Review: Contact sport-related chronic traumatic encephalopathy in the elderly: clinical expression and structural substrates.

A. Costanza, K. Weber, S. Gandy, C. Bouras, P. R. Hof, P. Giannakopoulos and A. Canuto (2011) Neuropathology and Applied Neurobiology37, 570-584 Contact sport-related chronic traumatic encephalopathy in the elderly: clinical expression and structural substrates Professional boxers and other contact sport athletes are exposed to repetitive brain trauma that may affect motor functions, cognitive performance, emotional regulation and social awareness. The term of chronic traumatic encephalopathy (CTE) was recently introduced to regroup a wide spectrum of symptoms such as cerebellar, pyramidal and extrapyramidal syndromes, impairments in orientation, memory, language, attention, information processing and frontal executive functions, as well as personality changes and behavioural and psychiatric symptoms. Magnetic resonance imaging usually reveals hippocampal and vermis atrophy, a cavum septum pellucidum, signs of diffuse axonal injury, pituitary gland atrophy, dilated perivascular spaces and periventricular white matter disease. Given the partial overlapping of the clinical expression, epidemiology and pathogenesis of CTE and Alzheimer's disease (AD), as well as the close association between traumatic brain injuries (TBIs) and neurofibrillary tangle formation, a mixed pathology promoted by pathogenetic cascades resulting in either CTE or AD has been postulated. Molecular studies suggested that TBIs increase the neurotoxicity of the TAR DNA-binding protein 43 (TDP-43) that is a key pathological marker of ubiquitin-positive forms of frontotemporal dementia (FTLD-TDP) associated or not with motor neurone disease/amyotrophic lateral sclerosis (ALS). Similar patterns of immunoreactivity for TDP-43 in CTE, FTLD-TDP and ALS as well as epidemiological correlations support the presence of common pathogenetic mechanisms. The present review provides a critical update of the evolution of the concept of CTE with reference to its neuropathological definition together with an in-depth discussion of the differential diagnosis between this entity, AD and frontotemporal dementia.

Body fat distribution in white and black women: different patterns of intraabdominal and subcutaneous abdominal adipose tissue utilization with weight loss.

BACKGROUND: Intraabdominal adipose tissue (IAAT) is the body fat depot most strongly related to disease risk. Weight reduction is advocated for overweight people to reduce total body fat and IAAT, although little is known about the effect of weight loss on abdominal fat distribution in different races. OBJECTIVE: We compared the effects of diet-induced weight loss on changes in abdominal fat distribution in white and black women. DESIGN: We studied 23 white and 23 black women, similar in age and body composition, in the overweight state [mean body mass index (BMI; in kg/m(2)): 28.8] and the normal-weight state (mean BMI: 24.0) and 38 never-overweight control women (mean BMI: 23.4). We measured total body fat by using a 4-compartment model, trunk fat by using dual-energy X-ray absorptiometry, and cross-sectional areas of IAAT (at the fourth and fifth lumbar vertebrae) and subcutaneous abdominal adipose tissue (SAAT) by using computed tomography. RESULTS: Weight loss was similar in white and black women (13.1 and 12.6 kg, respectively), as were losses of total fat, trunk fat, and waist circumference. However, white women lost more IAAT (P < 0.001) and less SAAT (P < 0.03) than did black women. Fat patterns regressed toward those of their respective control groups. Changes in waist circumference correlated with changes in IAAT in white women (r = 0.54, P < 0.05) but not in black women (r = 0.19, NS). CONCLUSIONS: Despite comparable decreases in total and trunk fat, white women lost more IAAT and less SAAT than did black women. Waist circumference was not a suitable surrogate marker for tracking changes in the visceral fat compartment in black women.

The importance of environmental exposures to physical, mental and social well-being

"Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity" states the WHO. However, the current focus in this important area seems to be on reducing diseases, while less attention is paid on aspects how to increase the well-being of populations. This paper reviews three examples where well-being has drawn attention of the public and policy makers, and compares the policies of two wealthy countries. The first example is noise. Noise can reduce sleep quality and cause physiological, mental, and social effects. In Switzerland, noise receives a lot of attention by the public. Swiss laws are extensive, e.g., they prohibit trucks and planes from traveling at night. In the USA, there is little public attention and no national strategy against environmental noise. The second example is aesthetics and recreation. Many humans seek contact with the beauty of nature. The USA and Switzerland have similar strategies for achieving clear waters, while the protection of scenic views is approached very differently. Lifestyle is the last example. In the USA, the desire for individual freedom is a leading cause for suburban sprawl, a car-dependent sedentary lifestyle resulting in obesity, asthma and loss of community spirit. In Switzerland, a strict land use planning seeks to balance individual and public interests and stresses public transportation, which seems to be a more promising approach. Paying attention to aspects of well-being while developing political strategies might be a promising model to tackle environmental problems. Successful strategies employed so far seem to include the public, local authorities, politicians and scientists in this process, which might have been a key for their success. [Authors]

