Germline gain-of-function MMP11 variant results in an aggressive form of colorectal cancer

Matrix metalloproteinase-11 (MMP11) is an enzyme with proteolytic activity against matrix and nonmatrix proteins. Although most MMPs are secreted as inactive proenzymes and are later activated extracellularly, MMP11 is activated intracellularly by furin within the constitutive secretory pathway. It is a key factor in physiological tissue remodeling and its alteration may play an important role in the progression of epithelial malignancies and other diseases. TCGA colon and colorectal adenocarcinoma data showed that upregulation of MMP11 expression correlates with tumorigenesis and malignancy. Here, we provide evidence that a germline variant in the MMP11 gene (NM_005940: c.232C>T; p.(Pro78Ser)), identified by whole exome sequencing, can increase the tumorigenic properties of colorectal cancer (CRC) cells. P78S is located in the prodomain region, which is responsible for blocking MMP11's protease activity. This variant was detected in the proband and all the cancer-affected family members analyzed, while it was not detected in healthy relatives. In silico analyses predict that P78S could have an impact on the activation of the enzyme. Furthermore, our in vitro analyses show that the expression of P78S in HCT116 cells increases tumor cell invasion and proliferation. In summary, our results show that this variant could modify the structure of the MMP11 prodomain, producing a premature or uncontrolled activation of the enzyme that may contribute to an early CRC onset in these patients. The study of this gene in other CRC cases will provide further information about its role in CRC development, which might improve patient treatment in the future.     

The impact of a total knee arthroplasty on jaw movements,upper body posture,plantar pressure distribution,and postural control

ABSTRACT

Objective: The purpose of this study was to examine the influence of a total knee arthroplasty (TKA) on linked cranial and caudal structures.

Methods: Thirty-five (14f/21m) subjects participated in this study: 15 subjects (9f, 6m) pre- and post- TKA and a control group of 20 subjects (5f, 15m). The measurements included: jaw condyle position and movement, back scan, plantar pressure distribution, and body sway.

Results: There were no significant differences in electronic position analysis of the jaw; however, the protrusion of the TKA group improved (p = 0.001). The test group had a more anteriorly inclined thoracic spine and a less pronounced lumbar lordosis. Before and after surgery, the body sway in the test group was larger.

Conclusion: The TKA affected most prominently the static mechanisms of the postural control and the spine position. The trajectories of the mandible during protrusion also changed slightly.     

Dengue vaccine: WHO position paper,September 2018 – Recommendations

This article presents the World Health Organization’s (WHO) recommendations on the use of dengue vaccine excerpted from the WHO position paper on dengue vaccine – September 2018, published in the Weekly Epidemiological Record [1]. This position paper replaces the July 2016 WHO position paper concerning the first licensed dengue vaccine, CYD-TDV [2]. The position paper presents new evidence that became available in November 2017. A retrospective analysis of data from clinical trials, using a new serological assay classified trial participants according to their dengue serostatus prior to receipt of the first vaccine dose. The analysis revealed an excess risk of severe dengue in seronegative vaccine recipients compared to seronegative non-vaccinated individuals, while confirming long-term protection in seropositive individuals [3]. The paper provides revised guidance on dengue vaccination strategies from a population health perspective.Footnotes to this paper provide a number of core references including references to grading tables that assess the quality of the scientific evidence, and to the evidence-to-recommendation table. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. Recommendations on the use of dengue vaccine CYD-TDV were discussed by SAGE in April 2018; evidence presented at the meeting can be accessed at: http://www.who.int/immunization/sage/meetings/2018/april/presentations_background_docs/en/     

