Locked intramedullary nailing for complex non-union of the tibia

Ten patients with complex non-union of the tibia were treated by locked intramedullary nailing. These patients had scarred skin as a result of initial severe open fractures, multiple debridement or fasciotomies with external fixators and skin grafts applied. Seven of the patients also had previous osteomyelitis or pin track infections. Fully pain-free walking was achieved in all patients and radiological union in nine patients without the need for a bone graft. Four patients developed infection after nailing, of which three resolved with treatment.     

Anticancer Mechanism of Curcumin on Human Glioblastoma

Glioblastoma (GBM) is the most malignant brain tumor and accounts for most adult brain tumors. Current available treatment options for GBM are multimodal, which include surgical resection, radiation, and chemotherapy. Despite the significant advances in diagnostic and therapeutic approaches, GBM remains largely resistant to treatment, with a poor median survival rate between 12 and 18 months. With increasing drug resistance, the introduction of phytochemicals into current GBM treatment has become a potential strategy to combat GBM. Phytochemicals possess multifarious bioactivities with multitarget sites and comparatively marginal toxicity. Among them, curcumin is the most studied compound described as a potential anticancer agent due to its multi-targeted signaling/molecular pathways properties. Curcumin possesses the ability to modulate the core pathways involved in GBM cell proliferation, apoptosis, cell cycle arrest, autophagy, paraptosis, oxidative stress, and tumor cell motility. This review discusses curcumin’s anticancer mechanism through modulation of Rb, p53, MAPK, P13K/Akt, JAK/STAT, Shh, and NF-κB pathways, which are commonly involved and dysregulated in preclinical and clinical GBM models. In addition, limitation issues such as bioavailability, pharmacokinetics perspectives strategies, and clinical trials were discussed.     

Prevalence of HIV and sexually transmitted and blood-borne infections,and related preventive and risk behaviours,among gay,bisexual and other men who have sex with men in Montreal,Toronto and Vancouver: results from the Engage Study

ObjectivesThe last Canadian biobehavioural surveillance study of HIV and other sexually transmitted and blood-borne infections (STBBI) among gay, bisexual and other men who have sex with men (GBM) was conducted in 2010. We designed a study to measure STBBI prevalence among GBM in metropolitan Montreal, Toronto and Vancouver and to document related preventive and risk behaviours.MethodsThe Engage Cohort Study used respondent-driven sampling (RDS) to recruit GBM who reported sex with another man in the past 6 months. At baseline, we examined recruitment characteristics of the samples, and the RDS-II-adjusted distributions of socio-demographics, laboratory-confirmed HIV and other STBBI prevalence, and related behaviours, with a focus on univariate differences among cities.ResultsA total of 2449 GBM were recruited from February 2017 to August 2019. HIV prevalence was lower in Montreal (14.2%) than in Toronto (22.2%) or Vancouver (20.4%). History of syphilis infection was similar across cities (14–16%). Vancouver had more HIV-negative/unknown participants who reported never being HIV tested (18.6%) than Toronto (12.9%) or Montreal (11.5%). Both Montreal (74.9%) and Vancouver (78.8%) had higher proportions of men who tested for another STBBI in the past 6 months than Toronto (67.4%). Vancouver had a higher proportion of men who used pre-exposure prophylaxis (PrEP) in the past 6 months (18.9%) than Toronto (11.1%) or Montreal (9.6%).ConclusionThe three largest cities of Canada differed in HIV prevalence, STBBI testing and PrEP use among GBM. Our findings also suggest the need for scale-up of both PrEP and STI testing among GBM in Canada.     

Improvements in the Engineering Properties of Cementitious Composites Using Nano-Sized Cement and Nano-Sized Additives

The findings of an extensive experimental research study on the usage of nano-sized cement powder and other additives combined to form cement–fine-aggregate matrices are discussed in this work. In the laboratory, dry and wet methods were used to create nano-sized cements. The influence of these nano-sized cements, nano-silica fumes, and nano-fly ash in different proportions was studied to the evaluate the engineering properties of the cement–fine-aggregate matrices concerning normal-sized, commercially available cement. The composites produced with modified cement–fine-aggregate matrices were subjected to microscopic-scale analyses using a petrographic microscope, a Scanning Electron Microscope (SEM), and a Transmission Electron Microscope (TEM). These studies unravelled the placement and behaviour of additives in controlling the engineering properties of the mix. The test results indicated that nano-cement and nano-sized particles improved the engineering properties of the hardened cement matrix. The wet-ground nano-cement showed the best result, 40 MPa 28th-day compressive strength, without mixing any additive compared with ordinary and dry-ground cements. The mix containing 50:50 normal and wet-ground cement exhibited 37.20 MPa 28th-day compressive strength. All other mixes with nano-sized dry cement, silica fume, and fly ash with different permutations and combinations gave better results than the normal-cement–fine-aggregate mix. The petrographic studies and the Scanning Electron Microscope (SEM) and Transmission Electron Microscope (TEM) analyses further validated the above findings. Statistical analyses and techniques such as correlation and stepwise multiple regression analysis were conducted to compose a predictive equation to calculate the 28th-day compressive strength. In addition to these methods, a repeated measures Analysis of Variance (ANOVA) was also implemented to analyse the statistically significant differences among three differently timed strength readings.     

