Improvement of patient localization repeatability using a light-section based optical surface guidance system in a pre-positioning procedure

PurposeSurface-guided radiotherapy is useful for the pre-positioning and monitoring of radiotherapy. The purpose of this study was to investigate the impact of surface guidance on the repeatability of patient localization and to estimate the specific point at which high positional errors occur.Materials and methodsTen patients without the VOXELAN system (non-VXLN group) and 10 patients with the VOXELAN as the pre-positioning procedure (VXLN group) were included in this analysis. Twelve regions of interest (ROI) were defined in all the patients to verify any misalignment during radiotherapy. Thirteen ROIs were defined on the isocenter.ResultsCompared with the non-VXLN group, the translational positional errors of the VXLN group were the same for all the ROIs. The mean translational positional errors of the VXLN group in the longitudinal direction were approximately 0.1 mm, and the standard deviation was the largest among the three directions in all the ROIs. The magnitude of the standard deviation in the non-VXLN group varied independently of the ROI and direction. The standard deviations of the VXLN group in the longitudinal direction were large in all the ROIs, while the standard deviations in the vertical and lateral directions were small.ConclusionPre-positioning with a surface guidance system reduced the body twist and rotation, which could not be corrected by image-guided radiotherapy alone. Since the VOXELAN can detect positioning errors quickly and without additional radiation exposure to the patient, it can be used as a tool for pre-positioning in radiotherapy.     

Hepatitis B and circadian rhythm of the liver

The circadian rhythm in humans is determined by the central clock located in the hypothalamus’s suprachiasmatic nucleus, and it synchronizes the peripheral clocks in other tissues. Circadian clock genes and clock-controlled genes exist in almost all cell types. They have an essential role in many physiological processes, including lipid metabolism in the liver, regulation of the immune system, and the severity of infections. In addition, circadian rhythm genes can stimulate the immune response of host cells to virus infection. Hepatitis B virus (HBV) infection is the leading cause of liver disease and liver cancer globally. HBV infection depends on the host cell, and hepatocyte circadian rhythm genes are associated with HBV replication, survival, and spread. The core circadian rhythm proteins, REV-ERB and brain and muscle ARNTL-like protein 1, have a crucial role in HBV replication in hepatocytes. In addition to influencing the virus’s life cycle, the circadian rhythm also affects the pharmacokinetics and efficacy of antiviral vaccines. Therefore, it is vital to apply antiviral therapy at the appropriate time of day to reduce toxicity and improve the effectiveness of antiviral treatment. For these reasons, understanding the role of the circadian rhythm in the regulation of HBV infection and host responses to the virus provides us with a new perspective of the interplay of the circadian rhythm and anti-HBV therapy. Therefore, this review emphasizes the importance of the circadian rhythm in HBV infection and the optimization of antiviral treatment based on the circadian rhythm-dependent immune response.     

Orchestration of the circadian clock and its association with Alzheimer's disease: Role of endocannabinoid signaling

Circadian rhythms are 24-hour natural rhythms regulated by the suprachiasmatic nucleus, also known as the "master clock". The retino-hypothalamic tract entrains suprachiasmatic nucleus with photic information to synchronise endogenous circadian rhythms with the Earth’s light-dark cycle. However, despite the robustness of circadian rhythms, an unhealthy lifestyle and chronic photic disturbances cause circadian rhythm disruption in the suprachiasmatic nucleus’s TTFL loops via affecting glutamate and γ-aminobutyric acid-mediated neurotransmission in the suprachiasmatic nucleus. Recently, considerable evidence has been shown correlating CRd with the incidence of Alzheimer's disease. The present review aims to identify the existence and signalling of endocannabinoids in CRd induced Alzheimer's disease through retino-hypothalamic tract- suprachiasmatic nucleus-cortex. Immunohistochemistry has confirmed the expression of cannabinoid receptor 1 in the suprachiasmatic nucleus to modulate the circadian phases of the master clock. Literature also suggests that cannabinoids may alter activity of suprachiasmatic nucleus by influencing the activity of their major neurotransmitter γ-aminobutyric acid or by interacting indirectly with the suprachiasmatic nucleus’s two other major inputs i.e., the geniculo-hypothalamic tract-mediated release of neuropeptide Y and serotonergic inputs from the dorsal raphe nuclei. Besides, the expression of cannabinoid receptor 2 ameliorates cognitive deficits via reduction of tauopathy and microglial activation. In conclusion, endocannabinoids may be identified as a putative target for correcting CRd and decelerating Alzheimer’s disease.     

