Age-matched Normal Control Group Research Articles

Longitudinal profiling of oligomeric A\u03b2 in human nasal discharge reflecting cognitive decline in probable Alzheimer\u2019s disease

Despite clinical evidence indicating a close relationship between olfactory dysfunction and Alzheimer’s disease (AD), further investigations are warranted to determine the diagnostic potential of nasal surrogate biomarkers for AD. In this study, we first identified soluble amyloid-β (Aβ), the key biomarker of AD, in patient nasal discharge using proteomic analysis. Then, we profiled the significant differences in Aβ oligomers level between patient groups with mild or moderate cognitive decline (n = 39) and an age-matched normal control group (n = 21) by immunoblot analysis and comparing the levels of Aβ by a self-standard method with interdigitated microelectrode sensor systems. All subjects received the Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), and the Global Deterioration Scale (GDS) for grouping. We observed higher levels of Aβ oligomers in probable AD subjects with lower MMSE, higher CDR, and higher GDS compared to the normal control group. Moreover, mild and moderate subject groups could be distinguished based on the increased composition of two oligomers, 12-mer Aβ*56 and 15-mer AβO, respectively. The longitudinal cohort study confirmed that the cognitive decline of mild AD patients with high nasal discharge Aβ*56 levels advanced to the moderate stage within three years. Our clinical evidence strongly supports the view that the presence of oligomeric Aβ proteins in nasal discharge is a potential surrogate biomarker of AD and an indicator of cognitive decline progression.

Associations of [18F]-APN-1607 Tau PET Binding in the Brain of Alzheimer's Disease Patients With Cognition and Glucose Metabolism.

Molecular imaging of tauopathies is complicated by the differing specificities and off-target binding properties of available radioligands for positron emission tomography (PET). [18F]-APN-1607 ([18F]-PM-PBB3) is a newly developed PET tracer with promising properties for tau imaging. We aimed to characterize the cerebral binding of [18F]-APN-1607 in Alzheimer’s disease (AD) patients compared to normal control (NC) subjects. Therefore, we obtained static late frame PET recordings with [18F]-APN-1607 and [18F]-FDG in patients with a clinical diagnosis of AD group, along with an age-matched NC group ([18F]-APN-1607 only). Using statistical parametric mapping (SPM) and volume of interest (VOI) analyses of the reference region normalized standardized uptake value ratio maps, we then tested for group differences and relationships between both PET biomarkers, as well as their associations with clinical general cognition. In the AD group, [18F]-APN-1607 binding was elevated in widespread cortical regions (P < 0.001 for VOI analysis, familywise error-corrected P < 0.01 for SPM analysis). The regional uptake in AD patients correlated negatively with Mini-Mental State Examination score (frontal lobe: R = -0.632, P = 0.004; temporal lobe: R = -0.593, P = 0.008; parietal lobe: R = -0.552, P = 0.014; insula: R = -0.650, P = 0.003; cingulum: R = -0.665, P = 0.002) except occipital lobe (R = -0.417, P = 0.076). The hypometabolism to [18F]-FDG PET in AD patients also showed negative correlations with regional [18F]-APN-1607 binding in some signature areas of AD (temporal lobe: R = -0.530, P = 0.020; parietal lobe: R = -0.637, P = 0.003; occipital lobe: R = -0.567, P = 0.011). In conclusion, our results suggested that [18F]-APN-1607 PET sensitively detected tau deposition in AD and that individual tauopathy correlated with impaired cerebral glucose metabolism and cognitive function.

In Vivo Mapping of the Choriocapillaris in High myopia: a Widefield Swept Source Optical Coherence Tomography Angiography

