Altered interregional molecular associations of the serotonin transporter in attention deficit/hyperactivity disorder assessed with PET

Altered serotonergic neurotransmission has been found to cause impulsive and aggressive behavior, as well as increased motor activity, all exemplifying key symptoms of ADHD. The main objectives of this positron emission tomography (PET) study were to investigate the serotonin transporter binding potential (SERT BP_ND) in patients with ADHD and to assess associations of SERT BP_ND between the brain regions. 25 medication‐free patients with ADHD (age ± SD; 32.39 ± 10.15; 10 females) without any psychiatric comorbidity and 25 age and sex matched healthy control subjects (33.74 ± 10.20) were measured once with PET and the highly selective and specific radioligand [¹¹C]DASB. SERT BP_ND maps in nine a priori defined ROIs exhibiting high SERT binding were compared between groups by means of a linear mixed model. Finally, adopted from structural and functional connectivity analyses, we performed correlational analyses using regional SERT binding potentials to examine molecular interregional associations between all selected ROIs. We observed significant differences in the interregional correlations between the precuneus and the hippocampus in patients with ADHD compared to healthy controls, using SERT BP_ND of the investigated ROIs (P < 0.05; Bonferroni corrected). When correlating SERT BP_ND and age in the ADHD and the healthy control group, we confirmed an age‐related decline in brain SERT binding in the thalamus and insula (R² = 0.284, R² = 0.167, Ps < 0.05; Bonferroni corrected). The results show significantly different interregional molecular associations of the SERT expression for the precuneus with hippocampus in patients with ADHD, indicating presumably altered functional coupling. Altered interregional coupling between brain regions might be a sensitive approach to demonstrate functional and molecular alterations in psychiatric conditions. Hum Brain Mapp 38:792–802, 2017. © 2016 Wiley Periodicals, Inc.     

Bariatric Surgery Outcomes in Sarcopenic Obesity

Background

Sarcopenic obesity is the combination of low muscle mass and strength with increased fat mass. This condition is associated with negative health outcomes. We hypothesized that sarcopenia could be a pejorative factor on surgical weight loss.

Objective

The objectives of the study are to determine the influence of sarcopenic obesity on gastric bypass and sleeve gastrectomy results regarding weight loss and comorbidities resolution at 3, 6, and 12 months.

Setting

The study was conducted at the University Hospital.

Methods

Sixty-nine obese patients who benefited from bariatric surgery were included. Skeletal muscle mass was determined by the Janssen’s equation. Physical performance and muscle strength were determined using the 6-min walk test and the wall sit test. Obese subjects from the lowest tertile of the Skeletal Muscle mass Index (SMI) of Baumgartner were set as sarcopenic.

Results

Weight loss outcomes and rate of weight loss failure were not influenced by sarcopenia. At 1 year, mean EBMIL% was 75.4 %?±?5 in sarcopenic subjects vs 67.8 % ±4 in the non-sarcopenic subjects (p?=?0.242). Improvement rates of co-morbidities were similar between groups. Skeletal muscle mass was no more different between groups at 1 year after surgery. There was no patient lost to follow-up.

Conclusions

Bariatric surgery remains effective in achieving weight loss target in sarcopenic patients, with similar remission rates of main comorbidities and similar safety profile than in the non-sarcopenic group. Whether bariatric surgery could result in improvement or deterioration of daily living activities disabilities and functional autonomy in sarcopenic obese patients still have to be evaluated.

     

p-ERK1/2 is a predictive factor of response to erythropoiesis-stimulating agents in low/int-1 myelodysplastic syndromes

Serum erythropoietin level less than 100U/L and a transfusion requirement of less than 2 units per month are the best predictive factors for response to treatment by erythropoiesis-stimulating agents in low/int-1 myelodysplastic syndromes. To investigate the factors influencing the response to erythropoiesis-stimulating agents, we enrolled 127 low/int-1 myelodysplastic syndrome patients at diagnosis in a biological study of erythropoiesis. The 54 non-responders had a significantly lower number of burst-forming unit-erythroid and colony-forming unit-erythroid than responders. Erythropoietin-dependent proliferation and survival, and phospho (p)-ERK1/2 expression in steady state and after erythropoietin stimulation were defective in cultured erythroblasts. By flow cytometry, p-ERK1/2 was significantly lower in bone marrow CD45⁻/CD71⁺/GPA⁻cells from non-responders compared to responders or controls. Receiver Operator Characteristic curve analysis showed that this flow cytometry test was a sensitive biomarker for predicting the response to erythropoiesis-stimulating agents.     

