Enhanced Bone Regeneration Using Porcine Small Intestinal Submucosa

Small instestinal submucosa (SIS) is an easily produced material that has been used experimentally for tissue engineering. To evaluate the ability of SIS to facilitate bone growth within a long-bone defect, a segment of the radius was surgically removed in adult, female Sprague-Dawley rats. The defect was either left unfilled or implanted with SIS, demineralized cortical bone (DMCB), or ovalbumin. The defect was evaluated radiographically and histologically after 3, 6, 12, and 24 weeks. Tissue remodeling within the defect was evident by week 3 in SIS- and DMCB-treated rats. Filling was characterized initially by infiltration of mononuclear cells and extracellular material in SIS-implanted rats and multifocal remodeling bone particles and cartilage formation in DMCB implanted rats. Cartilage was observed as early as 3 weeks and bone as early as 6 weeks in SIS-implanted rats. Filling of the defect arose from multiple foci in DMCB-implanted rats, but was contiguous with and parallel to the ulnar shaft in SIS-implanted rats, suggesting that defect repair by SIS may be conductive rather than inductive. Rats in which the defect was left unfilled demonstrated slow but progressive filling of the defect, characterized by mononuclear cell infiltrates and fibrous extracellular material. In summary, SIS facilitated rapid filling of a longbone defect. These results suggest that SIS may be useful as a bone repair material.     

Risk factors associated with having psoriatic arthritis in patients with cutaneous psoriasis

The aim of this study was to determine if the following characteristics were associated with the presence of psoriatic arthritis in a sample of psoriasis patients: race, family history of psoriasis and psoriatic arthritis, age of onset of psoriasis, smoking, alcohol consumption and the maximum body surface area (BSA) affected by psoriasis. This was a case–control study involving 400 psoriasis patients who attended the Psoriasis and Photo‐medicine clinic in the National Skin Center of Singapore over a 1‐year period. Cases were psoriasis patients with psoriatic arthritis while controls were psoriasis patients without psoriatic arthritis. The diagnosis of psoriatic arthritis was made by rheumatologists and participants completed a self‐administered standardized questionnaire. The maximum BSA involved was determined from the case notes. Psoriatic arthritis was not significantly associated with sex, race, age of onset of psoriasis, a family history of psoriasis, smoking and alcohol consumption but was significantly associated with a family history of psoriatic arthritis (P < 0.001) and the maximum body surface involved (P = 0.05). Using multivariate analysis to control for variables, the presence of psoriatic arthritis was significantly associated with a family history of psoriatic arthritis (odds ratio [OR] = 20.5; 95% confidence interval [CI] = 2.49–169.10) and the maximum BSA involved (OR = 2.52; 95% CI = 1.33–4.75). Indian psoriatic patients were more likely to have psoriatic arthritis compared to the other races. A family history of psoriatic arthritis and a greater maximum body surface involved may be associated with having psoriatic arthritis in this study population of psoriasis patients.     

Preoperative Risk Stratification of Adnexal Masses in the Pediatric and Adolescent Population: Evaluating the Decision Tree System

Study ObjectiveTo evaluate the diagnostic performance of the Decision Tree System (DTS) rules 2 and 3 for surgically managed adnexal masses in the North American population and to compare it with the risk stratification criteria used at The Hospital for Sick Children (≥8 cm and complex/solid).DesignA retrospective cohort study of patients who presented with adnexal masses and were surgically treated between April 2011 and March 2016.SettingThe Hospital for Sick Children (Toronto, Ontario, Canada).ParticipantsPatients 1-18 years of age with adnexal masses who underwent surgical treatment.Interventions and Main Outcome MeasuresMain outcome measures included diagnostic performance (preoperative sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV] for malignancy) of the DTS rules 2 and 3 and ≥8 cm and complex/solid criteria.ResultsThe malignancy rate was 10.4%. The DTS rules 2 and 3 had a sensitivity of 84% (95% confidence interval [CI], 79-90), specificity of 77% (95% CI, 71-83), PPV of 30% (95% CI, 17-42), and NPV of 98% (95% CI, 94-100). The 8 cm or larger and complex/solid criteria had a sensitivity of 89% (95% CI, 85-94), specificity of 71% (95% CI, 64-77), PPV of 27% (95% CI, 16-38), and NPV of 98% (95% CI, 96-100).ConclusionOur study showed that DTS rules 2 and 3 had similar diagnostic performance as the 8 cm or larger and complex/solid criteria in the same population, with a very high NPV and a low PPV. Future prospective investigations should be conducted to further assess how DTS components can be incorporated into future algorithms for the management of adnexal masses in the pediatric population.     

