Does Optic Nerve Head Surface Topography Change Prior to Loss of Retinal Nerve Fiber Layer Thickness: A Test of the Site of Injury Hypothesis in Experimental Glaucoma

Purpose

To test the hypothesis that optic nerve head (ONH) deformation manifesting as changes in its mean surface height precedes thinning of the peripapillary retinal nerve fiber layer (RNFL) in experimental glaucoma (EG).

Methods

68 rhesus macaque monkeys each had three or more baseline imaging sessions under manometric intraocular pressure (IOP) control to obtain average RNFL thickness (RNFLT) and the ONH surface topography parameter mean position of the disc (MPD). Laser photocoagulation was then applied to the trabecular meshwork of one eye to induce chronic, mild-to-moderate IOP elevation and bi-weekly imaging continued. Event analysis was applied to determine for each parameter when an ‘endpoint’ occurred (signficant change from baseline) for eight different endpoint criteria. Specificity was assessed in the group of 68 fellow control eyes. Classical signal detection theory and survival analysis were used to compare MPD with RNFLT.

Results

Regardless of the endpoint criterion, endpoints were always more frequent for MPD than for RNFLT. The discriminability index (d’) was 2.7 ± 0.2 for MPD and 1.9 ± 0.2 for RNFLT (p<0.0001). Endpoints were reached by MPD an average of 1-2 months earlier than by RNFLT (p<0.01). At the onset of the first specific, detectable MPD change in EG eyes, there was still no significant change in RNFLT on average (p=0.29) and only 25% of individual eyes exhibited signficant reduction. In contrast, at onset of signficant RNFLT change, MPD had already changed an average of 101 µm from baseline (p<0.0001) and 71% of the individual eyes had exhibited significant change. The magnitude of MPD change was more than could be explained on the basis of axon loss alone.

Conclusions

This study demonstrates that the average surface height of the ONH changes prior to any detectable loss of average peripapillary RNFL thickness in non-human primate eyes with experimental glaucoma.     

Comparison of Retinal Nerve Fiber Layer Thickness In Vivo and Axonal Transport after Chronic Intraocular Pressure Elevation in Young versus Older Rats

Purpose

To compare in young and old rats longitudinal measurements of retinal nerve fiber layer thickness (RNFLT) and axonal transport 3-weeks after chronic IOP elevation.

Method

IOP was elevated unilaterally in 2- and 9.5-month-old Brown-Norway rats by intracameral injections of magnetic microbeads. RNFLT was measured by spectral domain optical coherence tomography. Anterograde axonal transport was assessed from confocal scanning laser ophthalmolscopy of superior colliculi (SC) after bilateral intravitreal injections of cholera toxin-B-488. Optic nerve sections were graded for damage.

Results

Mean IOP was elevated in both groups (young 37, old 38 mmHg, p = 0.95). RNFL in young rats exhibited 10% thickening at 1-week (50.9±8.1 µm, p<0.05) vs. baseline (46.4±2.4 µm), then 7% thinning at 2-weeks (43.0±7.2 µm, p>0.05) and 3-weeks (43.5±4.4 µm, p>0.05), representing 20% loss of dynamic range. RNFLT in old rats showed no significant change at 1-week (44.9±4.1 µm) vs. baseline (49.2±5.3 µm), but progression to 22% thinning at 2-weeks (38.0±3.7 µm, p<0.01) and 3-weeks (40.0±6.6 µm, p<0.05), representing 59% loss of dynamic range. Relative SC fluorescence intensity was reduced in both groups (p<0.001), representing 77–80% loss of dynamic range and a severe transport deficit. Optic nerves showed 75–95% damage (p<0.001). There was greater RNFL thinning in old rats (p<0.05), despite equivalent IOP insult, transport deficit and nerve damage between age groups (all p>0.05).

Conclusion

Chronic IOP elevation resulted in severely disrupted axonal transport and optic nerve axon damage in all rats, associated with mild RNFL loss in young rats but a moderate RNFL loss in old rats despite the similar IOP insult. Hence, the glaucomatous injury response within the RNFL depends on age.     

