Disease-free Controls Research Articles

Psoriatic arthritis is associated with adverse body composition predictive of greater coronary heart disease and type 2 diabetes propensity - a cross-sectional study.

ObjectivesTo compare body composition in PsA with metabolic disease free (MDF) controls and type 2 diabetes and assess body-composition predicted propensity for cardiometabolic disease.MethodsDetailed MRI body composition profiles of 26 PsA participants from the IMAPA study were compared with 130 age, sex and BMI-matched MDF controls and 454 individuals with type 2 diabetes from UK Biobank. The body-composition predicted propensity for coronary heart disease (CHD) and type 2 diabetes was compared between PsA and matched MDF controls.ResultsPsA participants had a significantly greater visceral adipose tissue (VAT) volume [mean 5.89 l (s.d. 2.10 l)] compared with matched-MDF controls [mean 4.34 l (s.d. 1.83 l)] (P <0.001) and liver fat percentage [median 8.88% (interquartile range 4.42–13.18%)] compared with MDF controls [3.29% (1.98–7.25%)] (P <0.001). These differences remained significant after adjustment for age, sex and BMI. There were no statistically significant differences in VAT, liver fat or muscle fat infiltration (MFI) between PsA and type 2 diabetes. PsA participants had a lower thigh muscle volume than MDF controls and those with type 2 diabetes. Body composition-predicted propensity for CHD and type 2 diabetes was 1.27 and 1.83 times higher, respectively, for PsA compared with matched-MDF controls.ConclusionIndividuals with PsA have an adverse body composition phenotype with greater visceral and ectopic liver fat and lower thigh muscle volume than matched MDF controls. Body fat distribution in PsA is more in keeping with the pattern observed in type 2 diabetes and is associated with greater propensity to cardiometabolic disease. These data support the need for greater emphasis on weight loss in PsA management to lessen CHD and type 2 diabetes risk.

Distinct circulating cytokine levels in patients with angiography-proven coronary artery disease compared to disease-free controls

Abstract Background Systemic inflammation has a critical role in the development of coronary artery disease (CAD). Identification of inflammatory pathways may provide a platform for novel therapeutic approaches. Purpose We sought to determine whether there are differences in circulating cytokine profiles between patients with CAD and disease-free controls. Methods Study population consisted of 458 patients who underwent diagnostic invasive coronary angiography for clinical indications. Altogether 312 patients had angiographically significant CAD whereas 146 had no angiographically-detected coronary atherosclerosis. We measured the serum concentrations of 48 circulating cytokines. Results Patients with CAD had increased levels of interleukin-1 receptor antagonist (IL-1-RA), interleukin-2 receptor alpha (IL-2Rα), IL-3, IL-4, IL-6, IL-9, IL-10, IL-16, IL-17, IL-18, granulocyte-macrophage colony-stimulating factor (GM-CSF), platelet-derived growth factor-BB (PDGF-BB), macrophage inflammatory protein-1-beta (MIP-1-β), tumor necrosis factor-alpha (TNF-α), TNF-β, cutaneous T-cell-attracting chemokine (CTACK), growth regulated oncogene alpha (GRO-α), hepatocyte growth factor (HGF), interferon alpha-2 (IFNα-2), leukemia inhibitory factor (LIF), macrophage colony-stimulating factor (M-CSF), macrophage migration inhibitory factor (MIF), monokine induced by gamma interferon (MIG), beta-nerve growth factor (β-NGF), stem cell factor (SCF) and stromal cell-derived factor 1 alfa (SDF1α). On a logistic multivariate regression model adjusted with age, sex, hypertension and treatment for diabetes, increased levels of IL-4 (p=0.027, OR 1.090), IL-9 (p=0.000, OR 1.013), IL-17 (p=0.011, OR 1.005), CTACK (p=0.008, OR 1.001), MIP-1-β (p=0.004, OR 1.006), GRO-α (p=0.008, OR 1.004), TNF-α (p=0.019, OR 1.011) were independently associated with atherosclerosis. Conclusions Patients with CAD have distinct circulating cytokine profiles compared to disease-free controls. Based on these findings, certain cytokines may have a pivotal role in the development of atherosclerotic cardiovascular disease and cytokine-mediated pathway appear as a promising target for cardiovascular drug development. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): The Finnish Medical Foundation, Helsinki, Finland; The Finnish Foundation for Cardiovascular Research, Helsinki, Finland

Challenges and opportunities for using national animal datasets to support foot-and-mouth disease control.

