The Collaborative Approach for Asian Americans and Pacific Islanders Research and Education (CARE): A recruitment registry for Alzheimer's disease and related dementias, aging, and caregiver-related research.

INTRODUCTION: Clinical research focused on aging, Alzheimer's disease and related dementias (ADRD), and caregiving often does not recruit Asian Americans and Pacific Islanders (AAPIs). METHODS: With funding from the National Institute on Aging, we designed and launched the Collaborative Approach for AAPIs Research and Education (CARE), a research recruitment registry to increase AAPIs' participation in ADRD, aging, and caregiving research. We present the design of this novel recruitment program. RESULTS: CARE uses community-based participatory research methods that are culturally and linguistically appropriate. Since CARE's launch, it has enrolled >7000 AAPIs in a 1-year period. The majority enrolled in CARE via community organizations and reported never having participated in any kind of research before. CARE also engages researchers by establishing a recruitment referral request protocol. DISCUSSION: CARE provides a promising venue to foster meaningful inclusion of AAPIs who are under-represented in aging and dementia-related research.

Asian Americans' and Pacific Islanders' preferences in recruitment strategies and messaging for participation in the CARE registry: A discrete choice experiment.

INTRODUCTION: This discrete choice experiment (DCE) identified Asian American and Pacific Islander (AAPI) adults' preferences for recruitment strategies/messaging to enroll in the Collaborative Approach for AAPI Research and Education (CARE) registry for dementia-related research. METHODS: DCE recruitment strategy/messaging options were developed in English, Chinese, Korean, and Vietnamese. AAPI participants 50 years and older selected (1) who, (2) what, and (3) how they would prefer hearing about CARE. Analyses utilized conditional logistic regression. RESULTS: Participants self-identified as Asian Indian, Chinese, Filipino, Japanese, Korean, Samoan, or Vietnamese (N = 356). Overall, they preferred learning about CARE from the healthcare community (vs. community champions and faith-based organizations), joining CARE to advance research (vs. personal experiences), and hearing about CARE through social media/instant messaging (vs. flyer or workshop/seminar). Preferences varied by age, ethnic identity, and survey completion language. DISCUSSION: DCE findings may inform tailoring recruitment strategies/messaging to engage diverse AAPI in an aging-focused research registry.

Abietic acid alleviates endoplasmic reticulum stress and lipid accumulation in human primary hepatocytes through the AMPK/ORP150 signaling.

Abietic acid (AA), the main component of pine resin that has been traditionally used as Asian medicine, has been reported to demonstrate anti-inflammatory activities. Despite this, little is known about the effects of AA on hepatic endoplasmic reticulum (ER) stress and lipid metabolism. This study investigated the impacts of AA on ER stress and steatosis in in vitro obesity models. We found that Treatment with AA reduced lipid deposition and lipogenesis-related proteins expression in human primary hepatocytes. Augmented expression of ER stress markers (phospho-eukaryotic initiation factor-2α (eIF2α) and C/EBP homologous protein (CHOP)) in palmitate-treated hepatocytes were reversed by AA treatment. Further, AA treatment increased the expression of phospho-AMPK and oxygen-regulated protein 150 (ORP150) in hepatocytes. siRNA-associated knockdown of AMPK or ORP150 expression reduced the effects of AA on not only hepatic ER stress but also lipogenesis and apoptosis. These results denote that AA attenuates lipid accumulation in hepatocytes in the presence of palmitate through the suppression of ER stress by AMPK/ORP150 signaling. AA could be a potential candidate for treating non-alcoholic fatty liver disease.

Racial Bias Beliefs Related to COVID-19 Among Asian Americans, Native Hawaiians, and Pacific Islanders: Findings From the COVID-19 Effects on the Mental and Physical Health of Asian Americans and Pacific Islanders Survey Study (COMPASS).