To report variation of choriocapillaris (CC) flow in widefield in high in myopic subjects compared with an age-matched normal control group using ultra widefield optical coherence tomography angiography (UW-OCTA). This is a Prospective, cross-sectional study. Thirty high myopia subjects and fifty healthy subjects were enrolled. Healthy and high myopia subjects were imaged with the SS-OCTA system (PLEX Elite 9000, Carl Zeiss Meditec Inc., Dublin, CA, USA). For each eye, five 12 × 12-mm OCTA volume scans were acquired. The en face CC images were then exported to imageJ and a semi-automated algorithm was used for subsequent quantitative analysis. The main outcome was a quantitative analysis of the CC. This analysis was performed in three different regions: (i) peripapillary, (ii) macular, and (iii) periphery. In addition, CC variables were further investigated in distinct fields within these three different regions. Thirty myopic eyes (32 subjects; myopic group) and fifty eyes (50 subjects; control group) without elevated myopia were included in the analysis. Mean ± SD age was 26.9 ± 2.9 years [median: 27 years; range: 20.0–40.0 years]. Mean ± SD axial length was 26.6 ± 0.6 mm [median: 26.2 mm; range: 26.1 to 28.0 mm]. Mean ± SD axial length was 26.6 ± 0.6 mm [median: 26.2 mm; range: 26.1 to 28.0 mm] in the myopic group and 23.9 ± 1.1 mm [median: 23.9 mm; range: 21.8 to 25.9 mm] in the control group. The total signal void area was significantly greater in myopic eyes compared with control group. The peripapillary region exhibited the greatest total signal void area (p < 0.0001 vs macular region, p < 0.0001 vs peripheral region). Within the macular region, the foveal area exhibited a greater total signal void area in comparison with both the parafoveal area (p < 0.0001) and the perifoveal area (p < 0.0001). In conclusion we report quantitative mapping of the choriocapillaris in myopic eyes compared with an age-matched normal control group. The CC perfusion appears to have a wide topographical variation.

Do male esophageal cancer patients have impaired sexual function after esophagectomy? A self-reported outcomes study.

Sexual function is a significant part of patients' quality of life, which is another important aspect of cancer. This study assessed and compared the sexual function of male esophageal cancer patients to that of age-matched normal controls through postoperative follow-up surveys. The study included 105 male esophageal cancer patients aged 38-81years who underwent a curative-intent esophagectomy between April 2012 and May 2014. This observational study included sociodemographic and clinicopathological characteristics and responses to sexual function questionnaires International Index of Erectile Function (IIEF) at 6 and 12months after surgery. An age-matched normal control group was recruited. Non-parametric tests were used when appropriate. The median patient age was 59years. The factors significantly associated with sexual dysfunction on the 6-month survey included older age, and postoperative complications. At 12months after surgery, older age was significantly associated with poorer sexual function. The sexual function scores significantly increased from 6 to 12months after surgery (P<0.05); there was no difference in the patients' 12-month sexual function scores and those of the normal controls (P>0.05). Notably, compared to older patients (age ≥60years), the younger (age <60years) patients reported a significantly better sexual function scores (P<0.05). Age, and postoperative complications were the factors significantly associated with sexual function. Impaired sexual function after primary treatment can be recovered in male esophageal cancer patients; younger patients may regain sexual function better than their older counterparts.

Chronic administration of atorvastatin could partially ameliorate erectile function in streptozotocin-induced diabetic rats.

The efficacy of statins is related to the ‘common soil’ hypothesis, which proposes oxidative stress and inflammation as main pathophysiologic processes in the disease group of diabetes and endothelial dysfunction. This study evaluated the recovery of erectile function after administration of chronic statin alone in streptozotocin (STZ)-induced diabetes mellitus (DM) rats, focusing on the anti-oxidative effects and consequentially recuperated endothelial function. A total of 45 male Sprague-Dawley rats (8 weeks old) were divided into three groups (n = 15 each): an age-matched normal control group (Control group), an uncontrolled DM group (DM group), and a statin-treated group (Statin group). The rats in the DM and Statin group received an injection of STZ (60 mg/kg). Beginning 10 weeks after the establishment of DM, the Statin group received daily treatment with atorvastatin (10 mg/kg) via oral gavage for four weeks. After 14 weeks, the results of the experiment were evaluated. The ratios of intracavernosal pressure (ICP) to mean arterial pressure (MAP) were recorded with cavernosometry (20 Hz, 3 V, 0.2 msec for 30 seconds) before and after the intravenous administration of udenafil (1 mg/kg). Expression of alpha-smooth muscle actin (α-SMA) was evaluated using cavernosal tissue. In addition, changes in RhoA translocation ratio and myosin phosphatase target subunit 1 (MYPT1) phosphorylation were evaluated with western blot. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were also analyzed as measurements of oxidative stress levels. The ICP/MAP and area under the curve (AUC)/MAP ratios of the Statin group were obviously superior to the DM group, but were not comparable to the Control group (P<0.001). The level of oxidative stress, namely SOD activity, was also significantly lower in the Statin group than in the DM group (P = 0.015), and was comparable to the Control group. In contrast, MDA levels were not considerably different among the groups (P = 0.217). The RhoA translocation ratio was not significantly different among the groups (P = 0.668), whereas MYPT1 phosphorylation in the Statin group was significantly lower than in the DM group (P = 0.030), and similar to the Control group. Expression of α-SMA in the Statin group was higher than in the DM group (P<0.001), and comparable to the Control group. Chronic statin treatment alone showed anti-oxidative effects and helped to restore the erectile mechanism, but did not lead to the full recovery of erectile function in STZ-induced DM rats. Therefore, combination therapy rather than a single agent should be the preferred treatment strategy for DM-associated erectile dysfunction, especially in the setting of severe diabetes.

