Autoantibodies against myelin sheath and S100β are associated with cognitive dysfunction in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) has been associated with cognitive impairment and peripheral production of autoantibodies. Autoantibodies against central nervous system (CNS) proteins and S100 calcium-binding β (S100β) were found increased in diseases characterized by cognitive impairment like Alzheimer disease and Neuropsychiatric Systemic Lupus Erythematosus (NPSLE). The aim of this study was to investigate the plasma levels of autoantibodies against myelin basic protein (anti-MBP), myelin oligodendrocyte glycoprotein (anti-MOG) and S100β, and their relationships with cognitive performance in RA patients. Twenty patients with active rheumatoid arthritis and 19 age-, sex-, and schooling-matched healthy controls were recruited. Multiple dimensions of cognitive function were evaluated by structured clinical questionnaires. Autoantibodies and S100β levels were assessed by ELISAs. Patients had significantly higher levels of anti-MBP IgG (17.51 ± 1.36 vs. 5.24 ± 0.53 ng/mL), anti-MOG IgG (5.68 ± 1.34 vs. 0.51 ± 0.49 ng/mL), and S100β protein (2.24 ± 0.50 vs. 0.47 ± 0.06) than controls (all p < 0.0001). After adjusting for potential confounders, RA group presented worse cognitive performance involving the working memory and executive functions such as inhibition, flexibility, and mental control in parallel to higher autoantibodies and S100β levels than healthy controls (all p < 0.001). Levels of anti-MBP were negatively associated with delayed verbal recall (DVR; r = ?0.42, p = 0.005), Stroop Color-Word (r = ?0.48, p = 0.004), and N-Back Total scores (r = ?0.59, p < 0.0001) and positively with Trail Making Test B (TMB, r = 0.53, p = 0.001). Negative correlation was found between levels of anti-MOG and DVR (r = ?0.64, p < 0.0001), N-Back Total scores (r = ?0.35, p = 0.03), Stroop Color-Word (r = ?0.51, p = 0.001), and positively with TMB (r = 0.50, p = 0.003). S100β levels were associated with DVR (r = ?0.51, p = 0.002), TMB (r = 0.46, p = 0.008), Stroop Color-Word (r = ?0.67, p < 0.0001), and N-Back Total (r = ?0.52, p = 0.003). RA is associated with impaired cognitive performance associated with higher levels of CNS-related autoantibodies and S100β levels. Given the importance of myelin integrity to cognition, our data indicate that these autoantibodies may be harmful to proper cognitive function.     

The relationship of nitric oxide synthesis capacity,oxidative stress,and albumin-to-creatinine ratio in black and white men: the SABPA study

Inadequate substrate availability and increased nitric oxide synthase inhibitor levels attenuate nitric oxide (NO) synthesis, whereas increased vascular oxidative stress may lead to inactivation of NO. We compared markers of NO synthesis capacity and oxidative stress in a bi-ethnic male population. Inter-relationships of ambulatory blood pressure and urinary albumin-to-creatinine ratio with NO synthesis capacity and oxidative stress markers were investigated. NO synthesis capacity markers (L-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA)) and oxidative stress markers (serum peroxides, total glutathione, glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), and catalase) were measured. Black men displayed higher blood pressure and albumin-to-creatinine ratio (all p < 0.001), while NO synthesis capacity was more favorable (higher L-arginine and lower ADMA (p ≤ 0.003)). Antioxidant enzyme activities were similar except for the redox status markers (GR activity and GR/GPx ratio), which were upregulated in black men (p < 0.001). In black men, ADMA was inversely related to GPx activity (R ² = 0.15; β = ?0.20; p = 0.050) and GPx/SOD ratio (R ² = 0.24; β = ?0.37; p < 0.001), but none of these markers related to blood pressure or albumin-to-creatinine ratio. In white men, albumin-to-creatinine ratio was positively associated with ADMA (R ² = 0.18; β = 0.39; p < 0.001) while ADMA was inversely related to GR activity (R ² = 0.26; β = ?0.29; p = 0.002) and GR/GPx ratio (R ² = 0.25; β = ?0.28; p = 0.003). Black men with elevated blood pressure and albumin-to-creatinine ratio displayed a favorable NO synthesis capacity. This may be counteracted by increased inactivation of NO, although it was not linked to vascular or renal phenotypes. In white men, reduced NO synthesis capacity may lower NO bio-availability, thereby influencing the albumin-to-creatinine ratio.     