BACKGROUND: During the COVID-19 pandemic, there have been increased reports of racial biases against Asian American and Native Hawaiian and Pacific Islander individuals. However, the extent to which different Asian American and Native Hawaiian and Pacific Islander groups perceive and experience (firsthand or as a witness to such experiences) how COVID-19 has negatively affected people of their race has not received much attention. OBJECTIVE: This study used data from the COVID-19 Effects on the Mental and Physical Health of Asian Americans and Pacific Islanders Survey Study (COMPASS), a nationwide, multilingual survey, to empirically examine COVID-19-related racial bias beliefs among Asian American and Native Hawaiian and Pacific Islander individuals and the factors associated with these beliefs. METHODS: COMPASS participants were Asian American and Native Hawaiian and Pacific Islander adults who were able to speak English, Chinese (Cantonese or Mandarin), Korean, Samoan, or Vietnamese and who resided in the United States during the time of the survey (October 2020 to May 2021). Participants completed the survey on the web, via phone, or in person. The Coronavirus Racial Bias Scale (CRBS) was used to assess COVID-19-related racial bias beliefs toward Asian American and Native Hawaiian and Pacific Islander individuals. Participants were asked to rate the degree to which they agreed with 9 statements on a 5-point Likert scale (ie, 1=strongly disagree to 5=strongly agree). Multivariable linear regression was used to examine the associations between demographic, health, and COVID-19-related characteristics and perceived racial bias. RESULTS: A total of 5068 participants completed the survey (mean age 45.4, SD 16.4 years; range 18-97 years). Overall, 73.97% (3749/5068) agreed or strongly agreed with ≥1 COVID-19-related racial bias belief in the past 6 months (during the COVID-19 pandemic). Across the 9 racial bias beliefs, participants scored an average of 2.59 (SD 0.96, range 1-5). Adjusted analyses revealed that compared with Asian Indians, those who were ethnic Chinese, Filipino, Hmong, Japanese, Korean, Vietnamese, and other or multicultural had significantly higher mean CRBS scores, whereas no significant differences were found among Native Hawaiian and Pacific Islander individuals. Nonheterosexual participants had statistically significant and higher mean CRBS scores than heterosexual participants. Compared with participants aged ≥60 years, those who were younger (aged <30, 30-39, 40-49, and 50-59 years) had significantly higher mean CRBS scores. US-born participants had significantly higher mean CRBS scores than foreign-born participants, whereas those with limited English proficiency (relative to those reporting no limitation) had lower mean CRBS scores. CONCLUSIONS: Many COMPASS participants reported racial bias beliefs because of the COVID-19 pandemic. Relevant sociodemographic contexts and pre-existing and COVID-19-specific factors across individual, community, and society levels were associated with the perceived racial bias of being Asian during the pandemic. The findings underscore the importance of addressing the burden of racial bias on Asian American and Native Hawaiian and Pacific Islander communities among other COVID-19-related sequelae.

Correction: Racial Bias Beliefs Related to COVID-19 Among Asian Americans, Native Hawaiians, and Pacific Islanders: Findings From the COVID-19 Effects on the Mental and Physical Health of Asian Americans and Pacific Islanders Survey Study (COMPASS).

[This corrects the article DOI: 10.2196/38443.].

A Study on Superior Mesoporous Activated Carbons for Ultra Power Density Supercapacitor from Biomass Precursors.

A kenaf-derived activated carbon (KAC) for a high-power density supercapacitor was developed in this study through phosphoric acid activation. The N2/77K isothermal adsorption-desorption curve was used to estimate the textural properties of KAC based on BET and BJH and the pore size distribution based on NLDFT. The electrochemical properties of KAC were analyzed by using the coin-type cell applying 1 M SPBBF4/PC electrolyte, and the specific surface area and total pore volume were 1490-1942 m2/g and 1.18-3.18 cm3/g, respectively. The pore characteristics of KAC varied according to the activation temperature, and most KAC showed a mesoporous structure. As the activation temperature increased, the mesopore volume increased up to 700 °C, then decreased. The mesoporous structure of KAC resulted in a substantial decrease in the Warburg impedance as the ion diffusion resistance decreased. Hence, the specific capacitance of KAC decreased from 82.9 F/g to 59.48 F/g as the charge-discharge rate increased from 1 mA/g to 10 mA/g, with the rate of reduction at approximately 30%. The rate of reduction of KAC's specific capacitance was 50% lower compared with commercial activated carbon; hence, KAC is a more suitable electrode-active material for high power density supercapacitors.

3-hydroxymorphinan enhances mitochondrial biogenesis and adipocyte browning through AMPK-dependent pathway.

3-hydroxymorphinan (3-HM), a metabolite of dextromethorphan, has previously been reported to have anti-inflammatory, anti-oxidative stress, and neuroprotective effects. However, its effect on energy metabolism in adipocytes remains unclear. Herein, we investigated 3-hydroxymorphinan (3-HM) effects on mitochondrial biogenesis, oxidative stress, and lipid accumulation in 3T3-L1 adipocytes. Further, we explored 3-HM-associated molecular mechanisms. Mouse adipocyte 3T3-L1 cells were treated with 3-HM, and various protein expression levels were determined by western blotting analysis. Mitochondria accumulation and lipid accumulation were measured by staining methods. Cell toxicity was assessed by cell viability assay. We found that treatment of 3T3-L1 adipocytes with 3-HM increased expression of brown adipocyte markers, such as uncoupling protein-1 (UCP-1) and peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α). 3-HM promotes mitochondrial biogenesis and its-mediated gene expression. Additionally, 3-HM treatment suppressed mitochondrial ROS generation and superoxide along with improved mitochondrial complex I activity. We found that treatment of 3-HM enhanced AMPK phosphorylation. siRNA-mediated suppression of AMPK reversed all these changes in 3T3-L1 adipocytes. In sum, 3-HM promotes mitochondrial biogenesis and browning and attenuates oxidative stress and lipid accumulation in 3T3-L1 adipocytes via AMPK signaling. Thus, 3-HM-mediated AMPK activation can be considered a therapeutic approach for treating obesity and related diseases.

Low molecular polypeptide from oyster hydrolysate recovers photoaging in SKH-1 hairless mice.

When the human skin is chronically exposed to external stimuli such as ultraviolet (UV) radiation, the skin tissue suffers damage and the structure of the extracellular matrix (ECM) in the skin is disrupted. This eventually causes symptoms such as wrinkles loss of elasticity, skin sagging, and skin cancer. We previously found that hydrolysate extracted from pacific oyster (Crassostrea gigas) is effective in improving wrinkle formation. In this study, we selected a pentapeptide that was expected to have the most wrinkle reduction effect among the various peptides in oyster hydrolysate through preliminary in vitro screening and examined whether the pentapeptide derived from oyster hydrolysate (OHP) is effective in reducing wrinkles in vivo. We investigated the wrinkle-reducing effect of the OHP through 18-week SKH-1 hairless mice model. Our results showed that the OHP reduces wrinkles lengths, depths, and epidermal thickness which were increased by UVB radiation, and restores the amount of collagen. The OHP recovered the activity of antioxidant enzymes and regulated the expression of proinflammatory cytokines. We also found that OHP increases the expression of type I collagen through stimulating the TGFß/Smad signaling pathway and inhibits the MMPs expression by regulating the MAPK/AP-1 signaling pathway. This study has shown that the OHP plays crucial roles in collagen production and wrinkle reduction in hairless mice and we proved the possibility of the OHP as a component for inhibiting wrinkle formation which was induced by photoaging.

Oral administration of oyster (Crassostrea gigas) hydrolysates protects against wrinkle formation by regulating the MAPK pathway in UVB-irradiated hairless mice.

