Chronic pain, chronic stress and substance use: overlapping mechanisms and implications.

Chronic pain is among the most common reasons adults in the U.S. seek medical care. Despite chronic pain's substantial impact on individuals' physical, emotional, and financial wellness, the biologic underpinnings of chronic pain remain incompletely understood. Such deleterious impact on an individuals' wellness is also manifested in the substantial co-occurrence of chronic stress with chronic pain. However, whether chronic stress and adversity and related alcohol and substance misuse increases risk of developing chronic pain, and, if so, what the overlapping psychobiological processes are, is not well understood. Individuals suffering with chronic pain find alleviation through prescription opioids as well as non-prescribed cannabis, alcohol, and other drugs to control pain, and use of these substances have grown significantly. Substance misuse also increases experience of chronic stress. Thus, given the evidence showing a strong correlation between chronic stress and chronic pain, we aim to review and identify overlapping factors and processes. We first explore the predisposing factors and psychologic features common to both conditions. This is followed by examining the overlapping neural circuitry of pain and stress in order to trace a common pathophysiologic processes for the development of chronic pain and its link to substance use. Based on the previous literature and our own findings, we propose a critical role for ventromedial prefrontal cortex dysfunction, an overlapping brain area associated with the regulation of both pain and stress that is also affected by substance use, as key in the risk of developing chronic pain. Finally, we identify the need for future research in exploring the role of medial prefrontal circuits in chronic pain pathology. Critically, in order to alleviate the enormous burden of chronic pain without exacerbating the co-occurring substance misuse crisis, we emphasize the need to find better approaches to treat and prevent chronic pain.

Biomechanical evaluation of the impact of collared cementless total hip arthroplasty stems on implant subsidence: a cadaveric study in German Shepherd.

Background: With the increasing use of cementless total hip arthroplasty (THA), stem subsidence has emerged as one of the primary complications. Although electron beam melting (EBM)-manufactured stems have been demonstrated to prevent subsidence, there has been limited investigation into the comparative biomechanical impact of collarless and collared EBM cementless stems on stem subsidence in veterinary medicine. Aims: This study aimed to compare the stem implant resistance and failure mechanical properties between collarless and collared EBM-manufactured stems. Methods: Seven pairs of femurs were harvested from canine cadavers. In each pair of femurs, the left femur was implanted with a collarless, and the right femur with a same-sized collared cementless stem. Specimen constructs were mounted to the loading frame of a testing machine and load was transferred to the femoral stem parallel to the longitudinal axis of the femur until the stem subsided 5 mm. Load and stem displacement data acquired during the tests were used to generate load-displacement curves and obtain stiffness, yield, and failure data for each specimen construct. Yield and failure energies were calculated as the areas under the load-displacement curves to the respective points. The effects of implant type and load during subsidence were analyzed using paired t-tests. Results: The yield and failure loads for the collared stems were approximately 40% greater than for the collarless stems (156.39 ± 43.63 kgf vs. 112.01 ± 59.83 kgf, P<0.05). Conclusion: This study supported the advantages of collared EBM stems, including subsidence prevention and better initial stability for early osteointegration.

Comparison of major histocompatibility complex-B variability in Sri Lankan indigenous chickens with five global chicken populations using MHC-B SNP panel.

In the present study, we investigated the major histocompatibility complex (MHC)-B haplotypes diversity of Sri Lankan indigenous chickens from three different geographical sites consisting of highly mixed populations using 90 SNPs in the MHC-B region. A total of 48 haplotypes were identified. Those included 37 novel haplotypes and 11 previously identified 'standard' haplotypes. The MHC-linked marker, LEI0258, had 23 alleles showing less diversity than defined by MHC-B SNP haplotypes. Among those identified haplotypes, five standard haplotypes-BSNP-O02, BSNP-M01, BSNP-A04, BSNP-K03, BSNP-T04-were most commonly observed, suggesting past introgression of imported breeds. Comparison of the MHC-B haplotypes of Sri Lankan and four other global populations with previously defined haplotypes indicated the sharing of 23 standard haplotypes with common origins. Novel haplotypes are population-specific and not shared among the geographical boundaries. Backyard indigenous chickens are unselected, highly crossbred, and generally thrive under dynamic environmental conditions. Hence free-range production systems may be responsible for maintaining high diversity in the MHC-B region with novel haplotypes.

