Sympathetic innervation of interscapular brown adipose tissue is not a predominant mediator of oxytocin-elicited reductions of body weight and adiposity in male diet-induced obese mice.

Previous studies indicate that CNS administration of oxytocin (OT) reduces body weight in high fat diet-induced obese (DIO) rodents by reducing food intake and increasing energy expenditure (EE). We recently demonstrated that hindbrain (fourth ventricular [4V]) administration of OT elicits weight loss and elevates interscapular brown adipose tissue temperature (T IBAT , a surrogate measure of increased EE) in DIO mice. What remains unclear is whether OT-elicited weight loss requires increased sympathetic nervous system (SNS) outflow to IBAT. We hypothesized that OT-induced stimulation of SNS outflow to IBAT contributes to its ability to activate BAT and elicit weight loss in DIO mice. To test this hypothesis, we determined the effect of disrupting SNS activation of IBAT on the ability of 4V OT administration to increase T IBAT and elicit weight loss in DIO mice. We first determined whether bilateral surgical SNS denervation to IBAT was successful as noted by ≥ 60% reduction in IBAT norepinephrine (NE) content in DIO mice. NE content was selectively reduced in IBAT at 1-, 6- and 7-weeks post-denervation by 95.9±2.0, 77.4±12.7 and 93.6±4.6% ( P <0.05), respectively and was unchanged in inguinal white adipose tissue, pancreas or liver. We subsequently measured the effects of acute 4V OT (1, 5 µg ≈ 0.99, 4.96 nmol) on T IBAT in DIO mice following sham or bilateral surgical SNS denervation to IBAT. We found that the high dose of 4V OT (5 µg ≈ 4.96 nmol) elevated T IBAT similarly in sham mice as in denervated mice. We subsequently measured the effects of chronic 4V OT (16 nmol/day over 29 days) or vehicle infusions on body weight, adiposity and food intake in DIO mice following sham or bilateral surgical denervation of IBAT. Chronic 4V OT reduced body weight by 5.7±2.23% and 6.6±1.4% in sham and denervated mice ( P <0.05), respectively, and this effect was similar between groups ( P =NS). OT produced corresponding reductions in whole body fat mass ( P <0.05). Together, these findings support the hypothesis that sympathetic innervation of IBAT is not necessary for OT-elicited increases in BAT thermogenesis and reductions of body weight and adiposity in male DIO mice.

Shigella sonnei utilises colicins during inter-bacterial competition.

The mammalian colon is one of the most densely populated habitats currently recognised, with 1011-1013 commensal bacteria per gram of colonic contents. Enteric pathogens must compete with the resident intestinal microbiota to cause infection. Among these enteric pathogens are Shigella species which cause approximately 125 million infections annually, of which over 90 % are caused by Shigella flexneri and Shigella sonnei. Shigella sonnei was previously reported to use a Type VI Secretion System (T6SS) to outcompete E. coli and S. flexneri in in vitro and in vivo experiments. S. sonnei strains have also been reported to harbour colicinogenic plasmids, which are an alternative anti-bacterial mechanism that could provide a competitive advantage against the intestinal microbiota. We sought to determine the contribution of both T6SS and colicins to the anti-bacterial killing activity of S. sonnei. We reveal that whilst the T6SS operon is present in S. sonnei, there is evidence of functional degradation of the system through SNPs, indels and IS within key components of the system. We created strains with synthetically inducible T6SS operons but were still unable to demonstrate anti-bacterial activity of the T6SS. We demonstrate that the anti-bacterial activity observed in our in vitro assays was due to colicin activity. We show that S. sonnei no longer displayed anti-bacterial activity against bacteria that were resistant to colicins, and removal of the colicin plasmid from S. sonnei abrogated anti-bacterial activity of S. sonnei. We propose that the anti-bacterial activity demonstrated by colicins may be sufficient for niche competition by S. sonnei within the gastrointestinal environment.

Diagnostic performance of magnetic resonance imaging for diagnosing acute appendicitis during pregnancy.