Relationship between Optical Coherence Tomography and Electrophysiology of the Visual Pathway in Non-Optic Neuritis Eyes of Multiple Sclerosis Patients

Purpose

Loss of retinal ganglion cells in in non-optic neuritis eyes of Multiple Sclerosis patients (MS-NON) has recently been demonstrated. However, the pathological basis of this loss at present is not clear. Therefore, the aim of the current study was to investigate associations of clinical (high and low contrast visual acuity) and electrophysiological (electroretinogram and multifocal Visual Evoked Potentials) measures of the visual pathway with neuronal and axonal loss of RGC in order to better understand the nature of this loss.

Methods

Sixty-two patients with relapsing remitting multiple sclerosis with no previous history of optic neuritis in at least one eye were enrolled. All patients underwent a detailed ophthalmological examination in addition to low contrast visual acuity, Optical Coherence Tomography, full field electroretinogram (ERG) and multifocal visual evoked potentials (mfVEP).

Results

There was significant reduction of ganglion cell layer thickness, and total and temporal retinal nerve fibre layer (RNFL) thickness (p<0.0001, 0.002 and 0.0002 respectively). Multifocal VEP also demonstrated significant amplitude reduction and latency delay (p<0.0001 for both). Ganglion cell layer thickness, total and temporal RNFL thickness inversely correlated with mfVEP latency (r = −0.48, p<0.0001 respectively; r = −0.53, p<0.0001 and r = −0.59, p<0.0001 respectively). Ganglion cell layer thickness, total and temporal RNFL thickness also inversely correlated with the photopic b-wave latency (r = −0.35, p = 0.01; r = −0.33, p = 0.025; r = −0.36, p = 0.008 respectively). Multivariate linear regression model demonstrated that while both factors were significantly associated with RGC axonal and neuronal loss, the estimated predictive power of the posterior visual pathway damage was considerably larger compare to retinal dysfunction.

Conclusion

The results of our study demonstrated significant association of RGC axonal and neuronal loss in NON-eyes of MS patients with both retinal dysfunction and post-chiasmal damage of the visual pathway.     

Potential Role of M. tuberculosis Specific IFN-γ and IL-2 ELISPOT Assays in Discriminating Children with Active or Latent Tuberculosis

Background

Although currently available IGRA have been reported to be promising markers for TB infection, they cannot distinguish active tuberculosis (TB) from latent infection (LTBI).

Objective

Children with LTBI, active TB disease or uninfected were prospectively evaluated by an in-house ELISPOT assay in order to investigate possible immunological markers for a differential diagnosis between LTBI and active TB.

Methods

Children at risk for TB infection prospectively enrolled in our infectious disease unit were evaluated by in-house IFN-γ and IL-2 based ELISPOT assays using a panel of Mycobacterium tuberculosis antigens.

Results

Twenty-nine children were classified as uninfected, 21 as LTBI and 25 as active TB cases (including 5 definite and 20 probable cases). Significantly higher IFN-γ ELISPOT responses were observed in infected vs. uninfected children for ESAT-6 (p<0.0001), CFP-10 (p<0.0001), TB 10.3 (p = 0.003), and AlaDH (p = 0.001), while differences were not significant considering Ag85B (p = 0.063), PstS1 (p = 0.512), and HspX (16 kDa) (p = 0.139). IL-2 ELISPOT assay responses were different for ESAT-6 (p<0.0001), CFP-10 (p<0.0001), TB 10.3 (p<0.0001), HspX (16 kDa) (p<0.0001), PstS1 (p<0.0001) and AlaDH (p = 0.001); but not for Ag85B (p = 0.063). Comparing results between children with LTBI and those with TB disease differences were significant for IFN-γ ELISPOT only for AlaDH antigen (p = 0.021) and for IL-2 ELISPOT assay for AlaDH (p<0.0001) and TB 10.3 antigen (p = 0.043). ROC analyses demonstrated sensitivity of 100% and specificity of 81% of AlaDH-IL-2 ELISPOT assay in discriminating between latent and active TB using a cut off of 12.5 SCF per million PBMCs.

Conclusion

Our data suggest that IL-2 based ELISPOT with AlaDH antigen may be of help in discriminating children with active from those with latent TB.     

Postoperative Vision-Related Quality of Life in Macula-Off Rhegmatogenous Retinal Detachment Patients and Its Relation to Visual Function

Objective

To determine the vision-related quality of life (VR-QOL) after surgery for macula-off rhegmatogenous retinal detachment (RRD) in relation to visual acuity, contrast acuity, and color vision.