The effects of long- and short-term interdisciplinary treatment approaches in women with fibromyalgia: a randomized controlled trial

We investigated the effects of long- and short-term interdisciplinary treatment approaches for reducing symptoms and improving health-related quality of life (HRQoL) and physical functions of patients with fibromyalgia and compared the effects of two different interdisciplinary treatment approaches. We conducted a prospective, randomized, controlled trial involving 66 women with fibromyalgia eligible for the study at a university hospital setting. The patients were randomized into three groups (allocation ratio 1:1:1) using a computer-generated random numbers: a long-term interdisciplinary treatment group (LG, n = 22) that participated in 10 sessions (3-h once-weekly session for 10 weeks) of cognitive behavioral therapy (CBT) together with exercise training and other fibromyalgia related educational programs (two full days); a short-term interdisciplinary treatment group (SG, n = 22) that received two full days of educational, exercise, and CBT programs; and a control group (CG, n = 22). The patients were evaluated at baseline and 6 months after treatment using the visual analog scale (pain, fatigue, and sleep), Fibromyalgia Impact Questionnaire, Beck Depression Inventory, Short Form-36, tender point numbers, and pressure algometry as primary outcomes. The statistical analysis was confined to the ‘per-protocol’ set. No blinding was performed. The number of patients analyzed was 21 in the LG, 19 in the SG, and 19 in the CG. The intensity of pain (p < 0.001), severity of fatigue (p = 0.048), number of tender points (p = 0.002), and pressure pain threshold (p = 0.012) decreased significantly in both the LG and SG groups compared with controls. Moreover, physical functions (p = 0.017) and physical components of the HRQoL (p = 0.036) improved significantly in the intervention groups compared with the controls. However, there was no significant difference between intervention groups and the control group at the end of study in terms of quality of sleep (p = 0.055), severity of depressive symptoms (p = 0.696), and mental components of the HRQoL (p = 0.229). Finally, with the exception of the severity of fatigue and physical components of the HRQoL, there was no obvious significant difference between the efficacies of the two treatment approaches when compared with controls; the long-term treatment was found more effective in reducing pain than the short-term. Both, long- and short-term interdisciplinary treatments were effective in reducing the severity of some symptoms and disease activity in patients with fibromyalgia. The short-term program well meets the needs of women with fibromyalgia particularly in relation to pain and health status as measured using FIQ; however, a long-term program may be beneficial in reducing fatigue and improving physical function to a higher extent.     

A Moderated Mediation Model of HIV-Related Stigma,Depression, and Social Support on Health-Related Quality of Life among Incarcerated Malaysian Men with HIV and Opioid Dependence

Although it is well established that HIV-related stigma, depression, and lack of social support are negatively associated with health-related quality of life (HRQoL) among people living with HIV (PLH), no studies to date have examined how these psychosocial factors interact with each other and affect HRQoL among incarcerated PLH. We, therefore, incorporated a moderated mediation model (MMM) to explore whether depression mediates the effect of HIV-related stigma on HRQoL as a function of the underlying level of social support. Incarcerated HIV-infected men with opioid dependence (N = 301) were recruited from the HIV units in Kajang prison in Malaysia. Participants completed surveys assessing demographic characteristics, HIV-related stigma, depression, social support, and HRQoL. Results showed that the effect of HIV-related stigma on HRQoL was mediated via depression (a1:β = 0.1463, p < 0.001; b1:β = ?0.8392, p < 0.001), as demonstrated by the two-tailed significance test (Sobel z = ?3.8762, p < 0.001). Furthermore, the association between social support and HRQoL was positive (β = 0.4352, p = 0.0433), whereas the interaction between HIV-related stigma and depression was negatively associated with HRQOL (β = ?0.0317, p = 0.0133). This indicated that the predicted influence of HIV-related stigma on HRQoL via depression had negative effect on HRQoL for individuals with low social support. The results suggest that social support can buffer the negative impact of depression on HRQoL and highlights the need for future interventions to target these psychosocial factors in order to improve HRQoL among incarcerated PLH.     

Low serum fibroblast growth factor 2 levels not accompanied by increased serum pentraxin 3 levels in patients with systemic sclerosis