Stance Stability Analysis of below Fifty Years Age Post-Stroke Hemiplegic Patients by Stabilometric Method

In hemiplegia, caused by cerebrovascular accident or stroke, one-half of a patient's body is paralyzed. Post-stroke hemiplegic survivors have an increased risk of falling and hip fractures, leading to decreased physical activity, social deprivation and eventually, loss of independence. Balance deficits after stroke comprise reduced postural stability during quiet standing and delayed and less coordinated responses to both self-induced and external balance perturbations. Gait deficits include reduced propulsion at push-off, decreased hip and knee flexion during the swing phase, and reduced stability during the stance phase. This paper sheds lights on a comparative study on the stance stability between post-stroke hemiplegic patients group (age 28-50 yrs) and age-matched normal control group, using a force plate, also termed as stabilometer. Similar studies have rarely been performed in Indian health care system concerning the rehabilitation of post stroke hemiplegic patients. This research paper aims to quantify and assess the postural steadiness of 12 post stroke hemiplegic patients compared to age-matched normal control group (18 normal subjects) using standard COP (Centre of pressure) based parameters and identify the statistically significant variables using ANOVA test. The results of this study will help researchers and medical professionals to evaluate statistically significant COP-based parameters and clinically correlate them with static balance of hemiplegic patients.

Symbol Recurrence Plots based resting-state eyes-closed EEG deterministic analysis on amnestic mild cognitive impairment in type 2 diabetes mellitus

This paper proposes a new Recurrence Plots method—Symbol Recurrence Plots (SRP), and uses Determinism of SRP (SRP_DET) to quantify the determinism of EEG. The performances, including the effects of weighting coefficients and signal to noise ratios of the SRP are evaluated by using double kinetics Neural Mass Model. The simulation analysis illustrates that SRP had better performances than Permutation patterns Recurrence Plots (PRP). Then, the dynamic characteristics of resting-state eyes-closed EEG of amnestic MCI group and age-matched normal control group in T2DM are analyzed. The results show that SRP_DET of aMCI group has significantly higher values at 12 electrodes, which indicates an increase of EEG regularity in the temporal and occipital regions, but PRP_DET values only at one electrode C4. Correlation analysis shows that SRP_DET is strictly negative correlated to MoCA and memory functions at electrodes P4, whereas PRP_DET is not found to be correlated. Therefore, SRP_DET is suggested to be an effective index to understand the deterministic characteristics of cognitive impairment in T2DM.

Socio-cultural context of eating disorders in Poland.

