Cerebrovascular disease is a potential risk factor for Alzheimer's disease (AD). Although acute cerebral hypoperfusion causes neuronal necrosis and infarction, chronic cerebral hypoperfusion induces ...apoptosis in neurons, but its effects on the cognitive impairment are not clear. The purpose of this study was to evaluate the effects of chronic cerebral hypoperfusion on AD pathology and cerebral glucose metabolism. A model of chronic cerebral hypoperfusion was established by ligating the common carotid arteries bilaterally in adult male rats (CAL group). Sham-operated rats underwent the same procedures without artery ligation (control group). At 12 weeks after ligation, expression levels of amyloid-β (Aβ) and hyperphosphorylated tau (p-tau), as well as the regional cerebral glucose metabolism, were evaluated using Western blots and positron emission tomography with fluorine-18 fluorodeoxyglucose, respectively. The expression levels of Aβ in the frontal cortex and hippocampus and of p-tau in the temporal cortex were significantly higher in the CAL group than those in the control group. The cerebral glucose metabolism of the amygdala, entorhinal cortex, and hippocampus was significantly decreased in the CAL group compared to that in the control. These results suggest that chronic cerebral hypoperfusion can induce AD pathology and may play a significant role in AD development.
Isolation due to the management of infectious diseases is thought to affect mental health, but the effects are still unknown. We examined the prevalence of anxiety symptoms and anger in persons ...isolated during the Middle East Respiratory Syndrome (MERS) epidemic both at isolation period and at four to six months after release from isolation. We also determined risk factors associated with these symptoms at four to six months.
Of 14,992 individuals isolated for 2-week due to having contact with MERS patients in 2015, when MERS was introduced to Korea, 1,692 individuals were included in this study. Anxiety symptoms were evaluated with the Generalized Anxiety Disorder 7-item scale and anger was assessed with the State-Trait Anger Expression Inventory at four to six months after release from isolation for MERS.
Of 1,692 who came in contact with MERS patients, 1,656 were not diagnosed with MERS. Among 1,656, anxiety symptoms showed 7.6% (95% confidence interval CI, 6.3 to 8.9%) and feelings of anger were present in 16.6% (95% CI, 14.8 to 18.4%) during the isolation period. At four to six months after release from isolation, anxiety symptoms were observed in 3.0% (95%CI, 2.2 to 3.9%). Feelings of anger were present in 6.4% (95% CI, 5.2 to 7.6%). Risk factors for experiencing anxiety symptoms and anger at four to six months after release included symptoms related to MERS during isolation, inadequate supplies (food, clothes, accommodation), social networking activities (email, text, Internet), history of psychiatric illnesses, and financial loss.
Mental health problems at four to six month after release from isolation might be prevented by providing mental health support to individuals with vulnerable mental health, and providing accurate information as well as appropriate supplies, including food, clothes, and accommodation.
An unsaturated polymer's
/
-olefin content has a significant influence on its properties. For polymers obtained by ring-opening metathesis polymerization (ROMP), the
/
-olefin content can be tuned by ...using specific catalysts. However,
-selective ROMP has suffered from narrow monomer scope and lack of control over the polymerization (giving polymers with broad molecular weight distributions and prohibiting the synthesis of block copolymers). Herein, we report the versatile
-selective controlled living ROMP of various
-tricyclo4.2.2.0
deca-3,9-diene and various norbornene derivatives using a fast-initiating dithiolate-chelated Ru catalyst. Polymers with
-olefin content as high as 99% could be obtained with high molecular weight (up to
of 105.1 kDa) and narrow dispersity (<1.4). The living nature of the polymerization was also exploited to prepare block copolymers with high
-olefin content for the first time. Furthermore, owing to the successful control over the stereochemistry and narrow dispersity, we could compare
- and
-rich polynorbornene and found the former to have enhanced resistance to shear degradation.
DMNs with dual-release pattern for prime and boost immunization of HBsAg; CMC coating formulation for bolus release of HBsAg, PLA tip for slow release of HBsAg, PVA/PVP base for delivery of two ...formulations after insertion into skin.
Schematic image of dissolving microneedles with dual-release pattern. Insertion of HBsAg-PLA/CMC-DMNs into skin, dissolution of PVA/PVP base, bolus release of HBsAg from coating part, remaining PLA tip, slow release of HBsAg from PLA tip.
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In this study, dissolving microneedles (DMNs) with dual-release pattern, capable of both bolus release and slow release, were prepared. These DMNs were used with a hepatitis B vaccine that requires multiple shots to achieve immunological efficacy comparable to that obtained when two separate shots are administered.