National level databases of animal numbers, locations and movements provide the essential foundations for disease preparedness, outbreak investigations and control activities. These activities are particularly important for managing and mitigating the risks of high-impact transboundary animal disease outbreaks such as foot-and-mouth disease (FMD), which can significantly affect international trade access and domestic food security. In countries where livestock production systems are heavily subsidized by the government, producers are often required to provide detailed animal movement and demographic data as a condition of business. In the remaining countries, it can be difficult to maintain these types of databases and impossible to estimate the extent of missing or inaccurate information due to the absence of gold standard datasets for comparison. Consequently, competent authorities are often required to make decisions about disease preparedness and control based on available data, which may result in suboptimal outcomes for their livestock industries. It is important to understand the limitations of poor data quality as well as the range of methods that have been developed to compensate in both disease-free and endemic situations. Using FMD as a case example, this review first discusses the different activities that competent authorities use farm-level animal population data for to support (1) preparedness activities in disease-free countries, (2) response activities during an acute outbreak in a disease-free country, and (3) eradication and control activities in an endemic country. We then discuss (4) data requirements needed to support epidemiological investigations, surveillance, and disease spread modelling both in disease-free and endemic countries.

Age‐specific prevalence and determinants of depression in long‐term breast cancer survivors compared to female population controls

BackgroundDepression is more prevalent in breast cancer (BC) survivors than in the general population. However, little is known about depression in long‐term survivors. Study objectives were: (1) to compare the age‐specific prevalence of depressive symptoms (a) in BC survivors vs female population controls, (b) in disease‐free BC survivors vs BC survivors with self‐reported recurrence vs controls, and (2) to explore determinants of depression in BC survivors.MethodsAbout 3010 BC survivors (stage I‐III, 5‐16 years post‐diagnosis), and 1005 population controls were recruited in German multi‐regional population‐based studies. Depression was assessed by the Geriatric Depression Scale‐15. Prevalence of mild/severe and severe depression only were estimated via logistic regression, controlling for age and education. Multinomial logistic regression was used to explore determinants of mild and severe depression.ResultsCompared with population controls, BC survivors were more likely to report mild/severe depression (30.4% vs 23.8%, p = .0003), adjusted for age and education. At all age groups <80 years, prevalence of both mild/severe and severe depression only was significantly higher in BC survivors, while BC survivors ≥80 years reported severe depression less frequently than controls. BC survivors with recurrence reported significantly higher prevalence of mild/severe depression than disease‐free survivors and controls, but prevalence in disease‐free survivors and controls was comparable. Age, income, living independently, recurrence, and BMI were significant determinants of mild depression in BC survivors. Age, education, employment, income, recurrence, and BMI were significant determinants of severe depression.ConclusionsLong‐term BC survivors <80 years report significantly higher prevalence of depressive symptoms than controls, which might be explained by recurrence and individual factors. The findings suggest that depression in BC survivors is common, and even more after BC recurrence. Clinicians should routinize screening and normalize referral to psychological care.

