Summary
The plasma n-3 fatty acid level was 26.2% lower in patients with osteoporotic hip fracture than in those with osteoarthritis. In all patients, n-3 fatty acid was positively associated with ...bone mineral density and inversely associated with tartrate-resistant acid phosphatase-5b level in bone marrow aspirates, reflecting the bone microenvironment.
Introduction
Despite the potential beneficial role of n-3 fatty acid (FA) on bone metabolism, the specific mechanisms underlying these effects in humans remain unclear. Here, we assessed whether the plasma n-3 level, as an objective indicator of its status, is associated with osteoporosis-related phenotypes and bone-related markers in human bone marrow (BM) samples.
Methods
This was a case-control and cross-sectional study conducted in a clinical unit. n-3 FA in the blood and bone biochemical markers in the BM aspirates were measured by gas chromatography/mass spectrometry and immunoassay, respectively. BM fluids were collected from 72 patients who underwent hip surgery because of either osteoporotic hip fracture (HF;
n
= 28) or osteoarthritis (
n
= 44).
Results
After adjusting for confounders, patients with HF had 26.2% lower plasma n-3 levels than those with osteoarthritis (
P
= 0.006), and each standard deviation increment in plasma n-3 was associated with a multivariate-adjusted odds ratio of 0.40 for osteoporotic HF (
P
= 0.010). In multivariate analyses including all patients, a higher plasma n-3 level was associated with higher bone mass at the lumbar spine (β = 0.615,
P
= 0.002) and total femur (β = 0.244,
P
= 0.045). Interestingly, the plasma n-3 level was inversely associated with the tartrate-resistant acid phosphatase-5b level (
β
= − 0.633,
P
= 0.023), but not with the bone-specific alkaline phosphatase level, in BM aspirates.
Conclusions
These findings provide clinical evidence that n-3 FA is a potential inhibitor of osteoclastogenesis that favors human bone health.
Despite recent advances in understanding microbial diversity in skin homeostasis, the relevance of microbial dysbiosis in inflammatory disease is poorly understood. Here we perform a comparative ...analysis of skin microbial communities coupled to global patterns of cutaneous gene expression in patients with atopic dermatitis or psoriasis. The skin microbiota is analysed by 16S amplicon or whole genome sequencing and the skin transcriptome by microarrays, followed by integration of the data layers. We find that atopic dermatitis and psoriasis can be classified by distinct microbes, which differ from healthy volunteers microbiome composition. Atopic dermatitis is dominated by a single microbe (Staphylococcus aureus), and associated with a disease relevant host transcriptomic signature enriched for skin barrier function, tryptophan metabolism and immune activation. In contrast, psoriasis is characterized by co-occurring communities of microbes with weak associations with disease related gene expression. Our work provides a basis for biomarker discovery and targeted therapies in skin dysbiosis.
The transcription coactivator Yes-associated protein 1 (YAP1) is regulated by the Hippo tumor suppressor pathway. However, the role of YAP1 in thyroid cancer, which is frequently associated with the ...BRAF(V600E) mutation, remains unknown. This study aimed to investigate the role of YAP1 in thyroid cancer. YAP1 was overexpressed in papillary (PTC) and anaplastic thyroid cancer, and nuclear YAP1 was more frequently detected in BRAF(V600E) (+) PTC. In the thyroid cancer cell lines TPC-1 and HTH7, which do not have the BRAF(V600E) mutation, YAP1 was cytosolic and inactive at high cell densities. In contrast, YAP1 was retained in the nucleus and its target genes were expressed in the thyroid cancer cells 8505C and K1, which harbor the BRAF(V600E) mutation, regardless of cell density. Furthermore, the nuclear activation of YAP1 in 8505C was not inhibited by RAF or MEK inhibitor. In vitro experiments, YAP1 silencing or overexpression affected migratory capacities of 8505C and TPC-1 cells. YAP1 knockdown resulted in marked decrease of tumor volume, invasion and distant metastasis in orthotopic tumor xenograft mouse models using the 8505C thyroid cancer cell line. Taken together, YAP1 is involved in the tumor progression of thyroid cancer and YAP1-mediated effects might not be affected by the currently used RAF kinase inhibitors.
