Co‐occurring medical conditions in adults with Down syndrome: A systematic review toward the development of health care guidelines. Part II

Adults with Down syndrome (DS) represent a unique population who are in need of clinical guidelines to address their medical care. Many of these conditions are of public health importance with the potential to develop screening recommendations to improve clinical care for this population. Our workgroup previously identified and prioritized co‐occurring medical conditions in adults with DS. In this study, we again performed detailed literature searches on an additional six medical conditions of clinical importance. A series of key questions (KQ) were formulated a priori to guide the literature search strategy. Our KQs focused on disease prevalence, severity, risk‐factors, methodologies for screening/evaluation, impact on morbidity, and potential costs/benefits. The available evidence was extracted, evaluated and graded on quality. The number of participants and the design of clinical studies varied by condition and were often inadequate for answering most of the KQ. Based upon our review, we provide a summary of the findings on hip dysplasia, menopause, acquired cardiac valve disease, type 2 diabetes mellitus, hematologic disorders, and dysphagia. Minimal evidence demonstrates significant gaps in our clinical knowledge that compromises clinical decision‐making and management of these medically complex individuals. The creation of evidence‐based clinical guidance for this population will not be possible until these gaps are addressed.     

前臂后皮神经营养血管远端蒂复合瓣的应用解剖

目的:为前臂后皮神经营养血管远端蒂复合瓣设计提供解剖学基础。方法:30侧动脉灌注红色乳胶成人上肢标本,解剖观测前臂后皮神经营养血管的来源、分支、吻合及其与尺、桡骨膜血管的关系。结果:前臂后皮神经营养血管来自:桡侧副动脉皮支2～6支,外径(0.6±0.3) mm;骨间后动脉皮支6～9支,外径(0.7±0.3) mm;骨间前动脉腕背支皮支3~5支,外径(0.8±0.2) mm;尺、桡动脉腕背支皮支2~6支,外径(0.6±0.1) mm。尺骨中上段骨膜血管来自骨间后动脉的肌骨膜支6～8支,外径0.3～1.0 mm;骨间后动脉桡侧骨皮支与桡骨中段裸区骨膜血管吻合。上述支发出皮支、筋膜支、骨膜支和神经营养血管,形成皮神经干血管链以及深、浅筋膜和骨膜血管网。结论:前臂后皮神经营养血管与肌、骨、皮营养血管同源,其远端蒂复合瓣,旋转轴点在腕关节平面,适宜手背远处的组织缺损修复。     

The effect of automated landmark identification on morphometric analyses

Morphometric analysis of anatomical landmarks allows researchers to identify specific morphological differences between natural populations or experimental groups, but manually identifying landmarks is time‐consuming. We compare manually and automatically generated adult mouse skull landmarks and subsequent morphometric analyses to elucidate how switching from manual to automated landmarking will impact morphometric analysis results for large mouse (Mus musculus) samples (n = 1205) that represent a wide range of ‘normal’ phenotypic variation (62 genotypes). Other studies have suggested that the use of automated landmarking methods is feasible, but this study is the first to compare the utility of current automated approaches to manual landmarking for a large dataset that allows the quantification of intra‐ and inter‐strain variation. With this unique sample, we investigated how switching to a non‐linear image registration‐based automated landmarking method impacts estimated differences in genotype mean shape and shape variance‐covariance structure. In addition, we tested whether an initial registration of specimen images to genotype‐specific averages improves automatic landmark identification accuracy. Our results indicated that automated landmark placement was significantly different than manual landmark placement but that estimated skull shape covariation was correlated across methods. The addition of a preliminary genotype‐specific registration step as part of a two‐level procedure did not substantially improve on the accuracy of one‐level automatic landmark placement. The landmarks with the lowest automatic landmark accuracy are found in locations with poor image registration alignment. The most serious outliers within morphometric analysis of automated landmarks displayed instances of stochastic image registration error that are likely representative of errors common when applying image registration methods to micro‐computed tomography datasets that were initially collected with manual landmarking in mind. Additional efforts during specimen preparation and image acquisition can help reduce the number of registration errors and improve registration results. A reduction in skull shape variance estimates were noted for automated landmarking methods compared with manual landmarking. This partially reflects an underestimation of more extreme genotype shapes and loss of biological signal, but largely represents the fact that automated methods do not suffer from intra‐observer landmarking error. For appropriate samples and research questions, our image registration‐based automated landmarking method can eliminate the time required for manual landmarking and have a similar power to identify shape differences between inbred mouse genotypes.     