Habitat selection in zones of parapatric contact between the common shrew Sorex araneaus and Millet's shrew S. coronatus

(1) The common shrew Sorex araneus and Millet's shrew S. coronatusare sibling species.They are morphologically and genetically very similar but do not hybridize.Their parapatric distribution throughout south-western Europe, with a few narrow zones of distributional overlap, suggests that they are in competitive parapatry. (2) Two of these contact zones were studied; there was evidence of coexistence over periods of 2 years as well as habitat segregation. In both zones, the species segregated on litter thickness and humidity variables. (3) A simple analysis of spatial distribution showed that habitats visible in the field corresponded to the habitats selected by the species. Habitat selection was found throughout the annual life-cycle of the shrews. (4) In one contact zone, a removal experiment was performed to test whether habitat segregation is induced by interspecific interactions. The experiment showed that the species select habitats differentially when both are present and abandon habitat selection when their competitor removed. (5)These results confirm the role of resource partitioning in promoting narrow ranges of distributional overlap between such parapatric species and qualitatively support the prediction of habitat selection theory that, in a two-species system, coexistence may be achieved by differential habitat selection to avoid competition. The results also support the view that the common shrew and Millet's shrew are in competitive parapatry.

Fatigue and weight loss predict survival on circadian chemotherapy for metastatic colorectal cancer.

BACKGROUND: Chemotherapy-induced neutropenia has been associated with prolonged survival selectively in patients on a conventional schedule (combined 5-fluorouracil, leucovorin, and oxaliplatin [FOLFOX2]) but not on a chronomodulated schedule of the same drugs administered at specific circadian times (chronoFLO4). The authors hypothesized that the early occurrence of chemotherapy-induced symptoms correlated with circadian disruption would selectively hinder the efficacy of chronotherapy. METHODS: Fatigue and weight loss (FWL) were considered to be associated with circadian disruption based on previous data. Patients with metastatic colorectal cancer (nâeuro0/00=âeuro0/00543) from an international phase 3 trial comparing FOLFOX2 with chronoFLO4 were categorized into 4 subgroups according to the occurrence of FWL or other clinically relevant toxicities during the initial 2 courses of chemotherapy. Multivariate Cox models were used to assess the role of toxicity on the time to progression (TTP) and overall survival (OS). RESULTS: The proportions of patients in the 4 subgroups were comparable in both treatment arms (Pâeuro0/00=âeuro0/00.77). No toxicity was associated with TTP or OS on FOLFOX2. The median OS on FOLFOX2 ranged from 16.4 (95% confidence limits [CL], 7.2-25.6 months) to 19.8 months (95% CL, 17.7-22.0 months) according to toxicity subgroup (Pâeuro0/00=âeuro0/00.45). Conversely, FWL, but no other toxicity, independently predicted for significantly shorter TTP (Pâeuro0/00<âeuro0/00.0001) and OS (Pâeuro0/00=âeuro0/00.001) on chronoFLO4. The median OS on chronoFLO4 was 13.8 months (95% CL, 10.4-17.2 months) or 21.1 months (95% CL, 19.0-23.1 months) according to presence or absence of chemotherapy-induced FWL, respectively. CONCLUSIONS: Early onset chemotherapy-induced FWL was an independent predictor of poor TTP and OS only on chronotherapy. Dynamic monitoring to detect early chemotherapy-induced circadian disruption could allow the optimization of rapid chronotherapy and concomitant improvements in safety and efficacy.

Methicillin-resistant Staphylococcus aureus with intermediate susceptibility to vancomycin: are strict additional contact measures sufficient?