There are scarce clinical data regarding serum pentraxin 3 (PTX3) and fibroblast growth factor 2 (FGF2) in patients with systemic sclerosis (SSc). Study was conducted to evaluate serum levels in our SSc cohort. Serum PTX3 and FGF2 concentrations were compared among SSc, disease control (systemic lupus erythematosus (SLE)), and healthy control groups. We also examined the association of serum levels of PTX3 and FGF2 with disease manifestations. Serum PTX3 levels were similarly distributed among SSc (n = 93) and healthy groups (n = 66) (p = 1.00) while PTX3 levels were higher in SLE controls (n = 86) compared to both SSc and healthy groups. PTX3 levels were higher in limited SSc cases compared to diffuse cases (p = 0.016). Median PTX3 levels in SSc cases with lung involvement were lower compared to cases with no lung involvement (p = 0.006). Patients with SSc had significantly lower serum levels of FGF2 compared to SLE and healthy groups. Serum FGF2 concentration was undetectable in 61.3% of cases with SSc while 30.2% of SLE and only 4.5% of healthy cases had undetectable FGF2 levels (p < 0.01). Diffuse and limited SSc cases, as well as cases with and without lung involvement, had similar rates of undetectable serum FGF2 levels (p = 0.15 and p = 0.59, respectively). FGF2 levels were mostly undetectably low in patients with SSc, and serum PTX3 was lower in diffuse SSc and in cases with lung involvement compared to limited SSc and cases with no lung involvement, respectively, in our cohort.     

Increased serum levels of adhesion molecules ICAM-1 and VCAM-1 in systemic sclerosis are not specific for pulmonary manifestations

Studies suggest elevated serum intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels may be markers of pulmonary arterial hypertension in systemic sclerosis (SSc-PAH). We sought to evaluate whether ICAM-1 and VCAM-1 levels are useful screening biomarkers for incident SSc-PAH. In this cross-sectional study, four groups were selected from the Australian Scleroderma Cohort Study: group 1 (n?=?15) had definite PAH; group 2 (n?=?19) had interstitial lung disease (ILD); group 3 (n?=?30) were SSc-controls; and group 4 (n?=?34) were healthy controls. Serum ICAM-1 and VCAM-1 levels were measured using the Millipore Milliplex MAP Human 2-Plex Panel. There were no differences in ICAM-1 levels in the PAH versus ILD group (263.0?±?85.4 vs 380.4?±?168.3 ng/mL, p?=?0.136), SSc-controls (263.0?±?85.4 vs 253.1?±?98.0 ng/mL, p?=?1.00), or healthy controls (263.0?±?85.4 vs 201.8?±?57.2 ng/mL, p?=?0.093). Similarly, there were no differences in VCAM-1 level in PAH versus ILD groups (1476.2?±?434.9 vs 1424.8?±?527.6 ng/mL, p?=?1.00) and SSc-controls (1476.2?±?434.9 vs 1409.5?±?341.1 ng/mL, p?=?1.00). SSc subjects had significantly higher levels of ICAM-1 (297.4?±?134.0 vs 201.8?±?57.2 ng/mL, p?<?0.0001) and VCAM-1 compared to healthy controls (1432.7?±?427.4 vs 1125.6?±?273.4 ng/mL, p?<?0.0001). Neither ICAM-1 nor VCAM-1 is a specific screening biomarker of SSc-PAH. Instead, increased levels of these adhesion molecules in SSc, irrespective of pulmonary complications, suggest that they may play a role in SSc pathogenesis.     

Assessment of risk factors and left ventricular function in patients with slow coronary flow

Slow coronary flow (SCF) is characterized by delayed distal vessel opacification in the absence of significant epicardial coronary disease. Life-threatening arrhythmias and sudden cardiac death can occur; however, the pathological mechanism and influence on left ventricular function remain undetermined. We aimed to assess the risk factors and left ventricular (LV) function in SCF and evaluate the relationships between thrombolysis in myocardial infarction frame count (TFC) and the number of involved coronary arteries with LV function in patients with SCF. We included 124 patients who underwent coronary angiography because of symptoms of angina; 71 patients with angiographically proven SCF and 53 cases with normal coronary flow pattern. SCF was diagnosed as TFC >27 in at least one coronary artery. Complete blood count and biochemical parameters were compared between the two groups. Conventional echocardiography and tissue Doppler imaging were used to assess LV systolic and diastolic function. Platelet aggregation rate induced by ADP was an independent predictor of SCF and positively correlated with coronary artery mean TFC (mTFC) (r = 0.514, P < 0.001) and the number of coronary arteries with SCF (r = 0.628, P < 0.001). Early diastolic mitral inflow velocity (E) (0.66 ± 0.15 vs. 0.74 ± 0.17, P = 0.008), ratio of early to late diastolic mitral inflow velocity (E/A) (0.95 ± 0.29 vs. 1.15 ± 0.35, P = 0.002), global myocardial peak early diastolic velocity (gVe) (4.41 ± 1.25 vs. 4.96 ± 1.45, P = 0.037), and ratio of global myocardial peak early to late diastolic velocity (gVe/gVa: 1.09 ± 0.45 vs. 1.36 ± 0.58, P = 0.006) were decreased in patients with SCF compared with controls. gVe (3 vs. 0 branches, 4.08 ± 1.14 vs. 4.97 ± 1.45, respectively, P = 0.008) deteriorated significantly in patients with SCF involving three coronary arteries. mTFC negatively correlated with E and E/A (r = ?0.22, P = 0.02; r = ?0.20, P = 0.04, respectively). The number of coronary arteries with SCF negatively correlated with E, E/A, gVe and gVe/gVa (r = ?0.23, P = 0.02; r = ?0.25, P = 0.009; r = ?0.25, P = 0.008; r = ?0.21, P = 0.03, respectively). Platelet aggregation rate induced by ADP was an independent predictor of SCF and positively correlated with coronary artery TFC and the number of affected coronary arteries. Left ventricular global and regional diastolic function was impaired in SCF patients. Furthermore, the number of coronary arteries involved rather than coronary artery TFC determined the severity of left ventricular dysfunction in patients with SCF.     

