Understanding the Influence of Nanocarrier-Mediated Brain Delivery on Therapeutic Performance Through Pharmacokinetic-Pharmacodynamic Modeling

This study aimed at evaluating how encapsulation in a regular nanocarrier (NC) (providing extended circulation time) or in a brain-targeting NC (providing prolonged circulation time and increased brain uptake) may influence the therapeutic index compared with the unformulated drug and to explore the key parameters affecting therapeutic performance using a model-based approach. Pharmacokinetic (PK) models were built with chosen PK parameters. For a scenario where central effect depends on area under the unbound brain concentration curve and peripheral toxicity relates to peak unbound plasma concentration, dose-effect and drug-side effect curves were constructed, and the therapeutic index was evaluated. Regular NC improved the therapeutic index compared with the unformulated drug due to reduced peripheral toxicity, while brain-targeting NC enhanced the therapeutic index by lowering peripheral toxicity and increasing central effect. Decreasing drug release rate or systemic clearance of NC with drug still encapsulated could increase the therapeutic index. Also, a drug with shorter half-life would therapeutically benefit more from a NC encapsulation. This work provides insights into how a NC for brain delivery should be optimized to maximize the therapeutic performance and is helpful to predict if and to what extent a drug with certain PK properties would obtain therapeutic benefit from nanoencapsulation.     

Recent advances in construction of small molecule-based fluorophore-drug conjugates

As a powerful tool to advance drug discovery, molecular imaging may provide new insights into the process of drug effect and therapy at cellular and molecular levels. When compared with other detection methods, fluorescence-based strategies are highly attractive and can be used to illuminate pathways of drugs’ transport, with multi-color capacity, high specificity and good sensitivity. The conjugates of fluorescent molecules and therapeutic agents create exciting avenues for real-time monitoring of drug delivery and distribution, both in vitro and in vivo. In this short review, we discuss recent developments of small molecule-based fluorophore-drug conjugates, including non-cleavable and cleavable ones, that are capable of visualizing drug delivery.     

Percepciones y deseos sobre el parto en gestantes a término en Zamora

ObjectiveTo describe perceptions and wishes regarding childbirth in a group of full-term pregnant women in Zamora.MethodQualitative study of phenomenological character. Participants and scope of study: pregnant women (37-38 weeks), Zamora Sur and Santa Elena health centres (Zamora, Spain). Data collection: semi-structured interviews, until data saturation (16 interviews). Data analysis: analysis of thematic content.ResultsThe maternal feelings varied from joy to fear or stress. The interviewees said they did not feel capable of enduring the pain of childbirth. The needs that they felt most important were having support and accompaniment during delivery (especially of their partner) and receiving good treatment from the healthcare workers.ConclusionsThe importance and repercussion of childbirth for women are not only biological, but also largely mental, emotional and social. It is conditioned by multiple factors: maternal feelings, their ability to deal with the pain of childbirth, their needs, the changes they have made, the support they have and the health professionals who care for them.     

经皮电刺激联合导乐镇痛对分娩结局的影响及安全性分析

目的 探讨经皮电刺激联合导乐分娩镇痛对分娩结局的影响及安全性。方法 选择160例在我院住院待产的产妇作为研究对象,随机将其分为观察组与对照组,每组各80例;其中对照组予导乐分娩镇痛,观察组给予经皮电刺激联合导乐分娩镇痛。观察比较两组的VAS评分、产程时间、产后出血、剖宫产率、产妇满意度、新生儿情况、不良反应发生情况等。结果 与镇痛前比较,观察组镇痛后各时间段VAS评分降低,P＜0.05;与对照组比较,观察组的产后2 h出血量、剖宫产率降低,产妇满意度提高,P＜0.05。结论 经皮电刺激联合导乐镇痛可减轻产妇痛苦,降低剖宫产率,减少产后出血,提高产妇满意度,且无明显不良反应,值得在临床上推广应用。     