BackgroundThe goal of this study was to assess the relationship between sociocultural factors and clinical eating disorders during the intensive process of Westernisation in Poland that occurred after 1989. The study population included girls diagnosed with an eating disorder according to DSM-IV criteria (n = 47 anorexia nervosa restrictive type [ANR], n = 16 anorexia binge/purge type [ANBP], n = 34 bulimia nervosa [BN], n = 19 eating disorder not otherwise specified [EDNOS]) who received consultation for the first time between 2002 and 2004 in the Department of Clinical Child and Adolescent Psychiatry, University Hospital, Kraków, Poland. The study included an age-matched normal control group [NOR] of 85 schoolgirls from Kraków.MethodsRelationships between two given qualitative features were investigated using the chi-square test or Fisher’s exact test. Correspondence analysis was applied to graphically explore the relationship. The Kruskal-Wallis test with the Bonferroni was performed to compare quantitative results across groups.ResultsObjective sociodemographic variables and responses to the 62-item Questionnaire of Socio-cultural Context were measured. The mothers of ANBP and BN patients were less professionally active than mothers of ANR patients and NOR subjects. Subjective socio-cultural factors were more relevant for the BN group than the ANR group. Questionnaire responses in the ANBP group were more similar to those in the BN group than to those in the ANR group. The most unambiguous and specific characteristic of the ANR group was a sense of belonging to the middle class. Variables that differentiated the BN group from the NOR group included the importance attached to thinness treated as an expression of power and control over one’s self, as well as a multifaceted negative evaluation of one’s own family, including a negative assessment of the position of women and parental lack of concern for appearance and principles of nutrition. All patients, regardless of diagnosis, identified with other people with similar problems and considered anorexia and bulimia to be a major issue of their generation and social environment.ConclusionsThe results of this first in Poland exploratory study of socio-cultural context of eating disorders indicate the importance of both objective and subjective socio-cultural factors in eating disorders in the group studied.

Post-operative quality of life in children with severe perthes disease: differences to matched controls and correlation with clinical function.

The diagnosis of Legg-Calvé-Perthes disease (LCPD) has a considerable influence on the daily life of the patients with restrictions in their leisure time activities. This might influence their mood. Until now this aspect of the disease has been neglected. Therefore the objective of the study was to evaluate the health related quality of life (HRQoL) of children with severe LCPD who had an extensive surgery with pelvic/femoral osteotomy. The KIDSCREEN-10 and the modified Modified Harris Hip Score (mHHS) -questionnaire were administered to 17 children (16 boys and 1 girl) aged 5 to 11 years at the time of surgery. Analyses of mHHS were made preoperatively and at the time of the follow-up examination at least 2 years postoperatively. KIDSCREEN-analyses were made postoperatively. The follow-up results were compared to an age-matched normal control group. Correlations were computed between KIDSCREEN-10 and mHHS pre- and post-operatively. The postoperative calculated KIDSCREEN-10-T-value [70.2 (SD 12.7)] was higher than the mean T-value of the control-group [56.6 (SD 10.4)]. The mHHS improved from 54.4 (SD 19.9) to a score of 99.5 (SD 1.5) postoperatively. A strong correlation was found between the preoperative mHHS and the postoperative KIDSCREEN-10-T-value (Spearman’s-rho 0.67, P=0.003). After containment improving surgery and a mean follow-up period of 4.2 years the HRQoL-status is even better compared with a healthy age-matched control group. As well an excellent clinical function could be achieved.

Cubital Subchondral Joint Space Width and CT Osteoabsorptiometry in Dogs With and Without Fragmented Medial Coronoid Process

To evaluate subchondral joint space width measurements (SJSW) and CT-osteoabsorptiometry (CTOAM) measurements in the elbow of dogs with naturally occurring fragmented medial coronoid process (FMCP) preoperatively and 6 months postoperatively, and to compare these to normal dogs. Prospective randomized clinical trial. Large breed dogs <1 year of age (n = 15). Arthroscopic FMCP debridement was performed, followed by randomization to a proximal ulnar ostectomy with IM pin (PUO). CTs were performed pre-operatively and 6 months post-operatively. CTOAM and SJSW measurements were acquired in 7 locations within the joint and compared to an age-matched normal control group. Pearson correlation was performed on SJSW and CTOAM measurements. A linear mixed model determined the effect of disease and treatment on SJSW and CTOAM measurements. Fifteen dogs (28 elbows) with FMCP participated (11 arthroscopic FMCP removal, 17 with additional PUO). Data were normally distributed. Pearson correlation between CTOAM and SJSW measurements showed moderate to strong negative correlation in the control dogs. Preoperatively, affected elbows had lower medial compartment and higher lateral coronoid process CTOAM values than normal elbows. After treatment, CTOAM values of the medial compartment increased to normal. Treatment with PUO did not affect SJSW or CTOAM. Our data agree with these previous studies suggesting lower subchondral plate mineralization in dogs affected by FMCP. Arthroscopy may result in higher CTOAM values secondary to increased loading.

Abstract 7: Berg Interrogative Biology™ platform unravels novel biomarkers FLNB and LY9 in combination with PSA enhances specificity in serum of patients with prostate cancer.

