Nutrition education in postmenopausal women: Changes in dietary and cardiovascular indices

ObjectiveThe aim of the current study was to examine whether a diet rich in dairy products followed by a nutrition education program for the prevention of osteoporosis could have any adverse effect on certain cardiovascular disease (CVD) risk factors over a 5-month intervention period.MethodsA total sample of 82 women (55–65 years old) was randomized to a dietary intervention group (IG: n = 42), attending biweekly nutrition education program and provided with low-fat, fortified dairy products and to a control group (CG: n = 40). Changes in dietary, biochemical and clinical indices related to CVD were determined at the end of the 5-month intervention period.ResultsThe IG was found to have a higher decrease in the percentage of energy intake derived from total fat and a higher increase in the intake of calcium, phosphorus, magnesium and potassium compared to the CG (p < 0.05). Furthermore, the IG subjects were found to have a lower increase in BMI (0.7 ± 0.1 versus 1.4 ± 0.2 Kg/m², p = 0.011) and systolic blood pressure (SBP) (2.5 ± 2.9 versus 7.8 ± 2.2 mmHg, p = 0.040) and a higher decrease in serum total cholesterol (−5.2 ± 3.3 versus 6.9 ± 5.1 mg/dl, p = 0.042) and LDL-cholesterol levels (−20.0 ± 2.6 versus −12.4 ± 4.2 mg/dl, p = 0.034) compared to the CG.ConclusionsThe findings of the current study indicate that a dietary intervention aiming to minimize the risk for osteoporosis did not have any adverse effects on CVD risk factors. On the contrary, it has induced favourable changes in BMI, serum lipids and SBP.     

Quadriceps/hamstrings co-activation increases early after total knee arthroplasty

Quadriceps and hamstrings weakness and co-activation are present following total knee arthroplasty (TKA) and may impair functional performance. How surgery and post-operative rehabilitation influence muscle activation during walking early after surgery is unclear.PurposeExamine muscle strength and activation during walking before and one and 6-months post-TKA.MethodsTen patients (n = 6 female; age: 64.7 ± 7.9 years; body mass index[BMI]:29.2 ± 2.5 kg/m²) and 10 healthy adults (n = 6 female; age: 60.6 ± 7.4 years; BMI: 25.5 ± 4.0 kg/m²) participated. The patients underwent bilateral quadriceps and hamstrings strength testing and assessment of quadriceps/hamstrings co-activation and on/off timing using surface electromyography during a six-minute walk test (6MW). Groups, limbs, and changes with TKA surgery were compared.ResultsPatients reported greater 6MW knee pain pre- versus post-TKA and compared to controls (P < 0.05). Patients had weaker surgical limb hamstrings (P < 0.05) and bilateral quadriceps (P < 0.05) strength than controls pre- and post-TKA. Before and 1-month post-TKA, patients had side-to-side differences in quadriceps and hamstrings strength (P < 0.05). Controls walked farther than patients (P < 0.01). Patients demonstrated greater surgical limb co-activation pre-operatively than controls (P < 0.05). Co-activation was higher bilaterally one-month post-TKA compared to controls (P < 0.05). Patients turned off their quadriceps later during stance than controls before and 1-month post-TKA (P < 0.05).ConclusionsMuscle strength, co-activation, and timing differed between patients and controls before and early after surgery. Rehabilitation to improve strength and muscle activation seems imperative to restore proper muscle firing patterns early after surgery.     

A randomized trial to study the comparative efficacy of phenylbutyrate and benzoate on nitrogen excretion and ureagenesis in healthy volunteers

