Distinct firing activities of the hypothalamic arcuate nucleus neurons to appetite hormones

The hypothalamic arcuate nucleus (Arc) is a central unit that controls the appetite through the integration of metabolic, hormonal, and neuronal afferent inputs. Agouti-related protein (AgRP), proopiomelanocortin (POMC), and dopaminergic neurons in the Arc differentially regulate feeding behaviors in response to hunger, satiety, and appetite, respectively. At the time of writing, the anatomical and electrophysiological characterization of these three neurons has not yet been intensively explored. Here, we interrogated the overall characterization of AgRP, POMC, and dopaminergic neurons using genetic mouse models, immunohistochemistry, and whole-cell patch recordings. We identified the distinct geographical location and intrinsic properties of each neuron in the Arc with the transgenic lines labelled with cell-specific reporter proteins. Moreover, AgRP, POMC, and dopaminergic neurons had different firing activities to ghrelin and leptin treatments. Ghrelin led to the increased firing rate of dopaminergic and AgRP neurons, and the decreased firing rate of POMC. In sharp contrast, leptin resulted in the decreased firing rate of AgRP neurons and the increased firing rate of POMC neurons, while it did not change the firing rate of dopaminergic neurons in Arc. These findings demonstrate the anatomical and physiological uniqueness of three hypothalamic Arc neurons to appetite control

Distinct Firing Activities of the Hypothalamic Arcuate Nucleus Neurons to Appetite Hormones

The hypothalamic arcuate nucleus (Arc) is a central unit that controls the appetite through the integration of metabolic, hormonal, and neuronal afferent inputs. Agouti-related protein (AgRP), proopiomelanocortin (POMC), and dopaminergic neurons in the Arc differentially regulate feeding behaviors in response to hunger, satiety, and appetite, respectively. At the time of writing, the anatomical and electrophysiological characterization of these three neurons has not yet been intensively explored. Here, we interrogated the overall characterization of AgRP, POMC, and dopaminergic neurons using genetic mouse models, immunohistochemistry, and whole-cell patch recordings. We identified the distinct geographical location and intrinsic properties of each neuron in the Arc with the transgenic lines labelled with cell-specific reporter proteins. Moreover, AgRP, POMC, and dopaminergic neurons had different firing activities to ghrelin and leptin treatments. Ghrelin led to the increased firing rate of dopaminergic and AgRP neurons, and the decreased firing rate of POMC. In sharp contrast, leptin resulted in the decreased firing rate of AgRP neurons and the increased firing rate of POMC neurons, while it did not change the firing rate of dopaminergic neurons in Arc. These findings demonstrate the anatomical and physiological uniqueness of three hypothalamic Arc neurons to appetite control

THE IMPACT OF NATIONAL CULTURE ON BILATERAL TRADE IN VIETNAM

The purpose of this paper is to examine whether or to what extent national culture influences bilateral trade flows between Vietnam and its trading partners. Using a panel dataset of 52 countries from 2001 till 2011 and six cultural dimensions of Hofstede, the regression analysis performed by gravity model shows that national culture and bilateral trade flows between Vietnam and trading partners are significantly correlated. This study's implications may help macro-policy makers devise better export promotion policies and boost the volume of bilateral trade between Vietnam and other countries around the world

Altered Metabolic Phenotypes and Hypothalamic Neuronal Activity Triggered by Sodium-Glucose Cotransporter 2 Inhibition

