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The growth hormone secretagogue receptor (GHSR) is a G protein‐coupled receptor that is highly expressed in the central nervous system. GHSR acts as a receptor for ghrelin and for liver‐expressed antimicrobial peptide 2 (LEAP2), which blocks ghrelin‐evoked activity. GHSR also displays ligand‐independent activity, including a high constitutive activity that signals in the absence of ghrelin and is reduced by LEAP2. GHSR activity modulates a variety of food intake‐related behaviours, including binge eating. Previously, we reported that GHSR‐deficient mice daily and time‐limited exposed to a high‐fat (HF) diet display an attenuated binge‐like HF intake compared to wild‐type mice. In the present study, we aimed to determine whether ligand‐independent GHSR activity affects binge‐like HF intake in a 4‐day binge‐like eating protocol. We found that plasma levels of ghrelin and LEAP2 were not modified in mice exposed to this binge‐like eating protocol. Moreover, systemic administration of ghrelin or LEAP2 did not alter HF intake in our experimental conditions. Interestingly, we found that central administration of LEAP2 or K‐(D‐1‐Nal)‐FwLL‐NH2, which are both blockers of constitutive GHSR activity, reduced binge‐like HF intake, whereas central administration of ghrelin or the ghrelin‐evoked GHSR activity blockers [D‐Lys3]‐GHRP‐6 and JMV2959 did not modify binge‐like HF intake. Taken together, current data indicate that GHSR activity in the brain affects binge‐like HF intake in mice independently of plasma levels of ghrelin and LEAP2.  相似文献   
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Objective

To examine the association of placental levels of arsenic (As), cadmium (Cd), mercury (Hg), lead (Pb), manganese (Mn), and chromium (Cr) with birth outcomes (birth weight, length, and head circumference, low birth weight [LBW], gestational age, preterm delivery, and small for gestational age [SGA]) in mother-child pairs from the Environment and Childhood (INMA) Project in Spain.

Methods

Metal concentrations were measured in placenta tissue samples randomly selected from five INMA cohorts. Data on birth outcomes were obtained from medical records. Associations were assessed in a sub-sample of 327 mother-infant pairs by regression models adjusted for confounding factors and for all metals simultaneously. Effect modification by sex was also evaluated.

Results

Elevated placental Cd levels (>5.79 vs. <3.30?ng/g) were associated with reduced birth weight (?111.8?g, 95%CI?=??215.6; ?8.06, p-trend?=?0.01) and length (?0.62?cm, 95%CI?=??1.20; ?0.04, p-trend?=?0.02), while a 10% increase in Cd was associated with 1.21-fold increased odds (95%CI?=?1.01; 1.43) of LBW in the global sample but with 14% lower odds (95%CI?=?0.78; 0.96) of preterm delivery in males (Pinteraction?=?0.10). Detected (vs. undetected) Hg was associated with reduced head circumference (?0.49?cm, 95%CI?=??1.00; 0.03) in females (Pinteraction?=?0.03). A 10% increase in placental Mn was associated with slight increases in gestational age (0.04 weeks, 95%CI?=?0.01; 0.07) in the global sample and in head circumference (0.05?cm, 95%CI?=??0.01; 0.10) in females (Pinteraction?=?0.03). Elevated Cr levels (>99.6 vs. <56.1?ng/g) were associated with reduced birth length (?0.68?cm, 95%CI?=??1.33; ?0.04, p-trend?=?0.02) and slightly increased gestational age (0.35 weeks, 95%CI?=??0.07; 0.77, p-trend?=?0.08) in the global sample. As and Pb were detected in few placentas (27% and 13%, respectively) and were not associated with any studied birth outcome.

Conclusions

Data suggest that in utero exposure to Cd, Hg, and Cr could adversely affect fetal growth, whereas Mn and Cr appear to have a positive effect on gestational age. Given the relatively small number of subjects, sex-specific associations should be interpreted with caution.  相似文献   
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Context

Demoralization is a state of existential distress in patients with advanced illness, typically with coping difficulties, feelings of loss of sense, and purpose in life and despair, among other things. The New Demoralization Scale (DS-II) is an evaluation tool for this syndrome, which has recently been reformulated on a shorter scale.

Objectives

The objective of this study was to obtain a Spanish version of the DS-II and to assess its psychometric properties in advanced cancer patients in Spain and a number of Latin American countries.

Methods

Following a translation–back translation process, a validation study and a confirmatory analysis using structural equation models with their corresponding latent constructs were undertaken. Patients completed the DS-II in Spanish (DS-II (es)), the Hospital Anxiety and Depression Scale, and the Edmonton Symptom Assessment System–revised. Reliability was studied according to internal consistency; construct validity and concurrent validity with the Hospital Anxiety and Depression Scale and the Edmonton Symptom Assessment System–revised; discriminant validity using the Karnofsky Performance Status scale; and feasibility, with response ratio and required time. Cutoff points were established, and sensitivity and specificity were studied.

Results

The DS-II (es) was obtained. One hundred fifty patients completed the validation study. The confirmatory analysis showed coherence, and all items correlated positively with their subscales and with the overall scale. Cronbach's alpha for the DS-II (es) was 0.88, for the sense and purpose subscale 0.83, and for the coping ability 0.79. Demoralization correlated significantly with emotional distress (rho = 0.73, P < 0.001). The tool distinguished between patients with diverse functional levels (rho = ?0.319, P = 0.001). Cutoff points at 10 and 20 out of 32 were established. The scale showed high sensitivity (81.97%) and specificity (80.90%). The prevalence of demoralization was 33% in our sample.

Conclusion

The Spanish version of the new Kissane DS-II demoralization scale has shown to be valid, reliable, and feasible with adequate psychometric properties.  相似文献   
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