factor for BP (adjusted hazard ratio [aHR]: 1.29; 95% confidence interval [CI]: 1.17-1.42; p < 0.001). CKD patients were classified into the dialytic or non-dialytic groups and compared to non-CKD participants, and this revealed that patients with dialysis-dependent CKD had the highest risk of BP (aHR 1.75; 95% CI 1.51-2.03), followed by patients with non-dialysis-dependent CKD (aHR 1.20; 95% CI 1.08-1.32). LIMITATIONS: We lacked detailed laboratory data on the severity of CKD. CONCLUSIONS: Compared with individuals without CKD, those with CKD had a 1.3-fold increased risk of BP. Patients with dialysis-dependent CKD had an even higher BP risk (1.8-fold).

Fluorescent aptasensor based on conformational switch-induced hybridization for facile detection of ß-amyloid oligomers.

Aß oligomers (AßO) are a dominant biomarker for early Alzheimer's disease diagnosis. A fluorescent aptasensor coupled with conformational switch-induced hybridization was established to detect AßO. The fluorescent aptasensor is based on the interaction of fluorophore-labeled AßO-specific aptamer (FAM-Apt) against its partly complementary DNA sequence on the surface of magnetic beads (cDNA-MBs). Once the FAM-Apt binds to AßO, the conformational switch of FAM-Apt increases the tendency to be captured by cDNA-MBs. This causes a descending fluorescence of supernatant, which can be utilized to determine the levels of AßO. Thus, the base-pair matching above 12 between FAM-Apt and cDNA-MBs with increasing hybridizing free energies reached the ascending fluorescent signal equilibrium. The optimized aptasensor showed linearity from 1.7 ng mL-1 to 85.1 (R = 0.9977) with good recoveries (79.27-109.17%) in plasma. Furthermore, the established aptasensor possesses rational selectivity in the presence of monomeric Aß, fibrotic Aß, and interferences. Therefore, the developed aptasensor is capable of quantifying AßO in human plasma and possesses the potential to apply in clinical cases.

Resistin enhances IL-1ß and TNF-α expression in human osteoarthritis synovial fibroblasts by inhibiting miR-149 expression via the MEK and ERK pathways.

Resistin is a cysteine-rich adipokine that promotes the release of inflammatory cytokines, particularly interleukin 1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α), which are critical pro-inflammatory mediators in osteoarthritis (OA) pathogenesis. We describe evidence of significantly higher levels of resistin, IL-1ß, and TNF-α expression in OA knee synovial tissue compared with that from non-OA knees. Resistin-induced enhancement of IL-1ß and TNF-α expression in human OA synovial fibroblasts (OASFs) were attenuated by MEK and ERK inhibitors, as well as their respective siRNAs. Our data reveal that resistin enhances the expression of TNF-α and IL-1ß in OASFs by inhibiting miR-149 expression via MEK and ERK signaling. Our findings elucidate the inter-relationships between resistin and pro-inflammatory mediators during OA pathogenesis and could help to facilitate the development of synovium-targeted therapy in OA.

Dual-functional gold-iron oxide core-satellite hybrid nanoparticles for sensitivity enhancement in biosensors via nanoplasmonic and preconcentration effects.

A common strategy to improve the sensitivity of a biosensor for the detection of a low abundance analyte is to preconcentrate the analyte molecules before detection. A dual-functional gold-iron oxide core-satellite hybrid nanoparticle structure is proposed in this work to overcome the drawbacks of traditional sample pretreatment methods and the methods using non-magnetic nanomaterials for sample pretreatment. The new dual-functional hybrid nanoparticle structure can simultaneously serve as a signal reporter of a biorecognition event and a preconcentrator of a target at an extremely low concentration in a nanoplasmonic biosensor. By utilizing a fiber optic nanogold-linked sorbent assay in the fiber optic particle plasmon resonance (FOPPR) biosensor and an arbitrary DNA sequence as a target, we have demonstrated that the use of the new hybrid nanoparticle structure with magnetic preconcentration improves the limit of detection (LOD) for the DNA by 18 times as compared to the same method without magnetic preconcentration, so that the LOD for detecting the DNA can be as low as 2.6 fM. The new hybrid nanoparticle structure is easy to prepare and its use in the high-sensitivity and low-cost FOPPR biosensor provides vast opportunities in point-of-care applications.