Sarcopenia is associated with non-alcoholic fatty liver disease in men with type 2 diabetes.

AIMS: Recent epidemiological studies have suggested an association between sarcopenia and non-alcoholic fatty liver disease (NAFLD) in the general population, prompting our investigation into the gender-specific association between sarcopenia and NAFLD in patients with type 2 diabetes mellitus (T2DM). METHODS: In this cross-sectional study, 4210 patients with T2DM were recruited from the Seoul Metabolic Syndrome Cohort. Appendicular skeletal muscle mass (ASM) was estimated from bioimpedance analysis measurements, and the skeletal muscle mass index (SMI) was calculated by dividing the sum of ASM by body weight. Sarcopenia was defined as a gender-specific SMI value>2 standard deviations (SDs) below the mean for healthy young adults. NAFLD was defined as the presence of hepatic steatosis on ultrasonography with no other causes of chronic liver disease. RESULTS: Among the entire study population (mean age: 57.4±10.8 years), 1278 (30.4%) had NAFLD and 1240 (29.5%) had sarcopenia, and the prevalence of NAFLD was significantly higher in those with sarcopenia: 46.2% vs 25.1% (P<0.001) in men; 38.3% vs 25.4% (P<0.001) in women. Sarcopenia was significantly associated with higher risk of NAFLD in men (adjusted odds ratio [OR]: 1.58, 95% confidence interval [CI]: 1.15-2.17), whereas the association was attenuated in women after adjusting for clinical risk factors. CONCLUSION: Sarcopenia is independently associated with NAFLD in men with T2DM, which suggests that sarcopenia may be a risk factor for NAFLD in men with T2DM.

Non alcoholic fatty liver disease and risk of incident diabetes in subjects who are not obese.

BACKGROUND AND AIMS: It is not known whether non alcoholic fatty liver disease (NAFLD) is a risk factor for diabetes in non obese, non centrally-obese subjects. Our aim was to investigate relationships between fatty liver, insulin resistance and a biomarker score for liver fibrosis with incident diabetes at follow up, in subjects who were neither obese nor centrally-obese. METHODS AND RESULTS: As many as 70,303 subjects with a body mass index (BMI) < 25 kg/m2 and without diabetes were followed up for a maximum of 7.9 years. At baseline, fatty liver was identified by liver ultrasound, insulin resistance (IR) by homeostatic model assessment of insulin resistance (HOMA-IR) ≥2.0, and central obesity by waist circumference (waist circumference ≥90 cm (men) and ≥85 cm (women). The Fibrosis-4 (FIB-4 score) was used to estimate extent of liver fibrosis. Cox proportional hazards models adjusted for confounders were used to estimate hazard ratios (aHRs) for incident diabetes. As many as 852 incident cases of diabetes occurred during follow up (median [IQR] 3.71 [2.03] years). Mean ± SD BMI was 22.8 ± 1.8 and 21.7 ± 2.0 kg/m2 in subjects with and without diabetes at follow up. In subjects without central obesity and with fatty liver, aHRs (95% CI) for incident diabetes at follow up were 2.17 (1.56, 3.03) for men, and 2.86 (1.50,5.46) for women. Similar aHRs for incident diabetes occurred with fatty liver, IR and the highest quartile of FIB-4 combined, in men; and there was a non significant trend toward increased risk in women. CONCLUSIONS: In normal weight, non-centrally obese subjects NAFLD is an independent risk factor for incident diabetes.

Clinical characteristics of diabetic ketoacidosis in users and non-users of SGLT2 inhibitors.

AIM: This study investigated the clinical characteristics of diabetic ketoacidosis (DKA) and compared the DKA characteristics between patients treated with and without SGLT2 inhibitors. METHODS: Data were collected from patients aged ≥ 18 years admitted for DKA at nine centres in Korea between September 2014 and April 2017. The electronic medical records of these subjects were retrospectively reviewed. Based on their history of medications taken before admission, subjects were classified as either users or non-users of SGLT2 inhibitors and their clinical characteristics of DKA were compared. RESULTS: During the study, the main subtype of DKA episodes (n = 523) was identified as type 2 diabetes (51%). Average hospitalization duration was 11 days, and average intensive care unit (ICU) time was 2.5 days. The in-hospital mortality rate was 3%, but no users of SGLT2 inhibitors died during DKA treatment. In patients taking SGLT2 inhibitors (n = 15), DKA manifested at 124 days, on average, after starting the inhibitors (range: 7-380 days). Also, SGLT2 inhibitors users had significantly lower plasma glucose levels (413 mg/dL) compared with non-users (554 mg/dL), and longer ICU stays (4 vs. 2 days; P = 0.019). CONCLUSION: In this report of recent data on the clinical features of DKA in Korea, patients using SGLT2 inhibitors needed longer treatment in ICUs compared with non-users and had lower levels of blood glucose, whereas DKA associated with SGLT2 inhibitors was rare.

