MicroRNAs (miRNAs) are important regulators of many cellular processes and exist in a wide range of eukaryotes. High-throughput sequencing is a mainstream method of miRNA identification through which it is possible to obtain the complete small RNA profile of an organism. Currently, most approaches to miRNA identification rely on a reference genome for the prediction of hairpin structures. However, many species of economic and phylogenetic importance are non-model organisms without complete genome sequences, and this limits miRNA discovery. Here, to overcome this limitation, we have developed a contig-based miRNA identification strategy. We applied this method to a triploid species of edible banana (GCTCV-119, Musa spp. AAA group) and identified 180 pre-miRNAs and 314 mature miRNAs, which is three times more than those were predicted by the available dataset-based methods (represented by EST+GSS). Based on the recently published miRNA data set of Musa acuminate, the recall rate and precision of our strategy are estimated to be 70.6% and 92.2%, respectively, significantly better than those of EST+GSS-based strategy (10.2% and 50.0%, respectively). Our novel, efficient and cost-effective strategy facilitates the study of the functional and evolutionary role of miRNAs, as well as miRNA-based molecular breeding, in non-model species of economic or evolutionary interest.
High school students are an important target audience for organ donation education. A novel educational intervention focused on Hispanic American (HA) high school students might improve organ donation rates.
A prospective observational study was conducted in five Los Angeles High Schools with a high percentage of HA students. A ‘culturally sensitive’ educational program was administered to students in the 9th to 12th grades. Pre-intervention surveys that assessed awareness, knowledge, perception and beliefs regarding donation as well as the intent to become an organ donor were compared to post-intervention surveys.
A total of 10,146 high school students participated in the study. After exclusions, 4876 pre-intervention and 3182 post-intervention surveys were analyzed. A significant increase in the overall knowledge, awareness, and beliefs regarding donation was observed after the intervention, as evidenced by a significant increase in the percentage of correct answers on the survey (41% pre- v. 44% post-, p<0.0001). When specifically examining HA students, there was a significant increase in the intent to donate organs (AOR 1.21, 95%CI: 1.09, 1.34, p=0.0003).
This is the first study to demonstrate a significant increase in the intent to donate among HA high school students following an educational intervention.
High school; Organ Donation; Education; and Hispanic Americans
Religion is an important determinant in Hispanic Americans (HA) becoming organ donors as HA often believe religion forbids donation. We investigated the effect of an educational program targeting HA organ donation in places of worship. A prospective observational study was conducted at four Catholic churches with a high percentage of HA. A 45 minute ‘culturally sensitive’ educational program, conducted in Spanish, was implemented. Organ donation awareness, knowledge, perception and beliefs, as well as the intent to become an organ donor, were measured before and after the intervention. Differences between before and after the intervention were analyzed. A total of 182 surveys were collected before and 159 surveys were collected after the educational program. A significant increase was observed in organ donation knowledge (54% vs. 70%, p<0.0001), perception (43% vs. 58%, p<0.0001) and beliefs (50% vs. 60%, p=0.0001). However, no significant difference was found in the willingness to discuss donation with family, intent-to-donate, or registering to donate after the intervention. This study demonstrates that a focused educational program in places of worship can significantly improve HA knowledge, perceptions, and beliefs regarding organ donation. Further work is needed to understand why intent-to-donate does not increase despite the increase in organ donation awareness.
organ donation; Hispanic; church; religion; transplantation
AIM: To compare efficacy of combined lamivudine (LAM) and adefovir dipivoxil (ADV) therapy with that of entecavir (ETV) monotherapy for hepatitis B virus (HBV)-related decompensated liver cirrhosis.
METHODS: A total of 120 naïve patients with HBV-related decompensated cirrhosis participated in this study. Sixty patients were treated with combined LAM and ADV therapy (LAM + ADV group), while the other 60 were treated with ETV monotherapy (ETV group) for two years. Tests for liver and kidney function, alpha-fetoprotein, HBV serum markers, HBV DNA load, prothrombin time (PT), and ultrasonography or computed tomography scan of the liver were performed every 1 to 3 mo. Repeated measure ANOVA and the χ2 test were performed to compare the efficacy, side effects, and the cumulative survival rates at 48 and 96 wk.
