Predicted effects of small decreases in energy expenditure on weight gain in adult women.

Small daily positive energy imbalances of 200 to 800 kJ (about 50 to 200 kcal) due to reduced resting energy expenditure (REE), reduced diet-induced thermogenesis, or physical inactivity are believed to predispose to obesity. However, estimates of the magnitude of the weight gain often fail to account for concurrent changes in body composition and increases in maintenance energy requirements as weight increases and energy equilibrium is re-established. Using previously reported data on body composition and REE in women and the energy cost of tissue deposition, we used mathematical models to predict the theoretical effect of a persistent reduction in energy expenditure on long-term weight gain, assuming no adaptation in energy intake. The analyses indicate the following effects of a reduced level of energy expenditure in lean and obese women: (i) REE rises more slowly with increasing degrees of obesity due to a declining proportion of the more metabolically active fat-free mass; so, for the same positive energy balance, a significantly greater weight gain is expected for obese than for lean women before energy equilibrium is re-established; (ii) due to the greater energy density of adipose tissue, the time course of weight gain to achieve energy balance is longer for obese subjects: in general, this is approximately five years for lean and ten years for obese women; (iii) the magnitude of weight gain of lean women in response to a reduced energy expenditure of 200 to 800 kJ/day is only about 3 to 15 kg, amounts insufficient to explain severe obesity.

Transition from pediatric to adult health care: expectations of adolescents with chronic disorders and their parents.

The aim of this study was to assess the expectations of adolescents with chronic disorders with regard to transition from pediatric to adult health care and to compare them with the expectations of their parents. A cross-sectional study was carried out including 283 adolescents with chronic disorders, aged 14-25 years (median age, 16.0 years), and not yet transferred to adult health care, and their 318 parents from two university children's hospitals. The majority of adolescents and parents (64%/70%) perceived the ages of 18-19 years and older as the best time to transfer to adult health care. Chronological age and feeling too old to see a pediatrician were reported as the most important decision factors for the transfer while the severity of the disease was not considered important. The most relevant barriers were feeling at ease with the pediatrician (45%/38%), anxiety (20%/24%), and lack of information about the adult specialist and health care (18%/27%). Of the 51% of adolescents with whom the pediatric specialist had spoken about the transfer, 53% of adolescents and 69% of parents preferred a joint transfer meeting with the pediatric and adult specialist, and 24% of these adolescents declared that their health professional had offered this option. In summary, the age preference for adolescents with chronic disorders and their parents to transfer to adult health care was higher than the upper age limits for admission to pediatric health care in many European countries. Anxiety and a lack of information of both adolescents and their parents were among the most important barriers for a smooth and timely transfer according to adolescents and parents.

Temporal changes in mRNA expression of the brain nutrient transporters in the lithium-pilocarpine model of epilepsy in the immature and adult rat.

The lithium-pilocarpine model mimics most features of human temporal lobe epilepsy. Following our prior studies of cerebral metabolic changes, here we explored the expression of transporters for glucose (GLUT1 and GLUT3) and monocarboxylates (MCT1 and MCT2) during and after status epilepticus (SE) induced by lithium-pilocarpine in PN10, PN21, and adult rats. In situ hybridization was used to study the expression of transporter mRNAs during the acute phase (1, 4, 12 and 24h of SE), the latent phase, and the early and late chronic phases. During SE, GLUT1 expression was increased throughout the brain between 1 and 12h of SE, more strongly in adult rats; GLUT3 increased only transiently, at 1 and 4h of SE and mainly in PN10 rats; MCT1 was increased at all ages but 5-10-fold more in adult than in immature rats; MCT2 expression increased mainly in adult rats. At all ages, MCT1 and MCT2 up-regulation was limited to the circuit of seizures while GLUT1 and GLUT3 changes were more widespread. During the latent and chronic phases, the expression of nutrient transporters was normal in PN10 rats. In PN21 rats, GLUT1 was up-regulated in all brain regions. In contrast, in adult rats GLUT1 expression was down-regulated in the piriform cortex, hilus and CA1 as a result of extensive neuronal death. The changes in nutrient transporter expression reported here further support previous findings in other experimental models demonstrating rapid transcriptional responses to marked changes in cerebral energetic/glucose demand.

Biomechanical characterization and in vitro mechanical injury of elderly human femoral head cartilage: comparison to adult bovine humeral head cartilage.