Serum insulin-like growth factor 1 and serum growth-promoting activity during the first postnatal year in infants with intrauterine growth retardation

Follow-up from birth to age 12 months was obtained in 21 infants born with intrauterine growth retardation. Serum insulin-like growth factor 1 was measured by radioimmunoassay. The bioassayable growth-promoting activity of the serum was measured as the "thymidine activity" on lectin-activated lymphocytes at 5 days and 1, 3, 6, 9, and 12 months, and was compared with control values. Depending on their length at age 12 months, the intrauterine growth retardation infants were divided into three groups: at or above the average (n = 8, group A), between the mean and -2 SD (n = 7, group B), or less than -2 SD (n = 6, group C). No differences in nutritional indexes or in head circumference were found between the three groups. Insulin-like growth factor 1 was significantly lower at age 5 days in intrauterine growth retardation than in control infants. It increased slowly in groups A and B to reach the control values at age 9 and 12 months. In group C it remained significantly subnormal at 1 yr of age. Thymidine activity was also significantly lower at age 5 days in intrauterine growth retardation compared with control infants. It increased sharply at age 1-3 months in groups A and B but remained significantly lower in group C up to 1 yr of age. Although individual values of insulin-like growth factor 1 and thymidine activity were closely correlated, the increase of length during the first postnatal year correlated significantly with the thymidine activity levels at 1 and 3 months but not with the insulin-like growth factor 1 levels at 1, 3, and 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)     

A BRCA1/2 mutation,high breast density and prominent pushing margins of a tumor independently contribute to a frequent false-negative mammography

Female BRCA1/2 mutation carriers develop in up to 50% breast cancer (BC) before age 50 years. We investigated whether the specific histologic features of BRCA1/2-associated breast cancer influence imaging. We correlated the mammographic results with the histology of 34 BC in BRCA1/2 mutation carriers and 34 sporadic cancers in patients, matched for age and year of diagnosis. Mammography was significantly more frequently false-negative in carriers than controls (62% vs. 29% p = 0.01), despite comparable tumor size (mean solidus in circle 1.51 vs. 1.75) and breast density (high 41% vs. 53%). The image in carriers was significantly less as spiculated mass (6 vs. 18 p = 0.01). Cancers of BRCA1/2 mutation carriers had frequently higher mitotic counts (p < 0.0001) and prominent pushing margins around the tumor (p = 0.08) (p = 0.05 for 32 BRCA1). We also observed that prominent "pushing margins" correlated significantly with a false-negative mammography (p = 0.005) and with a mammographic image of a smooth, not a spiculated, mass (p = 0.01). False-negative mammography correlated independently with: BRCA1/2 mutation (p = 0.02), prominent pushing margins (p = 0.03) and high breast density (p = 0.01). MRI was carried out in 12 carriers, had 100% sensitivity and detected 5 cancers, still occult at physical examination and mammography. A BRCA1/2 mutation and high breast density at mammography contribute independently to false-negative mammography results. In mutation carriers any mammographic mass must be regarded with suspicion. Pushing margins of the tumor partly explain these results. For early BC detection in mutation carriers additional methods like MRI may be needed. This may not be necessary in other young women with breast symptoms.     

Bidirectional cooperative motion of molecular motors

Recently, in a beautiful set of experiments, it has been shown that a Ncd mutant, NK11, which lacks directionality in its individual motion, was able to exhibit a new kind of directed motion in motility assays (Endow, S. A. & Higuchi, H. (2000) Nature (London) 406, 913-916): the filaments keep a given velocity for a while and then suddenly move in the opposite direction with similar velocity. We show that these observations nicely illustrate the concept of dynamic transitions in motor collections introduced earlier in the case of an infinite number of motors. We investigate the experimentally relevant case of a finite number of motors both when directionality is present (kinesins, myosins, Ncd) and absent (NK11). Using a symmetric two-state model, we demonstrate that bidirectional motion is the signature of a dynamic transition that results from the collective behavior of many motors acting on the same filament. For motors exhibiting directional bias individually, an asymmetric two-state model is appropriate. In that case, dynamic transitions exist for motor collections in the presence of an external force. We give predictions for the dependence of motion on ATP concentration, external forces, and the number of motors involved. In particular, we show that the reversal time grows exponentially with the number of motors per filament.     

2型糖尿病的预测性遗传学检测可能引起不切实际的期望

今年年初，《纽约时报》头版头条报道了TCF7L2基因变异与2型糖尿病相关。主要研究者KariStefansson告诉《纽约时报》，这一发现可能会导致一种新的诊断性检测法产生，用于识别携带糖尿病变异基因的个体。他说，这将促使那些知道自己有糖尿病高风险的人们避免采取引起糖尿病的生活方式。一位苏格兰科学家领导着该研究小组，《格拉斯哥先驱报》曾率先报道他们的工作，“糖尿病致病基因的发现将有助于科学家治疗糖尿病”。