HR Group Research Articles

White matter hyperintensities in young individuals with bipolar disorder or at high genetic risk

BackgroundIncreased white matter hyperintensities (WMHs) is one of the most consistent imaging findings amongst participants with bipolar disorder (BD). This study investigated WMHs in a young population at high genetic risk for bipolar disorder (HR). MethodsMRI scans were conducted at baseline in HR individuals (n = 131), patients with BD (n = 47) and controls (CON) (n = 108). Most of the HR (n = 77) and CON (n = 74) group completed scans after two years. Scans were examined for the presence of WMHs. ResultsThere were significantly more periventricular WMHs in the BD compared to the CON group at baseline (p = .04). Although the prevalence of periventricular WMHs was intermediate in the HR group, there were no significant differences between the HR and CON or BD participants. Deep WMHs did not differ significantly between the groups. Over time, there was a significant increase in the prevalence of periventricular WMHs in both the HR and CON groups (p = .02). LimitationsThe use of a visual rating scale to examine WMHs is subjective. As the gradings were collapsed into ‘present’ or ‘absent’, we could not ascertain whether the severity of hyperintensities worsened over time. ConclusionsPeriventricular WMHs are more prevalent in young individuals with BD than controls. As these are not more prevalent in HR individuals, it is possible that these are either secondary to the development of bipolar disorder, its treatment, or resulting changes in lifestyle. In a novel finding, there were similar increases in the prevalence of WMHs in controls and HR youth over the 2-year period.

Treatment of latent tuberculous infection among health care workers at a tertiary hospital in Korea.

To evaluate the acceptance of, adherence to, and outcomes of latent tuberculous infection (LTBI) treatment among health care workers (HCWs). This was a retrospective study in a tertiary hospital in Korea. From May to August 2017, 2190 HCWs simultaneously underwent a tuberculin skin test (TST) and interferon-gamma release assay (IGRA). LTBI was diagnosed if the TST induration was 10 mm or IGRA results were positive. Of 2190 HCWs tested, 1006 (45.9%) were diagnosed with LTBI. Of these, 655 (65.1%) HCWs visited out-patient clinics, 234 (35.7%) of whom were advised treatment by physicians. Among these, 120 (51.3%) accepted the physicians' recommendations. In general, HCWs who were older, male and smoked were less likely to visit out-patient clinics. Sixty (50%) HCWs received 3 months of isoniazid plus rifampicin (3HR) and 57 (47.5%) HCWs received 4 months of rifampicin (4R). The proportion of HCWs with 2 side effects (3HR 20% vs. 4R 7.0%, P = 0.041) and drug stoppage rate (3HR 20% vs. 4R 5.3%, P = 0.017) were higher in the 3HR group than in the 4R group. Of the 120 HCWs, 78 (65%) completed LTBI treatment. Overall, the acceptance and completion rate for LTBI treatment was not adequate. For effective LTBI management in HCWs, further programmatic strategies are needed.

PO-306 The effect of four weeks hypoxic resistance training on myostatin and follistatin expression in skeletal muscle of rats