Association of HOTAIR (rs920778 and rs1899663) and NME1 (rs16949649 and rs2302254) gene polymorphisms with breast cancer risk in India

Until now, no study has reported the combined effect of genetic variants of HOTAIR and NME1 towards breast cancer (BC) pathogenesis. Hence, the aim of the present study is to determine the risk of breast cancer development with HOTAIR (rs920778 C>T and rs1899663 G>T) and NME1 (rs16949649 T>C and rs2302254 C>T) genetic polymorphisms in the Indian population for the first time. To investigate the genetic association of these four SNPs, we conducted a population-based case-control study involving 1011 subjects (502 histologically confirmed BC patients and 509 disease-free controls) using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. HOTAIR rs920778 TC genotype elevated the risk of BC (OR=1.39, 95% CI=1.06-1.83, p=0.018) and individuals carrying the mutant allele (T) of rs1899663 had increased BC risk (OR=1.23, 95% CI=1.02-1.47, p=0.026). The presence of the NME1 rs16949649 CC genotype increased the risk of BC (OR=1.76, 95% CI=1.15-2.71, p=0.009). Moreover, the HOTAIR rs920778 variant (TC+CC) increased the risk of BC in pre-menopausal women (OR=5.86; p<0.0001). Women carrying 2 or 3 mutant alleles for the investigated SNPs were observed to have an elevated risk of BC. The results of the present study highlight the presence of significant associations between NME1 rs16949649 and HOTAIR (rs920778 and rs1899663) polymorphisms and breast cancer development in Indian women.

Association of TCF7L2 rs7903146 Polymorphism with the Risk of Type 2 Diabetes Mellitus (T2DM) Among Kurdish Population in Erbil Province, Iraq.

The genetic predispositions responsible for developing type 2 diabetes mellitus (T2DM) in the Middle East are poorly understood. The rs7903146 single nucleotide polymorphism (SNP) located in transcription factor 7-like-2 (TCF7L2) gene has been recognized to have a vital role in the development of T2DM disorder. The current study is the first to have researched the possible association between TCF7L2 rs7903146 SNP and T2DM among Kurdish population in Kurdistan region of Iraq. The study included 212 participants, half of them were T2DM patients, and the other half were disease-free and normoglycemic controls. Genotyping was performed by using a high throughput cost and time effective tetra-primer amplification refractory mutation system-polymerase chain reaction (Tetra ARMS-PCR) assay. The rs7903146 genotypic frequencies for CC, CT and TT were 24.5%, 69.8%, and 5.7% in T2DM group respectively, and for the controls were 45.3%, 50.9%, and 3.8% respectively. The frequency of CT genotype was found significantly higher in the cases when compared to the controls (OR = 2.53, 95% CI 1.40-4.57, P value < 0.0019), which indicated that the genotype CT showed risk with diabetes. The T allele showed a high significant frequency in the patients compared to the controls (OR = 1.65, 95% CI 1.10-2.47, P value = 0.014). Our findings demonstrated that the T allele could be a risk factor for increasing the susceptibility of T2DM incidence among the Iraqi Kurdish population.

Transcriptomic identification of TMIGD1 and its relationship with the ileal epithelial cell differentiation in Crohn's disease.

Crohn's disease (CD) is a complex and multifactorial illness. There are still considerable gaps in our knowledge regarding its pathophysiology. A transcriptomic approach could shed some light on little-known biological alterations of the disease. We therefore aimed to explore the ileal transcriptome to gain knowledge about CD. We performed whole transcriptome gene expression analysis on ileocecal resections from CD patients and inflammatory bowel disease-free controls, as well as on a CD-independent cohort to replicate selected results. Normalized data were hierarchically clustered, and gene ontology and the molecular network were studied. Cell cultures and molecular methods were used for further evaluations. Genome-wide expression data analysis identified a robust transmembrane immunoglobulin domain-containing 1 (TMIGD1) gene underexpression in CD tissue, which was even more marked in inflamed ileum, and which was replicated in the validation cohort. Immunofluorescence showed TMIGD1 to be located in the apical microvilli of well-differentiated enterocytes but not in intestinal crypt. This apical TMIGD1 was lower in the noninflamed tissue and almost disappeared in the inflamed mucosa of surgical resections. In vitro studies showed hypoxic-dependent TMIGD1 decreased its expression in enterocyte-like cells. The gene enrichment analysis linked TMIGD1 with cell recovery and tissue remodeling in CD settings, involving guanylate cyclase activities. Transcriptomics may be useful for finding new targets that facilitate studies of the CD pathology. This is how TMIGD1 was identified in CD patients, which was related to multiciliate ileal epithelial cell differentiation.NEW & NOTEWORTHY This is a single-center translational research study that aimed to look for key targets involved in Crohn's disease and define molecular pathways through different functional analysis strategies. With this approach, we have identified and described a novel target, the almost unknown TMIGD1 gene, which may be key in the recovery of injured mucosa involving intestinal epithelial cell differentiation.

