First trimester urinary placental growth factor and development of pre-eclampsia

Objective  To compare urinary placental growth factor (PlGF) concentration at 11⁺⁰ to 13⁺⁶ weeks of gestation in women who subsequently develop pre-eclampsia with normotensive controls.
Design  Nested case–control study within a prospective study for first trimester prediction of pre-eclampsia.
Setting  Routine antenatal visit in a teaching hospital.
Population  Fifty-two women who developed pre-eclampsia and 52 controls matched for gestational age and sample storage time.
Methods  Urinary PlGF concentration and PlGF to creatinine ratio were measured in women who developed pre-eclampsia and their matched controls. Comparisons between groups were performed using Student's t test.
Main outcome measures  Development of pre-eclampsia.
Results  In the pre-eclampsia group, the median urinary PlGF concentration (20.6 pg/ml, interquartile range [IQR] 9.1–32.0 pg/ml) and median urinary PlGF to creatinine ratio (1.6 pg/mg, IQR 1.2–2.5 pg/mg) were not significantly different from the control group (11.8 pg/ml, IQR 5.5–29.8 pg/ml, P = 0.1 and 1.7 pg/mg, IQR 1.2–2.3 pg/mg, P = 0.3, respectively). There were no significant differences between women with early-onset pre-eclampsia requiring delivery before 34 weeks ( n = 13) and those with late-onset pre-eclampsia ( n = 39) and between women with pre-eclampsia and fetal growth restriction (FGR) ( n = 25) and those with pre-eclampsia and no FGR ( n = 27) in either median PlGF concentration or median urinary PlGF to creatinine ratio.
Conclusions  The development of pre-eclampsia is not preceded by altered urinary PlGF concentration in the first trimester of pregnancy.     

Diffusion MRI visualization

Modern diffusion magnetic resonance imaging (dMRI) acquires intricate volume datasets and biological meaning can only be found in the relationship between its different measurements. Suitable strategies for visualizing these complicated data have been key to interpretation by physicians and neuroscientists, for drawing conclusions on brain connectivity and for quality control. This article provides an overview of visualization solutions that have been proposed to date, ranging from basic grayscale and color encodings to glyph representations and renderings of fiber tractography. A particular focus is on ongoing and possible future developments in dMRI visualization, including comparative, uncertainty, interactive and dense visualizations.     

Immunotherapy in biliary tract cancers: Current evidence and future perspectives

Bile duct tumors are comprised of tumors that originate from both intrahepatic and extrahepatic bile ducts and gallbladder tumors. These are aggressive tumors and chemotherapy is still the main treatment for advanced-stage disease and most of these cases have a poor overall survival. Strategies are aimed at treatments with better outcomes and less toxicity which makes immunotherapy an area of ​​significant importance. Recent Food and Drug Administration approvals of immune checkpoint inhibitors (ICI) for agnostic tumors based on biomarkers such as microsatellite instability-high and tumor mutation burden-high are important steps in the treatment of patients with advanced bile duct tumors. Despite limited responses with isolated checkpoint inhibitors in later lines of systemic treatment in advanced disease, drug combination strategies have been demonstrating encouraging results to enhance ICI efficacy.     

常染色体16三体胎鼠和正常同窝鼠肠神经系发育

目的 研究Ｄｏｗｎ综合征动物模型常染色体１６三体胎鼠及其正常同窝鼠肠神经系发育状况。方法 （１）将ＮＭＲ－１雌鼠与携带有两个Ｒｏｂｅｒｔｓｏｎｉａｎ（Ｒｂ）易位（１１,１６）,Ｒｂ（１６,１７）８Ｌｕｂｔ＾ＷＬｕｂ３雄鼠进行交配,繁殖常染色体１６三体胎鼠。（２）采用细胞遗传学分析,以检出两条Ｒｂ染色体和４１条染色体者定为常染色体１６三体胎鼠。（３）采用高度特异的神经标记物蛋白基因产物９．５抗体进行     

Effect of some metallic cations and organic compounds on theO-hexylO-2,5-dichlorophenyl phosphoramidate hydrolysing activity in hen plasma

