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.     

The impact of successful cataract surgery on quality of life, household income and social status in South India

Background

To explore the hypothesis that sight restoring cataract surgery provided to impoverished rural communities will improve not only visual acuity and vision-related quality of life (VRQoL) but also poverty and social status.

Methods

Participants were recruited at outreach camps in Tamil Nadu, South India, and underwent free routine manual small incision cataract surgery (SICS) with intra-ocular lens (IOL) implantation, and were followed up one year later. Poverty was measured as monthly household income, being engaged in income generating activities and number of working household members. Social status was measured as rates of re-marriage amongst widowed participants. VRQoL was measured using the IND-VFQ-33. Associations were explored using logistic regression (SPSS 19).

Results

Of the 294 participants, mean age ± standard deviation (SD) 60±8 years, 54% men, only 11% remained vision impaired at follow up (67% at baseline; p<0.001). At one year, more participants were engaged in income generating activities (44.7% to 77.7%; p<0.001) and the proportion of households with a monthly income <1000 Rps. decreased from 50.5% to 20.5% (p<0.05). Overall VRQoL improved (p<0.001). Participants who had successful cataract surgery were less likely to remain in the lower categories of monthly household income (OR 0.05–0.22; p<0.02) and more likely to be engaged in income earning activities one year after surgery (OR 3.28; p = 0.006). Participants widowed at baseline who had successful cataract surgery were less likely to remain widowed at one year (OR 0.02; p = 0.008).

Conclusion

These findings indicate the broad positive impact of sight restoring cataract surgery on the recipients’ as well as their families’ lives. Providing free high quality cataract surgery to marginalized rural communities will not only alleviate avoidable blindness but also - to some extent - poverty in the long run.     

The effects of terlipressin on regional hemodynamics and kidney function in experimental hyperdynamic sepsis

Background and Aims

Although terlipressin (TP) may improve renal function in cirrhotic patients, its use in sepsis remains controversial due to concerns about regional ischemia. We investigated the effects of TP on regional hemodynamics and kidney function in experimental hyperdynamic sepsis.

Methods

We studied thirteen merino ewes in a university physiology laboratory using a randomized controlled cross over design. We implanted flow probes around the pulmonary, circumflex coronary, superior mesenteric, renal and iliac arteries. We injected live Escherichia coli and induced hyperdynamic sepsis. We treated animals with either bolus vehicle or a single dose of TP (sTP = 1 mg). In a second group, after 1 mg of TP, two additional bolus injections (mTP) of 0.5 mg were given at 2 hourly intervals.

Main Results

sTP (1 mg) significantly increased mean arterial pressure (MAP) (74 to 89 mmHg; P<0.0001) creatinine clearance (31 to 85 mL/min; P<0.0001) and urine output (24 to 307 mL/hr) (P<0.0001). However, it decreased CO (5.7 to 3.9 L/min; p<0.0001), coronary blood flow (CBF) (43 to 32 mL/min; p<0.0001) and mesenteric blood flow (MBF) (944 to 625 mL/min; p = 0.004) and increased blood lactate (2.1 to 4.0 mmol/L; p<0.0001). Extra doses of TP caused little additional effect.

Conclusions

In hyperdynamic sepsis, bolus TP transiently improves MAP and renal function, but reduces CO, CBF and MBF, and increases blood lactate. Caution should be applied when prescribing bolus TP in septic patients at risk of coronary or mesenteric ischemia.     

Prospective study on the association between harm avoidance and postpartum depressive state in a maternal cohort of Japanese women

Background

Recent studies have displayed increased interest in examining the relationship between personality traits and the onset, treatment response patterns, and relapse of depression. This study aimed to examine whether or not harm avoidance (HA) was a risk factor for postpartum depression measured by the Edinburgh Postnatal Depression Scale (EPDS) and the state dependency of HA.

Methods

Pregnant women (n=460; mean age 31.9±4.2 years) who participated in a prenatal program completed the EPDS as a measure of depressive state and the Temperament and Character Inventory (TCI) as a measure of HA during three periods: early pregnancy (T1), late pregnancy (around 36 weeks), and 1 month postpartum (T2). Changes in EPDS and HA scores from T1 to T2 were compared between the non depressive (ND) group and the postpartum depressive (PD) group.

