It’s all a matter of necessity and concern: A structural equation model of adherence to antihypertensive medication

Objective

Hypertension is often treated pharmacologically, yet adherence is poor. Beliefs about antihypertensive medicine, i.e., the necessity-concern framework (NCF), are valuable for explaining adherence. Therefore, a model structure is transferred from hypercholesterolemia to hypertension, assuming a mediating role of the NCF.

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.     

Expression of GAEC1 mRNA and protein and its association with clinical and pathological parameters of patients with colorectal adenocarcinoma

Aim

GAEC1 (Gene amplified in esophageal cancer 1) is an oncogene with key regulatory roles in the pathogenesis of oesophageal and colorectal carcinomas. The aim of this study was to investigate expression profiles and clinicopathological significance of GAEC1 mRNA and protein in patients with colorectal carcinomas.

Low-dose 17-β-estradiol cream for vaginal atrophy in a cohort without prolapse: Serum levels and vaginal response including tissue biomarkers associated with tissue remodeling

ObjectivesDescribe the effect of 50 mcg vaginal 17-β-estradiol (E2) cream on vaginal maturation, serum estrogen levels, atrophic symptoms, and biomarkers of oxidative stress and tissue remodeling in postmenopausal women without prolapse.MethodsSeventeen women, 65 years or older, applied intravaginal E2 cream nightly for eight weeks, then twice weekly for eight weeks. Vaginal biopsies, serial blood draws, and atrophic symptoms were obtained at baseline, eight, and sixteen weeks. Changes in atrophic symptoms, vaginal maturation indices (VMI), and serum E2 were measured. Immunohistochemical staining characterized levels of transforming growth factor-beta (TGF-β), nuclear factor kappa B (NFKB), inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and thrombospondin (TSP).ResultsSerum E2 levels (pg/ml) were unchanged from baseline (mean (SD)) 7.7 (3.3) to eight 9.7 (5.7) and sixteen 8.7 (5.8) (p = 0.24) weeks. VMI (mean (SD)) improved from baseline 34.2 (18.3) to eight 56.7 (13.1) and sixteen 54.5 (11.3) (p < 0.001) weeks with no difference between eight and sixteen weeks. Vaginal dryness (p = 0.03) and itching (p = 0.02) improved. Tissue biomarker levels did not change (TGF-β p = 0.35, NFKB p = 0.74, eNOS p = 0.80, iNOS p = 0.24, TSP p = 0.80).DiscussionVaginal E2 improved atrophic symptoms and VMI without elevating serum E2. Tissue remodeling biomarkers did not change.     

Effort-reward imbalance,overcommitment, and cellular immune measures among white-collar employees

We investigated whether chronic job stress, i.e., effort-reward imbalance (ERI) and overcommitment is associated with cellular immunity among 190 male and 157 female white-collar daytime employees (mean age 38; range 22–69 years). Participants provided a blood sample for the measurement of circulating immune (natural killer (NK), B, and T) cell counts and NK cell cytotoxicity (NKCC) and completed a questionnaire survey during April to June 2002. Stepwise multiple linear regression analyses revealed that NK cells were associated with effort (β = −.230; p = .013), reward (β = .169; p = .047), and ERI (β = −.182; p = .047) scores but not with overcommitment in men; reward score was positively associated with NKCC (β = .167; p = .049) and inversely associated with B cells (β = −.181; p = .030). No significant associations were found in women. Although the picture remains less clear in women, our findings suggest a potential immunological pathway linking adverse working conditions and stress-related disorders in men.     

Transformational leadership and depressive symptoms: A prospective study

ObjectiveThe aim of this study was to examine the association between transformational leadership and depressive symptoms in employees working within healthcare.Method447 employees completed a baseline survey and 274 completed a follow-up survey 18 months later. 188 completed both baseline and follow-up survey. Transformational leadership was measured using the Global Transformational Leadership Scale and depression was measured using with the Major Depression Inventory.ResultsTransformational leadership was negatively associated with depressive symptoms at baseline (β = ? 0.31, p < .01, 8% variance) follow-up (β = ? 0.25, p < .01, 3% variance) and prospectively (β = ? 0.21, p < .05, 4% variance).ConclusionManagers with a transformational leadership style may help toward protecting employees from developing major depression.     

