An online intervention for carers to manage behavioral symptoms in motor neuron disease (MiNDToolkit): a randomized parallel multi-center feasibility trial.

BACKGROUND: Evidence on management of behavioral symptoms in motor neuron disease (MND) is lacking. The MiNDToolkit, an online psychoeducational platform, supports carers dealing with behavioral symptoms (BehSymp). The study objectives were to ascertain recruitment and retention rates, carer and healthcare professional (HCP) use of the platform, and completion of online assessments, to inform a full-scale trial. Design: Randomized, parallel, multi-center, feasibility trial. SETTING: England and Wales, across diverse MND services; recruitment from July/21 to November/22; last participant follow-up in March/23. PARTICIPANTS: Carers of people with motor neuron disease (PwMND) with BehSymp, recruited through MND services. After confirming eligibility, participants completed screening and baseline assessments online via the MiNDToolkit platform and were randomized centrally in a 1:1 ratio to MiNDToolkit or control. INTERVENTION: MiNDToolkit offered tailored modules to carers for the 3-month study period. Carers in the intervention group could receive additional support from MiNDToolkit trained HCPs. The control group was offered access to the intervention at the end of the study. Data were collected on platform usage and psychosocial variables. MAIN OUTCOMES: One hundred and fifty-one carers from 11 sites were invited to join the study (letter, face-to-face); 30 were screened; 29 were randomized. Fifteen people were allocated to the control arm; 14 to intervention. Carers were mostly female; median age for was 62.5 (IQR: 58, 68; intervention) and 57 (IQR: 56, 70; controls). Study retention was high (24/29 = 82.76%); carers engaged with the platform on average 14 times (median (IQR):14.0 (10.0, 18.5)) during the study period. CONCLUSION: The MiNDToolkit study was feasible and well accepted by carers and trained HCPs. A definitive trial is warranted.

Predicted sensitivity to endocrine therapy for stage II-III hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancer before chemo-endocrine therapy.

BACKGROUND: We proposed that a test for sensitivity to the adjuvant endocrine therapy component of treatment for patients with stage II-III breast cancer (SET2,3) should measure transcription related to estrogen and progesterone receptors (SETER/PR index) adjusted for a baseline prognostic index (BPI) combining clinical tumor and nodal stage with molecular subtype by RNA4 (ESR1, PGR, ERBB2, and AURKA). PATIENTS AND METHODS: Patients with clinically high-risk, hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2-) breast cancer received neoadjuvant taxane-anthracycline chemotherapy, surgery with measurement of residual cancer burden (RCB), and then adjuvant endocrine therapy. SET2,3 was measured from pre-treatment tumor biopsies, evaluated first in an MD Anderson Cancer Center (MDACC) cohort (n = 307, 11 years' follow-up, U133A microarrays), cut point was determined, and then independent, blinded evaluation was carried out in the I-SPY2 trial (n = 268, high-risk MammaPrint result, 3.8 years' follow-up, Agilent-44K microarrays, NCI Clinical Trials ID: NCT01042379). Primary outcome measure was distant relapse-free survival. Multivariate Cox regression models tested prognostic independence of SET2,3 relative to RCB and other molecular prognostic signatures, and whether other prognostic signatures could substitute for SETER/PR or RNA4 components of SET2,3. RESULTS: SET2,3 added independent prognostic information to RCB in the MDACC cohort: SET2,3 [hazard ratio (HR) 0.23, P = 0.004] and RCB (HR 1.77, P < 0.001); and the I-SPY2 trial: SET2,3 (HR 0.27, P = 0.031) and RCB (HR 1.68, P = 0.008). SET2,3 provided similar prognostic information irrespective of whether RCB-II or RCB-III after chemotherapy, and in both luminal subtypes. Conversely, RCB was most strongly prognostic in cancers with low SET2,3 status (MDACC P < 0.001, I-SPY2 P < 0.001). Other molecular signatures were not independently prognostic; they could effectively substitute for RNA4 subtype within the BPI component of SET2,3, but they could not effectively substitute for SETER/PR index. CONCLUSIONS: SET2,3 added independent prognostic information to chemotherapy response (RCB) and baseline prognostic score or subtype. Approximately 40% of patients with clinically high-risk HR+/HER2- disease had high SET2,3 and could be considered for clinical trials of neoadjuvant endocrine-based treatment.