Reliability,validity, and cross-cultural adaptation of the Turkish version of the Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire

Up to 98% of rheumatoid arthritis (RA) patients experienced fatigue. It is an important physical and cognitive symptom which has overwhelming, uncontrollable, and unpredictable affects throughout their whole life. RA fatigue composes of complex and multi-dimensional components which are pain, stress, depression, inflammation, and disability. The acknowledgement of fatigue is important, and fatigue should be measured in all RA trials alongside the core set. The aim of this study was to determine reliability and validity of Turkish version of Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire in RA patients. One hundred RA patients were evaluated in the study. Exclusion criteria were determined as patients with cognitive impairment, illiterate patients, unable to understand and speak Turkish, under the age of 18, and over the age of 75. To validate Turkish version of Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire (BRAF-MDQ) (BRAF-MDQ-T), all participants answered BRAF-MDQ-T, Multidimensional Assessment of Fatigue (MAF) scale, and Short Form-36 vitality (SF-36 VT). BRAF-MDQ-T was applied again 7 days later for test–retest reliability. Validity, internal consistency, and test–retest results were based on a sample of 100 patients. Internal consistency reliability of BRAF-MDQ-T was Cronbach α?=?0.95 which was excellent. The correlation between the total scores of the BRAF-MDQ-T scale and the total scores of MAF-T was statistically significant (r?=?0.82, p?<?0.001). The correlation between the total scores of the BRAF-MDQ-T scale and the subscale scores of SF–36 VT was statistically significant (r?=???0.64, p?<?0.001). The BRAF-MDQ-T is a valid and reliable scale for the assessment of fatigue in Turkish rheumatoid arthritis patients.     

Serum 25-OH vitamin D levels in systemic sclerosis: analysis of 140 patients and review of the literature

Hypovitaminosis D is increasingly reported in autoimmune diseases. We investigated the 25-OH-vitamin D (25-OH-vitD) levels in systemic sclerosis (SSc) patients, in correlation with disease’s features. We measured the 25-OH-vitD serum levels in 140 consecutive patients (F/M 126/15; mean age 61 ± 15.1 years), 91 without (group A) and 49 with (group B) 25-OH-cholecalciferol supplementation. Patients of group A invariably showed low 25-OH-vitD levels (9.8 ± 4.1 ng/ml vs. 26 ± 8.1 ng/ml of group B); in particular, 88/91 (97%) patients showed vitamin D deficiency (<20 ng/ml), with very low vitamin D levels (<10 ng/ml) in 40 (44%) subjects. Only 15/49 (30.6%) patients of group B reached normal levels of 25-OH-vitD (≥30 ng/ml), whereas vitamin D deficiency persisted in 12/49 (24.5%) individuals. Parathormone levels inversely correlated with 25-OH-vitD (r = ?0.3, p < 0.0001). Of interest, hypovitaminosis D was statistically associated with autoimmune thyroiditis (p = 0.008), while calcinosis was more frequently observed in patients of group A (p = 0.057). Moreover, we found significantly higher percentage of serum anticentromere antibodies in group B patients with 25-OH-vitD level ≥30 ng/ml (8/15 vs. 6/34; p = 0.017). In literature, hypovitaminosis D is very frequent in SSc patients. An association with disease duration, calcinosis, or severity of pulmonary involvement was occasionally recognized. Hypovitaminosis D is very frequent in SSc and severe in a relevant percentage of patients; furthermore, less than one third of supplemented subjects reached normal levels of 25-OH-vitD. The evaluation of 25-OH-vitD levels should be included in the routine clinical work-up of SSc. The above findings expand previous observations and may stimulate further investigations.     