Results

There was no significant difference in the level of HA between the ND and PD groups at T1. In the ND group, EPDS and HA scores did not change significantly from T1 to T2. In the PD group, both scores increased significantly from T1 to T2 (EPDS, p<0.0001; HA, p<0.048). In the ND and PD groups, a significant positive correlation was observed in changes in EPDS and HA scores from T1 to T2 (r=0.31, p=0.002).

Conclusions

These results suggest that HA cannot be considered a risk factor for the development of postpartum depression measured by EPDS. Furthermore, HA may be state dependent.     

Intraduodenal administration of intact pea protein effectively reduces food intake in both lean and obese male subjects

Background

Human duodenal mucosa secretes increased levels of satiety signals upon exposure to intact protein. However, after oral protein ingestion, gastric digestion leaves little intact proteins to enter the duodenum. This study investigated whether bypassing the stomach, through intraduodenal administration, affects hormone release and food-intake to a larger extent than orally administered protein in both lean and obese subjects.

Methods

Ten lean (BMI:23.0±0.7 kg/m²) and ten obese (BMI:33.4±1.4 kg/m²) healthy male subjects were included. All subjects randomly received either pea protein solutions (250 mg/kg bodyweight in 0.4 ml/kg bodyweight of water) or placebo (0.4 ml/kg bodyweight of water), either orally or intraduodenally via a naso-duodenal tube. Appetite-profile, plasma GLP-1, CCK, and PYY concentrations were determined over a 2 h period. After 2 h, subjects received an ad-libitum meal and food-intake was recorded.

Results

CCK levels were increased at 10(p<0.02) and 20(p<0.01) minutes after intraduodenal protein administration (IPA), in obese subjects, compared to lean subjects, but also compared to oral protein administration (OPA)(p<0.04). GLP-1 levels increased after IPA in obese subjects after 90(p<0.02) to 120(p<0.01) minutes, compared to OPA. Food-intake was reduced after IPA both in lean and obese subjects (-168.9±40 kcal (p<0.01) and −298.2±44 kcal (p<0.01), respectively), compared to placebo. Also, in obese subjects, food-intake was decreased after IPA (−132.6±42 kcal; p<0.01), compared to OPA.

Conclusions

Prevention of gastric proteolysis through bypassing the stomach effectively reduces food intake, and seems to affect obese subjects to a greater extent than lean subjects. Enteric coating of intact protein supplements may provide an effective dietary strategy in the prevention/treatment of obesity.     

Liver and muscle in morbid obesity: the interplay of fatty liver and insulin resistance

Introduction

Nonalcoholic fatty liver disease (NAFLD) can be seen as a manifestation of overnutrition. The muscle is a central player in the adaptation to energy overload, and there is an association between fatty-muscle and -liver. We aimed to correlate muscle morphology, mitochondrial function and insulin signaling with NAFLD severity in morbid obese patients.

Methods

Liver and deltoid muscle biopsies were collected during bariatric surgery in NAFLD patients. NAFLD Activity Score and Younossi''s classification for nonalcoholic steatohepatitis (NASH) were applied to liver histology. Muscle evaluation included morphology studies, respiratory chain complex I to IV enzyme assays, and analysis of the insulin signaling cascade. A healthy lean control group was included for muscle morphology and mitochondrial function analyses.

Results

Fifty one NAFLD patients were included of whom 43% had NASH. Intramyocellular lipids (IMCL) were associated with the presence of NASH (OR 12.5, p<0.001), progressive hepatic inflammation (p = 0.029) and fibrosis severity (p = 0.010). There was a trend to an association between IMCL and decreased Akt phosphorylation (p = 0.059), despite no association with insulin resistance. In turn, hepatic steatosis (p = 0.015) and inflammation (p = 0.013) were associated with decreased Akt phosphoryation. Citrate synthase activity was lower in obese patients (p = 0.047) whereas complex I (p = 0.040) and III (p = 0.036) activities were higher, compared with controls. Finally, in obese patients, complex I activity increased with progressive steatosis (p = 0.049) and with a trend with fibrosis severity (p = 0.056).