Determination of 13-cis-Retinoic Acid and Its Metabolites in Plasma by Micellar Electrokinetic Chromatography Using Cyclodextrin-Assisted Sweeping for Sample Preconcentration.

The online preconcentration technique, cyclodextrin-assisted sweeping (CD-sweeping), coupled with micellar electrokinetic chromatography (MEKC) was established to determine 13-cis-retinoic acid (13-cis-RA), all-trans-retinoic acid (all-trans-RA) and 4-oxo-13-cis-retinoic acid (4-oxo-13-cis-RA) in human plasma. A CD-sweeping buffer (45 mM borate (pH 9.2), containing 80 mM sodium dodecyl sulfate (SDS) and 22 mM hydroxypropyl ß-CD (HP-ß-CD) was introduced into the capillary and, then, the sample dissolved in 70 mM borate (pH 9.2): methanol = 9:1 (v/v) was injected into capillary by pressure. The separation voltage was 23 kV. Compared to the conventional cyclodextrin-micellar electrokinetic chromatography (CD-MEKC) method, the new technique achieved 224-257-fold sensitivity enrichment of analytes. The limits of detection of 13-cis-RA, all-trans-RA were 1 ng/mL, whereas that of 4-oxo-13-cis-RA was 25 ng/mL in plasma. The linear ranges of 13-cis-RA, all-trans-RA were between 15 and 1000 ng/mL, whereas that of 4-oxo-13-cis-RA was between 75 and 1500 ng/mL. The coefficient of correlation between the concentration of analytes and peak area ratio of analytes and internal standard (2, 4-dihydroxy-benzophenone) for intra-day (n = 3) and inter-day (n = 5) analyses were both greater than 0.999. The optimized experimental conditions were successfully applied to determine 13-cis-retinoic acid and its metabolites in plasma samples from a patient during the administration of 13-cis-RA for treating acne.

Determinants of Employment Outcome for the People with Schizophrenia Using the WHODAS 2.0.

Purpose Since the vocational outcomes of people with schizophrenia should be viewed in a holistic way, the second edition of the World Health Organization Disability Assessment Schedule (WHODAS 2.0) might provide an evaluation regarding employment potential. To determine whether the WHODAS 2.0 scores can be used to predict employment status, we examined the probabilistic cut-off values of the scores and analyzed the relationship between work status and demographic characteristics. Methods We selected 31,793 people aged between 18 and 65 with schizophrenia or schizoaffective disorder from the disability evaluation database in Taiwan and separated them into two groups based on employment status (employed and unemployed). We used logistic regression to explore the association between employment and demographic characteristics. Moreover, we conducted a receiver operating characteristic (ROC) analysis to determine the cut-off point to assist in determining employment potential based on the WHODAS 2.0 score. Results Among the 31,793 participants, 3367 were employed and 18,801 were unemployed. The unemployed participants accounted for a higher percentage of disability in each domain of the WHODAS. The ROC analysis revealed that the optimal cut-off point of the WHODAS score to distinguish the people who were employed and unemployed was 25.78 (area under curve = 0.80). Conclusions The present study indicated that work status can be determined by the total score across the six domains of the WHODAS score. Furthermore, the probability of employment may be determined initially by the cut-off point of the WHODAS score in order to economize evaluation time and prepare prevocational training for those with scores above 25.78.

Diagnostic Efficiency of the Child and Adolescent Symptom Inventory (CASI-4R) Depression Subscale for Identifying Youth Mood Disorders.