Methods

In a prospective observational study, we included 55 patients with a macula-off RRD. Best corrected visual acuity (BCVA), color vision (saturated and desaturated color confusion indices (CCI)) and contrast acuity were measured at 12 months postoperatively in both the RRD eye and the fellow control eye, and the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was filled out.

Results

Operated and fellow control eyes differed significantly in mean LogMAR BCVA (P<0.0001), median Log contrast acuity (P<0.0001), saturated CCI (P = 0.009), and desaturated CCI (P = 0.016). Significant correlations were observed between the NEI VFQ-25 overall composite score and postoperative LogMAR BCVA (R = −0.551, P<0.0001), contrast acuity (R = 0.472, P<0.0001), saturated CCI (R = −0.315, P = 0.023), and desaturated CCI (R = −0.283, P = 0.044).

Conclusions

A lower VR-QOL was highly correlated to a worse postoperative BCVA and contrast acuity and to a lesser extent to color vision disturbances.     

Factors Affecting the Ability of the Spectral Domain Optical Coherence Tomograph to Detect Photographic Retinal Nerve Fiber Layer Defects

Purpose

To evaluate the ability of normative database classification (color-coded maps) of spectral domain optical coherence tomograph (SDOCT) in detecting wedge shaped retinal nerve fiber layer (RNFL) defects identified on photographs and the factors affecting the ability of SDOCT in detecting these RNFL defects.

Methods

In a cross-sectional study, 238 eyes (476 RNFL quadrants) of 172 normal subjects and 85 eyes (103 RNFL quadrants with wedge shaped RNFL defects) of 66 glaucoma patients underwent RNFL imaging with SDOCT. Logistic regression models were used to evaluate the factors associated with false positive and false negative RNFL classifications of the color-coded maps of SDOCT.

Results

False positive classification at a p value of <5% was seen in 108 of 476 quadrants (22.8%). False negative classification at a p value of <5% was seen in 16 of 103 quadrants (15.5%). Of the 103 quadrants with RNFL defects, 64 showed a corresponding VF defect in the opposite hemisphere and 39 were preperimetric. Higher signal strength index (SSI) of the scan was less likely to have a false positive classification (odds ratio: 0.97, p = 0.01). Presence of an associated visual field defect (odds ratio: 0.17, p = 0.01) and inferior quadrant RNFL defects as compared to superior (odds ratio: 0.24, p = 0.04) were less likely to show false negative classifications.

Conclusions

Scans with lower signal strengths were more likely to show false positive RNFL classifications, and preperimetric and superior quadrant RNFL defects were more likely to show false negative classifications on color-coded maps of SDOCT.     

Angiotensin-Induced Abdominal Aortic Aneurysms in Hypercholesterolemic Mice: Role of Serum Cholesterol and Temporal Effects of Exposure

Objective

Understanding variations in size and pattern of development of angiotensin II (Ang II)-induced abdominal aortic aneurysms (AAA) may inform translational research strategies. Thus, we sought insight into the temporal evolution of AAA in apolipoprotein (apo)E^−/− mice.

Approach

A cohort of mice underwent a 4-week pump-mediated infusion of saline (n = 23) or 1500 ng/kg/min of Ang II (n = 85) and AAA development was tracked via in vivo ultrasound imaging. We adjusted for hemodynamic covariates in the regression models for AAA occurrence in relation to time.

Results

The overall effect of time was statistically significant (p<0.001). Compared to day 7 of AngII infusion, there was no decrease in the log odds of AAA occurrence by day 14 (−0.234, p = 0.65), but compared to day 21 and 28, the log odds decreased by 9.07 (p<0.001) and 2.35 (p = 0.04), respectively. Hemodynamic parameters were not predictive of change in aortic diameter (Δ) (SBP, p = 0.66; DBP, p = 0.66). Mean total cholesterol (TC) was higher among mice with large versus small AAA (601 vs. 422 mg/ml, p<0.0001), and the difference was due to LDL. AngII exposure was associated with 0.43 mm (95% CI, 0.27 to 0.61, p<0.0001) increase in aortic diameter; and a 100 mg/dl increase in mean final cholesterol level was associated with a 12% (95% CI, 5.68 to 18.23, p<0.0001) increase in aortic diameter. Baseline cholesterol was not associated with change in aortic diameter (p = 0.86).

Conclusions

These are the first formal estimates of a consistent pattern of Ang II-induced AAA development. The odds of AAA occurrence diminish after the second week of Ang II infusion, and TC is independently associated with AAA size.     