Non-tuberculous Mycobacterium infection after transfer of autologous fat to the face: a rare case.

Autologous fat has long been used as a filler in the face, and has recently gained popularity in plastic surgery with a wound infection rate of 1% - 5%. The incidence of mycobacterial infections has increased over recent decades, which is attributed in part to the increased popularity of these procedures.2 Infections by non-tuberculosis mycobacteria often cause chronic inflammation and progressive infection that may eventually manifest themselves as severe scars, fistulas, and hollows, and irregular facial contours. However, few cases of mycobacterial infection have been reported to have been caused by plastic surgery. We present a rare case of non-tuberculosis mycobacterial infection after transfer of autologous fat to the face.

Establishment of optimal barley straw biochar application conditions for rice cultivation in a paddy field.

This study was conducted to establish the optimal application conditions of barley straw biochar (BC) for rice cultivation and to determine the effects of combined application of BC and inorganic fertilizer (IF) on rice cultivation in a paddy field. Based on the characteristics of rice growth in pot-based experiments, the selected optimal application conditions of BC were application of 20 ton ha-1 at 14 days before rice transplanting. The effects of BC application on rice cultivation in a paddy field when using those conditions were then evaluated. Each treatment was separated by a control (Cn), IF, BC, and combined BC + IF treatments, respectively. The rice yields in the BC + IF treatment were 38.6, 21.7, and 24.5% greater than those in the Cn, IF, and BC treatments, respectively. In addition, yield components of rice were significantly improved in the BC + IF treatment relative to the other treatments. Following rice harvest, soil status was improved, showing greater soil aggregation stability, decreased bulk density, and increased porosity in the BC-treated areas compared to those in the Cn- and IF-treated areas. At the time of rice harvesting, soil chemical properties such as pH, EC, SOC, TN, Avail. P2O5, and CEC in the BC-treated areas were improved over those in other areas. The results of this study indicate that using BC as a soil amendment is effective at improving rice cultivation and can benefit the soil environment.

Blood lactate concentration and shock index associated with massive transfusion in emergency department patients with primary postpartum haemorrhage.

BACKGROUND: We hypothesised that lactate concentrations are independently associated with massive transfusion in patients with primary postpartum haemorrhage. Moreover, combining lactate concentrations with the shock index, defined as the ratio of heart rate to systolic arterial blood pressure, can improve the predictive performance for massive transfusion. METHODS: We retrospectively analysed patients with primary postpartum haemorrhage in the emergency department of a tertiary referral centre in Korea between January 1, 2004 and December 31, 2015. RESULTS: Of the 302 patients, 101 (33.4%) patients required massive transfusion. Lactate concentration was independently associated with the requirement for massive transfusion [odds ratio, 1.56; 95% confidence interval (CI), 1.31-1.87; P<0.01]. The area under the receiver operating characteristic curve of lactate concentration and shock index for massive transfusion was 0.788 (95% CI: 0.736-0.840; P<0.01) and 0.776 (95% CI: 0.717-0.836; P<0.01), respectively. Lactate elevation (>4.0 mM L-1) was associated with 86.1% specificity and 67.8% positive predictive value for massive transfusion. When combining elevated lactate concentrations (>4.0 mM L-1) with a shock index >1.0, the specificity and positive predictive value increased to 95.5% and 82.4%, respectively. CONCLUSIONS: Point-of-care testing of lactate concentrations in the emergency department may be useful to predict massive transfusion requirements in primary postpartum haemorrhage. Combining initial lactate concentrations with the shock index improves the predictive performance for massive transfusion requirements and may contribute to rapid risk stratification of patients with primary postpartum haemorrhage in need of transfusion and further focus on early interventions to control bleeding.

The relationship between fatty liver index and bone mineral density in Koreans: KNHANES 2010-2011.