Eyeblinking During Problem Solving: The Effect of Problem Difficulty and Internally vs Externally Directed Attention

This study examined the eyeblink rate during non-visual problem solving. A 2 × 2 × 2 factorial design compared eyeblink rates for easy and difficult problems, internally and externally directed attention, and numerical and alphabetical tasks. The major finding was a higher eyeblink rate for difficult problems. There was also a significant interaction between difficulty and the direction of attention; internally directed attention yielded higher blink rates only during the solution of easy problems. Range-corrected data yielded the same pattern of results, but F-values were consistently higher and accounted for a larger proportion of the variance.     

Identification of a new HLA-B*15 allele,HLA-B*1569

We have identified a new HLA-B*15 allele (B*1569) by polymerase chain reaction (PCR) using sequence-specific primers (SSP) and sequence-based typing (SBT). This novel allele was found in a 67-year-old white Caucasian male and differs from HLA-B*1503 at 3 positions. The nucleotide substitutions at positions 544, 559 and 560 result in amino acid changes at codon 158 from GCC (alanine) to ACC (threonine), and at codon 163 from CTG (leucine) to ACG (threonine).     

以问题为基础的学习在病理生理学教学中的应用

目的： 与传统的教学方法进行比较，探讨在本科生病理生理学教学中开展以问题为基础的学习（PBL）的必要性，并进一步探索在我国开展PBL教学的可能方法和途径。 方法： 在大学三年级本科生中抽取1个大班作为试验班，其余3个大班作为对照班，在试验班中采用全程PBL教学，将病理生理学教材内容重新整合并划分为6个单元，分别由3位指导教师承担不同单元的教学。每个单元相互独立，但又相互联系、交叉，均以1-2个病历为主要内容，每个病历中均隐藏着所涉及的学习要点的全部内容，学生通过小班讨论、自学、小组讨论、大班讨论以及教师总结等几个环节，归纳、总结出该单元的学习要点，以备进一步学习。在课程结束之后，在学生中进行问卷调查，同时采用PBL教学试验班和对照班期末考试考同一份卷的方法比较PBL教学和传统教学方式的主要差别。 结果： 采用PBL教学方式能够更好地调动学生的学习积极性，启发学生自主学习，并且在提高学生分析问题和解决问题的能力方面相对于传统的教学方式具有明显的优势。     

Agreement between CBNAAT,liquid culture and line probe assay for detection of Mycobacterium tuberculosis and anti-tubercular drug resistance in extrapulmonary samples

PurposeCartridge based nucleic acid amplification test (CBNAAT) has been endorsed by the WHO as the screening test for diagnosing extrapulmonary tuberculosis (EPTB). In the present study we report the agreement between CBNAAT (Xpert MTB/RIF), liquid culture (LC) and line probe assay (LPA) for diagnosis of Mycobacterium tuberculosis and detection of drug resistance among EPTB cases.MethodsThe EP samples were subjected to CBNAAT (Xpert MTB/RIF, Cepheid, USA) and wherever possible, to LC (MGIT 960, Becton Dickinson, USA) followed sequentially by first line and second line-LPA (FL-LPA, SL-LPA, Hain Lifescience, Germany) on the isolates.ResultsTotal 566/4080 (13.9%) EP samples were detected positive for M. tuberculosis on CBNAAT. Aspirates from lymph nodes were most often positive (11/30; 36.6%), followed by pus (240/873; 27.5%) and CSF samples (166/104; 15.8%). The detection of M. tuberculosis was more in adults than children except in tissue biopsy samples. Rifampicin resistance was also higher among adults except CSF in which resistance was more in children. Total 185 of 566 (32.7%) CBNAAT positive and 770 of 3510 (21.9%) CBNAAT negative samples could be cultured of which 110/185 (59.4%) and 33/770 (4.3%) respectively turned positive. FL-LPA and SL-LPA of 143 culture isolates showed that 27 isolates had drug resistance, of which 3 (2.1%) were XDR, 11 (7.7%) were Pre-XDR (FQ) and 13 (9.1%) were MDR. Of these 27 resistant isolates, 12 were negative by CBNAAT and two were mislabeled as Rifampicin sensitive or indeterminate based on the unique RpoB gene mutation patterns on LPA. The positive and negative agreements between LC and CBNAAT for detection of M. tuberculosis were 67.1% and 92.7% respectively and between LPA and CBNAAT for rifampicin resistance detection were 98.9% and 92.9% respectively.ConclusionsFor EPTB, CBNAAT should be accompanied with LC wherever possible irrespective of the CBNAAT result.     