Chronic ultraviolet (UV) irradiation induces wrinkle formation. UV exposure increases reactive oxygen species (ROS) and upregulates the expression of matrix metalloproteinases (MMPs), which results in skin photoaging. Oyster (Crassostrea gigas), which is an abundant food resource in Asia and Europe, contains various sources of biological compounds and has several effects. Also, oyster hydrolysate (OH) has many biological activities. We investigated the inhibitory effects of OH on wrinkle formation in UVB-irradiated hairless mice. We induced UVB irradiation in hairless mice for 18 weeks and administered OH orally from the 9th week to the 18th week. We performed skin replicas and histological analyses in UVB-irradiated hairless mice dorsal skins. To determine the inhibitory mechanism of OH on wrinkle formation, we measured gene and protein expressions in dorsal skin using RT-qPCR and western blot analyses respectively. In our study, OH decreases wrinkle formation, epidermal thickness and collagen degradation in UVB-irradiated hairless mice. The gene expressions of MMPs were decreased and the gene expressions of collagen type I and TIMP-1 were increased in OH administered groups. Like gene expression tendencies, the protein expressions of MMPs were reduced and that of collagen type I was increased. Furthermore, the phosphorylation levels of ERK, JNK, and p38 were reduced in OH administered groups. We found that OH inhibits wrinkle formation, skin thickening, and collagen degradation by downregulating the MMP expression via the regulation of phosphorylation of MAPK. The results showed that OH significantly prevents UVB-induced photoaging in dorsal skin. Consistent with in vivo data, OH has potential as an anti-wrinkle agent.

p-Coumaric acid stimulates longitudinal bone growth through increasing the serum production and expression levels of insulin-like growth factor 1 in rats.

The aim of the present study was to examine the effects of p-coumaric acid on the longitudinal growth of the long bone in adolescent male rats. Teatment with p-coumaric acid significantly increased the tibial length and the height of each growth plate zone and the ratio of 5-bromo-2'-deoxyuridine-positive cells relative to total proliferative cells. Expression of insulin-like growth factor 1 and its receptor in the proliferative and hypertrophic zones, and serum levels of growth hormone and insulin-like growth factor 1 were significantly increased as well in the p-coumaric acid-treated group. Via increasing both the serum level of insulin-like growth factor 1 and its expression, p-coumaric acid could promote cell proliferation in growth plate zones. These results suggest that p-coumaric acid has the potential to increase height and may be a feasible alternative to growth hormone therapy.

Value of stress ultrasound for the diagnosis of chronic ankle instability compared to manual anterior drawer test, stress radiography, magnetic resonance imaging, and arthroscopy.

PURPOSE: Clinicians frequently diagnose chronic ankle instability using the manual anterior drawer test and stress radiography. However, both examinations can yield incorrect results and do not reveal the extent of ankle instability. Stress ultrasound has been reported to be a new diagnostic tool for the diagnosis of chronic ankle instability. The purpose of this study was to assess the diagnostic value of stress ultrasound for chronic ankle instability compared to the manual anterior drawer test, stress radiography, magnetic resonance imaging (MRI), and arthroscopy. METHODS: Twenty-eight consecutive patients who underwent ankle arthroscopy and subsequent modified Broström repair for treatment of chronic ankle instability were included. The arthroscopic findings were used as the reference standard. A standardized physical examination (manual anterior drawer test), stress radiography, MRI, and stress ultrasound were performed to assess the anterior talofibular ligament (ATFL) prior to operation. Ultrasound images were taken in the resting position and the maximal anterior drawer position. RESULTS: Grade 3 lateral instability was verified arthroscopically in all 28 cases with a clinical diagnosis (100%). Twenty-two cases showed grade III instability on the manual anterior drawer test (78.6%). Twenty-four cases displayed anterior translation exceeding 5 mm on stress radiography (86%), and talar tilt angle exceeded 15° in three cases (11 %). Nineteen cases displayed a partial chronic tear (change in thickness or signal intensity), and nine cases displayed complete tear on MRI (100%). Lax and wavy ATFL was evident on stress ultrasound in all cases (100 %). The mean value of the ATFL length was 2.8 ± 0.3 cm for the stressed condition and 2.1 ± 0.2 cm for the resting condition (p < 0.001). CONCLUSION: Stress ultrasound may be useful for the diagnosis of chronic ankle instability in addition to the manual anterior drawer test and stress radiography. LEVEL OF EVIDENCE: III.

Factors affecting clinical outcomes after treatment of extra-articular open tibial fractures.

BACKGROUND: Tibial fractures are the most common long bone fracture and are often associated with severe soft tissue and bone defects. The objectives of our study were to describe the management and clinical results of patients with extra-articular open tibial fractures and to identify factors associated with a poor functional outcome. METHODS: This study included 82 adults available for follow-up for over 1 year after surgery. According to the AO Foundation/Orthopedic Trauma Association fracture classification, 26 fractures were type 41 A, 34 were type 42, and 22 were type 43 A. In accordance with the Gustilo-Anderson classification system, 31 were type I, 19 were type II, and 32 were type III. Initial nerve injury was confirmed in 18 cases. RESULTS: Definitive fixation occurred at a mean of 6.73 days (range, 0-16 days) after the injury. Soft tissue reconstruction was as follows: primary closure with debridement, 50 patients; split-thickness skin graft, 5; perforator based rotational flaps, 10; and free flaps, 17. Complications occurred in 29 cases (35.4%): superficial infection, 5 patients; deep infection, 3; primary suture site skin necrosis, 7; partial flap necrosis, 4; malalignment, 7; joint stiffness, 2; and hardware breakage, 1. Thirty additional operations (36.6%) were performed during the hospital stay. Mean bone union time was 20.4 weeks (range, 13-63 weeks) and the mean Lower Extremity Functional Scale score (LEFS) was 70.93 (range, 36-79). Multiple linear regression analysis indicated that skin defect size (p = 0.002), and occurrence of complications (p < 0.001) correlated with the LEFS score. CONCLUSION: Functional outcome after treatment of extra-articular open tibial fractures was influenced by the skin defect size and the presence of any complications. This suggests that good clinical results can be expected if complications are prevented through proper reduction, firm fixation, early soft tissue reconstruction, and early rehabilitation.

The chalcone compound isosalipurposide (ISPP) exerts a cytoprotective effect against oxidative injury via Nrf2 activation.

The chalcone compound isosalipurposide (ISPP) has been successfully isolated from the native Korean plant species Corylopsis coreana Uyeki (Korean winter hazel). However, the therapeutic efficacy of ISPP remains poorly understood. This study investigated whether ISPP has the capacity to activate NF-E2-related factor (Nrf2)-antioxidant response element (ARE) signaling and induce its target gene expression, and to determined the protective role of ISPP against oxidative injury of hepatocytes. In HepG2 cells, nuclear translocation of Nrf2 is augmented by ISPP treatment. Consistently, ISPP increased ARE reporter gene activity and the protein levels of glutamate cysteine ligase (GCL) and hemeoxygenase (HO-1), resulting in increased intracellular glutathione levels. Cells pretreated with ISPP were rescued from tert-butylhydroperoxide-induced reactive oxygen species (ROS) production and glutathione depletion and consequently, apoptotic cell death. Moreover, ISPP ameliorated the mitochondrial dysfunction and apoptosis induced by rotenone which is an inhibitor of complex 1 of the mitochondrial respiratory chain. The specific role of Nrf2 activation by ISPP was demonstrated using an ARE-deletion mutant plasmid and Nrf2-knockout cells. Finally, we observed that extracellular signal-regulated kinase (ERK) and AMP-activated protein kinase (AMPK), but not protein kinase C (PKC)-δ or other mitogen-activated protein kinases (MAPKs), are involved in the activation of Nrf2 by ISPP. Taken together, our results demonstrate that ISPP has a cytoprotective effect against oxidative damage mediated through Nrf2 activation and induction of its target gene expression in hepatocytes.

