Conquering the cytokine storm in COVID-19-induced ARDS using placenta-derived decidua stromal cells

Acute respiratory distress syndrome (ARDS) is the most common cause of death in COVID-19 patients. The cytokine storm is the main driver of the severity and magnitude of ARDS. Placenta-derived decidua stromal cells (DSCs) have a stronger immunosuppressive effect than other sources of mesenchymal stromal cells. Safety and efficacy study included 10 patients with a median age of 50 (range 14–68) years with COVID-19-induced ARDS. DSCs were administered 1–2 times at a dose of 1 × 10⁶/kg. End points were safety and efficacy by survival, oxygenation and effects on levels of cytokines. Oxygenation levels increased from a median of 80.5% (range 69–88) to 95% (range 78–99) (p = 0.012), and pulmonary infiltrates disappeared in all patients. Levels of IL-6 decreased from a median of 69.3 (range 35.0–253.4) to 11 (range 4.0–38.3) pg/ml (p = 0.018), and CRP decreased from 69 (range 5–169) to 6 (range 2–31) mg/ml (p = 0.028). Two patients died, one of a myocardial infarction and the other of multiple organ failure, diagnosed before the DSC therapy. The other patients recovered and left the intensive care unit (ICU) within a median of 6 (range 3–12) days. DSC therapy is safe and capable of improving oxygenation, decreasing inflammatory cytokine level and clearing pulmonary infiltrates in patients with COVID-19.     

Motor unit number estimation and quantitative needle electromyography in stroke patients

ObjectiveTo evaluate the effect of upper motor neuron damage upon motor units’ function by means of two separate and supplementary electrophysiological methods.MethodsThe abductor digiti minimi muscle of the non-paretic and the paretic side was studied in forty-six stroke patients with (a) motor unit number estimation (MUNE) – adapted multiple point stimulation method and (b) computerized quantitative needle electromyography (EMG) assessing the configuration of voluntary recruited motor unit potentials. Main outcome comparisons were focused on differences between non-paretic and paretic side.ResultsOn the affected hands mean MUNE value was significantly lower and mean area of the surface recorded single motor unit potentials was significantly larger than the corresponding ones on the non-paretic hands. EMG findings did not reveal remarkable differences between the two sides. Neither severity nor chronicity of stroke was related to MUNE or EMG parameters.DiscussionMUNE results, which suggested reduced motor unit numbers in stroke patients, in conjunction with the normal EMG features in these same muscles has given rise to different interpretations. In a clinical setting, reinnervation type changes in the EMG similar to that occurring in neuronopathies or axonal neuropathies should not be expected in muscles with central neurogenic lesion.     

IMU-based ambulatory walking speed estimation in constrained treadmill and overground walking

This study evaluated the performance of a walking speed estimation system based on using an inertial measurement unit (IMU), a combination of accelerometers and gyroscopes. The walking speed estimation algorithm segments the walking sequence into individual stride cycles (two steps) based on the inverted pendulum-like behaviour of the stance leg during walking and it integrates the angular velocity and linear accelerations of the shank to determine the displacement of each stride. The evaluation was performed in both treadmill and overground walking experiments with various constraints on walking speed, step length and step frequency to provide a relatively comprehensive assessment of the system. Promising results were obtained in providing accurate and consistent walking speed/step length estimation in different walking conditions. An overall percentage root mean squared error (%RMSE) of 4.2 and 4.0% was achieved in treadmill and overground walking experiments, respectively. With an increasing interest in understanding human walking biomechanics, the IMU-based ambulatory system could provide a useful walking speed/step length measurement/control tool for constrained walking studies.     

Tumor profiling using protein biomarker panels in malignant melanoma: application of tissue microarrays and beyond

In the past decade, analysis of the urinary proteome (urinary proteomics) has intensified in response to the need for novel biomarkers that support early diagnosis of kidney diseases. In particular, this also applies to acute kidney injury, which is a heterogeneous complex syndrome with a still-increasing incidence at the intensive care unit. Unfortunately, this major need remains largely unmet to date. The current report aims to explain why attempts to implement urinary proteomic-discovered acute kidney injury diagnostic candidates in the intensive care unit setting have not yet led to success. Subsequently, some key notes are provided that should enhance the chance of translating selected urinary proteomic candidates to valuable tools for the nephrologist and intensivist in the near future.     

Influence of hydrocarbon-stapling on membrane interactions of synthetic antimicrobial peptides

Cyclization has been recognized as a valuable technique for increasing the efficacy of small molecule and peptide therapeutics. Here we report the application of a hydrocarbon staple to a rationally-designed cationic antimicrobial peptide (CAP) that acquires increased membrane targeting and interaction vs. its linear counterpart. The previously-described CAP, 6K-F17 (KKKKKK-AAFAAWAAFAA-NH₂) was used as the backbone for incorporation of an i to i?+?4 helical hydrocarbon staple through olefin ring closing metathesis. Stapled versions of 6K-F17 showed an increase in non-selective membrane interaction, where the staple itself enhances the degree of membrane interaction and rate of cell death while maintaining high potency against bacterial membranes. However, the higher averaged hydrophobicity imparted by the staple also significantly increases toxicity to mammalian cells. This deleterious effect is countered through stepwise reduction of the stapled 6K-F17’s backbone hydrophobicity through polar amino acid substitutions. Circular dichroism assessment of secondary structure in various bacterial membrane mimetics reveals that a helical structure may improve – but is not an absolute requirement for – antimicrobial activity of 6K-F17. Further, phosphorus-31 static solid state NMR spectra revealed that both non-toxic stapled and linear peptides bind bacterial membranes in a similar manner that does not involve a detergent-like mechanism of lipid removal. The overall results suggest that the technique of hydrocarbon stapling can be readily applied to membrane-interactive CAPs to modulate how they interact and target biological membranes.     