Conclusions

In morbid obese patients, presence of IMCL associates with NASH and advanced fibrosis. Muscle mitochondrial dysfunction does not appear to be a major driving force contributing to muscle fat accumulation, insulin resistance or liver disease. Importantly, insulin resistance in muscle might occur at a late point in the insulin signaling cascade and be associated with IMCL and NAFLD severity.     

CCND1 as a predictive biomarker of neoadjuvant chemotherapy in patients with locally advanced head and neck squamous cell carcinoma

Background

Cyclin D1 (CCND1) has been associated with chemotherapy resistance and poor prognosis. In this study, we tested the hypothesis that CCND1 expression determines response and clinical outcomes in locally advanced head and neck squamous cell carcinoma (HNSCC) patients treated with neoadjuvant chemotherapy followed by surgery and radiotherapy.

Methodology and Findings

224 patients with HNSCC were treated with either cisplatin-based chemotherapy followed by surgery and radiotherapy (neoadjuvant group, n = 100) or surgery and radiotherapy (non-neoadjuvant group, n = 124). CCND1 expression was assessed by immunohistochemistry. CCND1 levels were analyzed with chemotherapy response, disease-free survival (DFS) and overall survival (OS). There was no significant difference between the neoadjuvant group and non-neoadjuvant group in DFS and OS (p = 0.929 and p = 0.760) when patients treated with the indiscriminate administration of cisplatin-based chemotherapy. However, in the neoadjuvant group, patients whose tumors showed a low CCND1 expression more likely respond to chemotherapy (p<0.001) and had a significantly better OS and DFS than those whose tumors showed a high CCND1 expression (73% vs 8%, p<0.001; 63% vs 6%, p<0.001). Importantly, patients with a low CCND1 expression in neoadjuvant group received more survival benefits than those in non-neoadjuvant group (p = 0.016), however patients with a high CCND1 expression and treated with neoadjuvant chemotherapy had a significantly poor OS compared to those treated with surgery and radiotherapy (p = 0.032). A multivariate survival analysis also showed CCND1 expression was an independent predictive factor (p<0.001).

Conclusions

This study suggests that some but not all patients with HNSCC may benefit from neoadjuvant chemotherapy with cisplatin-based regimen and CCND1 expression may serve as a predictive biomarker in selecting patients undergo less than two cycles of neoadjuvant chemotherapy.     

Executive functions profile in extreme eating/weight conditions: from anorexia nervosa to obesity

Background

Extreme weight conditions (EWC) groups along a continuum may share some biological risk factors and intermediate neurocognitive phenotypes. A core cognitive trait in EWC appears to be executive dysfunction, with a focus on decision making, response inhibition and cognitive flexibility. Differences between individuals in these areas are likely to contribute to the differences in vulnerability to EWC. The aim of the study was to investigate whether there is a common pattern of executive dysfunction in EWC while comparing anorexia nervosa patients (AN), obese subjects (OB) and healthy eating/weight controls (HC).

Methods

Thirty five AN patients, fifty two OB and one hundred thirty seven HC were compared using the Wisconsin Card Sorting Test (WCST); Stroop Color and Word Test (SCWT); and Iowa Gambling Task (IGT). All participants were female, aged between 18 and 60 years.

Results

There was a significant difference in IGT score (F(1.79); p<.001), with AN and OB groups showing the poorest performance compared to HC. On the WCST, AN and OB made significantly more errors than controls (F(25.73); p<.001), and had significantly fewer correct responses (F(2.71); p<.001). Post hoc analysis revealed that the two clinical groups were not significantly different from each other. Finally, OB showed a significant reduced performance in the inhibition response measured with the Stroop test (F(5.11); p<.001) compared with both AN and HC.

Conclusions

These findings suggest that EWC subjects (namely AN and OB) have similar dysfunctional executive profile that may play a role in the development and maintenance of such disorders.     