Abstract Prostate Specific Antigen (PSA) test is the predominant screening test for prostate cancer. Utility is limited by the low predictive power to differentiate patients with indolent tumors from aggressive disease with potential for metastasis. Identification of potential biomarkers to increase prediction of patient population with propensity for progression to metastatic disease remains the overarching unmet need in prostate cancer screening. This study reports the identification of a panel of potential biomarkers using the Berg Interrogative Biology™ platform, a novel non-hypothesis driven approach to characterize disease specific molecular signatures for the identification of physiological drivers of disease etiology. Filamin B (FLNB) and lymphocyte antigen 9 (LY9) were two of several markers identified from a high confidence causal network of prostate cancer model using the Berg Interrogative Biology™ platform. Both FLNB and LY9 were validated in a small case-control retrospective study in human serum samples of patients with prostate cancer and age-matched normal controls. The utility of FLNB and LY9 as potential biomarkers in prostate cancer was determined by comparing the serum levels to that of PSA to establish benchmark comparison. Statistically significant elevation of the PSA, FLNB, and LY9 concentrations was detected in the prostate cancer group compared to the age-matched normal control group. Statistical analyses were performed to determine the sensitivity and specificity of the molecular markers by ROC curve analysis. The predictive power of FLNB or LY9 alone was comparable to that of the PSA test. The combination of FLNB and LY9 with PSA out-performed PSA alone with AUC=0.975 in the study. The study provides data in support of FLNB and LY9 as biomarkers with potential to improve screening outcomes when used in combination with PSA. Efforts are currently underway in large patient cohorts to validate the clinical utility of FLNB and LY9 as candidate biomarkers for use in the screening of prostate cancer with correlate to the Gleason score to enable more instructive data to the practitioner. Citation Format: Rangaprasad Sarangarajan, Joyce Chan, Eric Grund, Vivek K. Vishnudas, Shen Luan, Viatcheslav R. Akmaev, Niven R. Narain. Berg Interrogative Biology™ platform unravels novel biomarkers FLNB and LY9 in combination with PSA enhances specificity in serum of patients with prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 7. doi:10.1158/1538-7445.AM2013-7

NeuroQuant® Revealed Hippocampal Atrophy in a Patient With Traumatic Brain Injury

NeuroQuant® Revealed Hippocampal Atrophy in a Patient With Traumatic Brain Injury

Chronic macular edema associated with extrafoveal vitreoretinal traction.

To describe an association between extrafoveal vitreoretinal traction and chronic macular edema, either diffuse (DiME) or cystoid (CME), by the use of optical coherence tomography (OCT). Charts and OCT findings of two patients with persistent DiME or persistent DiME accompanied by CME, both associated with extrafoveal vitreous traction membranes were analyzed. Excluded were eyes that either had another vitreoretinopathy that could affect the analysis, had undergone pars plana vitrectomy or that had been treated by intravitreal medications. An age-matched normal control group for OCT (n=12) allowed for the quantification of the normal macular thicknesses. One patient (one eye) following perforating ocular injury and one patient (one eye) of idiopathic origin, both with chronic macular edema refractive to conventional treatment, were found to be associated with extrafoveal vitreoretinal traction in each eye. Retinal edema that was underlying the traction site in each eye was in continuum with the central macular edema, thus manifesting as diffuse macular edema. The automatic central 6-radial lines program in the OCT enabled the detection of the traction site in one eye, while in the other eye the diagnosis was achieved only with the additional use of the Line group program. Chronic diffuse macular edema might be related to extrafoveal vitreoretinal traction. Careful search with the diverse OCT programs should be made in order to detect extrafoveal traction sites. Further studies and a larger cohort are required to compare the efficacy of early vitrectomy or pharmacologic vitreolysis versus the current therapeutic approaches in these situations.