Discovery of heterocyclic replacements for the coumarin core of anti-tubercular FadD32 inhibitors

Previous work established a coumarin scaffold as a starting point for inhibition of Mycobacterium tuberculosis (Mtb) FadD32 enzymatic activity. After further profiling of the coumarin inhibitor 4 revealed chemical instability, we discovered that a quinoline ring circumvented this instability and had the advantage of offering additional substitution vectors to further optimize. Ensuing SAR studies gave rise to quinoline-2-carboxamides with potent anti-tubercular activity. Further optimization of ADME/PK properties culminated in 21b that exhibited compelling in vivo efficacy in a mouse model of Mtb infection.     

Comparative analysis of high butanol tolerance and production in clostridia

2016, was the 100 years anniversary from launching of the first industrial acetone-butanol-ethanol (ABE) microbial production process. Despite this long period and also revival of scientific interest in this fermentative process over the last 20 years, solventogenic clostridia, mainly Clostridium acetobutylicum, Clostridium beijerinckii, Clostridium saccharoperbutylacetonicum and Clostridium pasteurianum, still have most of their secrets. One such poorly understood mechanism is butanol tolerance, which seems to be one of the most significant bottlenecks obstructing industrial exploitation of the process because the maximum achievable butanol concentration is only about 21 g/L. This review describes all the known cellular responses elicited by butanol, such as modifications of cell membrane and cell wall, formation of stress proteins, extrusion of butanol by efflux pumps, response of regulatory pathways, and also maps both random and targeted mutations resulting in high butanol production phenotypes. As progress in the field is inseparably associated with emerging methods, enabling a deeper understanding of butanol tolerance and production, progress in these methods, including genome mining, RNA sequencing and constructing of genome scale models are also reviewed. In conclusion, a comparative analysis of both phenomena is presented and a theoretical relationship is described between butanol tolerance/high production and common features including efflux pump formation/activity, stress protein production, membrane modifications and biofilm growth.     

ICU中心发生胸腔感染的影响因素分析及预防对策

目的:探讨重症监护病房(ICU)中心发生胸腔感染的情况及其影响因素,并提出相应的预防对策。方法:选择2015年2月至2017年2月我院ICU中心收治的98例患者进行研究,均为全麻下行开胸术后住ICU者。收集所有患者临床资料,分析胸腔感染的发生情况,通过比较发生/未发生胸腔感染患者的临床资料,探讨ICU中心发生胸腔感染的危险因素,并提出相应的预防对策。结果:在98例患者中,有15例发生胸腔感染,发生率为15.31%,以铜绿假单胞菌所占比例最高,为40.00%。单因素分析结果显示:性别、术前抗菌药物的使用、胸管类型和ICU中心胸腔感染无相关性(P0.05),而年龄、手术时间、术前肺功能、引流管留置时间、手术创口污染、原发病灶蔓延均和ICU中心胸腔感染密切相关(P0.05);多因素logistic回归分析结果显示:年龄≥60岁、手术时间≥2h、术前肺功能、引流管留置时间≥3d、手术创口污染、原发病灶蔓延均是造成ICU中心胸腔感染的独立危险因素(OR=3.485、3.714、3.571、5.731、6.172、6.081,P0.05)。结论:ICU中心发生胸腔感染会对患者病情恢复造成较大影响,在今后临床工作中,需重视围术期管理,积极采取合理的预防措施,降低胸腔感染的发生率。     

Electronegative LDL induces MMP-9 and TIMP-1 release in monocytes through CD14 activation: Inhibitory effect of glycosaminoglycan sulodexide

Objective

Electronegative LDL (LDL(?)) is involved in atherosclerosis through the activation of the TLR4/CD14 inflammatory pathway in monocytes. Matrix metalloproteinases (MMP) and their inhibitors (tissue inhibitors of metalloproteinase [TIMP]) are also crucially involved in atherosclerosis, but their modulation by LDL(?) has never been investigated. The aim of this study was to examine the ability of LDL(?) to release MMPs and TIMPs in human monocytes and to determine whether sulodexide (SDX), a glycosaminoglycan-based drug, was able to affect their secretion.

Plasma N-glycome composition associates with chronic low back pain

Background

Low back pain (LBP) is the symptom of a group of syndromes with heterogeneous underlying mechanisms and molecular pathologies, making treatment selection and patient prognosis very challenging. Moreover, symptoms and prognosis of LBP are influenced by age, gender, occupation, habits, and psychological factors. LBP may be characterized by an underlying inflammatory process. Previous studies indicated a connection between inflammatory response and total plasma N-glycosylation. We wanted to identify potential changes in total plasma N-glycosylation pattern connected with chronic low back pain (CLBP), which could give an insight into the pathogenic mechanisms of the disease.