Introduction
To devise appropriate preventive strategies after stroke, knowledge of the association between post-stroke cognitive impairment (PSCI) and prognosis of stroke patients is important. We ...investigated the association between PSCI and the vascular outcomes in patients with ischemic stroke with best medical care considering their risk factors and adherence to medications.
Methods
Of the 1534 ischemic stroke patients who randomly assigned to aspirin or cilostazol treatment with best medical therapy by the PICASSO (PreventIon of CArdiovascular events in iSchemic Stroke patients with high risk of cerebral hemOrrhage) trial, 1240 with baseline mini-mental state examination (MMSE) scores were analysed retrospectively. The patients were classified into three groups based on MMSE scores. Recurrence of ischemic stroke, stroke of any type and composite of major vascular events were compared among them.
Results
Of the 1240 patients, 376 had MMSE scores of 28–30 (highest tertile), 419 had scores of 24–27 (middle tertile) and 445 had scores of 0–23 (lowest tertile). The average time from stroke onset to MMSE examination was 31.8 days. By trend analysis, lower tertile of MMSE score was significantly associated with recurrent ischemic stroke (
p
= 0.0017), stroke of any type (
p
= 0.0053) and composite vascular outcome (
p
= 0.0122). After adjustment for covariates, PSCI was independently associated with risk of recurrent ischemic stroke (HR 2.40, 95% confidence interval 1.12–5.14).
Conclusions
Cognitive impairment was associated with recurrence of ischemic stroke in high risk patients during adequate medical therapy including antiplatelet therapy. However, the other vascular events were not.
Biocompatibility is important for the 3D printing of resins used in medical devices and can be affected by photoinitiators, one of the key additives used in the 3D printing process. The choice of ...ingredients must be considered, as the toxicity varies depending on the photoinitiator, and unreacted photoinitiator may leach out of the polymerized resin. In this study, the use of ethyl (2,4,6-trimethylbenzoyl) phenylphosphinate (TPO-L) as a photoinitiator for the 3D printing of resin was considered for application in medical device production, where the cytotoxicity, colour stability, dimensional accuracy, degree of conversion, and mechanical/physical properties were evaluated. Along with TPO-L, two conventional photoinitiators, phenylbis (2,4,6-trimethylbenzoyl) phosphine oxide (BAPO) and diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide (TPO), were considered. A total of 0.1 mol% of each photoinitiator was mixed with the resin matrix to prepare a resin mixture for 3D printing. The specimens were printed using a direct light processing (DLP) type 3D printer. The 3D-printed specimens were postprocessed and evaluated for cytotoxicity, colour stability, dimensional accuracy, degree of conversion, and mechanical properties in accordance with international standards and the methods described in previous studies. The TPO-L photoinitiator showed excellent biocompatibility and colour stability and possessed with an acceptable dimensional accuracy for use in the 3D printing of resins. Therefore, the TPO-L photoinitiator can be sufficiently used as a photoinitiator for dental 3D-printed resin.
Blood pressure variability (BPV) is associated with higher cardiovascular morbidity risks; however, its association with cognitive decline remains unclear. We investigated whether higher BPV is ...associated with faster declines in cognitive function in ischemic stroke (IS) patients. Cognitive function was evaluated between April 2010 and August 2015 using the Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment in 1,240 Korean PICASSO participants. Patients for whom baseline and follow-up cognitive test results and at least five valid BP readings were available were included. A restricted maximum likelihood-based Mixed Model for Repeated Measures was used to compare changes in cognitive function over time. Among a total of 746 participants (64.6 ± 10.8 years; 35.9% female). Baseline mean-MMSE score was 24.9 ± 4.7. The median number of BP readings was 11. During a mean follow-up of 2.6 years, mean baseline and last follow-up MMSE scores were 25.4 ± 4.8 vs. 27.8 ± 4.4 (the lowest BPV group) and 23.9 ± 5.2 vs. 23.2 ± 5.9 (the highest BPV group). After adjusting for multiple variables, higher BPV was independently associated with faster cognitive decline over time. However, no significant intergroup difference in cognitive changes associated with mean systolic BP was observed. Further research is needed to elucidate how BPV might affect cognitive function.