Effect of lavage and brush preparation on cement penetration and primary stability in tibial unicompartmental total knee arthroplasty: An experimental cadaver study

Background

Unicompartmental total knee arthroplasty (UKA) is a well-established treatment option for unicondylar osteoarthritis, and generally leads to better functional results than tricompartimental total knee arthroplasty (TKA). However, revision rates of UKAs are reported as being higher; a major reason for this is aseptic loosening of the tibial component due to implant–cement–bone interface fatigue. The objective of this study was to determine the effects of trabecular bone preparation, prior to implantation of tibial UKAs, on morphological and biomechanical outcomes in a cadaver study.

Higher decidual EBI3 and HLA-G mRNA expression in preeclampsia: Cause or consequence of preeclampsia

The maternal immune system must adapt to tolerate the invasion of the allogeneic feto-placental unit. It is generally accepted that improper adaptation causes pregnancy complications like preeclampsia. The Epstein–Barr virus-induced gene 3 (EBI3) protein is a subunit of immune-modulatory cytokines interleukin 27 (IL-27) and IL-35. EBI3 has been reported to associate with HLA-G. In this small pilot study we find higher decidual EBI3 (p < 0.05) and HLA-G (p < 0.01) mRNA expression in preeclampsia (n = 7) compared to normotensive (n = 8) pregnancies. Whether the higher EBI3 and HLA-G mRNA expression is a consequence or cause of preeclampsia remains to be answered. Further research to determine the effects on IL-27 and IL-35 is needed.     

Roles of mammalian structural units,ligand cluster and polyvalency in the Abrus precatorius agglutinin and glycoprotein recognition process

Previous studies on one of the toxic type 2 ribosome inactivating proteins (RIP), Abrus precatorius agglutinin (APA), have shown that the recognition domains of APA are restricted to monomers of Galβ1-3GalNAc (T, Thomsen-Friedenreich glycotope) and Galβ1-3/4GlcNAc (blood group precursor type I/II sequences); which are essential but play a minor role in the recognition process. In this study, APA recognition factors were expanded to include ligand clusters and polyvalent glycotopes by enzyme-linked lectinosorbent binding and inhibition assays. Based on the results of molar relative potency, the essential mammalian structural units are Galβ1-3GalNAcα/β1- (T_α/T_β) > Galα1-4Gal (E) > Galβ1-3/4GlcNAc (I/II) and avidity for tri-/di-antennary II_β, T, E and II monomers was found to be 7.1 × 10², 4.0, 5.5, 3.7 and 2.4 times higher than monomeric Gal. Among natural polyvalent glycotopes or clusters, high-density polyvalent T_α and complex multivalent I_β/II_β glycotopes greatly enhanced the affinity for APA over 10⁴ times. Based on these results, it is concluded that contribution of monomeric T_α, II_β, I_β, E_β and their clusters and polyvalency play critical roles in this recognition process. The binding intensities of these factors in decreasing order are: polyvalent T_α, II_β/I_β and E_β > tri-antennary II_β ≫ monomeric T_α, T_β, I and II > Gal ≫ GalNAc (weak). As one of type 2 RIP lectins, these recognition factors of the B chain are likely to be crucial for attachment and endocytosis. A comparison of the differential recognition factors and combining sites of APA with those of other lectins (Ricinus communis agglutinin, RCA₁ and ricin) is also illustrated.     

Single-limb landing biomechanics are altered and patellar tendinopathy related pain is reduced with acute infrapatellar strap application

Background

Patellar tendinopathy, a common condition of the knee, is often treated with patellar tendon straps to control pain during dynamic activity. Little is known regarding their effect on pain, landing kinematics and kinetics with their application. The purpose of this study was to determine if patellar tendon straps influenced pain, kinematics at landing and ground reaction forces in individuals with patellar tendinopathy versus healthy controls.

