Changes in diatom-dominated biofilms during simulated improvements in water quality: implications for diatom-based monitoring in rivers

Although benthic diatoms are used to assess river water quality, there are few data on the rate at which diatom assemblages react to changes in water quality. The aim of this study was to assess the reaction time of diatoms and to discuss the changes occurring during water quality improvement on the basis of their autecological characteristics. In order to simulate this improvement, diatom-dominated biofilms grown on artificial sandstone substrata were transferred from several polluted rivers to an unpolluted river. They were sampled three times: before transfer and 1 and 2 months after transfer. The ecology and growth-forms of the taxa explained most of the changes in species composition observed during the experiment. Adnate diatoms gradually replaced motile and stalked taxa. Gomphonema parvulum, a stalked diatom positioned vertically in the biofilm, is adapted for light and space competition in high-density algal biofilms. When transferred to an unpolluted site, this growth-form is less competitive and does not tolerate the high grazing pressure. Fistulifera saprophila is a single celled motile diatom, living in organic matrices. When the artificial substrata were transferred to the unpolluted site, this particular ecological niche disappeared quickly. On the other hand, Achnanthidium minutissimum, which is considered to be cosmopolitan and an early colonizer, increased during the first month of transfer and then decreased. It was gradually replaced by A. biasolettianum, which was the taxon best suited to this pristine stream. The changes observed differed between treatments depending on the species composition and architecture of the biofilms. In particular, biofilms dominated by stalked and motile diatoms were more quickly modified than those dominated by small motile diatoms. The diatom index reflects these changes, and its values showed that about 60 days following a water quality improvement were necessary for transferred diatom assemblages to reach diatom index values similar as those at the unpolluted river.     

Quantitative Metaproteomics and Activity-based Protein Profiling of Patient Fecal Microbiome Identifies Host and Microbial Serine-type Endopeptidase Activity Associated With Ulcerative Colitis

The gut microbiota plays an important yet incompletely understood role in the induction and propagation of ulcerative colitis (UC). Organism-level efforts to identify UC-associated microbes have revealed the importance of community structure, but less is known about the molecular effectors of disease. We performed 16S rRNA gene sequencing in parallel with label-free data-dependent LC-MS/MS proteomics to characterize the stool microbiomes of healthy (n = 8) and UC (n = 10) patients. Comparisons of taxonomic composition between techniques revealed major differences in community structure partially attributable to the additional detection of host, fungal, viral, and food peptides by metaproteomics. Differential expression analysis of metaproteomic data identified 176 significantly enriched protein groups between healthy and UC patients. Gene ontology analysis revealed several enriched functions with serine-type endopeptidase activity overrepresented in UC patients. Using a biotinylated fluorophosphonate probe and streptavidin-based enrichment, we show that serine endopeptidases are active in patient fecal samples and that additional putative serine hydrolases are detectable by this approach compared with unenriched profiling. Finally, as metaproteomic databases expand, they are expected to asymptotically approach completeness. Using ComPIL and de novo peptide sequencing, we estimate the size of the probable peptide space unidentified (“dark peptidome”) by our large database approach to establish a rough benchmark for database sufficiency. Despite high variability inherent in patient samples, our analysis yielded a catalog of differentially enriched proteins between healthy and UC fecal proteomes. This catalog provides a clinically relevant jumping-off point for further molecular-level studies aimed at identifying the microbial underpinnings of UC.     

Secretases as therapeutic targets for Alzheimer's disease

Accumulation of amyloid-β (Aβ) is widely accepted as the key instigator of Alzheimer’s disease (AD). The proposed mechanism is that accumulation of Aβ results in inflammatory responses, oxidative damages, neurofibrillary tangles and, subsequently, neuronal/synaptic dysfunction and neuronal loss. Given the critical role of Aβ in the disease process, the proteases that produce this peptide are obvious targets. The goal would be to develop drugs that can inhibit the activity of these targets. Protease inhibitors have proved very effective for treating other disorders such as AIDS and hypertension. Mutations in APP (amyloid-β precursor protein), which flanks the Aβ sequence, cause early-onset familial AD, and evidence has pointed to the APP-to-Aβ conversion as a possible therapeutic target. Therapies aimed at modifying Aβ-related processes aim higher up the cascade and are therefore more likely to be able to alter the progression of the disease. However, it is not yet fully known whether the increases in Aβ levels are merely a result of earlier events that were already causing the disease.     

