Association of mild anemia with cognitive, functional, mood and quality of life outcomes in the elderly: the "Health and Anemia" study

Background

In the elderly persons, hemoglobin concentrations slightly below the lower limit of normal are common, but scant evidence is available on their relationship with significant health indicators. The objective of the present study was to cross-sectionally investigate the association of mild grade anemia with cognitive, functional, mood, and quality of life (QoL) variables in community-dwelling elderly persons.

Methods

Among the 4,068 eligible individuals aged 65–84 years, all persons with mild anemia (n = 170) and a randomly selected sample of non-anemic controls (n = 547) were included in the study. Anemia was defined according to World Health Organization (WHO) criteria and mild grade anemia was defined as a hemoglobin concentration between 10.0 and 11.9 g/dL in women and between 10.0 and 12.9 g/dL in men. Cognition and functional status were assessed using measures of selective attention, episodic memory, cognitive flexibility and instrumental and basic activities of daily living. Mood and QoL were evaluated by means of the Geriatric Depression Scale-10, the Short-Form health survey (SF-12), and the Functional Assessment of Cancer Therapy-Anemia.

Results

In univariate analyses, mild anemic elderly persons had significantly worse results on almost all cognitive, functional, mood, and QoL measures. In multivariable logistic regressions, after adjustment for a large number of demographic and clinical confounders, mild anemia remained significantly associated with measures of selective attention and disease-specific QoL (all fully adjusted p<.046). When the lower limit of normal hemoglobin concentration according to WHO criteria was raised to define anemia (+0.2 g/dL), differences between mild anemic and non anemic elderly persons tended to increase on almost every variable.

Conclusions

Cross-sectionally, mild grade anemia was independently associated with worse selective attention performance and disease-specific QoL ratings.     

Poor cognitive flexibility in eating disorders: examining the evidence using the Wisconsin Card Sorting Task

Background

People with eating disorders (ED) frequently present with inflexible behaviours, including eating related issues which contribute to the maintenance of the illness. Small scale studies point to difficulties with cognitive set-shifting as a basis. Using larger scale studies will lend robustness to these data.

Methodology/Principal Findings

542 participants were included in the dataset as follows: Anorexia Nervosa (AN) n = 171; Bulimia Nervosa (BN) n = 82; Recovered AN n = 90; Healthy controls (HC): n = 199. All completed the Wisconsin Card Sorting Task (WCST), an assessment that integrates multiple measurement of several executive processes concerned with problem solving and cognitive flexibility. The AN and BN groups performed poorly in most domains of the WCST. Recovered AN participants showed a better performance than currently ill participants; however, the number of preservative errors was higher than for HC participants.

Conclusions/Significance

There is a growing interest in the diagnostic and treatment implications of cognitive flexibility in eating disorders. This large dataset supports previous smaller scale studies and a systematic review which indicate poor cognitive flexibility in people with ED.     

The cognitive impact of the ANK3 risk variant for bipolar disorder: initial evidence of selectivity to signal detection during sustained attention

Background

Abnormalities in cognition have been reported in patients with Bipolar Disorder (BD) and their first degree relatives, suggesting that susceptibility genes for BD may impact on cognitive processes. Recent genome-wide genetic studies have reported a strong association with BD in a single nucleotide polymorphism (SNP) (rs10994336) within ANK3, which codes for Ankyrin 3. This protein is involved in facilitating the propagation of action potentials by regulating the assembly of sodium gated ion channels. Since ANK3 influences the efficiency of transmission of neuronal impulses, allelic variation in this gene may have widespread cognitive effects. Preclinical data suggest that this may principally apply to sequential signal detection, a core process of sustained attention.