Reasons for (non)participating in a telephone-based intervention program for families with overweight children

Objective

Willingness to participate in obesity prevention programs is low; underlying reasons are poorly understood. We evaluated reasons for (non)participating in a novel telephone-based obesity prevention program for overweight children and their families.

Method

Overweight children and adolescents (BMI>90^th percentile) aged 3.5–17.4 years were screened via the CrescNet database, a representative cohort of German children, and program participation (repetitive computer aided telephone counseling) was offered by their local pediatrician. Identical questionnaires to collect baseline data on anthropometrics, lifestyle, eating habits, sociodemographic and psychosocial parameters were analyzed from 433 families (241 participants, 192 nonparticipants). Univariate analyses and binary logistic regression were used to identify factors associated with nonparticipation.

Results

The number of overweight children (BMI>90^th percentile) was higher in nonparticipants than participants (62% vs. 41.1%,p<0.001), whereas the number of obese children (BMI>97^th percentile) was higher in participants (58.9% vs.38%,p<0.001). Participating girls were younger than boys (8.8 vs.10.4 years, p<0.001). 87.3% and 40% of participants, but only 72.2% and 24.7% of nonparticipants, respectively, reported to have regular breakfasts (p = 0.008) and 5 regular daily meals (p = 0.003). Nonparticipants had a lower household-net-income (p<0.001), but higher subjective physical wellbeing than participants (p = 0.018) and believed that changes in lifestyle can be made easily (p = 0.05).

Conclusion

An important reason for nonparticipation was non-awareness of their child''s weight status by parents. Nonparticipants, who were often low-income families, believed that they already perform a healthy lifestyle and had a higher subjective wellbeing. We hypothesize that even a low-threshold intervention program does not reach the families who really need it.     

Increased intrathecal high-avidity anti-tau antibodies in patients with multiple sclerosis

Background

Antibodies against tau protein indicate an interaction between the immune system and the neurocytoskeleton and therefore may reflect axonal injury in multiple sclerosis (MS).

Methodology/Principal Findings

The levels and avidities of anti-tau IgG antibodies were measured using ELISA in paired cerebrospinal fluid (CSF) and serum samples obtained from 49 MS patients and 47 controls. Anti-tau antibodies were significantly elevated intrathecally (p<0.0001) in the MS group. The CSF anti-tau antibody levels were lower in MS patients receiving therapy than those without treatment (p<0.05). The avidities of anti-tau antibodies were higher in the CSF than in the serum (MS group p<0.0001; controls p<0.005). Anti-tau avidities in the CSF were elevated in MS patients in comparison with controls (p<0.05), but not in serum.

Conclusions

MS patients have higher levels of intrathecal anti-tau antibodies. Anti-tau antibodies have different avidities in different compartments with the highest values in the CSF of MS patients.     

Fractionated Therapy of HER2-Expressing Breast and Ovarian Cancer Xenografts in Mice with Targeted Alpha Emitting (227)Th-DOTA-p-benzyl-trastuzumab

Background

The aim of this study was to investigate therapeutic efficacy and normal tissue toxicity of single dosage and fractionated targeted alpha therapy (TAT) in mice with HER2-expressing breast and ovarian cancer xenografts using the low dose rate radioimmunoconjugate ²²⁷Th-DOTA-p-benzyl-trastuzumab.

Methodology/Principal Findings

Nude mice carrying HER2-overexpressing subcutaneous SKOV-3 or SKBR-3 xenografts were treated with 1000 kBq/kg ²²⁷Th-trastuzumab as single injection or four injections of 250 kBq/kg with intervals of 4–5 days, 2 weeks, or 4 weeks. Control animals were treated with normal saline or unlabeled trastuzumab. In SKOV-3 xenografts tumor growth to 10-fold size was delayed (p<0.01) and survival with tumor diameter less than 16 mm was prolonged (p<0.05) in all TAT groups compared to the control groups. No statistically significant differences were seen among the treated groups. In SKBR-3 xenografts tumor growth to 10-fold size was delayed in the single injection and 4–5 days interval groups (p<0.001) and all except the 4 weeks interval TAT group showed improved survival to the control groups (p<0.05). Toxicity was assessed by blood cell counts, clinical chemistry measurements and body weight. Transient reduction in white blood cells was seen for the single injection and 4–5 days interval groups (p<0.05). No significant changes were seen in red blood cells, platelets or clinical chemistry parameters. Survival without life threatening loss of body weight was significantly prolonged in 4 weeks interval group compared to single injection group (p<0.05) for SKOV-3 animals and in 2 weeks interval group compared with the 4–5 days interval groups (p<0.05) for SKBR-3 animals.

