Greater loss of object than spatial mnemonic discrimination in aged adults

Previous studies across species have established that the aging process adversely affects certain memory‐related brain regions earlier than others. Behavioral tasks targeted at the function of vulnerable regions can provide noninvasive methods for assessing the integrity of particular components of memory throughout the lifespan. The present study modified a previous task designed to separately but concurrently test detailed memory for object identity and spatial location. Memory for objects or items is thought to rely on perirhinal and lateral entorhinal cortices, among the first targets of Alzheimer's related neurodegeneration. In line with prior work, we split an aged adult sample into “impaired” and “unimpaired” groups on the basis of a standardized word‐learning task. The “impaired” group showed widespread difficulty with memory discrimination, whereas the “unimpaired” group showed difficulty with object, but not spatial memory discrimination. These findings support the hypothesized greater age‐related impacts on memory for objects or items in older adults, perhaps even with healthy aging. © 2015 Wiley Periodicals, Inc.     

Histopathological studies in two strains of semi-immune mice infected with Plasmodium berghei ANKA after chronic exposure

To mimic a human malaria infection in the endemic condition, two strains of mice (Balb/c and CBA) were infected and treated several times to generate so-called semi-immune status. As previously reported, neither mice (Balb/c and CBA) strain showed cerebral malaria, even in the susceptible C57BL/6 (B6). The significant difference between the mice strains in our previous study was the rate of destruction of uninfected red blood cells (uRBCs) at infection. After the established repeated cycles of infection and treatment and the final challenge with 10⁴ Plasmodium berghei ANKA until minimum Hb, Balb/c and CBA mice were sacrificed. The spleen, liver, brain, kidney, lung, heart, and muscle were removed, stained with hematoxylin–eosin and analyzed with light microscopy. Previous observation suggested that Balb/c destroyed uRBC at much higher rate than the other strains although the parasitemia was very low. Pathological investigation carried out in this study revealed that this destruction was mainly contributed by the uRBCs as no parasite sequestration was observed in any of the organs. However, malaria pigment deposition was observed in spleen and liver of all the semi-immune mice strains. This histopathological study in the severe malaria anemia model, which is difficult to conduct in humans, will be helpful in taking into account different responses to malaria infection when designing therapeutic interventions and vaccine studies.     

Carboxyhemoglobin and its correlation to disease severity in cirrhotics

GOAL: To assess the correlation of serum carboxyhemoglobin (CO-Hb) to severity of liver disease as compared with Model for End Stage Liver Disease (MELD) score, Child Pugh score, and clinical parameters. BACKGROUND: There are 2 sources of carbon monoxide (CO) in humans, exogenous sources include those such as tobacco smoke and inhaled motor vehicle exhaust. The endogenous source is via the heme-oxygenase pathway, in which a heme molecule is broken down into biliverdin with release of an iron (Fe) and CO molecule. Normal serum CO-Hb levels in nonsmokers is 0% to 1.5% and 4% to 9% in smokers. Activity of the heme-oxygenase pathway may be increased in the cirrhotic patient, as measured indirectly by exhaled CO and serum CO-Hb. This may be due to alterations in vascular tone in the splanchnic circulation in cirrhotics that may lead to elevated CO production. One published study also showed that those with spontaneous bacterial peritonitis had higher levels of both CO and CO-Hb. The MELD score uses prothrombin time (INR), creatinine, and bilirubin in the prediction of short-term mortality in decompensated cirrhotics while awaiting liver transplant. Measurement of endogenous CO-Hb may correlate to severity of liver disease. STUDY: Retrospective analysis was done of 113 adult patients who were evaluated for liver transplantation between September 1996 and July 2003 and had pulmonary function testing with CO-Hb as part of their evaluation. We excluded any patients with a history of smoking. Clinical parameters used for comparison included grade of esophageal varices (n=75), spleen size (n=51) measured on abdominal ultrasound or computed tomography scan, aminotransferases, and disease duration. Serum CO-Hb levels were measured from whole blood, sent refrigerated to ARUP laboratories (Salt Lake City, UT) and analyzed via spectrophotometry. Bivariate analysis was performed by means of the Pearson product moment correlation. RESULTS: The mean CO-Hb level was 2.1%, which is higher than the expected normal population controls. No correlation was found, however, with MELD score, Child Turcotte Pugh score, or other biochemical or clinical measurements of disease severity. CONCLUSIONS: Although CO and CO-Hb production may be increased in the cirrhotic patient, in this study no correlation was found to disease severity as measured by the MELD score. Further studies are needed to assess the role of CO in other complications of cirrhosis including infection and circulatory dysfunction.     

