Methylenetetrahydrofolate reductase gene polymorphism in type 1 diabetes mellitus: Relationship to microvascular complications

In patients with type-I diabetes mellitus folate deficiency is associated with endothelial dysfunction. So, polymorphism in genes involved in folate metabolism may have a role in vascular disease. This study was designed to evaluate the relationship between methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and microvascular complications in adolescents with type I diabetes mellitus. A total of 99 patients with disease duration of more than 5 years aged 11–18 years participated in the study. History taking, physical, neurological and fundus examinations were performed. Laboratory investigations included mean glycated hemoglobin in the last year, urinary albumin excretion, serum creatinine, nerve conduction velocity and MTHFR genotype determination. Results revealed that 54 (54.5%) of our patients had normal MTHFR genotype (C/C subgroup), 36 (36.4%) had heterozygous MTHFR gene polymorphism (C/T subgroup) and 9 (9.1%) had homozygous MTHFR gene polymorphism (T/T subgroup). No significant difference was found between the three studied groups as regards age, disease duration or glycemic control. When testing for microalbuminuria, the T/T subgroup showed a significantly higher number of patients with microalbuminuria when compared with C/C and C/T subgroups. Regarding fundus changes, the C/C subgroup showed a significantly lower number of patients with fundus changes when compared with C/T and T/T subgroups .On the other hand the T/T subgroup showed a significantly higher number of patients with fundus changes when compared with the C/T subgroup. For nerve conduction abnormalities, the T/T subgroup showed a significantly higher number of patients with nerve conduction abnormalities when compared with C/C and C/T subgroups. Multivariate forward stepwise logistic regression analysis for determination of independent risk factors that best predicts the occurrence of microalbuminuria, fundus changes and nerve conduction abnormalities revealed MTHFR gene polymorphism to be the most important variable. MTHFR gene polymorphism (T/T) subtype is an important risk factor for the development of micro-vascular complications in patients with type I diabetes mellitus.Keywords: Methylenetetrahydrofolate reductase gene polymorphism; Microvascular complications; Type 1 diabetes; Microalbuminuri

An evaluation of the saw, dry and rip process for the conversion of Rubberwood.

A study was carried out to compare the volume recovery and product quality of two different sawing techniques in the conversion of rubberwood which is plagued with low yield. The study was undertaken in a sawmill in Peninsular Malaysia, using the conventional live sawing process and the Saw Dry and Rip (SDR) process. The results showed that the SDR process resulted in higher volume recovery as well as higher product quality, compared to the conventional live sawing process. Further, the application of high temperature drying for rubberwood sawn material resulted in lower drying defects and together with the SDR process, resulted in a more economical solution for the conversion of rubberwood. Accordingly, a survey of the current industrial practices as rubberwood 125 saw mills revealed that rubberwood sawmilling is plagued with a low yield of 27% and the SDR process, if applied offers a significant improvement both in terms of volume recovery as well as product quality. Therefore, the results of this study have far reaching industrial implications on the sawing and machining of rubberwood in the South East Asian region

Ultrasonic reflection coefficient and surface roughness index of OA articular cartilage: relation to pathological assessment

<p>Abstract</p> <p>Background</p> <p>Early diagnosis of Osteoarthritis (OA) is essential for preventing further cartilage destruction and decreasing severe complications. The aims of this study are to explore the relationship between OA pathological grades and quantitative acoustic parameters and to provide more objective criteria for ultrasonic microscopic evaluation of the OA cartilage.</p> <p>Methods</p> <p>Articular cartilage samples were prepared from rabbit knees and scanned using ultrasound biomicroscopy (UBM). Three quantitative parameters, including the roughness index of the cartilage surface (URI), the reflection coefficients from the cartilage surface (R) and from the cartilage-bone interface (R_bone) were extracted. The osteoarthritis grades of these cartilage samples were qualitatively assessed by histology according to the grading standards of International Osteoarthritis Institute (OARSI). The relationship between these quantitative parameters and the osteoarthritis grades was explored.</p> <p>Results</p> <p>The results showed that URI increased with the OA grade. URI of the normal cartilage samples was significantly lower than the one of the OA cartilage samples. There was no significant difference in URI between the grade 1 cartilage samples and the grade 2 cartilage samples. The reflection coefficient of the cartilage surface reduced significantly with the development of OA (p < 0.05), while the reflection coefficient of the cartilage-bone interface increased with the increase of grade.</p> <p>Conclusion</p> <p>High frequency ultrasound measurements can reflect the changes in the surface roughness index and the ultrasound reflection coefficients of the cartilage samples with different OA grades. This study may provide useful information for the quantitative ultrasonic diagnosis of early OA.</p

Endocrine therapy resistant ESR1 variants revealed by genomic characterization of breast cancer derived xenografts

To characterize patient-derived xenografts (PDXs) for functional studies, we made whole-genome comparisons with originating breast cancers representative of the major intrinsic subtypes. Structural and copy number aberrations were found to be retained with high fidelity. However, at the single-nucleotide level, variable numbers of PDX-specific somatic events were documented, although they were only rarely functionally significant. Variant allele frequencies were often preserved in the PDXs, demonstrating that clonal representation can be transplantable. Estrogen-receptor-positive PDXs were associated with ESR1 ligand-binding-domain mutations, gene amplification, or an ESR1/YAP1 translocation. These events produced different endocrine-therapy-response phenotypes in human, cell line, and PDX endocrine-response studies. Hence, deeply sequenced PDX models are an important resource for the search for genome-forward treatment options and capture endocrine-drug-resistance etiologies that are not observed in standard cell lines. The originating tumor genome provides a benchmark for assessing genetic drift and clonal representation after transplantation

Endocrine-Therapy-Resistant ESR1 Variants Revealed by Genomic Characterization of Breast-Cancer-Derived Xenografts

To characterize patient-derived xenografts (PDXs) for functional studies, we made whole-genome comparisons with originating breast cancers representative of the major intrinsic subtypes. Structural and copy number aberrations were found to be retained with high fidelity. However, at the single-nucleotide level, variable numbers of PDX-specific somatic events were documented, although they were only rarely functionally significant. Variant allele frequencies were often preserved in the PDXs, demonstrating that clonal representation can be transplantable. Estrogen-receptor-positive PDXs were associated with ESR1 ligand-binding-domain mutations, gene amplification, or an ESR1/YAP1 translocation. These events produced different endocrine-therapy-response phenotypes in human, cell line, and PDX endocrine-response studies. Hence, deeply sequenced PDX models are an important resource for the search for genome-forward treatment options and capture endocrine-drug-resistance etiologies that are not observed in standard cell lines. The originating tumor genome provides a benchmark for assessing genetic drift and clonal representation after transplantation

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe