Redistribution of monocarboxylate transporter 2 on the surface of astrocytes in the human epileptogenic hippocampus

Emerging evidence points to monocarboxylates as key players in the pathophysiology of temporal lobe epilepsy (TLE) with hippocampal sclerosis (mesial temporal lobe epilepsy, MTLE). Monocarboxylate transporters (MCTs) 1 and 2, which are abundantly present on brain endothelial cells and perivascular astrocyte endfeet, respectively, facilitate the transport of monocarboxylates and protons across cell membranes. Recently, we reported that the density of MCT1 protein is reduced on endothelial cells and increased on astrocyte plasma membranes in the hippocampal formation in patients with MTLE and in several animal models of the disorder. Because the perivascular astrocyte endfeet comprise an important part of the neurovascular unit, we now assessed the distribution of the MCT2 in hippocampal formations in TLE patients with (MTLE) or without hippocampal sclerosis (non-MTLE). Light microscopic immunohistochemistry revealed significantly less perivascular MCT2 immunoreactivity in the hippocampal formation in MTLE (n = 6) than in non-MTLE (n = 6) patients, and to a lesser degree in non-MTLE than in nonepilepsy patients (n = 4). Immunogold electron microscopy indicated that the loss of MCT2 protein occurred on perivascular astrocyte endfeet. Interestingly, the loss of MCT2 on astrocyte endfeet in MTLE (n = 3) was accompanied by an upregulation of the protein on astrocyte membranes facing synapses in the neuropil, when compared with non-MTLE (n = 3). We propose that the altered distribution of MCT1 and MCT2 in TLE (especially MTLE) limits the flux of monocarboxylates across the blood-brain barrier and enhances the exchange of monocarboxylates within the brain parenchyma.     

What is the long-term outcome of boys who steal at age eight? Findings from the Finnish nationwide “From A Boy To A Man” birth cohort study

Objective

The aim was to study predictive associations between childhood stealing behavior at the of age 8?years with later psychiatric disorders, criminality or suicide attempts and completed suicides up to the age 25?years in a large representative population-based birth cohort.

Method

The sample includes 2,592 Finnish males born in 1981 with information about stealing from both parents and teachers. Information about psychiatric disorders, criminality, suicide attempts requiring hospital admission and completed suicides was gathered from four different Finnish nationwide registries until the study participants were 25?years old.

Results

One out of ten boys had stealing behavior during the previous 12?months. After adjusting for parental education level and conduct problems or hyperactivity (i.e. potential confounds), stealing at eight independently predicted substance use and antisocial personality disorders, and high level of crimes. Stealing was also associated with completed suicide or severe suicide attempt requiring hospital admission. Comorbid stealing and frequent aggression had the strongest predictive association with any psychiatric diagnosis, crime and completed suicide or severe suicide attempt, while stealing without aggression was not associated with any of the negative outcomes.

Conclusions

Stealing accompanied with aggressivity at age eight is predictive of wide range of adversities. However, no increased risk was observed among the group with stealing behaviors but without aggression.     

Spiradenocarcinoma with low-grade basal cell adenocarcinoma pattern: report of a case with varied morphology and wild type TP53

We present a patient with a 2-cm spiradenocarcinoma of the left arm resembling low-grade salivary gland basal cell adenocarcinoma. In addition to showing attributes of conventional spiradenoma, the benign component showed prominent areas of cystic change with focal apocrine differentiation, glands with and without mucinous differentiation, clear cell change and focal adenoid cystic carcinoma-like areas. The malignant component was composed of nodules of basaloid cells arranged in sheets with variable tendency to luminal differentiation. The nuclear atypia was low-grade, and the mitotic index was high in the malignant component (to 8/10 high power fields). Immunohistochemically, there was diffuse but variable positivity for cytokeratin 7 in both the benign and malignant components. Epithelial membrane antigen was focally positive, highlighting cells with ductal (luminal) differentiation. Expression of p63 was observed in 50 and 80% of the cells in the benign and malignant components, respectively. Calponin was negative. The proliferative index (MIB-1/Ki-67) was <3% in the benign component and up to 10% in the malignant component. Although the malignant component displayed patchy areas with nuclear p53 immunoreactivity with variable intensity, no mutation in the TP53 gene was identified.     

