Neuromodulation in Psychiatric disorders: Experimental and Clinical evidence for reward and motivation network Deep Brain Stimulation: Focus on the medial forebrain bundle

Deep brain stimulation (DBS) in psychiatric illnesses has been clinically tested over the past 20 years. The clinical application of DBS to the superolateral branch of the medial forebrain bundle in treatment‐resistant depressed patients—one of several targets under investigation—has shown to be promising in a number of uncontrolled open label trials. However, there are remain numerous questions that need to be investigated to understand and optimize the clinical use of DBS in depression, including, for example, the relationship between the symptoms, the biological substrates/projections and the stimulation itself. In the context of precision and customized medicine, the current paper focuses on clinical and experimental research of medial forebrain bundle DBS in depression or in animal models of depression, demonstrating how clinical and scientific progress can work in tandem to test the therapeutic value and investigate the mechanisms of this experimental treatment. As one of the hypotheses is that depression engenders changes in the reward and motivational networks, the review looks at how stimulation of the medial forebrain bundle impacts the dopaminergic system.     

Impact and Predictors of Noncircular Left Ventricular Outflow Tract Shapes on Estimating Aortic Stenosis Severity by Means of Continuity Equations

Determining aortic stenosis (AS) severity is clinically important. Calculating aortic valve (AV) area by means of the continuity equation assumes a circular left ventricular outflow tract (LVOT). The full impact of this assumption in calculating AV area is unknown. Predictors of noncircular LVOT shape in patients with AS are undefined.In 109 adult patients with AS who underwent multiplanar transesophageal echocardiography, we calculated AV area by means of the standard continuity method and by a modified method involving planimetric LVOT area.We found 54 circular, 37 horizontal-oval, 8 vertical-oval, and 10 irregular LVOTs. Area derived by direct planimetry correlated better with the modified than the standard continuity method (r=0.89 vs r=0.85; both P=0.0001). Valve areas of patients with mild, moderate, or severe AS by planimetry were more often mischaracterized with use of the standard than modified method (29 vs 18; P <0.0001). Horizontal-oval AV area derived by planimetry (1.28 ± 0.55 cm²) was underestimated by the standard method (1.05 ± 0.47 cm²; P=0.001), but not by the modified method. Congenital AV morphology and low cardiac index were the only multivariate predictors of horizontal-oval shape. Low cardiac index was the only predictor of noncircular shape.More than half our patients with AS had noncircular LVOTs. Using the modified method reduces mischaracterizations of AS severity. Congenital AV morphology and low cardiac index predict horizontal-oval or noncircular shape. These data suggest the value of direct LVOT measurement to calculate AS severity in patients who have congenital AV or a low cardiac index.     

Development and approval of live attenuated influenza vaccines based on Russian master donor viruses: Process challenges and success stories

Influenza is a viral infection that affects much of the global population each year. Vaccination remains the most effective tool for preventing the disease. Live attenuated influenza vaccine (LAIV) has been used since the 1950s to protect humans against seasonal influenza. LAIVs developed by the Institute of Experimental Medicine (IEM), Saint Petersburg, Russia, have been successfully used in Russia since 1987.In 2006, the World Health Organization (WHO) announced a Global action plan for influenza vaccines (GAP). WHO, recognizing potential advantages of LAIV over the inactivated influenza vaccine in a pandemic situation, included LAIV in the GAP.BioDiem Ltd., a vaccine development company based in Melbourne, Australia which held the rights for the Russian LAIV, licensed this technology to WHO in 2009. WHO was permitted to grant sub-licenses to vaccine manufacturers in newly industrialized and developing countries to use the Russian LAIV for the development, manufacture, use and sale of pandemic and seasonal LAIVs. To date, WHO has granted sub-licenses to vaccine manufacturers in China (Changchun BCHT Biotechnology Co., Ltd.), India (Serum Institute of India Pvt. Ltd.) and Thailand (Government Pharmaceutical Organization). In parallel, in 2009, IEM signed an agreement with WHO, under which IEM committed to supply pandemic and seasonal candidate vaccine viruses to the sub-licensees.This paper describes the progress made by collaborators from China, India, Russia and Thailand in developing preventive measures, including LAIV against pandemic influenza.     

