Behavioral and genetic evidence for a novel animal model of Attention-Deficit/Hyperactivity Disorder Predominantly Inattentive Subtype

Background  

According to DSM-IV there are three subtypes of Attention-Deficit/Hyperactivity Disorder, namely: ADHD predominantly inattentive type (ADHD-PI), ADHD predominantly Hyperactive-Impulsive Type (ADHD-HI), and ADHD combined type (ADHD-C). These subtypes may represent distinct neurobehavioral disorders of childhood onset with separate etiologies. The diagnosis of ADHD is behaviorally based; therefore, investigations into its possible etiologies should be based in behavior. Animal models of ADHD demonstrate construct validity when they accurately reproduce elements of the etiology, biochemistry, symptoms, and treatment of the disorder. Spontaneously hypertensive rats (SHR) fulfill many of the validation criteria and compare well with clinical cases of ADHD-C. The present study describes a novel rat model of the predominantly inattentive subtype (ADHD-PI).     

Glutamate acting at NMDA receptors stimulates embryonic cortical neuronal migration

During cortical development, embryonic neurons migrate from germinal zones near the ventricle into the cortical plate, where they organize into layers. Mechanisms that direct neuronal migration may include molecules that act as chemoattractants. In rats, GABA, which localizes near the target destination for migrating cortical neurons, stimulates embryonic neuronal migration in vitro. In mice, glutamate is highly localized near the target destinations for migrating cortical neurons. Glutamate-induced migration of murine embryonic cortical cells was evaluated in cell dissociates and cortical slice cultures. In dissociates, the chemotropic effects of glutamate were 10-fold greater than the effects of GABA, demonstrating that for murine cortical cells, glutamate is a more potent chemoattractant than GABA. Thus, cortical chemoattractants appear to differ between species. Micromolar glutamate stimulated neuronal chemotaxis that was mimicked by microM NMDA but not by other ionotropic glutamate receptor agonists (AMPA, kainate, quisqualate). Responding cells were primarily derived from immature cortical regions [ventricular zone (vz)/subventricular zone (svz)]. Bromodeoxyuridine (BrdU) pulse labeling of cortical slices cultured in NMDA antagonists (microM MK801 or APV) revealed that antagonist exposure blocked the migration of BrdU-positive cells from the vz/svz into the cortical plate. PCR confirmed the presence of NMDA receptor expression in vz/svz cells, whereas electrophysiology and Ca2+ imaging demonstrated that vz/svz cells exhibited physiological responses to NMDA. These studies indicate that, in mice, glutamate may serve as a chemoattractant for neurons in the developing cortex, signaling cells to migrate into the cortical plate via NMDA receptor activation.     

The roles of von Willebrand factor and factor VIII in arterial thrombosis: studies in canine von Willebrand disease and hemophilia A

We have studied the roles of von Willebrand factor (vWF) and factor VIII in arterial thrombosis in four canine phenotypes: normal (n = 6), hemophilia A (n = 11), von Willebrand disease (vWD) (n = 9), and hemophilia A/vWD (n = 1). vWF activity was determined by botrocetin- induced agglutination of fixed human platelets and vWF antigen (vWF:Ag) by Laurell electroimmunoassay and crossed immunoelectrophoresis. Plasma from normal dogs and those with hemophilia A had vWF activity, vWF:Ag, and a full range of vWF:Ag multimers on gel electrophoresis equivalent to normal canine plasma pool. Platelet cytosol contents were isolated by freezing and thawing, triton X-100 solubilization, or sonication of washed platelets with and without protease inhibitors and inhibitors of platelet activation. Washed platelets were also stimulated with calcium ionophore and MgCl2. There was no measurable vWF activity or vWF:Ag in platelet lysates or releasates in any dog regardless of phenotype. All dogs were studied using a standard arterial stenosis and injury procedure to induce arterial thrombosis. Thromboses were detected by cyclic reductions in Doppler blood flow velocity. Vessels were examined by light and scanning electron microscopy. Thrombosis developed in the arteries of normal (9 of 10) and hemophilia A dogs (16 of 16) but in none of the vWD dogs (0 of 10). Infusion of canine vWF cryoprecipitate into vWD dogs markedly shortened bleeding time but did not support thrombosis as seen in dogs with vWF in the plasma and subendothelium. Thrombosis, then, fails to occur when vWF is absent from the plasma and subendothelial compartments or present only in the plasma compartment. These data are consistent with the hypothesis that vWF in the plasma and subendothelium supports thrombosis. Neither plasma FVIII nor platelet vWF is essential for thrombosis in this model.     

