A Randomized Controlled Trial of a Close Monitoring Program for Minor Depression and Distress

BACKGROUND  Minor depression is almost twice as common in primary care (PC) as major depression. Despite the high prevalence, few evidence-based algorithms exist for managing patients with minor depression or patients presenting solely with distress. OBJECTIVES  The aim of this study was to test the effectiveness of a telephone-based close monitoring program to manage PC patients with minor depression or distress. DESIGN  Subjects were randomly assigned to either the control arm (usual care; UC) or the intervention arm (close monitoring; CM). We hypothesized that those randomized to CM would exhibit less depression and be less likely to have symptoms progress to the point of meeting diagnostic criteria. SUBJECTS  Overall, 223 PC subjects with minor depression or distress consented to participation in this trial. MEASUREMENTS  At baseline, subjects completed a telephone-based evaluation comprised of validated diagnostic assessments of depression and other MH disorders. Outcomes were assessed at six months utilizing this same battery. Chart reviews were conducted to track care received, such as prescribed antidepressants and MH and primary care visits. RESULTS  Subjects in the CM arm exhibited fewer psychiatric diagnoses than those in the UC arm (χ² = 4.04, 1 df, p = 0.04). In addition, the intervention group showed improved overall physical health (SF-12 PCS scores) (M = 45.1, SD = 11.8 versus M = 41.5, SD = 12.4) (χ² = 5.90, 1 df, p = .02). CONCLUSIONS  Those randomized to CM exhibited less MH problems at the conclusion of the trial, indicating that the close monitoring program is effective, feasible and valuable. The findings of this study will allow us to enhance clinical care and support the integration of mental health services and primary care.     

Dynamical network of residue–residue contacts reveals coupled allosteric effects in recognition,catalysis, and mutation