Prognostic implications of residual disease tumor-infiltrating lymphocytes and residual cancer burden in triple-negative breast cancer patients after neoadjuvant chemotherapy.

BACKGROUND: For primary triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC), higher pretreatment tumor-infiltrating lymphocytes (TILs) correlates with increased pathologic complete response (pCR) rates, and improved survival. We evaluated the added prognostic value of residual disease (RD) TILs to residual cancer burden (RCB) in predicting survival post-NAC. PATIENTS AND METHODS: We combined four TNBC NAC patient cohorts who did not achieve pCR. RD TILs were investigated for associations with recurrence-free survival (RFS), and overall survival (OS) using Cox models with stromal TILs as a continuous variable (per 10% increment). The likelihood ratio test was used to evaluate added prognostic value of RD TILs. RESULTS: A total of 375 RD TNBC samples were evaluable for TILs and RCB. The median age was 50 years, with 62% receiving anthracycline/taxane chemotherapy. The RCB class after NAC was 11%, 50%, and 39% for I, II, and III, respectively. The median RD TIL level was 20% (IQR 10-40). There was a positive correlation between RD TIL levels and CD8+ T-cell density (ρ = 0.41). TIL levels were significantly lower with increasing post-NAC tumor (P = 0.005), nodal stage (P = 0.032), but did not differ by RCB class (P = 0.84). Higher RD TILs were significantly associated with improved RFS (HR: 0.86; 95% CI 0.79-0.92; P < 0.001), and improved OS (HR: 0.87; 95% CI 0.80-0.94; P < 0.001), and remained significant predictors in multivariate analysis (RFS P = 0.032; OS P = 0.038 for OS). RD TILs added significant prognostic value to multivariate models including RCB class (P < 0.001 for RFS; P = 0.021 for OS). The positive prognostic effect of RD TILs significantly differed by RCB class for RFS (PInt=0.003) and OS (PInt=0.008) with a greater magnitude of positive effect observed for RCB class II than class III. CONCLUSIONS: TIL levels in TNBC RD are significantly associated with improved RFS and OS and add further prognostic information to RCB class, particularly in RCB class II.

Radiation dose in paediatric cardiac catheterisation: A systematic literature review.

OBJECTIVES: It is believed that children are more sensitive to ionising radiation than adults. This work reviewed the reported radiation dose estimates for paediatric cardiac catheterisation. A systematic literature review was performed by searching healthcare databases for studies reporting radiation dose using predetermined key words relating to children having cardiac catheterisation. The quality of publications was assessed using relevant Critical Appraisal Skills Programme questions and their reported radiation exposures were evaluated. KEY FINDINGS: It is only in recent years that larger cohort observations have been undertaken. Although radiation dose from paediatric cardiac catheterisation has decreased in recent years, the literature indicated that it remains varied and potentially substantial. CONCLUSION: Standardisation of weight categories and procedure types such as those recommended by the PiDRL project could help compare current and future radiation dose estimates.

Effects of social reorganization on dopamine D2/D3 receptor availability and cocaine self-administration in male cynomolgus monkeys.

