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.

Genetic variants of TLR4 and TLR9 are risk factors for chronic Helicobacter pylori infection in South Indian Tamils

Toll like receptors (TLRs) are a class of molecular pattern recognition receptors, elicits a strong inflammatory immune response against pathogens. Helicobacter pylori (H. pylori), a gram negative flagellate colonizes the human stomach, is responsible for the development of chronic gastritis and gastric carcinoma. The higher incidence of H. pylori infection and gastric cancer in South Indian Tamils demands a genetic study to unravel the influence of TLR4 and TLR9 polymorphisms associated with chronic H. pylori infection. In this study, 230 healthy individuals and 77 patients diagnosed with H. pylori infection were screened for TLR4 (rs1927914, rs4986790, rs4986791) and TLR9 (rs352140, rs34399053, rs150459369) polymorphisms by PCR-RFLP and ARMS-PCR. We observed that the individuals harboring heterozygous and homozygous polymorphic variants of TLR4 conferred a significant risk to develop chronic H. pylori infection and peptic ulcer disease [rs4986790 AG, p = 0.001, OR-2.7, 95%CI: 1.5–5.03; GG, p = 0.0006, OR-9.8, 95%CI: 2.4–39.4; rs4986791CT, p = 0.0001, OR-7.2, 95%CI: 3.7–7.2; TT, p = 0.0001, OR-7.9, 95%CI: 2.6–23.7]. Also, the heterozygous variant of TLR9 rs352140, favoured the persistence of the H. pylori infection [p = 0.037, OR-1.87, 95%CI: 1.07–3.29]. Thus our findings suggest that TLR4 rs4986790, rs4986791 and TLR9 rs352140 polymorphisms are potential genetic risk factors influencing the disease susceptibility and clinical manifestation of chronic H. pylori infection in Indian Tamils.     

Interstitial lung disease in primary Sjögren's syndrome

Interstitial lung disease (ILD) has been reported in 3 to 11% of patients with primary Sjögren's syndrome (pSS). The aims of this retrospective multicenter study were to: 1) analyze characteristics and outcome of ILD in pSS; and 2) evaluate predictive factors associated with ILD onset and deterioration. Twenty-one of 263 patients with pSS (8%) developed ILD. ILD onset preceded pSS diagnosis (n = 5), was concurrently identified in association with pSS (n = 6) and developed after pSS onset (n = 9). Presenting ILD manifestations were: acute/subacute (n = 11) onset of ILD, symptomatic progressive onset of ILD (n = 5), and asymptomatic patients exhibiting abnormalities consistent with ILD on PFTs and HRCT-scan (n = 5). ILD therapy included: steroids (n = 21), cyclophosphamide (n = 1), azathioprine (n = 4) and rituximab (n = 1). The course of ILD was as follows: improvement (15.8%), stabilization (47.4%) or deterioration (36.8%). Predictive parameters of ILD onset were: older age (p = 0.044), Raynaud's phenomenon (p = 0.001) and esophageal involvement (p = 0.001). Factors associated with ILD deterioration were: older age (p = 0.038) and esophageal involvement (p = 0.038). Thus, this study underscores the poor outcome of ILD during pSS; thus, systematic screening of pulmonary involvement is required in pSS patients, resulting in both diagnosis and management at early stage of ILD. We also suggest that patients presenting predictive factors of ILD deterioration may need a closer follow-up and a more aggressive therapy.     

Efficacy and safety of rituximab in systemic sclerosis: French retrospective study and literature review

Objective

To describe safety and efficacy of rituximab in patients with systemic sclerosis.

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.

PADI4 polymorphisms and the functional haplotype are associated with increased rheumatoid arthritis susceptibility: A replication study in a Southern Mexican population

Rheumatoid arthritis (RA) is a common autoimmune disease with a complex genetic background. The peptidyl arginine deiminase type IV (PADI4) gene has been associated with RA susceptibility in several populations. We addressed the relationship between three exonic PADI4 gene single nucleotide polymorphisms (SNPs) PADI4_89 (rs11203366), PADI4_90 (rs11203367) and PADI4_92 (rs874881) and related haplotypes with RA in a population from Southern México. This study included 200 RA patients and 200 control subjects. The SNPs were evaluated using the polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) technique, and antibodies to cyclic citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent assay (ELISA). In this population, the minor alleles of PADI4_891G, PADI4_901T and PADI4_921G gene polymorphisms were associated with RA susceptibility (OR = 1.34, p = 0.04; OR = 1.35, p = 0.03; OR = 1.34, p = 0.04; respectively). The GTG haplotype was also significantly associated with RA (OR = 2.27 95%CI = 1.18–4.41; p = 0.008), but did not show association with levels of anti-CCP antibodies and clinical parameters. In conclusion, our replication study in a Southern Mexican population suggests that PADI4 individual polymorphisms and the related susceptibility haplotype (GTG) are also genetic risk markers for RA.     