Dissolving microneedles with HBsAg in PLA tips and CMC coating formulation together (HBsAg-PLA/CMC-DMNs) consist of polylactic acid (PLA) tips for slow release, a carboxy-methyl cellulose (CMC) coating formulation for bolus release, and a dissolving base of polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP) for dissolution in the skin. The in vitro release pattern of HBsAg from the CMC coating formulation and PLA tips was observed. Through an in vivo test, 1) the delivery efficiency of HBsAg-PLA/CMC-DMNs was observed, and 2) the immunological efficacy of this method was compared with the efficacy of two shots delivered by conventional intramuscular (IM) administration and two shots delivered by HBsAg-coated microneedle (CMNs) administration. HBsAg-PLA/CMC-DMNs punctured the skin successfully. The PVA/PVP base was completely dissolved within 10 min of insertion, resulting in the delivery of all microneedle tips into the skin. In the in vitro release experiment, all of the HBsAg in the CMC coating formulation was released within 20 min, and the HBsAg present in the PLA tips was gradually released over more than 55 days. The antibody titer of one shot of HBsAg-PLA/CMC-DMNs was the same as or higher than two shots delivered by conventional IM and CMN methods. DMNs with dual-release pattern can deliver two formulations simultaneously with a single shot, resulting in improved immunological efficacy of HBsAg that requires multiple doses. In addition, this dual-release MN system can be used for the delivery of other drugs that require multiple administrations.
Articular cartilage has been considered unsuitable as a load-bearing structure with the properties measured by the conventional compression test. To measure the material properties of cartilage as a ...load-bearing structure, four porcine hip joints were used, and a compressive load of 650 N was applied in a standing position. Cartilage deformation over time was observed by performing CT scans five times at 3-min intervals while the load was applied. In order to secure the cartilage properties of the samples used in the test, a conventional compression test was performed using a cartilage plug taken from each sample. A 3D femoro-acetabular joint finite element model was created from the CT images to simulate the hip joint compression test and compared with experiments results. Then, the deformation of the cartilage obtained from the CT image was optimized as an objective function, and the measured cartilage properties obtained from the conventional compression test were compared with the optimized properties. The femoro-acetabular joint simulation to which the measured properties were applied failed to converge. Young's modulus and Poisson’s ratio of cartilages optimized through optimization were approximately 19.6 and 1.7 times greater than the measured values, respectively. However, permeable parameters did not show significant differences between the optimized and measured values. Our results show this optimization method offers the potential to overcome the challenges associated with acquiring accurate boundary conditions for articular cartilage, ultimately facilitating the generation of realistic deformation patterns in in-vivo situations.
Understanding the stability and reactivity of the propagating species is critical in living polymerization. Therefore, most living olefin metathesis polymerizations require the stabilization of the ...catalyst by coordination of external ligands containing Lewis basic heteroatoms, e.g., phosphines and pyridines. However, in some cases, chemists postulated that the propagating metal carbene could also be stabilized by olefin chelation. Here, we disclose that stable 16-electron olefin-chelated Ru carbenes play a key role in previously reported living/controlled ring-opening metathesis polymerization of endo-tricyclo4.2.2.02,5deca-3,9-diene and cyclopolymerization of 1,8-nonadiynes using Grubbs catalysts. We successfully isolated these propagating species during polymerization and confirmed their olefin-chelated structures using X-ray crystallography and NMR analysis. DFT calculations and van ’t Hoff plots from the equilibrium between olefin-chelated Ru carbenes and 3-chloropyridine (Py)-coordinated carbenes revealed that entropically favored olefin chelation overwhelmed enthalpically more stable Py-coordinated Ru carbenes at room temperature. Therefore, olefin chelation stabilized the propagating species and slowed down the propagation relative to initiation, thereby lowering polydispersity. This finding provides a deeper understanding of the olefin metathesis polymerization mechanism using Grubbs catalysts and offers clues for designing new controlled/living polymerizations.
The facial artery is the main artery supplying blood to the face and is known to have facial branches of the inferior labial, superior labial, lateral nasal and angular arteries. These known major ...branches of facial artery run medially, however, there are sometimes branches of the facial artery heading laterally. The purpose of the present study was to investigate the lateral branches of the facial artery in face. We dissected facial branches of the facial artery in 74 cadaveric hemifaces. We investigated the presence of the lateral branches of the facial artery. Following parameters were investigated: lateral branch presence, the location of its origin, and the lateral branch diameter. Among the lateral branches, we evaluated the prevalence and diameter of the premasseteric branch. Lateral branches were observed in 48 of the 74 hemifaces (64.9%). The total number was 81 in the 48 hemifaces. The most common origin was between the inferior border of the mandible and inferior labial artery origin (42 of 81, 51.9%). The mean diameter of all lateral branches of the facial artery was 0.7 mm. Among the lateral branches, the premasseteric branches were present in 38 of 74 specimen (51.4%) and the mean diameter was 0.8 mm. The lateral branches of the facial artery may be registered in Terminologia Anatomica based on their prevalence. Accurate knowledge of the anatomy of the lateral branches of the facial artery is helpful for clinicians to avoid complications during facial procedures or maxillofacial surgeries.
