Objectives
HIV‐associated neurocognitive disorder (HAND) is an independent predictor of early mortality and is associated with many difficulties in activities of daily living. We sought to determine ...the prevalence of and risk factors for HAND in HIV‐infected Koreans. In addition, we investigated the performance of screening tools and components of neuropsychological (NP) tests for diagnosing HAND.
Methods
HIV‐infected patients were enrolled consecutively from two different urban teaching hospitals in Seoul, South Korea between March 2012 and September 2012. Participants completed a detailed NP assessment of six cognitive domains commonly affected by HIV. The Frascati criteria were used for diagnosing HAND. Four key questions, the International HIV Dementia Scale (IHDS) and Montreal Cognitive Assessment (MoCA)‐K were also assessed as potential tools for screening for HAND.
Results
Among the 194 participants, the prevalence of HAND was 26.3%. Asymptomatic neurocognitive impairment and minor neurocognitive disorder accounted for 52.9 and 47.1% of the patients with HAND, respectively. In multivariate analysis, haemoglobin (Hb) level ≤ 13 g/dL (P = 0.046) and current use of a protease inhibitor‐based regimen (P = 0.031) were independent risk factors for HAND. The sensitivity and specificity of the IHDS were 72.6 and 60.8%, and those of MoCA‐K were 52.9 and 73.4%, respectively. The IHDS (P < 0.001) and MoCA‐K (P < 0.001) were both useful for screening for HAND. Among NP tests, the sensitivity and specificity of the Grooved Pegboard Test were 90.2 and 72.0%, and those of the Wisconsin Card Sorting Test were 61.2 and 84.4%, respectively.
Conclusions
HAND is a prevalent comorbidity in HIV‐infected Koreans. Active screening and diagnosis with effective tools, such as the IHDS, MoCA‐K and Grooved Pegboard Test, could be used to identify this important complication.
Background and purpose
We analyzed the incidence and causes of oral anticoagulant (OAC) cessation and subsequent stroke after OAC withdrawal in a cohort of Korean stroke patients with atrial ...fibrillation.
Methods
The Korean Atrial Fibrillation Evaluation Registry in Ischemic Stroke patients (K‐ATTENTION) is a multicenter cohort study, merging stroke registries from 11 tertiary centers in Korea. The number of OAC interruption episodes and the reasons were reviewed from hospital records. Stroke after OAC withdrawal was defined when a patient experienced ischaemic stroke within 31 days after OAC withdrawal. Clinical variables were compared between patients who experienced stroke recurrence during OAC interruption and those who did not experience recurrence.
Results
Among 3213 stroke patients with atrial fibrillation, a total of 329 episodes of OAC interruption were detected in 229 patients after index stroke (mean age 72.9 ± 8.3 years, 113 female patients). The most frequent reason for OAC withdrawal was poor compliance 103 episodes (31.3%) followed by extracranial bleeding 96 episodes (29.2%). Stroke after OAC withdrawal was noted in 13 patients. Mean age, vascular risk factor profile and mean CHA2DS2‐VASc score were not significantly different between patients with and without recurrent stroke.
Conclusions
A considerable number of stroke patients with atrial fibrillation experienced temporary interruption of OAC after index stroke, which was associated with stroke recurrence of 4.0 cases per 100 interruption episodes.
Although outbreaks of Mycobacterium abscessus infection have been reported, none of these reports has identified the potential sources of infection and modes of transmission. In April 2008, we ...identified and investigated an outbreak of M. abscessus skin and soft tissue infections following acupuncture among the patients who visited an oriental medical clinic. Active surveillance of patients who had visited the clinic was conducted to define the extent of the outbreak. Environmental cultures and a case–control study were performed to elucidate the source of infection and mode of transmission. From 1002 patients interviewed, 109 patients were identified as having suffered M. abscessus skin and soft tissue infections at acupuncture sites. A single strain of M. abscessus was isolated from the wounds of 31 patients and nine environmental samples, including a diluted glutaraldehyde solution. The case–control study revealed that a higher numbers of visits to the clinic for acupuncture (adjusted OR (aOR) 20.12; 95% CI 4.34–93.35) and the use of interferential current therapy or low-frequency therapy (aOR 36.12; 95% CI 5.54–235.44) were associated with the development of M. abscessus infection. The contaminated diluted glutaraldehyde solution that was used to disinfect the physical therapy devices may have been the source of the outbreak of M. abscessus infection in the 109 patients who underwent acupuncture.
Triple-negative breast cancers (TNBC) are considered the most aggressive type of breast cancer, for which no targeted therapy exists at the moment. These tumors are characterized by having a high ...degree of chromosome instability and often overexpress the spindle assembly checkpoint kinase TTK. To explore the potential of TTK inhibition as a targeted therapy in TNBC, we developed a highly potent and selective small molecule inhibitor of TTK, NTRC 0066-0.