Nearly all forms of hereditary hemochromatosis are characterized by pathological iron accumulation in the liver, pancreas, and heart. These tissues preferentially load iron because they take up ...non-transferrin-bound iron (NTBI), which appears in the plasma during iron overload. Yet, how tissues take up NTBI is largely unknown. We report that ablation of Slc39a14, the gene coding for solute carrier SLC39A14 (also called ZIP14), in mice markedly reduced the uptake of plasma NTBI by the liver and pancreas. To test the role of SLC39A14 in tissue iron loading, we crossed Slc39a14−/− mice with Hfe−/− and Hfe2−/− mice, animal models of type 1 and type 2 (juvenile) hemochromatosis, respectively. Slc39a14 deficiency in hemochromatotic mice greatly diminished iron loading of the liver and prevented iron deposition in hepatocytes and pancreatic acinar cells. The data suggest that inhibition of SLC39A14 may mitigate hepatic and pancreatic iron loading and associated pathologies in iron overload disorders.
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•SLC39A14 mediates non-transferrin-bound iron uptake by the liver and pancreas•SLC39A14 is required for Hfe−/− and Hfe2−/− mice to develop hepatic iron overload•SLC39A14 is required for iron loading of hepatocytes and pancreatic acinar cells•SLC39A14 represents a possible therapeutic target for mitigating tissue iron loading
Plasma non-transferrin-bound iron (NTBI) is a main contributor to tissue iron loading in iron overload disorders such as hereditary hemochromatosis. Jenkitkasemwong et al. show that loss of the metal-ion transporter SLC39A14 impairs NTBI uptake by the liver and prevents hepatic iron overload in mouse models of hemochromatosis.
Sphingosine kinase1 (SphK1) is an acetyl-CoA dependent acetyltransferase which acts on cyclooxygenase2 (COX2) in neurons in a model of Alzheimer's disease (AD). However, the mechanism underlying this ...activity was unexplored. Here we show that N-acetyl sphingosine (N-AS) is first generated by acetyl-CoA and sphingosine through SphK1. N-AS then acetylates serine 565 (S565) of COX2, and the N-AS-acetylated COX2 induces the production of specialized pro-resolving mediators (SPMs). In a mouse model of AD, microglia show a reduction in N-AS generation, leading to decreased acetyl-S565 COX2 and SPM production. Treatment with N-AS increases acetylated COX2 and N-AS-triggered SPMs in microglia of AD mice, leading to resolution of neuroinflammation, an increase in microglial phagocytosis, and improved memory. Taken together, these results identify a role of N-AS in the dysfunction of microglia in AD.
Poly(methyl methacralyate) (PMMA) has long been used in dentistry as a base polymer for dentures, and it is recently being used for the 3D printing of dental materials. Despite its many advantages, ...its susceptibility to microbial colonization remains to be overcome. In this study, the interface between 3D-printed PMMA specimens and oral salivary biofilm was studied following the addition of zwitterionic materials, 2-methacryloyloxyethyl phosphorylcholine (MPC) or sulfobetaine methacrylate (SB). A significant reduction in bacterial and biofilm adhesions was observed following the addition of MPC or SB, owing to their protein-repellent properties, and there were no significant differences between the two test materials. Although the mechanical properties of the tested materials were degraded, the statistical value of the reduction was minimal and all the properties fulfilled the requirements set by the International Standard, ISO 20795-2. Additionally, both the test materials maintained their resistance to biofilm when subjected to hydrothermal fatigue, with no further deterioration of the mechanical properties. Thus, novel 3D-printable PMMA incorporated with MPC or SB shows durable oral salivary biofilm resistance with maintenance of the physical and mechanical properties.
Background
To compare the biomechanical stability of a novel, C-shaped nickel–titanium shape memory alloy (SMA) implant (C-clip) with traditional cerclage wiring in the fixation of a Vancouver B1 ...(VB1) periprosthetic femoral fracture (PFF).
Methods
In total, 18 synthetic femoral fracture models were constructed to obtain unstable VB1 fracture with an oblique fracture line 8 cm below the lesser trochanter. For each model, the distal portion was repaired using a 10-hole locking plate and four distal bi-cortical screws. The proximal portion was repaired using either three, threaded cerclage wirings or three, novel C-shaped implants. Specimens underwent biomechanical testing using axial compression, torsional and four-point bending tests. Each test was performed on three specimens.
Results
The C-clip was statistically significantly stronger (i.e., stiffer) than cerclage wiring in the three biomechanical tests. For axial compression, medians (ranges) were 39 (39–41) and 35 (35–35) N/mm, for the C-clip and cerclage wiring, respectively. For torsion, medians (ranges) were, 0.44 (0.44–0.45) and 0.30 (0.30–0.33) N/mm for the C-clip and cerclage wiring, respectively. For the four-point bending test, medians (ranges) were 39 (39–41) and 28 (28–31) N/mm; for the C-clip and cerclage wiring, respectively.
Conclusion
Results from this small study show that the novel, C-shaped SMA appears to be biomechanically superior to traditional cerclage wiring in terms of stiffness, axial compression, torsion and four-point bending, and may be a valuable alternative in the repair of VB1 PFF. Further research is necessary to support these results.
