Poly(ortho ester) nanoparticles targeted for chronic intraocular diseases: ocular safety and localization after intravitreal injection

Treatment of posterior eye diseases is more challenging than the anterior segment ailments due to a series of anatomical barriers and physiological constraints confronted by drug delivery to the back of the eye. In recent years, concerted efforts in drug delivery have been made to prolong the residence time of drugs injected in the vitreous humor of the eye. Our previous studies demonstrated that poly(ortho ester) (POE) nanoparticles were biodegradable/biocompatible and were capable of long-term sustained release. The objective of the present study was to investigate the safety and localization of POE nanoparticles in New Zealand white rabbits and C57BL/6 mice after intravitreal administration for the treatment of chronic posterior ocular diseases. Two concentration levels of POE nanoparticles solution were chosen for intravitreal injection: 1.5?mg/ml and 10?mg/ml. Our results demonstrate that POE nanoparticles were distributed throughout the vitreous cavity by optical coherence tomography (OCT) examination 14 days post-intravitreal injection. Intraocular pressure was not changed from baseline. Inflammatory or adverse effects were undetectable by slit lamp biomicroscopy. Furthermore, we demonstrate that POE nanoparticles have negligible toxicity assessed at the cellular level evidenced by a lack of glia activation or apoptosis estimation after intravitreal injection. Collectively, POE nanoparticles are a novel and nontoxic as an ocular drug delivery system for the treatment of posterior ocular diseases.     

Factors associated with clinically significant hypoglycemia in patients with type 1 diabetes using sensor-augmented pump therapy with predictive low-glucose management: A multicentric study on iberoamerica

Background and aimsDespite using sensor-augmented pump therapy (SAPT) with predictive low-glucose management (PLGM), hypoglycemia is still an issue in patients with type 1 Diabetes (T1D). Our aim was to determine factors associated with clinically significant hypoglycemia (<54 mg/dl) in persons with T1D treated with PLGM-SAPT.Methodology: This is a multicentric prospective real-life study performed in Colombia, Chile and Spain. Patients with T1D treated with PLGM-SAPT, using sensor ≥70% of time, were included. Data regarding pump and sensor use patterns and carbohydrate intake from 28 consecutive days were collected. A bivariate and multivariate Poisson regression analysis was carried out, to evaluate the association between the number of events of <54 mg/dl with the clinical variables and patterns of sensor and pump use.Results188 subjects were included (41 ± 13.8 years-old, 23 ± 12 years disease duration, A1c 7.2% ± 0.9). The median of events <54 mg/dl was four events/patient/month (IQR 1–10), 77% of these events occurred during day time. Multivariate analysis showed that the number of events of hypoglycemia were higher in patients with previous severe hypoglycemia (IRR1.38; 95% CI 1.19–1.61; p < 0.001), high glycemic variability defined as Coefficient of Variation (CV%) > 36% (IRR 2.09; 95%CI 1.79–2.45; p < 0.001) and hypoglycemia unawareness. A protector effect was identified for adequate sensor calibration (IRR 0.77; 95%CI 0.66–0.90; p:0.001), and the use of bolus wizard >60% (IRR 0.74; 95%CI 0.58–0.95; p:0.017).ConclusionIn spite of using advanced SAPT, clinically significant hypoglycemia is still a non-negligible risk. Only the identification and intervention of modifiable factors could help to prevent and reduce hypoglycemia in clinical practice.     

针刺京骨穴联合推拿治疗背肌筋膜炎临床研究

目的探讨针刺京骨穴联合推拿治疗背肌筋膜炎的临床疗效。方法将2016年10月—2018年10月收治的背肌筋膜炎患者86例纳入研究,采用随机数字表法分组。对照组43例予以推拿治疗,观察组43例予以针刺京骨穴联合推拿治疗。比较2组患者的治疗总有效率、VAS评分及Oswestry功能障碍指数、痊愈所用时间。结果观察组治疗总有效率为95.3%,而对照组仅为81.4%,差异有统计学意义(P<0.05);2组治疗后VAS评分、Oswestry功能障碍指数均有下降,观察组上述指标低于对照组,差异有统计学意义(P<0.05);观察组痊愈所用时间短于对照组,差异有统计学意义(P<0.05)。结论针刺京骨穴联合推拿治疗背肌筋膜炎的临床疗效突出,可缓解背部疼痛、恢复功能活动,并缩短了愈合时间,提高了生活质量,值得一定的临床推广。     