Background Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are currently used to treat patients with diabetes. Previous studies have demonstrated that treatment with SGLT-2 inhibitors is accompanied by altered metabolic phenotypes. However, it has not been investigated whether the hypothalamic circuit participates in the development of the compensatory metabolic phenotypes triggered by the treatment with SGLT-2 inhibitors. Methods Mice were fed a standard diet or high-fat diet and treated with dapagliflozin, an SGLT-2 inhibitor. Food intake and energy expenditure were observed using indirect calorimetry system. The activity of hypothalamic neurons in response to dapagliflozin treatment was evaluated by immunohistochemistry with c-Fos antibody. Quantitative real-time polymerase chain reaction was performed to determine gene expression patterns in the hypothalamus of dapagliflozin-treated mice. Results Dapagliflozin-treated mice displayed enhanced food intake and reduced energy expenditure. Altered neuronal activities were observed in multiple hypothalamic nuclei in association with appetite regulation. Additionally, we found elevated immunosignals of agouti-related peptide neurons in the paraventricular nucleus of the hypothalamus. Conclusion This study suggests the functional involvement of the hypothalamus in the development of the compensatory metabolic phenotypes induced by SGLT-2 inhibitor treatment

Risk Factors of Streptococcus suis Infection in Vietnam. A Case-Control Study

Background: Streptococcus suis infection, an emerging zoonosis, is an increasing public health problem across South East Asia and the most common cause of acute bacterial meningitis in adults in Vietnam. Little is known of the risk factors underlying the disease. Methods and Findings: A case-control study with appropriate hospital and matched community controls for each patient was conducted between May 2006 and June 2009. Potential risk factors were assessed using a standardized questionnaire and investigation of throat and rectal S. suis carriage in cases, controls and their pigs, using real-time PCR and culture of swab samples. We recruited 101 cases of S. suis meningitis, 303 hospital controls and 300 community controls. By multivariate analysis, risk factors identified for S. suis infection as compared to either control group included eating "high risk" dishes, including such dishes as undercooked pig blood and pig intestine (OR1 = 2.22; 95% CI = [1.15-4.28] and OR2 = 4.44; 95% CI = [2.15-9.15]), occupations related to pigs (OR1 = 3.84; 95% CI = [1.32-11.11] and OR2 = 5.52; 95% CI = [1.49-20.39]), and exposures to pigs or pork in the presence of skin injuries (OR1 = 7.48; 95% CI = [1.97-28.44] and OR2 = 15.96; 95% CI = [2.97-85.72]). S. suis specific DNA was detected in rectal and throat swabs of 6 patients and was cultured from 2 rectal samples, but was not detected in such samples of 1522 healthy individuals or patients without S. suis infection. Conclusions: This case control study, the largest prospective epidemiological assessment of this disease, has identified the most important risk factors associated with S. suis bacterial meningitis to be eating 'high risk' dishes popular in parts of Asia, occupational exposure to pigs and pig products, and preparation of pork in the presence of skin lesions. These risk factors can be addressed in public health campaigns aimed at preventing S. suis infectio

Standardised patient study to assess tuberculosis case detection within the private pharmacy sector in Vietnam.

BACKGROUND: Of the estimated 10 million people affected by (TB) each year, one-third are never diagnosed. Delayed case detection within the private healthcare sector has been identified as a particular problem in some settings, leading to considerable morbidity, mortality and community transmission. Using unannounced standardised patient (SP) visits to the pharmacies, we aimed to evaluate the performance of private pharmacies in the detection and treatment of TB. METHODS: A cross-sectional study was undertaken at randomly selected private pharmacies within 40 districts of Vietnam. Trained actors implemented two standardised clinical scenarios of presumptive TB and presumptive multidrug-resistant TB (MDR-TB). Outcomes were the proportion of SPs referred for medical assessment and the proportion inappropriately receiving broad-spectrum antibiotics. Logistic regression evaluated predictors of SPs' referral. RESULTS: In total, 638 SP encounters were conducted, of which only 155 (24.3%) were referred for medical assessment; 511 (80·1%) were inappropriately offered antibiotics. A higher proportion of SPs were referred without having been given antibiotics if they had presumptive MDR-TB (68/320, 21.3%) versus presumptive TB (17/318, 5.3%; adjusted OR=4.8, 95% CI 2.9 to 7.8). Pharmacies offered antibiotics without a prescription to 89.9% of SPs with presumptive TB and 70.3% with presumptive MDR-TB, with no clear follow-up plan. CONCLUSIONS: Few SPs with presumptive TB were appropriately referred for medical assessment by private pharmacies. Interventions to improve appropriate TB referral within the private pharmacy sector are urgently required to reduce the number of undiagnosed TB cases in Vietnam and similar high-prevalence settings

A serological framework to investigate acute primary and post-primary dengue cases reporting across the Philippines.