A current review for biological monitoring of manganese with exposure, susceptibility, and response biomarkers.

People can be easily exposed to manganese (Mn), the twelfth most abundant element, through various exposure routes. However, overexposure to Mn causes manganism, a motor syndrome similar to Parkinson disease, via interference of the several neurotransmitter systems, particularly the dopaminergic system in areas. At cellular levels, Mn preferentially accumulates in mitochondria and increases the generation of reactive oxygen species, which changes expression and activity of manganoproteins. Many studies have provided invaluable insights into the causes, effects, and mechanisms of the Mn-induced neurotoxicity. To regulate Mn exposure, many countries have performed biological monitoring of Mn with three major biomarkers: exposure, susceptibility, and response biomarkers. In this study, we review current statuses of Mn exposure via various exposure routes including food, high susceptible population, effects of genetic polymorphisms of metabolic enzymes or transporters (CYP2D6, PARK9, SLC30A10, etc.), alterations of the Mn-responsive proteins (i.e., glutamine synthetase, Mn-SOD, metallothioneins, and divalent metal trnsporter1), and epigenetic changes due to the Mn exposure. To minimize the effects of Mn exposure, further biological monitoring of Mn should be done with more sensitive and selective biomarkers.

Clinical effect of a polysaccharide-rich extract of Acanthopanax senticosus on alcohol hangover.

The present study aimed to examine the effects polysaccharide-rich extract of Acanthopanax senticosus (PEA) on blood alcohol concentration (BAC) and hangover as well as blood lab parameters. A randomized, placebo-controlled, double-blind crossover trial was conducted. The PEA was orally administered before and after consuming alcohol 1.75 g/kg of pure alcohol. After alcohol consumption, BAC was measured for evaluation of alcohol pharmacokinetics. In the second day morning, subjects were asked to complete the Acute Hangover Scale (AHS) questionnarie. BAC results showed little difference between placebo and PEA groups, indicating that PEA does not have an effect on the pharmacokinetics of alcohol. However, several AHS items (i.e., tired, headache, dizziness, stomachache and nausea) and AHS total score were significantly improved by PEA. Blood lab parameters were significantly altered by alcohol in the placebo group. The alteration by alcohol of glucose and C-reactive protein (CRP) level was significantly attenuated by PEA. Therefore, PEA may have potential to reduce the severity of the alcohol hangover by inhibiting the alcohol-induced hypoglycemia and inflammatory response.

Simultaneous determination of 7-O-succinyl macrolactin A and its active major metabolite, macrolactin A in dog plasma using high-performance liquid chromatography with UV detection.

We developed a method for the simultaneous quantification of 7-O-succinyl macrolactin A and its active metabolite, macrolactin A, in dog plasma. After protein precipitation with acetonitrile including flufenamic acid as an internal standard, 7-O-succinyl macrolactin A, macrolactin A, and flufenamic acid were chromatographed on a reverse-phase C18 analytical column. The mobile phase, consisting of 20 mM acetate buffer and acetonitrile, was eluted using a gradient program at 1 mL/min, and the UV absorbance was measured at 230 nm. The retention times of 7-O-succinyl macrolactin A, flufenamic acid, and macrolactin A were 3.4, 4.8, and 6.9 min, respectively. The coefficient of variation in the assay precision for both substances was less than 6%, and the accuracy ranged from 96 to 105%. This method was used to measure the concentrations of 7-O-succinyl macrolactin A and macrolactin A in dog plasma following an intravenous administration of a single dose (25 mg/kg) of 7-O-succinyl macrolactin A salt.

An 8-Year Prospective, Observational, Multi-centre Post-Marketing Safety Surveillance Study Conducted in South Korea (2014-2022) Following the Introduction of GSK's Inactivated Quadrivalent Seasonal Influenza Vaccine (Fluarix Tetra) for Subjects Aged 6 Months and Older.

