Complex Copy Number Variation of AMY1 does not Associate with Obesity in two East Asian Cohorts

The human amylase gene locus at chromosome 1p21.1 is structurally complex. This region contains two pancreatic amylase genes, AMY2B, AMY2A, and a salivary gene AMY1. The AMY1 gene harbors extensive copy number variation (CNV), and recent studies have implicated this variation in adaptation to starch‐rich diets and in association to obesity for European and Asian populations. In this study, we showed that by combining quantitative PCR and digital PCR, coupled with careful experimental design and calibration, we can improve the resolution of genotyping CNV with high copy numbers (CNs). In two East Asian populations of Chinese and Malay ethnicity studied, we observed a unique non‐normal distribution of AMY1 diploid CN genotypes with even:odd CNs ratio of 4.5 (3.3–4.7), and an association between the common AMY2A CN = 2 genotype and odd CNs of AMY1, that could be explained by the underlying haplotypic structure. In two further case–control cohorts (n = 932 and 145, for Chinese and Malays, respectively), we did not observe the previously reported association between AMY1 and obesity or body mass index. Improved methods for accurately genotyping multiallelic CNV loci and understanding the haplotype complexity at the AMY1 locus are necessary for population genetics and association studies.     

Complete remission of recalcitrant genital warts with a combination approach of surgical debulking and oral isotretinoin in a patient with systemic lupus erythematosus

Genital warts in immunocompromised patients can be extensive and recalcitrant to treatment. We report a case of recalcitrant genital warts in a female patient with systemic lupus erythematosus (SLE), who achieved complete remission with a combination approach of surgical debulking and oral isotretinoin at an initial dose of 20 mg/day with a gradual taper of dose over 8 months. She had previously been treated with a combination of topical imiquimod cream and regular fortnightly liquid nitrogen. Although there was partial response, there was no complete clearance. Her condition worsened after topical imiquimod cream was stopped because of her pregnancy. She underwent a combination approach of surgical debulking and oral isotretinoin after her delivery and achieved full clearance for more than 2 years duration. Oral isotretinoin, especially in the treatment of recalcitrant genital warts, is a valuable and feasible option when other more conventional treatment methods have failed or are not possible. It can be used alone or in combination with other local or physical treatment methods.     

A comparison of two systems of patient immobilization for prostate radiotherapy

Background

Reproducibility of different immobilization systems, which may affect set-up errors, remains uncertain. Immobilization systems and their corresponding set-up errors influence the clinical target volume to planning target volume (CTV-PTV) margins and thus may result in undesirable treatment outcomes. This study compared the reproducibility of patient positioning with Hipfix system and whole body alpha cradle with respect to localized prostate cancer and investigated the existing CTV-PTV margins in the clinical oncology departments of two hospitals.

Methods

Forty sets of data of patients with localized T1-T3 prostate cancer were randomly selected from two regional hospitals, with 20 patients immobilized by a whole-body alpha cradle system and 20 by a thermoplastic Hipfix system. Seven sets of the anterior-posterior (AP), cranial-caudal (CC) and medial-lateral (ML) deviations were collected from each patient. The reproducibility of patient positioning within the two hospitals was compared using a total vector error (TVE) parameter. In addition, CTV-PTV margins were computed using van Herk’s formula. The resulting values were compared to the current CTV-PTV margins in both hospitals.

Results

The TVE values were 5.1 and 2.8 mm for the Hipfix and the whole-body alpha cradle systems respectively. TVE associated with the whole-body alpha cradle system was found to be significantly less than the Hipfix system (p?<?0.05). The CC axis in the Hipfix system attained the highest frequency of large (23.6%) and serious (7.9%) set-up errors. The calculated CTV to PTV margin was 8.3, 1.9 and 2.3 mm for the Hipfix system, and 2.1, 3.4 and 1.8 mm for the whole body alpha cradle in CC, ML and AP axes respectively. All but one (CC axis using Hipfix) margin calculated did not exceed the corresponding hospital protocol. The whole body alpha cradle system was found to be significantly better than the Hipfix system in terms of reproducibility (p?<?0.05), especially in the CC axis.

Conclusions

The whole body alpha cradle system was more reproducible than the Hipfix system. In particular, the difference in CC axis contributed most to the results and the current CC margin for the Hipfix system might be considered as inadequate.     