Methodology/Principal Findings

One hundred and eighty-nine individuals of white British descent were genotyped for the ANK3 rs10994336 polymorphism and received diagnostic interviews and comprehensive neurocognitive assessment of their general intellectual ability, memory, decision making, response inhibition and sustained attention. Participants comprised euthymic BD patients (n = 47), their unaffected first-degree relatives (n = 75) and healthy controls (n = 67). The risk allele T was associated with reduced sensitivity in target detection (p = 0.0004) and increased errors of commission (p = 0.0018) during sustained attention regardless of diagnosis. We found no effect of the ANK3 genotype on general intellectual ability, memory, decision making and response inhibition.

Conclusions/Significance

Our results suggest that allelic variation in ANK3 impacts cognitive processes associated with signal detection and this mechanism may relate to risk for BD. However, our results require independent replication and confirmation that ANK3 (rs10994336) is a direct functional variant.     

Ethnic Differences in Cardiometabolic Risk Profile at Age 5-6 Years: The ABCD Study

Background

To examine ethnic differences in cardiometabolic risk profile in early age, and explore whether such differences can be explained by differences in body mass index (BMI) or waist circumference (WC).

Method

Anthropometric measurements, blood pressure and (in a subsample) fasting blood were collected during a health check of 2,509 children aged 5–6 years. Four ethnic groups were distinguished: Dutch (n = 2,008; blood n = 1,300), African descent (n = 199; blood n = 105), Turkish (n = 108; blood n = 57) and Moroccan (n = 194; blood n = 94). Ethnic differences in diastolic and systolic blood pressure (DBP/SBP), fasting glucose, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride levels were determined and the explanatory role of BMI and WC was examined with regression analysis.

Results

After adjustment for confounders, African descent children showed higher DBP (β2.22 mmHg; 95%CI:1.09–3.36) and HDL levels (β:0.09 mmol/l; 95%CI:0.03–0.16) compared to Dutch children (reference group). Turkish children showed higher SBP (β:1.89 mmHg; 95%CI:0.25–3.54), DBP (β:2.62 mmHg; 95%CI:1.11–4.13), glucose (β:0.12 mmol/L; 95%CI:0.00–0.25) and triglyceride levels (β:0.13 mmol/L; 95%CI:0.02–0.25). Higher BMI values were found in all non–Dutch groups (differences ranged from 0.53–1.03 kg/m²) and higher WC in Turkish (β:1.68 cm; 95%CI:0.99–2.38) and Moroccan (β:1.65 cm; 95%CI:1.11–2.19) children. BMI and WC partly explained the higher SBP/DBP and triglyceride levels in Turkish children.

Conclusion

Ethnic differences in cardiometabolic profile exist early in life and are partly explained by differences in BMI and WC. African children showed favourable HDL levels and Turkish children the most unfavourable overall profile, whereas their Moroccan peers have less increased cardiometabolic risk in spite of their high BMI and WC.     

The Association between Prenatal Psychosocial Stress and Blood Pressure in the Child at Age 5-7 Years

Objective

Prenatal maternal stress could have permanent effects on the offspring’s tissue structure and function, which may predispose to cardiovascular diseases. We investigated whether maternal psychosocial stress is a prenatal factor affecting the blood pressure (BP) of offspring.

Study Design

In the Amsterdam Born Children and their Development (ABCD) study, around gestational week 16, depressive symptoms, state-anxiety, pregnancy-related anxiety, parenting daily hassles and job strain were recorded by questionnaire. A cumulative stress score was also calculated (based on 80^th percentiles). Systolic and diastolic BP and mean arterial pressure (MAP) were measured in the offspring at age 5–7 years. Inclusion criteria were: no use of antihypertensive medication during pregnancy; singleton birth; no reported cardiovascular problems in the child (N = 2968 included).

Results

After adjustment for confounders, the single stress scales were not associated with systolic and diastolic BP, MAP and hypertension (p>0.05). The presence of 3–4 psychosocial stressors prenatally (4%) was associated with 1.5 mmHg higher systolic and diastolic BP (p = 0.046; p = 0.04) and 1.5 mmHg higher MAP in the offspring (p = 0.02) compared to no stressors (46%). The presence of 3–4 stressors did not significantly increase the risk for hypertension (OR 1.8; 95% CI 0.93.4). Associations did not differ between sexes. Bonferroni correction for multiple testing rendered all associations non-significant.