呼气末二氧化碳分压、C-反应蛋白/白蛋白比值及综合脱机指数对重型颅脑损伤机械通气患者撤机失败的预测价值

摘要 目的：探讨呼气末二氧化碳分压（PetCO₂）、C-反应蛋白/白蛋白比值（CRP/Alb）及综合脱机指数（IWI）对重型颅脑损伤机械通气患者撤机失败的预测价值。方法：选择2020年1月至2022年6月在安徽中医药大学附属六安医院进行机械通气的重型颅脑损伤患者96例作为研究对象,按照撤机结局分为撤机失败组（n=31）和撤机成功组（n=65）。比较两组撤机前PetCO₂、CRP/Alb、IWI及临床参数。应用多因素Logistic回归分析重型颅脑损伤机械通气患者撤机失败的危险因素。应用受试者工作特征（ROC）曲线评价PetCO₂、CRP/Alb、IWI对重型颅脑损伤机械通气患者撤机失败的预测价值。结果：撤机失败组PetCO₂、CRP/Alb、急性生理功能和慢性健康状况评分系统II（APACHE II）评分显著高于撤机成功组,机械通气时间长于撤机成功组,IWI、格拉斯哥昏迷评分（GCS）显著低于撤机成功组（P<0.05）。多因素Logistic回归分析显示,PetCO₂≥37.01 mmHg、CRP/Alb≥0.97、IWI≤78.23、GCS≤5.90分、APACHE II评分≥26.17分、机械通气时间≥4.49 d是重型颅脑损伤机械通气患者撤机失败的危险因素（P<0.05）。ROC曲线分析结果显示PetCO₂、CRP/Alb、IWI、GCS、APACHE II对重型颅脑损伤机械通气患者撤机失败均有较高的敏感度、特异度, PetCO₂、CRP/Alb、IWI三项联合检测对重型颅脑损伤机械通气患者撤机失败预测的曲线下面积（AUC）高于PetCO₂、CRP/Alb、IWI、GCS、APACHE II单独检测。结论：PetCO₂、CRP/Alb及IWI联合评估对重型颅脑损伤机械通气患者撤机失败具有较高的预测价值。     

齿痛消炎灵颗粒联合牙周激光对牙周炎的应用效果及对口气和舌苔指标的影响

摘要 目的：探讨齿痛消炎灵颗粒联合牙周激光对牙周炎的应用效果及对口气和舌苔指标的影响。方法：选取我院2020年7月到2023年7月收治的80例牙周炎患者,分为观察组与对照组,各40例。对照组采取常规治疗与口服齿痛消炎灵颗粒,观察组以对照组为基础,增加牙周激光治疗。对比两组患者临床疗效,对比其治疗前与治疗4周后菌斑指数（PLI）,出血指数（BI）、探诊深度（PD）、临床附着丧失（CAL）相关牙周健康指标,口气感官值（OS）、口腔挥发硫化物（VSCs）相关口气指标以及舌苔厚度（Tt）、舌苔面积（Ta）相关舌苔指标变化。结果：观察组治疗总有效率较对照组高（P＜0.05）;治疗前两组患者CAL、PD、BI、PLI水平对无差异（P＞0.05）,治疗后两组均降低,且与对照组相比,观察组较低（P＜0.05）;治疗前两组患者OS、VSCs水平对比无差异（P＞0.05）,治疗后两组均降低,且与对照组相比,观察组较低（P＜0.05）;治疗前两组患者Tt、Ta评分对比无差异（P＞0.05）,治疗后两组均降低,且观察组较对照组低（P＜0.05）。结论：齿痛消炎灵颗粒联合牙周激光治疗牙周炎效果较好,改善患者牙周健康程度,减少舌苔情况,改善口气情况。     