Analyses using a nationally representative cohort have revealed that high fatty liver index (FLI) is associated with low bone mineral density (BMD) regardless of insulin resistance in men, thereby supporting the deteriorated bone metabolism in nonalcoholic fatty liver disease (NAFLD). INTRODUCTION: NAFLD is linked to deteriorated bone health. We investigated the association of FLI, a scoring model for NAFLD, with BMD. METHODS: This was a population-based, cross-sectional study from the Korea National Health and Nutrition Examination Surveys including 4264 Koreans (1908 men and 2356 women). FLI was calculated using body mass index, waist circumference, serum triglyceride, and gamma-glutamyltranspeptidase level. Insulin resistance was evaluated using the homeostasis model assessment-estimated insulin resistance (HOMA-IR) index. BMD was measured using dual-energy X-ray absorptiometry at the lumbar spine, total hip, femoral neck, and whole body. RESULTS: Men had a higher FLI than women, while the HOMA-IR index was similar between men and women. The significant association between FLI and BMD was observed only in men, but not in women. FLI was negatively correlated with total hip, femoral neck, and whole body BMD in men after adjusting for all potential confounders, including HOMA-IR (P < 0.001 to 0.010). Lumbar spine, total hip, femoral neck, and whole body BMD in men showed a decreasing trend as the FLI tertile increased after adjusting for all potential confounders, including HOMA-IR (P for trends < 0.001 to 0.034). In men aged 50 years or older, odds ratios for combined osteopenia and osteoporosis increased across increasing FLI tertiles after adjusting for confounders (P for trends < 0.011 to 0.029). CONCLUSION: NAFLD is associated with low bone density regardless of insulin resistance in men. These findings suggest an undiscovered direct link between liver and bone that increases the risk of osteoporosis in men with NAFLD.

Electrostatic Screening of Charged Defects in Monolayer MoS2.

Defects in monolayer transition-metal dichalcogenides (TMDCs) may lead to unintentional doping, charge-carrier trapping, and nonradiative recombination. These effects impair electronic and optoelectronic technologies. Here we show that charged defects in MoS2 monolayers can be effectively screened when they are in contact with an ionic liquid (IL), leading to an increase in photoluminescence (PL) yield by up to two orders of magnitude. The extent of this PL enhancement by the IL correlates with the brightness of each pretreated sample. We propose the existence of two classes of nonradiative recombination centers in monolayer MoS2: (i) charged defects that relate to unintentional doping and may be electrostatically screened by ILs and (ii) neutral defects that remain unaffected by the presence of ILs.

Bidirectional Control of Anxiety-Related Behaviors in Mice: Role of Inputs Arising from the Ventral Hippocampus to the Lateral Septum and Medial Prefrontal Cortex.

Anxiety is an adaptive response to potentially threatening situations. Exaggerated and uncontrolled anxiety responses become maladaptive and lead to anxiety disorders. Anxiety is shaped by a network of forebrain structures, including the hippocampus, septum, and prefrontal cortex. In particular, neural inputs arising from the ventral hippocampus (vHPC) to the lateral septum (LS) and medial prefrontal cortex (mPFC) are thought to serve as principal components of the anxiety circuit. However, the role of vHPC-to-LS and vHPC-to-mPFC signals in anxiety is unclear, as no study has directly compared their behavioral contribution at circuit level. We targeted LS-projecting vHPC cells and mPFC-projecting vHPC cells by injecting the retrogradely propagating canine adenovirus encoding Cre recombinase into the LS or mPFC, and injecting a Cre-responsive AAV (AAV8-hSyn-FLEX-hM3D or hM4D) into the vHPC. Consequences of manipulating these neurons were examined in well-established tests of anxiety. Chemogenetic manipulation of LS-projecting vHPC cells led to bidirectional changes in anxiety: activation of LS-projecting vHPC cells decreased anxiety whereas inhibition of these cells produced opposite anxiety-promoting effects. The observed anxiety-reducing function of LS-projecting cells was in contrast with the function of mPFC-projecting cells, which promoted anxiety. In addition, double retrograde tracing demonstrated that LS- and mPFC-projecting cells represent two largely anatomically distinct cell groups. Altogether, our findings suggest that the vHPC houses discrete populations of cells that either promote or suppress anxiety through differences in their projection targets. Disruption of the intricate balance in the activity of these two neuron populations may drive inappropriate behavioral responses seen in anxiety disorders.