Objective Loss of skeletal muscle weight is a common phenomenon in hypoxic environment. It has been recognized that resistance training can reduce hypoxia-induced skeletal muscle atrophy, but its molecular mechanism is still unclear. Myostatin is a major factor that inhibits muscle growth and differentiation, and Follistatin can inhibit Myostatin. Therefore, this study is to clarify the effect of 4-week hypoxic resistance exercise on Myostatin and Follistatin gene expression in skeletal muscle of rats.
 Methods Twenty four 8-week-old male SD rats were randomly divided into normoxic control group (group C: 6 rats), normoxic exercise group (group R: 6 rats), hypoxic control group (group H: 6 rats) and hypoxic exercise group (group HR: 6 rats). Rats in each hypoxic group were fed in a hypoxic chamber (atmospheric hypoxia) with oxygen concentration of 12.7% (simulated 4000m altitude). Rats in each exercise group were trained according to the rat's resistance training program developed in our laboratory. After all the intervention, DEXA was used to analyze the body composition. The soleus, extensor digitorum longus and biceps brachii muscles of rats were taken and the wet weight of individual muscles was measured. The data were processed by SPSS17.0 statistical software. The expression level of skeletal muscle mRNA was expressed as "median (25-75%)" and the data of body composition and muscle wet weight were expressed as"mean±standard deviation". The differences between the groups were evaluated using a one-way analysis of variance (ANOVA) test. The significance level for the study was less than 0.05.
 Results Body composition analysis after 4 weeks of hypoxic intervention showed that the body weight of rats in group H decreased significantly (p=0.012), and the muscle mass decreased more significantly (p<0.001). But resistance exercises obviously reduced the muscle atrophy (p<0.01) caused by hypoxia. After analyzing the changes of the wet weight of individual muscles, it was found that the wet weight of biceps brachii in HR group was significantly higher than that in H group (p=0.048). After 4 weeks of hypoxic intervention and hypoxic resistance exercise, the expression of Myostatin mRNA in individual muscles of each group changed differently. The expression of Myostatin mRNA in soleus muscle of H group was significantly higher than that of C group (371.2%) after 4 weeks of hypoxia intervention. Myostatin mRNA expression in soleus and biceps brachii of HR group was significantly lower than that of H group (591.1% and 478.4% respectively). However, there was no significant difference in the expression level of Myostatin mRNA in the extensor digitorum longus between each group (p=0.259). The change of Follistatin mRNA expression in different groups also showed a different trend. The expression of Follistatin mRNA in soleus muscle and biceps brachii muscle was significantly different among groups (p=0.003, p=0.004, respectively). However, there was no significant difference in the expression level of Follistatin mRNA in the extensor digitorum longus between each group (p=0.734). Myostatin mRNA/Follistatin mRNA ratio (M/F) showed a more significant difference. The M/F ratio of soleus muscle in group H was significantly lower than that in group C (p<0.001), but the M/F ratio in group HR was significantly higher than that in group H (p<0.001). The M/F ratio of biceps brachii in group H was significantly lower than that in group C (p<0.001), but the M/F ratio in group HR showed a higher trend than that in group H (p=0.051).
 Conclusions Hypoxic exposure results in an increase in Myostatin mRNA expression in skeletal muscle, but hypoxic resistance exercise reduces such an increase. On the contrary, the level of Follistatin mRNA expression in skeletal muscle decreased after hypoxic exposure, and hypoxic resistance exercise could slow down the decline. As a result, rat resistance exercise significantly slowed down hypoxia-induced muscle atrophy. In conclusion, the mutual restriction between Myostatin and Follistatin is one of the main links of resistance exercise to reduce hypoxia-induced skeletal muscle atrophy. However, the process of resistance training to reduce the hypoxia-induced skeletal muscle atrophy is very complex. There are many molecular signaling pathways involved, which need further study.

PO-109 Resistance Training prevents Skeletal Muscle Atrophy Induced by hypoxia through regulating Akt-FoxO1 pathway

Objective Skeletal muscle atrophy induced by hypoxia on the plateau will lead to the decrease of muscle strength and the degeneration of athletic ability. Resistance training is an efficient method to stimulate the growth of muscle and improve protein synthesis. Akt-FoxO1 (Fork head box protein 1) pathway plays a significant role in the regulation of skeletal muscle protein degradation. However, it is not clear whether resistance training could prevent skeletal muscle atrophy induced by hypoxia and what is the regulation role of Akt-FoxO1 pathway. This study built a rat model that resistance training inhibited the skeletal muscle atrophy induced by hypoxia and explore the variation of Akt, FoxO1, Murf and Atrogin-1.
 Methods 40 male 8-week-old Sprague-Dawley (SD) rats were divided into 4 groups randomly: control group (C), resistance training group (R), hypoxia group (H) and hypoxia resistance training group (HR). H and HR group were placed into simulated 4000m altitude (12.4%, O2%) and R and HR group received ladder resistance training. Their incremental load is calculated by using average body weight. After 4 weeks intervention of hypoxia and resistance training, body composition, wet weight of skeletal muscle (soleus, musculus gastrocnemius,extensor digitorum longus and muscelus biceps brachii) and skeletal muscle cross-sectional area (CSA) were measured. The expression of Akt, FoxO1, Murf and Atrogin-1 were detected by Western blot and RT-PCR.Moreover,immunofluorescence technique was used to locate the phosphorylation of FoxO1. 
 Results The lean body mass of HR group was significantly higher than H group (P<0.05). The wet weight and CSA of muscelus biceps brachii in HR group were also higher than H group obviously (P<0.05). The results of real-time fluorescence quantitative PCR and western blot showed that the expression of FoxO1 and MuRF of hypoxia group (H group) were significantly higher than control group. However after the intervention of resistance training, the expression of Akt was significantly up-regulate and FoxO1, MuRF were significantly down-regulate. Immunofluorescence technique was used to observe the location of FoxO1 phosphorylation and the expression out of nucleus.
 Conclusions Resistance training contribute to prevent the occurrence of skeletal muscle atrophy induced by hypoxia and the form of climbing ladder training can stimulate the hypertrophy of biceps in rats. The results revealed that FoxO1 phosphorylation out of nucleus became higher after resistance training. All above revealed that resistance training could inhibit skeletal muscle atrophy induced by hypoxia. Akt promoted FoxO1 phosphorylation may become the molecular mechanisms that resistance training can inhibit the atrophy of skeletal muscle induced by hypoxia.

