Association of simple hematological parameters with disease manifestations,activity, and severity in patients with systemic sclerosis

Clinical Rheumatology - Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), mean platelet volume (MPV), and red cell distribution width (RDW) may potentially reflect...     

Toxicity of ayahuasca after 28 days daily exposure and effects on monoamines and brain-derived neurotrophic factor (BDNF) in brain of Wistar rats

Metabolic Brain Disease - Ayahuasca is a hallucinogenic beverage that affects the serotonergic system and have therapeutic potential for many diseases and disorders, including depression and drug...     

Collapsin response‐mediator protein 5 (CRMP5) phosphorylation at threonine 516 regulates neurite outgrowth inhibition

The collapsin response‐mediator proteins (CRMPs) are multifunctional proteins highly expressed during brain development but down‐regulated in the adult brain. They are involved in axon guidance and neurite outgrowth signalling. Among these, the intensively studied CRMP2 has been identified as an important actor in axon outgrowth, this activity being correlated with the reorganisation of cytoskeletal proteins via the phosphorylation state of CRMP2. Another member, CRMP5, restricts the growth‐promotional effects of CRMP2 by inhibiting dendrite outgrowth at early developmental stages. This inhibition occurs when CRMP5 binds to tubulin and the microtubule‐associated protein MAP2, but the role of CRMP5 phosphorylation is still unknown. Here, we have studied the role of CRMP5 phosphorylation by mutational analysis. Using non‐phosphorylatable truncated constructs of CRMP5 we have demonstrated that, among the four previously identified CRMP5 phosphorylation sites (T509, T514, T516 and S534), only the phosphorylation at T516 residue was needed for neurite outgrowth inhibition in PC12 cells and in cultured C57BL/6J mouse hippocampal neurons. Indeed, the expression of the CRMP5 non‐phosphorylated form induced a loss of function of CRMP5 and the mutant mimicking the phosphorylated form induced the growth inhibition function seen in wildtype CRMP5. The T516 phosphorylation was achieved by the glycogen synthase kinase‐3β (GSK‐3β), which can phosphorylate the wildtype protein but not the non‐phosphorylatable mutant. Furthermore, we have shown that T516 phosphorylation is essential for the tubulin‐binding property of CRMP5. Therefore, CRMP5‐induced growth inhibition is dependent on T516 phosphorylation through the GSK‐3β pathway. The findings provide new insights into the mechanisms underlying neurite outgrowth.     

Integration of Modern Molecular Tools with Geological Processes to Reveal Species Phylogeny,Biogeographical Niche Prediction,and Bio-Evolution

Nature is integrated, being simultaneously controlled by different natural aspects. Genetics, bioinformatics, biostatistics and geology are four diverse and broad scientific disciplines. But we believe that these can offer important insights into species distribution and evolution, if integrated. This perspective is grounded on a case study of the family Salvadoraceae, where species distribution and phylogeny show high correlation with the geological records. The results obtained from published and ongoing research indicate that we are pointing toward better visualizing the overlapping boundaries of these specific disciplines, which will be able to more accurately answer key evolutionary questions. We highlight: (1) the combined application of bedrock-soil geological data and bioinformatics to resolve evolutionary questions regarding species eco-distribution, niche prediction and bio-evolution; and (2) signifies the importance of relaxing boundaries between the disciplines to come to a better conclusion on species diversity and distribution-driven controls. Overall, we express and briefly explain our hypothesis to integrate modern analytical tools, viz., statistical correlation of geological data via. geo-statistics (Geo), and spatiotemporal biostatistics via. geo-informatics (Geo), with gene-based paleontological shreds of evidence, and sequence-based bioinformatics, to devise a practical analysis tool, namely “Geo² gene-bioinformatics”. We invoke the development of algorithms through computational-based programs that can provide useful correlations to understand evolutionary systematics and phylogeny, species distribution, and niche prediction.

     

High Frequency of Serum Chromium Deficiency and Association of Chromium with Triglyceride and Cholesterol Concentrations in Patients Awaiting Bariatric Surgery

Background

To our knowledge, the frequency of serum chromium deficiency in patients awaiting bariatric surgery has not been determined. This study was designed to assess chromium concentration and its association with glycemic levels and lipid profile in patients prior to bariatric surgery.

Methods

This study recruited 73 candidates for bariatric surgery between March and September 2012. Their sociodemographic, anthropometric, and biochemical data were collected.

Results

Of the 73 patients, 55 (75.3 %) were women (75.34 %). Mean patient age was 37.20?±?9.92 years, and mean body mass index was 47.48 kg/m² (range, 43.59 to 52.50 kg/m²). Chromium deficiency was observed in 64 patients (87.7 %). Correlation analysis showed significant negative relationships between chromium concentration and BMI and zinc concentration and a significant positive relationship between chromium and glycated hemoglobin. Multiple linear regression analysis showed that serum chromium concentration was significantly associated with total cholesterol (β?=?0.171, p?=?0.048) and triglyceride (β?=??0.181, p?=?0.039) concentrations.