PurposeBenzoate and phenylbutyrate are widely used in the treatment of urea cycle disorders, but detailed studies on pharmacokinetics and comparative efficacy on nitrogen excretion are lacking.MethodsWe conducted a randomized, three-arm, crossover trial in healthy volunteers to study pharmacokinetics and comparative efficacy of phenylbutyrate (NaPB; 7.15 g•m⁻²BSA•day⁻¹), benzoate (NaBz; 5.5 g•m⁻²BSA•day⁻¹), and a combination of two medications (MIX arm; 3.575 g NaPB and 2.75 g NaBz•m⁻²BSA•day⁻¹) on nitrogen excretion. Stable isotopes were used to study effects on urea production and dietary nitrogen disposal.ResultsThe conjugation efficacy for both phenylbutyrate and benzoate was 65%; conjugation was superior at the lower dose used in the MIX arm. Whereas NaPB and MIX treatments were more effective at excreting nitrogen than NaBz, nitrogen excretion as a drug conjugate was similar between phenylbutyrate and MIX arms. Nitrogen excreted per USD was higher with combination therapy compared with NaPB.ConclusionPhenylbutyrate was more effective than benzoate at disposing nitrogen. Increasing phenylbutyrate dose may not result in higher nitrogen excretion due to decreased conjugation efficiency at higher doses. Combinatorial therapy with phenylbutyrate and benzoate has the potential to significantly decrease treatment cost without compromising the nitrogen disposal efficacy.     

CD68+, but not stabilin-1+ tumor associated macrophages in gaps of ductal tumor structures negatively correlate with the lymphatic metastasis in human breast cancer

Tumor associated macrophages (TAM) support tumor growth and metastasis in several animal models of breast cancer, and TAM amount is predictive for efficient tumor growth and metastatic spread via blood circulation. However, limited information is available about intratumoral TAM heterogeneity and functional role of TAM subpopulations in tumor progression. The aim of our study was to examine correlation of TAM presence in various morphological segments of human breast cancer with clinical parameters. Thirty six female patients with nonspecific invasive breast cancer T1-4N0-3M0 were included in the study. Morphological examination was performed using Carl Zeiss Axio Lab.A1 and MiraxMidiZeiss. Immunohistochemical and immunofluorescence/confocal microcopy analysis was used to detect CD68 and stabilin-1 in 5 different tumor segments: (1) areas with soft fibrous stroma; (2) areas with coarse fibrous stroma; (3) areas of maximum stromal-and-parenchymal relationship; (4) parenchymal elements; (5) gaps of ductal tumor structures. The highest expression of CD68 was in areas with soft fibrous stroma or areas of maximum stromal-and-parenchymal relationship (79%). The lowest expression of CD68 was in areas with coarse fiber stroma (23%). Inverse correlation of tumor size and expression of CD68 in gaps of tubular tumor structures was found (R = −0.67; p = 0.02). In case of the lymph node metastases the average score of CD68 expression in ductal gaps tumor structures was lower (1.4 ± 0.5) compared to negative lymph nodes case (3.1 ± 1.0; F = 10.9; p = 0.007). Confocal microscopy identified 3 phenotypes of TAM: CD68⁺/stabilin-1⁻; CD68⁺/stabilin-1⁺ (over 50%); and CD68⁻/stabilin-1⁺. However, expression of stabilin-1 did not correlate with lymph node metastasis. We concluded, that increased amount of CD68+TAM in gaps of ductal tumor structures is protective against metastatic spread in regional lymph nodes.     

EphA2 knockdown attenuates atherosclerotic lesion development in ApoE−/− mice

BackgroundThe inflammatory response of vascular endothelial cells plays important roles in the initiation and progression of atherosclerotic lesions. EphA2 receptor activation promotes the endothelial cell inflammatory response, and its expression is increased in the endothelial cell layer of atherosclerotic plaques. However, the association between EphA2 and atherosclerosis has not been determined.MethodsEight-week-old male ApoE^−/− mice were systemically infected with adenoassociated virus serotype 9 carrying a small hairpin RNA specifically targeting the EphA2 gene to knock down EphA2 expression in aortic endothelial cells. These mice were then fed a high-cholesterol diet for 12 weeks. Blood was collected for the measurement of plasma lipids. The aortas were harvested to evaluate the atherosclerotic lesion size, macrophage components, and expression of proinflammatory genes using Oil Red O staining, immunofluorescence staining, and molecular biology analysis.ResultsThe lesions formed in the entire aorta and aortic sinus of the ApoE^−/− mice with EphA2 knockdown were significantly smaller than those in the control mice (10.7% ± 3.1% versus 25.1% ± 4.2%; 0.51 ± 0.02 mm² versus 0.85 ± 0.03 mm²; n = 10; P < .05). Furthermore, the lesions in the ApoE^−/− mice with EphA2 knockdown displayed reduced inflammation compared with the control mice, as reflected by the decreased macrophage infiltration (8.2% ± 2.9% versus 22.7% ± 4%; n = 10; P < .05); decreased nuclear factor-κβ activation; and diminished expression of vascular cell adhesion molecule-1, E-selectin, and monocyte chemotactic protein-1 (all P < .05).ConclusionsOur data demonstrate that the EphA2 receptor silencing attenuates the extent and inflammation of atherosclerotic lesions in ApoE^−/− mice. Thus, EphA2 knockdown in endothelial cells represents a novel therapeutic strategy for patients with atherosclerosis.     