This study examined the diagnostic and clinical utility of the Child and Adolescent Symptom Inventory-4 R (CASI-4 R) Depressive and Dysthymia subscale for detecting mood disorders in youth (ages 6-12; M = 9.37) visiting outpatient mental health clinics. Secondary analyses (N = 700) utilized baseline data from the Longitudinal Assessment of Manic Symptoms study. Semistructured interviews with youth participants and their parents/caregivers determined psychiatric diagnoses. Caregivers and teachers completed the CASI-4 R. CASI-4 R depressive symptom severity and symptom count scores each predicted mood disorder diagnoses. Both caregiver scores (symptom severity and symptom count) of the CASI-4 R subscale significantly identified youth mood disorders (areas under the curve [AUCs] = .78-.79, ps < .001). The symptom severity version showed a small but significant advantage. Teacher symptom severity report did not significantly predict mood disorder diagnosis (AUC = .56, p > .05), whereas the teacher symptom count report corresponded to a small effect size (AUC = .61, p < .05). The CASI-4 R Depression scale showed strong incrememental validity even controlling for the other CASI-4 R scales. Caregiver subscale cutoff scores were calculated to assist in ruling in (diagnostic likelihood ratio [DLR] = 3.73) or ruling out (DLR = 0.18) presence of a mood disorder. The CASI-4 R Depressive subscale caregiver report can help identify youth mood disorders, and using DLRs may help improve diagnostic accuracy.

Determining lead, cadmium and mercury in cosmetics using sweeping via dynamic chelation by capillary electrophoresis.

International limits have been established for metal impurities in cosmetics to prevent overexposure to heavy metal ions. Sweeping via dynamic chelation was developed using capillary electrophoresis to analyze lead (Pb), cadmium (Cd) and mercury (Hg) impurities in cosmetics. The sweeping via dynamic chelation mechanism involves a large volume of metal ions being swept by a small quantity of chelating agents that were electrokinetically injected into the capillary to chelate metal ions and increase the detection sensitivity. The optimized conditions were as follows: Firstly, the capillary was rinsed by a 0.6 mM TTAB solution to reverse the EOF. The sample solution, which was diluted using 25 mM ammonium acetate (pH 6.0), was injected into the capillary using a pressure of 3.5 psi for 99.9 s. Then, EDTA was injected at -25 kV for 1 min from the EDTA buffer (25 mM ammonium acetate containing 0.6 mM TTAB and 5 mM EDTA), and the metal ions were swept and stacked simultaneously. Finally, the separation was performed at -20 kV using a separation buffer (100 mM ammonium acetate (pH 6.0)). A small quantity of chelating agents introduced into the capillary could yield 33-, 50- and 100-fold detection improvements for Pb, Cd and Hg, respectively, more sensitive than conventional capillary zone electrophoresis. Correlation coefficients greater than 0.998 indicated that this method exhibited good linearity. The relative standard deviation and relative error were less than 8.7%, indicating high precision and accuracy. The recovery value of the homemade lotion, which was employed to simulate the real sample matrix, was 93-104%, which indicated that the sample matrix does not affect the quantitative results. Finally, commercial cosmetics were employed to demonstrate the feasibility of the method to determine Pb, Cd and Hg without complicated sample pretreatment. Graphical Abstract The procedure of analyzing metal ions in cosmetics by sweeping via dynamic chelation.

Application of a multivariate approach for analyte focusing by micelle collapse-micellar electrokinetic chromatography for analyzing sunscreen agents in cosmetics.