OBJECTIVE: This retrospective study evaluated the diagnostic efficacy of magnetic resonance imaging (MRI) for identifying acute appendicitis during pregnancy. PATIENTS AND METHODS: This retrospective study enrolled a total of 46 pregnant patients with clinically suspected acute appendicitis who underwent 1.5 T MRI and received a final pathological diagnosis. We evaluated the imaging characteristics associated with patients diagnosed with acute appendicitis, including the appendix diameter, the appendix wall thickness, intra-appendiceal fluid collection, and peri-appendiceal fat infiltration. A bright appendix on T1-weighted 3-dimensional imaging was identified as a negative sign for appendicitis. RESULTS: Peri-appendiceal fat infiltration had the highest specificity of 97.1% for diagnosing acute appendicitis, whereas increasing appendiceal diameter had the highest sensitivity of 91.7%. The cut-off values for increasing appendiceal diameter and appendiceal wall thickness were 6.55 mm and 2.7 mm, respectively. Using these cut-off values, appendiceal diameter had a sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) of 91.7%, 91.2%, 78.4%, and 96.9%, respectively, whereas these values for appendiceal wall thickness were 75.0%, 91.2%, 75.0%, and 91.2%. The combination of increasing appendiceal diameter and appendiceal wall thickness resulted in an area under the receiver operating characteristic curve value of 0.958 with Se, Sp, PPV, and NPV values of 75.0%, 100.0%, 100.0%, and 91.9%, respectively. CONCLUSIONS: All five MRI signs examined in this study had significant diagnostic value for detecting acute appendicitis during pregnancy, with p-values <0.01. The combined use of increasing appendiceal diameter and appendiceal wall thickness displayed the excellent ability to diagnose acute appendicitis in pregnant women.

Residency application content and considerations based on residency director review of a fictitious CV: What really matters?

PURPOSE: This research was conducted to evaluate the influence of a pharmacy residency candidate's prior work or research experience on the potential for selection for an interview. Additionally, residency program directors (RPDs) were asked to evaluate the importance of letters of intent and recommendation, rank the importance of typical curriculum vitae (CV) items along with general preferences, and provide advice for a standout CV. METHODS: This cross-sectional, survey-based study recruited RPDs to review a work-focused or research-focused fictitious residency candidate CV and complete a 33-question survey regarding interest in interviewing the fictitious candidate and their general perceptions of significant factors in interview candidate selection. RESULTS: A total of 456 RPDs responded to the survey, with 229 respondents assigned to evaluate the work-focused CV and 227 assigned to review the research-focused CV. Among RPDs who provided CV evaluations, 81.2% (147/181) of those who reviewed the research-focused CV and 78.3% (137/175) of those who reviewed the work-focused CV gave a positive evaluation (P > 0.05). Work experience and extracurricular activities were considered the most important CV sections, and high-quality advanced pharmacy practice experience (APPE) rotations and pharmacy work experience were perceived to have the highest correlation with success in residency. CONCLUSION: This work supports the importance of candidates creating a well-rounded CV in preparing themselves for residency. Pharmacy-related work experience and high-quality APPE rotations seem to be key in an RPD's opinions of predicted success in a residency program. The CV remains a vital document in the residency candidate review process, and it deserves a high degree of effort in ensuring it adequately reflects professional experiences.

Feline panleukopenia virus DNA shedding following modified live virus vaccination in a shelter setting.

This study assessed the frequency and timing of feline panleukopenia virus (FPV) shedding in feces following administration of a modified live FPV vaccine. Feces were collected from 37 shelter cats that did not meet clinical criteria for panleukopenia on the day of vaccination or on days 3, 7, 14, and 21 post-vaccination (NCL group). A commercial quantitative PCR (qPCR) fecal pathogen panel and a canine parvovirus point-of-care antigen test were performed. FPV DNA copy numbers from a concurrent study of 39 cats with panleukopenia (CL group) were compared with the NCL group. Of the 165 samples from the NCL group, one had a weak positive antigen test result on day 7, while nine samples (5.5%) from eight cats (21.6%) produced positive FPV qPCR test results, one on day 3 and eight on day 7. There were no day 21-positive qPCR results in the 11 cats that were revaccinated on day 14. There was no association between the number of additional fecal pathogens identified and a positive FPV qPCR result. Of the cats with positive results, FPV DNA copy numbers differed between NCL group and CL group (median 1.13 × 107 and 5.01 × 108 copies/g feces, respectively; P < 0.001). The FPV qPCR cannot differentiate subclinical infection from vaccine virus shedding. To avoid unnecessary isolation and euthanasia, shelters should therefore limit FPV PCR testing to cats with a high index of suspicion of panleukopenia. The timing of recent vaccination should also be considered when interpreting test results.

School problems among left-behind children of labor migrant parents: a study in Vietnam.