Relationship between perilipin gene polymorphisms and body weight and body composition during weight loss and weight maintenance

BackgroundGenetic variation in the perilipin (PLIN) gene may play a role in the etiology and treatment of obesity.ObjectiveTo examine different polymorphisms in the PLIN gene in relation to body-weight regulation.Methods118 subjects followed a 6 wk VLCD, followed by 1 year weight maintenance. Body-weight (BW), body-composition, leptin concentration, and polymorphisms of the PLIN gene: PLIN1:rs2289487, PLIN4:rs894160, PLIN6:rs1052700, PLIN5:rs2304795 and PLIN7:rs 2304796 were determined.ResultsBW loss during VLCD was 7.0 ± 3.1 kg (p < 0.05), and BW regain was 3.7 ± 1.4 kg (p < 0.05), including changes in body mass index (BMI), waist-circumference, body-composition and leptin concentrations (p < 0.05).Linkage disequilibria were observed between PLIN1 and PLIN4: D' > 0.9, r² = 0.72; PLIN5 and PLIN7: D' > 0.9, r² = 0.85.In men, body weight, BMI, waist circumference, body fat, leptin concentrations were significantly lower for the haplotype of PLIN1 (C-alleles) and PLIN4 (A-alleles). In women weight loss and loss of fat mass were larger for the haplotype of PLIN1 (C-alleles) and PLIN4 (A-alleles). For PLIN6 genotypes body weight and body fat were lower for homozygotes of the minor allele (T/T) in the men; in the women leptin concentrations were lower.The haplotype of PLIN5 and PLIN7 consisting of A/G and G/G of PLIN5 and A/A of PLIN7 showed a reduction in FM: 5.9 ± 0.6 kg vs 3.1 ± 0.4 kg, % body fat: 5.5 ± 0.6% vs 2.2 ± 0.2%, and leptin: 20.5 ± 10.8 ng/ml vs 12.9 ± 6.7 ng/ml over time in the women (p < 0.05).ConclusionSince the haplotype of the minor alleles PLIN1–4, PLIN5–7 and PLIN6, was related to body-weight regulation at a lower level of body-weight in the men as well in the women we conclude that the PLIN1–4, 6, and 5–7 locus appears as a genetic influencer of obesity risk in humans.     

Can a 15 m-overground wheelchair sprint be used to assess wheelchair-specific anaerobic work capacity?

ObjectiveTo evaluate whether outcomes based on stopwatch time and power output (PO) over a 15 m-overground wheelchair sprint test can be used to assess wheelchair-specific anaerobic work capacity, by studying their relationship with outcomes on a Wingate-based 30 s-wheelchair ergometer sprint (WAnT).MethodsAble-bodied persons (N = 19, 10 men, aged 18–26 y) performed a 15 m overground sprint test in an instrumented wheelchair and a WAnT. 15 m-outcomes were based on stopwatch time (time and mean velocity over 15 m) and on PO (primary outcome: highest mean unilateral PO over successive 5 s-intervals (P5-15m)). WAnT-outcomes were mean unilateral PO over 30 s and the highest mean unilateral PO over successive 5 s-intervals. Correlation coefficients (Pearson's r) and coefficients of determination (R²) were calculated between 15 m-sprint outcomes and WAnT-outcomes.ResultsTime over 15 m (7.2 s (±1.0)) was weakly related to WAnT-outcomes (r = −0.61 and −0.60, R² = 0.38 and 0.36, p < 0.01), similar to mean velocity over 15 m (2.1 m·s⁻¹ (±0.3), R² = 0.43 and 0.39, p < 0.01). P5-15m (38.1 W (±14.0)) showed a moderate relationship to WAnT-outcomes (r = 0.77 and 0.75, R² = 0.59 and 0.56, p < 0.001).ConclusionsIt seems that outcomes based on stopwatch time over a 15 m-overground sprint cannot be used to assess wheelchair-specific anaerobic work capacity, in contrast to an outcome based on PO (P5-15m). The 15 m-sprint with an instrumented wheel can be implemented in rehabilitation practice and research settings when WAnT equipment is not available, although care is needed when interpreting P5-15m as an outcome of anaerobic work capacity given that it seems more skill-dependent than the WAnT.     

Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants

PurposeWe assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks for BRCA1 and BRCA2 pathogenic variant carriers.MethodsRetrospective cohort data on 18,935 BRCA1 and 12,339 BRCA2 female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)–negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort.ResultsThe ER-negative PRS showed the strongest association with BC risk for BRCA1 carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25–1.33], P = 3×10⁻⁷²). For BRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27–1.36], P = 7×10⁻⁵⁰). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk for BRCA1 (HR = 1.32 [95% CI 1.25–1.40], P = 3×10⁻²²) and BRCA2 (HR = 1.44 [95% CI 1.30–1.60], P = 4×10⁻¹²) carriers. The associations in the prospective cohort were similar.ConclusionPopulation-based PRS are strongly associated with BC and EOC risks for BRCA1/2 carriers and predict substantial absolute risk differences for women at PRS distribution extremes.     

Comparison of the pedalling performance induced by magnetic and electrical stimulation cycle ergometry in able-bodied subjects

The purpose of the study was to compare the mechanical power and work generated by able-bodied subjects during functional magnetic stimulation (FMS) vs. functional electrical stimulation (FES) induced ergometer training conditions. Both stimulation methods were applied at a 30 Hz frequency to the quadriceps muscles of 22 healthy able-bodied subjects to induce cycling for 4× four minutes or until exhaustion. FMS was performed via large surface, cooled coils, while FES was applied with a typical stimulation setup used for cycling. Significantly more (p < 10⁻³) muscular power was generated by FMS (23.8 ± 9.1 W [mean ± SD]) than by FES (11.3 ± 11.3 W). Additionally, significantly more (p < 10⁻⁶) work was produced by FMS than by FES (4.413 ± 2.209 kJ vs. 0.974 ± 1.269 kJ). The increase in the work was paralleled by a significant prolongation of time to cycling failure (181.8 ± 33.4 s vs. 87.0 ± 54.0 s, respectively, p < 10⁻⁵). Compared to FES, FMS can produce more intense and longer cycling exercise in able-bodied subjects. The differing dynamic behaviour of FMS and FES in the presented measurement setup might be related to stimulation induced pain and fatigue mechanisms of the neuromuscular system.     

Clinical implications of hepatitis B surface antigen quantitation in the natural history of chronic hepatitis B virus infection

BackgroundHBsAg quantitation may be useful for managing patients with hepatitis B virus (HBV) infection.ObjectivesWe explored the clinical implications of HBsAg quantitation for patients with HBsAg levels >250 IU/ml (Abbott Diagnostics).Study designTwo hundred and thirty-three HBV-infected patients comprising 29 immune tolerance cases, 49 treatment-naïve HBeAg-positive chronic hepatitis B (CHB) cases, 91 inactive HBV carrier cases, and 64 treatment-naïve HBeAg-negative CHB cases were analyzed. HBsAg was quantified by the Architect HBsAg assay (Abbott Diagnostics) after a 1:500 automated dilution.Results and conclusionsHBsAg (log 10 IU/ml) was established for immune tolerance (4.50 ± 0.43), HBeAg-positive CHB (4.17 ± 0.66), inactive HBV carrier (3.32 ± 0.44), and HBeAg-negative CHB (3.23 ± 0.40); (p = 4.92 × 10⁻³⁵). No significant difference was observed between inactive HBV carrier and HBeAg-negative CHB (p = 0.247). The proportions of HBsAg <2000 IU/ml for inactive HBV carrier and HBeAg-negative CHB were 51.6% and 59.3%, respectively (p = 0.341). Positive correlations between HBsAg and HBV DNA were observed for immune tolerance (p = 1.23 × 10⁻⁴) and HBeAg-positive CHB (p = 0.003), but not for HBeAg-negative CHB (p = 0.432). A negative correlation between HBsAg and age was observed for immune tolerance (p = 0.030), HBeAg-positive CHB (p = 0.016), and inactive HBV carrier (p = 0.001), but not in HBeAg-negative CHB (p = 0.249). No significant differences between HBsAg and ALT for HBeAg-positive (p = 0.338) or HBeAg-negative CHB (p = 0.564) were observed. For patients with HBsAg quantitation >250 IU/ml, HBsAg may reflect HBV DNA replication for HBeAg-positive cases. HBsAg is not a suitable marker for evaluating hepatitis activity and distinguishing between cases of HBeAg-negative CHB and inactive HBV carrier state.     