The compound is characterized by long residence time on the target and inhibits the proliferation of a wide variety of human cancer cell lines with potency in the same range as marketed cytotoxic agents. In cell lines and in mice, NTRC 0066-0 inhibits the phosphorylation of a TTK substrate and induces chromosome missegregation. NTRC 0066-0 inhibits tumor growth in MDA-MB-231 xenografts as a single agent after oral application. To address the effect of the inhibitor in breast cancer, we used a well-defined mouse model that spontaneously develops breast tumors that share key morphologic and molecular features with human TNBC. Our studies show that combination of NTRC 0066-0 with a therapeutic dose of docetaxel resulted in doubling of mouse survival and extended tumor remission, without toxicity. Furthermore, we observed that treatment efficacy is only achieved upon co-administration of the two compounds, which suggests a synergistic in vivo effect. Therefore, we propose TTK inhibition as a novel therapeutic target for neoadjuvant therapy in TNBC.
Summary
The incidence of atypical femoral fractures (AFFs) was 2.95% among 6644 hip and femoral fractures. Independent risk factors included the use of bisphosphonates (BPs), osteopenia or ...osteoporosis, rheumatoid arthritis, increased femoral curvatures, and thicker femoral cortices. Patients with AFFs and BP treatment were more likely to have problematic healing than those with typical femoral fractures (TFFs) and no BP treatment.
Introduction
To determine the incidence and risk factors of atypical femoral fractures (AFFs), we performed a multicenter case-control study. We also investigated the effects of bisphosphonates (BPs) on AFF healing.
Methods
We retrospectively reviewed the medical records and radiographs of 6644 hip and femoral fractures of patients from eight tertiary referral hospitals. All the radiographs were reviewed to distinguish AFFs from TFFs. Univariate and multivariate logistic regression analyses were performed to identify risk factors, and interaction analyses were used to investigate the effects of BPs on fracture healing.
Results
The incidence of AFFs among 6644 hip and femoral fractures was 2.95% (90 subtrochanter and 106 femoral shaft fractures). All patients were females with a mean age of 72 years, and 75.5% were exposed to BPs for an average duration of 5.2 years (range, 1–17 years). The use of BPs was significantly associated with AFFs (
p
< 0.001, odds ratio = 25.65; 95% confidence interval = 10.74–61.28). Other independent risk factors for AFFs included osteopenia or osteoporosis, rheumatoid arthritis, increased anterior and lateral femoral curvatures, and thicker lateral femoral cortex at the shaft level. Interaction analyses showed that patients with AFFs using BPs had a significantly higher risk of problematic fracture healing than those with TFFs and no BP treatment.
Conclusions
The incidence of AFFs among 6644 hip and femoral fractures was 2.95%. Osteopenia or osteoporosis, use of BPs, rheumatoid arthritis, increased anterior and lateral femoral curvatures, and thicker lateral femoral cortex were independent risk factors for the development of AFFs. Patients with AFFs and BP treatment were more likely to have problematic fracture healing than those with TFFs and no BP treatment.
MicroRNAs are noncoding regulatory RNAs strongly implicated in carcinogenesis, cell survival, and chemosensitivity. Here, microRNAs associated with chemoresistance in ovarian carcinoma, the most ...lethal of gynaecological malignancies, were identified and their functional effects in chemoresistant ovarian cancer cells were assessed.
MicroRNA expression in paclitaxel (PTX)-resistant SKpac sublines was compared with that of the PTX-sensitive, parental SKOV3 ovarian cancer cell line using microarray and qRT-PCR. The function of differentially expressed microRNAs in chemoresistant ovarian cancer was further evaluated by apoptosis, cell proliferation, and migration assays.
Upregulation of miR-106a and downregulation of miR-591 were associated with PTX resistance in ovarian cancer cells and human tumour samples. Transfection with anti-miR-106a or pre-miR-591 resensitized PTX-resistant SKpac cells to PTX by enhancing apoptosis (23 and 42% increase), and inhibited their cell migration (43 and 56% decrease) and proliferation (64 and 65% decrease). Furthermore, ZEB1 was identified as a novel target gene of miR-591, and BCL10 and caspase-7 were target genes of miR-106a, as identified by immunoblotting and luciferase assay.
MiR-106a and miR-591 have important roles in conferring PTX resistance to ovarian cancer cells. Modulation of these microRNAs resensitizes PTX-resistant cancer cells by targeting BCL10, caspase-7, and ZEB1.
Abstract
Superconductivity in the cuprates is found to be intertwined with charge and spin density waves. Determining the interactions between the different types of order is crucial for ...understanding these important materials. Here, we elucidate the role of the charge density wave (CDW) in the prototypical cuprate La
1.885
Sr
0.115
CuO
4
, by studying the effects of large magnetic fields (
H
) up to 24 Tesla. At low temperatures (
T
), the observed CDW peaks reveal two distinct regions in the material: a majority phase with short-range CDW coexisting with superconductivity, and a minority phase with longer-range CDW coexisting with static spin density wave (SDW). With increasing magnetic field, the CDW first grows smoothly in a manner similar to the SDW. However, at high fields we discover a sudden increase in the CDW amplitude upon entering the vortex-liquid state. Our results signify strong coupling of the CDW to mobile superconducting vortices and link enhanced CDW amplitude with local superconducting pairing across the
H
−
T
phase diagram.
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