BACKGROUND: Many studies have shown the effects of parental migration on the psychological and daily life of left-behind children (LBC) of labor migrant parents, but the results on school-related problems of LBC remain inconsistent. Additionally, there is a dearth of research on the factors affecting school problems among LBC, especially in the socio-cultural context of Vietnam. The purpose of this study was to confirm the school problems encountered by LBC in comparison with non-left-behind children (non-LBC). The study also aimed to examine variables of bonding of caregivers with children and resilience of children affecting school problems of LBC. PARTICIPANTS AND PROCEDURE: The convenient sampling approach was used in the study. The study sample included 792 Vietnamese school students (Mage = 12.65, SD = 1.60), with 439 children of labor migrant parents and a control group of 353 children of non-migrant parents. The School Problem Questionnaire, Parental Bonding Instrument and the Resilience Scale were employed in this study. RESULTS: There was no difference in school problems between the LBC and non-LBC groups. Resilience by goal planning (RGP), resilience by affect control (RAC), and resilience by family support (RFS) were identified as protective variables for children to overcome difficulties encountered in schools, with regression coefficients of -.21, -.33 and -.20, respectively. Meanwhile, bonding of caregivers with children by control (BCCo), and resilience by positive thinking (RPT) were found to be factors that increase school problems among LBC with the same regression coefficient of .12. CONCLUSIONS: Activities to support LBC should pay attention to improving resilience, namely affect control, goal planning, and promoting the role of caregivers for LBC.

Hindbrain Administration of Oxytocin Reduces Food Intake, Weight Gain and Activates Catecholamine Neurons in the Hindbrain Nucleus of the Solitary Tract in Rats.

Existing studies show that CNS oxytocin (OT) signaling is important in the control of energy balance, but it is unclear which neurons may contribute to these effects. Our goals were to examine (1) the dose-response effects of acute OT administration into the third (3V; forebrain) and fourth (4V; hindbrain) ventricles to assess sensitivity to OT in forebrain and hindbrain sites, (2) the extent to which chronic 4V administration of OT reduces weight gain associated with the progression of diet-induced obesity, and (3) whether nucleus tractus solitarius (NTS) catecholamine neurons are downstream targets of 4V OT. Initially, we examined the dose-response effects of 3V and 4V OT (0.04, 0.2, 1, or 5 µg). 3V and 4V OT (5 µg) suppressed 0.5-h food intake by 71.7 ± 6.0% and 60 ± 12.9%, respectively. 4V OT (0.04, 0.2, 1 µg) reduced food intake by 30.9 ± 12.9, 42.1 ± 9.4, and 56.4 ± 9.0%, respectively, whereas 3V administration of OT (1 µg) was only effective at reducing 0.5-h food intake by 38.3 ± 10.9%. We subsequently found that chronic 4V OT infusion, as with chronic 3V infusion, reduced body weight gain (specific to fat mass) and tended to reduce plasma leptin in high-fat diet (HFD)-fed rats, in part, through a reduction in energy intake. Lastly, we determined that 4V OT increased the number of hindbrain caudal NTS Fos (+) neurons (156 ± 25) relative to vehicle (12 ± 3). The 4V OT also induced Fos in tyrosine hydroxylase (TH; marker of catecholamine neurons) (+) neurons (25 ± 7%) relative to vehicle (0.8 ± 0.3%). Collectively, these findings support the hypothesis that OT within the hindbrain is effective at reducing food intake, weight gain, and adiposity and that NTS catecholamine neurons in addition to non-catecholaminergic neurons are downstream targets of CNS OT.

Effects of Combined Oxytocin and Beta-3 Receptor Agonist (CL 316243) Treatment on Body Weight and Adiposity in Male Diet-Induced Obese Rats.