BACKGROUND: In dengue-endemic countries, targeting limited control interventions to populations at risk of severe disease could enable increased efficiency. Individuals who have had their first (primary) dengue infection are at risk of developing more severe secondary disease, thus could be targeted for disease prevention. Currently, there is no reliable algorithm for determining primary and post-primary (infection with more than one flavivirus) status from a single serum sample. In this study, we developed and validated an immune status algorithm using single acute serum samples from reporting patients and investigated dengue immuno-epidemiological patterns across the Philippines. METHODS: During 2015/2016, a cross-sectional sample of 10,137 dengue case reports provided serum for molecular (anti-DENV PCR) and serological (anti-DENV IgM/G capture ELISA) assay. Using mixture modelling, we re-assessed IgM/G seroprevalence and estimated functional, disease day-specific, IgG:IgM ratios that categorised the reporting population as negative, historical, primary and post-primary for dengue. We validated our algorithm against WHO gold standard criteria and investigated cross-reactivity with Zika by assaying a random subset for anti-ZIKV IgM and IgG. Lastly, using our algorithm, we explored immuno-epidemiological patterns of dengue across the Philippines. RESULTS: Our modelled IgM and IgG seroprevalence thresholds were lower than kit-provided thresholds. Individuals anti-DENV PCR+ or IgM+ were classified as active dengue infections (83.1%, 6998/8425). IgG- and IgG+ active dengue infections on disease days 1 and 2 were categorised as primary and post-primary, respectively, while those on disease days 3 to 5 with IgG:IgM ratios below and above 0.45 were classified as primary and post-primary, respectively. A significant proportion of post-primary dengue infections had elevated anti-ZIKV IgG inferring previous Zika exposure. Our algorithm achieved 90.5% serological agreement with WHO standard practice. Post-primary dengue infections were more likely to be older and present with severe symptoms. Finally, we identified a spatio-temporal cluster of primary dengue case reporting in northern Luzon during 2016. CONCLUSIONS: Our dengue immune status algorithm can equip surveillance operations with the means to target dengue control efforts. The algorithm accurately identified primary dengue infections who are at risk of future severe disease

Induction of Heme Oxygenase-1 with Hemin Reduces Obesity-Induced Adipose Tissue Inflammation via Adipose Macrophage Phenotype Switching

Adipose macrophages with the anti-inflammatory M2 phenotype protect against obesity-induced inflammation and insulin resistance. Heme oxygenase-1 (HO-1), which elicits antioxidant and anti-inflammatory activity, modulates macrophage phenotypes and thus is implicated in various inflammatory diseases. Here, we demonstrate that the HO-1 inducer, hemin, protects against obesity-induced adipose inflammation by inducing macrophages to switch to the M2 phenotype. HO-1 induction by hemin reduced the production of proinflammatory cytokines (TNF-α and IL-6) from cocultured adipocytes and macrophages by inhibiting the activation of inflammatory signaling molecules (JNK and NF-κB) in both cell types. Hemin enhanced transcript levels of M2 macrophage marker genes (IL-4, Mrc1, and Clec10a) in the cocultures, while reducing transcripts of M1 macrophage markers (CD274 and TNF-α). The protective effects of hemin on adipose inflammation and macrophage phenotype switching were confirmed in mice fed a high-fat diet, and these were associated with PPARγ upregulation and STAT6 activation. These findings suggest that induction of HO-1 with hemin protects against obesity-induced adipose inflammation through M2 macrophage phenotype switching, which is induced by the PPARγ and STAT6 pathway. HO-1 inducers such as hemin may be useful for preventing obesity-induced adipose inflammation