Conclusions

The presence of multiple psychosocial stressors during pregnancy was associated with higher systolic and diastolic BP and MAP in the child at age 5–7. Further investigation of maternal prenatal stress may be valuable for later life cardiovascular health.     

Biomarkers of extracellular matrix metabolism (MMP-9 and TIMP-1) and risk of stroke, myocardial infarction, and cause-specific mortality: cohort study

Objective

Turnover of the extracellular matrix in all solid organs is governed mainly by a balance between the degrading matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). An altered extracellular matrix metabolism has been implicated in a variety of diseases. We investigated relations of serum levels of MMP-9 and TIMP-1 to mortality risk from an etiological perspective.

Design

The prospective Uppsala Longitudinal Study of Adult Men (ULSAM) cohort, followed from 1991–1995 for up to 18.1 years. A random population-based sample of 1,082 71-year-old men, no loss to follow-up. Endpoints were all-cause (n = 628), cardiovascular (n = 230), non-cardiovascular (n = 398) and cancer mortality (n = 178), and fatal or non-fatal myocardial infarction (n = 138) or stroke (n = 163).

Results

Serum MMP-9 and TIMP-1 levels were associated with risk of all-cause mortality (Cox proportional hazard ratio [HR] per standard deviation 1.10, 95% confidence interval [CI] 1.03–1.19; and 1.11, 1.02–1.20; respectively). TIMP-1 levels were mainly related to risks of cardiovascular mortality and stroke (HR per standard deviation 1.22, 95% CI 1.09–1.37; and 1.18, 1.04–1.35; respectively). All relations except those of TIMP-1 to stroke risk were attenuated by adjustment for cardiovascular disease risk factors. Relations in a subsample without cardiovascular disease or cancer were similar to those in the total sample.

Conclusion

In this community-based cohort of elderly men, serum MMP-9 and TIMP-1 levels were related to mortality risk. An altered extracellular matrix metabolism may be involved in several detrimental pathways, and circulating MMP-9 or TIMP-1 levels may be relevant markers thereof.     

Soluble serum CD81 is elevated in patients with chronic hepatitis C and correlates with alanine aminotransferase serum activity

Aim

Cellular CD81 is a well characterized hepatitis C virus (HCV) entry factor, while the relevance of soluble exosomal CD81 in HCV pathogenesis is poorly defined. We performed a case-control study to investigate whether soluble CD81 in the exosomal serum fraction is associated with HCV replication and inflammatory activity.

Patients and Methods

Four cohorts were investigated, patients with chronic hepatitis C (n = 37), patients with chronic HCV infection and persistently normal ALT levels (n = 24), patients with long term sustained virologic response (SVR, n = 7), and healthy volunteers (n = 23). Concentration of soluble CD81 was assessed semi-quantitatively after differential centrifugation ranging from 200 g to 100,000 g in the fifth centrifugation fraction by immunoblotting and densitometry.

Results

Soluble CD81 was increased in patients with chronic hepatitis C compared to healthy subjects (p = 0.03) and cured patients (p = 0.017). Patients with chronic HCV infection and persistently normal ALT levels and patients with long term SVR had similar soluble CD81 levels as healthy controls (p>0.2). Overall, soluble CD81 levels were associated with ALT levels (r = 0.334, p = 0.016) and severe liver fibrosis (p = 0.027).

Conclusion

CD81 is increased in the exosomal serum fraction in patients with chronic hepatitis C and appears to be associated with inflammatory activity and severity of fibrosis.     

