Increased expression of Gab2, a scaffolding adaptor of the tyrosine kinase signalling, in gastric carcinomas

AIMS: Mounting evidence indicates that alterations of protein kinase signalling pathways play crucial roles in the pathogenesis of cancers. Gab2 (Grb2-associated binding protein 2), a member of the family of Gab scaffolding adaptors, transmits and amplifies the signals from receptor tyrosine kinases. A recent study demonstrated that Gab protein was over-expressed in breast cancers, and the over-expressed Gab2 increased proliferation and invasion of the cells, indicating that Gab2 is an oncogenic protein. However, the roles of Gab in other cancers are largely unknown. METHODS: In this study, to see whether Gab2 expression could be a characteristic of gastric cancers, we analysed the expression of Gab2 in 60 gastric adenocarcinomas by immunohistochemistry using a tissue microarray. RESULTS: In the normal gastric mucosal epithelial cells, Gab2 protein was expressed in parietal and zymogen cells, but not in other mucosal epithelial cells. In the cancer cells, Gab2 expression was detected in 40 (67%) of the 60 gastric adenocarcinomas. The Gab2 expression was observed in 12 (60%) of the 20 early gastric carcinomas and 28 (70%) of the 40 advanced gastric carcinomas. There was no significant association of Gab2 expression with clinocopathological characteristics, including invasion, metastasis and stage. CONCLUSION: Our data indicate that Gab2 over-expression is a feature not only of breast cancers, but also of gastric cancers. Increased expression of Gab2 in malignant gastric cells compared with normal epithelial cells suggests that Gab2 expression may play a role in gastric cancer development.     

A pilot study of Trabajadora de salud,a lay health worker intervention for Latinas/os with traumatic brain injuries and their caregivers

Background

Latinas/os with traumatic brain injuries (TBIs) and their caregivers experience worse outcomes than others.

Phosphatidylcholine attenuated docetaxel-induced peripheral neurotoxicity in rats

Docetaxel is a taxane chemotherapeutic agent used in the treatment of breast cancer, prostate cancer and gastric cancer, but several side effects such as peripheral neurotoxicity could occur. The present study was designed to investigate the therapeutic potential of phosphatidylcholine (PC) on docetaxel-induced peripheral neurotoxicity. Rats were randomly divided into three groups and treated for 4 weeks. Behavioral tests were conducted to measure the effects of PC on docetaxel-induced decreases in mechanical & thermal nociceptive threshold. Biochemical tests were conducted to measure the level of oxidative stress on sciatic nerve. Histopathological and immunohistochemical experiments were also conducted to assess neuronal damage and glial activation. PC treatment significantly attenuated docetaxel-induced changes in mechanical & thermal nociceptive response latencies. PC decreased oxidative stress in sciatic nerve by increasing antioxidant levels (glutathione, glutathione peroxidase and superoxide dismutase activity). In immunohistochemical evaluation, PC treatment ameliorated docetaxel-induced neuronal damage and microglial activation in the sciatic nerve and spinal cord. Thus, PC showed protective effects against docetaxel-induced peripheral neurotoxicity. These effects may be attributed to its antioxidant properties and modulation of microglia.     

Development of a simultaneous LC–MS/MS method to predict in vivo drug–drug interaction in mice

Cocktail substrates are useful in investigating drug–drug interactions (DDI) that can rapidly identify the cytochrome P450 (CYP) isoforms that interact with test drugs. In this study, we developed and validated five probe drugs for CYP1A, CYP2B, CYP2C, CYP2D, and CYP3A using LC–MS/MS to determine CYP activities in mice. The five probe substrates were caffeine (2 mg/kg), bupropion (30 mg/kg), omeprazole (4 mg/kg), dextromethorphan (40 mg/kg), and midazolam (2 mg/kg) for CYP1A, CYP2B, CYP2C, CYP2D, and CYP3A, respectively. The cocktail substrates were orally administered to male 5-week-old ICR mice over 0–240 min. The analytical method was validated; it showed high selectivity, linearity, and acceptable accuracy. We confirmed the lack of interaction of this cocktail in the control state (no effect of CYP inducer or inhibitor) and suggested AUC_ratio (metabolite/substrate) as a unit to evaluate DDI in vivo. In addition, the cocktail assay was applied for the determination of pharmacokinetic parameters against phenobarbital as a selective CYP2B inducer and ketoconazole as a strong CYP3A inhibitor. The concentration of cocktail substrates and the LC–MS/MS method were optimized. In conclusion, we developed a simultaneous and comprehensive analysis system for predicting potential DDI in mice.     