RESULTS: Forty-five patients in each group were observed for 96 wk. No significant differences in HBV DNA negative rates and alanine aminotransferase (ALT) normalization rates at weeks 48 (χ2 = 2.12 and 2.88) and 96 (χ2 = 3.21 and 3.24) between the two groups were observed. Hepatitis B e antigen seroconversion rate in the LAM + ADV group at week 96 was significantly higher in the ETV group (43.5% vs 36.4%, χ2 = 4.09, P < 0.05). Viral breakthrough occurred in 2 cases (4.4%) by week 48 and in 3 cases (6.7%) by week 96 in the LAM + ADV group, and no viral mutation was detected. In the ETV group, viral breakthrough occurred in 1 case (2.2%) at the end of week 96. An increase in albumin (F = 18.9 and 17.3), decrease in total bilirubin and in ALT (F = 16.5, 17.1 and 23.7, 24.8), reduced PT (F = 22.7 and 24.5), and improved Child-Turcotte-Pugh and the model for end-stage liver disease scores (F = 18.5, 17.8, and 24.2, 23.8) were observed in both groups. The cumulative rates of mortality and liver transplantation were 16.7% (10/60) and 18.3% (11/60) in the LAM + ADV and ETV groups, respectively.
CONCLUSION: Both LAM + ADV combination therapy and ETV monotherapy can effectively inhibit HBV replication, improve liver function, and decrease mortality.
Chronic hepatitis B; Decompensated liver cirrhosis; Lamivudine; Adefovir dipivoxil; Combination therapy; Entecavir
White matter hyperintensities (WMH) and silent brain infarcts (SBI) have been associated with both vascular factors and cognitive decline. We examined among cognitively normal elderly, whether vascular factors predict cognitive decline and whether these associations are mediated by MRI measures of subclinical vascular brain injury.
Prospective multi-site longitudinal study of subcortical ischemic vascular diseases
Memory and aging centers in California
We studied 74 participants who were cognitively normal at entry and received at least 2 neuropsychological evaluations and 2 MRI exams over an average follow-up of 6.9 years.
Item response theory was used to create composite scores of global, verbal memory, and executive functioning. Volumetric MRI measures included WMH, SBI, hippocampus, and cortical gray matter (CGM). We used linear mixed effects models to examine the associations between vascular factors, MRI measures, and cognitive scores.
History of coronary artery disease (CAD) was associated with greater declines in global, verbal memory, and executive cognition. The CAD associations remained after controlling for changes in WMH, SBI, hippocampal and CGM volumes.
History of CAD may be a surrogate marker for clinically significant atherosclerosis which also affects the brain. Structural MRI measures of WMH and SBI do not fully capture the potential adverse effects of atherosclerosis on the brain. Future longitudinal studies of cognition should incorporate direct measures of atherosclerosis in cerebral arteries, as well as more sensitive neuroimaging measures.
cognitively normal elderly; coronary artery disease; cognitive decline; MRI
Colorectal cancer is a leading cause of cancer mortality in both developed and developing countries. Transforming basic research results into clinical practice is one of the key tasks of translational research, which will greatly improve the diagnosis and treatments of colorectal cancer. In this paper, a translational research platform for colorectal cancer, named crcTRP, is introduced. crcTRP serves the colorectal cancer translational research by providing various types of biomedical information related with colorectal cancer to the community. The information, including clinical data, epidemiology data, individual omics data, and public omics data, was collected through a multisource biomedical information collection solution and then integrated in a clinic-omics database, which was constructed with EAV-ER model for flexibility and efficiency. A preliminary exploration of conducting translational research on crcTRP was implemented and worked out a set of clinic-genomic relations, linking clinical data with genomic data. These relations have also been applied to crcTRP to make it more conductive for cancer translational research.