Transoesophageal echocardiographic evaluation of central venous catheter positioning using Peres' formula or a radiological landmark-based approach: a prospective randomized single-centre study.

BACKGROUND: The lower superior vena cava (SVC), near its junction with the right atrium (RA), is considered the ideal location for the central venous catheter tip to ensure proper function and prevent injuries. We determined catheter insertion depth with a new formula using the sternoclavicular joint and the carina as radiological landmarks, with a 1.5 cm safety margin. The accuracy of tip positioning with the radiological landmark-based technique (R) and Peres' formula (P) was compared using transoesophageal echocardiography. METHODS: Real-time ultrasound-guided central venous catheter insertion was done through the right internal jugular or subclavian vein. Patients were randomly assigned to either the P group (n=93) or the R group (n=95). Optimal catheter tip position was considered to be within 2 cm above and 1 cm below the RA-SVC junction. Catheter tip position, abutment, angle to the vascular wall, and flow stream were evaluated on a bicaval view. RESULTS: The distance from the skin insertion point to the RA-SVC junction and determined depth of catheter insertion were more strongly correlated in the R group [17.4 (1.2) and 16.7 (1.5) cm; r=0.821, P<0.001] than in the P group [17.3 (1.2) and 16.4 (1.1) cm; r=0.517, P<0.001], with z=3.96 (P<0.001). More tips were correctly positioned in the R group than in the P group (74 vs 93%, P=0.001). Abutment, tip angle to the lateral wall >40°, and disrupted flow stream were comparable. CONCLUSIONS: Catheter tip position was more accurate with a radiological landmark-based technique than with Peres' formula. CLINICAL TRIAL REGISTRATION: Clinical Trial Registry of Korea: https://cris.nih.go.kr/cris/index.jsp KCT0001937.

TET-mediated hydroxymethylcytosine at the Pparγ locus is required for initiation of adipogenic differentiation.

BACKGROUND/OBJECTIVES: Adipose tissue is one of the main organs regulating energy homeostasis via energy storage as well as endocrine function. The adipocyte cell number is largely determined by adipogenesis. While the molecular mechanism of adipogenesis has been extensively studied, its role in dynamic DNA methylation plasticity remains unclear. Recently, it has been shown that Tet methylcytosine dioxygenase (TET) is catalytically capable of oxidizing DNA 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) toward a complete removal of the methylated cytosine. We investigate whether expression of the Tet genes and production of hydroxymethylcytosine are required for preadipocyte differentiation. SUBJECTS/METHODS: Murine 3T3-L1 preadipocytes were used to evaluate the role of Tet1 and Tet2 genes during adipogenesis. Changes in adipogenic ability and in epigenetic status were analyzed, with and without interfering Tet1 and Tet2 expression using small interfering RNA (siRNA). The adipogenesis was evaluated by Oil-Red-O staining and induced expression of adipogenic genes using quantitative polymerase chain reaction (qPCR). Levels of 5-hmC and 5-mC were measured by MassARRAY, immunoprecipitation and GC mass spectrometry at specific loci as well as globally. RESULTS: Both Tet1 and Tet2 genes were upregulated in a time-dependent manner, accompanied by increased expression of hallmark adipogenic genes such as Pparγ and Fabp4 (P<0.05). The TET upregulation led to reduced DNA methylation and elevated hydroxymethylcytosine, both globally and specifically at the Pparγ locus (P<0.05 and P<0.01, respectively). Knockdown of Tet1 and Tet2 blocked adipogenesis (P<0.01) by repression of Pparγ expression (P<0.05). In particular, Tet2 knockdown repressed conversion of 5-mC to 5-hmC at the Pparγ locus (P<0.01). Moreover, vitamin C treatment enhanced adipogenesis (P<0.05), while fumarate treatment inhibited it (P<0.01) by modulating TET activities. CONCLUSIONS: TET proteins, particularly TET2, were required for adipogenesis by modulating DNA methylation at the Pparγ locus, subsequently by inducing Pparγ gene expression.

Relationship between serum testosterone and nocturia in men without benign prostate enlargement.