OBJECTIVES: In vitro mechanical injury of articular cartilage is useful to identify events associated with development of post-traumatic osteoarthritis (OA). To date, many in vitro injury models have used animal cartilage despite the greater clinical relevance of human cartilage. We aimed to characterize a new in vitro injury model using elderly human femoral head cartilage and compare its behavior to that of an existing model with adult bovine humeral head cartilage. DESIGN: Mechanical properties of human and bovine cartilage disks were characterized by elastic modulus and hydraulic permeability in radially confined axial compression, and by Young's modulus, Poisson's ratio, and direction-dependent radial strain in unconfined compression. Biochemical composition was assessed in terms of tissue water, solid, and glycosaminoglycan (GAG) contents. Responses to mechanical injury were assessed by observation of macroscopic superficial tissue cracks and histological measurements of cell viability following single injurious ramp loads at 7 or 70%/s strain rate to 3 or 14 MPa peak stress. RESULTS: Confined compression moduli and Young's moduli were greater in elderly human femoral cartilage vs adult bovine humeral cartilage whereas hydraulic permeability was less. Radial deformations of axially compressed explant disks were more anisotropic (direction-dependent) for the human cartilage. In both cartilage sources, tissue cracking and associated cell death during injurious loading was common for 14 MPa peak stress at both strain rates. CONCLUSION: Despite differences in mechanical properties, acute damage induced by injurious loading was similar in both elderly human femoral cartilage and adult bovine humeral cartilage, supporting the clinical relevance of animal-based cartilage injury models. However, inherent structural differences such as cell density may influence subsequent cell-mediated responses to injurious loading and affect the development of OA.

Clustering of health behaviours in adult survivors of childhood cancer and the general population.

BACKGROUND: Little is known about engagement in multiple health behaviours in childhood cancer survivors. METHODS: Using latent class analysis, we identified health behaviour patterns in 835 adult survivors of childhood cancer (age 20-35 years) and 1670 age- and sex-matched controls from the general population. Behaviour groups were determined from replies to questions on smoking, drinking, cannabis use, sporting activities, diet, sun protection and skin examination. RESULTS: The model identified four health behaviour patterns: 'risk-avoidance', with a generally healthy behaviour; 'moderate drinking', with higher levels of sporting activities, but moderate alcohol-consumption; 'risk-taking', engaging in several risk behaviours; and 'smoking', smoking but not drinking. Similar proportions of survivors and controls fell into the 'risk-avoiding' (42% vs 44%) and the 'risk-taking' cluster (14% vs 12%), but more survivors were in the 'moderate drinking' (39% vs 28%) and fewer in the 'smoking' cluster (5% vs 16%). Determinants of health behaviour clusters were gender, migration background, income and therapy. CONCLUSION: A comparable proportion of childhood cancer survivors as in the general population engage in multiple health-compromising behaviours. Because of increased vulnerability of survivors, multiple risk behaviours should be addressed in targeted health interventions.

Doublecortin-positive cells in the adult primate cerebral cortex and possible role in brain plasticity and development.

We have demonstrated that cortical cell autografts might be a useful therapy in two monkey models of neurological disease: motor cortex lesion and Parkinson's disease. However, the origin of the useful transplanted cells obtained from cortical biopsies is not clear. In this report we describe the expression of doublecortin (DCX) in these cells based on reverse-transcription polymerase chain reaction (RT-PCR) and immunodetection in the adult primate cortex and cell cultures. The results showed that DCX-positive cells were present in the whole primate cerebral cortex and also expressed glial and/or neuronal markers such as glial fibrillary protein (GFAP) or neuronal nuclei (NeuN). We also demonstrated that only DCX/GFAP positive cells were able to proliferate and originate progenitor cells in vitro. We hypothesize that these DCX-positive cells in vivo have a role in cortical plasticity and brain reaction to injury. Moreover, in vitro these DCX-positive cells have the potential to reacquire progenitor characteristics that confirm their potential for brain repair.

Severe primary cytomegalovirus infection in the immunocompetent adult patient: A case series.

Abstract Primary cytomegalovirus (CMV) infection is rare in immunocompetent adults, even rarer in elderly patients. Little is known about the severity of symptoms and the clinical course in this patient group. In children and younger adults, CMV mostly presents as an asymptomatic disease or a self-limiting mild mononucleosis-like syndrome. We describe the clinical course of an unusually severe primary CMV infection in a 69-y-old otherwise healthy man, as well as 6 other severe cases in immunocompetent adults at our institution, and compare them to adult cases from the literature. CMV primary infection and antiviral treatment should be considered in immunocompetent elderly persons presenting with a severe mononucleosis-like syndrome.

D-serine increases adult hippocampal neurogenesis.