Background: A hospitalised patient infected with MRSA was found to harbour a VISA strain after 6 weeks of treatment with vancomycin. Additional contact measures were reinforced according to CDCs recommendations. We decide to evaluate if these applied control measures were effective. Objective: To evaluate the efficacy of strict additional contact measures to contain the dissemination of VISA from an infected patient. Methods: All patients from the unit were screened weekly for MRSA during a 6-week period, whereas health care workers (HCW) were screened only once. Screening specimen included nose, throat, groin, and clinical specimens for patients, and only nose and throat for HCW. Broth enrichment and chromogenic agar (MRSA-select) were used for MRSA detection. All MRSA isolates were tested on Van screen plates, and growing colonies were tested for MIC of vancomycin. MIC was performed using Etest. Population analysis was done for VISA confirmation. One strain per person was typed by Double Locus Sequence Typing (based on clfB and spa sequencing). Results: 66 patients hospitalized in the same service during the 6 weeks and 55 HCW were screened for MRSA and VISA. MRSA was found in 16/66 (24%) patients and 1/55 (2%) HCW. 16/17 MRSA from patients belonged to the same genotype that the VISA strain. The remaining patient had a MRSA identical to the HCW isolate. Among the 16 MRSA isolates sharing the same genotype than the VISA strain, two showed Etests vancomycin MIC of only 4 mg/L. MIC results were confirmed by the population analysis. They were not considered as VISA, but as MRSA with increased vancomycin MICs. Both isolates were obtained from two roommates. Conclusion: Strict additional contact measures were found to be effective to contain VISA dissemination. However, the identification of two isolates with increased vancomycin MIC (4 mg/L) in two roommates raised the question of the need to routinely test this susceptibility and of adequate control measures for patients harbouring such isolates.

Human-to-bovine jump of Staphylococcus aureus CC8 is associated with the loss of a β-hemolysin converting prophage and the acquisition of a new staphylococcal cassette chromosome.

Staphylococcus aureus can colonize and infect both humans and animals, but isolates from both hosts tend to belong to different lineages. Our recent finding of bovine-adapted S. aureus showing close genetic relationship to the human S. aureus clonal complex 8 (CC8) allowed us to examine the genetic basis of host adaptation in this particular CC. Using total chromosome microarrays, we compared the genetic makeup of 14 CC8 isolates obtained from cows suffering subclinical mastitis, with nine CC8 isolates from colonized or infected human patients, and nine S. aureus isolates belonging to typical bovine CCs. CC8 isolates were found to segregate in a unique group, different from the typical bovine CCs. Within this CC8 group, human and bovine isolates further segregated into three subgroups, among which two contained a mix of human and bovine isolates, and one contained only bovine isolates. This distribution into specific clusters and subclusters reflected major differences in the S. aureus content of mobile genetic elements (MGEs). Indeed, while the mixed human-bovine clusters carried commonly human-associated β-hemolysin converting prophages, the bovine-only isolates were devoid of such prophages but harbored an additional new non-mec staphylococcal cassette chromosome (SCC) unique to bovine CC8 isolates. This composite cassette carried a gene coding for a new LPXTG-surface protein sharing homologies with a protein found in the environmental bacterium Geobacillus thermoglucosidans. Thus, in contrast to human CC8 isolates, the bovine-only CC8 group was associated with the combined loss of β-hemolysin converting prophages and gain of a new SCC probably acquired in the animal environment. Remaining questions are whether the new LPXTG-protein plays a role in bovine colonization or infection, and whether the new SCC could further acquire antibiotic-resistance genes and carry them back to human.

Azole resistance by loss of function of the sterol Δ⁵,⁶-desaturase gene (ERG3) in Candida albicans does not necessarily decrease virulence.

The inactivation of ERG3, a gene encoding sterol Δ⁵,⁶-desaturase (essential for ergosterol biosynthesis), is a known mechanism of in vitro resistance to azole antifungal drugs in the human pathogen Candida albicans. ERG3 inactivation typically results in loss of filamentation and attenuated virulence in animal models of disseminated candidiasis. In this work, we identified a C. albicans clinical isolate (VSY2) with high-level resistance to azole drugs in vitro and an absence of ergosterol but normal filamentation. Sequencing of ERG3 in VSY2 revealed a double base deletion leading to a premature stop codon and thus a nonfunctional enzyme. The reversion of the double base deletion in the mutant allele (erg3-1) restored ergosterol biosynthesis and full fluconazole susceptibility in VSY2, confirming that ERG3 inactivation was the mechanism of azole resistance. Additionally, the replacement of both ERG3 alleles by erg3-1 in the wild-type strain SC5314 led to the absence of ergosterol and to fluconazole resistance without affecting filamentation. In a mouse model of disseminated candidiasis, the clinical ERG3 mutant VSY2 produced kidney fungal burdens and mouse survival comparable to those obtained with the wild-type control. Interestingly, while VSY2 was resistant to fluconazole both in vitro and in vivo, the ERG3-derived mutant of SC5314 was resistant only in vitro and was less virulent than the wild type. This suggests that VSY2 compensated for the in vivo fitness defect of ERG3 inactivation by a still unknown mechanism(s). Taken together, our results provide evidence that contrary to previous reports inactivation of ERG3 does not necessarily affect filamentation and virulence.