Exosomal Glypican-1 and Pancreatic Adenocarcinoma: Prime Time for Early Diagnosis?

Introduction: Glypican-1(GPC1), a cell surface proteoglycan, is overexpressed in pancreatic cancer and specifically enriched on cancer-cell-derived circulating exosomes(crExos). Levels of GPC1+ crExos correlate with tumour burden and survival of patients with pancreatic adenocarcinoma(PDAC). Aim: Characterize GPC1+ crExos levels in PDAC patients and associated risk groups. Methods: Unicentric prospective cohort study, with PDAC(cytology/histology confirmation), cystic mucinous neoplasm(CMN), chronic pancreatitis(CP) and hereditary risk for PDAC(HR), namely Peutz-Jeghers and Lynch Syndrome patients and Familial PDAC siblings. Controls were patients submitted to endoscopic ultrasound(EUS) for other reasons than pancreatic pathology, with a normal pancreas and absence of hereditary risk factors. In all cases, EUS, blood tests (total CrExos and GPC1+ crExos by flow cytometry;CA19.9 by ELISA); clinico-demographic data was collected. GPC1 antibody Abnova® was used in all cases. Results: Included 115 patients (54%women, median age 61(IQR:51.5-76.5y). Excluded patients: 1-poor sample preservation and 4-altered final pathological diagnosis (3 neuroendocrine tumor and 1 serous cystadenoma). Cases analyzed: 43(39%) PDAC, 24(22%) CMN, 23(21%) CP, 11(10%) HR and 9(8%) controls. Mean levels of GPC1+crExos(n=102) were 74.4±21.4%, 57.9±37.1%, 4.2±4.6%, 43.4±37.4% and 4.42±2.97% in PDAC, CMN, CP, HR and Control groups, respectively. This difference was significantly different between PDAC patients comparing to CP and controls (p<0.001) but not to CMN and HR groups (p=NS). Levels of CA 19.9(U/mL) were significantly higher in patients with PDAC compared to all other groups (280.7±234.8 vs. 51.3±11.8; p<0.001, n=90). GPC1+ crExos levels presented good accuracy for overall PDAC diagnosis: AUROC of 0.79(p<0.001). For a cut-off of 18.9%: sensitivity (Se)=100%, specificity(Sp)=57%, positive predictive value (PPV)=59%, and negative predictive value(NPV)=100%. CA 19.9 also presented good accuracy: AUROC of 0.82 (p<0.001). For a cut-off of 28.2U/mL: Se=81%, Sp=71%, PPV=61% and NPV=87%. Conclusion: In our cohort, GPC1+ crExos levels were significantly higher in patients with PDAC comparing to CP and controls, but not to patients with CMN (a well-known potentially malignant precursor lesion) or documented hereditary risk for PDAC. These findings may be a clue to identify subpopulations at higher risk for developing PDAC, suggesting prompt investigation.

Comparison between Glidescope, Airtraq and Macintosh laryngoscopy for emergency endotracheal intubation in intensive care unit: Randomized controlled trial

BackgroundEmergency endotracheal intubation in intensive care is a major challenge that can be associated with life-threatening complications. The aim of this study was to evaluate the success of the first attempt of endotracheal intubation and incidence of complications using Macintosh laryngoscopy, Airtraq or Glidescope during emergency intubation in intensive care.Patients and methodsOne hundred twenty adult intensive care patients of ASA physical status III and IV who required emergency endotracheal intubation were randomly allocated into 3 groups. Group M (40 patients) were intubated using Macintosh laryngoscopy. Group G (40 patients) were intubated using Glidescope. Group A (40 patients) were intubated using Airtraq. The primary outcome was the success of the first attempt of endotracheal intubation. Secondary outcomes included the number of intubation attempts, duration of intubation, glottic view as assessed by Cormack-Lehane grade (C&L grade) and incidence of complications.ResultsSuccess of the first attempt of endotracheal intubation was significantly higher in both groups G and A compared to group M (p < 0.05). The number of intubation attempts was significantly higher in group M compared to both groups G and A (p < 0.05). The duration of endotracheal intubation was 28.80 ± 10.27 s in group M compared to 31.45 ± 12.17 s in group G and 32.25 ± 11.96 s in group A (p > 0.05). The C&L grade was significantly better in both groups G and A compared to group M (p < 0.05). No statistically significant difference between the three groups in HR or MAP. The incidence of oxygen desaturation was significantly more in group M compared to groups G and A. No statistically significant difference between the 3 studied groups regarding the incidence of other complications.ConclusionBoth Glidescope and Airtraq have higher first attempt success rate with a better glottic view and less incidence of oxygen desaturation than Macintosh laryngoscopy during emergency intubation in intensive care.

Calving duration and obstetric assistance influence pulmonary function of Holstein calves during immediate fetal-to-neonatal transition.