Trends in Low-Density Lipoprotein Cholesterol Goal Achievement in High Risk United States Adults: Longitudinal Findings from the 1999–2008 National Health and Nutrition Examination Surveys

Background

Previous studies have demonstrated gaps in achievement of low-density lipoprotein-cholesterol (LDL-C) goals among U.S. individuals at high cardiovascular disease risk; however, recent studies in selected populations indicate improvements.

Objective

We sought to define the longitudinal trends in achieving LDL-C goals among high-risk United States adults from 1999–2008. Methods We analyzed five sequential population-based cross-sectional National Health and Nutrition Examination Surveys 1999–2008, which included 18,656 participants aged 20–79 years. We calculated rates of LDL-C goal achievement and treatment in the high-risk population.

Results

The prevalence of high-risk individuals increased from 13% to 15.5% (p = 0.046). Achievement of LDL-C <100 mg/dL increased from 24% to 50.4% (p<0.0001) in the high-risk population with similar findings in subgroups with (27% to 64.8% p<0.0001) and without (21.8% to 43.7%, p<0.0001) coronary heart disease (CHD). Achievement of LDL-C <70 mg/dL improved from 2.4% to 17% (p<0.0001) in high-risk individuals and subgroups with (3.4% to 21.4%, p<0.0001) and without (1.7% to 14.9%, p<0.0001) CHD. The proportion with LDL-C ≥130 mg/dL and not on lipid medications decreased from 29.4% to 18% (p = 0.0002), with similar findings among CHD (25% to 11.9% p = 0.0013) and non-CHD (35.8% to 20.8% p<0.0001) subgroups.

Conclusion

The proportions of the U.S. high-risk population achieving LDL-C <100 mg/dL and <70 mg/dL increased over the last decade. With 65% of the CHD subpopulation achieving an LDL-C <100 mg/dL in the most recent survey, U.S. LDL-C goal achievement exceeds previous reports and approximates rates achieved in highly selected patient cohorts.     

Histological Criteria for Encapsulating Peritoneal Sclerosis – A Standardized Approach

Background

The two most relevant pathologies of long-term peritoneal dialysis (PD) are simple sclerosis and encapsulating peritoneal sclerosis (EPS). The histological differentiation of those two entities is difficult. The Aim of the study was to establish a method to standardize and facilitate the differentiation between simple sclerosis and EPS

Methods

We investigated 58 peritoneal biopsies - 31 EPS patients and 27 PD patients. Two blinded investigators analyzed 20 histological characteristics in EPS and PD patients.

Results

The following findings were significantly more common in EPS than in patients on PD without EPS: fibroblast like cells (FLC) (p<0.0001), mesothelial denudation (p<0.0001), decreased cellularity (p = 0.008), fibrin deposits (p<0.03), Fe deposits (p = 0.05), podoplanin vascular (p<0.0001), podoplanin avascular (p<0.0001). Using all predictor variables we trained the classification method Random Forest to categorize future cases. Podoplanin vascular and avascular were taken together (p<0.0001), FLC (p<0.0001), mesothelial denudation (p = 0.0005), calcification (p = 0.0026), acellular areas (p = 0.0094), and fibrin deposits (p = 0.0336) showed up as significantly important predictor variables. Estimated misclassification error rate when classifying new cases turned out to be 14%.

Conclusion

The introduced statistical method allows discriminating between simple sclerosis and EPS. The misclassification error will likely improve with every new case added to the database.     

Multimodal Retinal Vessel Analysis in CADASIL Patients

Purpose

To further elucidate retinal findings and retinal vessel changes in Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients by means of high resolution retinal imaging.

Methods

28 eyes of fourteen CADASIL patients and an equal number of control subjects underwent confocal scanning laser ophthalmoscopy (cSLO), spectral-domain optical coherence tomography (SD-OCT), retinal nerve fibre layer (RNFL) measurements, fluorescein and indocyanine angiography. Three vessel measurement techniques were applied: RNFL thickness, a semiautomatic software tool based on cSLO images and manual vessel outlining based on SD-OCT.