Identification of candidate microRNA markers of endometriosis with the use of next-generation sequencing and quantitative real-time polymerase chain reaction

To identify novel candidate diagnostic microRNA (miRNA) markers of endometriosis by means of an unbiased search with confirmation by means of targeted polymerase chain reaction (PCR). Retrospective cohort. University teaching hospitals. Women with endometriosis and control women, confirmed with the use of laparoscopy. Diagnostic laparoscopy and blood sample. Next-generation sequencing (NGS) and quantitative real-time PCR (qRT-PCR). Candidate miRNAs differentially expressed in women with endometriosis compared with control women were identified by means of NGS and selected for qRT-PCR. Plasma samples from another cohort of women with surgically confirmed endometriosis (n = 53) and disease-free control women (n = 53) were checked for hemolysis using spectrophotometry and the ratio of miR-23a and miR-451 by means of qRT-PCR. MicroRNA signatures were quantified by means of qRT-PCR in hemolysis-free plasma samples ofcase subjects (n = 25) and control subjects (n = 28) with the use of miRcury LNA miRNA. Circulating levels of eight miRNAs (miR-199a-3p, miR-143-3p, miR-340-5p, let-7b-5p, miR-21-5p, miR-17-5p, miR-20a-5p, and miR-103a-3p) were significantly lower in case subjects compared to control subjects. The sensitivity and specificity for individual miRNAs ranged from 0.36 to 1.00 and from 0.43 to 1.00, respectively, but when combined produced sensitivity and specificity of 0.92 and 0.86 with positive (PPV) and (NPV) predictive values of 0.85 and 0.92, respectively. However, combination of five miRNAs (miR-17-5p, miR-20a-5p, miR-199a-3p, miR-143-3p, and let-7b-5p) produced sensitivity and specificity of 0.96 and 0.79 with PPV and NPV of 0.80 and 0.96, respectively. We conclude that a panel of candidate miRNAs was comparable to laparoscopy in distinguishing between women with endometriosis and control women.

PND16 HEALTHCARE RESOURCE UTILIZATION AND COSTS IN MEDICARE BENEFICIARIES WITH PARKINSON’S DISEASE

Parkinson’s disease (PD) is thought to be the fastest growing cause of neurologic disability in the US. We wanted to estimate its impact on healthcare resource utilization (HCRU) and costs. This retrospective, cross-sectional, matched case-control study was conducted using 2016 data from the 5% Medicare Limited Data Set. Patients ≥65 years with PD (cases) were identified if they had at least one inpatient or two outpatient claims for PD, were enrolled in the Medicare fee-for-service program, and had Part A and B coverage for all of 2016. Patients without PD (disease-free controls) were matched 1:1 to cases by age, gender, race, and geographic region (census regions: Northeast, South, Midwest, West). All-cause healthcare utilization and costs were compared between cases and controls. Descriptive results were reported. A total of 14,689 matched case-control pairs were included in the study sample; mean (SD) age 78 (7.3) years, 42.7% female, 92.1% white with all regions represented (36.7% South, 26.7% Midwest, 20.1% Northeast and 16.4% West). Compared to controls, patients with PD had more outpatient office visits (mean [SD]:16 [15.0] vs. 12 [12.2]), and higher rates of home health (31.1% vs. 10.3%), hospice (4.4% vs. 0.9%), ED (39.4% vs. 23.3%), and inpatient (34.2% vs. 16.9%) use (all p>0.001). Mean (SD) annual all-cause Part A and Part B medical costs were statistically significantly higher in patients with PD than in controls ($94,780 [$220,636] vs. $50,489 [$194,980]) (p<0.001). The majority of costs were for non-ED outpatient services ($81,536 [$213,598] vs. $45,588 [$191,109]) and inpatient services ($12,221 [$25,858] vs. $4,406 [$14,736]) (p<0.001). PD has dramatic effect on HCRU and costs. Based on our data, we estimate the excess annual Medicare expenditure on PD could exceed $40 billion. Therapies that prevent or slow the progression of PD may reduce HCRU and costs in affected populations.