INTRODUCTION: Seasonal influenza is associated with substantial public health burden. The objective of this study was to assess the safety of inactivated quadrivalent seasonal influenza vaccine (IIV4, Fluarix Tetra, GSK, Belgium) in subjects aged ≥ 6 months in Korea. METHODS: This prospective, observational, non-comparative, multi-centre post-marketing surveillance study was conducted in Korea in subjects aged ≥ 3 years for 6 years (2014-2020) and extended to subjects aged 6-35 months for 4 years (2018-2022). Subjects received IIV4 in routine clinical practice according to local prescribing information. Adverse events (AEs) were recorded over 21 days post-vaccination. RESULTS: The group aged ≥ 3 years included 701 subjects (mean 31.97 years, range 3-86 years, 46.36% male), and the group aged 6-35 months included 687 subjects (mean 16.31 months, 47.02% male). In the group aged ≥ 3 years, 98 subjects (13.98%) reported 140 AEs, of which 42 events in 34 subjects (4.85%) were adverse reactions to vaccine (ARVs). Most of the ARVs were expected, mainly administration site reactions. There were seven mild unexpected ARVs. In the group aged 6-35 months, 248 AEs were reported in 149/687 subjects (21.69%). ARVs were reported in 25/687 subjects (3.64%, 29 events); one was considered unexpected. There were five serious AEs overall, none of which were considered related. CONCLUSION: No safety concerns were found during this surveillance study of IIV4 in subjects aged ≥ 6 months in Korea. The findings of this study suggest IIV4 is safe and well tolerated for use in all age groups with a vaccine indication.

Seasonal influenza is associated with over 5000 deaths annually in Korea, mainly in older adults. Annual vaccination is the most effective way of preventing seasonal influenza. The influenza virus strains in the vaccine are updated each year as the strains circulating change constantly. Monitoring of any unwanted medical incidents (adverse events) after vaccination is required to help assess vaccine safety. In this study, we monitored adverse events reported within 21 days of administration of Fluarix Tetra seasonal influenza vaccine (IIV4) in participants aged 6 months and older in Korea over a period of 4­6 years. Of the participants aged ≥ 3 years, 98 (14%) reported 140 adverse events, most commonly infections and infestations (most commonly nasopharyngitis such as the common cold), or general disorders and administration site conditions (most commonly pain or swelling at the injection site). In the participants aged 6­35 months, 149 (22%) reported 248 adverse events, also most commonly infections and infestations (such as the common cold) or general disorders and administration site conditions (most commonly fever or swelling at the injection site). There were five serious adverse events in total (adverse events that are life threatening or require hospitalization), but none of them were related to IIV4. In this study, we did not find any safety concerns for IIV4 in participants aged ≥ 6 months in Korea. The findings of this study suggest IIV4 is safe and well tolerated in all age groups with a vaccine indication.

Effect of Kaempferol on Modulation of Vascular Contractility Mainly through PKC and CPI-17 Inactivation.

In this study, we investigated the efficacy of kaempferol (a flavonoid found in plants and plant-derived foods such as kale, beans, tea, spinach and broccoli) on vascular contractibility and aimed to clarify the detailed mechanism underlying the relaxation. Isometric contractions of divested muscles were stored and linked with western blot analysis which was carried out to estimate the phosphorylation of myosin phosphatase targeting subunit 1 (MYPT1) and phosphorylation-dependent inhibitory protein for myosin phosphatase (CPI-17) and to estimate the effect of kaempferol on the RhoA/ROCK/CPI-17 pathway. Kaempferol conspicuously impeded phorbol ester-, fluoride- and a thromboxane mimetic-derived contractions regardless of endothelial nitric oxide synthesis, indicating its direct effect on smooth muscles. It also conspicuously impeded the fluoride-derived elevation in phospho-MYPT1 rather than phospho-CPI-17 levels and phorbol 12,13-dibutyrate-derived increase in phospho-CPI-17 and phospho-ERK1/2 levels, suggesting the depression of PKC and MEK activities and subsequent phosphorylation of CPI-17 and ERK1/2. Taken together, these outcomes suggest that kaempferol-derived relaxation incorporates myosin phosphatase retrieval and calcium desensitization, which appear to be modulated by CPI-17 dephosphorylation mainly through PKC inactivation.