Bisphenol A (BPA) is a chemical compound widely used in manufacturing plastic products. Recent epidemiological studies suggest BPA exposure is positively associated with the incidence of type 2 diabetes mellitus (T2DM), however the mechanisms underlying this link remain unclear. Human islet amyloid polypeptide (hIAPP) is a hormone synthesized and secreted by the pancreatic β-cells. Misfolding of hIAPP into toxic oligomers and mature fibrils can disrupt cell membrane and lead to β-cell death, which is regarded as one of the causative factors of T2DM. To test whether there are any connections between BPA exposure and hIAPP misfolding, we investigated the effects of BPA on hIAPP aggregation using thioflavin-T based fluorescence, transmission electronic microscopy, circular dichroism, dynamic light scattering, size-exclusion chromatography,fluorescence-dye leakage assay in an artificial micelle system and the generation of reactive oxygen species in INS-1 cells. We demonstrated that BPA not only dose-dependently promotes the aggregation of hIAPP and enhances the membrane disruption effects of hIAPP, but also promotes the extent of hIAPP aggregation related oxidative stress. Taken together, our results suggest that BPA exposure increased T2DM risk may involve the exacerbated toxic aggregation of hIAPP.
The title compound, C6H4ClN3, is essentially planar, with a maximum deviation of 0.007 (3) Å. In the crystal, a short contact of 2.818 (3) Å is observed between N and Cl atoms of adjacent molecules.
The Montreal Cognitive Assessment Chinese-Language Los Angeles version (MoCA-ChLA) was developed and administered during an in-home interview to 1,192 participants (mean age 62.5 years, mean education 11.6 years) in a population-based Chinese American Eye Study (CHES) in Los Angeles. The MoCA-ChLA score (mean ± SD) was 23.8 ± 4.2 with little ceiling and no floor effects. The score increased with higher education, decreased with advancing age, and was not related to gender. Compared to the education 1–6 years group, the mean MoCA-ChLA score was 2.6 and 4.6 higher in the education 7–11 and 12–20 years groups, respectively. The Mandarin- (n = 612) and Cantonese- (n = 612) speaking subgroups performed comparably; Cronbach's alpha of the MoCA-ChLA score was 0.78 and 0.79 for these two groups, respectively. Item response theory analysis showed good discriminating power for executive function and memory. These properties support the MoCA-ChLA as a useful screening tool for aging and dementia studies for Mandarin or Cantonese speakers.
Recent epidemiologic studies have noted that risk factors for atherosclerosis (for example, diabetes mellitus, hypertension, and hyperlipidemia) are associated with increased risk of incident Alzheimer's disease (AD). In this evidence-based review, we frame the proposition as a question: are vascular risk factors also risk factors for plaques and tangles or just for concomitant vascular pathology that increases the likelihood of dementia? To date, no representative, prospective studies with autopsy (evidence level A) show significant positive associations between diabetes mellitus, hypertension, or intracranial atherosclerosis and plaques or tangles. Some prospective, representative, epidemiologic studies (evidence level B) show associations between diabetes, hypertension, hyperlipidemia, and aggregated risk factors with clinically diagnosed incident AD. However, the strength of association diminishes in the following order: vascular dementia (VaD) > AD + VaD > AD. This pattern is arguably more consistent with the hypothesis that atherosclerosis promotes subclinical vascular brain injury, thereby increasing the likelihood of dementia and in some cases making symptoms present earlier. Several autopsy studies from AD brain banks (evidence level C) have observed positive associations between intracranial atherosclerosis and severity of plaques and tangles. However, these studies may reflect selection bias; these associations are not confirmed when cases are drawn from non-dementia settings. We conclude that, at the present time, there is no consistent body of evidence to show that vascular risk factors increase AD pathology.