One of the main detoxification mechanisms of organophosphorus (OP) compounds is hydrolysis by OP hydrolysing enzymes (OP-hydrolases) or phosphoric triester hydrolases. We previously reported an OP-hydrolase from hen plasma which hydrolysesO-hexylO-2,5-dichlorophenyl phosphoramidate (HDCP). In this study, a total of 18 cations, as well as several thiol blocking reagents, ethylenediaminetetraacetic acid (EDTA) and mipafox (N,N-diisopropyl phosphorodiamidofluoridate) were assayed as activators or inhibitors of the HDCP hydrolysing activity of hen plasma in vitro. Of the 18 inorganic cations only 1 M Na⁺ caused any inhibition. Most of the cations, including Ca²⁺, exerted no detectable effect; however, 1 mM Cu²⁺ was found to produce an activation of up to 263%, with a lesser activation of up to 168% for 1 mM Zn²⁺. The thiol blocking reagents methyl vinyl ketone (MVK) andN-ethylmaleimide (NEM) inhibited the enzyme in a time-dependent manner, the maximum effect depending upon concentration in the case of NEM, but not in the case of MVK; however, 5,5-dithiobis (2-nitrobenzoic acid) caused inhibition that was concentration dependent but which was independent of time. Other thiol blocking reagents such as p-hydroxymercuribenzoic acid (sodium salt), phenylmercuric acetate, iodoacetic acid (sodium salt) and iodoacetamide produced only slight inhibition, as did EDTA. Finally, the OP compound mipafox exerted no detectable effect.     

铒激光擦皮术后色素沉着的防治对策

０　引言　东方人接受皮肤磨削术治疗后色素沉着的发生率明显高于西方人．尽管采用了目前被认为是最适宜亚洲人的铒激光治疗,色素沉着仍可发生．因此,在实施该手术治疗前应严格掌握适应证,制定严密的预防治疗措施,使得色素沉着的发生率降至最低,从而最大限度的防止医疗纠纷的发生．１　对象和方法１．１　对象　２１例患者,男２例,女１９例,平均年龄２９．２（０８～４８）岁．皱纹祛除８例,浅表疤痕７例,浅咖啡斑、黑子５例,不良纹眉１例．铒激光其它适应证：①老年斑;②细小皱纹;③“白皮肤”雀斑;④痤疮后疤痕⑤色素减退…     

Resolving pathways of interaction of mipafox and a sarin analog with human acetylcholinesterase by kinetics,mass spectrometry and molecular modeling approaches

The hydroxyl oxygen of the catalytic triad serine in the active center of serine hydrolase acetylcholinesterase (AChE) attacks organophosphorus compounds (OPs) at the phosphorus atom to displace the primary leaving group and to form a covalent bond. Inhibited AChE can be reactivated by cleavage of the Ser–phosphorus bond either spontaneously or through a reaction with nucleophilic agents, such as oximes. At the same time, the inhibited AChE adduct can lose part of the molecule by progressive dealkylation over time in a process called aging. Reactivation of the aged enzyme has not yet been demonstrated. Here, our goal was to study oxime reactivation and aging reactions of human AChE inhibited by mipafox or a sarin analog (Flu-MPs, fluorescent methylphosphonate). Progressive reactivation was observed after Flu-MPs inhibition using oxime 2-PAM. However, no reactivation was observed after mipafox inhibition with 2-PAM or the more potent oximes used. A peptide fingerprinted mass spectrometry (MS) method, which clearly distinguished the peptide with the active serine (active center peptide, ACP) of the human AChE adducted with OPs, was developed by MALDI-TOF and MALDI-TOF/TOF. The ACP was detected with a diethyl-phosphorylated adduct after paraoxon inhibition, and with an isopropylmethyl-phosphonylated and a methyl-phosphonylated adduct after Flu-MPs inhibition and subsequent aging. Nevertheless, nonaged nonreactivated complexes were seen after mipafox inhibition and incubation with oximes, where MS data showed an ACP with an NN diisopropyl phosphoryl adduct. The kinetic experiments showed no reactivation of activity. The computational molecular model analysis of the mipafox-inhibited hAChE plots of energy versus distance between the atoms separated by dealkylation showed a high energy demand, thus little aging probability. However, with Flu-MPs and DFP, where aging was observed in our MS data and in previously published crystal structures, the energy demand calculated in modeling was lower and, consequently, aging appeared as a more likely reaction. We document here direct evidence for a phosphorylated hAChE refractory to oxime reactivation, although we observed no aging.     

Two case reports of perineal hernia after laparoscopic abdominoperineal resection with a proposed modification to the operative technique

Perineal hernia is a rare complication following laparoscopic abdominoperineal resection (APR) for rectal cancer. We present two case reports of perineal hernia following laparoscopic APR and discuss their management. We suggest that they developed because the pelvic peritoneum was left open during laparoscopic APR and propose that closure of the pelvic peritoneum should be routine in this operation.