Neonatal immediate adaptation to extrauterine life depends mainly on adequate lung function, which is under the influence of previous fetal maturation and obstetrical condition, both acting to stimulate the efficient liquid removal from the pulmonary parenchyma during the immediate transition period. The objective of the present study is to identify chest radiographic changes of neonatal calves born under the influence of different duration of calving and obstetric assistance and correlate with clinical analysis and blood acid-base balance. Experimental groups were determined according to the duration of calving: 2 h (n = 16), 2–4 h (n = 16) and >4 h (n = 12), and additionally by two sub-groups: no-intervention calving (n = 22) and intervention calving (n = 22). Neonatal calves were evaluated for heart and respiratory rate at birth, 5 min, every 10 min until 90 min. Arterial acid-base balance was determined immediately after calving and thoracic radiographs were made at 10 min of life. Lung radiopacity was higher in the 2–4 hr Group compared to the 2 hr Group. When calving duration was greater than 4 hours, a significant respiratory depression was observed. Calving greater than 2 hours slower neonatal pulmonary clearance, 100% and 91.6% of the calves born in the 2–4 hr and >4 hr Groups, respectively, had mild to moderate lung parenchyma opacity. There was a positive correlation between lung radiographic changes and blood TCO2 and negative correlation between pulmonary opacity score and blood PaO2 and SO2. Hence, it is possible to infer that neonatal hypoxia during prolonged calving has an imperative influence on pulmonary fluid absorption in calves. In conclusion, calving greater than 2 hours impacts pulmonary function at birth, leading to altered lung gas exchange, pulmonary clearance, cardiac and respiratory pattern. Conversely, obstetric intervention when calving has duration greater than 4 hours is beneficial for neonatal oxygenation.

Melatonin supplementation during prolonged in vitro maturation improves the quality and development of poor-quality porcine oocytes via anti-oxidative and anti-apoptotic effects.

Poor-quality oocytes (those with 1-2 layers of cumulus cells) typically possess low meiotic competence and development. Prolonging the duration of in vitro maturation (IVM; 52 hr) can enhance the maturation rate of poor-quality oocytes, but it does not improve subsequent embryonic development. This likely reflects the increased reactive oxygen species (ROS) production and apoptosis seen in these oocytes compared with the non-prolonged IVM (44 hr) group. Melatonin is a free radical scavenger, anti-oxidant and anti-apoptotic agent that reported to enhance the quality of embryos by inhibiting ROS generation and apoptosis. Therefore, we herein investigated whether melatonin combined with prolonged IVM (52 hr) could improve the quality and development of poor-quality oocytes. We supplemented IVM and/or in vitro culture (IVC) media with various concentrations (0, 10-7 , 10-6 , 10-5 M) of melatonin, and estimated parameters related to oocyte quality and development. The addition of melatonin (10-6 M) to a prolonged IVM system improved the oocyte quality and development compared with those of the melatonin-free poor-quality oocytes group, and that this was due to decreases in ROS generation, apoptosis, and DNA damage. When melatonin was added during both IVM (10-6 M) and IVC (10-6 M), we observed a cumulative positive influence on the embryonic development and quality; this treatment enhanced the expression level of Oct4 and decreased the levels of ROS, DNA damage, and apoptosis. Together, these findings suggest that the combination of melatonin plus prolonged IVM can improve the quality and development of poor-quality porcine oocytes via anti-oxidative and anti-apoptotic effects.

Lymph node evaluation in high-risk early stage endometrial cancer: A multi-institutional retrospective analysis comparing the sentinel lymph node (SLN) algorithm and SLN with selective lymphadenectomy

ObjectiveThe aim of this study was to determine the impact of the sentinel lymph node mapping algorithm (SLN-A) on the staging in high-risk endometrial cancer (EC) compared to SLN plus selective lymphadenectomy (S-LND). MethodsWe retrospectively analyzed the database from a multicenter collaboration that included women with high risk features who underwent primary surgical staging. ResultsOne-hundred and seventy-one women were identified (171), 66 in the SLN-A and 105 in the S-LND group, respectively. Pelvic LD was performed on 115 patients (67.2%) and aortic dissection was performed in 54/105 of the women in the S-LND group (51%). The 5-year comparison did not show a significant difference in the strategy adopted for nodal staging, regarding disease-free survival (DFS) [HR: 0.82; 95% CI 0.53–1.28; p = 0.390]. ConclusionsIn this study focusing on women with EC in the HR groups, we did not find a difference in the 5-year DFS when comparing the SLN-A strategy with S-LND. The SLN strategy did not seem to compromise the prognosis of patients with a higher risk of recurrence.