The present paper was designed to investigate the effect of pine pollen against aging in human diploid fibroblast 2BS cells and in an accelerated aging model, which was established by subcutaneous injections with D-galactose daily for 8 weeks in C57BL/6J mice. Pine pollen (1 mg/mL and 2 mg/mL) is proved to delay the replicative senescence of 2BS cells as evidenced by enhanced cell proliferation, decreased SA-β-Gal activity, and reversed expression of senescence-associated molecular markers, such as p53, p21Waf1, p16INK4a, PTEN, and p27Kip1 in late PD cells. Besides, pine pollen reversed D-galactose-induced aging effects in neural activity and inflammatory cytokine levels, as indicated by improved memory latency time and reduced error rate in step-down test and decreased concentrations of IL-6 and TNF-α in model mice. Similar to the role of AGEs (advanced glycation endproducts) formation inhibitor aminoguanidine (AG), pine pollen inhibited D-galactose-induced increment of AGEs levels thus reversed the aging phenotypes in model mice. Furthermore, the declined antioxidant activity was obviously reversed upon pine pollen treatment, which may account for its inhibitory effect on nonenzymatic glycation (NEG) in vivo. Our finding presents pine pollen as an attractive agent with potential to retard aging and attenuate age-related diseases in humans.
The impact of the atypical antipsychotics, olanzapine, quetiapine and risperidone on cognition in patients with Alzheimer’s disease is unclear. This report describes the effects of time and treatment on neuropsychological function during the Clinical Antipsychotic Trials of Intervention Effectiveness Alzheimer’s disease study (CATIE-AD).
CATIE-AD included 421 Alzheimer’s disease outpatients with psychosis or agitated/aggressive behavior, randomized to masked, flexible-dose olanzapine, quetiapine, risperidone or placebo. Based on clinician’s judgment, patients could discontinue originally assigned medication and be randomized to another medication. They were followed for 36 weeks. Cognitive assessments were obtained at baseline, 12 weeks, 24 weeks and 36 weeks. Outcomes were compared among 357 patients with baseline and at least one follow-up cognitive measure obtained while on their prescribed medication or placebo for at least 2 weeks before cognitive testing.
Overall, patients showed steady, significant declines over time in most cognitive areas, including Mini-mental State Examination (2.4 points over 36 weeks) and Alzheimer’s Disease Assessment Scale-cog (4.4 points). Patients on antipsychotics declined more than patients on placebo on multiple cognitive measures, including the MMSE (p=0.004), BPRS cognitive subscale (p=0.05), and a cognitive summary score summarizing change on 18 cognitive tests (p=0.004).
In CATIE-AD atypical antipsychotics were associated with worsening cognitive function at a magnitude consistent with one year’s deterioration compared with placebo. Further cognitive impairment is an additional risk of atypical antipsychotic treatment for Alzheimer’s disease patients that should be considered when considering treatment.
There is limited information available regarding the phenotype and function of leukocytes involved in the earliest stages of psoriatic lesion development. In this study, we examined the presence of different types of leukocytes in psoriatic point lesions collected at three 1-week interval time points from a recent and simultaneously formed group of point lesions. The cells were quantified and compared with K16 expression and epidermal thickness, both typically increased in this disease and considered as hallmarks. We found a significant correlation between K16+ cell increment and the increase in epidermal thickness in the timeframe of 14 days. The change in CD3+, CD4+, and CD8+ T-cell numbers in the dermis showed a significant association with these two features from d7 to d14, whereas in the epidermis only CD8+ T cells demonstrated a significant correlation. Remarkably, the relationship between T cells and disease progression was preceded by a significant correlation of CD11c+ dendritic cells (DCs) with K16 expression and epidermal thickness from baseline onwards. Interestingly, there was also a numeric correlation of CD11c+ DCs with the CD3+ T-cell shifts from d7 to d14. A significant correlation was also found between dermal CD14+ cells and K16 expression from d7 to d14. BDCA-2+ plasmacytoid DCs were absent in non-lesional skin, but found at low numbers in most lesions. The change in plasmacytoid DC or neutrophil numbers did not correlate with lesion development. In conclusion, our study suggests a relevant role for T cells, and in particular dermal CD11c+ DCs, in the earliest stage of psoriatic lesion development.