Relationships between serum uric acid,adiponectin and arterial stiffness in postmenopausal women

ObjectivesCardiovascular disease (CVD) is a leading cause of death in postmenopausal women. Elevated serum uric acid levels, hypoadiponectinemia and arterial stiffness are strongly associated with cardiovascular diseases. We investigated the relationships among uric acid, adiponectin and arterial stiffness in postmenopausal women.Study design9555 subjects who had the routine health check-ups, 841 postmenopausal women aged 50 years or older who had not had a menstrual period for more than 12 consecutive months were included in this study.Main outcome measuresBMI, WC, and serum concentrations of uric acid, adiponectin, glucose, lipids (total cholesterol, triglycerides, LDL cholesterol, and HDL cholesterol) were measured. Insulin resistance was estimated by the insulin resistance index of homeostasis model assessment (HOMA-IR). Pulse wave velocity (PWV) was evaluated to assess arterial stiffness.ResultsThe subjects were stratified into three groups according to uric acid values. PWV values gradually increased and adiponectin level decreased with uric acid tertiles. Serum uric acid levels in postmenopausal women correlated significantly with age, BMI, WC, TG, HDL-C, insulin, HOMA-IR, adiponectin and PWV. Multiple regression analysis showed that WC (β = 0.141, P < 0.01), HOMA (β = 0.137, P < 0.01), adiponectin (β = −0.104, P < 0.01), and PWV (β = 0.129, P < 0.01) were independently correlated with uric acid levels. In multiple logistic regression analysis after adjusting for risk factors, uric acid was a significant contributor to increased PWV.ConclusionsThese findings indicate that serum uric acid is independently associated with adiponectin and arterial stiffness in postmenopausal women.     

Micro-CT evaluation of bone defects: Applications to osteolytic bone metastases,bone cysts,and fracture

Bone defects can occur in various forms and present challenges to performing a standard micro-CT evaluation of bone quality because most measures are suited to homogeneous structures rather than ones with spatially focal abnormalities. Such defects are commonly associated with pain and fragility. Research involving bone defects requires quantitative approaches to be developed if micro-CT is to be employed. In this study, we demonstrate that measures of inter-microarchitectural bone spacing are sensitive to the presence of focal defects in the proximal tibia of two distinctly different mouse models: a burr-hole model for fracture healing research, and a model of osteolytic bone metastases. In these models, the cortical and trabecular bone compartments were both affected by the defect and were, therefore, evaluated as a single unit to avoid splitting the defects into multiple analysis regions. The burr-hole defect increased mean spacing (Sp) by 27.6%, spacing standard deviation (SpSD) by 113%, and maximum spacing (Sp_max) by 72.8%. Regression modeling revealed SpSD (β = 0.974, p < 0.0001) to be a significant predictor of the defect volume (R² = 0.949) and Sp_max (β = 0.712, p < 0.0001) and SpSD (β = 0.271, p = 0.022) to be significant predictors of the defect diameter (R² = 0.954). In the mice with osteolytic bone metastases, spacing parameters followed similar patterns of change as reflected by other imaging technologies, specifically bioluminescence data which is indicative of tumor burden. These data highlight the sensitivity of spacing measurements to bone architectural abnormalities from 3D micro-CT data and provide a tool for quantitative evaluation of defects within a bone.     

Strong correlation between tax and HBZ mRNA expression in HAM/TSP patients: Distinct markers for the neurologic disease

BackgroundHTLV-1 proviral load is a risk marker for HAM/TSP, but it is insufficient to determine the disease outcome. HTLV-1 Tax and HBZ proteins have been implicated in HAM/TSP pathogenesis in inducing cell proliferation and cytotoxic T lymphocytes response.ObjectivesTo quantify the expression of tax and HBZ mRNA in asymptomatic carriers (AC) and HAM patients, and to investigate their association with HAM/TSP.Study designWe quantified the expression of HTLV-1 tax and HBZ mRNA in 37 AC and 26 HAM patients classified according to proviral load as low (AC_L and HAM_L: <1% infected cells) or high (AC_H and HAM_H: >1%).ResultsThe AC_L subgroup showed the lowest frequency of individuals expressing tax mRNA in comparison with AC_H, HAM_L and HAM_H, and tax mRNA load normalized by proviral load was significantly lower in the AC_L. In turn, normalized HBZ mRNA expression was similar in all subgroups. Both tax and HBZ mRNA expression were moderately correlated with proviral load in AC (r = 0.6, p < 0.001) and were weaker in HAM (r = 0.4, p < 0.05). In contrast, the correlation between tax and HBZ mRNA load was moderate in AC (r = 0.5, p = 0.001) and was much stronger in HAM (r = 0.8, p < 0.001). In addition, HBZ mRNA load, but not tax, was significantly associated with motor disability in HAM patients (p = 0.036).ConclusionsThe expression of tax mRNA seems to be best to estimate the risk of HAM/TSP, whereas HBZ mRNA appears to be a surrogate marker to disease progression, indicating that they have important but distinct roles in HAM/TSP pathogenesis.     