RATIONALE: Studies have demonstrated that brain dopamine D2/D3 receptors (D2/D3R) and the reinforcing effects of cocaine can be influenced by a monkey's position in the social dominance hierarchy. OBJECTIVE: In this study, we manipulated the social ranks of monkeys by reorganizing social groups and assessed effects on D2/D3R availability and cocaine self-administration. METHODS: Male cynomolgus monkeys (N = 12) had been trained to self-administer cocaine under a concurrent cocaine-food reinforcement schedule. Previously, PET measures of D2/D3R availability in the caudate nucleus and putamen had been obtained with [18F]fluoroclebopride during cocaine abstinence, while monkeys lived in stable social groups of four monkeys/pen. For this study, monkeys were reorganized into groups that consisted of (1) four previously dominant, (2) four previously subordinate, and (3) a mix of previously dominant and subordinate monkeys. After 3 months, D2/D3R availability was redetermined and cocaine self-administration was reexamined. RESULTS: D2/D3R availability significantly increased after reorganization in monkeys who were formerly subordinate, with the greatest increases observed in those that became dominant. No consistent changes in D2/D3R availability were observed in formerly dominant monkeys. Cocaine self-administration did not vary according to rank after reorganization of social groups. However, when compared to their previous cocaine self-administration data, the potency of cocaine as a reinforcer decreased in 9 of 11 monkeys. CONCLUSIONS: These results indicate that changing the social conditions can alter D2/D3R availability in subordinate monkeys in a manner suggestive of environmental enrichment. In most monkeys, social reorganization shifted the cocaine dose-response curve to the right, also consistent with environmental enrichment.

Effects of electromagnetic fields emitted by GSM phones on working memory: a meta-analysis.

BACKGROUND AND OBJECTIVE: Current treatments for Alzheimer's Disease (AD) do not affect the course of the illness and brain stimulation techniques are increasingly promoted as potential therapeutic interventions for AD. This study reviews the effects of electromagnetic field (EMF) exposure versus sham exposure on working memory (WM) performance of healthy human participants. METHOD: Online literature databases and previous systematic reviews were searched for studies of EMF and WM in participants without reported memory problems. Two thousand eight hundred and fifty seven studies were identified, and 10 studies met the inclusion criteria. An assessment of study quality was completed, and separate, random effects meta-analyses were conducted for each of the three WM tasks included: n-back, substitution and digit span forward. RESULTS: No differences were found between participants exposed to active EMF versus sham conditions in any of the three working memory tasks examined. CONCLUSION: Results indicate that EMF does not affect WM during the n-back, substitution and digit-span tasks. Future studies should focus on the possible effects of chronic exposure to EMF in older adults with AD using a battery of comparable WM and attention tasks, before EMF can be seriously considered as a potential modulator of WM in AD. Copyright © 2016 John Wiley & Sons, Ltd.

Role for the M1 Muscarinic Acetylcholine Receptor in Top-Down Cognitive Processing Using a Touchscreen Visual Discrimination Task in Mice.

The M1 muscarinic acetylcholine receptor (mAChR) subtype has been implicated in the underlying mechanisms of learning and memory and represents an important potential pharmacotherapeutic target for the cognitive impairments observed in neuropsychiatric disorders such as schizophrenia. Patients with schizophrenia show impairments in top-down processing involving conflict between sensory-driven and goal-oriented processes that can be modeled in preclinical studies using touchscreen-based cognition tasks. The present studies used a touchscreen visual pairwise discrimination task in which mice discriminated between a less salient and a more salient stimulus to assess the influence of the M1 mAChR on top-down processing. M1 mAChR knockout (M1 KO) mice showed a slower rate of learning, evidenced by slower increases in accuracy over 12 consecutive days, and required more days to acquire (achieve 80% accuracy) this discrimination task compared to wild-type mice. In addition, the M1 positive allosteric modulator BQCA enhanced the rate of learning this discrimination in wild-type, but not in M1 KO, mice when BQCA was administered daily prior to testing over 12 consecutive days. Importantly, in discriminations between stimuli of equal salience, M1 KO mice did not show impaired acquisition and BQCA did not affect the rate of learning or acquisition in wild-type mice. These studies are the first to demonstrate performance deficits in M1 KO mice using touchscreen cognitive assessments and enhanced rate of learning and acquisition in wild-type mice through M1 mAChR potentiation when the touchscreen discrimination task involves top-down processing. Taken together, these findings provide further support for M1 potentiation as a potential treatment for the cognitive symptoms associated with schizophrenia.

A novel SDS-stable dimer of a heterogeneous nuclear ribonucleoprotein at presynaptic terminals of squid neurons.

The presence of mRNAs in synaptic terminals and their regulated translation are important factors in neuronal communication and plasticity. Heterogeneous nuclear ribonucleoprotein (hnRNP) complexes are involved in the translocation, stability, and subcellular localization of mRNA and the regulation of its translation. Defects in these processes and mutations in components of the hnRNP complexes have been related to the formation of cytoplasmic inclusion bodies and neurodegenerative diseases. Despite much data on mRNA localization and evidence for protein synthesis, as well as the presence of translation machinery, in axons and presynaptic terminals, the identity of RNA-binding proteins involved in RNA transport and function in presynaptic regions is lacking. We previously characterized a strongly basic RNA-binding protein (p65), member of the hnRNPA/B subfamily, in squid presynaptic terminals. Intriguingly, in sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), p65 migrated as a 65-kDa protein, whereas members of the hnRNPA/B family typically have molecular masses ranging from 35 to 42kDa. In this report we present further biochemical and molecular characterization that shows endogenous p65 to be an SDS-stable dimer composed of ∼37-kDa hnRNPA/B-like subunits. We cloned and expressed a recombinant protein corresponding to squid hnRNPA/B-like protein and showed its propensity to aggregate and form SDS-stable dimers in vitro. Our data suggest that this unique hnRNPA/B-like protein co-localizes with synaptic vesicle protein 2 and RNA-binding protein ELAV and thus may serve as a link between local mRNA processing and presynaptic function and regulation.

Do cognitive interventions improve general cognition in dementia? A meta-analysis and meta-regression.

OBJECTIVES: To review the efficacy of cognitive interventions on improving general cognition in dementia. METHOD: Online literature databases and trial registers, previous systematic reviews and leading journals were searched for relevant randomised controlled trials. A systematic review, random-effects meta-analyses and meta-regression were conducted. Cognitive interventions were categorised as: cognitive stimulation (CS), involving a range of social and cognitive activities to stimulate multiple cognitive domains; cognitive training (CT), involving repeated practice of standardised tasks targeting a specific cognitive function; cognitive rehabilitation (CR), which takes a person-centred approach to target impaired function; or mixed  CT and stimulation (MCTS). Separate analyses were conducted for general cognitive outcome measures and for studies using 'active' (designed to control for non-specific therapeutic effects) and non-active (minimal or no intervention) control groups. RESULTS: 33 studies were included. Significant positive effect sizes (Hedges' g) were found for CS with the mini-mental state examination (MMSE) (g=0.51, 95% CI 0.35 to 0.66; p<0.001) compared to non-active controls and (g=0.35, 95% CI 0.06 to 0.64; p=0.019) compared to active controls. Significant benefit was also seen with the Alzheimer's disease Assessment Scale-Cognition (ADAS-Cog) (g=-0.26, 95% CI -0.445 to -0.08; p=0.005). There was no evidence that CT or MCTS produced significant improvements on general cognition outcomes and not enough CR studies for meta-analysis. The lowest accepted minimum clinically important difference was reached in 11/17 CS studies for the MMSE, but only 2/9 studies for the ADAS-Cog. Additionally, 95% prediction intervals suggested that although statistically significant, CS may not lead to benefits on the ADAS-Cog in all clinical settings. CONCLUSIONS: CS improves scores on MMSE and ADAS-Cog in dementia, but benefits on the ADAS-Cog are generally not clinically significant and difficulties with blinding of patients and use of adequate placebo controls make comparison with the results of dementia drug treatments problematic.