Bone mineral density in pediatric survivors of Hodgkin and non-Hodgkin lymphomas

PurposeTo assess skeletal mass in survivors of childhood Hodgkin disease (HD) and non-Hodgkin lymphoma (NHL) 1–5 years after treatment, and to identify potential risk factors influencing bone mineral density (BMD).Patients/methodsThis cross-sectional study was conducted in a cohort of 43 survivors (HD = 31; NHL = 12); mean age: 16.21 ± 4.4. Total body bone mineral content (TBMC) and density (TBBMD), and lumbar spine density (LSBMD) were determined using dual-energy X-ray absorptiometry.ResultsThree of all 43 patients developed low BMD. No significant differences in height, weight, and/or BMD Z-scores were found between HD and NHL survivors, children who received and did not receive radiotherapy, and the groups with different chemotherapeutic blocks. No differences were noted between the Z-scores of BMC (mean ± SD: 0.31 ± 1.29 vs. −0.089 ± 0.61, p = 0.165), TBBMD (mean ± SD: −0.32 ± 1.21 vs. −0.27 ± 0.91, p = 0.76), or the LSBMD (mean ± SD: −0.183 ± 1.54 vs. −0.17 ± 0.87, p = 0.637) in subgroups, in accordance with time after therapy (subgroup I < 2 years and subgroup II > 2 years after treatment). In HD survivors, age at diagnosis only affected the TBBMD Z-score (a decrease of 0.127 in total BMD Z-score per each year, R² = 0.999, p < 0.001).ConclusionsChildhood lymphoma survivors demonstrate no significant deficits in bone mass and tend to maintain their BMD within the normal range when presenting during one to five years’ follow-up. However, this specific group requires longitudinal investigation to assess the pattern of peak bone mass achievement and the risk of future bone loss.     

A 4-year study of the efficacy and tolerability of enzyme replacement therapy with agalsidase alfa in 36 women with Fabry disease

PurposeAlthough Fabry disease is X linked and considered to affect primarily male hemizygotes, female heterozygotes may experience all the signs and symptoms of this metabolic disorder. This prospective, single-center, open-label, clinical trial was performed to evaluate the long-term response of female patients with Fabry disease to enzyme replacement therapy.MethodsSymptomatic women (average age = 47 years) enrolled in this 4-year study were treated with agalsidase alfa (Replagal®, Shire HGT, Inc.) at a dose of 0.2 mg/kg, every other week for 4 years (N = 36). Clinical and biochemical assessments were conducted at 12-month intervals.ResultsThe Mainz Severity Score Index, a measure of total disease burden, was significantly reduced after 12 months (P < 0.01) of treatment and continuously improved over 4 years. Brief Pain Inventory “pain at its worst” score was reduced from 4.6 ± 2.9 at baseline to 3.3 ± 2.9 after 12 months (P = 0.001) and remained reduced through 4 years. Mean left-ventricular mass decreased from 89.4 ± 29.3 g/m^2.7 at baseline to 66.5 ± 29.3 g/m^2.7 after 12 months (P < 0.001) and remained reduced through 4 years. Average kidney function (estimated glomerular filtration rate and proteinuria) remained constant during the study. No safety issues were identified.ConclusionsLong-term agalsidase alfa is effective and was well tolerated in women with Fabry disease.     