The Prevalence of Autism Spectrum Disorders in Toddlers: A Population Study of 2-Year-Old Swedish Children

Autism Spectrum Disorder (ASD) is more common than previously believed. ASD is increasingly diagnosed at very young ages. We report estimated ASD prevalence rates from a population study of 2-year-old children conducted in 2010 in Gothenburg, Sweden. Screening for ASD had been introduced at all child health centers at child age 21/2 years. All children with suspected ASD were referred for evaluation to one center, serving the whole city of Gothenburg. The prevalence for all 2-year-olds referred in 2010 and diagnosed with ASD was 0.80%. Corresponding rates for 2-year-olds referred to the center in 2000 and 2005 (when no population screening occurred) were 0.18 and 0.04%. Results suggest that early screening contributes to a large increase in diagnosed ASD cases.     

A new screening programme for autism in a general population of Swedish toddlers

The evidence from early intervention studies of autism has emphasised the need for early diagnosis. Insight into the early presentation of autism is crucial for early recognition, and routine screening can optimise the possibility for early diagnosis. General population screening was conducted for 2.5-year-old children at child health centres in Gothenburg, Sweden, and the efficacy of the screening instruments in predicting a clinical diagnosis of autism was studied. The tools used for autism screening comprised the Modified Checklist for Autism in Children (M-CHAT) and an observation made by trained nurses of the child's joint attention abilities (JA-OBS). From the new screening procedure a "definitive" suspicion of autism spectrum disorder (ASD) was raised in 64 individuals in the study population of 3999 young children. Fifty-four of these were clinically assessed in detail. Forty-eight children had a confirmed diagnosis of ASD, three had severe language disorder, and three (6%) were classified as having typical development. The Positive predictive Value (PPV) for the combination of M-CHAT and the JA-OBS was 90%. The combination of instruments used showed promise for early detection of autism as a routine in the developmental programme at child health centres. Trained medical staff is a basic requirement and enables earlier detection and the use of screening tools beyond routine population screening regardless of the age at which a suspicion of autism is raised.     

Synthesis and evaluation of a set of para-substituted 4-phenylpiperidines and 4-phenylpiperazines as monoamine oxidase (MAO) inhibitors

A series of para-substituted 4-phenylpiperidines/piperazines have been synthesized and their affinity to recombinant rat cerebral cortex monoamine oxidases A (MAO A) and B (MAO B) determined. Para-substituents with low dipole moment increased the affinity to MAO A, whereas groups with high dipole moment yielded compounds with no or weak affinity. In contrast, the properties affecting MAO B affinity were the polarity and bulk of the para-substituent, with large hydrophobic substituents producing compounds with high MAO B affinity. In addition, these compounds were tested in freely moving rats and the effect on the post-mortem neurochemistry was measured. A linear correlation was demonstrated between the affinity for MAO A, but not MAO B, and the levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxytyramine (3-MT) in the striatum.     

Differentiating frailty in older people using the Swedish ambulance service: A retrospective audit

The elderly population in Sweden is increasing. This will lead to an increased need for healthcare resources and put extra demands on healthcare professionals. Consequently, ambulance personnel will be faced with the challenge of meeting extra demands from increasing numbers of older people with complex and atypical clinical presentations. Therefore we highlight that great problems exist for ambulance personnel to understand and meet these patients’ care needs. Using a caring science approach, we apply the patient’s perspective, and the aim of this study is to identify and illuminate the conditions that affect elderly people assessed with the assessment category “general affected health condition”. Thus, we have analyzed the characteristics belonging to this specific condition. The method is a retrospective audit, involving a qualitative content analysis of a total of 88 emergency service records. The conclusion is that by using caring science, the concept of frailty which is based on a comprehensive understanding of human life can clarify the state of “general affected health condition”, as either illness or ill-health. This offers a new assessment category and outlines care and treatment that strengthen and support the health and wellbeing of the individual elderly person. Furthermore, the concept of frailty ought to be included in “The International Statistical Classification of Diseases and Related Health Problems” (ICD-10).