Psoriasis; Point lesion; Early infiltrate; T cell; Dendritic cell; CD11c
To elucidate the different neuromechanisms of subjects with strabismic and anisometropic amblyopia compared with normal vision subjects using blood oxygen level–dependent functional magnetic resonance imaging (BOLD-fMRI) and pattern-reversal visual evoked potential (PR-VEP).
Fifty-three subjects, age range seven to 12 years, diagnosed with strabismic amblyopia (17 cases), anisometropic amblyopia (20 cases), and normal vision (16 cases), were examined using the BOLD-fMRI and PR-VEP of UTAS-E3000 techniques. Cortical activation by binocular viewing of reversal checkerboard patterns was examined in terms of the calcarine region of interest (ROI)-based and spatial frequency–dependent analysis. The correlation of cortical activation in fMRI and the P100 amplitude in VEP were analyzed using the SPSS 12.0 software package.
In the BOLD-fMRI procedure, reduced areas and decreased activation levels were found in Brodmann area (BA) 17 and other extrastriate areas in subjects with amblyopia compared with the normal vision group. In general, the reduced areas mainly resided in the striate visual cortex in subjects with anisometropic amblyopia. In subjects with strabismic amblyopia, a more significant cortical impairment was found in bilateral BA 18 and BA 19 than that in subjects with anisometropic amblyopia. The activation by high-spatial-frequency stimuli was reduced in bilateral BA 18 and 19 as well as BA 17 in subjects with anisometropic amblyopia, whereas the activation was mainly reduced in BA 18 and BA 19 in subjects with strabismic amblyopia. These findings were further confirmed by the ROI-based analysis of BA 17. During spatial frequency–dependent VEP detection, subjects with anisometropic amblyopia had reduced sensitivity for high spatial frequency compared to subjects with strabismic amblyopia. The cortical activation in fMRI with the calcarine ROI-based analysis of BA 17 was significantly correlated with the P100 amplitude in VEP recording.
This study suggested that different types of amblyopia had different cortical responses and combinations of spatial frequency–dependent BOLD-fMRI with PR-VEP could differentiate among various kinds of amblyopia according to the different cortical responses. This study can supply new methods for amblyopia neurology study.
Epidural plasmacytoma is a rare clinical entity of plasma cell neoplasms. The optimal management of extra medullary plasmacytoma remains unclear, particularly for bulky masses. In this study, we report the case of a 35-year-old male who presented with the inability to walk, urinary incontinence and superficial and deep sensory disturbance. Spinal magnetic resonance imaging revealed a large epidural mass compressing the spinal cord at the level of T2–T4. The patient underwent surgical T2–T4 vertebral canal decompression. Histopathological examination and other findings confirmed the diagnosis of extramedullary plasmacytoma. The patient was treated with bortezomib in combination with dexamethasone and thalidomide. Following 4 cycles of chemotherapy, the patient achieved an excellent clinical response. Over 1 year following the initial diagnosis, the patient was in complete remission with no evidence of local relapse or evolution to multiple myeloma. This is the first case of a previously untreated epidural plasmacytoma, which was successfully treated with bortezomib-containing chemotherapy.
bortezomib; epidural; plasmacytoma
Relapse is a major challenge in the successful treatment of childhood acute lymphoblastic leukemia (ALL). Despite intensive research efforts, the mechanisms of ALL relapse are still not fully understood. An understanding of the molecular mechanisms underlying treatment outcome, therapy response and the biology of relapse is required. In this study, we carried out a genome-wide microRNA (miRNA) microarray analysis to determine the miRNA expression profiles and relapse-associated miRNA patterns in a panel of matched diagnosis–relapse or diagnosis–complete remission (CR) childhood ALL samples. A set of miRNAs differentially expressed either in relapsed patients or at diagnosis compared with CR was further validated by quantitative real-time polymerase chain reaction in an independent sample set. Analysis of the predicted functions of target genes based on gene ontology ‘biological process’ categories revealed that the abnormally expressed miRNAs are associated with oncogenesis, classical multidrug resistance pathways and leukemic stem cell self-renewal and differentiation pathways. Several targets of the miRNAs associated with ALL relapse were experimentally validated, including FOXO3, BMI1 and E2F1. We further investigated the association of these dysregulated miRNAs with clinical outcome and confirmed significant associations for miR-708, miR-223 and miR-27a with individual relapse-free survival. Notably, miR-708 was also found to be associated with the in vivo glucocorticoid therapy response and with disease risk stratification. These miRNAs and their targets might be used to optimize anti-leukemic therapy, and serve as novel targets for development of new countermeasures of leukemia. This fundamental study may also contribute to establish the mechanisms of relapse in other cancers.