The miR-25-3p/Sp1 pathway is dysregulated in ovarian endometriosis.

ObjectiveThe transcription factor Specificity protein 1 (Sp1) plays important roles in many critical biological functions; however, its expression and underlying functions in endometriosis remain undefined. Bioinformatics has suggested that Sp1 is potentially regulated by miR-25-3p. This study investigated Sp1 and miR-25-3p expression and their interaction during the pathogenesis of endometriosis.MethodsFifteen women with American Fertility Society stage III/IV ovarian endometriosis and 14 disease-free controls were included. Sp1 expression was detected by qPCR, immunohistochemistry, and western blotting. Using both bioinformatics and genetics, we identified that Sp1 was a potential target of miR-25-3p. Then, the relationship between miR-25-3p and Sp1 was investigated by knockdown and overexpression experiments.ResultsSp1 mRNA and protein levels were increased in ectopic and eutopic endometrium compared with normal endometrium samples, with the highest expression in ectopic endometrium samples. In vitro experiments and luciferase reporter assays demonstrated that Sp1 was upregulated when miR-25-3p was depleted and that Sp1 was a direct target of miR-25-3p, respectively.ConclusionsOur study revealed increased Sp1 expression in ovarian endometriosis and subsequently demonstrated that miR-25-3p directly targets Sp1. This suggests a novel miRNA/Sp1 pathway in the pathogenesis of endometriosis, which should be further explored for other potential therapeutic targets.

Association of oral health-related quality of life measures with aggressive and chronic periodontitis.

Evidence suggests that periodontitis has a negative effect on the quality of life of an individual, with increased impacts by greater disease severity. The aim of this study was to assess the association between quality of life and the presence of different severity and forms of periodontitis (aggressive and chronic), compared to a disease-free control group. Four hundred and seventy one study participants were classified according to periodontal diagnosis using the 1999 Consensus Classification into chronic periodontitis (CP), aggressive periodontitis (AgP) and periodontally healthy. Oral health-related quality of life was assessed using the OHIP-14 questionnaire. Outcomes consisted of the prevalence of oral impacts reported occasionally, fairly often or very often (OFOVO) as well as fairly often or very often (FOVO), OHIP-14 total and domain scores. Logistic and linear regression analyses were carried out to test associations between periodontal diagnosis and quality of life outcomes, adjusted for smoking, age, ethnicity and body mass index. Over 90% of periodontitis patients reported at least one oral impact experienced occasionally, fairly often or very often (OFOVO) compared with 53.8% of periodontally healthy controls (P<.001). After adjustment for covariates, significant differences were found between the periodontitis groups and healthy controls for OHIP-14 outcome scores (P<.001) and across all of the OHIP-14 domains (P<.005). These differences were clinically meaningful as they were higher than the measurement errors. No significant differences were identified between AgP and CP in adjusted analysis when comparing OHIP-14 scores. Patients with periodontitis have worse quality of life than periodontally healthy individuals, with differences being clinically meaningful. AgP patients reported worse OHRQoL overall compared to CP patients, but these moderate and meaningful differences were explained through the adjustment process.

Gamma-Synuclein Levels Are Elevated in Peritoneal Fluid of Patients with Endometriosis.