Results

Mean age of patients was 56.2±11.6 years. Arteriovenous nicking was present in 22 (78.6%) eyes and venous dilation in 24 (85.7%) eyes. Retinal volume and choroidal volume were 8.77±0.46 mm³ and 8.83±2.24 mm³. RNFL measurements showed a global increase of 105.2 µm (Control group: 98.4 µm; p = 0.015). Based on semi-automatic cSLO measurements, maximum diameters of arteries and veins were 102.5 µm (106.0 µm; p = 0.21) and 128.6 µm (124.4 µm; p = 0.27) respectively. Manual SD-OCT measurements revealed significantly increased mean arterial 138.7 µm (125.4 µm; p<0.001) and venous 160.0 µm (146.9; p = 0.003) outer diameters as well as mean arterial 27.4 µm (19.2 µm; p<0.001) and venous 18.3 µm (15.7 µm; p<0.001) wall thicknesses in CADASIL patients.

Conclusions

The findings reflect current knowledge on pathophysiologic changes in vessel morphology in CADASIL patients. SD-OCT may serve as a complementary tool to diagnose and follow-up patients suffering from cerebral small-vessel diseases.     

Multiple Marker Detection in Peripheral Blood for NSCLC Diagnosis

Background

Non-invasive early detection of lung cancer could reduce the number of patients diagnosed with advanced disease, which is associated with a poor prognosis. We analyzed the diagnostic accuracy of a panel of peripheral blood markers in detecting non small cell lung cancer (NSCLC).

Methods

100 healthy donors and 100 patients with NSCLC were enrolled onto this study. Free circulating DNA, circulating mRNA expression of peptidylarginine deiminase type 4 (PAD4/PADI4), pro-platelet basic protein (PPBP) and haptoglobin were evaluated using a Real-Time PCR-based method.

Results

Free circulating DNA, PADI4, PPBP and haptoglobin levels were significantly higher in NSCLC patients than in healthy donors (p<0.0001, p<0.0001, p = 0.0002 and p = 0.0001, respectively). The fitted logistic regression model demonstrated a significant direct association between marker expression and lung cancer risk. The odds ratios of individual markers were 6.93 (95% CI 4.15–11.58; p<0.0001) for free DNA, 6.99 (95% CI 3.75–13.03; p<0.0001) for PADI4, 2.85 (95% CI 1.71–4.75; p<0.0001) for PPBP and 1.16 (95% CI 1.01–1.33; p = 0.031) for haptoglobin. Free DNA in combination with PPBP and PADI4 gave an area under the ROC curve of 0.93, 95% CI = 0.90–0.97, with sensitivity and specificity over 90%.

Conclusions

Free circulating DNA analysis combined with PPBP and PADI4 expression determination appears to accurately discriminate between healthy donors and NSCLC patients. This non-invasive multimarker approach warrants further research to assess its potential role in the diagnostic or screening workup of subjects with suspected lung cancer.     

Eradication of Helicobacter pylori Infection Improves Levodopa Action,Clinical Symptoms and Quality of Life in Patients with Parkinson's Disease

Background

Previous studies have demonstrated a higher prevalence of Helicobacter pylori (H. pylori) infection in patients with Parkinson''s disease (PD) compared to controls. H. pylori infection affects levodopa absorption and its eradication significantly improves clinical response to levodopa. Here, we studied the prevalence of H. pylori infection and its eradication effects among our PD patients.

Methods

A prospective study involving idiopathic PD patients on levodopa therapy. ¹³C-urea breath test (UBT) was used to detect H. pylori. UBT-positive patients were given standard eradication therapy and followed up at 6 and 12 weeks in an open label single arm design. Repeat UBT was performed at 12 weeks. The UPDRS, PD NMQ, PD NMSS and PDQ-39 were administered at baseline and post-eradication (6 and 12 weeks). Levodopa ‘onset’ time and ON-duration were recorded.

Results

Of 82 patients recruited, 27 (32.9%) had positive UBT. H. pylori-positive patients had significantly poorer total UPDRS (p = 0.005) and PDQ39 (p<0.0001) scores compared to H. pylori-negative patients. At 12 weeks post-eradication, the mean levodopa onset time shortened by 14 minutes (p = 0.011). The mean ON duration time increased by 56 minutes at week 6 (p = 0.041) and 38 minutes at week 12 (p = 0.035). The total UPDRS scores (p<0.0001), scores for parts II (p = 0.001), III (p<0.0001) and IV (p = 0.009) were significantly better. The total PDQ-39 scores (p = 0.001) and subdomains mobility (p = 0.002), ADL (p = 0.001), emotional well being (p = 0.026) and stigma (p = 0.034) significantly improved. The PD NMSQ did not show significant improvement.