Conclusions/Significance

The same concentration of radioactivity split into several fractions may improve toxicity of ²²⁷Th-radioimmunotherapy while the therapeutic effect is maintained. Thus, it might be possible to increase the cumulative absorbed radiation dose to tumor with acceptable toxicity by fractionation of the dosage.     

Transitional probability-based model for HPV clearance in HIV-1-positive adolescent females

Background

HIV-1-positive patients clear the human papillomavirus (HPV) infection less frequently than HIV-1-negative. Datasets for estimating HPV clearance probability often have irregular measurements of HPV status and risk factors. A new transitional probability-based model for estimation of probability of HPV clearance was developed to fully incorporate information on HIV-1-related clinical data, such as CD4 counts, HIV-1 viral load (VL), highly active antiretroviral therapy (HAART), and risk factors (measured quarterly), and HPV infection status (measured at 6-month intervals).

Methodology and Findings

Data from 266 HIV-1-positive and 134 at-risk HIV-1-negative adolescent females from the Reaching for Excellence in Adolescent Care and Health (REACH) cohort were used in this study. First, the associations were evaluated using the Cox proportional hazard model, and the variables that demonstrated significant effects on HPV clearance were included in transitional probability models. The new model established the efficacy of CD4 cell counts as a main clearance predictor for all type-specific HPV phylogenetic groups. The 3-month probability of HPV clearance in HIV-1-infected patients significantly increased with increasing CD4 counts for HPV16/16-like (p<0.001), HPV18/18-like (p<0.001), HPV56/56-like (p = 0.05), and low-risk HPV (p<0.001) phylogenetic groups, with the lowest probability found for HPV16/16-like infections (21.60±1.81% at CD4 level 200 cells/mm³, p<0.05; and 28.03±1.47% at CD4 level 500 cells/mm³). HIV-1 VL was a significant predictor for clearance of low-risk HPV infections (p<0.05). HAART (with protease inhibitor) was significant predictor of probability of HPV16 clearance (p<0.05). HPV16/16-like and HPV18/18-like groups showed heterogeneity (p<0.05) in terms of how CD4 counts, HIV VL, and HAART affected probability of clearance of each HPV infection.

Conclusions

This new model predicts the 3-month probability of HPV infection clearance based on CD4 cell counts and other HIV-1-related clinical measurements.     

Seeking clarity within cloudy effluents: differentiating fungal from bacterial peritonitis in peritoneal dialysis patients

Background

Fungal peritonitis is a serious complication of peritoneal dialysis (PD) therapy with the majority of patients ceasing PD permanently. The aims of this study were to identify risk factors and clinical associations that may discriminate between fungal from bacterial peritonitis.

Methods

We retrospectively identified episodes of fungal peritonitis from 2001–2010 in PD patients at Liverpool and Westmead Hospitals (Australia). Fungal peritonitis cases were matched in a 1∶2 ratio with patients with bacterial peritonitis from each institution''s dialysis registry, occurring closest in time to the fungal episode. Patient demographic, clinical and outcome data were obtained from the medical records.

Results

Thirty-nine episodes of fungal peritonitis (rate of 0.02 episodes per patient-year of dialysis) were matched with 78 episodes of bacterial peritonitis. Candida species were the commonest pathogens (35/39; 90% episodes) with Candida albicans (37%), Candida parapsilosis (32%) and Candida glabrata (13%) the most frequently isolated species. Compared to bacterial peritonitis, fungal peritonitis patients had received PD for significantly longer (1133 vs. 775 catheter-days; p = 0.016), were more likely to have had previous episodes of bacterial peritonitis (51% vs. 10%; p = 0.01), and to have received prior antibacterial therapy (51% vs. 10%; p = 0.01). Patients with fungal peritonitis were less likely to have fever and abdominal pain on presentation, but had higher rates of PD catheter removal (79% vs. 22%; p<0.005), and permanent transfer to haemodialysis (87% vs. 24%; p<0.005). Hospital length of stay was significantly longer in patients with fungal peritonitis (26.1 days vs. 12.6 days; p = 0.017), but the all-cause 30-day mortality rate was similar in both groups. Fluconazole was a suitable empiric antifungal agent; with no Candida resistance detected.