Association of Quantitative and Qualitative Abnormalities of Von Willebrand Factor and Risk of Death In Hemodialysis Patients

AbstractAbstract 2217In order to evaluate the possible role of abnormalities of von Willebrand factor in the hemostatic defects seen in indivdiuals with chronic kidney disease (CKD), a cohort study was performed evaluating pre- and post-dialysis levels of von Willebrand factor (VWF), VWF multimer profiles and levels of its cleaving protease, ADAMTS-13. There were 57 subjects (31 males, 26 females) enrolled with CKD with a mean age of 75 years (range 60 – 90). Subjects with known vascular disease were recruited; 49 (86%) had documented ischemic heart disease, 16 (29%) had cerebrovascular disease and 17 (31%) had peripheral vascular disease. A little over half had diabetes mellitus (30 subjects or 54%), 37 (67%) were on antiplatelet therapy and 7 (13%) were chronically anticoagulated with warfarin. Blood samples were drawn immediately pre- and again post-dialysis and all results were compared with a group of age-matched normal controls (Table 1). As has been previously reported, VWF antigen levels (VWF:Ag) and VWF functional activity as measured by the ristocetin cofactor assay (VWF:RCo) were higher in the pre-dialysis samples compared with controls, and both levels were increased even further following dialysis. Additionally, the percentage of high molecular weight VWF multimers (% HMWM) were significantly increased in the pre-dialysis samples compared with controls. This is a novel finding, and the level of % HMWM seen in the subjects is similar to what has been reported in individuals with Thrombotic Thrombocytopenic Purpura (TTP). This difference decreased following dialysis, potentially due to the effect of shear stress on VWF and the resultant proteolytic processing, however still remained significantly higher when compared with controls. ADAMTS-13 functional activity was lower in the subjects compared with controls, providing a possibly explanation for the increase in % HMWM. IL-6 levels are higher in subjects compared with controls. IL-6, which is an inflammatory cytokine known to be increased in patients with CKD, has been previously reported as a marker of inactivation of ADAMTS-13. Two years after enrollment, follow up of the subjects revealed that 22 had died, 17 from documented cardiovascular events. Higher VWF levels at the time of enrollment significantly correlated with risk of death (p=0.041) during the study period. The increase in % HMWM suggests that a “TTP-like phenotype” may also be playing a role. Taken together, these data suggest that both quantitative and qualitative abnormalities of VWF contribute to the risk of thrombotic death in chronic kidney disease.Table 1Controls n=30Pre-Dialysis n=56Post-Dialysis n=56P value (ANOVA)Mean VWF:Ag IU/mL (range)1.39 (0.55–2.72)2.26 (0.64–4.71)2.70 (0.90–5.28)<0.001Mean VWF:RCo IU/mL (range)1.00 (0.59–1.43)2.03 (0.53–4.22)2.16 (0.59–3.98)<0.001Mean HMWM (%) (range)12 (4–20)18 (6–30)16 (4–29)<0.001Mean ADAMTS-13 IU/mL (range)1.10 (0.60–1.51)0.84 (0.44–1.29)0.91 (0.49–1.45)0.001Mean IL-6 pg/mL (range)2.43 (0.10–10)19 (0.24–371)20 (0.81–286)<0.001 Disclosures:No relevant conflicts of interest to declare.

Menorrhagia Impact Questionnaire: assessing the influence of heavy menstrual bleeding on quality of life

Objective:Menorrhagia, or heavy menstrual bleeding (HMB), has a negative impact on women’s quality of life (QOL). The objective was to develop, validate, and assess the performance of a disease-specific patient-reported outcome (PRO) measurement instrument for HMB (the Menorrhagia Impact Questionnaire [MIQ]).Research design and methods:The MIQ was designed to measure the effect of HMB on a woman’s self-assessment of menstrual blood loss (MBL), limitations in social/leisure activities, physical activities, and ability to work. Meaningfulness of these observed MBL changes were also measured. The development and psychometric validation of the MIQ was performed utilizing data from a long-term safety study of tranexamic acid (Lysteda*Lysteda is a registered trade name of Ferring Pharmaceuticals Inc., Parsippany, NJ, USA.), with comparison to an age-matched normal control group recruited from the general population. Performance of the MIQ was also evaluated using data from a six-cycle, randomized, double-blind, clinical study of tranexamic acid for the treatment of HMB. Correlations and sensitivity of each pertinent MIQ item to the treatment-induced changes in MBL were assessed, and the minimally important differences (MID) for the individual MIQ items were determined.Results:The psychometric properties of the MIQ were fully validated. Correlations between individual MIQ items and changes in MBL were statistically significant (p < 0.001). A clear differentiation between tranexamic acid and placebo groups confirmed sensitivity of the MIQ and its ability to detect treatment-induced changes in MBL. MIDs were estimated for the individual MIQ items, with sensitivities and specificities in the 64–79% and 63–82% ranges using receiver operating characteristic (ROC) curve analyses, respectively. MIDs were found to be equal to or greater than 0.5. Statistically significant treatment differences were also observed for the proportions of subjects achieving at least 1-point improvement in MIQ scores.Conclusion:The MIQ contains validated constructs important to women with HMB.Clinical trial registration: NCT00113568 and NCT00386308 (ClinicalTrials.gov ID)Trial registration: ClinicalTrials.gov identifier: NCT00113568.Trial registration: ClinicalTrials.gov identifier: NCT00386308.