SIRT1 as a potential biomarker of response to treatment with glatiramer acetate in multiple sclerosis

SIRT1, a NAD dependent histone and protein deacetylase, is a member of the histone deacetylase class III family. We previously showed that SIRT1 mRNA expression is significantly lower in peripheral blood mononuclear cells (PBMCs) of multiple sclerosis (MS) patients during relapses than in stable patients. We have now investigated SIRT1 as a possible biomarker to predict relapse as well as responsiveness to glatiramer acetate (GA) treatment in relapsing-remitting MS (RRMS) patients. Over the course of 2 years, a cohort of 15 GA-treated RRMS patients were clinically monitored using the Expanded Disability Status Scale and assessed for MS relapses. Blood samples collected from MS patients were analyzed for levels of SIRT1 and histone H3 lysine 9 (H3K9) acetylation and dimethylation. During relapses, MS patients had a lower expression of SIRT1 mRNA than did stable MS patients. In addition, there was a significant decrease in H3K9 dimethylation (H3K9me2) during relapses in MS patients when compared to stable patients (p = 0.01). Responders to GA treatment had significantly higher SIRT1 mRNA (p = 0.01) and H3K9me2 levels than did non-responders (p = 0.018). Receiver operating characteristic analysis was used to assess the predictive power of SIRT1 and H3K9me2 as putative biomarkers: for SIRT1 mRNA, the predictive value for responsiveness to GA treatment was 70% (p = 0.04) and for H3K9me2 was 71% (p = 0.03). Our data suggest that SIRT1 and H3K9me2 could serve as potential biomarkers for evaluating patients' responsiveness to GA therapy in order to help guide treatment decisions in MS.     

Evaluation of a CT-based technique to measure the transfer accuracy of a virtually planned osteotomy

Accurate transfer of a preoperatively planned osteotomy plane to the bone is of significance for corrective surgery, tumor resection, implant positioning and evaluation of new osteotomy techniques. Methods for comparing a preoperatively planned osteotomy plane with a surgical cut exist but the accuracy of these techniques are either limited or unknown. This paper proposes and evaluates a CT-based technique that enables comparing virtual with actual osteotomy planes. The methodological accuracy and reproducibility of the technique is evaluated using CT-derived volume data of a cadaver limb, which serves to plan TKA osteotomies in 3-D space and to simulate perfect osteotomies not hampered by surgical errors. The methodological variability of the technique is further investigated with repeated CT scans after actual osteotomy surgery of the same cadaver specimen. Plane displacement (d_err) and angulation errors in the sagittal and coronal plane (β_err, γ_err) are measured with high accuracy and reproducibility (d_err = −0.11 ± 0.06 mm; β_err = 0.08 ± 0.04°, γ_err = −0.03 ± 0.03°). The proposed method for evaluating an osteotomy plane position and orientation has a high intrinsic accuracy and reproducibility. The method can be of great value for measuring the transfer accuracy of new techniques for positioning and orienting a surgical cut in 3-D space.     