Detailed understanding of how conformational dynamics orchestrates function in allosteric regulation of recognition and catalysis remains ambiguous. Here, we simulate CypA using multiple-microsecond-long atomistic molecular dynamics in explicit solvent and carry out NMR experiments. We analyze a large amount of time-dependent multidimensional data with a coarse-grained approach and map key dynamical features within individual macrostates by defining dynamics in terms of residue–residue contacts. The effects of substrate binding are observed to be largely sensed at a location over 15 Å from the active site, implying its importance in allostery. Using NMR experiments, we confirm that a dynamic cluster of residues in this distal region is directly coupled to the active site. Furthermore, the dynamical network of interresidue contacts is found to be coupled and temporally dispersed, ranging over 4 to 5 orders of magnitude. Finally, using network centrality measures we demonstrate the changes in the communication network, connectivity, and influence of CypA residues upon substrate binding, mutation, and during catalysis. We identify key residues that potentially act as a bottleneck in the communication flow through the distinct regions in CypA and, therefore, as targets for future mutational studies. Mapping these dynamical features and the coupling of dynamics to function has crucial ramifications in understanding allosteric regulation in enzymes and proteins, in general.As a biomolecule samples various conformations governed by its free energy landscape, it undergoes a wide spectrum of motions that range over a broad timescale and length scale (1). Except for certain cases in which large-scale displacements are observed upon ligand binding (2), these motions, in general, account for modest fluctuations around an average native structure (3). Despite extensive studies, detailed understanding of how conformational dynamics lead to or facilitate function remains formidable (4–6). It has been frequently observed that enzymes in their free unliganded state sample 3D conformations that consist of those visited in the presence of the ligand (7). Differences in intrinsic conformational dynamics in the wild type and the mutant maltose-binding proteins have been shown to be related to association and dissociation of ligand and thereby to affect dissociation constants (8). Enzyme dynamics in Cyclophilin A (CypA), a peptidyl prolyl cis–trans isomerase, have been demonstrated to occur on the same millisecond timescale as the catalytic turnover (9). Mutants of dihydrofolate reductase that lead to suppressed conformational dynamics in the active site have exhibited concomitant loss in enzymatic activity (10).These exemplary studies are suggestive of a key role for conformational dynamics in recognition and catalysis. This notion has been controversial (10–13) due to limited or, in some cases, a complete lack of microscopic analysis of experimental observations. The suppressed catalytic activity in mutants may be a result of an increase in activation energy and not decreased dynamics (14, 15). Although enzyme dynamics may not be responsible for catalytic speed up relative to the uncatalyzed reaction, CypA dynamics has been shown to be coupled to catalytic function (16). Allosteric regulation, i.e., modification of binding or catalysis at the active site due to binding of a ligand at a distal nonoverlapping site, is widespread in biochemical signaling (17, 18). It is natural that allosteric regulation depends on modulation of protein motions, because substrate binding and catalysis are linked to conformational dynamics (19, 20). Unlike static X-ray structures, solution NMR relaxation dispersion techniques have been instrumental in providing high-resolution conformational exchange information using site-specific isotope labeling (21). In NMR studies of CypA, a dynamic continuum has been identified such that the relaxation profiles cannot be globally fit to one or two exchange phenomena and are instead indicative of more localized motions (22). Exchange rates coalesce somewhat during turnover, perhaps suggesting an increase in coordination throughout the protein, but appear to still consist of localized motions that are not fully coherent (23). However, dynamical signals during catalytic turnover could be affected by substrate binding and unbinding, especially if the substrate binding affinity is low, thereby leading to ambiguity in the interpretation of NMR analysis (23).Complementary to experiments, long-timescale molecular dynamics (MD) simulations can be greatly instrumental in providing a microscopic picture of biomolecular dynamics and establishing its exact linkage to function. However, the challenge at hand is to elucidate the key dynamical features and correlations between different parts of the protein from a vast amount of multidimensional time-dependent data from MD. Principal component analysis (PCA) is often used to reduce the dimensionality of conformational space and map the differences in conformational ensembles. PCA, which is usually performed on Cartesian coordinates, may sometimes mask certain important long-range dynamical relations and complex features of biomolecular conformational dynamics. Comparing residue–residue contacts in various isoforms from difference contact maps built from simulation trajectories has aided in determining certain similar structural properties and some unique to a particular isoform (24). Another analysis that involves monitoring the time evolution of residue–residue contact formation and breaking has been proven useful in identifying certain characteristic events during conformational transitions (25). Correlated motions between different biomolecular segments have been identified using cross-correlation analysis and building dynamical networks (25–29). However, interpretation of the results of such analysis in case of CypA, which exhibit subtle changes upon substrate binding and catalysis, has been ambiguous.Here, we characterize the conformational dynamics of CypA using very long atomistic standard MD simulations in explicit solvent, and the results are validated using NMR experiments. CypA is an archetypal and extensively studied enzyme belonging to the family of peptidyl prolyl isomerases (PPIases), speeding the cis–trans isomerization of peptidyl prolyl ω-bond in its protein substrates by more than 10⁵ times (30–34). In five independent microsecond-long simulations, we monitored the dynamics in wild-type CypA, V29L variant of CypA, CypA bound to a substrate analogue in the trans, transition state, and cis configurations. When we apply our method of analyzing the trajectories at a coarse-grained level, i.e., interresidue contact interactions, and use PCA in contact space, the specific differences in CypA dynamics upon association to its substrate, during the catalytic process and upon alteration of a single residue distant from the active site are revealed.     

闭合复位交叉克氏针固定治疗儿童肱骨髁上骨折46例分析

目的:观察闭合复位交叉克氏针固定治疗儿童肱骨髁上骨折的临床效果.方法:对46例无血管、神经损伤的GartlandⅡ、Ⅲ型小儿肱骨髁上骨折采用闭合手法复位交叉克氏针固定,辅以石膏夹板固定2周,4周后拔除克氏针,行肘关节伸屈功能锻炼.结果:按Dodgt′s疗效评价标准,优33例,良11例,差2例,优良率95.7%.结论:儿童肱骨髁上骨折采用闭合复位交叉克氏针固定,创伤小,操作简单,疗效满意,是临床上可以推广的技术.     

一起学校耐药肺结核聚集性疫情的调查

目的 对北京市朝阳区某学校一起耐药肺结核疫情进行分析,为今后耐药结核病疫情的处置提供参考。方法 对病例进行流行病学调查,对病例密切接触者采用PPD试验、X线胸片和CT相结合的方式筛查。结果 2018年10月—2019年6月,该校共发生36例肺结核病例,发病率为4.5%。其中5例耐多药,3例耐利福平。36例病例分布在四个班,15a班27例、15b班4例、15c班2例、17d班3例。各班发病率分别为56.3%、8.3%、5.7%、7.1%,差异有统计学意义(P<0.01)。8例耐药病例中6例为15a班学生,占耐药病例总数的75.0%。经CT筛查68名密切接触者中确诊23例肺结核患者,检出率33.8%。结论 该起学校聚集性疫情为全国首起耐药肺结核聚集性疫情,首发病例未及时就医,传染源隐匿存在时间长,是导致该起疫情发生的主要原因。疫情处置中开展密切接触者筛查对于及时发现新病例非常重要。     

新型冠状病毒肺炎流行病学特征分析

  目的  探讨广州市新冠肺炎（COVID-19）密切接触者感染的危险因素,为分类管理提供科学依据。  方法  纳入2020年1月24日 — 3月2日广州市报告的新冠肺炎确诊病例、疑似病例、阳性检测者相关的密切接触者共2 593人,收集密切接触者一般人口学信息、暴露信息及转归等信息。比较不同转归密切接触者的人口学和流行病学特征,采用多因素logistic回归分析密切接触者感染的危险因素。  结果  共127例转归为新冠肺炎确诊病例或阳性检测者,占全部报告病例的36.71 %（127/346）;与关联病例最主要的社会关系为家庭亲属关系（88.98 %,113/127）;最主要的接触地点为家中（81.89 %,104/127）;90.55 %（115/127）的密接感染者与关联病例经常接触,主要接触方式依次是同餐、同住、同屋,分别占84.25 %（107/127）、69.29 %（88/127）和60.63 %（77/127）。logistic回归分析显示家人亲属关系（OR = 4.331,95 % CI = 1.009～17.063））、同餐（OR = 2.030,95 % CI = 1.037～3.975）、年龄（OR = 1.205,95 % CI = 1.095～1.326）和经常接触（OR = 5.516,95 % CI = 3.180～9.569）是密切接触者感染的危险因素。  结论  提倡家庭内个人卫生习惯、加强物表消毒、保持安全社交距离、及早集中隔离医学观察是切断家庭内传播的重要措施。建立密接者管理的风险等级评估标准,可指导分类管理、精准防控。     

采用PFN/PFNA 治疗股骨粗隆下骨折的回顾性研究

 目的探讨采用闭合复位股骨近端髓内钉/股骨近端髓内钉螺旋刀片（PFN/PFNA）内固定治疗股骨粗隆下骨折的临床效
果。方法收集2005 年1 月以来我科收治的股骨粗隆下骨折病例36 例,其中男22 例,女14 例,年龄16~86 岁（平均45 岁）,
Seinsheiner 分型Ⅱ型4 例（Ⅱ型A 1例,Ⅱ型B 2例,Ⅱ型C 1例）,Ⅲ型16 例（Ⅲ型A 10 例,Ⅲ型B 6例）,郁型10 例,Ⅴ型6 例。
采用麻醉及C 臂的帮助下牵引床闭合复位满意后,行PFN/PFNA 内固定治疗。其中闭合复位32 例,4 例行有限切开复位。结
果34例患者获得随访,平均随访时间为18 个月（3~36 个月）,所有患者切口玉期愈合,均获得骨性愈合,平均愈合时间为4.5
个月（3.5~7.5 个月）。根据改良Harris 髋关节评分标准进行功能评价：优25 例,良5 例,可4 例,优良率88.2%。结论PFN/
PFNA治疗股骨粗隆下骨折,闭合复位,切开损伤小,术中出血少,有利于骨折的愈合,术后能辅以髋膝关节的早期功能锻炼减
少骨折的并发症,同时又较易掌握,是治疗股骨粗隆下骨折较好的内固定选择。     

A Convenient Method to Produce Close‐ and Non‐close‐Packed Monolayers using Direct Assembly at the Air–Water Interface and Subsequent Plasma‐Induced Size Reduction