Previous studies have indicated that oxytocin (OT) reduces body weight in diet-induced obese (DIO) rodents through reductions in energy intake and increases in energy expenditure. We recently demonstrated that hindbrain [fourth ventricular (4V)] administration of OT evokes weight loss and elevates interscapular brown adipose tissue temperature (T IBAT ) in DIO rats. What remains unclear is whether OT can be used as an adjunct with other drugs that directly target beta-3 receptors in IBAT to promote BAT thermogenesis and reduce body weight in DIO rats. We hypothesized that the combined treatment of OT and the beta-3 agonist, CL 316243, would produce an additive effect to decrease body weight and adiposity in DIO rats by reducing energy intake and increasing BAT thermogenesis. We assessed the effects of 4V infusions of OT (16 nmol/day) or vehicle (VEH) in combination with daily intraperitoneal injections of CL 316243 (0.5 mg/kg) or VEH on food intake, T IBAT , body weight and body composition. OT and CL 316243 alone reduced body weight by 7.8 ± 1.3% (P < 0.05) and 9.1 ± 2.1% (P < 0.05), respectively, but the combined treatment produced more pronounced weight loss (15.5 ± 1.2%; P < 0.05) than either treatment alone. These effects were associated with decreased adiposity, adipocyte size, energy intake and increased uncoupling protein 1 (UCP-1) content in epididymal white adipose tissue (EWAT) (P < 0.05). In addition, CL 316243 alone (P < 0.05) and in combination with OT (P < 0.05) elevated T IBAT and IBAT UCP-1 content and IBAT thermogenic gene expression. These findings are consistent with the hypothesis that the combined treatment of OT and the beta-3 agonist, CL 316243, produces an additive effect to decrease body weight. The findings from the current study suggest that the effects of the combined treatment on energy intake, fat mass, adipocyte size and browning of EWAT were not additive and appear to be driven, in part, by transient changes in energy intake in response to OT or CL 316243 alone as well as CL 316243-elicited reduction of fat mass and adipocyte size and induction of browning of EWAT.

Determining student-level characteristics predictive of successful matching in PGY1 community-based residency programs: A curriculum vitae analysis.

INTRODUCTION: The purpose of this analysis was to determine which characteristics increase a candidate's likelihood of matching with a post-graduate year 1 (PGY1) community-based residency program (CBRP). METHODS: Current and former CBRP residents' curriculum vitae (CVs) were collected and reviewed utilizing a survey and standardized rubric. Eligible participants were current PGY1 CBRP residents or had completed a PGY1 program no earlier than 2015. Primary endpoints included number of participants with extensive leadership experience, relevant experiential rotations, presentation history, and involvement in pharmacy organizations. Descriptive statistics were performed to identify the most common characteristics and their relative quantities. RESULTS: A total of 50 eligible CVs were submitted and reviewed. The majority of participants had extensive (defined as four or more) presentation experiences, at least three mid- to high-level leadership experiences, multiple ambulatory/outpatient pharmacy experiential rotations, and involvement in pharmacy organizations. Few participants (26%) had previous teaching experience. CONCLUSIONS: Residency candidates who matched with CBRPs tended to have extensive mid- to high-level leadership experiences and presentation experience. Based on these findings, additional studies are warranted to compare existing and/or redesigned postgraduate training preparation curricula and their impact on residency match rates.

Chronic hindbrain administration of oxytocin elicits weight loss in male diet-induced obese mice.

Previous studies indicate that oxytocin (OT) administration reduces body weight in high-fat diet (HFD)-induced obese (DIO) rodents through both reductions in food intake and increases in energy expenditure. We recently demonstrated that chronic hindbrain [fourth ventricular (4V)] infusions of OT evoke weight loss in DIO rats. Based on these findings, we hypothesized that chronic 4V OT would elicit weight loss in DIO mice. We assessed the effects of 4V infusions of OT (16 nmol/day) or vehicle over 28 days on body weight, food intake, and body composition. OT reduced body weight by approximately 4.5% ± 1.4% in DIO mice relative to OT pretreatment body weight (P < 0.05). These effects were associated with reduced adiposity and adipocyte size [inguinal white adipose tissue (IWAT)] (P < 0.05) and attributed, in part, to reduced energy intake (P < 0.05) at a dose that did not increase kaolin intake (P = NS). OT tended to increase uncoupling protein-1 expression in IWAT (0.05 < P < 0.1) suggesting that OT stimulates browning of WAT. To assess OT-elicited changes in brown adipose tissue (BAT) thermogenesis, we examined the effects of 4V OT on interscapular BAT temperature (TIBAT). 4V OT (1 µg) elevated TIBAT at 0.75 (P = 0.08), 1, and 1.25 h (P < 0.05) postinjection; a higher dose (5 µg) elevated TIBAT at 0.75-, 1-, 1.25-, 1.5-, 1.75- (P < 0.05), and 2-h (0.05 < P < 0.1) postinjection. Together, these findings support the hypothesis that chronic hindbrain OT treatment evokes sustained weight loss in DIO mice by reducing energy intake and increasing BAT thermogenesis at a dose that is not associated with evidence of visceral illness.

