Summary
Background
Aspirin increases the risk of gastrointestinal bleeding.
Aim
To investigate the risk of lower gastrointestinal bleeding (LGIB) in aspirin users.
Methods
Low‐dose (75‐325 mg daily) ...aspirin users and controls matched by age, gender and enrollment time in a 1:5 ratio were selected from 1 million randomly sampled subjects in the National Health Insurance Research Database of Taiwan. Cox proportional hazard regression models were developed to evaluate the predictors of LGIB with adjustments for age, gender, comorbidities including coronary artery disease, ischaemic stroke, diabetes, hypertension, chronic kidney disease, liver cirrhosis, chronic obstructive pulmonary disease, dyslipidemia, uncomplicated peptic ulcer disease, history of peptic ulcer bleeding, and concomitant use of clopidogrel, ticlopidine, warfarin, nonsteroidal anti‐inflammatory drugs (NSAIDs), cyclooxygenase‐2 inhibitors, steroids, proton pump inhibitors (PPIs), histamine‐2 receptor antagonists (H2RAs), nitrates, alendronate, selective serotonin reuptake inhibitors (SSRIs) and calcium channel blockers.
Results
A total of 53 805 aspirin users and 269 025 controls were included. Aspirin group had a higher incidence of LGIB within 1 year than control group (0.20% vs 0.06%, P<.0001). Aspirin (hazard ratio HR: 2.75, 95% confidence interval CI: 2.06‐3.65), NSAIDs (HR: 8.61, 95% CI: 3.28‐22.58), steroids (HR: 10.50, 95% CI: 1.98‐55.57), SSRIs (HR: 11.71, 95% CI: 1.40‐97.94), PPIs (HR: 8.47, 95% CI: 2.26‐31.71), and H2RAs (HR: 10.83, 95% CI: 2.98‐39.33) were significantly associated with LGIB.
Conclusions
The risk of LGIB was higher in low‐dose aspirin users than in aspirin nonusers in this nationwide cohort. Low‐dose aspirin, NSAIDs, steroids, SSRIs, PPIs and H2RAs were independent risk factors for LGIB.
Linked ContentThis article is linked to Taha and Chen et al papers. To view these articles visit https://doi.org/10.1111/apt.14114 and https://doi.org/10.1111/apt.14138.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The antiferroelectricity in HfZrO 2 (HZO) annealed at 600 °C with an abrupt turn ON of FET characteristics with SSmin = 23 mV/dec and SSavg = 50 mV/dec over 4 decades of IDS is demonstrated. The near ...non-hysteresis is achieved with an antiferroelectric-like HZO due to a small remanent polarization and a coercive field. A feasible concept of coupling the antiferroelectric and ferroelectric type HZO are used for low-power electronics and the memory applications, respectively.
Abstract Background The contralateral femur is often used as reference for reconstruction in unilateral hip joint pathology. The objective of this study was to quantify the side-to-side variation in ...proximal femur. We hypothesized that significant side-to-side differences exist between left and right femur with implications for preoperative planning and leg length discrepancy following hip arthroplasty. Materials and methods CT-based 3D femoral models were reconstructed for 122 paired femurs in 61 young healthy subjects (46.9 ± 6.8 years) with no history of hip pathology. Side-to-side differences of several femoral morphologic parameters, including femoral head diameter, femoral anteversion, horizontal offset and femoral head center location, were compared and correlated with demographic factors using multiple linear regression. Results Significant side-to-side differences ( P < 0.01) were found in femoral anteversion (4.3 ± 3.8°; range: 0.2° to 17.3°), horizontal offset (2.5 ± 2.1 mm; range: 0.1 to 10.3 mm), and femoral head center location (7.1 ± 3.8 mm; range: 0.5 to 19.4 mm). The difference in femoral anteversion was strongly correlated with the difference in neck diameter (R2 = 0.79), whereas the difference in horizontal femoral offset was highly correlated with the head diameter difference (R2 = 0.72). Femoral head center difference was correlated with the femoral anteversion, horizontal offset and neck-shaft-angle difference (R2 = 0.82). Discussion Relying on the anatomic landmarks of the contralateral femur during hip arthroplasty may not necessarily result in restoration of native anatomy and leg-length. Knowledge of the baseline side-to-side asymmetry could provide a range of error that would be tolerable following hip reconstruction. Level of evidence Level IV. Type of study Retrospective observational study.