The homeostatic chemokine CCL21 predicts mortality and may play a pathogenic role in heart failure

Background

CCL19 and CCL21, acting through CCR7, are termed homeostatic chemokines. Based on their role in concerting immunological responses and their proposed involvement in tissue remodeling, we hypothesized that these chemokines could play a pathogenic role in heart failure (HF).

Methodology/Principal Findings

Our main findings were: (i) Serum levels of CCL19 and particularly CCL21 were markedly raised in patients with chronic HF (n = 150) as compared with healthy controls (n = 20). A CCL21 level above median was independently associated with all-cause mortality. (ii) In patients with HF following acute myocardial infarction (MI; n = 232), high versus low CCL21 levels 1 month post-MI were associated with cardiovascular mortality, even after adjustment for established risk factors. (iii). Explanted failing human LV tissue (n = 29) had markedly increased expression of CCL21 as compared with non-failing myocardium (n = 5). (iv) Our studies in CCR7^−/− mice showed improved survival and attenuated increase in markers of myocardial dysfunction and wall stress in post-MI HF after 1 week, accompanied by increased myocardial expression of markers of regulatory T cells. (v) Six weeks post-MI, there was an increase in markers of myocardial dysfunction and wall stress in CCR7 deficient mice.

Conclusions/Significance

High serum levels of CCL21 are independently associated with mortality in chronic and acute post-MI HF. Our findings in CCR7 deficient mice may suggest that CCL21 is not only a marker, but also a mediator of myocardial failure. However, while short term inhibition of CCR7 may be beneficial following MI, a total lack of CCR7 during long-term follow-up could be harmful.     

Analysis of clonal type-specific antibody reactions in Toxoplasma gondii seropositive humans from Germany by peptide-microarray

Background

Different clonal types of Toxoplasma gondii are thought to be associated with distinct clinical manifestations of infections. Serotyping is a novel technique which may allow to determine the clonal type of T. gondii humans are infected with and to extend typing studies to larger populations which include infected but non-diseased individuals.

Methodology

A peptide-microarray test for T. gondii serotyping was established with 54 previously published synthetic peptides, which mimic clonal type-specific epitopes. The test was applied to human sera (n = 174) collected from individuals with an acute T. gondii infection (n = 21), a latent T. gondii infection (n = 53) and from T. gondii-seropositive forest workers (n = 100).

Findings

The majority (n = 124; 71%) of all T. gondii seropositive human sera showed reactions against synthetic peptides with sequences specific for clonal type II (type II peptides). Type I and type III peptides were recognized by 42% (n = 73) or 16% (n = 28) of the human sera, respectively, while type II–III, type I–III or type I–II peptides were recognized by 49% (n = 85), 36% (n = 62) or 14% (n = 25) of the sera, respectively. Highest reaction intensities were observed with synthetic peptides mimicking type II-specific epitopes. A proportion of the sera (n = 22; 13%) showed no reaction with type-specific peptides. Individuals with acute toxoplasmosis reacted with a statistically significantly higher number of peptides as compared to individuals with latent T. gondii infection or seropositive forest workers.

Conclusions

Type II-specific reactions were overrepresented and higher in intensity in the study population, which was in accord with genotyping studies on T. gondii oocysts previously conducted in the same area. There were also individuals with type I- or type III-specific reactions. Well-characterized reference sera and further specific peptide markers are needed to establish and to perform future serotyping approaches with higher resolution.     

Subjective Cognitive Complaints in Schizophrenia: Relation to Antipsychotic Medication Dose,Actual Cognitive Performance,Insight and Symptoms

Background

Subjective cognitive complaints are prevalent in those affected by functional psychoses and a variety of possible associated factors have been investigated. However, few studies have examined these potential factors within single studies or analyses.

Methods

Patients with a history of a schizophrenia spectrum disorder (n = 115) and a non-clinical comparison group (n = 45) completed the Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS) and the Brief Assessment of Cognition in Schizophrenia (BACS). The patient group also completed the Positive and Negative Syndromes Scale (PANSS), the Birchwood Insight Scale (IS), and the Hospital Anxiety and Depression Scale (HADS).