Effects of anti-osteoporosis medications on radiological and clinical results after acute osteoporotic spinal fractures: a retrospective analysis of prospectively designed study.

Effects of anti-osteoporosis medications such as anti-resorptive and anabolic agents on healing of osteoporotic spinal fracture were retrospectively investigated. The use of anabolic agent significantly enhanced fracture healing, reduced progressive collapse, and presented good pain relief. These findings suggest that proper selection of medication could improve initial management of acute osteoporotic spinal fractures (OSFs). INTRODUCTION: Although anti-osteoporosis medications have beneficial effects on prevention of osteoporotic spinal fractures (OSFs), few studies have compared effects of medications on fracture healing following OSFs. Therefore, the purpose of this study was to elucidate the effects of different anti-osteoporosis medications on radiological and clinical outcomes after acute OSFs. METHODS: A total of 132 patients diagnosed with acute OSFs were enrolled and allocated into three groups [group I (n = 39, no anti-osteoporosis medication), group II (n = 66, bisphosphonate), and group III (n = 27, parathyroid hormone (PTH)]. Radiological parameters including magnetic resonance (MR) classification, occurrence of intravertebral cleft (IVC), and clinical outcomes such as numerical rating scale (NRS) and Oswestry disability index were assessed. Risk analyses for IVC and progressive collapse were done along the related factors and medication type. RESULTS: IVC sign was observed in 30 patients. The rate of IVC sign was lower in group III (7.4%) than that in group I (20.5%) or group II (30.3%), although the difference was not statistically significant. Moreover, the degree of NRS improvement was better in group III than that in group I or group II (5.7 vs. 3.1 vs. 3.5, p < 0.001). On multiple regression analysis, mid-portion type fracture in MR classification was a significant risk factor for progressive OSFs. The use of PTH showed significant lower incidences of occurrence of IVC (odds ratio (OR) = 0.160) and increase in height loss (OR = 0.325). CONCLUSIONS: Different anti-osteoporosis medications presented different clinical and radiological results after acute OSFs. The use of anabolic agent significantly enhanced fracture healing, reduced progressive collapse, and presented better clinical outcomes. Proper selection of medication might improve initial management of acute OSFs.

Conservation of the behavioral and transcriptional response to social experience among Drosophilids.

While social experience has been shown to significantly alter behaviors in a wide range of species, comparative studies that uniformly measure the impact of a single experience across multiple species have been lacking, limiting our understanding of how plastic traits evolve. To address this, we quantified variations in social feeding behaviors across 10 species of Drosophilids, tested the effect of altering rearing context on these behaviors (reared in groups or in isolation) and correlated observed behavioral shifts to accompanying transcriptional changes in the heads of these flies. We observed significant variability in the extent of aggressiveness, the utilization of social cues during food search, and social space preferences across species. The sensitivity of these behaviors to rearing experience also varied: socially naive flies were more aggressive than their socialized conspecifics in some species, and more reserved or identical in others. Despite these differences, the mechanism of socialization appeared to be conserved within the melanogaster subgroup as species could cross-socialize each other, and the transcriptional response to social exposure was significantly conserved. The expression levels of chemosensory-perception genes often varied between species and rearing conditions, supporting a growing body of evidence that behavioral evolution is driven by the differential regulation of this class of genes. The clear differences in behavioral responses to socialization observed in Drosophilids make this an ideal system for continued studies on the genetic basis and evolution of socialization and behavioral plasticity.

Low-carbohydrate diet and the risk of metabolic syndrome in Korean adults.

BACKGROUND & AIMS: The association of low-carbohydrate diet with weight loss and the risk of cardiovascular diseases has recently been the focus of increasing research attention. However, studies on low-carbohydrate diet in the Asian population are limited. The present study was aimed to examine the association between low-carbohydrate diet and metabolic syndrome among Korean adults. METHODS AND RESULTS: A total of 16,349 participants aged 30 years or older who participated in a 24-h dietary recall survey of the fifth and sixth Korea National Health and Nutrition Examination Survey were included in this study. Low-carbohydrate diet was evaluated using the low-carbohydrate-diet score, which was calculated based on the percentage of energy from carbohydrate, protein, and fat by sex. The association between the low-carbohydrate-diet score and metabolic syndrome was analyzed using multiple logistic regression analysis. A low-carbohydrate diet was not associated with metabolic syndrome and its components such as waist circumference, blood pressure, and triglyceride levels. However, women in the highest decile of the animal- or plant-based low-carbohydrate-diet score showed a decreased risk of reduced high-density lipoprotein (HDL)-cholesterol levels, and men in the highest decile of the animal-based low-carbohydrate-diet score showed a decreased risk of reduced HDL-cholesterol levels than those in the lowest decile of the low-carbohydrate-diet score. CONCLUSION: These findings indicate that, in Korea, a low-carbohydrate diet did not increase the risk of metabolic syndrome among adults who typically consume a high-carbohydrate low-fat diet. However, it may moderately decrease the risk of reduced HDL-cholesterol levels.