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Metastasis is the major cause of cancer death. An increased level of circulating tumor cells (CTCs), metastatic cancer cells that have intravasated into the circulatory system, is particularly ...associated with colonization of distant organs and poor prognosis. However, the key factors required for tumor cell dissemination and colonization remain elusive. We found that high expression of desmoglein2 (DSG2), a component of desmosome-mediated intercellular adhesion complexes, promoted tumor growth, increased the prevalence of CTC clusters, and facilitated distant organ colonization. The dynamic regulation of DSG2 by hypoxia was key to this process, as down-regulation of DSG2 in hypoxic regions of primary tumors led to elevated epithelial-mesenchymal transition (EMT) gene expression, allowing cells to detach from the primary tumor and undergo intravasation. Subsequent derepression of DSG2 after intravasation and release of hypoxic stress was associated with an increased ability to colonize distant organs. This dynamic regulation of DSG2 was mediated by Hypoxia-Induced Factor1α (HIF1α). In contrast to its more widely observed function to promote expression of hypoxia-inducible genes, HIF1α repressed DSG2 by recruitment of the polycomb repressive complex 2 components, EZH2 and SUZ12, to the DSG2 promoter in hypoxic cells. Consistent with our experimental data, DSG2 expression level correlated with poor prognosis and recurrence risk in breast cancer patients. Together, these results demonstrated the importance of DSG2 expression in metastasis and revealed a mechanism by which hypoxia drives metastasis.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Summary
Kefir treatment in ovariectomized (OVX) rats could significantly decrease the levels of bone turnover markers and prevent OVX-induced bone loss, deterioration of trabecular microarchitecture, ...and biomechanical dysfunction that may be due to increase intracellular calcium uptake through the TRPV6 calcium channel.
Introduction
Osteoporosis is a disease characterized by low bone mass and structural deterioration of bone tissue, leading to an increased fracture risk. The incidence of osteoporosis increases with age and occurs most frequently in postmenopausal women due to estrogen deficiency, as the balance between bone resorption and bone formation shifts towards increased levels of bone resorption. Among various methods of prevention and treatment for osteoporosis, an increase in calcium intake is the most commonly recommended preventive measure. Kefir is a fermented milk product made with kefir grains that degrade milk proteins into various peptides with health-promoting effects, including immunomodulating-, antithrombotic-, antimicrobial-, and calcium-absorption-enhancing bioactivities.
Methods
The aim of this study is to investigate the effect of kefir on osteoporosis prophylaxis in an ovariectomized rat model. A total of 56 16-week-old female Sprague-Dawley (SD) rats were divided into 7 experimental groups: sham (normal), OVX/Mock, OVX/1X kefir (164 mg/kg BW/day), OVX/2X kefir (328 mg/kg BW/day), OVX/4X kefir (656 mg/kg BW/day), OVX/ALN (2.5 mg/kg BW/day), and OVX/REBONE (800 mg/kg BW/day). After 12-week treatment with kefir, the bone physiology in the OVX rat model was investigated. Accordingly, the aim of this study was to investigate the possible transport mechanism involved in calcium absorption using the Caco-2 human cell line.
Results
A 12-week treatment with kefir on the OVX-induced osteoporosis model reduced the levels of C-terminal telopeptides of type I collagen (CTx), bone turnover markers, and trabecular separation (Tb. Sp.). Additionally, treatment with kefir increased trabecular bone mineral density (BMD), bone volume (BV/TV), trabecular thickness (Tb. Th), trabecular number (Tb. N), and the biomechanical properties (hardness and modulus) of the distal femur with a dose-dependent efficacy. In addition, in in vitro assay, we found that kefir increased intracellular calcium uptake in Caco-2 cell through TRPV6 calcium channels and not through L-type voltage-operated calcium channels.
Conclusion
The protective effect of kefir in the OVX rat model may occur through increasing intracellular calcium uptake through the TRPV6 calcium channel.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Summary
Background HLA‐Cw*06 has a strong influence on the clinical features and the susceptibility to psoriasis in different ethnicities. It is also used as a biomarker to predict the therapeutic ...efficacy of biologics, with inconsistent results. Additionally, most Asian patients with psoriasis do not carry HLA‐Cw*06.
Objectives To determine additional HLA alleles which confer susceptibility or affect the severity of psoriasis in Chinese Han individuals. In addition, the potential of using HLA to predict treatment outcomes was also investigated.
Methods We conducted a case–control association study in 199 Chinese patients with psoriasis and 200 unrelated healthy controls. HLA‐B and HLA‐C genotyping was performed and correlated with the therapeutic efficacy of the biologics, including alefacept, efalizumab, etanercept and ustekinumab. Patients with psoriasis were divided into group A (high‐need patients with moderate to severe psoriasis) and B (general patients with psoriasis).
