Magnetic resonance imaging measurements of the response of murine and human tumors to the vascular-targeting agent ZD6126.

PURPOSE: ZD6126 is a novel vascular targeting agent currently undergoing clinical evaluation. It acts by destabilizing the microtubulin of fragile and proliferating neoendothelial cells in tumors. The drug leads to blood vessel congestion, the selective destruction of the vasculature, and extensive necrosis in experimental tumors. The aim of the study reported here was to assess the ability of dynamic contrast enhanced magnetic resonance imaging (MRI) to measure the antivascular effects of ZD6126 in tumors. EXPERIMENTAL DESIGN: The work was carried out in mice bearing C38 colon adenocarcinoma and in patients with advanced cancers. MRI was performed before and 6 h (human tumors) or 24 h (C38 tumors) after i.v. drug administration. Contrast agent (gadolinium diethylenetriaminepentaacetate) enhancement was characterized by the initial area under the gadolinium diethylenetriaminepentaacetate uptake versus time curve (IAUC). IAUC reflects blood flow, vascular permeability, and the fraction of interstitial space. RESULTS: The median IAUC was reduced in all C38 tumors after ZD6126 administration [by 6-48% at 50 mg/kg (n = 3)], 58-91% at 100 mg/kg (n = 4), and 11-93% at 200 mg/kg (n = 6). In contrast, the administration of vehicle only led to no consistent change in median IAUC (n = 4). The ZD6126-induced changes in median IAUC appeared to be dose dependent (P = 0.045). No ZD6126-induced changes were apparent in murine muscle. Similar effects were seen in preliminary data from human tumors (11 tumors studied, 9 patients). At doses of 80 mg/m(2) and higher, the median IAUC post-ZD6126 treatment was reduced in all of the tumors studied (8 tumors, 6 patients) to 36-72% from the baseline value. There was a significant trend of increasing reductions with increasing exposure (P < 0.01). No drug-induced changes in human muscle or spleen IAUC were apparent. The reproducibility of the median IAUC parameter was investigated in patients. In 19 human tumors (measured in 19 patients) inter- and intratumor coefficients of variation were 64 and 18%. CONCLUSIONS: The contrast enhanced-MRI measured median IAUC is a useful end point for quantifying ZD6126 antivascular effects in human tumors.     

Glomerulocystic disease with hepatoblastoma in a neonate: a case report

Glomerulocystic disease (GCD) is a very rare condition. Only two previous reports have linked this condition with hepatoblastoma. We report a neonate with US evidence of grossly enlarged echogenic kidneys and features typical of hepatic fibrosis, complicated by the presence of a hepatoblastoma. The report discusses the differential diagnosis and highlights GCD as one cause of large, bright kidneys on US. It also adds further evidence to the suggested association between GCD and hepatoblastoma. Received: 15 May 1997 Accepted: 24 February 1998     

英国补充治疗的成本效果：系统性综述

补充治疗（包括针灸和草药——编者注）是否应该整合纳入英国国民医疗卫生服务体系（NHS），成本效益的数据资料成为争论的关键问题。但是，就我们所知，以前没有人对英国补充疗法的成本效益做过研究。     

Early-Life Colonization by Anelloviruses in Infants

Anelloviruses (AVs) are found in the vast majority of the human population and are most probably part of a healthy virome. These viruses infect humans in the early stage of life, however, the characteristics of the first colonizing AVs are still unknown. We screened a collection of 107 blood samples from children between 0.4 and 64.8 months of age for the presence of three AV genera: the Alpha-, Beta- and Gammatorquevirus. The youngest child that was positive for AV was 1.2 months old, and a peak in prevalence (100% of samples positive) was reached between the twelfth and eighteenth months of life. Intriguingly, the beta- and gammatorqueviruses were detected most at the early stage of life (up to 12 months), whereas alphatorqueviruses, the most common AVs in adults, increased in prevalence in children older than 12 months. To determine whether that order of colonization may be related to oral transmission and unequal presence of AV genera in breast milk, we examined 63 breast milk samples. Thirty-two percent of the breast milk samples were positive in a qPCR detecting beta- and gammatorqueviruses, while alphatorqueviruses were detected in 10% of the samples, and this difference was significant (p = 0.00654). In conclusion, we show that beta- and gammatorqueviruses colonize humans in the first months of life and that breastfeeding could play a role in AV transmission.     