Conclusions

Serum chromium deficiency is frequent in candidates for bariatric surgery and is associated with total cholesterol and triglyceride concentrations. Early nutritional interventions are needed to reduce nutritional deficiencies and improve the lipid profile of these patients.     

Pelvis width associated with bone mass distribution at the proximal femur in children 10–11 years old

Differences in skeletal geometry may generate different patterns of mechanical loading to bone. Impact and muscle loading during physical activity have been shown to influence skeletal geometry. The purpose of this study was to compare geometric measures of the pelvis and proximal femur (PF) of young children and to analyze the contribution and potential interaction of these geometric measures with physical activity on PF bone mass distribution. Participants were 149 girls and 145 boys, aged 10–11 years. Total body and left hip DXA scans were used to derive pelvic and PF geometric measures and PF bone mineral density (BMD) at the femoral neck (FN), trochanter (TR), and intertrochanter (IT). These subregions were used to represent bone mass distribution via three BMD ratios: FN:PF, TR:PF, and IT:PF. Physical activity was objectively measured using accelerometry, and maturity was estimated as the years of distance from peak height velocity. When compared to boys, girls had a wider pelvic diameter and greater interacetabular distances (p < 0.001), lower BMD at FN, TR, and IT (p < 0.05), and higher TR:PF (p < 0.001). After controlling for maturity, body height, and lean body mass, the interacetabular distance in girls explained 21.1 % (β = 0.713, p < 0.001) in TR:PF and 2.9 % (β = ?0.179, p = 0.031) in the IT:PF. Neck–shaft angle explained 5.6 % (β = ?0.265, p = 0.001) of the IT:PF and 3.1 % (β = 0.194, p = 0.018) of the FN:PF. In boys, FN axis length explained 2.9 % (β = 0.195, p = 0.040) of TR:PF. There was no main effect of physical activity or interaction effect with pelvic geometry in explaining BMD differences among the subregions of the PF. Even before sexual dimorphism, girls have a wider pelvis than boys, which accounted for proportionally greater BMD of the TR than other subregions of the PF.     

C3 nephritic factor associated with C3 glomerulopathy in children

Background

C3 glomerulopathy (C3G) is characterized by predominant C3 deposits in glomeruli and dysregulation of the alternative pathway of complement. Half of C3G patients have a C3 nephritic factor (C3NeF). C3G incorporated entities with a range of features on microscopy including dense deposit diseases (DDD) and C3 glomerulonephritis (C3GN). The aim of this work was to study children cases of C3G associated with C3NeF.

Methods

We reviewed 18 cases of C3G with a childhood onset associated with C3NeF without identified mutations in CFH, CFI, and MCP genes.

Results

Clinical histories started with recurrent hematuria for seven patients, nephrotic syndrome for four, acute post-infectious glomerulonephritis for three and acute renal failure for four. Twelve patients had a low C3 at first investigation. Kidney biopsy showed ten C3GN and eight DDD. Twenty-three percent of the patients tested presented elevated sC5b9. Seven patients relapsed 3 to 6 years after the onset. At the end of follow-up, two patients were under dialysis, 11 had a persistent proteinuria, five had none; four patients did not follow any treatment. Steroids were first used in 80 % of cases.

Conclusions

C3NeF associated C3G has a heterogeneous presentation and outcome. Anti-proteinuric agents may control the disease during follow-up, even after nephrotic syndrome at the onset. The efficiency of immunosuppressive therapy remains questionable.     

The biomaterial-mediated healing of critical size bone defects in the ovariectomized rat

Summary

This study demonstrated an impaired biomaterial-mediated bone regeneration in a critical sized calvarial defect established within an ovariectomized rat model. Histological and microtomographic evidences were supported by an impaired osteoblastic gene expression and altered expression of estrogen receptors and adipogenic markers.

Introduction

This work aims to address the bone regeneration process in the ovariectomized rat model, by assessing a calvarial critical size defect implanted with a biocompatible bovine bone mineral graft.

Methods

Animals were randomly divided into two groups: Ovx (bilateral ovariectomy) and Sham (control surgery). Following 8 weeks, all animals were submitted to a surgical bicortical craniotomy (5-mm circular critical size defect), which was filled with a biocompatible mineral graft. Animals were euthanized at 1, 3, and 6 months following graft implantation (n?=?10), and results on the orthotopic bone regeneration process were blindly evaluated by radiographic, microtomographic, histological, histomorphometric, and gene expression techniques.

Results

In the attained model, in both Sham and Ovx groups, the bone regenerative process was found to occur in a slow-paced manner. Likewise, a qualitative evaluation of the microtomographic and histological analysis, as well as quantitative data from histomorphometric indexes, revealed reduced bone regeneration in Ovx animals, at the assayed time points. Significant differences were attained at the 3 and 6 months. Gene expression analysis revealed a reduced expression of osteoblastic-related genes and an altered expression of estrogen receptors and adipogenic markers, within the regenerating bone of Ovx animals.

Conclusions

Due to the similarities between the osteoporotic animal model and the human condition of postmenopausal osteoporosis, it might be relevant to consider the potential clinical implication of the osteoporotic condition in the biomaterial-mediated bone tissue healing/regeneration process.