Results The frequencies of HLA‐B*60, HLA‐B*75, HLA‐Cw*06 and HLA‐Cw*10 were significantly increased in patients with psoriasis compared with the healthy controls. However, the prevalence of HLA‐Cw*06 was lower in group A compared with group B (6% vs. 17%, Pc = 0·04). HLA‐B*46 was found to be strongly associated with group A but not with group B patients with psoriasis. HLA‐Cw*01/HLA‐B*46 was also identified as a risk haplotype for Chinese patients with psoriasis, compatible with the results in Thais. Significant differences in response to biologics were observed between HLA‐Cw*01+ and HLA‐Cw*01− individuals in the alefacept treatment group, and between HLA‐B*37+ and HLA‐B*37−, and HLA‐B*58+ and HLA‐B*58− individuals in the efalizumab treatment group.
Conclusions In addition to HLA‐Cw*06, the HLA‐Cw*01/HLA‐B*46 haplotype was also increased in Chinese patients with psoriasis. High‐need patients with psoriasis had a lower frequency of HLA‐Cw*06 but a higher prevalence of HLA‐B*46 compared with general patients with psoriasis in our population.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Highlights • 2 kidneys 1 clip method (2K1C) constricts 1 renal artery and induces hypertension. • 2K1C-induced hypertension impairs long-term, but not short-term, memory in mice. • 2K1C reduces ...dendritic complexity of CA1 neurons and hippocampal neurogenesis. • 2K1C doesn’t alter vascular density or glial activation status in the hippocampus. • 2K1C-induced impairments in the hippocampus are related to downregulation of BDNF.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Dysregulation of cell surface proteolysis has been strongly implicated in tumorigenicity and metastasis. In this study, we delineated the role of hepatocyte growth factor activator inhibitor-2 ...(HAI-2) in prostate cancer (PCa) cell migration, invasion, tumorigenicity and metastasis using a human PCa progression model (103E, N1, and N2 cells) and xenograft models. N1 and N2 cells were established through serial intraprostatic propagation of 103E human PCa cells and isolation of the metastatic cells from nearby lymph nodes. The invasion capability of these cells was revealed to gradually increase throughout the serial isolations (103E<N1<N2). In this series of cells, the expression of HAI-2 but not HAI-1 was significantly decreased throughout the progression and occurred in parallel with increased activation of matriptase. The expression level and activity of matriptase increased whereas the HAI-2 protein level decreased over the course of orthotopic tumor growth in mice, which was consistent with the immunohistochemical profiles of matriptase and HAI-2 in archival PCa specimens. Knockdown of matriptase reduced the PCa cell invasion induced by HAI-2 knockdown. HAI-2 overexpression or matriptase silencing in N2 cells downregulated matriptase activity and significantly decreased tumorigenicity and metastatic capability in orthotopically xenografted mice. These results suggest that during the progression of human PCa, matriptase activity is primarily controlled by HAI-2 expression. The imbalance between HAI-2 and matriptase expression led to matriptase activation, thereby increasing cell migration, invasion, tumorigenicity and metastasis.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In nowadays 3-D integrated circuits (3DICs) technology, through silicon via (TSV) is the most important component, which connects homogeneous or heterogeneous dies vertically with each other. Based ...on our previous research, carbon nanotubes (CNTs) have been considered as TSV filling materials due to their outstanding mechanical and electrical properties. However, the operating temperatures would significantly affect the performance of signal transmission in CNT TSV. To evaluate the electrical characteristics of CNT TSV with different realistic temperatures, the considerations of temperature-dependent electron mean free path (MFP, <inline-formula> <tex-math notation="LaTeX">\lambda </tex-math></inline-formula>), and number of conducting channels of CNTs are necessary. In this work, the equivalent circuit model of CNTs as TSV is presented and the simulated electrical behaviors are benchmarked with other literatures. Based on our proposed model, multiwall (MW) CNTs' electrical performance in multilayers stacking system under different operating temperatures is investigated. In addition, we also compare the electrical performance of CNTs as TSV with the conventional filling material (Cu). It shows that CNT TSV has more advantages than Cu TSV when the operating temperature becomes higher. In summary, the proposed equivalent circuit model in this work is more comprehensive and yields more realistic results. Meanwhile, CNT is a promising material for TSV under varying operation temperatures.
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