An enzyme-based in situ hybridisation method for the identification of Streptococcus suis

A method for enzyme-based in situ hybridisation of Streptococcus suis was developed. It enables the light microscopic localization of bacterial ribosomal RNA (rRNA) in formalin-fixed paraffin-embedded tissues. A unique sequence in the 16S rRNA of S. suis was targeted. Different pretreatment protocols were applied to facilitate probe penetration and multiple detection systems were tested. The results were compared to those obtained by immunohistochemistry. Pretreatment was necessary to obtain a signal by in situ hybridisation. The use of proteinase-K pretreatment was optimal regarding sensitivity and preservation of tissue morphology. A strong specific in situ hybridisation signal was achieved in tissue sections containing S. suis in microcolonies and the microanatomy of the surrounding tissue was easily assessed. However, the signal distribution differed from that found immunohistochemically and low-grade infection could not be detected by in situ hybridisation. These findings were interpreted as reflecting the physiological state of the bacteria. Thus, this method could prove useful in future studies of the infection pathogenesis.     

Ocular pharmacokinetic models of clonidine-3H hydrochloride

A single topical instillation of clonidine-³H HCl solution (0.2%) was administered to the rabbit eye (30 μl) in order to study the drug's ocular pharmacokinetics. Seven different tissues and plasma were excised and assayed for drug over 180min. By 45–60 min pseudoequilibrium is reached for the cornea, iris/ciliary body, and aqueous humor. Thereafter, drug levels in these tissues decline in parallel. The data are fit separately to a physiological model and a classical diffusion model for which seven ocular tissue compartments and a plasma reservoir are constructed for each model. Clearance terms and distribution equilibrium coefficients are determined from the tissue level data and used as parameters in fitting the mass balance differential equations representing the physiological model. The model parameters can also be fit to a 0.4% single dose. In a separate experiment, a topical infusion technique was designed to provide a constant rate input to the cornea until an apparent steady state was reached in aqueous humor at 55 min. Aqueous humor levels were assayed for clonidine over the infusion and postinfusion periods. The physiological model parameters are fit to the topical infusion data and show good agreement between the predicted and experimental data. The classical model is too complex to fit the data to integrated exponential equations primarily because the method of residuals is inadequate in determining a sufficient set of initial estimates. This is overcome by dividing the eight-compartment model into seven fragmental models, each representing one to five compartments. A stepwise procedure is developed in which initial estimates are obtained for each separate fragmental model and refined. The refined parameter values can then be used as initial estimates for the complex model. Differential equations for the complex model are fit simultaneously to tissue levels representing each compartment. By observation, the classical model fit the data more closely than the physiological model. Statistical moment theory is also applied to the topical infusion data to determine ocular pharmacokinetic parameters for clonidine. The calculated values are: corneal absorption rate constantk _a , 0.00139 min^?1; aqueous humor elimination rate constantk ₁₀ , 0.0658min^?1; mean residence timeMRT _d , 35.6 min; apparent steadystate volume of distributionV _ss, 0.530 ml; and ocular clearanceQ _e , 14.9 =μl/min. The fraction absorbed from the single instillation is estimated as 0.0163.     

降低重症患者人工气道湿化不足发生率

目的降低重症患者人工气道湿化不足发生率。方法开展品管圈活动,通过医护双方合作,优化气道管理团队,完善人工气道湿化评估方案,改良气道湿化装置,增加气道湿化途径,实行复合序贯式湿化-排痰护理管理模式等,实现了气道湿化、辅助排痰、气道廓清一体化。结果重症患者人工气道湿化不足发生率从28.57%降低至11.26%,目标达标率为100.58%,进步率为60.59%。结论通过开展品管圈活动,规范了重症患者人工气道湿化方案,降低了气道相关并发症发生率,有效改善了患者治疗结局,提升了医疗质量。