Results

The BACS and SSTICS scores were associated in the non-clinical comparison group, but not in the patient group. In the patient group worse subjective cognition was associated positively with good insight, greater dysphoria and greater positive symptoms. Linear regression revealed that, once other variables had been accounted for, dysphoria (HADS anxiety and depression factor) was the only significant predictor of SSTICS scores.

Conclusions

Subjective cognitive impairment in patients with psychosis in the absence of formal testing should not be taken as evidence of impaired cognitive functioning. Mood should be investigated when patients present with subjective cognitive complaints.     

A preliminary evaluation of limb salvage surgery for osteosarcoma around knee joint

Objective

To evaluate the effectiveness and drawbacks of diversified procedures of limb salvage surgery (LSS), providing a reference of rational surgical criterion of LSS.

Methods

Fifty eight patients with stage IIB extremity osteosarcoma around knee joint area between 1992 and 2002 were studied retrospectively. Among them, 43 patients were treated by LSS followed by reconstruction. Reconstruction approaches included re-implantation of irradiation-devitalized tumor bone (n = 12), autoclaving-devitalized tumor bone (n = 8), prosthetic replacement (n = 11), allograft transplantation (n = 8) and vascularized fibula autograft implantation (n = 4). Amputations were performed in 15 patients. Patients were followed up for 6–16 years.

Results

There were no significant difference between LSS and amputation groups regarding disease free survival and local recurrence rates. The actuarial 5-year continuous disease free survival and local recurrence rate were 30.0% and 25.0% in patients of devitalized LSS group, whereas those were 56.5% and 8.7% in patients of non-devitalized reconstruction group. The complication rate was significantly higher in LSS group compared to amputation group (P = 0.003).

Conclusion

LSS with non-devitalized procedures is the optimal treatment for osteosarcoma around knee joint area. Prosthesis implantation is the preferred option for bone reconstruction following LSS. Prevention and treatment of post-operative complications should be paid more attention to get good long-term outcomes of surgery.     

The effectiveness of online cognitive behavioral treatment in routine clinical practice

Context

Randomized controlled trails have identified online cognitive behavioral therapy as an efficacious intervention in the management of common mental health disorders.

Objective

To assess the effectiveness of online CBT for different mental disorders in routine clinical practice.

Design

An uncontrolled before-after study, with measurements at baseline, posttest, 6-week follow-up, and 1-year follow-up.

Participants & Setting

1500 adult patients (female: 67%; mean age: 40 years) with a GP referral for psychotherapy were treated at a Dutch online mental health clinic for symptoms of depression (n = 413), panic disorder (n = 139), posttraumatic stress (n = 478), or burnout (n = 470).

Interventions

Manualized, web-based, therapist-assisted CBT, of which the efficacy was previously demonstrated in a series of controlled trials. Standardized duration of treatment varied from 5 weeks (online CBT for Posttraumatic stress) to 16 weeks (online CBT for Depression).

Main Outcome Measures

Validated self-report questionnaires of specific and general psychopathology, including the Beck Depression Inventory, the Impact of Event Scale, the Panic Disorder Severity Scale-Self Report, the Oldenburg Burnout Inventory, and the Depression Anxiety Stress Scales.

Results

Treatment adherence was 71% (n = 1071). Study attrition was 21% at posttest, 33% at 6-week FU and 65% at 1-year FU. Mixed-model repeated measures regression identified large short-term reductions in all measures of primary symptoms (d = 1.9±0.2 to d = 1.2±0.2; P<.001), which sustained up to one year after treatment. At posttest, rates of reliable improvement and recovery were 71% and 52% in the completer sample (full sample: 55%/40%). Patient satisfaction was high.