Conclusions

H. pylori eradication improved levodopa onset time, ON duration, motor severity and quality of life parameters. Screening and eradication of H. pylori is inexpensive and should be recommended in PD patients, particularly those with erratic response to levodopa.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02112812","term_id":"NCT02112812"}}NCT02112812     

Localized Retinal Nerve Fiber Layer Defects Detected by Optical Coherence Tomography: The Beijing Eye Study

Objective

To assess the prevalence of localized retinal nerve fiber layer defects (LRNFLD) and associated factors in adult Chinese.

Methods

The population-based Beijing Eye Study 2011 included 3468 individuals (mean age: 64.6±9.8 years (range: 50–93 years)). The study participants underwent a detailed ophthalmological examination including spectral-domain optical coherence tomography (Spectralis^R-OCT) assisted measurement of the RNFL. A LRNFLD was defined as a sector in which the RNFL contour line dipped into the red zone for a length of <180°.

Results

Readable OCT images were available for 3242 (93.5%) subjects. LRNFLDs were detected in 640 eyes (9.9±0.4%) of 479 subjects (14.8±0.6%). In the age groups of 50–59 years, 60–69 years, 70–79 years, and 80+ years, the prevalence of LRNFLD per person increased from 9.9±0.9%, 11.6±1.0% and 20.6±1.4% to 33.0±3.2%, respectively. In multivariate analysis, prevalence of LRNFLDs was significantly associated with older age (P = 0.001; Odds Ratio (OR): 1.03; 95% Confidence Interval (CI): 1.01,1.05), myopic refractive error (P<0.001;OR:0.79;95%CI:0.74,0.85), larger beta zone of parapapillary atrophy (P<0.001; OR:1.34;95%CI:1.20,1.50), presence of glaucomatous optic neuropathy (P<0.001;OR:7.02;95%CI:3.87,12.7), presence of non-glaucomatous optic nerve damage (P = 0.001;OR:43.3;95%CI:8.24,227.1), and presence of diabetic retinopathy (P = 0.003;OR:2.79;95%CI:1.43,5.44).

Conclusions

OCT-defined LRNFLDs were present in a prevalence of 14.8±0.6% in a population-based study sample of subjects aged 50+ years. Prevalence of LRNFLDs increased with higher age, myopic refractive error, and larger parapapillary beta zone. Major ocular diseases associated with LRNFLs were glaucoma, non-glaucomatous optic nerve damage and diabetic retinopathy. These data may be helpful for a semiautomatic assessment of the RNFL.     

Heart Failure Induces Significant Changes in Nuclear Pore Complex of Human Cardiomyocytes

Aims

The objectives of this study were to analyse the effect of heart failure (HF) on several proteins of nuclear pore complex (NPC) and their relationship with the human ventricular function.

Methods and Results

A total of 88 human heart samples from ischemic (ICM, n = 52) and dilated (DCM, n = 36) patients undergoing heart transplant and control donors (CNT, n = 9) were analyzed by Western blot. Subcellular distribution of nucleoporins was analysed by fluorescence and immunocytochemistry. When we compared protein levels according to etiology, ICM showed significant higher levels of NDC1 (65%, p<0.0001), Nup160 (88%, p<0.0001) and Nup153 (137%, p = 0.004) than those of the CNT levels. Furthermore, DCM group showed significant differences for NDC1 (41%, p<0.0001), Nup160 (65%, p<0.0001), Nup153 (155%, p = 0.006) and Nup93 (88%, p<0.0001) compared with CNT. However, Nup155 and translocated promoter region (TPR) did not show significant differences in their levels in any etiology. Regarding the distribution of these proteins in cell nucleus, only NDC1 showed differences in HF. In addition, in the pathological group we obtained good relationship between the ventricular function parameters (LVEDD and LVESD) and Nup160 (r = −0382, p = 0.004; r = −0.290, p = 0.033; respectively).

Conclusions

This study shows alterations in specific proteins (NDC1, Nup160, Nup153 and Nup93) that compose NPC in ischaemic and dilated human heart. These changes, related to ventricular function, could be accompanied by alterations in the nucleocytoplasmic transport. Therefore, our findings may be the basis for a new approach to HF management.     