Recent studies have focused on the relationship between nocturia and serum testosterone because testosterone is thought to be an important factor of prostate growth. However, it remains unclear whether altered serum concentrations of testosterone is associated with an increased risk of nocturia because patients who were taking diuretics or who had a large prostate, which may precipitate nocturia, were not excluded from most previous studies. We analyzed the clinical records of 596 non-benign prostatic enlargement (BPE) male patients to explore the relationship between serum total testosterone and nocturia. All patients were evaluated using a serum prostate-specific antigen (PSA) assay, measurement of serum total testosterone, transrectal ultrasonography, uroflowmetry, and a compilation of the International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF) questionnaires. Nocturia was defined as ≥2 nocturnal voiding episodes. The number of nocturia episodes was assessed using IPSS question 7. To evaluate the effect of serum testosterone on nocturia, multivariate regression analysis was performed including the covariates of age, IPSS, IIEF score, body mass index, PSA, prostate volume, and maximal urine flow rate. Based on multivariate linear analysis, serum testosterone level was not significantly associated with the severity of nocturia. However, with regard to the relationship between prevalence of nocturia and serum testosterone, prevalence of nocturia was significantly positively associated with age (OR = 1.048, p = 0.005), total IPSS (OR = 1.217, p < 0.001), and testosterone level (OR = 1.150, p = 0.041). Therefore, in men without an enlarged prostate, testosterone may play an opposing role in the etiology of nocturia.

Genome-wide linkage disequilibrium and past effective population size in three Korean cattle breeds.

The routine collection and use of genomic data are useful for effectively managing breeding programs for endangered populations. Linkage disequilibrium (LD) using high-density DNA markers has been widely used to determine population structures and predict the genomic regions that are associated with economic traits in beef cattle. The extent of LD also provides information about historical events, including past effective population size (Ne ), and it allows inferences on the genetic diversity of breeds. The objective of this study was to estimate the LD and Ne in three Korean cattle breeds that are genetically similar but have different coat colors (Brown, Brindle and Jeju Black Hanwoo). Brindle and Jeju Black are endangered breeds with small populations, whereas Brown Hanwoo is the main breeding population in Korea. DNA samples from these cattle breeds were genotyped using the Illumina BovineSNP50 Bead Chip. We examined 13 cattle breeds, including European taurines, African taurines and indicines, and hybrids to compare their LD values. Brown Hanwoo consistently had the lowest mean LD compared to Jeju Black, Brindle and the other 13 cattle breeds (0.13, 0.19, 0.21 and 0.15-0.22 respectively). The high LD values of Brindle and Jeju Black contributed to small Ne values (53 and 60 respectively), which were distinct from that of Brown Hanwoo (531) for 11 generations ago. The differences in LD and Ne for each breed reflect the breeding strategy applied. The Ne for these endangered cattle breeds remain low; thus, effort is needed to bring them back to a sustainable tract.

Novel deletion mutation of HLA-B*40:02 gene in acquired aplastic anemia.

Despite prevalence of clonal evolution in patients with aplastic anemia (AA), somatic mutation of human leukocyte antigen (HLA) gene is rarely reported. Herein, we reported a case of acquired AA (aAA) harboring a new four-base-pair deletion mutation within exon 4 of HLA-B*40:02 leading to frameshift and premature stop codon. The HLA-B*40:02 mutant allele was detected in the patient's peripheral blood sample not in patient's buccal epithelial cells. The patient received allogenic hematopoietic stem cell transplantation (HSCT) from HLA-matched sibling donor. On day 30 after HSCT, the mutant HLA allele was not detected by high-resolution sequence-based HLA typing. Serial chimerism analyses showed mixed chimeric status indicative of coexisting donor and recipient hematopoietic cells. Our data could provide additional support in view of pathophysiology of aAA that somatic mutation of HLA-B*40:02 allele is one of the possible origin of clonal escape to evade immune attack in patient with aAA.

Food image-induced brain activation is not diminished by insulin infusion.