Interhemispheric visual competition after multisensory reversal of hemianopia

Unilateral lesions of visual cortex have the secondary consequence of suppressing visual circuits in the midbrain superior colliculus (SC), collectively producing blindness in contralesional space (“hemianopia”). Recent studies have demonstrated that SC visual responses and contralesional vision can be reinstated by a non‐invasive multisensory training procedure in which spatiotemporally concordant visual‐auditory pairs are repeatedly presented within the blind hemifield. Despite this recovery of visual responsiveness, the loss of visual cortex was expected to result in permanent deficits in that hemifield, especially when visual events in both hemifields compete for attention and access to the brain's visuomotor circuitry. This was evaluated in the present study in a visual choice paradigm in which the two visual hemifields of recovered cats were simultaneously stimulated with equally valent visual targets. Surprisingly, the expected disparity was not found, and some animals even preferred stimuli presented in the previously blind hemifield. This preference persisted across multiple stimulus intensity levels and there was no indication that animals were less aware of cues in the previously blind hemifield than in its spared counterpart. Furthermore, when auditory cues were combined with visual cues, the enhanced performance they produced on a visual task was no greater in the normal than in the previously blind hemifield. These observations suggest that the multisensory rehabilitation paradigm revealed greater inherent visual information processing potential in the previously blind hemifield than was believed possible given the loss of visual cortex.     

不同规格怀牛膝不同极性部位HPLC指纹图谱

目的研究并比较不同规格怀牛膝不同极性部位的HPLC指纹图谱,探索其内部质量差异,为该药材的规格标准完善及临床用药提供参考。方法将怀牛膝用体积分数75%乙醇水浴回流提取,得体积分数75%乙醇回流提取物,用40 mL水溶解后,依次用石油醚、三氯甲烷、乙酸乙酯、正丁醇进行萃取,得到各萃取相及萃取后的水相,浓缩至浸膏,采集各部位HPLC指纹图谱;运用相似度、综合聚类法进行数据分析,同时对其不同部位的指纹图谱进行比对分析。结果石油醚、氯仿部位均标定了11个共有峰,乙酸乙酯部位标定了10个共有峰,正丁醇部位标定了19个共有峰,水部位标定8个共有峰;氯仿部位指纹图谱相似度差异较大,其他部位指纹图谱相似度差异较小,均在0.9以上;石油醚部位指纹图谱差异主要体现在峰高,乙酸乙酯部位、氯仿部位、水部位的化学成分种类及峰高均存在差异;综合聚类分析能将不同规格怀牛膝区分开。结论不同规格怀牛膝内部质量存在差异;实验中所建立的HPLC指纹图谱可以全面反映不同规格怀牛膝的化学成分分布,为不同规格怀牛膝的整体质量评价提供参考。     

Effects of box handle position and carrying range on bi-manual carrying capacity for females

This study utilizes a psychophysical approach to examine the effects on carrying capacity for bi-manual carrying tasks involving different handle positions and carrying ranges. A total of 16 female subjects participated in the experiment in groups of two people, and each group of subjects performed the tasks in a random order with 12 different combinations of carrying task. The independent variables are handle position (upper, middle, lower) and carrying range (F–F: floor height carried to floor height, F–W: floor height carried to waist height, W–W: waist height carried to waist height, W–F: waist height carried to floor height), the dependent variable is the maximum acceptable carried weight (MAWC), heart rate (HR), and the rating of perceived exertion (RPE). The results show that the handle position has a significant effect on MAWC and overall RPE but no significant effect on HR. Carrying range has a significant effect on the MAWC and HR, but no significant effect on overall HR. The handle position and carrying range have a significant interaction on the MAWC and HR. The RPE for different body parts shows significant differences, and the hands feel the most tired. Overall, this study confirms that the lower handle position with the W–W carrying range is the best combination for a two-person carrying task.     

改良俯卧位对俯卧位通气临床疗效及并发症的影响

目的观察改良俯卧位对俯卧位通气(PPV)临床疗效及并发症的影响。方法将该院呼吸和危重症医学科行PPV的52例患者随机分为对照组和实验组各26例,对照组应用常规方法进行PPV,实验组采用改良俯卧位进行PPV。比较两组患者PPV的临床效果和并发症发生情况。结果两组间俯卧位前和俯卧位后12 h的氧合指数无明显差异(P>0.05);两组患者俯卧位后12 h的氧合指数均较各组俯卧位前明显改善(P<0.05);两组患者气管插管脱出、血流动力学显著波动、误吸和面部水肿的发生率无显著差异(P>0.05);实验组皮肤压疮的发生率明显低于对照组(P<0.05)。结论改良俯卧位对PPV的临床疗效无显著影响,但可以降低皮肤压疮的发生率。