Combined effects of diabetes and low household income on mortality: a 12-year follow-up study of 505 677 Korean adults.

AIM: To examine the effects of diabetes, low income and their combination on mortality in the Korean population. METHODS: We analysed a total of 505 677 people (53.9% male) aged 40-79 years old from the National Health Insurance Service-National Health Screening (NHIS-HEALS) cohort. Ten levels of household income were used as indicators of economic status. Diabetes was defined as elevated fasting blood glucose (≥ 6.9 mmol/l) and/or use of glucose-lowering drugs or insulin. Covariates of age, sex, BMI, smoking and Charlson Comorbidity Index were determined at baseline. Outcomes were total and cause-specific mortality over 12 years. Cox's proportional hazard regression models were used to estimate hazard ratios (HRs) for mortality according to the presence of diabetes, household income and their combination. RESULTS: Lower household income was associated with higher mortality from all causes, cardiovascular disease, cancer and non-cancer non-cardiovascular causes. Excessive mortality due to low incomes was observed in both people with and without diabetes. In men, the adjusted HR [95% confidence interval (CI)] of mortality was 1.38 (1.34 to 1.42) for low-income only, 1.48 (1.42 to 1.55) for diabetes only and 1.95 (1.86 to 2.05) for diabetes and low-income combined, relative to the normal glucose and high income group. Corresponding HR (95% CI) in women were 1.19 (1.14 to 1.24), 1.54 (1.44 to 1.64) and 1.87 (1.75 to 2.01), respectively. CONCLUSION: Both low household income and the presence of diabetes independently increase the risk of mortality, but their combined effects on mortality may be different between men and women.

Chemical evidence of inter-hemispheric air mass intrusion into the Northern Hemisphere mid-latitudes.

The East Asian Summer Monsoon driven by temperature and moisture gradients between the Asian continent and the Pacific Ocean, leads to approximately 50% of the annual rainfall in the region across 20-40°N. Due to its increasing scientific and social importance, there have been several previous studies on identification of moisture sources for summer monsoon rainfall over East Asia mainly using Lagrangian or Eulerian atmospheric water vapor models. The major source regions for EASM previously proposed include the North Indian Ocean, South China Sea and North western Pacific. Based on high-precision and high-frequency 6-year measurement records of hydrofluorocarbons (HFCs), here we report a direct evidence of rapid intrusion of warm and moist tropical air mass from the Southern Hemisphere (SH) reaching within a couple of days up to 33°N into East Asia. We further suggest that the combination of direct chemical tracer record and a back-trajectory model with physical meteorological variables helps pave the way to identify moisture sources for monsoon rainfall. A case study for Gosan station (33.25°N, 126.19°E) indicates that the meridional transport of precipitable water from the SH accompanying the southerly/southwesterly flow contributes most significantly to its summer rainfall.

Can persistent organic pollutants distinguish between two opposite metabolic phenotypes in lean Koreans?

AIMS: This study investigated the association of persistent organic pollutants (POPs), an emerging new risk factor for type 2 diabetes and the metabolic syndrome, with the presence of opposite phenotypes of glucose and lipid metabolism among normal-weight Koreans of similar body composition. METHODS: Fifty subjects, randomly selected from an ongoing community-based cohort study, from two opposite phenotype groups - metabolically unhealthy normal weight (MUHNW) and metabolically healthy normal weight (MHNW) - were matched for waist circumference, visceral fat mass and demographic variables, then compared for serum concentrations of POPs. RESULTS: Most POPs (10 out of 13 compounds) were present in higher serum concentrations in the MUHNW than in the MHNW. In particular, serum concentrations of all compounds of the organochlorine pesticide class were 2.2 to 4.7 times higher in cases than in controls. Compared with the lowest tertile of summary measures of POPs, Odds ratios (95% confidence interval) for the second and third tertiles were 7.4 (1.9-29.4) and 10.4 (2.6-41.2), respectively. Adjusting for possible confounders did not change the results. CONCLUSION: Taken altogether, these findings from the present and previous studies suggest that increased serum POP concentrations may play an important role in the development of unhealthy metabolic phenotypes in lean people.