84例产褥感染的临床特点及常见致病微生物耐药性分析

目的 研究产褥感染的危险因素及常见致病微生物耐药情况，为临床治疗提供参考。方法 回顾性分析我院2017 年1 月～2019 年12 月发生的84 例产褥感染病例的临床资料，与同时期未发生产褥感染的200 例产妇进行对照研究，分析产褥感染的影响因素，并对分离获得的致病微生物进行耐药性分析。结果 感染组妊娠糖尿病、产钳助产、宫口开全后中转剖宫产患者的分布率高于对照组，差异有统计学意义（P＜0.05）；经多因素Logistic 回归分析，妊娠糖尿病是产褥感染的独立影响因素（P＜0.05）。本研究中共检出致病微生物40 株，其中革兰阴性菌13 株（占32.50%），革兰阳性菌10 株（占25.00%），支原体16 株（占40.00%），衣原体1 株（占2.50%），革兰阴性菌中以大肠埃希菌最常见，对二代头孢菌素类抗生素耐药率20%。革兰阳性菌以金黄色葡萄球菌最常见，对青霉素及头孢菌素耐药率高，未发现对亚胺培南及万古霉素耐药。结论 产钳助产、妊娠糖尿病、宫口开全后中转剖宫产是产褥感染可能的危险因素，其中，妊娠糖尿病是产褥感染的独立危险因素。目前临床常见致病微生物谱及耐药率未发生明显变化。     

Therapeutics and delivery vehicles for local treatment of osteomyelitis

Osteomyelitis, or the infection of the bone, presents a major complication in orthopedics and may lead to prolonged hospital visits, implant failure, and in more extreme cases, amputation of affected limbs. Typical treatment for this disease involves surgical debridement followed by long-term, systemic antibiotic administration, which contributes to the development of antibiotic-resistant bacteria and has limited ability to eradicate challenging biofilm-forming pathogens including Staphylococcus aureus—the most common cause of osteomyelitis. Local delivery of high doses of antibiotics via traditional bone cement can reduce systemic side effects of an antibiotic. Nonetheless, growing concerns over burst release (then subtherapeutic dose) of antibiotics, along with microbial colonization of the nondegradable cement biomaterial, further exacerbate antibiotic resistance and highlight the need to engineer alternative antimicrobial therapeutics and local delivery vehicles with increased efficacy against, in particular, biofilm-forming, antibiotic-resistant bacteria. Furthermore, limited guidance exists regarding both standardized formulation protocols and validated assays to predict efficacy of a therapeutic against multiple strains of bacteria. Ideally, antimicrobial strategies would be highly specific while exhibiting a broad spectrum of bactericidal activity. With a focus on S. aureus infection, this review addresses the efficacy of novel therapeutics and local delivery vehicles, as alternatives to the traditional antibiotic regimens. The aim of this review is to discuss these components with regards to long bone osteomyelitis and to encourage positive directions for future research efforts.     

Delivery during extracorporeal membrane oxygenation (ECMO) support of pregnant woman with severe respiratory distress syndrome caused by influenza: a case report and review of the literature

Objective: To report a case of labour induction during extracorporeal membrane oxygenation (ECMO) support in a patient with acute respiratory distress syndrome (ARDS) caused by influenza and review of the literature.

Methods: Case report and the literature search of all English articles on delivery while on ECMO in patients with ARDS caused by influenza.

Results: A 25-year-old pregnant woman was initiated with ECMO due to severe ARDS caused by influenza A (H1N1) virus. When the patient had symptoms of colporrhagia and uterine contractions, the medical team decided to start labour induction while on ECMO. There were in total five case reports identified. Maternal oxygenation was improved after delivery and ECMO was successfully discontinued.

Conclusions: Maternal oxygenation was improved after delivery, which may be beneficial to reduce the duration of ECMO. Caesarean section (CS) may be the most used mode and labour induction could be another option. The procedure should be performed by an experienced ECMO team, cooperating with the obstetrician, anaesthesiologist, and ICU doctors.     

孕期宣教对孕妇影响的调查与分析

[目的]了解孕期宣教对孕妇在保健知识方面的需求性,孕期检查的必要性及心理健康状况、分娩方式选择方面的影响。[方法]采用自制问卷调查表对1500例孕妇进行调查,其中接受孕期宣教1000例,未接受孕期宣教500例。[结果]孕期宣教对孕妇在保健知识的需求性和孕期检查的必要性上,在心理健康状况和对分娩方式的选择上有显著影响(P<0.005)。[结论]开办孕妇学校对孕妇实施针对有效的孕期宣教和保健指导是必要的。