Conclusion

Prompt recognition of clinical risk factors, initiation of antifungal therapy and removal of PD catheters are key considerations in optimising outcomes.     

TIA-1 cytotoxic granule-associated RNA binding protein improves the prognostic performance of CD8 in mismatch repair-proficient colorectal cancer

Background

Evidence suggests a confounding effect of mismatch repair (MMR) status on immune response in colorectal cancer. The identification of innate and adaptive immune cells, that can complement the established prognostic effect of CD8 in MMR-proficient colorectal cancers patients, representing 85% of all cases, has not been performed.

Methodology/Principal Findings

Colorectal cancers from a test (n = 1197) and external validation (n = 209) cohort of MMR-proficient colorectal cancers were mounted onto single and multiple punch tissue microarrays. Immunohistochemical quantification (score 0-3) was performed for CD3, CD4, CD8, CD45RO, CD68, CD163, FoxP3, GranzymeB, iNOS, mast cell tryptase, MUM1, PD1 and TIA-1 tumor-infiltrating (TILs) reactive cells. Coexpression experiments on fresh colorectal cancer specimens using specific cell population markers were performed. In the test group, higher numbers of CD3+ (p<0.001), CD4+ (p = 0.029), CD8+ (p<0.001), CD45RO+ (p = 0.048), FoxP3+ (p<0.001), GranzymeB+ (p<0.001), iNOS+ (p = 0.035), MUM1+ (p = 0.014), PD1+ (p = 0.034) and TIA-1+ TILs (p<0.001) were linked to favourable outcome. Adjusting for age, gender, TNM stage and post-operative therapy, higher CD8+ (p<0.001; HR (95%CI): 0.66 (0.64-0.68)) and TIA-1+ (p<0.001; HR (95%CI): 0.56 (0.5-0.6)) were independent prognostic factors. Moreover, among patients with CD8+ infiltrates, TIA-1 further stratified 355 (35.6%) patients into prognostic subgroups (p<0.001; HR (95%CI): 0.89 (95%CI: 0.8-0.9)). Results were confirmed on the validation cohort (p = 0.006). TIA-1+ cells were mostly CD8+ (57%), but also stained for TCRγδ (22%), CD66b (13%) and only rarely for CD4+, macrophage and NK cell markers.

Conclusions

TIA-1 adds prognostic information to TNM stage and adjuvant therapy in MMR-proficient colorectal cancer patients. The prognostic effect of CD8+ TILs is confounded by the presence of TIA-1+ which translates into improved risk stratification for approximately 35% of all patients with MMR-proficient colorectal cancers.     

Modifications of default-mode network connectivity in patients with cerebral glioma

Purpose

The aim of the study was to evaluate connectivity modifications in the Default Mode Network (DMN) in patients with cerebral glioma, and to correlate these modifications to tumor characteristics.

Methods

Twenty-four patients with a left-hemisphere cerebral tumor (14 grade II and 10 grade IV gliomas) and 14 healthy age-matched right-hand volunteers were enrolled in the study. Subjects underwent fMRI while performing language tasks for presurgical mapping. Data was analyzed with independent component analysis in order to identify the DMN. DMN group maps were produced by random-effect analysis (p<0.001, FDR-corrected). An analysis of variance across the three groups (p<0.05) and post-hoc t-test contrasts between pairs of groups were calculated (p<0.05, FDR-corrected).

Results

All three groups showed typical DMN areas. However, reduced DMN connectivity was detected in tumor patients with respect to controls. A significantly increased and reduced integration of DMN areas was observed in the hippocampal and prefrontal regions, respectively. Modifications were closely related to tumor grading. Moreover, the DMN lateralized to the hemisphere contralateral to tumor in the low-grade, but not in the high-grade tumor patients.