Likely damaging de novo variants in congenital diaphragmatic hernia patients are associated with worse clinical outcomes

PurposeCongenital diaphragmatic hernia (CDH) is associated with significant mortality and long-term morbidity in some but not all individuals. We hypothesize monogenic factors that cause CDH are likely to have pleiotropic effects and be associated with worse clinical outcomes.MethodsWe enrolled and prospectively followed 647 newborns with CDH and performed genomic sequencing on 462 trios to identify de novo variants. We grouped cases into those with and without likely damaging (LD) variants and systematically assessed CDH clinical outcomes between the genetic groups.ResultsComplex cases with additional congenital anomalies had higher mortality than isolated cases (P = 8 × 10⁻⁶). Isolated cases with LD variants had similar mortality to complex cases and much higher mortality than isolated cases without LD (P = 3 × 10⁻³). The trend was similar with pulmonary hypertension at 1 month. Cases with LD variants had an estimated 12–17 points lower scores on neurodevelopmental assessments at 2 years compared with cases without LD variants, and this difference is similar in isolated and complex cases.ConclusionWe found that the LD genetic variants are associated with higher mortality, worse pulmonary hypertension, and worse neurodevelopment outcomes compared with non-LD variants. Our results have important implications for prognosis, potential intervention and long-term follow up for children with CDH.     

Postprandial ghrelin responses are associated with the intermeal interval in time-blinded normal weight men,but not in obese men

ObjectiveTo investigate the relation between ghrelin responses and meal initiation and the effects of BMI and energy status on this.DesignThe experiment had a randomised, cross-over design.Setting and subjectsNine normal-weight (age: 33.2 ± 4.8 y, BMI: 23.2 ± 0.5 kg/m²) and eleven obese (age: 40.8 ±4.7 y, BMI: 33.2 ± 0.8 kg/m²) healthy men were recruited from a pool of volunteers and by advertisements.InterventionsSubjects followed a three-day energy restrictive and a three-day energy balanced diet separated by one month. Each diet was followed by a time-blinded (overnight) stay at the research facility. Subjects received a breakfast (preload) and were instructed to ask for lunch when they felt hungry. Ghrelin, insulin, glucose, free fatty acids, appetite, IMI and energy intake during lunch were assessed.ResultsPostprandial decreases in ghrelin (r = ? 0.54; p < 0.05) and the AUC of the ghrelin response (r = ? 0.57, p = 0.01) were associated with the intermeal interval, independent of diet, but in normal weight subjects only. Lunch request was preceded by an increase in ghrelin, reaching at least 93% of fasting values. These preprandial increases in ghrelin were correlated with IMI, after energy restriction only. Ghrelin concentrations but not changes in ghrelin were correlated with appetite.ConclusionMeal-related changes in ghrelin are correlated with the IMI in normal weight subjects only, independent of diet. Ghrelin concentrations may need to reach a certain threshold level before the next meal is initiated.SponsorshipSupported by Dutch Ministry of Education, Culture and Science, Dutch Ministry of Health, Welfare and Sport and Danone Research.     

Aortic elastic properties and cognitive function in elderly individuals: The Ikaria Study

BackgroundThe aim of this work was to evaluate the association between aortic elastic properties and cognitive function in elderly individuals, permanent inhabitants of Ikaria Island.MethodsIn 535 individuals (75 ± 6 years, 53% males) aortic distensibility (AoD) was non-invasively calculated from the aortic diameters measured with echocardiography and brachial artery pressure using the formula by Stefanadis et al.; cognitive status was evaluated using the Mini Mental State Examination (MMSE).Results88% of the elders had normal values of MMSE score (i.e., ≥24). Elders who achieved MMSE score ≥24 had higher values of AoD (1.90 ± 2.06 vs. 1.08 ± 1.42, p < 0.001), as well as were more physically active (85% vs. 69%, p = 0.05), had higher educational status (8.5 ± 2.8 years vs. 6 ± 2 years, p = 0.001), higher creatinine clearance levels (70 ± 21 vs. 63 ± 23, p = 0.05) and lower pulse pressure (PP) values (63 ± 16 vs. 68 ± 18, p = 0.06), as compared with those individuals with MMSE < 24. Logistic regression analysis showed that for every unit increase in AoD there was a 25% higher likelihood of having MMSE ≥ 24 (OR per 1000 × mmHg^?1 = 1.25, 95%CI 0.99–1.58), after adjustments for age, gender, current smoking, cardiovascular disease, creatinine clearance, hypertension, diabetes mellitus, obesity, physical activity status and education status. Furthermore having PP levels in the upper tertile (>70 mmHg), increases by 55% the likelihood of having MMSE < 24 (OR for above 70 mmHg = 0.45, 95%CI 0.22, 0.92), after the same adjustments were made.ConclusionArterial aging seems to affect cognitive function; a finding that states a novel research hypothesis about the pathophysiological mechanisms of mental functioning.     