Health service utilization,unmet healthcare needs,and the potential of telemedicine services among Korean expatriates

Background

With the significant growth of migration and expatriation, facilitated by increased global mobility, the number of Koreans living abroad as of 2016 is approximately 7.4 million (15% of the Korean population). Healthcare utilization or health problems, especially among expatriates in developing countries, have not been well researched despite the various health risks these individuals are exposed to. Consequently, we identified the health utilization patterns and healthcare needs among Korean expatriates in Vietnam, Cambodia, and Uzbekistan.

Methods

This cross-sectional survey examined 429 Korean expatriates living in Vietnam (n?=?208), Cambodia (n?=?60), and Uzbekistan (n?=?161) who had access to the Internet and were living abroad for at least 6?months. A 67-item questionnaire was used, and feedback was received via an online survey program. Stepwise logistic regression analyses were performed to evaluate factors associated with unmet healthcare needs and preferences of certain type of telemedicine.

Results

We found that 45.5% (195/429) of respondents had used medical services in their country of stay. Among those who visited health institutions >?3 times, the most popular choice was general hospitals (39.4%, 15/38); however, they initially visited Korean doctors’ or local doctors’ offices. The most essential criteria for healthcare service facilities was a “skilled professional” (39.3%, 169/429), 42% wanted a health program for chronic disease management, and 30% wanted specialized internal medicine. A substantial number wanted to access telemedicine services and were willing to pay for this service. They were particularly interested in experts’ second opinion (61.5%, 264/429) and quick, 24-h medical consultations (60.8%, 261/429). Having unmet healthcare needs and being younger was strongly associated with all types of telemedicine networks.

Conclusions

Nearly half of the expatriates in developing countries had unmet healthcare needs. Telemedicine is one potential solution to meet these needs, especially in developing countries.

     

Early administration of appropriate antimicrobial agents to improve the outcome of carbapenem-resistant Acinetobacter baumannii complex bacteraemic pneumonia

Carbapenem-resistant Acinetobacter baumannii complex (CRABC) is an emerging pathogen that causes bloodstream infections and nosocomial pneumonia. This study aimed to describe severe infection associated with CRABC bacteraemic pneumonia and to investigate risk factors for 28-day mortality. All patients aged ≥18 years with CRABC bacteraemic pneumonia were enrolled retrospectively at five teaching hospitals in South Korea. Empirical antimicrobial therapy was defined as appropriate if administration of at least one antimicrobial agent, to which the causative pathogen was susceptible, for >48?h, within 5 days of the onset of bacteraemia. During the study period, 146 patients with CRABC bacteraemic pneumonia were enrolled. Among them, 128 (87.7%) patients were treated in the intensive care unit; of these, 110 (75.3%) had ventilator-associated pneumonia. A total of 42 patients (28.8%) received appropriate empirical therapy. There was no difference in baseline characteristics between the appropriate and inappropriate empirical treatment groups. However, 28-day mortality was higher in the inappropriate therapy group (54.8% vs. 76.9%; P?=?0.008). Multivariate Cox regression analysis revealed that Acute Physiology and Chronic Health Evaluation (APACHE) II score ≥20 [hazard ratio (HR)? =?1.28, 95% confidence interval (CI) 1.04–1.58; P?=?0.02], septic shock (HR?=?3.49, 95% CI 2.15–5.67; P?<0.001) and inappropriate empirical therapy (HR?=?3.24, 95% CI 1.94–5.42; P?<0.001) were independently associated with an adverse outcome. In conclusion, the mortality rate of CRABC bacteraemic pneumonia was extremely high. Appropriate empirical therapy might improve the outcome of patients with CRABC bacteraemic pneumonia.     

The Chinese and Korean American immigrant experience: a mixed-methods examination of facilitators and barriers of colorectal cancer screening

Objective: Among Asian Americans, colorectal cancer (CRC) is the second leading cause of cancer deaths. Despite strong evidence that screening can reduce CRC-related mortality, fewer Chinese and Koreans receive screening as compared to non-Hispanic whites and blacks. The objective of this study was to examine facilitators and barriers as well as strategies to promote CRC screening in this population.