Tumor necrosis factor-α -308 A/G gene polymorphism in children with juvenile idiopathic arthritis: relation to disease activity,damage, and functional status

The study aims to evaluate the clinical significance of serum levels of tumor necrosis factor alpha (TNF-α) and -308 A/G promoter polymorphism in juvenile idiopathic arthritis (JIA) patients and find any association to the subsets, clinical and laboratory features, disease activity, and damage as well as functional disability. Forty-eight JIA children and 30 controls were included in the present study. Juvenile arthritis disease activity score in 27 joints (JADAS-27) was calculated, juvenile arthritis damage index (JADI) was assessed, and Childhood Health Assessment Questionnaire (CHAQ) measured the functional status. Serum TNF-α was assayed by ELISA and gene (-308) promoter polymorphism was determined by polymerase chain reaction. The 48 JIA children (mean age 11.5 ± 2.8 years) were 13 systemic, 17 oligoarticular, and 18 polyarticular onset. The serum TNF-α was significantly higher in patients (90.4 ± 6.3 ng/ml) compared to control (3.5 ± 2.6 ng/ml) (p < 0.0001) with a tendency to be higher in the polyarticular subtype. All controls had TNF-α -308 GG alleles. The frequency of GG genotype tended to be higher in systemic onset compared to oligoarticular and polyarticular subtypes. The serum TNF-α significantly correlated with JADAS-27 (r = 0.32, p = 0.03) and CHAQ (r = 0.37, p = 0.01) and negatively with the presence of GG alleles (r = ?0.48, p = 0.001). The GG alleles were significantly negatively associated with C-reactive protein (r = ?0.32, p = 0.03) with a tendency to negatively correlate with JADAS-27, CHAQ, and JADI-extrarticular (r = ?0.28, p = 0.06; r = ?0.25, p = 0.09 and r = ?0.25, p = 0.09, respectively). There is evidence of a possible influence of the ?308 SNP promoter position on the production of TNF-α, the severity of JIA which may consequently influence the response to anti-TNF-α treatment.     

Polymorphisms of the <Emphasis Type="Italic">TGF-β1</Emphasis> gene and the risk of acquired aplastic anemia in a Chinese population

Acquired aplastic anemia (AA) is a hematological disease characterized by failure of bone marrow hematopoiesis resulting in pancytopenia. While immune-mediated destruction of hematopoietic stem/progenitor cells (HSPCs) plays a central role in the pathophysiology of acquired AA, the transforming growth factor-β1 (TGF-β1) is crucial in adjusting the immune system. The aim of our study was to investigate the role of TGF-β1 gene polymorphisms rs1800469 and rs2317130 in susceptibility to acquired AA. Via the approach of SNaPshot, we genotyped rs1800469 and rs2317130 in 101 patients with acquired AA and 165 controls. It derived us to the conclusion that the genotype TT of rs1800469 (C/T) was significantly associated with decreased risk of acquired AA (adjusted OR = 0.39, 95% CI = 0.18–0.83, P = 0.014). Furthermore, this decreased risk was more pronounced among male patients (adjusted OR = 0.35, 95% CI = 0.13–0.95, P = 0.038) and SAA/vSAA (severe AA/very severe AA) patients (adjusted OR = 0.31, 95% CI = 0.12–0.77, P = 0.02) compared with controls in subgroup analysis. However, a significant increased risk was observed in the genotype distributions of rs2317130 for TT genotype (adjusted OR = 2.52, 95% CI = 1.03–6.19, P = 0.04) compared with the CC genotype among the SAA/vSAA patients and controls in the severity stratification analysis. Our results indicated that TGF-β1 gene polymorphisms might be involved in the munity of acquired AA in a Chinese population. This initial analysis provides valuable clues for further study of TGF-β1 pathway genes in acquired AA.     

The clinical utility of serum IL-35 in patients with polymyositis and dermatomyositis