CCR2-64I and CXCL12 3′A alleles confer a favorable prognosis to AIDS patients undergoing HAART therapy

BackgroundThe chemokine receptor polymorphisms CCR5Δ32, CXCL12 3′A, CCR2-64I and CCR5-59029 G/A have been demonstrated to affect HIV-1 infection and progression.ObjectiveWe studied the impact of the above polymorphisms on the effectiveness of a 30-month treatment with highly active antiretroviral therapy (HAART) in 149 HIV-1 patients.Study designWe stratified the patients according to CD4 CDC criteria and applied Kaplan–Meier analysis using the following end-point criteria: (a) the time from HAART initiation to undetectable viral load (VL) counts (VL < 50 copies/ml), (b) the duration of undetectable VL status and (c) the time required for CD4+ T-cell counts to pass over the 500 cells/ml threshold.ResultsOur results in the second group (CD4 201–500) revealed that patients with the CCR2-64I allele achieved undetectable VL counts at 3.5 ± 0.48 months as compared to 10.26 ± 1.42 months in the control group (p = 0.018). The VL remained undetectable for 28 ± 2 months, in contrast to 20 ± 2 months in the control group (p = 0.048). Patients carrying CXCL12 3′A restored the CD4 population faster than the control group (9 ± 2 and 14 ± 2 months, respectively, p = 0.023). The CCR5Δ32 and CCR5-59029 G/A alleles did not appear to affect the parameters studied.ConclusionsOur results suggest that patients carrying either CCR2-64I or CXCL12 3′A have a more favorable prognosis during HAART treatment.     

Procalcitonin and macrophage inflammatory protein-1 beta (MIP-1β) in serum and peritoneal fluid of patients with decompensated cirrhosis and spontaneous bacterial peritonitis

PurposeSpontaneous bacterial peritonitis (SBP) is the most frequent infection in patients with cirrhosis causing significant mortality which requires rapid recognition for effective antibiotic therapy, whereas ascitic fluid cultures are frequently negative. The aim of this study was to evaluate the SBP diagnostic efficacy of procalcitonin (PCT) and macrophage inflammatory protein-1 beta (MIP-1β) measured in serum and peritoneal fluid.Material/methodsThirty-two participants with liver cirrhosis and ascites were included into the study (11 females and 21 males, mean age 49.5 ± 11.9 years). The peritoneal fluid and venous blood were collected for routine laboratory examinations and measurements of PCT and MIP-1β. Patients were divided into two groups according to the ascitic absolute polymorphonuclear leukocytes count (≥250 mm⁻³ and <250 mm^–3).ResultsAscites was sterile in 22 participants and SBP was diagnosed in 10 patients. Serum and ascitic levels of PCT and MIP-1β did not correlate with clinical and routine laboratory parameters. MIP-1β in the ascitic fluid was significantly higher in patients with SBP (213 ± 279 pg/ml vs. 66.3 ± 49.8 pg/ml; p = 0.01). The sensitivity and specificity for diagnosis of SBP with ascitic MIP-1β were 80% and 72.7%, respectively (cut-off value 69.4 pg/ml) with AUROC 0.77 (95%CI 0.58–0.96). Serum levels of MIP-1β showed lower diagnostic yield. Serum and ascitic PCT levels were not different in patients with and without SBP.ConclusionsMIP-1β concentration in ascitic fluid may distinguish patients with and without SBP with satisfactory sensitivity and specificity. Chemokines should be further explored for diagnostic use.     