Evodiamine-inspired dual inhibitors of histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) with potent antitumor activity

A great challenge in multi-targeting drug discovery is to identify drug-like lead compounds with therapeutic advantages over single target inhibitors and drug combinations. Inspired by our previous efforts in designing antitumor evodiamine derivatives, herein selective histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) dual inhibitors were successfully identified, which showed potent in vitro and in vivo antitumor potency. Particularly, compound 30a was orally active and possessed excellent in vivo antitumor activity in the HCT116 xenograft model (TGI = 75.2%, 150 mg/kg, p.o.) without significant toxicity, which was more potent than HDAC inhibitor vorinostat, TOP inhibitor evodiamine and their combination. Taken together, this study highlights the therapeutic advantages of evodiamine-based HDAC1/TOP2 dual inhibitors and provides valuable leads for the development of novel multi-targeting antitumor agents.     

Multiple pipeline embolization devices improves aneurysm occlusion without increasing morbidity: A single center experience of 140 cases

IntroductionRates of aneurysm occlusion with the pipeline embolization device (PED) has varied widely in the literature from 55.7% to 93.3% at 6 months, which may reflect a difference in technique including sizing and number of devices used.Methods140 cases at our institution were retrospectively reviewed, and aneurysms treated with a single PED vs. multiple were compared.ResultsComplete aneurysm occlusion was achieved in 86.9% at 6 months, 91.8% at 1 year, and 97.6% at longest follow-up. Retreatment with an additional device was required in 7 (5.1%). Major and minor complication rate within 30 days was 1.4% and 5.0%, and at greater than 30 days was 0.8% and 3.1%.Patients treated with multiple PEDs had significantly higher rates of aneurysm occlusion at 6 months (92.9% vs. 75.6%, p = 0.017) and 12 months (98.4% vs. 81.1%, p = 0.014), with no difference in complications. The two groups were similar aside from a higher number of ophthalmic and paraophthalmic aneurysms treated with multiple PEDs (23.4% vs. 6.5%, p = 0.004; and 35.1% vs. 17.4%, p = 0.020), and more posterior communicating artery and recurrent aneurysms treated with a single PED (28.3% vs. 3.2%, p = 0.001; 23.9% vs. 8.5%, p = 0.031). The use of multiple PEDs was found to be an independent predictor of aneurysm occlusion in a multivariate analysis (p = 0.015).ConclusionsThe use of multiple PEDs for intracranial aneurysms leads to significantly higher occlusion rates without added morbidity. This benefit is particularly appropriate for ophthalmic segment aneurysms, while more distal segments with eloquent perforating branches should be managed with caution.     

Participatory research in Northwest Atlanta's Proctor Creek Watershed: Using photovoice to explore environmental health risks at the water's edge

In this study we used a participatory research method, photovoice, to explore community perceptions about environmental health risks, community assets, and strengths in and around an urban, degraded watershed in Northwest Atlanta, Georgia. This watershed, formed by Proctor Creek, is a focal point for redevelopment and infrastructure investments for years to come. Using a community-based participatory research approach, 10 Proctor Creek residents (watershed researchers), and a university partner, engaged in data collection; participatory data analysis; internal discussions; translation of research findings into watershed restoration, community revitalization, remedial action, and policy solutions; and dissemination of results to fellow watershed residents, stakeholders, and decision makers. We present a conceptual model linking the watershed researchers' understanding of urban policies and practice in the Proctor Creek Watershed to environmental, neighborhood and housing conditions and their influence on health outcomes and quality of life. Engaging community members in defining their own community environmental health challenges and assets yielded the following primary themes: 1) threats to the natural environment, 2) built environment stressors that influence health, 3) blight and divestment of public resources, and 4) hope for the future. Residents’ vision for the future of the watershed - a restored creek, revitalized neighborhoods, and restored people - is fueled by a strong connection to history, memory, and sense of place. We demonstrate the value of local knowledge in identifying previously unaddressed environmental health risks in the Proctor Creek Watershed as well as solutions to reduce or eliminate them.     