Prevalence and Burden of Carotid and Femoral Atherosclerosis in Subjects Without Known Cardiovascular Disease in a Large Community Hospital in South-America.

INTRODUCTION: Clinical guidelines recommend measurement of arterial (carotid and femoral) plaque burden by vascular ultrasound (VUS) as a risk modifier in individuals at low or moderate risk without known atherosclerotic cardiovascular disease (ASCVD). AIM: To evaluate the prevalence of carotid and femoral plaques by age and sex, the burden of subclinical atherosclerosis (SA), and its association with classic CVRF in subjects over 30 years of age without ASCVD. METHODS: We prospectively enrolled 5775 consecutive subjects referred for cardiovascular evaluation and determined the prevalence and burden of SA using 2D-VUS in carotid and femoral arteries. RESULTS: Sixty-one percent were men with a mean age of 51.3 (SD 10.6) years. Overall, plaque prevalence was 51% in carotid arteries, 39.3% in femoral arteries, 62.4% in carotid or femoral arteries, and 37.6% in neither. The prevalence of plaques and SA burden showed an increasing trend with age, being higher in men than in women and starting before the age of 40, both in the carotid and femoral sites. There was also an increasing prevalence of plaques according to the number of CVRF, and interestingly we found a high prevalence of plaques in subjects with 0 or 1 classic CVRF. CONCLUSIONS: We observed an increased prevalence and burden of carotid or femoral SA, higher in men, beginning before the fourth decade of life and increasing with age. Despite a significant association with classic CVRF, a significant number of subjects with low CVRF were diagnosed with SA.

Effects of Fluvastatin on the Pharmacokinetics of Repaglinide: Possible Role of CYP3A4 and P-glycoprotein Inhibition by Fluvastatin.

The purpose of this study was to investigate the effects of fluvastatin on the pharmacokinetics of repaglinide in rats. The effect of fluvastatin on P-glycoprotein and CYP3A4 activity was evaluated. The pharmacokinetic parameters and blood glucose concentrations were also determined after oral and intravenous administration of repaglinide to rats in the presence and absence of fluvastatin. Fluvastatin inhibited CYP3A4 activity in a concentration-dependent manner with a 50% inhibition concentration(IC50) of 4.1 µM and P-gp activity. Compared to the oral control group, fluvastatin significantly increased the AUC and the peak plasma level of repaglinide by 45.9% and 22.7%, respectively. Fluvastatin significantly decreased the total body clearance (TBC) of repaglinide compared to the control. Fluvastatin also significantly increased the absolute bioavailability (BA) of repaglinide by 46.1% compared to the control group. Moreover, the relative BA of repaglinide was 1.14- to 1.46-fold greater than that of the control. Compared to the i.v. control, fluvastatin significantly increased the AUC0-∞ of i.v. administered repaglinide. The blood glucose concentrations showed significant differences compared to the oral controls. Fluvastatin enhanced the oral BA of repaglinide, which may be mainly attributable to the inhibition of the CYP3A4-mediated metabolism of repaglinide in the small intestine and/or liver, to the inhibition of the P-gp efflux transporter in the small intestine and/or to the reduction of TBC of repaglinide by fluvastatin. The study has raised the awareness of potential interactions during concomitant use of repaglinide with fluvastatin. Therefore, the concurrent use of repaglinide and fluvastatin may require close monitoring for potential drug interactions.