BackgroundThe role of gamma-synuclein (SNCG) has been widely examined in malignant conditions due to its possible role in disease progression, but very little information is available on its theoretical function on endometriosis formation.Material/MethodsBetween January 2016 and December 2016, we collected peritoneal fluid and plasma samples from 45 consecutive female patients, of which 15 were without endometriosis, 15 had minimal to mild endometriosis, and 15 had moderate to severe endometriosis. The statistical power was 0.98. We evaluated SNCG levels in the peritoneal fluid and plasma of patients diagnosed with endometriosis, and we compared them with the levels obtained from disease-free control subjects by using enzyme-linked immunosorbent assay.ResultsSNCG levels were statistically significantly (1.2-fold) higher in the peritoneal fluid of patients with endometriosis compared to controls (p=0.04). We did not find a significant difference between SNCG levels in the plasma of our endometriosis patients and the control group (p=0.086). However, despite previous data showing very limited expression of SNCG in healthy tissues, we found SNCG in the peritoneal fluid of all of the patients in our healthy control group.ConclusionsLevels of SNCG were statistically significantly higher in the peritoneal fluid of patients with endometriosis compared to disease-free controls, which may indicate its possible role the formation and progression of the disease. Moreover, its biological function should be further investigated due to the conflicting results concerning its expression in healthy tissues.

Induced pluripotency and spontaneous reversal of cellular aging in supercentenarian donor cells

Supercentenarians (≥110-year-old, SC) are a uniquely informative population not only because they surpass centenarians in age, but because they appear to age more slowly with fewer incidences of chronic age-related disease than centenarians. We reprogramed donor B-lymphoblastoid cell lines (LCL) derived from a 114-year-old (SC), a 43-year-old healthy disease-free control (HDC) and an 8-year-old with a rapid aging disease (Hutchinson-Gilford progeria syndrome (HGPS)) and compared SC-iPSC to HDC-iPSC and HGPS-iPSCs. Reprogramming to pluripotency was confirmed by pluripotency marker expression and differentiation to 3 germ-layers. Each iPSC clone differentiated efficiently to mesenchymal progenitor cells (MPC) as determined by surface marker expression and RNAseq analysis. We identified supercentenarian and HGPS associated gene expression patterns in the differentiated MPC lines that were not evident in the parental iPSC lines. Importantly, telomere length resetting occurred in iPSC from all donors albeit at a lower incidence in supercentenarian iPSCs. These data indicate the potential to use reprogramming to reset both developmental state and cellular age in the “oldest of the old.” We anticipate that supercentenarian iPSC and their differentiated derivatives will be valuable tools for studying the underlying mechanisms of extreme longevity and disease resistance.

Tumor control of cervical lymph node metastases of unknown primary origin: the impact of the radiotherapy target volume.

Debate on the extent of treatment of neck metastasis of cancer of unknown primary tumors (CUPs) is still ongoing. In two Dutch tertiary referral centers, the post-surgical radiation target volume changed from the bilateral neck including the pharyngeal axis to the unilateral neck only, in the course of the last decade. This study aims to investigate the outcome of patients with CUP before and after de-escalation of post-surgical radiotherapy. Data of two Dutch tertiary referral centers were merged. Disease-free survival (DFS), overall survival (OS), and regional control rate (RCR) of 80 patients diagnosed with CUP (squamous cell and undifferentiated carcinomas) between 1990 and 2009 were retrospectively analyzed. Thirty patients received bilateral neck and pharyngeal axis radiotherapy and 42 patients ipsilateral radiotherapy only. In another eight patients, the postsurgical radiation target volume was expanded to the contralateral neck or to the pharyngeal axis, due to suspicious lesions on imaging. The 5-year DFS, OS and RCR were 60%, 51.2%, and 80%, respectively, in the total patient population. RCR did not differ in patients treated with ipsilateral as compared to bilateral radiotherapy nor did 5-year OS and DFS. No tumors occurred in the pharyngeal axis. In this study, omittingelective treatment of the contralateral neck and pharyngeal axis did not lead to a decrease in locoregional control or survival rates when treating patients with CUP.

CD8+ T cells in HIV control, cure and prevention.