Autonomic Dysfunction in Normal Tension Glaucoma: The Short-term Heart Rate Variability Analysis

The purpose of this study was to investigate the dysfunction of autonomic control that may be a contributing factor in normal tension glaucoma (NTG) by showing the short-term heart rate variability in NTG patients. Newly diagnosed NTG patients and an age-matched normal control group were enrolled in this prospective study. Blood pressure was obtained and the electrocardiogram was monitored for 5 minutes after 30-minute rest in a supine position. Electrocardiographic signals were transferred to a heart rate analyzer. The time and frequency domain parameters of heart rate variability were analyzed between two groups. In all, 77 NTG patients and 30 healthy controls were included in the study. There were no significant differences between NTG and controls with respect to age, sex, and a hypertensive history, heart rate, systolic pressure, and diastolic pressure. NTG patients showed a significant reduction in the standard deviation of the mean of qualified normal-to-normal intervals in comparison with controls (27.64+/-10.90 vs. 36.22+/-10.21, P=0.041). Low-frequency values in NTG patients were statistically lower than in healthy controls (P=0.001) and the low-frequency/high-frequency ratio was significantly higher in the NTG group (P=0.000). Our study results showed that the dysfunction of an autonomic control is associated with NTG patients.

Estimation of global aortic pulse wave velocity by flow‐sensitive 4D MRI

The aim of this study was to determine the value of flow-sensitive four-dimensional MRI for the assessment of pulse wave velocity as a measure of vessel compliance in the thoracic aorta. Findings in 12 young healthy volunteers were compared with those in 25 stroke patients with aortic atherosclerosis and an age-matched normal control group (n = 9). Results from pulse wave velocity calculations incorporated velocity data from the entire aorta and were compared to those of standard methods based on flow waveforms at only two specific anatomic landmarks. Global aortic pulse wave velocity was higher in patients with atherosclerosis (7.03 +/- 0.24 m/sec) compared to age-matched controls (6.40 +/- 0.32 m/sec). Both were significantly (P < 0.001) increased compared to younger volunteers (4.39 +/- 0.32 m/sec). Global aortic pulse wave velocity in young volunteers was in good agreement with previously reported MRI studies and catheter measurements. Estimation of measurement inaccuracies and error propagation analysis demonstrated only minor uncertainties in measured flow waveforms and moderate relative errors below 16% for aortic compliance in all 46 subjects. These results demonstrate the feasibility of pulse wave velocity calculation based on four-dimensional MRI data by exploiting its full volumetric coverage, which may also be an advantage over standard two-dimensional techniques in the often-distorted route of the aorta in patients with atherosclerosis.

The Relative Atrial Index (RAI)—A Novel, Simple, Reliable, and Robust Transthoracic Echocardiographic Indicator of Atrial Defects

The detection of atrial septal defects (ASDs) and other shunts is sometimes difficult on transthoracic echocardiography. In addition, the quantitative assessment of right-heart volume loading as an indicator of significant shunting can be difficult, with subjective estimation commonly used. Thus, the initial aim of this study was to test the accuracy of a simple, noninvasive index using atrial area dimensions to detect the presence of an ASD. Subsequently, the index was used to assess the degree of normalization and remodeling of atrial size following percutaneous ASD device closure. The relative atrial index (RAI) was derived from standard apical 4-chamber views as right atrial area divided by left atrial area. RAI was calculated in patients with previously diagnosed secundum atrial defects (n=219) with no concomitant lesions and then compared with those calculated in age-matched controls (n=219). 101 of the 219 patients with secundum atrial defects underwent percutaneous device closure. Measurements were obtained before and 1 day after percutaneous closure as well as in the early (mean, 124 days) and late (mean, 390 days) stages of follow-up. The mean RAI in patients with ASDs (1.23+/-0.23) was significantly higher than that in the age-matched normal control group (0.78+/-0.1) (P<.0001). The mean RAI in patients with ASD was also significantly higher than that in the general population (0.81+/-0.15) (P<.0001). Receiver operating characteristic curve analysis suggested that a nominal RAI cutoff value of >0.92 predicted patients with ASDs versus matched controls with 99.1% sensitivity and 90.5% specificity. After percutaneous closure, significant atrial remodeling occurred immediately, with a reduction in the mean RAI at day 1 to 0.93+/-0.16 (P<.0001) and complete normalization at early follow-up to 0.81+/-0.12. The RAI, a novel and simple transthoracic parameter, reliably identifies patients with possible atrial shunting. The resolution of right atrial enlargement occurs remarkably early after percutaneous ASD closure, as demonstrated by this novel parameter.