Adult hippocampal neurogenesis results in the continuous formation of new neurons and is a process of brain plasticity involved in learning and memory. The neurogenic niche regulates the stem cell proliferation and the differentiation and survival of new neurons and a major contributor to the neurogenic niche are astrocytes. Among the molecules secreted by astrocytes, D-serine is an important gliotransmitter and is a co-agonist of the glutamate, N-methyl-D-aspartate (NMDA) receptor. D-serine has been shown to enhance the proliferation of neural stem cells in vitro, but its effect on adult neurogenesis in vivo is unknown. Here, we tested the effect of exogenous administration of D-serine on adult neurogenesis in the mouse dentate gyrus. We found that 1 week of treatment with D-serine increased cell proliferation in vivo and in vitro and increased the density of neural stem cells and transit amplifying progenitors. Furthermore, D-serine increased the survival of newborn neurons. Together, these results indicate that D-serine treatment resulted in the improvement of several steps of adult neurogenesis in vivo.

Primate adult brain cell autotransplantation produces behavioral and biological recovery in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian St. Kitts monkeys.

The potential for "replacement cells" to restore function in Parkinson's disease has been widely reported over the past 3 decades, rejuvenating the central nervous system rather than just relieving symptoms. Most such experiments have used fetal or embryonic sources that may induce immunological rejection and generate ethical concerns. Autologous sources, in which the cells to be implanted are derived from recipients' own cells after reprogramming to stem cells, direct genetic modifications, or epigenetic modifications in culture, could eliminate many of these problems. In a previous study on autologous brain cell transplantation, we demonstrated that adult monkey brain cells, obtained from cortical biopsies and kept in culture for 7 weeks, exhibited potential as a method of brain repair after low doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused dopaminergic cell death. The present study exposed monkeys to higher MPTP doses to produce significant parkinsonism and behavioral impairments. Cerebral cortical cells were biopsied from the animals, held in culture for 7 weeks to create an autologous neural cell "ecosystem" and reimplanted bilaterally into the striatum of the same six donor monkeys. These cells expressed neuroectodermal and progenitor markers such as nestin, doublecortin, GFAP, neurofilament, and vimentin. Five to six months after reimplantation, histological analysis with the dye PKH67 and unbiased stereology showed that reimplanted cells survived, migrated bilaterally throughout the striatum, and seemed to exert a neurorestorative effect. More tyrosine hydroxylase-immunoreactive neurons and significant behavioral improvement followed reimplantation of cultured autologous neural cells as a result of unknown trophic factors released by the grafts. J. Comp. Neurol. 522:2729-2740, 2014. © 2014 Wiley Periodicals, Inc.

Transitory glutathione deficit during brain development induces cognitive impairment in juvenile and adult rats: relevance to schizophrenia.

Glutathione (GSH) metabolism dysfunction is one risk factor in schizophrenia. A transitory brain GSH deficit was induced in Wistar (WIS) and mutant (ODS; lacking ascorbic acid synthesis) rats using BSO (l-buthionine-(S,R)-sulfoximine) from post-natal days 5-16. When GSH was re-established to physiological levels, juvenile BSO-ODS rats were impaired in the water maze task. Long after treatment cessation, adult BSO-WIS/-ODS rats showed impaired place discrimination in the homing board with distributed visual or olfactory cues. Their accuracy was restored when a single cue marked the trained position. Similarly, more working memory errors were made by adult BSO-WIS in the radial maze when several olfactory cues were present. These results reveal that BSO rats did not suffer simple sensory impairment. They were selectively impaired in spatial memory when the task required the integration of multimodal or olfactory cues. These results, in part, resemble some of the reported olfactory discrimination and cognitive impairment in schizophrenia.

Spaced training facilitates long-term retention of place navigation in adult but not in adolescent rats

Young and adult Long Evans rats were tested in the water maze according to two different procedures: half of the subjects were given one session of four trials a day for 6 days, whereas the other subjects had the same amount of training massed in 1 day. For both conditions, a 14-day retention interval was then introduced to test long-term memory. This was followed by a four-trial reversal session. All groups showed a significant learning curve, but escape latencies were shorter for the adult than for the young rats, without differential effect of the training procedure. A first probe trial (PT1) confirmed similar accurate short-term retention in all the groups. But unimpaired long-term memory was only seen in the adult rats trained with the spaced procedure. The young rats trained over 1 day also showed some retention of the platform location after 14 days, but not the other two groups. Reversal acquisition of the new platform location was rapid in the four groups. These results indicate that although accurate short-term spatial memory in the water maze is seen after a 1-day massed training in both age groups, unimpaired long-term retention is only observed in adult rats trained with 24-h inter-session intervals.