Conclusions

Results suggest that online therapist-assisted CBT may be as effective in routine practice as it is in clinical trials. Although pre-treatment withdrawal and long-term outcomes require further study, results warrant continued implementation of online CBT.     

Insomnia,Daytime Sleepiness and Cardio-Cerebrovascular Diseases in the Elderly: A 6-Year Prospective Study

Objective

To examine 1) the associations between history of cardio-cerebrovascular diseases (CVD) and insomnia complaints and excessive daytime sleepiness (EDS), and 2) the relationships between sleep complaints and future CVD in persons over 65.

Methods

CVD was assessed at baseline and during two, four, and six-year follow-up in 5494 non-demented subjects. Self-reported insomnia complaints (poor sleep quality, difficulty in initiating sleep, difficulty in maintening sleep, and early morning awakening), EDS and sleep medication use were evaluated at baseline. Logistic regression models and Cox proportional hazard models, with delayed entry and age of participants as the time scale, were adjusted for socio-demographic, lifestyle and clinical variables.

Results

At baseline, 748 participants had a past-history of CVD. A past-history of CVD was associated with EDS (OR = 1.28 95%CI = [1.05–1.57]) and the number of insomnia complaints (OR = 1.26 95%CI = [1.03–1.55] for 1–2 insomnia complaints; OR = 1.32 95%CI = [1.03–1.71] for ≥3 complaints). In longitudinal analyses, neither the four components of insomnia nor the number of insomnia complaints were significantly associated with first or recurrent CVD events (n = 391 events). EDS was independently associated with future CVD events even after adjusting for prescribed sleep medication and past-history of CVD (HR = 1.35 95%CI = [1.06–1.71]).

Conclusion

Our results suggest that the relationships between sleep complaints and CVD could be complex. Insomnia complaints are more likely a consequence of CVD, whereas EDS appears to be a determinant of CVD independently of past-history of CVD. EDS screening may thus constitute a means of detecting persons at high risk of CVD.     

Consent for use of clinical leftover biosample: a survey among Chinese patients and the general public

Background

Storage of leftover biosamples generates rich biobanks for future studies, saving time and money and limiting physical impact to sample donors.

Objective

To investigate the attitudes of Chinese patients and the general public on providing consent for storage and use of leftover biosamples.

Design, Setting and Participants

Cross-sectional surveys were conducted among randomly selected patients admitted to a Shanghai city hospital (n = 648) and members of the general public (n = 492) from May 2010 to July 2010.

Main Outcome Measures

Face-to-face interviews collected respondents-report of their willingness to donate residual biosample, trust in medical institutions, motivation for donation, concerns of donated sample use, expectations for research results return, and so on.

Results

The response rate was 83.0%. Of the respondents, 89.1% stated that they completely understood or understood most of questions. Willingness to donate residual sample was stated by 64.7%, of which 16.7% desired the option to withdraw their donations anytime afterwards. Only 42.3% of respondents stated they “trust" or “strongly trust" medical institutions, the attitude of trusting or strongly trusting medical institutions were significantly associated with willingness to donate in the general public group.(p<0.05) The overall assent rate for future research without specific consents was also low (12.1%). Hepatitis B virus carriers were significantly less willing than non-carriers to donate biosamples (32.1% vs. 64.7%, p<0.001).

Conclusions

Low levels of public trust in medical institutions become serious obstacle for biosample donation and biobanking in China. Efforts to increase public understanding of human medical research and biosample usage and trust in the ethical purposes of biobanking are urgently needed. These efforts will be greatly advanced by the impending legislation on biobanking procedures and intent, and our results may help guide the structure of such law.     

Aberrant hippocampal subregion networks associated with the classifications of aMCI subjects: a longitudinal resting-state study

Background

Altered hippocampal structure and function is a valuable indicator of possible conversion from amnestic type mild cognitive impairment (aMCI) to Alzheimer''s disease (AD). However, little is known about the disrupted functional connectivity of hippocampus subregional networks in aMCI subjects.