Alteration of Glial Fibrillary Acidic Proteins Immunoreactivity in Astrocytes of the Spinal Cord Diabetic Rats

Diabetes affects retinal and nervous glial cells, especially the astrocytes. A key indicator of this response is the alteration in the level of intermediate filament glial fibrillary acidic protein (GFAP) and number of GFAP-immunoreactive astrocytes. To date, no study has investigated the effect of diabetes on the distribution of GFAP-immunoreactive astrocytes in the spinal cord. Therefore, the present study investigated the effect of diabetes on the number of GFAP-immunoreactive astrocytes in the gray matter of the spinal cord of streptozotocin-induced diabetic Wistar rats. Animals were divided into six groups (n = 7); 6 weeks and 12 weeks diabetic duration groups and their respective age-matched normal control and sham control groups. Our results demonstrated a significant (P < 0.001) decrease in the number of GFAP-immunoreactive astrocytes in different areas of the spinal cord sections of the 6 weeks and 12 weeks long diabetic rats when compared with the spinal cord of normal and sham control groups of comparable age. The mean percentage in total number of GFAP-immunoreactive astrocytes in the whole gray matter areas of the spinal cord of the 6 and 12 weeks diabetic groups were approximately 28% and 41% less than control groups. Furthermore, the 12 weeks diabetic group showed a significant (P < 0.001) reduction in the number of GFAP-immunoreactive astrocytes when compared with the 6 weeks diabetic animals. These results suggest that the induction of diabetes is associated with a reduction in GFAP-positive astrocytes in the spinal cord, which may affect the functional support and role of astrocytic cells in the nervous tissue. This in turn may contribute to the pathological changes associated with diabetic state in the central nervous system.

Respiratory Muscles and Dyspnea in Obese Nonsmoking Subjects

To our knowledge no data have been reported on the contribution to acute increase in dyspnea by the respiratory muscles in obese nonsmoking subjects. To better focus on this topic, we studied seven obese subjects and an age-matched normal control group, assessing baseline pulmonary function, breathing pattern, esophageal pressure (Pes), and gastric (Pga) and transdiaphragmatic (Pdi) pressures. Pes was also recorded during a sniff maneuver (Pessn). During a hypercapnic rebreathing test we recorded inspiratory swing in Pes (Pessw), expiratory changes in Pga, and inspiratory swings in Pdi (Pdisw). Change in inspiratory capacity was considered the mirror image of end-expiratory lung volume (EELV). Dyspnea was assessed by a modified Borg scale. Under control conditions, patients exhibited a reduced expiratory reserve volume and intrinsic positive end-expiratory pressure (PEEPi). At the end of hypercapnic stimulation, compared with controls our obese subjects exhibited greater respiratory frequency (Rf), shorter expiratory time, greater Pessw, and lower Pdisw. Increases in EELV and PEEPi were found in the obese subjects but not in controls. Changes in Borg correlated with changes in PETCO2, VE, Pessw (%Pessn), and Pdisw to a greater extent in patients than in controls. Stepwise regression analysis indicated the amount of variability in Borg that was predicted by both Pdisw (r2 = 0.31, p < 0.0004), and Pessw (%Pessn) (r2 = 0.09, p < 0.005) in controls, and by Pessw (%Pessn) (r2 = 0.40, p < 0.00001) in obese subjects. We conclude that the rib cage muscles contributed to dyspnea to a greater extent in this subset of obese subjects.