Nutritional risk screening of inpatient children with singer-center gastroenterological diseases in Sichuan province

Objective To evaluate the application of clinical Screening Tool for the Assessment of Malnutrition in Pediatrics(STAMP), and to investigate the nutritional risks of inpatient children with gastroenterological diseases in Sichuan province and their associated clinical characteristics and the features of hygiene economics. Methods STAMP was utilized for nutrition screening of inpatient children with gastroenterological diseases in Chengdu Women and Children′s Central Hospital from January 2015 to March 2017.All the enrolled children were divided into 3 groups accor-ding to the STAMP scores: low risk group (LR group), moderate risk group (MR group) and high risk group (HR group). Clinical and economic data were compared among 3 groups. Results A total of 3 672 assessments were accomplished, including 2 372 times for males and 1 300 times for females( 5 years old: 848 times). Among them, 147 children were identified as LR(4.00%), 2 296 children as MR (62.53%), and 1 229 children as HR (33.47%). Statistically significant differences were observed among 3 groups in average length of hospital stay (P 0.05). Malnutrition rate was 4.08%(6/147 cases) in LR group, 2.05%(47/2 296 cases) in MR group and 31.90%(392/1 229 cases) in HR group, respectively, and among them 146 patients were diagnosed as severe malnutrition.Digestive tract infections were the most common diseases in MR group(66.33%, 1 523/2 296 cases) and HR group(68.27%, 839/1 229 cases). Moreover, children with stomatitis, gastrointestinal postoperation, acute pancreatitis, inflammatory bowel disease, esophageal diseases, digestive malformations, cyclic vomiting, malnutrition, and acute intestinal obstruction were all in HR group. Conclusions Nutritional risk is likely to raise the burden of disease.STAMP is applicabile clinically when it is utilized for nutrition risk screening of inpatient children with gastroenterological diseases in Sichuan province and provides evidence for nutrition support treatment. Key words: Nutrition risk screening; Screening Tool for the Assessment of Malnutrition in Pediatrics; Gas-troenterological disease

Mitochondrial haplotypes are not associated with mice selectively bred for high voluntary wheel running

Mitochondrial haplotypes have been associated with human and rodent phenotypes, including nonshivering thermogenesis capacity, learning capability, and disease risk. Although the mammalian mitochondrial D-loop is highly polymorphic, D-loops in laboratory mice are identical, and variation occurs elsewhere mainly between nucleotides 9820 and 9830. Part of this region codes for the tRNAArg gene and is associated with mitochondrial densities and number of mtDNA copies. We hypothesized that the capacity for high levels of voluntary wheel-running behavior would be associated with mitochondrial haplotype. Here, we analyzed the mtDNA polymorphic region in mice from each of four replicate lines selectively bred for 54 generations for high voluntary wheel running (HR) and from four control lines (Control) randomly bred for 54 generations. Sequencing the polymorphic region revealed a variable number of adenine repeats. Single nucleotide polymorphisms (SNPs) varied from 2 to 3 adenine insertions, resulting in three haplotypes. We found significant genetic differentiations between the HR and Control groups (Fst = 0.779, p ≤ 0.0001), as well as among the replicate lines of mice within groups (Fsc = 0.757, p ≤ 0.0001). Haplotypes, however, were not strongly associated with voluntary wheel running (revolutions run per day), nor with either body mass or litter size. This system provides a useful experimental model to dissect the physiological processes linking mitochondrial, genomic SNPs, epigenetics, or nuclear-mitochondrial cross-talk to exercise activity.

Adaptive Behaviour and Cognitive Skills: Stability and Change from 7\xa0Months to 7\xa0Years in Siblings at High\xa0Familial Risk of Autism Spectrum Disorder

Cognitive and adaptive behaviour abilities early in life provide important clinical prognostic information. We examined stability of such skills in children at high familial risk for ASD who either met diagnostic criteria for ASD at age 7 years (HR-ASD, n = 15) or did not (HR-non-ASD, n = 24) and low-risk control children (LR, n = 37), prospectively studied from infancy. For both HR groups, cognitive skills were consistently lower across time than those of LR children. HR-ASD children showed increasing difficulties in adaptive behaviour over time compared to LR children, while the HR-non-ASD children showed no such difficulties. This pattern of change may inform our understanding of developmental profiles of HR siblings beyond core ASD symptoms.

Hyper response to ovarian stimulation affects the follicular fluid metabolomic profile of women undergoing IVF similarly to polycystic ovary syndrome.