Abstract Background The goal of this study is to better understand the trend in epidemiological features and the outcomes of emergency medical service (EMS)-assessed out-of-hospital cardiac arrest ...(OHCA) according to the community urbanization level: metropolitan, urban, and rural. Methods This study was performed within a nationwide EMS system with a single-tiered basic-to-intermediate service level and approximately 900 destination hospitals for eligible OHCA cases in South Korea (with 48 million people). A nationwide OHCA database, which included information regarding demographics, Utstein criteria, EMS, and hospital factors and outcomes, was constructed using the EMS run sheets of eligible cases who were transported by 119 EMS ambulances and followed by a medical record review from 2006 to 2010. Cases with an unknown outcome were excluded. The community urbanization level was categorized according to population size, with metropolitan areas (more than 500,000 residents), urban areas (100,000–500,000 residents), and rural areas (<100,000 residents). The primary end point was the survival to discharge rate. Age- and sex-adjusted survival rates (ASRs) and standardized survival ratios (SSRs) with 95% confidence intervals (CIs) were calculated compared to a standard population. The adjusted odds ratios (AORs) and 95% CIs for survival were calculated and adjusted for potential risk factors using stratified multivariable logistic regression analysis. Results There were 97,291 EMS-assessed OHCAs with 73,826 (75.9%) EMS-treated cases analyzed, after excluding the patients with unknown outcome ( N = 4172). The standardized incidence rate increased from 37.5 in 2006 to 46.8 in 2010 per 100,000 person-years for EMS-assessed OHCAs, and the survival rate was 3.0% for EMS-assessed OHCAs (3.3% for cardiac etiology and 2.3% for non-cardiac etiology) and 3.6% for EMS-treated OHCAs. Significantly different trends were found by urbanization level for bystander CPR, EMS performance, and the level of the destination hospital. The ASRs for survival were significantly improved by year in the metropolitan areas (3.6% in 2006 to 5.3% in 2010) but remained low in the urban areas (1.4% in 2006 to 2.3% in 2010) and very low in the rural areas (0.5 in 2006 and 0.8 in 2010). The SSRs (95% CIs) in the metropolitan areas were 1.19 (1.06–1.34) in 2006 and 1.77 (1.64–1.92) in 2010, whereas the SSRs were observed to be less than 1.00 during the five-year period in both urban and rural areas. The AORs (95% CIs) for survival significantly increased to 1.42 (1.22–1.66) in the metropolitan areas and to 1.58 (1.18–2.11) in the urban areas while not increasing in the rural areas, compared to the level of each group of areas in 2006. Conclusions In this nationwide cohort study from 2006 to 2010, the standardized incidence rate and survival to discharge rate of EMS-assessed OHCAs increased annually in metropolitan and urban communities but did not increase in rural communities. Further investigations should be undertaken to improve the performance and outcomes in rural communities.
Herein, we report the development of a scalable and synthetically robust building block based on norbornadiene (NBD) that can be broadly incorporated into a variety of macromolecular architectures ...using traditional living polymerization techniques. By taking advantage of a selective and rapid deprotection with tetrazine, highly reactive “masked” cyclopentadiene (Cp) functionalities can be introduced into synthetic polymers as chain-end groups in a quantitative and efficient manner. The orthogonality of this platform further enables a cascade “click” process where the “unmasked” Cp can rapidly react with dienophiles, such as maleimides, through a conventional Diels–Alder reaction. Coupling proceeds with quantitative conversions allowing high molecular weight star and dendritic block copolymers to be prepared in a single step under ambient conditions.
Studies into the cyclopolymerization (CP) of diyne derivatives using metal carbenes have focused on the formation of five- and six-membered rings because these small rings can be easily synthesized ...while the preparation of medium-sized seven-membered rings are more difficult. For the first time, we achieved the CP forming challenging seven-membered rings as repeat units using Grubbs catalysts by novel design of 1,8-nonadiyne monomers. The key to the successful CP was the introduction of the appropriate aminal and acetal groups, which have short C–N and C–O bonds, and low rotational barriers, thus greatly enhancing the cyclization efficiency. During our mechanistic investigation, we directly observed an actual 14-electron Ru propagating carbene by 1H NMR spectroscopy for the first time during olefin metathesis reaction, presumably because the great steric hindrance from the propagating carbene containing a larger seven-membered ring than five- or six-membered ring retarded the coordination of ligands. We also observed decomposition of the catalysts to ruthenium hydrides during polymerization for the first time. Kinetic studies revealed three interesting features of this 1,8-nonadiyne CP: (i) in contrast to conventional polymerizations, the rate-determining step for the CP of 1,8-nonadiynes was the cyclization step; (ii) the intrinsic reactivity of the acetal monomers was higher than that of the aminal monomers; but (iii) the overall polymerization efficiency of the aminal monomers was higher than that of the acetal monomers because of the higher stability of their carbenes. Finally, we achieved a controlled CP of the aminal monomers using a fast-initiating third-generation Grubbs catalyst. This allowed the synthesis of not only the diblock copolymer containing five- and seven-membered rings but also the triblock copolymer containing five-, six-, and seven-membered rings.
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