Recurrent herpes labialis in the pediatric population: Prevalence,therapeutic studies,and associated complications

Recurrent herpes labialis (RHL) is an incredibly common condition, though the medical literature evaluating pediatric aspects is limited. This paper assesses prevalence and therapeutic studies of pediatric RHL as well as disease complications. A comprehensive literature search of English‐language citations based on PubMed queries of selected terms was performed, with exclusion if methodology was not discussed, or if studies had 10 or fewer patients. RHL prevalence in pediatrics has been assessed by measures of point and periodic prevalence, though methodologic limitations may under‐ or over‐estimate the true prevalence of RHL. Studies have been conducted to evaluate therapeutic safety, tolerability, and efficacy of antivirals in the pediatric population. Pediatric RHL point prevalence ranges from 0.72% to 5.2% depending on the population study and the methodologies used. Pediatric RHL carries a significant public health burden and is often implicated in patients with eczema herpeticum, erythema multiforme, reactive infectious mucositis eruptions, and hypersensitivity reactions. There are few studies that evaluate the rates of occurrence of these sequelae associated with pediatric RHL.     

Long-term health-related quality of life of breast cancer survivors remains impaired compared to the age-matched general population especially in young women. Results from the prospective controlled BREX exercise study

ObjectiveTo investigate long-term health-related quality of life (HRQoL) changes over time in younger compared to older disease-free breast cancer survivors who participated in a prospective randomized exercise trial.MethodsSurvivors (aged 35–68 years) were randomized to a 12-month exercise trial after adjuvant treatment and followed up for ten years. HRQoL was assessed with the generic 15D instrument during follow-up and the younger (baseline age ≤ 50) and older (age >50) survivors’ HRQoL was compared to that of the age-matched general female population (n = 892). The analysis included 342 survivors.ResultsThe decline of HRQoL compared to the population was steeper and recovery slower in the younger survivors (p for interaction < 0.001). The impairment was also larger among the younger survivors (p = 0.027) whose mean HRQoL deteriorated for three years after treatment and started to slowly improve thereafter but still remained below the population level after ten years (difference −0.017, 95% CI: −0.031 to −0.004). The older survivors’ mean HRQoL gradually approached the population level during the first five years but also remained below it at ten years (difference −0.019, 95% CI: −0.031 to −0.007). The largest differences were on the dimensions of sleeping and sexual activity, on which both age groups remained below the population level throughout the follow-up.ConclusionsHRQoL developed differently in younger and older survivors both regarding the most affected dimensions of HRQoL and the timing of the changes during follow-up. HRQoL of both age groups remained below the population level even ten years after treatment.     

异常灌注评分法评价肺血栓栓塞症患者治疗效果的价值

目的 分析异常灌注评分法对肺血栓栓塞症（PTE）疗效的评估价值。方法 选择明确诊断为急性PTE的患者46例，在治疗前及治疗后14d行肺灌注显像，2位核医学科医师分别对肺灌注显像图进行定性分析，随后采用异常灌注评分法和Parker创建的肺段评分法进行肺灌注显像结果判读，比较两者在判读结果方面的一致性及其相关性，并比较2种方法所示的治疗后灌注改善率。结果 2位医师对左肺灌注结果判读的一致性为100％（Kappa值为1．0），对右肺灌注结果判读的一致性为91．3％（Kappa值为0．69）。治疗前后2种灌注评分结果均有较高度的一致性（Kappa值分别为0．657和0．665，P均〈0．001）。在治疗前和治疗后通过2种评分方法所计算的联合评分均呈显著正相关（r值分别为0．770和0．771，P均〈0．001）。肺灌注改善率在2种评分方法之间无显著差异（P=0．128）。结论 异常灌注评分法判读简单，是评价PTE治疗效果的较好方法。