Design: This study employed a mixed-methods design. We conducted 17 key informant interviews and 12 focus groups in the Washington, D.C. metropolitan area. 120 Chinese and Korean focus group participants, aged 50 to 85, also provided quantitative data through self-administered surveys. All participants were asked to discuss facilitators and barriers of CRC screening, including in relation to culture.

Results: Participants who had a regular physician and doctor’s recommendation for CRC screening were more likely to ever receive a colonoscopy (adjusted odds ratio (aOR)?=?3.51; 95% confidence interval (CI): 1.26, 9.79 and aOR?=?6.61; 95% CI: 2.63, 16.65, respectively). A doctor’s recommendation was also significantly associated with receipt of a fecal occult blood test (FOBT) (aOR?=?4.00; 95% CI: 1.43, 11.15). In terms of barriers, those who reported having no time and not having symptoms were less likely to have a colonoscopy (aOR?=?0.15; 95% CI: 0.03, 0.82 and aOR?=?0.02; 95% CI: 0.002, 0.23, respectively) than those who had time and symptoms. Preventive healthcare was often not viewed as a priority, particularly for those living the‘immigrant life,’ who gave precedence to work. Cultural barriers to CRC screening included language (e.g. limited English proficiency and low health literacy); fear of finding CRC and burdening the family especially children; fatalism; and stigma towards cancer.

Conclusions: Future interventions and programs aiming to increase CRC screening among Chinese and Korean Americans should address both cultural and non-cultural factors that influence CRC screening uptake.     

Seltene Erkrankungen in der Zahn‑, Mund- und Kieferheilkunde

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Am 25.&nbsp;November wurde unter der Schirmherrschaft von ACHSE e. V. und Orphanet erstmalig ein nationaler Kongress...     

The effect of almonds on vitamin E status and cardiovascular risk factors in Korean adults: a randomized clinical trial

Purpose

Almonds have shown to beneficially modify some cardiovascular risk factors in clinical trials conducted in diverse ethnic populations but this relationship has never been tested in Koreans. Thus, we tested the impact of almonds consumed as a snack within the context of a typical Korean diet on cardiovascular risk factors.

Methods

We conducted a randomized, crossover trial in a free-living setting with a 2-week run-in period, two 4-week intervention phases, and a 2-week washout period between interventions. Eighty four overweight/obese participants (11 M/73 F; 52.4 ± 0.6 year; 25.4 ± 0.22 kg/m²) consumed either 56 g of almonds or isocaloric cookies daily for 4 weeks.

Results

Mean % daily energy intake at baseline was 64.8, 21.3, and 14.9% from carbohydrate, fat, and protein, respectively. The addition of 56 g of almonds daily decreased carbohydrate energy to 55.0%, increased fat to 32.0%, and maintained protein at 14.7%. Consuming the almonds increased intake of MUFA by 192.3%, PUFA by 84.5%, vitamin E by 102.7%, and dietary fiber by 11.8% and decreased % energy from carbohydrate by 14.1%. Total caloric intake was increased by the almonds, but body weight, waist circumference, and body composition were not affected. Almonds in overweight and obese Korean adults decreased TC, LDL-C, and non-HDL-C by 5.5, 4.6, and 6.4%, respectively, compared to the cookie control (P ≤ 0.05). Almonds increased plasma α-tocopherol by 8.5% (P ≤ 0.05) from the baseline and tended to increase its value as compared to cookies (P = 0.055). Neither the almonds nor cookies altered plasma protein carbonyls, MDA or oxLDL. Of serum inflammatory markers, IL-10 was decreased by almond intake (P ≤ 0.05), and ICAM-1, IL-1β, and IL-6 tended to be lower with almonds, compared to the cookies.

Conclusions

Almonds at 56 g/day consumed as a snack favorably modified the Korean diet by increasing MUFA, PUFA, vitamin E, and dietary fiber intake and decreasing % energy intake from carbohydrate. Almonds also enhanced plasma α-tocopherol status and serum TC and LDL-C in overweight and obese Koreans. Thus, including almonds in typical Korean diets as a snack can help healthy overweight/obese individuals improve nutritional status and reduce their risk for CVD.