Cardiovascular events associated with second-line anti-diabetes treatments: analysis of real-world Korean data.

AIM: To compare the risks of cardiovascular disease (CVD) and all-cause mortality associated with sulfonylurea (SU), dipeptidyl peptidase-4 inhibitor (DPP4i) and thiazolidinedione (TZD) as add-on medications to metformin (MET) therapy in people with Type 2 diabetes. METHODS: We identified 40 263 individuals who used SU (n = 11 582), DPP4i (n = 26 623) or TZD (n = 2058) in addition to MET between January 2013 and June 2015 from the database of the Korean National Health Insurance, the single-payer healthcare system in South Korea. Cox proportional hazard models were used to estimate hazard ratios for major CVD event (coronary artery disease, heart failure, stroke or transient ischaemic attack) development and all-cause mortality by second-line anti-diabetes medication type. Age, sex, duration of MET monotherapy, calendar year and comorbid conditions were adjusted as potential confounders. RESULTS: The observed numbers of CVD events (total observed person-time) were 485 (18 778 person-years) for MET + SU, 744 (40 374 person-years) for MET + DPP4i and 60 (3014 person-years) for MET + TZD users. Compared with MET + SU users, the fully adjusted hazard ratios for CVD events were 0.79 [95% confidence interval (CI): 0.71-0.89] for MET + DPP4i users and 0.85 (95% CI: 0.65-1.11) for MET + TZD users. The corresponding hazard ratios for all-cause mortality were 0.84 (95% CI: 0.66-1.07) for MET + DPP4i users and 0.67 (95% CI: 0.35-1.28) for MET + TZD users. CONCLUSION: Analysis of Korea National Health Insurance database showed that MET + DPP4i treatment for diabetes had a lower CVD risk than MET + SU treatment.

Identification of Novel Macropinocytosing Human Antibodies by Phage Display and High-Content Analysis.

Internalizing antibodies have great potential for the development of targeted therapeutics. Antibodies that internalize via the macropinocytosis pathway are particularly promising since macropinocytosis is capable of mediating rapid, bulk uptake and is selectively upregulated in many cancers. We hereby describe a method for identifying antibodies that internalize via macropinocytosis by screening phage-displayed single-chain antibody selection outputs with an automated fluorescent microscopy-based high-content analysis platform. Furthermore, this method can be similarly applied to other endocytic pathways if other fluorescent, pathway-specific, soluble markers are available.

Stimulation of Phenolics, Antioxidant and α-Glucosidase Inhibitory Activities During Barley (Hordeum vulgare L.) Seed Germination.

The rationale of this study was to enhance the nutritional quality of dry barley seeds. In this study we are evaluating the effect of germination on barley seeds relevant to total phenolic contents, antioxidant activity (in terms of DPPH free-radical scavenging) and the in vitro α-glucosidase inhibitory activities. Barley seeds were germinated for 18.5, 24, 30, 48, and 67 h and then extracted in water. The total phenolic contents, antioxidant activities and α-glucosidase inhibitory activities changed with germination time. More specifically, within the first 48 h of germination the total phenolic content increased from 1.1 mg/g fresh weight (0 h) to 3.4 mg/g fresh weight (48 h) and then slightly reduced by 67 h. Similarly, α-glucosidase inhibitory activity was significantly increased from an IC50 128.82 mg/mL (0 h) to an IC50 18.88 mg/mL (48 h) and then slightly reduced by 67 h. Significant maltase inhibitory activity was observed only with 48 h-germinated extract. Antioxidant activities increased continuously from an IC50 15.72 mg/mL at 0 h to and IC50 5.72 mg/mL after 48 h of germination. Based on our observations, barley seed germination was over after 48 h. During the progress of germination phenolic compounds are becoming available and are more easily extracted. After 48 h, lignification is initiated resulting to the decreased total phenolic content and observed antioxidant and carbohydrate hydrolyzing enzyme inhibition activities. The above results indicate the positive effect of germination in barley seeds for enhanced antioxidant and α-glucosidase inhibitory activities.