HIV infection can be effectively treated by lifelong administration of combination antiretroviral therapy, but an effective vaccine will likely be required to end the HIV epidemic. Although the majority of current vaccine strategies focus on the induction of neutralizing antibodies, there is substantial evidence that cellular immunity mediated by CD8+ T cells can sustain long-term disease-free and transmission-free HIV control and may be harnessed to induce both therapeutic and preventive antiviral effects. In this Review, we discuss the increasing evidence derived from individuals who spontaneously control infection without antiretroviral therapy as well as preclinical immunization studies that provide a clear rationale for renewed efforts to develop a CD8+ T cell-based HIV vaccine in conjunction with B cell vaccine efforts. Further, we outline the remaining challenges in translating these findings into viable HIV prevention, treatment and cure strategies.

Correlation of Visual Quality of Life With Clinical and Visual Status in Friedreich Ataxia.

The primary objective was to determine the association of patient-reported vision-specific quality of life to disease status and visual function in patients with Friedreich's ataxia (FRDA). Patients with FRDA were assessed with the 25-Item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) along with measures of disease status (ataxia stage) and visual function (low- and high-contrast letter acuity scores). The relations of NEI-VFQ-25 scores to those for disease status and visual function were examined. Scores for the NEI-VFQ-25 were lower in patients with FRDA (n = 99) compared with published disease-free controls, particularly reduced in a subgroup of FRDA patients with features of early onset, older age, and abnormal visual function. The NEI-VFQ-25 captures the subjective component of visual function in patients with FRDA.

Rapid picture naming in Parkinson's disease using the Mobile Universal Lexicon Evaluation System (MULES)

ObjectiveThe Mobile Universal Lexicon Evaluation System (MULES) is a test of rapid picture naming that captures extensive brain networks, including cognitive, language and afferent/efferent visual pathways. MULES performance is slower in concussion and multiple sclerosis, conditions in which vision dysfunction is common. Visual aspects captured by the MULES may be impaired in Parkinson's disease (PD) including color discrimination, object recognition, visual processing speed, and convergence. The purpose of this study was to compare MULES time scores for a cohort of PD patients with those for a control group of participants of similar age. We also sought to examine learning effects for the MULES by comparing scores for two consecutive trials within the patient and control groups. MethodsMULES consists of 54 colored pictures (fruits, animals, random objects). The test was administered in a cohort of PD patients and in a group of similar aged controls. Wilcoxon rank-sum tests were used to determine statistical significance for differences in MULES time scores between PD patients and controls. Spearman rank-correlation coefficients were calculated to examine the relation between MULES time scores and PD motor symptom severity (UPDRS). Learning effects were assessed using Wilcoxon rank-sum tests. ResultsAmong 51 patients with PD (median age 70 years, range 52–82) and 20 disease-free control participants (median age 67 years, range 51–90), MULES scores were significantly slower (worse performance) in PD patients (median 63.2 s, range 37.3–296.3) vs. controls (median 53.9 s, range 37.5–128.6, P = .03, Wilcoxon rank-sum test). Slower MULES times were associated with increased motor symptom severity as measured by the Unified Parkinson's Disease Rating Scale, Section III (rs = 0.37, P = .02). Learning effects were greater among patients with PD (median improvement of 14.8 s between two MULES trials) compared to controls (median 7.4 s, P = .004). ConclusionThe MULES is a complex test of rapid picture naming that captures numerous brain pathways including an extensive visual network. MULES performance is slower in patients with PD and our study suggests an association with the degree of motor impairment. Future studies will determine the relation of MULES time scores to other modalities that test visual function and structure in PD.

ANRIL rs1333049 C/G polymorphism and coronary artery disease in a North Indian population - Gender and age specific associations.