Is multiple SNP testing in BRCA2 and BRCA1 female carriers ready for use in clinical practice? Results from a large Genetic Centre in the UK

BRCA1 and BRCA2 are major breast cancer susceptibility genes. Nineteen single nucleotide polymorphisms (SNPs) at 18 loci have been associated with breast cancer. We aimed to determine whether these predict breast cancer incidence in women with BRCA1/BRCA2 mutations. BRCA1/2 mutation carriers identified through the Manchester genetics centre between 1996 and 2011 were included. Using published odds ratios (OR) and risk allele frequencies, we calculated an overall breast cancer risk SNP score (OBRS) for each woman. The relationship between OBRS and age at breast cancer onset was investigated using the Cox proportional hazards model, and predictive ability assessed using Harrell's C concordance statistic. In BRCA1 mutation carriers we found no association between OBRS and age at breast cancer onset: OR for the lowest risk quintile compared to the highest was 1.20 (95% CI 0.82–1.75, Harrell's C = 0.54), but in BRCA2 mutation carriers the association was significant (OR for the lowest risk quintile relative to the highest was 0.47 (95% CI 0.33–0.69, Harrell's C = 0.59). The 18 validated breast cancer SNPs differentiate breast cancer risks between women with BRCA2 mutations, but not BRCA1. It may now be appropriate to use these SNPs to help women with BRCA2 mutations make maximally informed decisions about management options.     

Hoechst staining and exposure to UV laser during flow cytometric sorting does not affect the frequency of detected endogenous DNA nicks in abnormal and normal human spermatozoa

Controlling the sex of offspring by the separation of X and Y chromosome-bearing spermatozoa using flow cytometry has been reported as a clinical technique aiding prevention of X-linked diseases. Although this technique has resulted in several hundred normal births in animals and at least one human birth, there is still concern over its genetic safety due to the involvement of two potentially mutagenic agents: UV light and the fluorochrome dye, Hoechst 33342 (H33342). Human spermatozoa, particularly those considered abnormal, may be more likely to suffer DNA damage following exposure to mutagenic agents, compared with other mammalian species. The stability of normal fresh and decondensed human spermatozoa were examined after exposure to a range of levels of UV and H33342 staining, using an assay that detects endogenous nicks in the DNA of spermatozoa. The stability of abnormal and normal, fresh and frozen-thawed human spermatozoa was examined following UV laser, H33342 staining and flow cytometry treatments utilizing the same assay. There was an increase in the presence of endogenous nicks when spermatozoa were decondensed compared with fresh spermatozoa. There was no increase in the incidence of nicks in any group of spermatozoa after UV and fluorochrome exposure compared with controls without exposure.      

Modulation of disease severity of dystrophic epidermolysis bullosa by a splice site mutation in combination with a missense mutation in the COL7A1 gene