The operating parameters that affect the performance of the online preconcentration technique "analyte focusing by micelle collapse-MEKC (AFMC-MEKC)" were examined using a multivariate approach involving experimental design to determine the sunscreen agents in cosmetics. Compared to the single-variable approach, the advantage of the multivariate approach was that many factors could be investigated simultaneously to obtain the best separation condition. A fractional factorial design was used to identify the fewest significant factors in the central composite design (cCD). The cCD was adopted for evaluating the location of the minimum or maximum response in this study. The influences of the experimental variables on the response were investigated by applying a chromatographic exponential function. The optimized condition and the relationship between the experimental variables were acquired using the JMP software. The ANOVA analysis indicated that the Tris pH value, SDS concentration, and ethanol percentage influenced the separation quality and significantly contributed to the model. The optimized condition of the running buffer was 10 mM Tris buffer (pH 9.5) containing 60 mM SDS, 7 mM γ-CD, and 20% v/v ethanol. The sample was prepared in 100 mM Tris buffer (pH 9.0) containing 7.5 mM SDS and 20% v/v ethanol. The SDS concentration in the sample matrix was slightly greater than the CMC value that makes the micelle be easily collapsed and the analytes be accumulated in the capillary. In addition, sunscreen agents in cosmetics after 1000-fold dilution were successfully determined by AFMC-MEKC.

Characterization of Functional Ingredients Extracted with Ethanol Solvents from Ponkan (Citrus reticulata) By-Products Using the Microwave Vacuum Drying Method Combined with Ultrasound-Assisted Extraction.

For this study, microwave vacuum drying (MVD) was combined with ultrasound-assisted extraction to compare the effects of different ethanol volumes on ponkan extract and to evaluate the total phenolic content (TPC), total flavonoid content (TFC), and total ascorbic acid content (TAAC). High-performance liquid chromatography with photodiode array detection (HPLC-PDA) was used to analyze the flavanone contents and antioxidant activity of ponkan (Citrus reticulata) peels. The experimental results showed that the TPC and TFC increase with ethanol volume. Ethanol extraction (75%) showed significant advantages by increasing the TPC to 17.48 mg GAE/g (DW) and the TFC to 2.96 mg QE/g (DW) of ponkan extract and also exhibited the highest antioxidant activity. The TAAC improved along with increased water content. Water extraction showed the highest content (13.07 mg VitC/100 g, DW). The hesperidin content analyzed by HPLC-PDA was 102.95-622.57 mg/100 g (DW), which was the highest among the flavanones. Then, the ethanol insoluble residue extracts were taken from the pectin with four different solvents, evaluating TPC, TFC, and antioxidant activity. The TPC, TFC, and antioxidant capacity of pectin are significantly lower than those of the peels. Combining MVD and 75% ethanol with ultrasound-assisted extraction in the pre-treatment process can effectively eliminate polyphenols, flavonoids, and other compounds, thus enabling the extraction of high-methoxyl pectin. The total dietary fiber (TDF) content of MVD ponkan by-products was 25.83%. Ponkan by-products have the potential for the future development of functional foods and supplements.

Analysis of anabolic androgenic steroids in urine by full-capillary sample injection combined with a sweeping CE stacking method.

This study describes an on-line stacking CE approach by sweeping with whole capillary sample filling for analyzing five anabolic androgenic steroids in urine samples. The five anabolic steroids for detection were androstenedione, testosterone, epitestosterone, boldenone, and clostebol. Anabolic androgenic steroids are abused in sport doping because they can promote muscle growth. Therefore, a sensitive detection method is imperatively required for monitoring the urine samples of athletes. In this research, an interesting and reliable stacking capillary electrophoresis method was established for analysis of anabolic steroids in urine. After liquid-liquid extraction by n-hexane, the supernatant was dried and reconstituted with 30 mM phosphate buffer (pH 5.00) and loaded into the capillary by hydrodynamic injection (10 psi, 99.9 s). The stacking and separation were simultaneously accomplished at -20 kV in phosphate buffer (30 mM, pH 5.0) containing 100 mM sodium dodecyl sulfate and 40 % methanol. During the method validation, calibration curves were linear (r≥0.990) over a range of 50-1,000 ng/mL for the five analytes. In the evaluation of precision and accuracy for this method, the absolute values of the RSD and the RE in the intra-day (n=3) and inter-day (n=5) analyses were all less than 6.6 %. The limit of detection for the five analytes was 30 ng/mL (S/N=5, sampling 99.9 s at 10 psi). Compared with simple MECK, this stacking method possessed a 108- to 175-fold increase in sensitivity. This simple and sensitive stacking method could be used as a powerful tool for monitoring the illegal use of doping.