During in vitro fertilization (IVF), the hyper response to controlled ovarian stimulation (COS) is a common characteristic among patients diagnosed with polycystic ovary syndrome (PCOS), although non-diagnosed patients may also demonstrate this response. In an effort to investigate follicular metabolic characteristics associated with hyper response to COS, the present study analyzed follicular fluid (FF) samples from patients undergoing IVF. FF samples were obtained from patients with PCOS and hyper response during IVF (PCOS group, N = 15), patients without PCOS but with hyper response during IVF (HR group, N = 44), and normo-responder patients receiving IVF (control group, N = 22). FF samples underwent Bligh and Dyer extraction, followed by metabolomic analysis by ultra-performance liquid chromatography mass spectrometry, considering two technical replicates. Clinical data was analyzed by ANOVA and chi-square tests. The metabolomic dataset was analyzed by multivariate statistics, and the significance of biomarkers was confirmed by ANOVA. Clinical data showed differences regarding follicles production, oocyte and embryo quality. From the 15 proposed biomarkers, 14 were of increased abundance in the control group and attributed as fatty acids, diacylglycerol, triacylglycerol, ceramide, ceramide-phosphate, phosphatidylcholine, and sphingomyelin. The PCOS patients showed increased abundance of a metabolite of m/z 144.0023 that was not attributed to a class. The clinical and metabolic similarities observed in the FF of hyper responders with and without PCOS diagnosis indicate common biomarkers that could assist on the development of accessory tools for assessment of IVF parameters.

Reduced serotonin levels after a lifestyle intervention in obese children: association with glucose and anthropometric measurements.

serotonin signaling participates in body weight regulation and glucose metabolism. However, little information is available on circulating serotonin levels in obese subjects after a weight loss program. We aimed to assess the effect of a lifestyle intervention on serotonin levels in obese children and possible associations with anthropometric and blood glucose measurements. forty-four obese children were enrolled in a ten-week lifestyle intervention consisting of a moderate caloric restriction diet, nutritional education and familial involvement. They were distributed according to the weight loss response. Subjects who lost > 0.5 BMI-SDS were considered as high responders (HR; n = 22) and those who lost ≤ 0.5 BMI-SDS, as low responders (LR; n = 22). Anthropometric, biochemical parameters and plasma serotonin levels were measured as pre and post-intervention values. obese children (HR and LR groups) were able to reduce anthropometric indices and to improve glucose profile after the intervention. Interestingly, plasma serotonin levels were significantly (p ˂0.05) reduced in all subjects (-35.14 nmol/l HR group and -30.63 nmol/l LR group). Moreover, multiple-adjusted regression models showed a significant association between pre-intervention (R2 = 0.224, B = 0.047; p = 0.004) and post-intervention (R2 = 0.140; B = 0.055; p = 0.042) plasma serotonin and glucose levels. In addition, in HR subjects changes in plasma serotonin were associated with changes in glucose levels (R2 = 0.292; b = 0.04; p = 0.045). Interestingly, pre and post-intervention plasma serotonin levels were inversely associated (p ˂0.05) with anthropometric measures. serotonin levels were reduced after a lifestyle intervention independently of the program response. Moreover, plasma serotonin levels were associated with glucose and anthropometric measures in obese children.

Perioperative Outcomes are Adversely Affected by Poor Pretransfer Adherence to Acute Limb Ischemia Practice Guidelines

The accepted treatment for acute limb ischemia (ALI) is immediate systemic anticoagulation and timely reperfusion to restore blood flow. In this study, we describe the retrospective assessment of pretransfer management decisions by referring hospitals to an academic tertiary care facility and its impact on perioperative adverse events. A retrospective analysis of ALI patients transferred to us via our Level I Vascular Emergency Program from 2010 to 2013 was performed. Patient demographics, comorbidities, Rutherford ischemia classification, time to anticoagulation, and time to reperfusion were tabulated and analyzed for correlation to incidence of major adverse limb events (MALEs), mortality, and bypass patency in the perioperative period (30-day postoperative). All intervals were calculated from the onset of symptoms and categorized into 3 subcohorts (<6hr, 6-48hr, and >48hr). Eighty-seven patients with an average age of 64.0 (±16.2) years presented to outlying hospitals and were transferred to us with lower extremity ALI. The mean delay from symptom onset to initial referring physician evaluation was 18.3hr. At that time of evaluation, 53.8% had Rutherford class IIA ischemia and 36.3% had class IIB ischemia. Seventy-six patients (87.4%) were started on heparin previous to transfer. However, only 44 patients (57.9%) reached therapeutic levels as measured by activated partial thromboplastin time before definitive revascularization. A delay of anticoagulation initiation >48hr from symptom onset was associated with increased 30-day reintervention rates compared with the <6hr group (66.7% vs. 23.5%; P<0.05). However, time to reperfusion had no statistically significant impact on MALE, 30-day mortality, or 30-day interventional patency in our small cohorts. Additionally, patients with a previous revascularization had a higher 30-day reintervention rate (46.5%; P<0.05). The practice of timely therapeutic anticoagulation of patients referred for ALI from community facilities occurs less frequently than expected and is associated with an increased perioperative reintervention rate.