Conclusion

Modifications of DMN connectivity were induced by gliomas and differed for high and low grade tumors.     

Case control polysomnographic studies of sleep disorders in Parkinson's disease

Background

The relationship between a number of primary sleep disorders and Parkinson''s disease (PD) is still debated. There are limited case control polysomnographic studies in PD and most of these study sample sizes are small.

Methodology/Findings

We conducted one of the largest case-control studies involving overnight polysomnographic evaluation, with prospective recruitment of unselected Parkinson''s disease patients and healthy controls from an Asian population. The cases were recruited from the specialized movement disorder outpatient clinics in a tertiary referral center, and controls from the same geographical locations. All subjects underwent an overnight polysomnographic study and a multiple sleep latency test.A total of 124 subjects including 56 patients and 68 controls frequency-matched for age and sex were included. Multivariate analysis revealed that patients had significantly shorter total sleep time than controls (p = 0.01), lower sleep efficiency (p = 0.001) and increased REM latency (p = 0.007). In patients, multivariate analysis showed that reduced total sleep time was significantly associated with increased age (p = 0.001) and increased levodopa dose (p = 0.032). The mean Insomnia Severity Index was higher in PD patients (9.0±7.1) compared to controls (3.3±3.9, p<0.001). The mean Epworth Sleepiness Scale score was higher in PD patients (9.3±5.9 vs. 5.7±4.8, p<0.001). Nocturnal arousals, obstructive sleep apnea, periodic leg movements and objective abnormal sleepiness were not increased in our patients.

Conclusions/Significance

Our case-control polysomnographic study, the first-ever performed in an Asian population, revealed altered sleep architecture and reduced sleep in PD patients compared to controls. Reduced total sleep time was associated with increased age and levodopa dose. However, nocturnal arousals, primary sleep disorders and abnormal sleepiness were not increased in our PD patients suggesting that ethnic/genetic differences may be a factor in the pathophysiology of these conditions.     

Long-Term Effect of Bariatric Surgery on Liver Enzymes in the Swedish Obese Subjects (SOS) Study

Background and Aim

Obesity is associated with elevated serum transaminase levels and non-alcoholic fatty liver disease and weight loss is a recommended therapeutic strategy. Bariatric surgery is effective in obtaining and maintaining weight loss. Aim of the present study was to examine the long-term effects of bariatric surgery on transaminase levels in obese individuals.

Methods

The Swedish Obese Subjects (SOS) study is a prospective controlled intervention study designed to compare the long-term effects of bariatric surgery and usual care in obese subjects. A total of 3,570 obese participants with no excess of alcohol consumption at baseline (1,795 and 1,775 in the control and surgery group, respectively) were included in the analyses. Changes in transaminase levels during follow-up were compared in the surgery and control groups.

Results

Compared to usual care, bariatric surgery was associated with lower serum ALT and AST levels at 2- and 10- year follow up. The reduction in ALT levels was proportional to the degree of weight loss. Both the incidence of and the remission from high transaminase levels were more favorable in the surgery group compared to the control group. Similarly, the prevalence of ALT/AST ratio <1 was lower in the surgery compared to the control group at both 2- and 10-year follow up.

Conclusions

Bariatric surgery results in a sustained reduction in transaminase levels and a long-term benefit in obese individuals.     

Early markers of glycaemic control in children with type 1 diabetes mellitus

Background

Type 1 diabetes mellitus (T1DM) may lead to severe long-term health consequences. In a longitudinal study, we aimed to identify factors present at diagnosis and 6 months later that were associated with glycosylated haemoglobin (HbA_1c) levels at 24 months after T1DM diagnosis, so that diabetic children at risk of poor glycaemic control may be identified.

Methods

229 children <15 years of age diagnosed with T1DM in the Auckland region were studied. Data collected at diagnosis were: age, sex, weight, height, ethnicity, family living arrangement, socio-economic status (SES), T1DM antibody titre, venous pH and bicarbonate. At 6 and 24 months after diagnosis we collected data on weight, height, HbA_1c level, and insulin dose.