Increased expression of TIPE2 mRNA in PBMCs of patients with ankylosing spondylitis is negatively associated with the disease severity

Ankylosing spondylitis (AS) is an autoimmune disease and characterized by chronic inflammatory arthritis. Tumor necrosis factor α induced protein-8 like-2 (TIPE2) is responsible for maintaining immune homeostasis by inhibiting the secretion of inflammatory cytokines in the condition of inflammation. However, whether TIPE2 participates in the development of AS remains unknown. In this study, we measured the mRNA expression of TIPE2 and TIPE1 in peripheral blood mononuclear cells (PBMCs) from 45 AS patients and 40 healthy controls by qRT-PCR. The results showed TIPE2 expression was significantly increased in AS patients compared with controls (P=0.0066), while there was no significant difference for TIPE1 between two groups (P = 0.2302). Moreover, the expression of TIPE2 mRNA in AS patients were decreased after treatment with TNF-α blocker (P < 0.001). In addition, we found that TNF-α or plasma from AS patients induced TIPE2 expression in THP-1 cells in vitro. More importantly, the TIPE2 mRNA expression levels were negatively correlated with TNF-α, hsCRP and bath ankylosing spondylitis disease activity index (BASDAI) (r = ?0.3574, P = 0.0159; r = ?0.3174, P = 0.0336; r = ?0.6000, P < 0.0001; respectively) in the AS patients. These results indicated that TIPE2 contributes to the pathogenesis of AS.     

Clinical predictors of the leading pathogens in human immunodeficiency virus-infected adults with community-onset bacteremia in the emergency department: The importance of transmission routes

Background/Purpose

To investigate the clinical characteristics and pathogens of community-onset bacteremia among human immunodeficiency virus (HIV)-infected adults as well as to establish the clinical predictors of the major microorganisms.

Association of rs1285933 single nucleotide polymorphism in CLEC5A gene with dengue severity and its functional effects

Outbreaks of the Zika, dengue, and chikungunya viruses, especially in the Americas, pose a global threat due to their rapid spread and difficulty controlling the vector. Extreme phenotypes are often observed, from asymptomatic to severe clinical manifestations, which are well-studied in dengue. Host variations are also important contributors to disease outcomes, and many case-control studies have associated single nucleotide polymorphisms (SNPs) with severe dengue. Here, we found that the TC genotype and T-carriers for SNP rs1285933 in the C-type lectin superfamily member 5 (CLEC5A) gene was associated with severe dengue in a Northern Brazilian population (OR = 2.75 and p-value = 0.01, OR = 2.11 and p-value = 0.04, respectively). We also tested the functional effect of the CLEC5A protein and found that it is upregulated on the surface of human monocytes after in vitro dengue infection. CLEC5A was correlated with viral load inside the monocytes (Spearman r = 0.55, p = 0.008) and TNF production in culture supernatants (Spearman r = 0.72, p = 0.03). Analysis of mRNA in blood samples from DENV4-infected patients exhibiting mild symptoms showed that CLEC5A mRNA expression is correlated with TNF (r = 0.67, p = 0.0001) and other immune mediators. Monocytes from rs1285933 TT/TC individuals showed lower CLEC5A expression compared to CC genotypes. However, in these cells, CLEC5A was not correlated with TNF production. In summary, we confirmed that CLEC5A is genetically associated with dengue severity outcome, playing a central role during the immune response triggered by a dengue viral infection, and rs1285933 is a relevant SNP that is able to regulate signaling pathways after interactions between the dengue virus and CLEC5A receptors.     

Clinical characteristics and outcome of invasive fungal infections in pediatric acute myeloid leukemia patients in a medical center in Taiwan

Background

Invasive fungal infection (IFI) causes significant morbidity and mortality in patients with hematological malignancies, especially those with acute myeloid leukemia (AML), recurrent acute leukemia, high-risk acute lymphoblastic leukemia, and after allogeneic hematopoietic stem cell transplantation. The study aimed to investigate the clinical characteristics and outcome of IFIs in pediatric AML patients in a medical center in Taiwan.

Revisiting the systemic vasculitis in eosinophilic granulomatosis with polyangiitis (Churg-Strauss): A study of 157 patients by the Groupe d'Etudes et de Recherche sur les Maladies Orphelines Pulmonaires and the European Respiratory Society Taskforce on eosinophilic granulomatosis with polyangiitis (Churg-Strauss)

Objective

To guide nosology and classification of patients with eosinophilic granulomatosis with polyangiitis (EGPA) based on phenotype and presence or absence of ANCA.