Who should do endovascular repair of complex aortic aneurysms and how should they do them?

BackgroundCure of aneurysms which involve the aorta at the level of the visceral arteries and the thoracoabdominal segment remains a considerable surgical enterprise with a relatively high mortality and morbidity despite improvements of the surgical procedure and anesthetic technique. Fenestrated and branched endovascular stent grafts are currently available offering an attractive less invasive option especially for most frail patients. These grafts are relatively recent, technically more demanding to insert than the current stent graft for infrarenal aneurysm and besides, given the relative low frequency of the disease, they are much less used by practitioners. Thus, unconditional widespread of this sophisticated technique may not necessarily benefit patients.MethodsWe reviewed our experiences and articles regarding this concern, 1) who should perform this new technique and 2) in what kind of setting.ConclusionBased on the combined complexities of 1) patients selection, 2) proper planning and manufacturing of the graft, 3) the need for outstanding imaging and operating facilities, 4) and the required endovascular skill of physicians involved in the procedure, we feel that only highly specialized centers should be allowed to perform this complex procedure.     

PCI和静脉溶栓治疗急性心肌梗死的疗效比较

目的探讨经皮冠状动脉介入(PCI)和静脉溶栓在急性心肌梗死患者中的应用价值。方法选择我院2013年1月至2014年9月收治的60例急性心肌梗死患者作为研究对象,随机分为实验组和对照组各30例。实验组患者采用PCI治疗,对照组患者采用静脉溶栓治疗,比较两组患者血管再通率、死亡发生率、ST段回落情况、住院时间、近远期不良事件发生率、左室舒张末径和左室射血分数变化情况。结果实验组血管再通率显著高于对照组,差异有统计学意义(P<0.05),而近期和远期不良事件发生率均低于对照组,近期不良事件发生率组间比较差异有统计学意义(P<0.05),而远期不良事件发生率比较差异无统计学意义(P>0.05)。实验组患者死亡发生率、ST段回落和住院时间均低于对照组,差异均有统计学意义(P<0.05)。实验组左室射血分数在术后1个月、3个月和6个月时均显著高于对照组,差异均有统计学意义(P<0.05)。结论急性心肌梗死患者应用PCI治疗可显著提高血管再通率、降低死亡和不良事件发生率,有效改善心功能。     

Residential Greenness Alters Serum 25(OH)D Concentrations: A Longitudinal Cohort of Chinese Older Adults

ObjectivesVitamin D deficiency is prevalent among older adults. We aimed to study whether residential greenness could alter serum 25(OH)D concentrations as a possible mechanism of residential greenness's positive health effects.DesignA longitudinal cohort study.Setting and ParticipantsWe included older adults aged ≥65 years from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) with follow-up between 2012 and 2014.MethodsWe measured residential greenness by calculating annual average Normalized Difference Vegetation Index (NDVI) in a 500 m radius by using satellite images around each participant's residential address. Serum 25-hydroxyvitamin D (25(OH)D) concentration was dichotomized into 2 categories: nondeficiency (≥50 nmol/L) and deficiency (<50 nmol/L). We used the generalized estimating equation to examine the relationship between annual average NDVI and serum 25(OH)D.ResultsWe included 1336 participants in our analysis. The annual average NDVI was 0.49, and mean serum 25(OH)D was 43 nmol/L at baseline. Each 0.1-unit increase in annual average NDVI was associated with a 13% higher odds of vitamin D nondeficiency [95% confidence interval (CI): 1.01, 1.26]. The association was stronger among men [odds ratio (OR): 1.17, 95% CI: 1.02, 1.35] than women (OR: 1.08, 95% CI: 0.91, 1.29) and also stronger among those who were free of activities of daily living (ADL) disability at baseline (OR: 1.12, 95% CI: 1.00, 1.25). During the follow-up period, the participants who lived in greener areas were more likely to have an improved, rather than stable or deteriorated, vitamin D status (OR: 1.94, 95% CI: 1.51, 2.51).Conclusions and ImplicationsOur study suggests that higher levels of residential greenness are associated with higher serum 25(OH)D concentrations, which has implications for prevention of vitamin D deficiency among older adults.