BACKGROUND/OBJECTIVES: The obesity epidemic appears to be driven in large part by our modern environment inundated by food cues, which may influence our desire to eat. Although insulin decreases food intake in both animals and humans, the effect of insulin on motivation for food in the presence of food cues is not known. Therefore, the aim of this study was to evaluate the effect of an intravenous insulin infusion on the brain response to visual food cues, hunger and food craving in non-obese human subjects. SUBJECTS/METHODS: Thirty-four right-handed healthy non-obese subjects (19F/15M, age: 29±8 years.; BMI: 23.1±2.1 kg m-2) were divided in two groups matched by age and BMI; the insulin group (18 subjects) underwent a hyperinsulinemic-euglycemic-clamp, and the control group (16 subjects) received an intravenous saline infusion, while viewing high and low-calorie food and non-food pictures during a functional MRI scan. Motivation for food was determined via analog scales for hunger, wanting and liking ratings. RESULTS: Food images induced brain responses in the hypothalamus, striatum, amygdala, insula, ventromedial prefrontal cortex (PFC), dorsolateral PFC and occipital lobe (whole brain correction, P<0.05). Wanting (P<0.001) and liking (P<0.001) ratings were significantly higher for the food than the non-food images, but not different between insulin and saline infusion groups. Hunger ratings increased throughout the MRI scan and correlated with preference for high-calorie food pictures (r=0.70; P<0.001). However, neither brain activity nor food cravings were affected by hyperinsulinemia or hormonal status (leptin and ghrelin levels) (P=NS). CONCLUSIONS: Our data demonstrate that visual food cues induce a strong response in motivation/reward and cognitive-executive control brain regions in non-obese subjects, but that these responses are not diminished by hyperinsulinemia per se. These findings suggest that our modern food cue saturated environment may be sufficient to overpower homeostatic hormonal signals, and thus contribute to the current obesity epidemic.

A Major Locus for Quantitatively Measured Shank Skin Color Traits in Korean Native Chicken.

Shank skin color of Korean native chicken (KNC) shows large color variations. It varies from white, yellow, green, bluish or grey to black, whilst in the majority of European breeds the shanks are typically yellow-colored. Three shank skin color-related traits (i.e., lightness [L*], redness [a*], and yellowness [b*]) were measured by a spectrophotometer in 585 progeny from 68 nuclear families in the KNC resource population. We performed genome scan linkage analysis to identify loci that affect quantitatively measured shank skin color traits in KNC. All these birds were genotyped with 167 DNA markers located throughout the 26 autosomes. The SOLAR program was used to conduct multipoint variance-component quantitative trait locus (QTL) analyses. We detected a major QTL that affects b* value (logarithm of odds [LOD] = 47.5, p = 1.60×10-49) on GGA24 (GGA for Gallus gallus). At the same location, we also detected a QTL that influences a* value (LOD = 14.2, p = 6.14×10-16). Additionally, beta-carotene dioxygenase 2 (BCDO2), the obvious positional candidate gene under the linkage peaks on GGA24, was investigated by the two association tests: i.e., measured genotype association (MGA) and quantitative transmission disequilibrium test (QTDT). Significant associations were detected between BCDO2 g.9367 A>C and a* (PMGA = 1.69×10-28; PQTDT = 2.40×10-25). The strongest associations were between BCDO2 g.9367 A>C and b* (PMGA = 3.56×10-66; PQTDT = 1.68×10-65). However, linkage analyses conditional on the single nucleotide polymorphism indicated that other functional variants should exist. Taken together, we demonstrate for the first time the linkage and association between the BCDO2 locus on GGA24 and quantitatively measured shank skin color traits in KNC.

Utility of blood pressure genetic risk score in admixed Hispanic samples.

Hypertension is strongly influenced by genetic factors. Although hypertension prevalence in some Hispanic sub-populations is greater than in non-Hispanic whites, genetic studies on hypertension have focused primarily on samples of European descent. A recent meta-analysis of 200 000 individuals of European descent identified 29 common genetic variants that influence blood pressure, and a genetic risk score derived from the 29 variants has been proposed. We sought to evaluate the utility of this genetic risk score in Hispanics. The sample set consists of 1994 Hispanics from 2 cohorts: the Northern Manhattan Study (primarily Dominican/Puerto Rican) and the Miami Cardiovascular Registry (primarily Cuban/South American). Risk scores for systolic and diastolic blood pressure were computed as a weighted sum of the risk alleles, with the regression coefficients reported in the European meta-analysis used as weights. Association of risk score with blood pressure was tested within each cohort, adjusting for age, age2, sex and body mass index. Results were combined using an inverse-variance meta-analysis. The risk score was significantly associated with blood pressure in our combined sample (P=5.65 × 10-4 for systolic and P=1.65 × 10-3 for diastolic) but the magnitude of the effect sizes varied by degree of European, African and Native American admixture. Further studies among other Hispanic sub-populations are needed to elucidate the role of these 29 variants and identify additional genetic and environmental factors contributing to blood pressure variability in Hispanics.