视神经周围炎的研究进展

视神经周围炎(OPN)是指涉及视神经鞘膜的一系列病理性炎症.OPN的经典三联征包括单侧视神经病变伴随疼痛和/或视盘水肿,此病症与其它视神经病变相似,导致诊断延迟和治疗欠佳.2016年1月,我们对发表于Medline和Ovid数据库的关键词为“视神经周围炎”的各种语言的文献进行了检索,共查找到60篇文献,发表于1956-2015年.两位作者(Tai ELM和Tevaraj JMP)分别对论文摘要进行了独立筛选,并筛选出相关文章.本次综述,我们强调OPN的特点,特别是OPN和视神经炎之间的临床差异.虽然大多数OPN的病例是特发性的,但仍需进行调查以排除特异性感染和继发性OPN的炎症原因.MRI是非常重要的检查方法,由于OPN视神经周围炎症的影像学诊断.糖皮质激素治疗可使症状与体征迅速好转,长期口服糖皮质激素并慢速递减可以降低复发的风险.     

分期实施异体角膜缘干细胞移植与穿透性角膜移植术治疗严重化学伤

有1位于1996年实施右眼穿透性角膜移植术失败的双眼严重眼表化学伤的患者, 62岁,右眼视力手动,左眼视力光感。于2006-09-16/2007-02-07分别对右眼实施了异体角膜缘干细胞移植术和穿透性角膜移植术,经过术后5m的药物治疗观察,最终获得了右眼最佳矫正视力为6/30,角膜移植片透明,眼表得以重建,并未发现明显排斥迹象的良好效果。     

A first-in-human Phase I dose-escalation trial of the novel therapeutic peptide,ALM201, demonstrates a favourable safety profile in unselected patients with ovarian cancer and other advanced solid tumours

Background We aimed to assess the safety, tolerability and pharmacokinetics of a novel anti-angiogenic peptide.Methods We used an open-label, multicentre, dose-escalation Phase I trial design in patients with solid tumours. ALM201 was administered subcutaneously once daily for 5 days every week in unselected patients with solid tumours.Results Twenty (8 male, 12 female) patients with various solid tumours were treated (18 evaluable for toxicity) over eight planned dose levels (10–300 mg). ALM201 was well-tolerated at all dose levels without CTCAE grade 4 toxicities. Adverse events were predominantly grades 1–2, most commonly, localised injection-site reactions (44.4%), vomiting (11%), fatigue (16.7%), arthralgia (5.6%) and headache (11%). Thrombosis occurred in two patients at the 100 mg and 10 mg dose levels. The MTD was not reached, and a recommended Phase II dose (RP2D) based on feasibility was declared. Plasma exposure increased with dose (less than dose-proportional at the two highest dose levels). No peptide accumulation was evident. The median treatment duration was 11.1 (range 3–18) weeks. Four of 18 evaluable patients (22%) had stable disease.Conclusions Doses up to 300 mg of ALM201 subcutaneously are feasible and well-tolerated. Further investigation of this agent in selected tumour types/settings would benefit from patient-selection biomarkers.Subject terms: Drug development, Drug safety     

Prenatal Bisphenol a Exposure and Postnatal Trans Fat Diet Alter Small Intestinal Morphology and Its Global DNA Methylation in Male Sprague-Dawley Rats,Leading to Obesity Development

In this study, we aimed to determine whether a postnatal trans fat diet (TFD) could aggravate prenatal bisphenol A (BPA) exposure effects on offspring’s small intestine and adulthood obesity, due to the relatively sparse findings on how the interaction between these two variables interrupt the small intestinal cells. Twelve pregnant rats were administered with either unspiked drinking water (control; CTL) or BPA-spiked drinking water throughout pregnancy. Twelve weaned pups from each pregnancy group were then given either a normal diet (ND) or TFD from postnatal week (PNW) 3 until PNW14, divided into control offspring on normal diet (CTL-ND), BPA-exposed offspring on normal diet (BPA-ND), control offspring on trans fat diet (CTL-TFD), and BPA offspring on trans fat diet (BPA-TFD) groups. Body weight (BW), waist circumference, and food and water intake were measured weekly in offspring. At PNW14, small intestines were collected for global DNA methylation and histological analyses. Marked differences in BW were observed starting at PNW9 in BPA-TFD (389.5 ± 10.0 g; p < 0.05) relative to CTL-ND (339.0 ± 7.2 g), which persisted until PNW13 (505.0 ± 15.6 g). In contrast, water and food intake between offspring were significantly different (p < 0.01–0.05) at earlier ages only (PNW4–6 and PNW7–9, respectively). Furthermore, substantial differences in the general parameters of the intestinal structures were exclusive to ileum crypt length alone, whereby both BPA-ND (150.5 ± 5.1 μm; p < 0.001), and BPA-TFD (130.3 ± 9.9 μm; p < 0.05) were significantly longer than CTL-ND (96.8 ± 8.9 μm). Moreover, BPA-ND (2.898 ± 0.147%; p < 0.05) demonstrated global small intestinal hypermethylation when compared to CTL-ND and CTL-TFD (1.973 ± 0.232% and 1.913 ± 0.256%, respectively). Prenatal BPA exposure may significantly affect offspring’s physiological parameters and intestinal function. Additionally, our data suggest that there might be compensatory responses to postnatal TFD in the combined BPA prenatal group (BPA-TFD).