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.

Lower levels of IL-4 and IL-10 influence lipodystrophy in HIV/AIDS patients under antiretroviral therapy

Background

The role of interleukins in the pathogenesis of lipodystrophy in HIV/AIDS-patients is still not understood. The aim of this study was to evaluate the relationship between serum levels of interleukins between HIV/AIDS-patients with or without lipodystrophy, as well as between different subgroups of lipodystrophy (lipoatrophy, lipohypertrophy, mixed-fat-redistribution) and patients without lipodystrophy.

Coronal alignment predicts the use of semi-constrained implants in contemporary total knee arthroplasty

Background

Semi-constrained, or varus–valgus constrained, implants are occasionally necessary to achieve stability in primary total knee arthroplasty (TKA). However, outcomes with these implants are largely unknown. Therefore, the primary goals of this study were to determine 1) can we identify preoperatively which patients might require a semi-constrained implant and 2) are there any clinical and or radiographic differences for those that require a semi-constrained implant?

Cogan syndrome: Characteristics,outcome and treatment in a French nationwide retrospective study and literature review

Background

Cogan syndrome is mainly treated with steroids. We aimed to determine the place of DMARDs and biologic-targeted treatments.

Exploring individual adaptations to an anterior cruciate ligament injury prevention programme

Background

Individual responses to anterior cruciate ligament injury prevention programmes (ACL IPPs) have received little attention. This study examined the effects of an ACL IPP on neuromuscular control and lower limb biomechanics during landing at the group and individual levels.

Learning styles and gross anatomy assessment outcomes at a Colombian School of Medicine

The term, “learning styles” refers to the concept that individuals have as regards the method of instruction or study that is most efficient for them. It has been proposed that optimal learning occurs when the preferences of the primary learning style of the student correspond to the course content and the method of instruction. The Visual, Aural, Written/Read and Kinesthetic (VARK) model is a preferred instruction model. The objective of the study was to investigate the relationship between the VARK preferences and the Gross Anatomy test results of a group of students from the Universidad del Norte. The study included 111 (61 female and 50 male) students enrolled in their third semester of medical school in the skeletomuscular system during the summer of 2015. The VARK Aural and Kinesthetic modes were the most common (34.2% and 26.1%, respectively), while Visual was the learning style with the lowest number of representatives (9%). The multimodal style was preferred by 12.6% of the students involved. There was no significant statistical relationship (X² = 2.61; p = .62 and X² = 5.4; p = .24) between the VARK modes and the mid-term test results. The Aural and Kinesthetic modes showed significant negative correlations with the mid-term electronic multiple-choice assessment (r_s = ?0.19; p = .03; and (r_s = ?0.24; p = .01). Although different teaching strategies were offered to the students, no significant differences were observed. However, the students with Aural and Kinesthetic modes did show a negative correlation with the mid-term electronic multiple-choice assessment.     

Large-vessel involvement and aortic dilation in giant-cell arteritis. A multicenter study of 549 patients

Objectives

Large-vessel involvement (LVI) can occur in giant-cell arteritis (GCA) and may represent a distinct disease subgroup with a higher risk for aortic dilation. This study aimed to better characterize the presentation and evolution of LVI in patients with GCA.

Endurance training reduces exercise-induced acidosis and improves muscle function in a mouse model of sickle cell disease

Sickle cell disease (SCD) mice (Townes model of SCD) presented exacerbated exercise-induced acidosis and fatigability as compared to control animals. We hypothesize that endurance training could represent a valuable approach to reverse these muscle defects. Endurance-trained HbAA (HbAA-END, n = 10), HbAS (HbAS-END, n = 11) and HbSS (HbSS-END, n = 8) mice were compared to their sedentary counterparts (10 HbAA-SED, 10 HbAS-SED and 9 HbSS-SED mice) during two rest – exercise – recovery protocols during which muscle energetics and function were measured. In vitro analyses of some proteins involved in muscle energetics, pH regulation and oxidative stress were also performed. Exercise-induced acidosis was lower in HbSS-END mice as compared to their sedentary counterparts during both moderate (p < 0.001) and intense (p < 0.1) protocols. The total force production measured during both protocols was higher in trained mice compared to sedentary animals. In vitro analyses revealed that enolase/citrate synthase ratio was reduced in HbSS-END (p < 0.001) and HbAS-END (p < 0.01) mice compared to their sedentary counterparts. In addition, malondialdehyde concentration was reduced in trained mice (p < 0.05). In conclusion, endurance training would reverse the more pronounced exercise-induced acidosis, reduce oxidative stress and ameliorate some of the muscle function parameters in SCD mice.