High serum and ascitic soluble interleukin-2 receptor alpha levels in advanced epithelial ovarian cancer [see comments]

This study was undertaken to determine if advanced epithelial ovarian cancer was associated with increased serum and ascitic levels of soluble interleukin-2 receptor alpha (sIL-2R alpha). Serum and ascitic fluid samples from 23 ovarian cancer patients were analyzed for sIL-2R alpha using an enzyme-linked immunosorbent assay and compared with the serum and peritoneal levels in 18 normal females. The samples were analyzed for CA-125 levels using a radioimmunoassay and the total protein was also measured. Normal individuals had low serum levels of sIL-2R alpha (367.5 +/- 44.6 U/mL), with similar levels of sIL-2R alpha in the normal peritoneal fluid (438.6 +/- 48.8 U/mL). In contrast, the serum and ascitic fluid levels in ovarian cancer patients were significantly higher (746.7 +/- 82.9 U/mL, P = .0006; 2,656.7 +/- 373.7 U/mL, P = .00002, respectively). The results for sIL-2R alpha were also significant when the levels were expressed per milligram of total protein. More importantly, in almost every ovarian cancer patient the ascitic sIL-2R alpha level far exceeded the serum level, a pattern also observed for CA-125. There was no correlation between the serum and ascitic sIL-2R alpha levels, or between the serum and ascitic CA-125 levels. Although the serum levels of sIL-2R alpha and CA-125 were elevated in the same patient, overall there was no correlation between the serum sIL-2R alpha and serum CA-125 levels, either when the levels were expressed in absolute units or per milligram of total protein. Similarly, there was no correlation between sIL-2R alpha and CA-125 levels in individual ascitic samples. While CA-125 levels may reflect an independent index of tumor burden, these results suggest that selective accumulation of sIL-2R alpha in the ascites may be one of the factors associated with the known nonresponsiveness of the infiltrating lymphocytes against ovarian carcinoma cells.     

来那度胺＋低剂量地塞米松治疗多发性骨髓瘤疗效佳毒性低

高剂量地塞米松为多发性骨髓瘤常用治疗方案。本研究比较了高、低剂量地塞米松分别联合来那度胺治疗多发性骨髓瘤的临床疗效及毒副作用。     

Association between Short Maternal Height and Low Birth Weight: a Hospital-based Study in Japan

Anthropometry measurements, such as height and weight, have recently been used to predict poorer birth outcomes. However, the relationship between maternal height and birth outcomes remains unclear. We examined the effect of shorter maternal height on low birth weight (LBW) among 17,150 pairs of Japanese mothers and newborns. Data for this analysis were collected from newborns who were delivered at a large hospital in Japan. Maternal height was the exposure variable, and LBW and admission to the neonatal intensive care unit were the outcome variables. Logistic regression models were used to estimate the associations. The shortest maternal height quartile (131.0–151.9 cm) was related to LBW (OR 1.91 [95% CI 1.64, 2.22]). The groups with the second (152.0–157.9 cm) and the third shortest maternal height quartiles (158.0–160.9 cm) were also related to LBW. A P trend with one quartile change also showed a significant relationship. The relationship between maternal height and NICU admission disappeared when the statistical model was adjusted for LBW. A newborn’s small size was one factor in the relationship between shorter maternal height and NICU admission. In developed countries, shorter mothers provide a useful prenatal target to anticipate and plan for LBW newborns and NICU admission.     

Self-reported health assessments in the 2002 World Health Survey: how do they correlate with education?

Objective

To assess the value of self-rated health assessments by examining the association between education and self-rated poor health.

Methods

We used the globally representative population-based sample from the 2002 World Health Survey, composed of 219 713 men and women aged 25 and over in 69 countries, to examine the association between education and self-rated poor health. In a binary regression model with a logit link function, we used self-rated poor health as the binary dependent variable, and age, sex and education as the independent variables.

Findings

Globally, there was an inverse association between years of schooling and self-rated poor health (odds ratio, OR: 0.929; 95% confidence interval, CI: 0.926–0.933). Compared with the individuals in the highest quintile of years of schooling, those in the lowest quintile were twice as likely to report poor health (OR: 2.292; 95% CI: 2.165–2.426). We found a dose–response relationship between quintiles of years of schooling and the ORs for reporting poor health. This association was consistent among men and women; low-, middle- and high-income countries; and regions.

Conclusion

Our findings suggest that self-reports of health may be useful for epidemiological investigations within countries, even in low-income settings.