A Review on Rhubarb-Derived Substances as Modulators of Cardiovascular Risk Factors—A Special Emphasis on Anti-Obesity Action

The currently available anti-obesity therapies encounter many associated risks and side effects often causing the ineffectiveness of treatment. Therefore, various plant-derived substances have been extensively studied as a promising support or even an alternative for existing anti-obesity therapies. This review is dealing with the anti-obesity potential of edible and ethnomedicinal rhubarb species and emerging possible role of the rhubarb-derived extracts or individual compounds in the prevention of obesity and perspectives for their use in an anti-obesity treatment. A special emphasis is put on the most popular edible specimens, i.e., Rheum rhabarbarum L. (garden rhubarb) and Rheum rhaponticum L. (rhapontic rhubarb, Siberian rhubarb); however, the anti-obesity potential of other rhubarb species (e.g., R. officinale, R. palmatum, and R. emodi) is presented as well. The significance of rhubarb-derived extracts and low-molecular specialized rhubarb metabolites of diversified chemical background, e.g., anthraquinones and stilbenes, as potential modulators of human metabolism is highlighted, including the context of cardiovascular disease prevention. The available reports present multiple encouraging rhubarb properties starting from the anti-lipidemic action of rhubarb fibre or its use as purgative medicines, through various actions of rhubarb-derived extracts and their individual compounds: inhibition of enzymes of cholesterol and lipid metabolism, targeting of key molecular regulators of adipogenesis, regulators of cell energy metabolism, the ability to inhibit pro-inflammatory signalling pathways and to regulate glucose and lipid homeostasis contributing to overall in vivo and clinical anti-obesity effects.     

Comparative Analysis of Postoperative Complications of Sentinel Node Identification Using the SentiMag® Method and the Use of a Radiotracer in Patients with Breast Cancer

(1) Background: The purpose of the study was a retrospective, comparative assessment of complications of the surgical sentinel node biopsy (SNB) procedure in breast cancer using the radiotracer method and the SentiMag^® method on groups of patients after 3.5 years of use. (2) Methods: The material was a group of 345 patients with primary surgical breast cancer who underwent the SNB procedure with the use of a radiotracer in combination with wide local excision (WLE), simple amputation (SA) with SNB and an independent SNB procedure in the period from May 2018 to January 2021 in the Department of Oncological Surgery. Of the patients who were monitored in the Hospital Outpatient Clinic, 300 were enrolled. The analyzed group was compared in terms of the occurrence of the same complications with the group of 303 patients also operated on in our center in the period from January 2014 to September 2017, in which SN identification was performed using the SentiMag^® method. (3) Results: The most common complications found were sensation disorders in the arm, which occurred in 16 (14.1%) patients using the radiotracer method, SentiMag^®-11 (9.9%). By comparing the complication rate between the methods with the radiotracer (n = 300) and SentiMag^® (n = 303), no significant differences were found. (4) Conclusions: Sentinel node (SN) identification using the radiotracer method and the SentiMag^® method are comparable diagnostic methods in breast cancer, with a low risk of complications.     

A Longitudinal Cohort Study of Youth Mental Health and Substance use Before and During the COVID-19 Pandemic in Ontario,Canada: An Exploratory Analysis