Perceived neighborhood social cohesion and the 10-year risk of cardiovascular disease in low- and middle-income countries: The World Health Organization Study on Global Aging and Adult Health

Low- and middle-income countries (LMICs) bear the greatest burden of cardiovascular disease (CVD) worldwide. Emerging evidence, mostly from industrialized countries, suggest that neighborhood characteristics influence cardiovascular health. This study presents results from 27,797 participants living in six LMICs on the association of perceived neighborhood social cohesion, the degree of connectedness among neighbors, with 10-year risk of CVD. We observed that greater perceived neighborhood social cohesion was associated with lower odds of high (>20%) 10-year CVD risk (OR = 0.67, 95%CI: 0.53–0.86). These novel findings, suggest that interventions to enhance social cohesion may have beneficial effects on cardiovascular health in LMICs.     

Advanced vaccinology training globally: Update and impact of the COVID-19 crisis

The rapid development of innovations and new technologies, the focus on the life-course approach to immunization and equity, and the prevalent hesitancy towards vaccines requires immunization staff to be well-trained and updated regularly in order to deliver quality immunization services to the public. The need for advanced vaccinology training is therefore paramount. In preparation for a second Global Workshop on Advanced Vaccinology Training that took place in March 2022, this paper presents the results of a survey aiming to provide a thorough update of a landscape analysis on advanced vaccinology courses conducted in 2018 and a look at the impact of the COVID-19 crisis. Thirty-three course organizers responded to a survey to provide information on their respective course. Of those, 17 courses are short courses, 11 post-graduate courses and 5 are Master level courses. Most courses are organized on an annual basis. Even though some courses were not sustained overtime, the number of courses has been increasing during the last few years, and at least one vaccinology course is now being offered in each WHO region. Although the training capacity has increased tremendously, the need still exceeds the capacity and many courses have way more applicants than they can select. The most frequent challenges reported included sustainable funding and identifying faculty. The COVID-19 pandemic impacted the delivery of several vaccinology courses, which have been postponed or reformatted to an online or hybrid training event. An e-portal of the global collaboration has been established to facilitate communication between the different courses and to assist future course participants to identify the most suitable course for their needs.     

MR-safety in clinical practice at 7T: Evaluation of a multistep screening process in 1819 subjects

IntroductionMR facilities must implement and maintain adequate screening and safety procedures to ensure safety during MR examinations. The aim of this study was to evaluate a multi-step MR safety screening process used at a 7T facility regarding incidence of different types of safety risks detected during the safety procedure.MethodsSubjects scheduled for an MR examination and having entered the 7T facility during 2016–2019 underwent a pre-defined multi-step MR safety screening process. Screening documentation of 1819 included subjects was reviewed, and risks identified during the different screening steps were compiled. These data were also related to documented decisions made by a 7T MR safety committee and reported MR safety incidents.ResultsPassive or active implants (n = 315) were identified in a screening form and/or an additional documented interview in 305 subjects. Additional information not previously self-reported by the subject, regarding implants necessitating safety decisions performed by the staff was revealed in the documented interview in 102 subjects (106 items). In total, the 7T MR safety committee documented a decision in 36 (2%) of the included subjects. All of these subjects were finally cleared for scanning.ConclusionA multi-step screening process allows a thorough MR screening of subjects, avoiding safety incidents. Different steps in the process allow awareness to rise and items to be detected that were missed in earlier steps.Implications for practiceSafety questions posed at a single timepoint during an MR screening process might not reveal all safety risks. Repetition and rephrasing of screening questions leads to increased detection of safety risks. This could be effectively mitigated by a multi-step screening process. A multi-disciplinary safety committee is efficient at short notice responding to unexpected safety issues.     