The molecular mechanisms of the degeneration of the aortic wall in abdominal aortic aneurysm (AAA) are poorly understood. The monomeric form of C-reactive protein (mCRP) is deposited in damaged ...cardiovascular organs and aggravates the prognosis; however, it is unknown whether mCRP is deposited in the degenerated aorta of abdominal aortic aneurysm (AAA). We investigated whether mCRP is deposited in AAA and examined the associated pathogenic signaling pathways.
Twenty-four cases of AAA were analyzed and their histological features were compared according to the level of serum CRP and the degree of mCRP deposition. Proteomic analysis was performed in AAA cases with strong and diffuse CRP immunopositivity (n = 7) and those with weak, focal, and junctional CRP immunopositivity (n = 3).
mCRP was deposited in the aortic specimens of AAA in a characteristic pattern that coincided with the lesion of the diminished elastic layer of the aortic wall. High serum CRP level was associated with stronger mCRP immunopositivity and a larger maximal diameter of aortic aneurysm. Proteomic analysis in AAA showed that multiple proteins were differentially expressed according to mCRP immunopositivity. Also, ingenuity pathway analysis showed that pathways associated with atherosclerosis, acute phase response, complement system, immune system, and coagulation were enriched in AAA cases with high mCRP immunopositivity.
AAA showed a characteristic deposition of mCRP, and multiple potentially pathologic signaling pathways were upregulated in AAA cases with strong CRP immunopositivity. mCRP and the aforementioned pathological pathways may serve as targets for managing the progression of AAA.
Mammalian oocytes remain arrested at the first prophase of meiosis in ovarian follicles for an extended period. During this protracted arrest, oocytes are remarkably susceptible to the accumulation ...of DNA damage. Melatonin (N‐acetyl‐5‐methoxytryptamine), a hormone secreted by the pineal gland, has diverse effects on various physiological processes. However, the effect of melatonin on DNA damage response in mammalian oocytes has not been explored. Here, we showed that melatonin protected mouse oocytes from DNA damage induced by double‐strand breaks (DSBs) during prophase arrest and subsequently improved oocyte quality. We found that DNA damage during prophase arrest impaired subsequent meiotic maturation and deteriorated oocyte quality, increasing chromosome fragmentation, spindle abnormality, mitochondrial aggregation, and oxidative stress. However, melatonin treatment during DNA damage accumulation at prophase improved meiotic maturation and relieved the quality decline of oocytes. In addition, melatonin inhibited the accumulation of DNA damage during prophase arrest by reducing the γ‐H2AX levels. Although activated ATM levels were decreased by melatonin treatment, the effect of melatonin on DNA damage response was not a direct consequence of ATM inhibition. Instead, melatonin enhanced DNA repair via nonhomologous end‐joining (NHEJ) pathway. Interestingly, these actions of melatonin on DNA damage response are receptor‐independent in mouse oocytes. Therefore, our results demonstrated that melatonin protects oocytes from DNA damage during prophase arrest by enhancing DNA repair via NHEJ and subsequently prevents the deterioration of oocyte quality during meiotic maturation.
Poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) is most commonly used as an anode buffer layer in bulk-heterojunction (BHJ) polymer solar cells (PSCs). However, its hygroscopic ...and acidic nature contributes to the insufficient electrical conductivity, air stability and restricted photovoltaic (PV) performance for the fabricated PSCs. In this study, a new multifunctional additive, 2,3-dihydroxypyridine (DOH), has been used in the PEDOT: PSS buffer layer to obtain modified properties for PEDOT: PSS@DOH and achieve high PV performances. The electrical conductivity of PEDOT:PSS@DOH films was markedly improved compared with that of PEDOT:PSS. The PEDOT:PSS@DOH film exhibited excellent optical characteristics, appropriate work function alignment, and good surface properties in BHJ-PSCs. When a poly(3-hexylthiohpene):6,6-phenyl C
-butyric acid methyl ester blend system was applied as the photoactive layer, the power conversion efficiency of the resulting PSCs with PEDOT:PSS@DOH(1.0%) reached 3.49%, outperforming pristine PEDOT:PSS, exhibiting a power conversion enhancement of 20%. The device fabricated using PEDOT:PSS@DOH (1.0 wt%) also exhibited improved thermal and air stability. Our results also confirm that DOH, a basic pyridine derivative, facilitates adequate hydrogen bonding interactions with the sulfonic acid groups of PSS, induces the conformational transformation of PEDOT chains and contributes to the phase separation between PEDOT and PSS chains.
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