Evaluation of Pichia pastoris-expressed recombinant rhoptry protein 2 of Toxoplasma gondii for its application in diagnosis of toxoplasmosis

Rhoptry protein 2 (ROP2) of Toxoplasma gondii is a rhoptry-secreted protein that plays a critical role in parasitophorous vacuole membrane formation during invasion. In previous studies, ROP2 has been shown to be efficient in triggering humoral and cell-mediated responses. High immunogenicity of ROP2 makes it a potential candidate for diagnosis and vaccination against toxoplasmosis. In this study, the ROP2 gene was cloned into pPICZα A expression vector and extracellularly expressed in the yeast Pichia pastoris, which has numerous advantages over other expression systems for eukaryotic proteins expression. The effectiveness of the secreted recombinant ROP2 as a diagnosis agent was assessed by Western Blot with 200 human serum samples. Recombinant ROP2 reacted with toxoplasmosis-positive human serum samples and yielded an overall sensitivity of 90% and specificity of 95%. However, recombinant ROP2 is a better marker for detection of IgG (91.7%) rather than IgM (80%).     

Neuroprotective effects of minocycline on double-stranded RNA-induced neurotoxicity in cultured cortical neurons

1. Minocycline, memantine,and glycoconjugate were assessed for their ability to protect cultured primary cortical neurons against double-stranded RNA-induced neurotoxicity. 2. Minocycline but not memantine or glycoconjugate protected cultured cells and warrants further investigation.     

Structural Strength Analyses for Low Brass Filler Biomaterial with Anti-Trauma Effects in Articular Cartilage Scaffold Design

The existing harder biomaterial does not protect the tissue cells with blunt-force trauma effects, making it a poor choice for the articular cartilage scaffold design. Despite the traditional mechanical strengths, this study aims to discover alternative structural strengths for the scaffold supports. The metallic filler polymer reinforced method was used to fabricate the test specimen, either low brass (Cu₈₀Zn₂₀) or titanium dioxide filler, with composition weight percentages (wt.%) of 0, 2, 5, 15, and 30 in polyester urethane adhesive. The specimens were investigated for tensile, flexural, field emission scanning electron microscopy (FESEM), and X-ray diffraction (XRD) tests. The tensile and flexural test results increased with wt.%, but there were higher values for low brass filler specimens. The tensile strength curves were extended to discover an additional tensile strength occurring before 83% wt.%. The higher flexural stress was because of the Cu solvent and Zn solute substituting each other randomly. The FESEM micrograph showed a cubo-octahedron shaped structure that was similar to the AuCu₃ structure class. The XRD pattern showed two prominent peaks of 2θ of 42.6° (110) and 49.7° (200) with d-spacings of 1.138 Å and 1.010 Å, respectively, that indicated the typical face-centred cubic superlattice structure with Cu and Zn atoms. Compared to the copper, zinc, and cart brass, the low brass indicated these superlattice structures had ordered–disordered transitional states. As a result, this additional strength was created by the superlattice structure and ordered–disordered transitional states. This innovative strength has the potential to develop into an anti-trauma biomaterial for osteoarthritic patients.     

Deciphering the “obesity paradox” in the elderly: A systematic review and meta-analysis of sarcopenic obesity

Aging and obesity are two global concerns in public health. Sarcopenic obesity (SO), defined as the combination of age-related sarcopenia and obesity, has become a pressing issue. This systematic review and meta-analysis summarize the current clinical evidence relevant to SO. PubMed, Embase, and Web of Science were searched, and 106 clinical studies with 167,151 elderlies were included. The estimated prevalence of SO was 9% in both men and women. Obesity was associated with 34% reduced risk of sarcopenia (odds ratio [OR] 0.66, 95% CI 0.48–0.91; p < 0.001). The pooled hazard ratio (HR) of all-cause mortality was 1.51 (95% CI 1.14–2.02; p < 0.001) for people with SO compared with healthy individuals. SO was associated with increased risk of cardiovascular disease and related mortality, metabolic disorders, cognitive impairment, arthritis, functional limitation, and lung diseases (all ORs > 1.0, p < 0.05). The attenuated risk of sarcopenia in elderlies with obesity (“obesity paradox”) was dependent on higher muscle mass and strength. Apart from unifying the diagnosis of SO, more research is needed to subphenotype people with obesity and sarcopenia for individualized treatment. Meanwhile, the maintenance of proper body composition of muscle and fat may delay or attenuate the adverse outcomes of aging.