Investigating the CT localizer radiograph: acquisition parameters, patient centring and their combined influence on radiation dose.

OBJECTIVE: To systematically investigate the effect of CT localizer radiograph acquisition on the tube current modulation and thus radiation dose of the subsequent diagnostic scan. METHODS: Localizer radiographs of an abdominal section CT phantom were taken, and the resulting volume CT dose index (CTDIvol) for the diagnostic scan was recorded. Variables included tube potential, the phantom's alignment within the CT scanner gantry in both the vertical and horizontal directions and the X-ray source angle at which the localizer was acquired. RESULTS: Diagnostic scan CTDIvol decreased with increasing tube potential. Vertical (table height) movement was found to affect radiation dose more than horizontal movement, with ±50 mm table movement resulting in a standard deviation in the diagnostic scan CTDIvol of 4.4 mGy, compared with 2.5 mGy with ±50 mm horizontal movement. Correspondingly, localizer angles of 90° or 270° (3 o'clock and 9 o'clock X-ray source positions) were less sensitive overall to alignment errors, with a standard deviation of 2.5 mGy, compared with a 0° or 180° angle, which had a standard deviation of 3.8 mGy. CONCLUSION: To achieve a consistently optimized radiation dose, the localizer protocol should be paired with the diagnostic acquisition protocol. A final acquisition angle of 90° should be used when possible to minimize dose variation resulting from alignment errors. ADVANCES IN KNOWLEDGE: Localizer parameters that affect radiation output were identified for this scanner system. The importance of tube potential and acquisition angle was highlighted.

Socioeconomic inequalities in cause-specific mortality after disability retirement due to different diseases.

AIMS: Socioeconomic inequalities in both disability retirement and mortality are large. The aim of this study was to examine socioeconomic differences in cause-specific mortality after disability retirement due to different diseases. METHODS: We used administrative register data from various sources linked together by Statistics Finland and included an 11% sample of the Finnish population between the years 1987 and 2007. The data also include an 80% oversample of the deceased during the follow-up. The study included men and women aged 30-64 years at baseline and those who turned 30 during the follow-up. We used Cox regression analysis to examine socioeconomic differences in mortality after disability retirement. RESULTS: Socioeconomic differences in mortality after disability retirement were smaller than in the population in general. However, manual workers had a higher risk of mortality than upper non-manual employees after disability retirement due to mental disorders and cardiovascular diseases, and among men also diseases of the nervous system. After all-cause disability retirement, manual workers ran a higher risk of cardiovascular and alcohol-related death. However, among men who retired due to mental disorders or cardiovascular diseases, differences in social class were found for all causes of death examined. For women, an opposite socioeconomic gradient in mortality after disability retirement from neoplasms was found. Conclusions: The disability retirement process leads to smaller socioeconomic differences in mortality compared with those generally found in the population. This suggests that the disability retirement system is likely to accurately identify chronic health problems with regard to socioeconomic status.

Blastocystis tropism in the pig intestine.

Blastocystis has been reported in pig feces but the sites of development in the gastrointestinal tract are unknown. The present study was undertaken to determine predilection sites of Blastocystis in 11 naturally infected pigs examined at 20 weeks of age. At necropsy, feces and contents of the duodenum, jejunum, ileum, and cecum were examined by immunofluorescence (IFA) microscopy and PCR and tissues from these sites as well as the proximal and distal colon were processed for histology from pigs 1 to 5. Feces were examined by IFA microscopy, and segments from the jejunum and ileum were processed for histology from pigs 6 to 11. Multiple sections were cut from each tissue segment, and each was stained with the following: hematoxylin and eosin, polyclonal rabbit antibody to Blastocystis, and ParaFlor B monoclonal antibody to Blastocystis. Blastocystis was detected in feces of all 11 pigs by IFA microscopy and determined by PCR and gene sequencing to be subtype 5 for pigs 1-5. Blastocystis was also detected in the lumen contents removed from the cecum of pigs 1-5 examined by IFA microscopy and in the cecum of pigs 4 and 5 by PCR. Blastocystis was also observed in tissue sections from the jejunum of 7 of the 11 pigs, in the proximal and distal colon of pigs 1-5, and in the cecum of 4 of these 5 pigs but was not detected in the duodenum or ileum of any pigs. In tissue sections, Blastocystis was found primarily in the lumen usually associated with digested food debris, sometimes in close proximity or appearing to adhere to the epithelium, but no stages were found to penetrate the epithelium or the lamina propria.