Neuron loss, glial activation and vascular degeneration are common sequelae of ischemia-reperfusion (I/R) injury in ocular diseases. The present study was conducted to explore the ability of curcumin to inhibit retinal I/R injury, and to investigate underlying mechanisms of the drug effects.
Different dosages of curcumin were administered. I/R injury was induced by elevating the intraocular pressure for 60 min followed by reperfusion. Cell bodies, brn3a stained cells and TUNEL positive apoptotic cells in the ganglion cell layer (GCL) were quantitated, and the number of degenerate capillaries was assessed. The activation of glial cells was measured by the expression level of GFAP. Signaling pathways including IKK-IκBα, JAK-STAT1/3, ERK/MAPK and the expression levels of β-tubulin III and MCP-1 were measured by western blot analysis. Pre-treatment using 0.01%–0.25% curcumin in diets significantly inhibited I/R-induced cell loss in GCL. 0.05% curcumin pre-treatment inhibited I/R-induced degeneration of retinal capillaries, TUNEL-positive apoptotic cell death in the GCL, brn3a stained cell loss, the I/R-induced up-regulation of MCP-1, IKKα, p-IκBα and p-STAT3 (Tyr), and down-regulation of β-tubulin III. This dose showed no effect on injury-induced GFAP overexpression. Moreover, 0.05% curcumin administered 2 days after the injury also showed a vaso-protective effect.
Curcumin protects retinal neurons and microvessels against I/R injury. The beneficial effects of curcumin on neurovascular degeneration may occur through its inhibitory effects on injury-induced activation of NF-κB and STAT3, and on over-expression of MCP-1. Curcumin may therefore serve as a promising candidate for retinal ischemic diseases.
Mitochondrial dysfunction is a prominent feature of various neurodegenerative diseases. A deeper understanding of the remarkably dynamic nature of mitochondria, characterized by a delicate balance of fission and fusion, has helped to fertilize a recent wave of new studies demonstrating abnormal mitochondrial dynamics in neurodegenerative diseases. This review highlights mitochondrial dysfunction and abnormal mitochondrial dynamics in Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, and Huntington disease and discusses how these abnormal mitochondrial dynamics may contribute to mitochondrial and neuronal dysfunction. We propose that abnormal mitochondrial dynamics represents a key common pathway that mediates or amplifies mitochondrial dysfunction and neuronal dysfunction during the course of neurodegeneration.
Mitochondrial Dynamics; Mitochondrial Dysfunction; Mitochondrial Distribution; Synaptic Dysfunction; DLP1; Alzheimer Disease; Parkinson's disease
Our aim was to test the hypothesis that exposure to whole diesel exhaust (WDE) would enhance angiogenesis/vasculogenesis. Male apolipoprotein E-deficient mice, with either scaffold implantation subcutaneously or hindlimb ischemia, were exposed to either WDE (containing diesel exhaust particle [DEP] at a concentration of about 1 mg/m3) or filtered air 6 hours/day, 5 days/week in a whole body exposure chamber for 2, 5, or 8 weeks, respectively. WDE exposure significantly increased total cell counts in the scaffolds, aortic, and perivascular fat tissues. Macrophage infiltration was enhanced and CD31 expression increased in the scaffolds, which was coupled by increased α-smooth muscle actin (α-SMA) expression. WDE exposure led to increased CD31 expression, while decreasing endothelial nitric oxide synthase in the aortic wall. The vessel volume measured by micro-CT was increased in ischemic and non-ischemic hindlimbs in response to WDE exposure. DEP exposure induced capillary-like tube formation in endothelial cells in vitro, and caused capillary sprouting from aortic rings ex vivo. In addition, WDE exposure significantly increased mRNA expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1α, while decreasing prolylhydroxylase (PHD) 2 expression. WDE exposure increases inflammatory cell infiltration, enhances the vessel volume/flow, and increases capillary tube formation and sprouting, thereby inducing angiogenesis and vasculogenesis. The angiogenic effects may occur through increasing HIF-1α and VEGF while decreasing PHD2 expression.