Decreased glucose-induced thermogenesis after weight loss in obese subjects: a predisposing factor for relapse of obesity?

Glucose-induced thermogenesis (GIT) after a 100-g oral glucose load was measured by continuous indirect calorimetry in 32 nondiabetic and diabetic obese subjects and compared to 17 young and 13 middle aged control subjects. The obese subjects were divided into three groups: A (n = 12) normal glucose tolerance, B (n = 13) impaired glucose tolerance, and C (n = 7) diabetics, and were studied before and after a body weight loss ranging from 9.6 to 33.5 kg consecutive to a 4 to 6 months hypocaloric diet. GIT, measured over 3 h and expressed as percentage of the energy content of the load, was significantly reduced in obese groups A and C (6.2 +/- 0.6, and 3.8 +/- 0.7%, respectively) when compared to their age-matched control groups: 8.6 +/- 0.7 (young) and 5.8 +/- 0.3% (middle aged). Obese group B had a GIT of 6.1 +/- 0.6% which was lower than that of the young control group but not different from the middle-aged control group. After weight loss, GIT in the obese was further reduced in groups A and B than before weight loss: ie, 3.4 +/- 0.6 (p less than 0.001), 3.7 +/- 0.5 (p less than 0.01) respectively, whereas in group C, weight loss induced no further diminution in GIT (3.8 +/- 0.6%). These results support the concept of a thermogenic defect after glucose ingestion in obese individuals which is not the consequence of their excess body weight but may be one of the factors favoring the relapse of obesity after weight loss.

NR2A at CA1 synapses is obligatory for the susceptibility of hippocampal plasticity to sleep loss.

A loss in the necessary amount of sleep alters expression of genes and proteins implicated in brain plasticity, but key proteins that render neuronal circuits sensitive to sleep disturbance are unknown. We show that mild (4-6 h) sleep deprivation (SD) selectively augmented the number of NR2A subunits of NMDA receptors on postsynaptic densities of adult mouse CA1 synapses. The greater synaptic NR2A content facilitated induction of CA3-CA1 long-term depression in the theta frequency stimulation range and augmented the synaptic modification threshold. NR2A-knock-out mice maintained behavioral response to SD, including compensatory increase in post-deprivation resting time, but hippocampal synaptic plasticity was insensitive to sleep loss. After SD, the balance between synaptically activated and slowly recruited NMDA receptor pools during temporal summation was disrupted. Together, these results indicate that NR2A is obligatory for the consequences of sleep loss on hippocampal synaptic plasticity. These findings could advance pharmacological strategies aiming to sustain hippocampal function during sleep restriction.

Persistence of Increased Eotaxin-1 (CCL11) Level in Tears of Patients Wearing Contact Lenses: A Long-Term Follow-Up Study.

BACKGROUND: Eotaxin-1 (CCL11) is a potent eosinophil chemotactic and activating peptide that may be implicated in the pathogenesis of chronic allergic eye disease and has been associated with the wearing of contact lenses (CL) in patients with contact lens papillary conjunctivitis (CLPC). The purpose of this study was to study eotaxin-1 expression in the tears of long-term CL wearers. PATIENTS AND METHODS: Tears were collected with glass capillaries from 15 patients (2 male, 13 female) with various degree of CLPC at 2-year intervals. CLPC severity was graded from 0 to 4 with reference to standard slit-lamp photographs of the superior tarsal conjunctiva. The eotaxin-1 level in the tears was measured by an ELISA, using mouse anti-human eotaxin monoclonal antibodies. RESULTS: The mean age was 32.5 ± 13.3 years (range: 17 - 69 years). The mean interval between the tear collections was 30 ± 4.8 months. The mean concentration of eotaxin was 2150 ± 477 pg/mL and 2486 ± 810 pg/mL for the first and second series, respectively. The difference was not statistically significant (paired Wilcoxon/Kruskal-Wallis, p = 0.803). The mean score of papilla grade was 1.26 ± 0.18 for the first sample and 1.40 ± 0.19 two years later. There was no significant difference of grading between the two time periods (paired Wilcoxon/Kruskal-Wallis, p = 0.751). CONCLUSIONS: the eotaxin-1 level remains up-regulated over a long time period in patients wearing CL, most of them with chronic CLPC. Eotaxin may play a role in the pathogenesis of contact lens intolerance.