Abstract P1-07-12: Correlation of breast cancer index (BCI) prognostic and predictive results to clinicopathologic risk groups in early stage HR+ breast cancer

Abstract Background: Both clinicopathologic factors and genomic tests have been shown to be prognostic for risk of late distant recurrence (DR); however, few studies have characterized differential patient stratification.Breast Cancer Index (BCI) is a validated gene expression assay for patients with early-stage HR+ breast cancer that provides a prognostic result for high vs low risk of late distant recurrence and a separate predictive result (based on the HoxB13/IL17BR [H/I] ratio) for high vs low likelihood of benefit from extended endocrine therapy. Thus four categories of results are possible based on a patient's tumor biology. To better understand how patient stratification is affected by a combination of clinicopathologic and genomic factors, this study examined BCI assay results within clinicopathologic risk categories based on tumor size and grade. Methods: This study utilized data from the BCI Clinical Database for Correlative Studies, an IRB-approved de-identified database which contains clinicopathologic and molecular variables from 19,126 clinical cases submitted for BCI testing. Clinicopathologic variables, abstracted from pathology reports, were available for a subset of these cases. This analysis evaluated cases from LN- patients with available clinicopathologic data. Chi-squared tests were used to compare BCI results between tumor size and grade subgroups. Results: Analyses included 3843 LN- patients (median age 59.1y; range 26-89y; 74% ≥50y), of which 31%, 52%, 17% were Grade 1, 2, and 3, respectively, and 5%, 22.7%, 48.9%, 21.7%, and 1.6% were T1mi/a, T1b, T1c, T2, and T3, respectively. In analysis based on tumor size, there was a wide distribution of individual BCI Prognostic scores in all tumor size subsets; however, the proportion of patients classified as high risk increased with larger tumor size (T1a/b 39.0%, T1c 50.1%, T2 61.0%; p&amp;lt;.0001). In contrast, BCI Predictive (H/I) was not as strongly correlated with size, with a modestly larger proportion of patients classified as High H/I with larger tumor size (T1a/b 37.2%, T1c 40.5%, and T2 45.3%; p=.005). Within each tumor size category, the proportion of patients classified as BCI High Risk and High H/I increased with tumor grade (p&amp;lt;.0001). However, there was a wide distribution of individual risk assessments by BCI Prognostic and stratification by BCI Predictive (H/I) in all size + grade subsets. In patients with the most favorable clinicopathologic risk profile (T1a/b, G1), BCI classified 20% as high risk, 68% of whom also had High H/I. Conclusion: While BCI results correlated with tumor size and grade, BCI identified substantial proportions of patients with favorable clinicopathologic features as high risk for late DR and apparent high likelihood of benefit from EET; conversely, BCI also identified patients with high risk clinicopathologic features as low risk for late distant recurrence and apparent low likelihood of benefit from EET. These findings help to differentiate between genomic-based and clinicopathologic-based risk/benefit assessment for patients considering EET. Citation Format: Mayordomo J, Falkson C, Kepes J, Israel MA, Schroeder BE, Schnabel CA, Elias A. Correlation of breast cancer index (BCI) prognostic and predictive results to clinicopathologic risk groups in early stage HR+ breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-07-12.

The effects of energy concentration in roughage and allowance of concentrates on performance, health and energy efficiency of pluriparous dairy cows during early lactation

ABSTRACTThe aim of this study was to investigate the effects of different energy supplies from roughage and concentrates on performance, health and energy efficiency during early lactation. For this purpose an experiment was conducted containing 64 pluriparous German Holstein cows from 3 weeks prepartum until 16 weeks postpartum. During dry period all cows received an equal dry cow ration. After calving, cows were assigned in a 2 × 2 factorial arrangement to one of four groups, receiving either a moderate (MR, 6.0 MJ NEL) or a high (HR, 6.4 MJ NEL) energy concentration in roughage and furthermore moderate (MC, 150 g/kg energy-corrected milk (ECM)) or high amounts of concentrates (HC, 250 g/kg ECM) on dry matter (DM) basis, which were allocated from an automatic feeding system. Higher allocation of concentrates resulted in an increase of DM intake at expense of roughage intake. HC cows had a higher milk yield than MC cows, whereas ECM was higher in HR cows due to a decrease of milk fat yield in MR groups. Energy balance and body condition score were elevated in HC cows, but no differences occurred in development of subclinical ketosis. Furthermore, energy efficiency variables were lower in HC groups because the greater energy intake was not associated with a considerable elevation of milk yield. Consistency of faeces did not indicate digestive disorders in any of the treatment groups although the faecal manure score was significantly lower in HR groups. Our results underline the importance of a high energy uptake from roughage, which can contribute to an adequate performance and beneficial efficiency, especially at lower amounts of concentrates in ration. Feeding concentrates on an average amount of 9.4 kg/d compared to 6.4 kg/d on DM basis improved the energy balance in our trial, but without consequences for metabolic blood variables and general health of the cows.