An extremely facile approach to produce close‐packed colloidal monolayers over large areas using direct assembly at the air–water interface is presented. The influence of small amounts of sodium dodecyl sulfate (SDS) as well as the influence of the pH value of the subphase on the quality of the resulting monolayer is investigated. It is found that small amounts of SDS at the interface influence capillary forces and form a soft barrier that facilitates the crystallization process. Increased electrostatic repulsion arising from a higher pH of the subphase induced a higher order using carboxylic acid functionalized particles. The deposited close‐packed monolayers were subjected to plasma treatment in order to shrink the colloids and produce non‐close packed monolayers with lattice spacing and symmetry reflecting the order of the initial close‐packed monolayer. A detailed examination of etching conditions and their influence on the shrinkage of the particles was performed, including effects of plasma power, composition, flow rates as well as polymeric‐ and substrate material. The monolayers exhibit vivid coloration, which is determined by their size and packing density. UV–Vis–NIR spectroscopy was used to investigate the change of monolayer color during the size reduction of the individual particles. A simple theoretical model was elaborated to explain the optical properties. Finally, the non‐close‐packed monolayers were used as masks to produce gold nanostructures to exemplify the versatility of the monolayer architectures in nanosphere lithography.

     

Oral mucosa as a source of Mycobacterium leprae infection and transmission,and implications of bacterial DNA detection and the immunological status

Leprosy is an important health problem in Brazil despite extensive use of multidrug therapy. The nasal mucosa is the preferential site of entry and exit of Mycobacterium leprae, and although lesions have been found in the oral mucosa, its potential involvement in the transmission of leprosy bacilli has never been investigated. We investigated the presence of the M. leprae DNA in buccal swabs of leprosy patients (334) and household contacts (1288) through polymerase chain reaction (PCR), and correlated this with clinical and laboratorial evaluations. The overall positivity for patients and contacts was 18.26% and 6.83%, respectively. Subclinical infection among contacts was considered when PCR and anti-PGL-1 ELISA presented positive results. This study provides evidence that the oral mucosa may be a secondary site of M. leprae transmission and infection, and contacts with bacillary DNA may be actively involved in transmission. We have also shown that bacilli DNA is more frequently found in the oral mucosa of PB patients. Our findings have great epidemiological relevance and indicate an additional strategy for leprosy control programmes and dental clinics.     

Participation in daytime activities among people with mild or moderate intellectual disability

Background Community participation has been defined as performing daytime activities by people while interacting with others. Previous studies on community participation among people with intellectual disability (ID) have mainly focused on the domestic life aspect. This study investigates the variation in community participation in the domains work, social contacts and leisure activities among people with ID in the Netherlands. A number of categories of people with ID were distinguished by: (1) gender; (2) age; (3) type of education; (4) severity of ID; and (5) accommodation type. Methods Data were gathered on 653 people with mild or moderate ID, of whom 513 by oral interviews and 140 by structured questionnaires filled in by representatives of those who could not be interviewed. Pearson chi‐square tests were used to test differences between categories of people with ID in the distributions of the participation variables. Additional logistic regression analyses were conducted to correct for differences between the categories in other variables. Results Most people with mild or moderate ID in the Netherlands have work or other daytime activities, have social contacts and have leisure activities. However, people aged 50 years and over and people with moderate ID participate less in these domains than those under 50 years and people with mild ID. Moreover, people with ID hardly participate in activities with people without ID. Conclusion High participation among people with a mild or moderate ID within the domains of work, social contact and leisure activities does not necessarily indicate a high level of interaction with the community, because the majority hardly interact with people without ID. Furthermore, older people with ID and people with a more severe level of ID seem to be more at risk for social exclusion.     

原位脾切除联合贲门周围血管离断术的改进

目的：探讨脾切除联合贲门周围血管离断术的改进方法。方法：采取改进的原位脾切除术,在保持脾脏原位状态下紧贴脾脏离断脾蒂及脾周韧带,最后离断脾上极的胃短血管。在贲门周围血管离断时采取紧贴胃及食管分离的选择性血管离断术,保留迷走神经前后干。经脾静脉插管并于术后向脾静脉内持续滴注肝素盐水以预防门静脉系血栓形成。结果：用该法治疗31例,术后门静脉自由压力（FPP）平均下降8cm水柱,手术出血量平均420mL,无手术死亡,术后近期无胃排空障碍及门静脉血栓形成。随访12～36个月,无复发出血及肝性脑病,术后6个月彩超发现门静脉矢状部血栓3例（9.68%）。结论：三贴近法脾切除加贲门周围血管离断术出血少,可有效降低门静脉压力;经脾静脉插管滴注肝素盐水可有效降低术后门静脉血栓发生率。