Dystrophic epidermolysis bullosa (EBD) is a clinically heterogeneous skin disorder, characterized by abnormal anchoring fibrils (AF) and loss of dermal-epidermal adherence. EBD has been linked to the COL7A1 gene at chromosome 3p21 which encodes collagen VII, the major component of the AF. Here we investigated two unrelated EBD families with different clinical phenotypes and novel combinations of recessive and dominant COL7A1 mutations. Both families shared the same recessive heterozygous 14 bp deletion at the exon-intron 115 boundary of the COL7A1 gene. The deletion caused in-frame skipping of exon 115 and the elimination of 29 amino acid residues from the pro-alpha1(VII) polypeptide chain. As a result, procollagen VII was not converted to collagen VII and the C-terminal NC-2 propeptide which is normally removed from the procollagen VII prior to formation of the anchoring fibrils was retained in the skin. All affected individuals also carried missense mutations in exon 73 of COL7A1 which lead to different glycine- to-arginine substitutions in the triple-helical domain of collagen VII. Combination of the deletion mutation with a G2009R substitution resulted in a mild phenotype. In contrast, combination of the deletion with a G2043R substitution led to a severe phenotype. The G2043R substitution was a de novo mutation which alone caused a mild phenotype. Thus, different combinations of dominant and recessive COL7A1 mutations can modulate disease activity of EBD and alter the clinical presentation of the patients.      

清除骨髓中癌细胞的磁性微球研究 II.聚苯乙烯磁性微球的研制

为制备能用于清除骨髓中癌细胞的磁性微球,首先合成了单分散、大粒径的多孔聚苯乙烯交联微球,借助微球多孔结构对其进行磁化。探讨了影响磁化效果的主要因素。为使其与单抗连接紧密,在微球表面聚合了一层聚丙烯醛膜,使其表面带上易与单抗反应的醛基。同时测定了所制微球的磁响应性。X-射线衍射证明磁性物质为γ-Fe₂O₃。     

阿克拉霉素A聚氰基丙烯酸异丁酯毫微粒冻干针剂体内外抗肝癌活性

阿克拉霉素A聚氰基丙烯酸异丁酯毫微粒的冻干针剂,能明显抑制体外培养人肝癌细胞株7703的生长,IC50为0.28μg·ml^-1。在0.8μg·ml^-1浓度时,克隆形成抑制率为90%,抑制作用有明显剂量依赖关系而未见明显时间依赖关系。静脉给药后,对常位移植人肝癌模型裸小鼠的抑瘤率为86.84%,肿瘤细胞增殖活性阳性率为20.83%。体内外均显示明显的抗肝癌活性,且体内抗肝癌活性比阿克拉霉素A冻干针剂强。     

Development and psychometric evaluation of the Bipolar Functional Status Questionnaire (BFSQ)

Goldberg JF, McLeod LD, Fehnel SE, Williams VSL, Hamm LR, Gilchrist K. Development and psychometric evaluation of the Bipolar Functional Status Questionnaire (BFSQ). Bipolar Disord 2010: 12: 32–44. © 2010 The Authors.
Journal compilation © 2010 John Wiley & Sons A/S. Objectives: Persistently impaired psychosocial functioning has been recognized in many individuals with bipolar disorder. However, existing measures of functional disability have been adapted for use in bipolar disorder based mainly on those developed for use in other conditions. The present study involved the development and validation of a new patient self‐report measure specific to bipolar disorder, the Bipolar Functional Status Questionnaire (BFSQ). Methods: Relevant constructs were identified, evaluated, and refined through an expert advisory panel in conjunction with patient interviews. Questionnaire items were vetted through iterative patient interviews. Psychometric properties were determined based on patient responses from implementation of the proposed 33‐item questionnaire in an 11‐site study of 596 patients with bipolar disorder across varied phases of illness. Results: Eight constructs were identified as fundamental to functional status in bipolar disorder: cognitive function, sleep, role functioning, emotional functioning, energy/vitality, social functioning, personal management, and sexual functioning. Psychometric validation supported item reduction to a 24‐item unidimensional scale, with high internal consistency (coefficient α’s = 0.93–0.95), high test‐retest reliability (intraclass correlation coefficient = 0.86, 95% confidence interval = 0.82–0.89), strong convergent validity with other functional disability measures (r’s > 0.70), and highly significant discriminant validity across illness phases, with large effect sizes (Cohen’s d > 0.70). Conclusions: The BFSQ is a psychometrically sound self‐report measure that can be used to effectively quantify functional status across different clinical states in patients with bipolar disorder.