MammaPrint, a prognostic 70-gene profile for early-stage breast cancer, has been available for fresh tissue. Improvements in RNA processing have enabled microarray diagnostics for formalin-fixed, ...paraffin-embedded (FFPE) tissue. Here, we describe method optimization, validation, and performance of MammaPrint using analyte from FFPE tissue. Laboratory procedures for enabling the assay to be run on FFPE tissue were determined using 157 samples, and the assay was established using 125 matched FFPE and fresh tissues. Validation of MammaPrint-FFPE, compared with MammaPrint-fresh, was performed on an independent series of matched tissue from five hospitals ( n = 211). Reproducibility, repeatability, and precision of the FFPE assay ( n = 87) was established for duplicate analysis of the same tumor, interlaboratory performance, 20-day repeat experiments, and repeated analyses over 12 months. FFPE sample processing had a success rate of 97%. The MammaPrint assay using FFPE analyte demonstrated an overall equivalence of 91.5% (95% confidence interval, 86.9% to 94.5%) between the 211 independent matched FFPE and fresh tumor samples. Precision was 97.3%, and repeatability was 97.8%, with highly reproducible results between replicate samples of the same tumor and between two laboratories (concordance, 96%). Thus, with 580 tumor samples, MammaPrint was successfully translated to FFPE tissue. The assay has high precision and reproducibility, and FFPE results are substantially equivalent to results derived from fresh tissue.
Intense femtosecond laser excitation can produce transient states of matter that would otherwise be inaccessible to laboratory investigation. At high excitation densities, the interatomic forces that ...bind solids and determine many of their properties can be substantially altered. Here, we present the detailed mapping of the carrier density-dependent interatomic potential of bismuth approaching a solid-solid phase transition. Our experiments combine stroboscopic techniques that use a high-brightness linear electron accelerator-based x-ray source with pulse-by-pulse timing reconstruction for femtosecond resolution, allowing quantitative characterization of the interatomic potential energy surface of the highly excited solid.
•The OR of moderate hearing loss for social frailty were statistically significant.•Neighbor meeting and someone love and affection were associated with hearing loss.•More depression and lower ...cognitive function in the social frailty group.•After adjusting physical activity, OR of hearing loss for social frailty remained.
To determine whether hearing loss is associated with social frailty in older adults.
Cross-sectional analysis of cohort study data. Hearing was measured using of Pure-tone audiometry. Hearing loss was determined based on the average of hearing thresholds at 0.5, 1, and 2 kHz in the ear that had better hearing. Social frailty was defined based on the summation of the following 5 social components (1. Neighborhood meeting attendance 2. Talking to friend(s) sometimes 3.Someone gives you love and affection 4. Living alone 5. Meeting someone every day). Participants who had no correspondence to the components were considered non-social frailty; those with 1–2 components were considered social prefrailty; and those having 3 or more components were considered social frailty.
The prevalence of non-social frailty, social prefrailty, social frailty was 27.6%, 60.7% and 11.7% respectively. Of the five questions, two components (Neighborhood meeting attendance and Presence of someone who shows love and affection to the participants) were associated with hearing loss (p < 0.001). Compared to non-social frailty, the odds ratio of social frailty for hearing loss was 2.24 (95% CI 1.48–3.38) after adjusting for age, residential area, economic status, smoking, depressive disorder and MMSE, and 2.17 (95% CI 1.43–3.30) after further adjustments with physical frailty.
Hearing loss was associated with social frailty even after controlling confounding factors even including physical frailty.
Background and purpose
Recent studies have demonstrated that Alzheimer's disease (AD) and subcortical vascular dementia (SVaD) have white matter (WM) microstructural changes. However, previous ...studies on AD and SVaD rarely eliminated the confounding effects of patients with mixed Alzheimer's and cerebrovascular disease pathologies. Therefore, our aim was to evaluate the divergent topography of WM microstructural changes in patients with pure AD and SVaD.
Methods
Patients who were clinically diagnosed with AD and SVaD were prospectively recruited. Forty AD patients who were Pittsburgh compound B (PiB) positive PiB(+) AD without WM hyperintensities and 32 SVaD patients who were PiB negative PiB(−) SVaD were chosen. Fifty‐six cognitively normal individuals were also recruited (NC). Tract‐based spatial statistics of diffuse tensor imaging were used to compare patterns of fractional anisotropy (FA) and mean diffusivity (MD).
Results
Compared with the NC group, the PiB(+) AD group showed decreased FA in the bilateral frontal, temporal and parietal WM regions and the genu and splenium of the corpus callosum as well as increased MD in the left frontal and temporal WM region. PiB(−) SVaD patients showed decreased FA and increased MD in all WM regions. Direct comparison between PiB(+) AD and PiB(−) SVaD groups showed that the PiB(−) SVaD group had decreased FA across all WM regions and increased MD in all WM regions except occipital regions.
Conclusion
Our findings suggest that pure AD and pure SVaD have divergent topography of WM microstructural changes including normal appearing WM.
Myocarditis and/or pericarditis (also known as myopericarditis) are inflammatory diseases involving the myocardium (with non-ischemic myocyte necrosis) and/or the pericardial sac. ...Myocarditis/pericarditis (MPC) may present with variable clinical signs, symptoms, etiologies and outcomes, including acute heart failure, sudden death, and chronic dilated cardiomyopathy. Possible undiagnosed and/or subclinical acute myocarditis, with undefined potential for delayed manifestations, presents further challenges for diagnosing an acute disease and may go undetected in the setting of infection as well as adverse drug/vaccine reactions.
The most common causes of MPC are viral, with non-infectious, drug/vaccine associated hypersensitivity and/or autoimmune causes being less well defined and with potentially different inflammatory mechanisms and treatment responses. Potential cardiac adverse events following immunization (AEFIs) encompass a larger scope of diagnoses such as triggering or exacerbating ischemic cardiac events, cardiomyopathy with potential heart failure, arrhythmias and sudden death. The current published experience does not support a potential causal association with vaccines based on epidemiologic evidence of relative risk increases compared with background unvaccinated incidence. The only evidence supporting a possible causal association of MPC with a vaccine comes from case reports.
Hypersensitivity MPC as a drug/vaccine induced cardiac adverse event has long been a concern for post-licensure safety surveillance, as well as safety data submission for licensure. Other cardiac adverse events, such as dilated cardiomyopathy, were also defined in the CDC definitions for adverse events after smallpox vaccination in 2006. In addition, several groups have attempted to develop and improve the definition and adjudication of post-vaccination cardiovascular events. We developed the current case definitions for myocarditis and pericarditis as an AEFI building on experience and lessons learnt, as well as a comprehensive literature review. Considerations of other etiologies and causal relationships are outside the scope of this document.
Three clusters of coronavirus disease 2019 (COVID-19) linked to a tour group from China, a company conference, and a church were identified in Singapore in February, 2020.
We gathered epidemiological ...and clinical data from individuals with confirmed COVID-19, via interviews and inpatient medical records, and we did field investigations to assess interactions and possible modes of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Open source reports were obtained for overseas cases. We reported the median (IQR) incubation period of SARS-CoV-2.
As of Feb 15, 2020, 36 cases of COVID-19 were linked epidemiologically to the first three clusters of circumscribed local transmission in Singapore. 425 close contacts were quarantined. Direct or prolonged close contact was reported among affected individuals, although indirect transmission (eg, via fomites and shared food) could not be excluded. The median incubation period of SARS-CoV-2 was 4 days (IQR 3–6). The serial interval between transmission pairs ranged between 3 days and 8 days.
SARS-CoV-2 is transmissible in community settings, and local clusters of COVID-19 are expected in countries with high travel volume from China before the lockdown of Wuhan and institution of travel restrictions. Enhanced surveillance and contact tracing is essential to minimise the risk of widespread transmission in the community.
None.
Alcohol and tobacco are the most commonly used addictive substances, with high comorbidity rates between alcohol use disorder and tobacco use disorder. Risk for alcohol and nicotine addiction is ...highly heritable, and they share common genetic factors. A GWAS in over 1 million individuals has revealed 566 genetic variants in 406 loci associated with multiple stages of alcohol and tobacco use. Three novel genes-SLC39A8, GRK4 and HGFAC-within loci associated with altered alcoholic drinks per week (ADW) or cigarettes per day (CPD) were selected to further study their role in alcohol and tobacco use disorder. The role of these genes was assessed using the two-bottle choice addiction paradigm in transgenic mice for each of the genes. We found significant decreases in chronic alcohol consumption and preference in female Hgfac knockout (KO) mice, and decreased nicotine preference in male Hgfac KO compared with wild-type (WT) mice. Additionally, male Slc39a8 hypomorph mice showed greater overall nicotine preference compared with WT mice, while no differences were detected for Grk4 KO mice in alcohol or nicotine consumption and preference in either sex. Thus, this study implicates Hgfac and Slc39a8 in alcohol and tobacco use in a sex-specific manner.
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