The objectives of this study are to assess the levels of serum Interleukin-35 (IL-35) in patients with idiopathic inflammatory myopathies (IIMs) and to evaluate the association between IL-35 levels and IIM-related features. Serum IL-35 was detected in 76 patients with dermatomyositis (DM), 28 patients with polymyositis (PM), 98 disease controls (40 rheumatoid arthritis (RA), 34 systemic lupus erythematosus (SLE), 12 systemic sclerosis (SSc), and 12 sjogren syndrome (SS)), and 43 healthy controls by ELISA. Follow-up was conducted on 34 patients. Serum IL-35 was higher in myositis (PM/DM) patients than in healthy controls (median 76.6 pg/ml [interquartile range (IQR) 57.9–136.2] vs. 29.9 pg/ml (IQR 21.9–65.5), P < 0.001) and disease controls. Serum IL-35 in IIM patients negatively correlated with disease duration moderately (r = ?0.35, P < 0.01). Patients with dysphagia had higher IL-35 than those without (median149.35 pg/ml (IQR 87.97–267.32) vs. 70.72 pg/ml (IQR 54.49–123.42), P = 0.001). Cross-sectional correlation analysis showed a weak positive correlation between serum IL-35 and CK (r = 0.293, P = 0.003), moderate positive correlation with erythrocyte sedimentation rate (ESR) (r = 0.304, P = 0.002), serum ferritin (SF) (r = 0.467, P = 0.001) and LDH levels (r = 0.401, P < 0.001). Additionally, serum IL-35 was higher in patients who were positive for anti-HMGCR (median 292.04 pg/ml (IQR 67.9–442.86) vs. 74.66 pg/ml (IQR 57.24–131.32), P = 0.038) and anti-SRP antibody (median 130.33 pg/ml (IQR 88.04–481.28) vs. 73.06 pg/ml (IQR 56.78–134.28), P = 0.009) than in negative patients, respectively. Follow-up study showed that changes in IL-35 levels after treatment correlated with changes in MYOACT scores moderately (r = 0.375, P = 0.029). These data indicate that increased serum IL-35 could act as a disease activity marker and as a risk factor for esophageal involvement in IIM. IL-35 may participate in the pathophysiological processes of IIM, but it still needs further study to confirm.     

Malnutrition and sarcopenia in a large cohort of patients with systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune disease which may lead to malnutrition. Previous studies have defined it with different criteria. No thorough evaluations of sarcopenia in SSc are available. The aim of the present study was to assess the prevalence and the potential association of malnutrition and sarcopenia in a large cohort of SSc cases. A total of 141 SSc consecutive outpatients were enrolled. Body composition was analyzed by densitometry. Malnutrition was defined according to recently published ESPEN criteria, whereas sarcopenia was diagnosed in patients with reduced skeletal muscle index. Malnutrition was diagnosed in 9.2% of patients (95% CI, 4.4–14.0%). Malnourished patients had worse gastrointestinal symptoms according to UCLA SCTC GIT 2.0 questionnaire (p?=?0.007), lower physical activity (p?=?0.028), longer disease duration (p?=?0.019), worse predicted DLCO/VA and FVC (p?=?0.009, respectively), worse disease severity according to Medsger severity score (p?<?0.001), lower hemoglobin (p?=?0.023), and fat-free mass (p?<?0.001) and were more often sarcopenic (p?<?0.001). In multivariate analysis, only FVC (p?=?0.006) and disease severity (p?=?0.003), in particular for the lungs (p?=?0.013), were confirmed to be worse in malnourished patients. Sarcopenia was diagnosed in 29\140 patients (20.7%; 95% CI, 14.0–27.4%); 11\29 were also malnourished. In multivariate analysis, sarcopenic patients had longer disease duration (p?=?0.049), worse DLCO/VA (p?=?0.002), and lung (p?=?0.006) and skin (p?=?0.014) involvement. In SSc, malnutrition defined with ESPEN criteria was found to be lower than previously reported. Sarcopenia was found to be somewhat common. Lung involvement was significantly associated with nutritional status and may not be explained only by muscle weakness.     

Impact of age on intermittent hypoxia in obstructive sleep apnea: a propensity-matched analysis

Purpose

To determine independent relationship of aging with chronic intermittent hypoxia, we compared hypoxia-related polysomnographic variables of geriatric patients (aged ≥ 65 years) with an apnea–hypopnea index (AHI)-, gender-, body mass index (BMI)-, and neck circumference-matched cohort of non-geriatric patients.

Methods

The study was conducted using clinical and polysomnographic data of 1280 consecutive patients who underwent complete polysomnographic evaluation for suspected sleep-disordered breathing (SDB) at a single sleep disorder center. A propensity score-matched analysis was performed to obtain matched cohorts of geriatric and non-geriatric patients, which resulted in successful matching of 168 patients from each group.

Results

Study groups were comparable for gender (P = 0.999), BMI (P = 0.940), neck circumference (P = 0.969), AHI (P = 0.935), and severity of SDB (P = 0.089). The oximetric variables representing the duration of chronic intermittent hypoxia such as mean (P = 0.001), the longest (P = 0.001) and total apnea durations (P = 0.003), mean (P = 0.001) and the longest hypopnea durations (P = 0.001), and total sleep time with oxygen saturation below 90% (P = 0.008) were significantly higher in the geriatric patients as compared with younger adults. Geriatric patients had significantly lower minimum (P = 0.013) and mean oxygen saturation (P = 0.001) than non-geriatric patients.