免疫抑制儿童感染新型冠状病毒Omicron变异株病毒清除时间的回顾性队列研究

背景：儿童新型冠状（新冠）病毒Omicron变异株流行期间，免疫抑制状态儿童新冠病毒清除时间定量分析研究较少。 目的：探讨新冠病毒Omicron株感染后免疫抑制和非免疫抑制儿童病毒清除的时间差别，为公共卫生政策制定和精准疫情防控措施提供临床数据。 设计：回顾性队列研究。 方法：以新冠病毒Omicron变异株感染住院患儿为队列人群，分为免疫抑制组和非免疫抑制组，免疫抑制分为绝对免疫抑制、相对免疫抑制和实施免疫抑制疗法，以免疫抑制组病例的性别、年龄和新冠病毒感染的分型与非免疫抑制组行1∶3匹配。以鼻咽拭子新冠病毒PCR检测拷贝数阈（Ct）值≥35为队列终点。 主要结局指标：新冠病毒清除时间。 结果：2022年4月12日至2022年5月12日在上海市新冠病毒感染定点收治医院符合本文共同纳入和排除标准的连续病例728例。免疫抑制组33例，其中绝对免疫抑制8例，相对免疫抑制23例，接受免疫抑制疗法2例（不包括绝对和相对免疫抑制患儿）。非免疫抑制组匹配后99例。2组临床症状、新冠病毒感染治疗和疫苗接种次数差异均无统计学意义。免疫抑制组和非免疫抑制组新冠病毒清除时间分别为（16.5±6.8）和（10.3±4.4）d，差异有统计学意义。免疫抑制组和非免疫抑制组新冠病毒感染轻型病例病毒清除时间分别为（14.0 ± 8.3）和（9.7 ± 3.1）d，普通型病例病毒清除时间分别为（18.3 ± 4.9）和（11.2 ± 5.9）d，差异均有统计学意义。2组单日病毒清除率在第9~14天时差异有统计学意义（P为0.005~0.039）。2组普通型病例单日病毒清除率在第10~15天时差异有统计学意义。免疫抑制组新冠病毒感染2周后核酸检测再次呈阳性3例（9%），临床分型均较前轻，3例均未接种新冠疫苗。 结论：Omicron株感染的免疫抑制患儿病毒清除时间较非免疫抑制患儿显著延长，主要反映在第9~14天，免疫抑制患儿病毒复阳风险高，提示需要更长的隔离时间和转阴后严格的病毒监测。     

胶质淋巴系统——脑部疾病机制研究新方向

胶质淋巴系统是一个主要由星形胶质细胞水通道蛋白4介导的依靠动脉、静脉周围血管间隙的脑脊液-脑组织液交换流动的系统，是阿尔茨海默病、脑卒中、帕金森病、失眠、抑郁症等脑病的共同特征，是一条新的脑代谢途径，可以清除包括β-淀粉样蛋白、乳酸在内的代谢产物。本文综合分析了全球有关胶质淋巴系统在脑部疾病的研究，得出：胶质淋巴系统可能为神经退行性疾病等发病机制和诊治策略研究带来新视角；胶质淋巴系统有望为一些脑部疾病诊断提供新的有效证据；胶质淋巴系统可能是脑部疾病治疗给药方式的新途径。     

Repurposing of parenterally administered active substances used to treat pain both systemically and locally

Pain is a constant in our lives. The efficacy of drug therapy administered by the parenteral route is often limited either by the physicochemical characteristics of the drug itself or its adsorption–distribution–metabolism–excretion (ADME) mechanisms. One promising alternative is the design of innovative drug delivery systems that can improve the pharmacokinetics |(PK) and/or reduce the toxicity of traditionally used drugs. In this review, we discuss several products that have been approved by the main regulatory agencies (i.e., nano- and microsystems, implants, and oil-based solutions), highlighting the newest technologies that govern both locally and systemically the delivery of drugs. Finally, we also discuss the risk assessment of the scale-up process required, given the impact that this approach could have on drug manufacturing.Teaser: The management of pain by way of the parenteral route can be improved using complex drug delivery systems (e.g., micro- and nanosystems) which require high-level assessment and shorten the regulatory pathway.