Results

Factors at diagnosis that were associated with higher HbA_1c levels at 6 months: female sex (p<0.05), lower SES (p<0.01), non-European ethnicity (p<0.01) and younger age (p<0.05). At 24 months, higher HbA_1c was associated with lower SES (p<0.001), Pacific Island ethnicity (p<0.001), not living with both biological parents (p<0.05), and greater BMI SDS (p<0.05). A regression equation to predict HbA_1c at 24 months was consequently developed.

Conclusions

Deterioration in glycaemic control shortly after diagnosis in diabetic children is particularly marked in Pacific Island children and in those not living with both biological parents. Clinicians need to be aware of factors associated with poor glycaemic control beyond the remission phase, so that more effective measures can be implemented shortly after diagnosis to prevent deterioration in diabetes control.     

Sedentary behavior is not associated with cardiometabolic risk in adults with abdominal obesity

Objective

The primary aim of this study was to determine whether time spent in sedentary behaviors (SED) was associated with 2-hour glucose and insulin resistance in adults with abdominal obesity. We also examined the association between light physical activity (LPA) and sporadic (accumulated in bouts <10 minutes in duration) moderate-to-vigorous physical activity (MVPA) with glucose metabolism.

Methods

Participants were 135 inactive, abdominally obese adults recruited from Kingston, Canada. SED and physical activity were determined by accelerometry over 7 days and summarized as SED (accelerometer counts/min <100), LPA (counts/min 100–1951), and MVPA (counts/min ≥1952). A 75 g oral glucose tolerance test was used to ascertain 2-hour glucose; the homeostasis model of assessment was used to determine insulin resistance (HOMA-IR); lipid, lipoproteins and blood pressure were determined using standard protocols. Secondary analyses considered the association between SED and physical activity with other cardiometabolic risk factors.

Results

Participants spent 627.2±82.9 min/d in SED, 289.0±91.7 min/d in LPA and 19.2±13.5 min/d in MVPA. Neither SED nor the physical activity variables were associated with 2-hour glucose or HOMA-IR (p>0.05). In secondary analyses, SED was not associated with any cardiometabolic risk factor (p>0.1); with the exception of blood pressure (p<0.05), LPA was not associated with any cardiometabolic risk factor (p>0.1); and MVPA was independently associated with total cholesterol and triglycerides (p<0.05).

Conclusions

Objectively measured SED was not associated with 2-hr glucose or HOMA-IR. Our findings also suggest that the accumulation of LPA and sporadic MVPA is not associated with glucose metabolism in adults with abdominal obesity.     

Dietary intake and rural-urban migration in India: a cross-sectional study

Background

Migration from rural areas of India contributes to urbanisation and lifestyle change, and dietary changes may increase the risk of obesity and chronic diseases. We tested the hypothesis that rural-to-urban migrants have different macronutrient and food group intake to rural non-migrants, and that migrants have a diet more similar to urban non-migrants.

Methods and findings

The diets of migrants of rural origin, their rural dwelling sibs, and those of urban origin together with their urban dwelling sibs were assessed by an interviewer-administered semi-quantitative food frequency questionnaire. A total of 6,509 participants were included. Median energy intake in the rural, migrant and urban groups was 2731, 3078, and 3224 kcal respectively for men, and 2153, 2504, and 2644 kcal for women (p<0.001). A similar trend was seen for overall intake of fat, protein and carbohydrates (p<0.001), though differences in the proportion of energy from these nutrients were <2%. Migrant and urban participants reported up to 80% higher fruit and vegetable intake than rural participants (p<0.001), and up to 35% higher sugar intake (p<0.001). Meat and dairy intake were higher in migrant and urban participants than rural participants (p<0.001), but varied by region. Sibling-pair analyses confirmed these results. There was no evidence of associations with time in urban area.

Conclusions

Rural to urban migration appears to be associated with both positive (higher fruit and vegetables intake) and negative (higher energy and fat intake) dietary changes. These changes may be of relevance to cardiovascular health and warrant public health interventions.