Methodology/Principal Findings

aMCI group-1 (n = 26) and controls group-1 (n = 18) underwent baseline and after approximately 20 months follow up resting-state fMRI scans. Integrity of distributed functional connectivity networks incorporating six hippocampal subregions (i.e. cornu ammonis, dentate gyrus and subicular complex, bilaterally) was then explored over time and comparisons made between groups. The ability of these extent longitudinal changes to separate unrelated groups of 30 subjects (aMCI-converters, n = 6; aMCI group-2, n = 12; controls group-2, n = 12) were further assessed. Six longitudinal hippocampus subregional functional connectivity networks showed similar changes in aMCI subjects over time, which were mainly associated with medial frontal gyrus, lateral temporal cortex, insula, posterior cingulate cortex (PCC) and cerebellum. However, the disconnection of hippocampal subregions and PCC may be a key factor of impaired episodic memory in aMCI, and the functional index of these longitudinal changes allowed well classifying independent samples of aMCI converters from non-converters (sensitivity was 83.3%, specificity was 83.3%) and controls (sensitivity was 83.3%, specificity was 91.7%).

Conclusions/Significance

It demonstrated that the functional changes in resting-state hippocampus subregional networks could be an important and early indicator for dysfunction that may be particularly relevant to early stage changes and progression of aMCI subjects.     

Apathy, but not depression, reflects inefficient cognitive strategies in Parkinson's disease

Background

The relationship between apathy, depression and cognitive impairment in Parkinson''s disease (PD) is still controversial. The objective of this study is to investigate whether apathy and depression are associated with inefficient cognitive strategies in PD.

Methods

In this prospective clinical cohort study conducted in a university-based clinical and research movement disorders center we studied 48 PD patients. Based on clinical evaluation, they were classified in two groups: PD with apathy (PD-A group, n = 23) and PD without apathy (PD-NA group, n = 25). Patients received clinical and neuropsychological evaluations. The clinical evaluation included: Apathy Evaluation Scale-patient version, Hamilton Depression Rating Scale-17 items, the Unified Parkinson''s Disease Rating Scale and the Hoehn and Yahr staging system; the neuropsychological evaluation explored speed information processing, attention, working memory, executive function, learning abilities and memory, which included several measures of recall (immediate free, short delay free, long delay free and cued, and total recall).

Findings

PD-A and PD-NA groups did not differ in age, disease duration, treatment, and motor condition, but differed in recall (p<0.001) and executive tasks (p<0.001). Immediate free recall had the highest predictive value for apathy (F =  10.94; p = 0.002). Depression and apathy had a weak correlation (Pearson index  = 0.3; p<0.07), with three items of the depression scale correlating with apathy (Pearson index between .3 and.4; p<0.04). The depressed and non-depressed PD patients within the non-apathetic group did not differ.

Conclusion

Apathy, but not depression, is associated with deficit in implementing efficient cognitive strategies. As the implementation of efficient strategies relies on the fronto-striatal circuit, we conclude that apathy, unlike depression, is an early expression of executive impairment in PD.     

Expression of human beta-defensins in children with chronic inflammatory bowel disease

Background

Human beta-defensins (hBDs) are antimicrobial peptides known to play a major role in intestinal innate host defence. Altered mucosal expression of hBDs has been suggested to be implicated in chronic inflammatory bowel disease pathogenesis. However, little is known about expression of these peptides in children.

Methods

Intestinal biopsies were obtained from the duodenum (n = 88), terminal ileum (n = 90) and ascending colon (n = 105) of children with Crohn''s disease (n = 26), ulcerative colitis (n = 11) and healthy controls (n = 16). Quantitative real-time (RT) PCR was performed and absolute mRNA copy numbers analyzed for hBD1-3 as well as inflammatory cytokines IL-8 and TNF-alpha.