Association between Medicare high-risk criteria and outcomes after carotid revascularization procedures

BackgroundThe U.S. Centers for Medicare and Medicaid Services (CMS) has defined a set of high-risk criteria to help define patients who are appropriate for carotid artery stenting (CAS), but these criteria have never been validated. We aimed to validate the CMS high-risk criteria in a nationally representative cohort of patients undergoing CAS and carotid endarterectomy (CEA). MethodsAll patients undergoing CAS (with embolic protection) or CEA in the Vascular Quality Initiative (VQI) database (2013-2016) were included. Patients were stratified as being at normal risk (Nr) or high risk (Hr) for undergoing CEA on the basis of CMS criteria. Thirty-day and 2-year stroke outcomes were compared for CAS vs CEA in both the Nr and Hr groups using 1:1 coarsened exact matching and multivariable Cox proportional hazards modeling. ResultsA total of 51,942 patients (CAS, 7030; CEA, 44,912) underwent carotid revascularization during the study period. Thirty-day (Nr, 1.7% vs 1.0%; Hr, 2.5% vs 1.4%) and 2-year (Nr, 1.9% vs 1.0%; Hr, 2.4% vs 1.3%) stroke occurred more frequently after CAS vs CEA on crude analysis (P < .001). After matching 2920 pairs of patients on 18 preoperative variables, the risk of 30-day and 2-year stroke remained higher after CAS in the Hr group (30-day risk: hazard ratio [HR], 1.90; 95% confidence interval [CI], 1.26-2.85; 2-year risk: HR, 1.65; 95% CI, 1.05-2.60) but was similar for CAS vs CEA in the Nr group (30-day risk: HR, 0.97; 95% CI, 0.48-1.95; 2-year risk: HR, 1.49; 95% CI, 0.76-2.90). ConclusionsThese data suggest that the utility of CAS in Nr patients may be underappreciated, whereas the potential benefit of CAS in Hr patients may be overestimated. Re-evaluation of the criteria for identifying patients at high risk for CEA and the national guidelines on the indications for CAS is strongly indicated.

Emergence of No-collar Work force and Challenges from HR Perspectives

As automation, cognitive technologies and artificial intelligence gain transaction, companies may need to reinvent worker roles, assigning some to humans, others to machines and still others to a hybrid model in which technology augments human performance. Managing both humans and machines will present new challenges to the human resources organisation, including how to simultaneously retrain augmented workers and to pioneer new HR processes for managing virtual workers, cognitive agents, robots and the other artificial intelligence driven capabilities comprising the ‘no-collar’ workforce. By redesigning legacy practices, systems and talent models around the tenets of autonomous, HR groups can begin transforming themselves into nimble, fast-moving, dynamic organisations better positioned to support the talent-both mechanised and human of tomorrow.

Metabolomics Reveals Protection of Resveratrol in Diet-Induced Metabolic Risk Factors in Abdominal Muscle

Background/Aims: Abdominal obesity is recognized as the main reason of metabolic syndrome, which is closely related to disordered skeletal and/or abdominal muscle metabolic functions. Metabolomics is a comprehensive assessment system in biological metabolites. The aim of our present study is to investigate the diet-induced metabolic risk factors by metabolic in the abdominal muscles and clarify the relationship between atheroprotective effects of Resveratrol (Rev) and abdominal muscles metabolic components during the development of atherosclerosis. Methods: The mice were randomly divided into three groups including normal group (N), high fat diet (HFD or H) group and high fat diet with Rev treated group (HR). GC-MS combined with pattern recognition approaches were employed to obtain comprehensive metabolic signatures and related differential metabolites after 24 week HFD feeding. Oil Red O staining and Electron microscopy technology (EMT) were employed to detect the size of fatty plaques and intracellular lipid accumulation, respectively. Results: The result indicated that 22 types of metabolites in the abdominal muscles were obviously altered by HFD feeding group. Moreover, Rev treatment obviously increased 11 different kinds of metabolites, most of which were involved in the carbohydrate, amino acid and lipid metabolisms. Importantly, these elevated different metabolites were involved in pathways mainly related to galactose metabolism, alanine, aspartate and glutamate metabolism, glyoxylate and dicarboxylate metabolism in abdominal muscles. Oil Red O staining and Electron microscopy showed less lipid accumulation in the lesions and decreased intracellular lipid deposition in the foam cells in HR group. Conclusions: We concluded that Rev produced a beneficial effect partially by modulating multiple metabolism pathways and metabolites in the abdominal muscles, which may provide a new protective mechanism of Rev on the progression of atherosclerosis. These notably changed metabolites might be potential biomarkers or therapeutic targets during development of metabolic syndrome and atherosclerosis.