A Machine-Learning Approach to Assess Factors Associated With Hospitalization of Children and Youths in Psychiatric Crisis.

OBJECTIVE: The authors used a machine-learning approach to model clinician decision making regarding psychiatric hospitalization of children and youths in crisis and to identify factors associated with the decision to hospitalize. METHODS: Data consisted of 4,786 mobile crisis response team assessments of children and youths, ages 4.0-19.5 years (mean±SD=14.0±2.7 years, 56% female), in Nevada. The sample assessments were split into training and testing data sets. A random-forest machine-learning algorithm was used to identify variables related to the decision to hospitalize a child or youth after the crisis assessment. Results from the training sample were externally validated in the testing sample. RESULTS: The random-forest model had good performance (area under the curve training sample=0.91, testing sample=0.92). Variables found to be important in the decision to hospitalize a child or youth were acute suicidality, followed by poor judgment or decision making, danger to others, impulsivity, runaway behavior, other risky behaviors, nonsuicidal self-injury, psychotic or depressive symptoms, sleep problems, oppositional behavior, poor functioning at home or with peers, depressive or schizophrenia spectrum disorders, and age. CONCLUSIONS: In crisis settings, clinicians were found to mostly focus on acute factors that increased risk for danger to self or others (e.g., suicidality, poor judgment), current psychiatric symptoms (e.g., psychotic symptoms), and functioning (e.g., poor home functioning, problems with peer relationships) when deciding whether to hospitalize or stabilize a child or youth. To reduce psychiatric hospitalization, community-based services should target interventions to address these important factors associated with the need for a higher level of care among youths in psychiatric crisis.

Fluorescence detection of apolipoprotein E gene polymorphisms based on oligonucleotide ligation and magnetic separation.

Alzheimer's disease is a progressive neurodegenerative condition that causes brain cell death and is the leading cause of dementia. Most patients with Alzheimer's disease are diagnosed with late-onset Alzheimer's disease (LOAD), with apolipoprotein E (APOE) genotypes being highly associated with the frequency of LOAD risk. A fluorescence detection system coupled with oligonucleotide ligation and magnetic separation was developed to identify two single-nucleotide polymorphisms (SNPs) for the APOE gene and recognize APOE alleles for LOAD. The system utilized a fluorescence probe with one base-discriminating nucleoside for SNP (F probe) and a perfectly complementary biotin-modified sequence against the target DNA (P probe). When the F and P probes matched the target DNA sequences, DNA ligation occurred, and ligation products were produced. Streptavidin magnetic beads were subsequently employed to remove the ligation products, and a decrease in fluorescence intensity was observed in the supernatant compared to when there was no target DNA. This system detected two SNPs of APOE alleles, namely rs429358 and rs7412. The results indicated that the R-values ((F0 - F1)/F0) for rs429358 were 0.92 ± 0.002 for the T/T target, 0.47 ± 0.004 for the T/C target and 0.11 ± 0.004 for the C/C target, respectively. The R-values for rs7412 were 0.73 ± 0.009 for the C/C target, 0.42 ± 0.001 for the C/T target and 0.16 ± 0.007 for the T/T target, respectively. F0 and F1 represent the fluorescence intensity of the F probe without and with target DNA, respectively. Based on fluorescence intensity, the fluorescence detection system was able to identify the genotypes of the APOE gene accurately to evaluate the risk of Alzheimer's disease.

CVM-1118 (foslinanib), a 2-phenyl-4-quinolone derivative, promotes apoptosis and inhibits vasculogenic mimicry via targeting TRAP1.