Results

Significant induction of hBD2 and hBD3 was observed in the inflamed terminal ileum and ascending colon of IBD children. In the ascending colon induction of hBD2 was found to be significantly lower in children with Crohn''s disease compared to ulcerative colitis. A strong correlation was found between inducible defensins hBD2 and 3 and the inflammatory cytokines IL-8 and TNF-alpha, both in the terminal ileum and ascending colon.

Conclusion

Our study demonstrates distinct changes in hBD expression throughout the intestinal tract of children with IBD, lending further support for their potential role in disease pathogenesis.     

Characterization of a large group of individuals with huntington disease and their relatives enrolled in the COHORT study

Background

Careful characterization of the phenotype and genotype of Huntington disease (HD) can foster better understanding of the condition.

Methods

We conducted a cohort study in the United States, Canada, and Australia of members of families affected by HD. We collected demographic and clinical data, conducted the Unified Huntington''s Disease Rating Scale and Mini-Mental State Examination, and determined Huntingtin trinucleotide CAG repeat length. We report primarily on cross-sectional baseline data from this recently completed prospective, longitudinal, observational study.

Results

As of December 31, 2009, 2,318 individuals enrolled; of these, 1,985 (85.6%) were classified into six analysis groups. Three groups had expanded CAG alleles (36 repeats or more): individuals with clinically diagnosed HD [n = 930], and clinically unaffected first-degree relatives who had previously pursued [n = 248] or not pursued [n = 112] predictive DNA testing. Three groups lacked expanded alleles: first-degree relatives who had previously pursued [n = 41] or not pursued [n = 224] genetic testing, and spouses and caregivers [n = 430]. Baseline mean performance differed across groups in all motor, behavioral, cognitive, and functional measures (p<0.001). Clinically unaffected individuals with expanded alleles weighed less (76.0 vs. 79.6 kg; p = 0.01) and had lower cognitive scores (28.5 vs. 29.1 on the Mini Mental State Examination; p = 0.008) than individuals without expanded alleles. The frequency of “high normal” repeat lengths (27 to 35) was 2.5% and repeat lengths associated with reduced penetrance (36 to 39) was 2.7%.

Conclusion

Baseline analysis of COHORT study participants revealed differences that emerge prior to clinical diagnosis. Longitudinal investigation of this cohort will further characterize the natural history of HD and genetic and biological modifiers.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00313495","term_id":"NCT00313495"}}NCT00313495     

Sarcoidosis and tuberculosis cytokine profiles: indistinguishable in bronchoalveolar lavage but different in blood

Background

The clinical, radiological and pathological similarities between sarcoidosis and tuberculosis can make disease differentiation challenging. A complicating factor is that some cases of sarcoidosis may be initiated by mycobacteria. We hypothesised that immunological profiling might provide insight into a possible relationship between the diseases or allow us to distinguish between them.

Methods

We analysed bronchoalveolar lavage (BAL) fluid in sarcoidosis (n = 18), tuberculosis (n = 12) and healthy volunteers (n = 16). We further investigated serum samples in the same groups; sarcoidosis (n = 40), tuberculosis (n = 15) and healthy volunteers (n = 40). A cross-sectional analysis of multiple cytokine profiles was performed and data used to discriminate between samples.

Results

We found that BAL profiles were indistinguishable between both diseases and significantly different from healthy volunteers. In sera, tuberculosis patients had significantly lower levels of the Th2 cytokine interleukin-4 (IL-4) than those with sarcoidosis (p = 0.004). Additional serum differences allowed us to create a linear regression model for disease differentiation (within-sample accuracy 91%, cross-validation accuracy 73%).

Conclusions

These data warrant replication in independent cohorts to further develop and validate a serum cytokine signature that may be able to distinguish sarcoidosis from tuberculosis. Systemic Th2 cytokine differences between sarcoidosis and tuberculosis may also underly different disease outcomes to similar respiratory stimuli.