particulate matter; diesel exhaust; hypoxia-inducible factor 1; prolylhydroxylase 2
Background and Aims
The protective component of the host response to dextran sodium sulfate colitis in the mouse is mediated through the activation of TLR4, the induction of COX-2 and PGE2 production. TLR4 ligands include bacterial lipolysaccharide and hyaluronic acid a, component of the extracellular matrix. Our hypothesis is that hyaluronic acid, through TLRs, plays a protective role in the host response to dextran sodium sulfate colitis.
Dextran sodium sulfate (2.5%) was administered for seven days in wild type and MyD88−/− mice. The mice also received intraperitoneal hyaluronic acid. The expression of hyaluronic acid, COX-2, and MIP2 were evaluated by immunohistochemistry.
Dextran sodium sulfate induced a marked increase in hyaluronic acid in the lamina propria of wild type but not MyD88−/− mice. Treatment with DSS also induced the MyD88-dependent expression of hyaluronic acid synthases 2 and 3, enzymes involved in hyaluronic acid synthesis, in lamina propria macrophages. Exogenous hyaluronic acid induced the expression of TNFα, MIP-2 and COX-2 in the colon in a MyD88-dependent manner. In wild type, but not MyD88−/−, TLR4−/−, COX-2−/− mice, hyaluronic acid was protective against dextran sodium sulfate colitis. In wild type mice hyaluronic acid was therapeutic in established DSS colitis.
Endogenous hyaluronic acid expression is markedly increased in dextran sodium sulfate colitis and preserves the epithelium through TLR activation and COX-2 expression. Furthermore exogenous hyaluronic acid, through the activation of TLRs and the production of PGE2 through COX-2 has protective effects in dextran sodium sulfate colitis.
IgM multiple myeloma (MM) is an extremely rare lymphoproliferative disease associated with an aggressive clinical course. However, the diagnosis of IgM MM may be complicated by Waldenstrom’s macroglobulinemia (WM), particularly when clinical manifestations and morphological features are not typical. It is crucial to distinguish between IgM MM and WM as their prognoses and treatment strategies are different. We report a case of IgM MM presenting with bleeding tendency and an immunophenotype analysis using flow cytometry and immunohistochemistry. Bone marrow cells exhibited a typical phenotype for plasma cells, expressing monoclonal cytoplasmatic IgL-λ, CD38 and CD138 instead of pan-B cell antigens CD19, CD20 and CD22, which are characteristic of the typical immunophenotype of WM. Therefore, the diagnosis of IgM MM was confirmed in this case, highlighting the significance of detailed immuno-phenotypic evaluation when clinical and morphological features are atypical.
IgM; multiple myeloma; immunophenotype
The title compound, C33H45NO10, has an aconitine carbon skeleton with four six-membered rings and two five-membered rings. The five-membered rings adopt envelope configurations and the six-membered N-containing heterocyclic ring displays a chair conformation. Two intramolecular O—H⋯O hydrogen bonds occur.
The second-generation antipsychotics are associated with metabolic abnormalities in patients with schizophrenia. Elderly patients with Alzheimer’s disease are frequently treated with these antipsychotics but there is little data available on their metabolic effects.