Association study of rs924080 and rs11209032 polymorphisms of IL23R-IL12RB2 in a Northern Chinese Han population with Behcet’s disease

ObjectivesTwo genome-wide association studies (GWAS) have identified the IL-23 receptor- IL-12 receptor β2 (IL23R-IL12RB2) as the susceptibility genetic region in Turkish and Japanese population with Behçet’s disease (BD). We investigated the association of this region with BD in a Northern Chinese Han population.MethodsA total of 407 patients with BD and 421 healthy controls were genotyped for single nucleotide polymorphisms (SNPs) rs924080 and rs11209032 using the Sequenom MassArray system.ResultsStatistically significant associations with BD were detected at two SNPs namely, rs924080 and rs11209032, both, by allele analysis (OR = 1.58, 95% CI = 1.25–2.00, P_c = 2.52 × 10⁻⁴, and OR = 1.45, 95% CI = 1.19–1.76, P_c = 3.46 × 10⁻⁴, respectively), and genotype analysis (P_c = 1.22 × 10⁻³ and P_c = 1.77 × 10⁻³, respectively). Significant differences were observed in the genotype frequency distribution for these SNPs under the additive, dominant and recessive models (all P_c < 0.05). The haplotypes (AT and GC) formed by the two SNPs were associated with BD (all permutation P < 0.05). A meta-analysis also appeared to support the association of the two SNPs with BD.ConclusionSNPs (rs924080 and rs11209032) of the IL23R-IL12RB2 region were found to be associated with BD in a Northern Chinese Han population.     

Patient adoption of an internet based diabetes medication tool to improve adherence: A pilot study

ObjectiveTo investigate the effect of a video intervention, Managing Your Diabetes Medicines, on patient self-efficacy, problems with using medication, and medication adherence in a rural, mostly African American population.MethodsPatients selected their problem areas in medication use and watched one of nine 2-min videos with a research assistant at a clinic or pharmacy and were given an access code to watch all the videos at their convenience. Outcomes were measured at baseline and 3-month follow-up.ResultsFifty-one patients were enrolled; 84% were African American and 80% were female (mean age: 54 years). Seventy-three percent watched at least one module after the initial visit. Improved self-efficacy was associated with a decrease in concerns about medications (r = −0.64). Low literate patients experienced greater improvement in self-efficacy than more literate patients (t = 2.54, p = 0.02). Patients’ mean number of problems declined from 6.14 to 5.03. The number of patients with high or medium adherence rose from 33% at baseline to 43% at 3-month follow-up.ConclusionsA practical, customized video intervention may help improve patient self-efficacy, reduce problems with medication use, and improve medication adherence in diabetes patients.Practice implicationsProviders should consider implementing technology-based interventions in the clinic to address common problems that patients have with self-management.     

Sialylation of antibodies in kidney recipients with de novo donor specific antibody,with or without antibody mediated rejection

BackgroundDSA are associated with reduced long-term transplant function and increased prevalence of chronic rejection in some patients, whereas others do not: our goal was to determine whether the sialylation of IgG and DSA could help to explain in these last cases their “non-aggressive” and/or “protective” biological activity.MethodsThe sialylation level of total IgG in blood from two groups of kidney-transplant patients with de novo DSA, one with an AMR (DSA⁺AMR⁺), and the other without were studied.ResultsIn the DSA⁺AMR⁻ patients total IgG were more sialylated at time of transplant, and at the first detection of DSA, class I DSA were 2.6-fold more sialylated (mean 9.943 ± 1.801 versus 3.898 ± 2.475, p = 0.058); DSA⁺AMR⁺ patients exhibited higher levels of class II DSA.ConclusionsIn our study, higher levels of sialylated IgG are detectable on day of transplant in patients who do not develop AMR, they have higher sialylated class I DSA at the initial detection of DSA, whereas class II DSA are significantly higher in patients who develop AMR. This is the first report suggesting that transplant outcome, and particularly AMR, is associated with levels of sialylated IgG antibodies. Our data suggest that DSA are functionally heterogeneous and that further studies with an enlarged cohort may improve our understanding of their clinical impact.