Analysis of IL10 haplotypes in primary Sjögren’s syndrome patients from Western Mexico: Relationship with mRNA expression,IL-10 soluble levels,and autoantibodies

Primary Sjögren’s syndrome (pSS) is an autoimmune disease characterized by lymphocytic infiltration of salivary and lacrimal glands. Interleukin-10 (IL-10) plays a role in autoimmune diseases by promoting B-cell activation and autoantibodies production. IL10-1082A > G, -819C > T, -592C > A polymorphisms and their haplotypes have been associated with IL-10 production. The aim of this study was to associate IL10 haplotypes with mRNA expression and soluble IL-10 levels with susceptibility to pSS in 111 Mexican patients and 111 healthy subjects (HS). Primary Sjögren’s syndrome patients showed high levels of sIL-10 (p = 0.0001 vs HS) correlating with anti-Ro and anti-La antibodies (p < 0.05). In addition, IL10 mRNA expression in pSS was higher than HS (0.8 vs 0.1, p = 0.1537). However, no difference was observed in sIL-10 levels between haplotypes. Patients carriers of GCC haplotype showed higher mRNA expression than ACC + ATA (1.4 vs 0.6, p = 0.2424) and high foci number (p = 0.04 vs ACC). Our results suggest a strong relationship of IL10 with pSS which is demonstrated by the increased mRNA expression and also high sIL-10 levels positively correlated with autoantibodies. Besides that, the GCC haplotype carriers expressed high mRNA. However, IL10 haplotypes were not associated with sIL-10 in pSS from Western Mexico which suggest that diverse biological factors may regulate the IL10 expression in pSS.     

Predicted 3D-structure of melanopsin, the non-rod, non-cone photopigment of the mammalian circadian clock, from Djungarian hamsters (Phodopus sungorus)

Melanopsin is the photopigment of the retinal ganglion cells, which are involved in the synchronization of the biological clock in the suprachiasmatic nucleus (SCN) of mammals with the exogenous photoperiod. So far, no information about the three-dimensional (3D) structure of melanopsin is available. Here we report the predicted structure based on the protein-coding region of the nucleotide sequence of the gene for melanopsin, originating from isolated mRNA from the eyes of Djungarian hamsters (Phodopus sungorus). The nucleotide sequence shares the largest homologies with melanopsin of mice and rats (each 89%) and humans (84%). Based on the amino-acid sequence, and in comparison with the known structure of bovine rhodopsin, the three-dimensional melanopsin protein structure was modeled by using automated homology modeling approaches that were subsequently refined. Melanopsin consists of highly conserved seven-transmembrane domains and a long cytoplasmatic tail with multiple putative phosphorylation sites. In the binding site of the chromophore, a 11-cis-retinal is likely to be bound to lysine at position 336 as Schiff's base. The modeling results may indicate different photoisomerization within the melanopsin molecule compared with bovine rhodopsin.     

Subchronic inhalation of coal dust particulate matter 10 induces bronchoalveolar hyperplasia and decreases MUC5AC expression in male Wistar rats

Coal dust is a pollutant found in coal mines that are capable of inducing oxidative stress and inflammation, but the effects on lung metaplasia as an early step of carcinogenesis remain unknown. The purpose of the present study was to evaluate the effects of PM₁₀ coal dust on lung histology, MUC5AC expression, epidermal growth factor (EGF) expression, and epidermal growth factor receptor (EGFR) expression. An experimental study was done on male Wistar rats, which were divided into the following groups: control groups exposed to coal dust for 14 days (at doses of 6.25 mg/m³, 12.5 mg/m³, and 25 mg/m³), and the groups exposed to coal dust for 28 days (at doses of 6.25 mg/m³, 12.5 mg/m³, and 25 mg/m³). EGF expressions in rat lungs were measured by ELISA. EGFR and MUC5AC were measured by a confocal laser scanning microscope. The bronchoalveolar epithelial image of the group exposed to coal dust for 14 and 28 days showed a epithelial rearrangement, hyperplastic (metaplastic) goblet cells, and scattered massive inflammatory cells. The pulmonary parenchymal image of the group of exposed to coal dust for 14 and 28 days showed scattered inflammatory cells filling up the pulmonary alveolar networks, leading to an appearance of thickened parenchymal alveoli until emphysema-like structure. There was no significant difference in MUC5AC, EGF, and EGFR expressions for 14-d exposure (p > 0.05). There was no significant difference in EGF and EGFR expressions for 28-d exposure (p > 0.05), but there was a significant difference in MUC5AC expression (p < 0.05). We concluded that subchronic inhalation of coal dust particulate matter 10 induces bronchoalveolar reactive hyperplasia and rearrangement of epithelial cells which accompanied by decrease expression MUC5AC in male rats.