Reducing patient radiation dose during CT-guided procedures: demonstration in spinal injections for pain.

BACKGROUND AND PURPOSE: CT guidance may improve precision for diagnostic and therapeutic spinal injections, but it can increase patient radiation dose. This study examined the impact of reducing tube current on patient radiation exposure and the technical success for these procedures, by using axial acquisitions for short scan lengths and eliminating nonessential imaging. MATERIALS AND METHODS: Our institutional review board approved retrospective analysis of records from 100 consecutive outpatients undergoing spinal injections for pain before and after the CT protocol modification to reduce radiation dose. Data collected included patient age and sex, response to injection, number of sites and spinal levels treated, injection type, performing physician, CT acquisition method, number of imaging series, tube current, scan length, and DLP. RESULTS: Image contrast was reduced with the low-dose protocol, but this did not affect technical success or immediate pain relief. Mean DLP for all procedures decreased from 1458 ± 1022 to 199 ± 101 mGy · cm (P < .001). The range of radiologist-dependent DLP per procedure also was reduced significantly with the modified protocol. Selective nerve root blocks, lumbar injections, multiple injection sites, and the lack of prior imaging were each associated with a slightly higher DLP (<50 mGy · cm). CONCLUSIONS: Radiation to patients undergoing CT-guided spinal injections can be decreased significantly without affecting outcome by reducing tube current, using axial acquisitions for short scan lengths, and eliminating nonessential imaging guidance. These measures also decrease variability in radiation doses between different practitioners and should be useful for other CT-guided procedures in radiology.

Influence of cocaine history on the behavioral effects of Dopamine D(3) receptor-selective compounds in monkeys.

Although dopamine D(3) receptors have been associated with cocaine abuse, little is known about the consequences of chronic cocaine on functional activity of D(3) receptor-preferring compounds. This study examined the behavioral effects of D(3) receptor-selective 4-phenylpiperazines with differing in vitro functional profiles in adult male rhesus monkeys with a history of cocaine self-administration and controls. In vitro assays found that PG 619 (N-(3-hydroxy-4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-4-(pyridin-2-yl)benzamide HCl) was a potent D(3) antagonist in the mitogenesis assay, but a fully efficacious agonist in the adenylyl cyclase assay, NGB 2904 (N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)-9H-fluorene-2-carboxamide HCl) was a selective D(3) antagonist, whereas CJB 090 (N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)-4-(pyridin-2-yl)benzamide HCl) exhibited a partial agonist profile in both in vitro assays. In behavioral studies, the D(3) preferential agonist quinpirole (0.03-1.0 mg/kg, i.v.) dose-dependently elicited yawns in both groups of monkeys. PG 619 and CJB 090 elicited yawns only in monkeys with an extensive history of cocaine, whereas NGB 2904 did not elicit yawns, but did antagonize quinpirole and PG 619-elicited yawning in cocaine-history monkeys. In another experiment, doses of PG 619 that elicited yawns did not alter response rates in monkeys self-administering cocaine (0.03-0.3 mg/kg per injection). Following saline extinction, cocaine (0.1 mg/kg) and quinpirole (0.1 mg/kg), but not PG 619 (0.1 mg/kg), reinstated cocaine-seeking behavior. When given before a cocaine prime, PG 619 decreased cocaine-elicited reinstatement. These findings suggest that (1) an incongruence between in vitro and in vivo assays, and (2) a history of cocaine self-administration can affect in vivo efficacy of D(3) receptor-preferring compounds PG 619 and CJB 090, which appear to be dependent on the behavioral assay.