We assessed 186 male and 235 female Alzheimer’s disease outpatients from the Clinical Antipsychotic Trials of Intervention Effectiveness–Alzheimer’s Disease (CATIE-AD) for changes in weight, waist circumference, blood pressure, fasting glucose, and lipids in relation to duration of second-generation antipsychotics (i.e., olanzapine, quetiapine, and risperidone) use throughout the 36-week trial, using logistic regression and mixed-effects models.
Females showed significant weight gain of 0.14 lb per week of use (p = 0.006) while change was nonsignificant in males. The odds ratios of significant weight gain (i.e., ≥ 7% of body weight) compared to patients who did not use antipsychotics were 1.56 (95% CI 0.53 to 4.58), 2.89 (95% CI 0.97 to 8.64), and 3.38 (95% CI 1.24 to 9.23) among patients with antipsychotics use ≤ 12 weeks, > 12 to 24 weeks, and > 24 weeks during the trial, respectively. Olanzapine and quetiapine treatments were significantly associated with weight gain (0.12 and 0.14 pounds/week, respectively). In addition, olanzapine was significantly associated with decreases in HDL cholesterol (−0.19mG/dL/week), and increased girth (0.07 inches/week) relative to the placebo group. No treatment effects were noted for changes in blood pressure, glucose, and triglycerides.
Second-generation antipsychotics use was associated with weight gain in females, with olanzapine and quetiapine in particular, and with unfavorable change in HDL cholesterol and girth with olanzapine. The potential consequences of these effects suggest that patients with Alzheimer’s disease treated with second-generation antipsychotics should be monitored closely.
The authors examined predictors of mortality in individuals age 50 or older with or without cognitive impairment in a 12-year prospective naturalistic study of subcortical ischemic vascular disease focusing on symptoms of depressed mood, apathy, anhedonia, or anergia.
A total of 498 participants were recruited from the community and from memory clinics into a multicenter longitudinal study of subcortical ischemic vascular disease. For baseline cognitive status, 36% of participants were assessed as cognitively intact, 31% as cognitively impaired, and 33% as demented. All participants underwent a research protocol MRI, and 41% were classified as having subcortical lacunes. Depressed mood, anhedonia, anergia, and apathy were assessed at baseline using a structured behavioral assessment. Cox regression models were used to investigate the associations between neuropsychiatric symptoms and mortality, controlling for age, gender, race, education level, cognitive status, presence of vascular lacunes, and vascular risk factors.
Of 498 participants, 175 (35%) died over the follow-up period, with a median survival time of 5.6 years. In the multivariate analyses, cognitive impairment, age, male gender, depressed mood, and the presence of lacunes predicted higher mortality. Participants with both lacunes and depressed mood had the shortest survival among all cognitive groups. The mortality hazard ratio for participants with depressed mood was 2.2 (95% CI=1.5–3.2) after adjustment for cognitive status, age, gender, education level, race, lacunes, and all vascular conditions.
These findings suggest the importance of detecting depressed mood in individuals with cerebrovascular disease and of developing more aggressive treatment and preventive interventions for this vulnerable population.
Few longitudinal studies evaluate differences in patterns of change of category compared to letter fluency across the spectrum of cognitive impairment.
We compared change in category (animal and supermarket) and letter (F,A,S) fluency among 239 participants in three groups: remained cognitively normal throughout follow-up (n=96), developed AD (preclinical AD, n=21), and with AD at initial testing (prevalent AD, n=122).
At baseline, prevalent and preclinical AD groups scored lower on animal than letter fluency. On all fluency measures, the prevalent AD declined faster than other groups (all p<0.0001), and preclinical AD declined faster than unimpaired (all p≤0.02). Overall, animal fluency declined faster than letter fluency; animal fluency declined significantly faster than letter fluency among cognitively normal and prevalent AD subjects.
Greater longitudinal declines in category compared to letter fluency are consistent with cross-sectional studies. Steeper declines on both fluency measures distinguish preclinical AD from cognitively unimpaired individuals.
dementia; neuropsychology; fluency; Alzheimer disease; semantic memory; cognitive impairment