凝血与纤溶指标与颅脑损伤后急性创伤性凝血病的关系及对脑心综合征的预测效能研究

摘要 目的：分析凝血与纤溶指标与颅脑损伤（TBI）后急性创伤性凝血病（ATC）的关系及对脑心综合征（CCS）的预测效能。方法：选取2020年1月～2022年12月本院收治的80例TBI患者作为研究对象,分别检测并计算非ATC患者与ATC患者、非CCS患者与CCS患者的凝血酶原时间（PT）、活化部分凝血酶原时间（APTT）、D-二聚体（D-D）、凝血酶-抗凝血酶复合物（TAT）、纤溶酶-α2纤溶酶抑制物复合物（PIC）水平和国际标准化比值（INR）、TAT/PIC比值;并采用双变量Spearman相关性检验凝血与纤溶指标的相关性,建立多因素Logistic模型分析TBI后ATC和TBI合并CCS的影响因素,同时分析凝血与纤溶指标对TBI合并CCS的预测效能。结果：80例TBI患者的ATC发生率为27.50%;与非ATC组比较,ATC组PT、APTT、D-D水平较高,TAT/PIC比值较低（P＜0.05）。PT、APTT、D-D与颅脑损伤后ATC呈正相关性,TAT/PIC与ATC呈负相关性。多因素logistic分析结果显示,TAT/PIC是颅脑损伤后ATC的独立危险因素（P＜0.05）。80例TBI患者的CCS发生率为20.00%;与非CCS组比较,CCS组PT、APTT、D-D水平较高,TAT/PIC比值较低（P＜0.05）。多因素logistic分析结果显示,PT、APTT、D-D、TAT/PIC是TBI合并CCS的独立危险因素（P＜0.05）。TBI合并CCS预测中,PT、APTT、D-D的ACU均＞0.70,TAT/PIC＞0.85。结论：TAT/PIC与TBI后ATC存在一定关联,同时还能预测CCS的发生,在TBI患者预后预测方面具有指导意义。     

Preparation of pure populations of covalently stabilized amyloid β-protein oligomers of specific sizes

Evidence suggests that amyloid β-protein (Aβ) oligomers may be seminal pathogenic agents in Alzheimer's disease (AD). If so, developing oligomer-targeted therapeutics requires an understanding of oligomer structure. This has been difficult due to the instability of these non-covalently associated Aβ assemblies. We previously used rapid, zero-length, in situ chemical cross-linking to stabilize oligomers of Aβ40. These enabled us to isolate pure, stable populations of dimers, trimers, and tetramers and to determine their structure-activity relationships. However, equivalent methods applied to Aβ42 did not produce stable oligomers. We report here that the use of an Aβ42 homologue, [F10, Y42]Aβ42, coupled with sequential denaturation/dissociation and gel electrophoresis procedures, provides the means to produce highly pure, stable populations of oligomers of sizes ranging from dimer through dodecamer that are suitable for structure-activity relationship determination.     

COMPETENCE,PRACTICAL RATIONALITY AND WHAT A PATIENT VALUES

According to the principle of patient autonomy, patients have the right to be self‐determining in decisions about their own medical care, which includes the right to refuse treatment. However, a treatment refusal may legitimately be overridden in cases where the decision is judged to be incompetent. It has recently been proposed that in assessments of competence, attention should be paid to the evaluative judgments that guide patients' treatment decisions. In this paper I examine this claim in light of theories of practical rationality, focusing on the difficult case of an anorexic person who is judged to be competent and refuses treatment, thereby putting themselves at risk of serious harm. I argue that the standard criteria for competence assess whether a treatment decision satisfies the goals of practical decision‐making, and that this same criterion can be applied to a patient's decision‐guiding commitments. As a consequence I propose that a particular understanding of practical rationality offers a theoretical framework for justifying involuntary treatment in the anorexia case.