Relationship between social rank and cortisol and testosterone concentrations in male cynomolgus monkeys (Macaca fascicularis).

In nonhuman primate social groups, biological differences related to social status have proven useful for investigating the mechanisms of sensitivity to various disease states. Physiological and neurobiological differences between dominant and subordinate monkeys have been interpreted in the context of chronic social stress. The present experiments were designed to investigate the relationships between basal cortisol and testosterone concentrations and the establishment and maintenance of the social hierarchy in male cynomolgus monkeys. Cortisol concentrations were measured at baseline and following suppression with dexamethasone (DEX) and subsequent administration of adrenocorticotrophic hormone (ACTH) while monkeys were individually housed (n = 20) and after 3 months of social housing (n = 4/group), by which time dominance hierarchies had stabilised. Cortisol was also measured during the initial 3 days of social housing. Neither pre-social housing hormone concentrations, nor hypothalamic-pituitary-adrenal (HPA) axis sensitivity predicted eventual social rank. During initial social housing, cortisol concentrations were significantly higher in monkeys that eventually became subordinate; this effect dissipated within 3 days. During the 12 weeks of social housing, aggressive and submissive behaviours were observed consistently, forming the basis for assignment of social ranks. At this time, basal testosterone and cortisol concentrations were significantly higher in dominant monkeys and, after DEX suppression, cortisol release in response to a challenge injection of ACTH was significantly greater in subordinates. These results indicate that basal cortisol and testosterone concentrations and HPA axis function are state variables that differentially reflect position in the dominance hierarchy, rather than trait variables that predict future social status.

Occupational burnout as a predictor of disability pension: a population-based cohort study.

OBJECTIVES: The aim of this study was to investigate whether burnout predicts new disability pension at population level during a follow-up of approximately 4 years. The diagnosis for which the disability pension was granted was also examined in relation to the level of burnout. METHODS: We used a population-based cohort sample (n = 3125) of 30-60-year-old employees from an epidemiological health study, the Health 2000 Study, gathered during 2000-2001 in Finland. The data collection comprised an interview, a clinical health examination including a standardised mental health interview, and a questionnaire including the Maslach Burnout Inventory-General Survey. Disability pensions and their causes until December 2004 were extracted from national pension records. The association between burnout and new disability pension was analysed with logistic regression models adjusted for sociodemographic factors and health at baseline. RESULTS: Altogether 113 persons were granted a new disability pension during the follow-up: 22% of those with severe burnout, 6% of those with mild burnout, and 2% of those with no burnout at baseline. After sociodemographic factors and health were adjusted for, each one-point increase in the overall burnout sum score was related to 49% increase in the odds for a future disability pension. A disability pension was most often granted on the basis of mental and behavioural disorders and diseases of the musculoskeletal system among those with burnout. After adjustments, exhaustion dimension among men and cynicism dimension among a combined group of men and women predicted new disability pensions. CONCLUSION: Burnout predicts permanent work disability and could therefore be used as a risk marker of chronic health-related work stress. To prevent early exit from work life, working conditions and employee burnout should be regularly assessed with the help of occupational health services.

Characterization of the shark myelin Po protein.

Myelin, the insulating sheath made by extensive plasma membrane wrapping, is dependent on the presence of highly adhesive molecules that keep the two sides of the membrane in tight contact. The Po glycoprotein (Po) is the major component of the peripheral nervous system (PNS) myelin of mammals. The exact role that Po protein has played in the evolution of myelin is still unclear, but several phylogenetic observations suggest that it is a crucial component in the development of myelin as a multi-lamellar membrane structure. Sharks, which appeared in the fossil record about 400 million years ago, are the first fully myelinated organisms. In this study we investigated the expression pattern of shark myelin Po to suggest a way it might have played a role in the evolution of myelin in the central nervous system. We found that sharks have more than two isoforms (32, 28 and 25 kD), and that some of these might not be fully functional because they lack the domains known for Po homophilic adhesion.