Conclusions

The study provides evidence that elderly patients exhibit more severe and deeper nocturnal intermittent hypoxia than the younger adults, independent of severity of obstructive sleep apnea, BMI, gender, and neck circumference. Hypoxia-related polysomnographic variables in geriatric patients may in fact reflect a physiological aging process rather than the severity of a SDB.

     

Impact of depressive symptoms and hepatic encephalopathy on health-related quality of life in cirrhotic hepatitis C patients

Depression, common in chronic medical conditions, and hepatic encephalopathy (HE), a reversible neuropsychiatric syndrome due to liver dysfunction, are associated with impaired health-related quality of life (HRQOL) in cirrhosis and hepatitis C (HCV). This study investigated the impact of depression and HE on HRQOL in cirrhotic patients with HCV. A convenience sample of 43 ambulatory patients, with varying degrees of cirrhosis secondary to HCV, was prospectively enrolled in this study. Participants were assessed for any current depressive, fatigue, and daytime sleepiness symptoms and underwent a psychometric evaluation to determine the presence of HE symptoms. Participants reported current HRQOL on general health and liver disease-specific questionnaires. Diagnosis and current health status were confirmed via medical records. The associations between disease severity, depressive symptoms, HE, fatigue, and daytime sleepiness were measured. Predictors of HRQOL in this sample were determined. Depressive symptoms (70 %) and HE (77 %) were highly prevalent in this sample, with 58 % actively experiencing both conditions at the time of study participation. A significant positive association was found between depressive symptoms and HE severity (P = .05). Depressive symptoms were significantly associated with fatigue (P < .001), daytime sleepiness (P < .001), general HRQOL (P < .001), and disease-specific HRQOL (P < .001). HE was significantly associated with fatigue (P = .02), general HRQOL (P < .001), and disease-specific HRQOL (P < .001). Depressive symptoms and HE were significant predictors of reduced HRQOL (P < .001), with depressive symptoms alone accounting for 58.8 % of the variance. Depressive symptoms and HE accounted for 68.0 % of the variance. Findings suggest a possible pathophysiological link between depression and HE in cirrhosis, and potentially a wider-reaching benefit of treating minimal and overt HE than previously appreciated.     

Circulating Bone Marrow-Derived CD45−/CD34+/CD133+/VEGF+ Endothelial Progenitor Cells in Adults with Crohn’s Disease

Background

Circulating endothelial progenitor cells (EPCs) are bone marrow-derived stem cells able to migrate to sites of damaged endothelium and differentiate into endothelial cells. Altered EPC level and function have been described in various inflammatory diseases and have been shown to augment vasculogenesis in murine models. Previous studies of EPC in the context of Crohn’s disease (CD) have yielded conflicting results.

Aim

To determine whether the circulating levels of EPCs are changed in the context of CD.

Methods

CD patients and healthy controls were recruited. Disease activity was assessed by CDAI. Peripheral blood mononuclear cells were isolated and EPC numbers evaluated by FACS analysis using anti-CD34, anti-VEGF receptor-2, anti-CD133, and anti-CD45 markers.

Results

Eighty-three subjects, including 32 CD patients and 51 controls were recruited, including 19 (59.4 %) and 23 (45 %) males (p = 0.26), aged 34.8 ± 14.9 and 43.3 ± 18.5 years (p = 0.64), in cases and controls, respectively. Mean CDAI was 147 ± 97, disease duration was 12.7 ± 11.1 years, and 28 (87.5 %) were receiving biologics for a mean duration of 21.7 ± 16.8 months. The mean level of peripheral EPCs in CD patients was 0.050 ± 0.086 percent and 0.007 ± 0.013 % in controls (p < 0.01). There was no significant correlation between EPC levels and age (r = ?0.13, p = 0.47), CDAI (r = ?0.26, p = 0.15), disease duration (r = ?0.04, p = 0.84), or duration of treatment with biologics (r = 0.004, p = 0.99).

Conclusion

EPCs are elevated in patients with CD. Further studies are needed to examine the function of EPCs and their possible role as a marker of disease severity or therapeutic response.