Multimodality treatment of posterior fossa arteriovenous malformations

OBJECT: Posterior fossa arteriovenous malformations (AVMs) are relatively uncommon and often difficult to treat. The authors present their experience with multimodality treatment of 76 posterior fossa AVMs, with an emphasis on Spetzler-Martin Grades III-V AVMs. METHODS: Seventy-six patients with posterior fossa AVMs treated with radiosurgery, surgery, and endovascular techniques were analyzed. RESULTS: Between 1982 and 2006, 36 patients with cerebellar AVMs, 33 with brainstem AVMs, and 7 with combined cerebellar-brainstem AVMs were treated. Natural history data were calculated for all 76 patients. The risk of hemorrhage from presentation until initial treatment was 8.4% per year, and it was 9.6% per year after treatment and before obliteration. Forty-eight patients had Grades III-V AVMs with a mean follow-up of 4.8 years (range 0.1-18.4 years, median 3.1 years). Fifty-two percent of patients with Grades III-V AVMs had complete obliteration at the last follow-up visit. Three (21.4%) of 14 patients were cured with a single radiosurgery treatment, and 4 (28.6%) of 14 with 1 or 2 radiosurgery treatments. Twenty-one (61.8%) of 34 patients were cured with multimodality treatment. The mean Glasgow Outcome Scale (GOS) score after treatment was 3.8. Multivariate analysis performed in the 48 patients with Grades III-V AVMs showed radiosurgery alone to be a negative predictor of cure (p = 0.0047). Radiosurgery treatment alone was not a positive predictor of excellent clinical outcome (GOS Score 5; p > 0.05). Nine (18.8%) of 48 patients had major neurological complications related to treatment. CONCLUSIONS: Single-treatment radiosurgery has a low cure rate for posterior fossa Spetzler-Martin Grades III-V AVMs. Multimodality therapy nearly tripled this cure rate, with an acceptable risk of complications and excellent or good clinical outcomes in 81% of patients. Radiosurgery alone should be used for intrinsic brainstem AVMs, and multimodality treatment should be considered for all other posterior fossa AVMs.     

Sub clinical vitamin A deficiency and anemia among Vietnamese children less than five years of age

The objective of the study was to assess the prevalence of sub clinical vitamin A deficiency and anemia in Vietnamese children. For this, a cross-sectional survey was conducted in 40 villages (clusters) of four ecological regions in Vietnam during Apr-May 2001. In total 1657 children less than 5 years old were included by a cluster random sampling method. The prevalence of sub clinical vitamin A deficiency (serum retinol <0.70 mumol/l) was 12.0% and the prevalence of anemia (hemoglobin <110g/l) was 28.4 %. 35.1%. In the children under 6 months the prevalence of sub clinical vitamin A deficiency was 35.1 % whereas the prevalence of anemia in this group was as high as 61.7%. The prevalence of children with both sub clinical vitamin A deficiency and anemia was 6.1%. Sub clinical vitamin A deficiency and anemia prevalence differed significantly across the regions, with highest prevalence in the Northern Mountainous areas for vitamin A deficiency and in the Northern Mountainous area and Mekong River Delta for anemia. It is concluded that sub clinical vitamin A deficiency and anemia are still important public health problems in Vietnam. Sustainable strategies for combating vitamin A deficiency and nutritional anemia are needed and should concentrate on target groups, especially infants and malnourished children in high risk regions.     

H3K27M-mutant diffuse midline gliomas should be further molecularly stratified: an integrated analysis of 669 patients

Journal of Neuro-Oncology - H3K27M-mutated diffuse midline gliomas (H3-DMGs) are aggressive tumors with a fatal outcome. This study integrating individual patient data (IPD) from published studies...     

WAY-163909 [(7bR,10aR)-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta-[b][1,4]diazepino[6,7,1hi]indole]: A novel 5-hydroxytryptamine 2C receptor-selective agonist with preclinical antipsychotic-like activity.

Serotonin-2C (5-HT2C) receptor antagonists and agonists have been shown to affect dopamine (DA) neurotransmission, with agonists selectively decreasing mesolimbic DA. As antipsychotic efficacy is proposed to be associated with decreased mesolimbic DA neurotransmission by virtue of DA D2 receptor antagonism, the 5-HT2C-selective receptor agonist, WAY-163909 [(7bR,10aR)-1,2, 3,4,8,9,10,10a-octahydro-7bH-cyclopenta-[b][1,4]diazepino[6,7, 1hi]indole], was evaluated in animal models of schizophrenia and in vivo microdialysis and electrophysiology to determine the effects on mesolimbic and nigrostriatal DA neurotransmission. Similar to clozapine, WAY-163909 (1.7-30 mg/kg i.p.) decreased apomorphine-induced climbing with little effect on stereotypy and no significant induction of catalepsy. WAY-163909 (0.3-3 mg/kg s.c.) more potently reduced phencyclidine-induced locomotor activity compared with d-amphetamine with no effect on spontaneous activity. WAY-163909 (1.7-17 mg/kg i.p.) reversed MK-801 (5H-dibenzo[a,d]cyclohepten-5,10-imine (dizocilpine maleate)- and DOI [1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane]-disrupted prepulse inhibition of startle (PPI) and improved PPI in DBA/2N mice. In conditioned avoidance responding, WAY-163909 (0.3-3 mg/kg i.p.; 1-17 mg/kg p.o.) reduced avoidance responding, an effect blocked by the 5-HT(2B/2C) receptor antagonist SB 206553 [5-methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f]indole]. WAY-163909 (10 mg/kg s.c.) selectively decreased extracellular levels of DA in the nucleus accumbens without affecting the striatum. Likewise, in vivo electrophysiological recordings showed a decrease in the number of spontaneously firing DA neurons in the ventral tegmental area but not in the substantia nigra with both acute and chronic (21-day) administration of WAY-163909 (1-10 mg/kg i.p.). Thus, the profile of the 5-HT2C selective receptor agonist WAY-163909 is similar to that of an atypical antipsychotic and additionally may have rapid onset properties.