Comparison of rectal and infrared thermometry for obtaining body temperature in cynomolgus macaques (Macaca fascicularis).

BACKGROUND: It would be clinically advantageous to develop a method of body temperature evaluation in cynomolgus macaques (Macaca fascicularis) that did not require sedation, restraint, surgical manipulation, or expensive equipment. METHODS: Body temperatures of 51 cynomolgus macaques were taken with rectal thermometry and non-contact infrared thermometry (NIFT) on the shoulder, face, abdomen, and axillary region. RESULTS AND CONCLUSIONS: Body temperature measurements from NIFT were statistically different (P < 0.0001) from rectal thermometry. In addition, there was greater between- and within-subject variability in values using NIFT. There was no correlation between any sites of the NIFT and rectal thermometry. It was concluded that NIFT was not a valid alternative to rectal thermometry in cynomolgus macaques.

Radiation dose-reduction strategies for neuroradiology CT protocols.

Within the past 2 decades, the number of CT examinations performed has increased almost 10-fold. This is in large part due to advances in multidetector-row CT technology, which now allows faster image acquisition and improved isotropic imaging. The increased use, along with multidetector technique, has led to a significantly increased radiation dose to the patient from CT studies. This places increased responsibility on the radiologist to ensure that CT examinations are indicated and that the "as low as reasonably achievable" concept is adhered to. Neuroradiologists are familiar with factors that affect patient dose such as pitch, milliamperes, kilovolt peak (kVp), collimation, but with increasing attention being given to dose reduction, they are looking for additional ways to further reduce the radiation associated with their CT protocols. In response to increasing concern, CT manufacturers have developed dose-reduction tools, such as dose modulation, in which the tube current is adjusted along with the CT acquisition, according to patient's attenuation. This review will describe the available techniques for reducing dose associated with neuroradiologic CT imaging protocols.

Temperature-dependent sex determination in Hd-rR medaka Oryzias latipes: gender sensitivity, thermal threshold, critical period, and DMRT1 expression profile.

The developmental time and thermal threshold for temperature-dependent sex determination (TSD), gender differences in temperature sensitivity, the fertility of thermally sex reversed fish, and the effect of temperature on the expression of two major sex determination/differentiation genes (DMY/DMRT1bY and DMRT1) were examined in the Hd-rR strain of medaka, Oryzias latipes. Fertilized eggs were exposed from either shortly after fertilization (8-16 cells; embryonic stages 5-6) or from middle embryogenesis (heart development stage; stage 36) until hatching to temperatures ranging from 17 degrees C to 34 degrees C. Secondary sexual characteristics, gonadal histology, progeny testing, sex-linked body coloration and gene expression were used to determine phenotypic and genotypic sex. Sex determination was unaffected by low or high temperatures in genotypic (XY) males. In contrast, genotypic (XX) females treated from stages 5-6 showed increasing rates of sex reversal into phenotypic males at temperatures above 27 degrees C up to 100% at 34 degrees C. Thermal manipulation of sex was ineffective after stage 36, indicating that gonadal fate in medaka is determined considerably earlier than histological differentiation (stage 39). High temperature induced DMRT1 expression in genotypic females, which was observed already from stage 36. Sex-reversed males had histologically normal testes, were capable of sexual courtship and, with the exception of fish from 34 degrees C, sired viable progeny when mating with fertile females. These results clarify the pattern of TSD in medaka and provide important clues to understand the mechanism of sex determination in this species. They also suggest that a brief exposure to high temperature early in life could impair the fertility of medaka as adults.