     

Role of DNA Methylation on the Expression of the Anthracycline Metabolizing Enzyme AKR7A2 in Human Heart

The intracardiac synthesis of anthracycline alcohol metabolites by aldo–keto reductases (AKRs) contributes to the pathogenesis of anthracycline-related cardiotoxicity. AKR7A2 is the most abundant anthracycline reductase in hearts from donors with and without Down syndrome (DS), and its expression varies between individuals (≈tenfold). We investigated whether DNA methylation impacts AKR7A2 expression in hearts from donors with (n = 11) and without DS (n = 30). Linear models were used to test for associations between methylation status and cardiac AKR7A2 expression. In hearts from donors without DS, DNA methylation status at CpG site ?865 correlated with AKR7A2 mRNA (Pearson’s regression coefficient, r = ?0.4051, P = 0.0264) and AKR7A2 protein expression (r = ?0.5818, P = 0.0071). In heart tissue from donors with DS, DNA methylation status at CpG site ?232 correlated with AKR7A2 protein expression (r = 0.8659, P = 0.0025). Multiple linear regression modeling revealed that methylation at several CpG sites is associated with the synthesis of cardiotoxic daunorubicinol. AKR7A2 methylation status in lymphoblastoid cell lines from donors with and without DS was examined to explore potential parallelisms between cardiac tissue and lymphoid cells. These results suggest that DNA methylation impacts AKR7A2 expression and the synthesis of cardiotoxic daunorubicinol.     

Physiological determinants of walking effort in older adults: should they be targets for physical activity intervention?

Older adults do not get enough physical activity increasing risk for chronic disease and loss of physical function. The purpose of this study was to determine whether neuromuscular, metabolic, and cardiorespiratory indicators of walking effort explain daily activity in community-dwelling older adults. Sixteen women and fourteen men, 78?±?8 years, performed a steady-state walk on a treadmill at 1.25 m s^?1 while muscle activation, heart rate, lactate, respiratory exchange ratio, oxygen consumption (VO₂), ventilation, and rating of perceived exertion (RPE) were recorded as markers of Walking Effort. Daily walking time, sitting/lying time, energy expenditure, and up-down transitions were recorded by accelerometers as markers of Daily Activity. Structural equation modeling was used to explore the relationship between the latent variables Walking Effort and Daily Activity controlling for age and BMI. Participants spent 9.4?±?1.9 h of the waking day sedentary and 1.9?±?0.6 h walking. In the structural equation model, the latent variable Walking Effort explained 64% of the variance in the Daily Activity latent variable (β?=?0.80, p?=?0.004). Walking Effort was identified by heart rate (β?=?0.64), ventilation (β?=?0.88), vastus lateralis activation (β?=?0.49), and lactate (β?=?0.58), all p?<?0.05, but not RPE or VO₂. Daily Activity was identified by stepping time (β?=?0.75) and up-down transitions (β?=?0.52), all p?<?0.05. Walking effort mediated the effects of age and BMI on older adults’ daily activity making physiological determinants of walking effort potential points of intervention.     

Influence of hippocampal GABA<Subscript>B</Subscript> receptor inhibition on memory in rats with acute β-amyloid toxicity

The neurotransmitter γ-aminobutyric acid (GABA) is involved in the process of memory. It has been reported that the inhibition of GABA_B receptors has beneficial effects on cognition. The aim of this study was to investigate the role of CGP35348 (a GABA_B receptor antagonist) on dentate gyrus GABA_B receptor inhibition and its effects on learning and memory impairments that had been induced in adult male rats by microinjection of β-amyloid (Aβ). Seventy Wistar male rats were randomly divided into seven groups: control, sham (receiving the Aβ vehicle only), Aβ, Aβ + CGP35348 (1, 10, and 100 μg/μL), and CGP35348 alone (10 μg/μL). Memory impairment was induced by unilateral interventricular microinjection of Aβ (6 μg/6 μL). Rats were cannulated bilaterally in the dentate gyrus, and then, they were treated for 20 consecutive days. Learning and memory were assessed using the novel object recognition and passive avoidance learning tests. The discrimination index and the step-through latency were significantly increased in the Aβ + CGP35348 group in comparison to the Aβ only group (P?<?0.05 and P?<?0.01, respectively). Data showed that the discrimination index was decreased in the Aβ + CGP35348 group in comparison with the control group (P?<?0.05) and sham group (P?<?0.01). Moreover, the step-through latency was significantly decreased in the Aβ + CGP35348 group in comparison to the control and sham groups (P?<?0.01). Data from this study indicated that intra-hippocampal microinjection of the GABA_B receptor antagonist counteracts the learning, memory, and cognitive impairments induced by Aβ. It can be concluded that the GABA_B receptor antagonist is a possible therapeutic agent against the progression of acute Aβ toxicity-induced memory impairment.