BackgroundYouth mental health appears to have been negatively impacted by the COVID-19 pandemic. The impact on substance use is less clear, as is the impact on subgroups of youth, including those with pre-existing mental health or substance use challenges.ObjectiveThis hypothesis-generating study examines the longitudinal evolution of youth mental health and substance use from before the COVID-19 pandemic to over one year into the pandemic among youth with pre-existing mental health or substance use challenges.MethodA total of 168 youth aged 14–24 participated. Participants provided sociodemographic data, as well as internalizing disorder, externalizing disorder, and substance use data prior to the pandemic’s onset, then every two months between April 2020–2021. Linear mixed models and Generalized Estimating Equations were used to analyze the effect of time on mental health and substance use. Exploratory analyses were conducted to examine interactions with sociodemographic and clinical characteristics.ResultsThere was no change in internalizing or externalizing disorder scores from prior to the pandemic to any point throughout the first year of the pandemic. Substance use scores during the pandemic declined compared to pre-pandemic scores. Exploratory analyses suggest that students appear to have experienced more mental health repercussions than non-students; other sociodemographic and clinical characteristics did not appear to be associated with mental health or substance use trajectories.ConclusionsWhile mental health remained stable and substance use declined from before the COVID-19 pandemic to during the pandemic among youth with pre-existing mental health challenges, some youth experienced greater challenges than others. Longitudinal monitoring among various population subgroups is crucial to identifying higher risk populations. This information is needed to provide empirical evidence to inform future research directions.     

Outbreak of Salmonella Newport linked to imported frozen cooked crayfish in dill brine,Sweden, July to November 2019

In autumn 2019, the Public Health Agency of Sweden identified a cluster of Salmonella Newport cases by whole genome sequencing (WGS). Cases’ distribution in place and time indicated a nation-wide ongoing outbreak. An investigation was initiated to identify the source and prevent further cases. We conducted a case–case study based on notified salmonellosis cases and a Salmonella trawling questionnaire, comparing 20 outbreak cases and 139 control cases. Food exposures were compared by adjusted odds ratios (aOR) with 95% confidence interval (CI) using logistic regression. Implicated foods were sampled. Outbreak cases were more likely to have consumed crayfish (aOR = 26; 95% CI: 6.3–105). One specific brand of imported frozen, pre-cooked whole crayfish in dill brine was identified as the source. Salmonella Newport was later detected in different batches from retail and in one sample from border control. Isolates from food samples clustered with the human outbreak strain by WGS. Although the retailer made a complete recall, two more cases were identified long afterwards. This investigation demonstrated the successful use of a case–case study and targeted microbiological testing to identify the source. The immediate action taken by the retailer was important to confirm the source and stop the outbreak.     

The effect of incisions for cataract on corneal curvature

PURPOSE: To determine the magnitude and duration of change on the horizontal and vertical meridians of the cornea after five different incisions for cataract. DESIGN: Retrospective comparative interventional study of five commonly used incisions for cataract surgery: extracapsular cataract extraction (ECCE), 6-mm superior scleral tunnel (6Sup), 3-mm superior scleral tunnel (3Sup), 3-mm temporal scleral tunnel (3Temp), and 3-mm temporal corneal incision (3Cor). PARTICIPANTS: A total of 662 cases with preoperative regular astigmatism, measured with keratometry. METHODS: The mean net change on each meridian was computed at 1 day, 1 week, 2 weeks, 1 month, 1.5 months, 2 months, 4 months, 6 months, and 12 months and at succeeding 6-month intervals after surgery. Best-fit parameters were calculated for the observed changes in the horizontal and vertical keratometry values after each incision. To determine when the cornea stabilized, average change on the horizontal and vertical meridians was compared with an estimate of the accuracy of keratometry measurement. MAIN OUTCOME MEASURES: The pattern of change on the horizontal and vertical meridians and time for the cornea to stabilize after each incision. RESULTS: The initial and final net changes after a superior incision decrease with length. A sigmoid equation describes the course of the changes on the horizontal and vertical meridians after the superior incisions. The changes after the temporal incisions depend linearly on time after surgery. Considering the uncertainty of keratometry, the corneal meridians stabilized 4.5 months after ECCE, 1.2 months after 6Sup, and 0.3 months after 3Sup. No significant change was detected on the horizontal and vertical meridians after 3Temp and 3Cor. CONCLUSIONS: The magnitude and the duration of keratometric change on the horizontal and vertical meridians of the cornea depend on the length and location of the incision. Within the limits of measurement error, no significant change in corneal curvature was detected after either small temporal incision.