Many studies conducted worldwide substantiate a role of genetic polymorphisms in non-coding regions linked with coronary artery disease (CAD). One such single nucleotide polymorphism (SNP) of a non-coding RNA in the INK4 locus (ANRIL) i.e. rs1333049 C/G in the vicinity of cell cycle regulating genes is documented to have a role in CAD risk. In this study we aimed to determine the association of ANRIL rs1333049 C/G with CAD in a North Indian population. Five hundred disease free controls and 500 CAD patients were genotyped using allele specific ARMS-PCR method. High risk association of rs1333049 was seen in both heterozygous and mutant genotypes (OR=2.883, 95% CI=1.475-5.638 and p=0.002 and OR=6.717, 95% CI=3.444-13.102 and p < 0.001 respectively). Gender stratified analysis revealed risk association in both heterozygous and mutant genotypes in males. However, risk association in the mutant genotype and females was documented. Similarly, risk association was seen in subjects above 40 years of age in heterozygous and mutant genotypes. Similarly, risk association was reported in obese, sedentary lifestyle, positive family history and smoking in the heterozygous and mutant genotype and with diabetes in the mutant GG genotype. The study revealed high risk association of ANRIL rs1333049 with CAD and other risk factors.

Prospective analysis of macular and optic disc changes after non-arteritic anterior ischemic optic neuropathy

To prospectively analyse macular and optic disc changes after the occurrence of non-arteritic anterior ischemic optic neuropathy (NAION) and study possible predictors of final visual outcome. Patients with NAION underwent a complete ophthalmic examination, including spectral-domain optical coherence tomography of the macula and optic nerve head. The examination was repeated 1, 3, 6, 9 and 12 months after onset. Final visual prognosis was evaluated by visual field (VF) and best-corrected visual acuity (BCVA) at the final visit. Data within the NAION group were analysed over the course of the disease and compared to a disease-free control group at each visit. Twenty-two eyes with NAION and 43 eyes from a control group were included. The retinal nerve fiber layer (RNFL) was significantly thicker in NAION eyes than controls at presentation (P=0.00), and significantly decreased during the next 3 months after presentation (P=0.02). The ganglion cell+inner plexiform layer (GCIPL) was thinner in the NAION group throughout the course of the disease (all P<0.05). Although the acute NAION eyes had significantly lower cup/disc ratios and higher neuroretinal and disc sizes (all P=0.00), there were no significant differences between groups from the third month onwards (all P>0.05). The best predictors of BCVA and VF were GCIPL at 3 months of follow-up (r2=0.32; P=0.03) and RNFL at 6 months of follow-up (r2=0.41; P=0.01) respectively. RNFL and optic disc changes occur during the first 3 months after the onset of NAION, whereas GCIPL is affected soon after the onset of symptoms. GCIPL and RNFL are useful predictors of final visual outcome.

Peripheral blood monocyte counts are elevated in the pre-diagnostic phase of pancreatic cancer: A population based study

BackgroundEarly diagnosis of pancreatic ductal adenocarcinoma (PDAC) is associated with improved outcomes. A biomarker with incremental change in the pre-diagnostic phase of the disease would be valuable for early detection. In our clinical experience, we have observed elevated peripheral blood monocyte (PBM) counts in PDAC patients at diagnosis. In this study, we aimed to compare PBM counts in PDAC cases and healthy controls at diagnosis and in the 2-year pre-diagnostic period. MethodsUsing the Rochester Epidemiology Project database, we identified all patients diagnosed with PDAC between 2000 and 2015 (n = 219) and age-and gender-matched disease-free controls (n = 438). PBM counts and temporal trends were analyzed over a 24 month period before PDAC diagnosis. The groups were compared using Fisher’s exact test and t-test. ResultsAt diagnosis, compared to controls PDAC cases more often had monocytosis (23% vs 8%; p < 0.001) and higher mean PBM count (x109/L) (0.73 vs 0.59; p < 0.001). In the 2-year pre-diagnostic period, mean PBM counts were significantly higher in PDAC cases in the interval from 6 months to diagnosis (0.69 vs 0.61; p = 0.03). PDAC cases with monocytosis at diagnosis had a significantly lower median survival (1.9 months vs. 7.6 months; p = 0.001). ConclusionMonocytosis is more prevalent in PDAC patients at diagnosis compared to controls and is associated with lower median survival. In a subset of patients, PBM count elevation precedes PDAC diagnosis by 6 months. This novel observation can possibly augment strategies for early diagnosis of PDAC but needs further study.