Effect of Peer Counselling by Mother Support Groups on Infant and Young Child Feeding Practices: The Lalitpur Experience

Objective

Our primary objective was to evaluate the effect of peer counselling by mother support groups (MSG''s) in improving the infant and young child feeding (IYCF) practices in the community.

Methods

We conducted this repeated-measure before and after study in the Lalitpur district of Uttar Pradesh, India between 2006 and 2011. We assessed the IYCF practices before and after creating MSG''s within the community. The feeding practices were reassessed at two time points–2 (T1) and 5 years (T2) after the intervention and compared with that of the pre-intervention phase (T0).

Results

The total population covered by the project from the time of its initiation was 105000. A total of 425 (T0), 480 (T1) and 521 (T2) mother infant pairs were selected from this population. There was significant improvement in the following IYCF practices in the community (represented as %; adjOR (95% CI, p) such as initiation of breast feeding within 1 hour at both T1 (71% vs. 11%); 19.6 (13.6, 28.2, p = <0.0001)and T2 (62% vs. 11%); 13.3 (9.4, 18.9, p = <0.0001); use of prelacteal feeds at both T1 (67% vs. 15%); 12.6 (CI: 9.0, 17.6, p<0.0001) and T2 (67% vs. 5%); 44.4 (28.8, 68.4, p = <0.0001); rates of exclusive breast feeding for 6 months at both T1 (50% vs. 7%); 13.6 (7.6, 25.0, p = <0.0001) and T2 (60% vs. 7%); 20.5 (11.3, 37.2, p = <0.0001); initiation of complementary feeding at T1 (85% vs. 54%); 5.6 (3.6, 8.7, p = <0.0001) and T2 (96% vs. 54%); 22.9 (11.8, 44.1, p = <0.0001) and complementary feeding along with continued breast feeding at both T1 (36% vs. 4.5%); 6 (1.15, 31.4, p = 0.033) and T2 (42% vs. 4.5%); 8.06 (1.96, 49.1, p = 0.005) as compared to pre-intervention period (T0) after adjusting for important social and demographic variables.

Conclusions

Peer counseling by MSG''s improved the IYCF practices in the district and could be sustained.     

Effects of Age,Gender, BMI,and Anatomical Site on Skin Thickness in Children and Adults with Diabetes

Objective

We aimed to assess the effects of age, sex, body mass index (BMI), and anatomical site on skin thickness in children and adults with diabetes.

Methods

We studied 103 otherwise healthy children and adolescents with type 1 diabetes aged 5–19 years, and 140 adults with type 1 and type 2 diabetes aged 20–85 years. The thicknesses of both the dermis and subcutis were assessed using ultrasound with a linear array transducer, on abdominal and thigh skin.

Results

There was an age-related thickening of both dermis (p<0.0001) and subcutis (p = 0.013) in children and adolescents. Girls displayed a substantial pubertal increase in subcutis of the thigh (+54%; p = 0.048) and abdomen (+68%; p = 0.009). Adults showed an age-related decrease in dermal (p = 0.021) and subcutis (p = 0.009) thicknesses. Pubertal girls had a thicker subcutis than pubertal boys in both thigh (16.7 vs 7.5 mm; p<0.0001) and abdomen (16.7 vs 8.8 mm; p<0.0001). Men had greater thigh dermal thickness than women (1.89 vs 1.65 mm; p = 0.003), while the subcutis was thicker in women in thigh (21.3 vs 17.9 mm; p = 0.012) and abdomen (17.7 vs 9.8 mm; p<0.0001). In boys, men, and women, both dermis and subcutis were thicker on the abdomen compared to thigh; in girls this was only so for dermal thickness. In both children and adults, the skin (dermis and subcutis) became steadily thicker with increasing BMI (p<0.0001).

Conclusions

Skin thickness is affected by age, pubertal status, gender, BMI, and anatomical site. Such differences may be important when considering appropriate sites for dermal/subcutaneous injections and other transdermal delivery systems.     

Retinal Nerve Fiber Layer Thickness Changes in Parkinson Disease: A Meta-Analysis

Background

Parkinson disease (PD) is a neurodegenerative process that leads to a selective loss of dopaminergic neurons, mainly in the basal ganglia of the brain. Numerous studies have analyzed the ability of optical coherence tomography (OCT) to detect retinal nerve fiber layer (RNFL) thickness abnormalities and changes in PD, but the results have not always been consistent. Therefore, we carried out a meta-analysis to evaluate the RNFL thickness measured with OCT in PD.