CVM-1118 (foslinanib) is a phosphoric ester compound selected from 2-phenyl-4-quinolone derivatives. The NCI 60 cancer panel screening showed CVM-1125, the major active metabolite of CVM-1118, to exhibit growth inhibitory and cytotoxic effects at nanomolar range. CVM-1118 possesses multiple bioactivities, including inducing cellular apoptosis, cell cycle arrest at G2/M, as well as inhibiting vasculogenic mimicry (VM) formation. The TNF receptor associated protein 1 (TRAP1) was identified as the binding target of CVM-1125 using nematic protein organization technique (NPOT) interactome analysis. Further studies demonstrated CVM-1125 reduced the protein level of TRAP1 and impeded its downstream signaling by reduction of cellular succinate levels and destabilization of HIF-1α. The pharmacogenomic biomarkers associated with CVM-1118 were also examined by Whole Genome CRISPR Knock-Out Screening. Two hits (STK11 and NF2) were confirmed with higher sensitivity to the drug in cell knock-down experiments. Biological assays indicate that the mechanism of action of CVM-1118 is via targeting TRAP1 to induce mitochondrial apoptosis, suppress tumor cell growth, and inhibit vasculogenic mimicry formation. Most importantly, the loss-of-function mutations of STK11 and NF2 are potential biomarkers of CVM-1118 which can be applied in the selection of cancer patients for CVM-1118 treatment. CVM-1118 is currently in its Phase 2a clinical development.

Microstructural white matter abnormalities in type 2 diabetes mellitus: a diffusion tensor imaging study.

This study investigated whether diffusion tensor imaging (DTI) could identify potential abnormalities in type 2 diabetes mellitus (T2DM) patients without cognitive complaints compared to healthy controls. In addition, the existence of associations between diffusion measures and clinical parameters was examined. Forty T2DM patients and 97 non-diabetic controls completed a clinical and biochemistry examination. Structural MRI scans (DTI, T1, T2, FLAIR) were subsequently acquired with a 1.5 Tesla scanner. In addition to a global DTI analysis, voxel-based analysis was performed on the fractional anisotropy (FA), mean diffusivity (MD), and axial (AD) and transverse (TD) diffusivity maps to investigate regions that exhibit (i) WM differences between patients and controls; and (ii) associations between clinical measurements and these DTI indices. There were no significant differences in age, gender, and WM hyperintensity scores derived by the conventional MRI scans between controls and T2DM patients. For the T2DM patients, however, the MD of the brain parenchyma was significantly increased compared to controls and was positively correlated with disease duration. The voxel based analyses revealed (i) a significantly decreased FA in the bilateral frontal WM compared to controls which was mainly caused by an increased TD and not a decreased AD within these regions; (ii) a significant association between disease duration and microstructural properties in several brain regions including bilateral cerebellum, temporal lobe WM, right caudate, bilateral cingulate gyrus, pons, and parahippocampal gyrus. Our findings indicate that microstructural WM abnormalities and associations with clinical measurements can be detected with DTI in T2DM patients.

Determination of hydroxy acids in cosmetics by chemometric experimental design and cyclodextrin-modified capillary electrophoresis.

A CD-modified CE method was established for quantitative determination of seven hydroxy acids in cosmetic products. This method involved chemometric experimental design aspects, including fractional factorial design and central composite design. Chemometric experimental design was used to enhance the method's separation capability and to explore the interactions between parameters. Compared to the traditional investigation that uses multiple parameters, the method that used chemometric experimental design was less time-consuming and lower in cost. In this study, the influences of three experimental variables (phosphate concentration, surfactant concentration, and methanol percentage) on the experimental response were investigated by applying a chromatographic resolution statistic function. The optimized conditions were as follows: a running buffer of 150 mM phosphate solution (pH 7) containing 0.5 mM CTAB, 3 mM γ-CD, and 25% methanol; 20 s sample injection at 0.5 psi; a separation voltage of -15 kV; temperature was set at 25°C; and UV detection at 200 nm. The seven hydroxy acids were well separated in less than 10 min. The LOD (S/N = 3) was 625 nM for both salicylic acid and mandelic acid. The correlation coefficient of the regression curve was greater than 0.998. The RSD and relative error values were all less than 9.21%. After optimization and validation, this simple and rapid analysis method was considered to be established and was successfully applied to several commercial cosmetic products.