Methods and Findings

Case-control studies were selected through an electronic search of the Cochrane Controlled Trials Register, PUBMED and EMBASE. For the continuous outcomes, we calculated the weighted mean difference (WMD) and 95% confidence interval (CI). The statistical analysis was performed by RevMan 5.0 software. Thirteen case-control studies were included in the present meta-analysis, containing a total of 644 eyes in PD patients and 604 eyes in healthy controls. The results of our study showed that there was a significant reduction in average RNFL thickness in patients with PD compared to healthy controls (WMD = −5.76, 95% CI: −8.99 to −2.53, P = 0.0005). Additionally, differences of RNFL thickness in superior quadrant (WMD = −4.44, 95% CI: −6.93 to −1.94, P = 0.0005), inferior quadrant (WMD = −7.56, 95% CI: −11.33 to −3.78, P<0.0001), nasal quadrant (WMD = −3.12, 95% CI: −5.63 to −0.61, P = 0.01) and temporal quadrant (WMD = −4.63, 95% CI: −7.20 to −2.06, P = 0.0004) were all significant between the two groups.

Conclusion

In view of these results and the noninvasive nature of OCT technology, we surmise that OCT could be a useful tool for evaluating the progression of the Parkinson disease.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01928212","term_id":"NCT01928212"}}NCT01928212     

Complete Blood Count and Retinal Vessel Calibers

Objective

The influence of hematological indices such as complete blood count on microcirculation is poorly understood. Retinal microvasculature can be directly visualized and vessel calibers are associated with a range of ocular and systemic diseases. We examined the association of complete blood count with retinal vessel calibers.

Methods

Cross-sectional population-based Blue Mountains Eye Study, n = 3009, aged 49+ years. Complete blood count was measured from fasting blood samples taken at baseline examination, 1992–4. Retinal arteriolar and venular calibers were measured from digitized retinal photographs using a validated semi-automated computer program.

Results

All analyses adjusted for age, sex, systolic blood pressure, diabetes, smoking and fellow vessel caliber. Higher hematocrit, white cell count and platelet count were associated with narrower arteriolar caliber (p = 0.02, 0.03 and 0.001 respectively), while higher hemoglobin, hematocrit, red cell count, white cell count and platelet count were associated with wider venular caliber (p<0.0001 for all). Each quintile increase in hematocrit, white cell count and platelet count was associated with approximately 0.5 µm narrower arteriolar caliber; whereas each quintile increase in all of the complete blood count components was associated with approximately 1–2 µm wider venular caliber.

Conclusions

These associations show that elevated levels of hematological indices can have adverse effects on the microcirculation.     

Relationships between Mitochondrial Function and Metabolic Flexibility in Type 2 Diabetes Mellitus

Introduction

Mitochondrial dysfunction, lipid accumulation, insulin resistance and metabolic inflexibility have been implicated in the etiology of type 2 diabetes (T2D), yet their interrelationship remains speculative. We investigated these interrelationships in a group of T2D and obese normoglycemic control subjects.

Methods

49 non-insulin dependent male T2D patients and 54 male control subjects were enrolled, and a hyperinsulinemic-euglycemic clamp and indirect calorimetry were performed. A muscle biopsy was taken and intramyocellular lipid (IMCL) was measured. In vivo mitochondrial function was measured by PCr recovery in 30 T2D patients and 31 control subjects.

Results

Fasting NEFA levels were significantly elevated in T2D patients compared with controls, but IMCL was not different. Mitochondrial function in T2D patients was compromised by 12.5% (p<0.01). Whole body glucose disposal (WGD) was higher at baseline and lower after insulin stimulation. Metabolic flexibility (ΔRER) was lower in the type 2 diabetic patients (0.050±0.033 vs. 0.093±0.050, p<0.01). Mitochondrial function was the sole predictor of basal respiratory exchange ratio (RER) (R² = 0.18, p<0.05); whereas WGD predicted both insulin-stimulated RER (R² = 0.29, p<0.001) and metabolic flexibility (R² = 0.40, p<0.001).

Conclusions

These results indicate that defects in skeletal muscle in vivo mitochondrial function in type 2 diabetic patients are only reflected in basal substrate oxidation and highlight the importance of glucose disposal rate as a determinant of substrate utilization in response to insulin.