Complement-dependent synergistic effects of rat monoclonal IgG antibodies in vivo

We describe studies aimed at maximizing the effector mechanisms responsible for eliminating target erythrocytes from the circulation in a fully homologous opsonization system in vivo. The effects on the subsequent fate of target erythrocytes were examined in both normal and decomplemented rats preinjected with a variety of rat IgG monoclonal antibodies (mAb) directed against different epitopes on the RTlA^a, the classical class I major histocompatibiliy complex antigen of the DA rat. In general, the clearance of both DA and (DA × PVG)F₁ erythrocytes in normal rats preinjected with various pairs of noncompetitive mAb was very rapid when compared with the overall clearance patterns seen with individual antibodies. With all mAb combinations containing IgG2b or IgG2a, an intact complement system was an essential requirement for augmenting the initial clearance and promoting hepatic sequestration of these target cells. The removal of (DA × PVG)F₁ erythrocytes, expressing half as much antigen, was considerably slower than the DA cells for each antibody pair tested although a notable degree of heterogeneity was observed in the overall behavior of both types of target cells with different mAb combinations. Our results suggest that the limiting effects of low antigen density on the target cells combined with the use of mAb of an isotype like the rat IgG2a can be overcome using pairs of mAb that recognize different epitopes on the same target antigen.     

Temporal expression and cellular origin of CC chemokine receptors CCR1, CCR2 and CCR5 in the central nervous system: insight into mechanisms of MOG-induced EAE

Background  

The CC chemokine receptors CCR1, CCR2 and CCR5 are critical for the recruitment of mononuclear phagocytes to the central nervous system (CNS) in multiple sclerosis (MS) and other neuroinflammatory diseases. Mononuclear phagocytes are effector cells capable of phagocytosing myelin and damaging axons. In this study, we characterize the regional, temporal and cellular expression of CCR1, CCR2 and CCR5 mRNA in the spinal cord of rats with myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (MOG-EAE). While resembling human MS, this animal model allows unique access to CNS-tissue from various time-points of relapsing neuroinflammation and from various lesional stages: early active, late active, and inactive completely demyelinated lesions.     

An Overview of the Treatment Options Used for the Management of COVID-19 in Pakistan: Retrospective Observational Study

BackgroundSince the first reports of COVID-19 infection, the foremost requirement has been to identify a treatment regimen that not only fights the causative agent but also controls the associated complications of the infection. Due to the time-consuming process of drug discovery, physicians have used readily available drugs and therapies for treatment of infections to minimize the death toll.ObjectiveThe aim of this study is to provide a snapshot analysis of the major drugs used in a cohort of 1562 Pakistani patients during the period from May to July 2020, when the first wave of COVID-19 peaked in Pakistan.MethodsA retrospective observational study was performed to provide an overview of the major drugs used in a cohort of 1562 patients with COVID-19 admitted to the four major tertiary-care hospitals in the Rawalpindi-Islamabad region of Pakistan during the peak of the first wave of COVID-19 in the country (May-July 2020).ResultsAntibiotics were the most common choice out of all the therapies employed, and they were used as first line of treatment for COVID-19. Azithromycin was the most prescribed drug for treatment. No monthly trend was observed in the choice of antibiotics, and these drugs appeared to be a random but favored choice throughout the months of the study. It was also noted that even antibiotics used for multidrug resistant infections were prescribed irrespective of the severity or progression of the infection. The results of the analysis are alarming, as this approach may lead to antibiotic resistance and complications in immunocompromised patients with COVID-19. A total of 1562 patients (1064 male, 68.1%, and 498 female, 31.9%) with a mean age of 47.35 years (SD 17.03) were included in the study. The highest frequency of patient hospitalizations occurred in June (846/1562, 54.2%).ConclusionsGuidelines for a targeted treatment regime are needed to control related complications and to limit the misuse of antibiotics in the management of COVID-19.     

稳定型圆锥角膜患者植入新型Phakic角膜接触镜的视觉效果分析

目的：评估可植入式Phakic角膜接触镜治疗稳定型圆锥角膜患者的疗效、安全性、稳定性和可预测性。

方法：共14例患者采用植入式Phakic角膜接触镜(IPCL)矫正屈光不正,测量了未矫正视力、最佳矫正视力、离焦曲线、对比敏感度、屈光度及可能的副作用。评估结果超过6mo。

结果：平均等效球镜度(SE)和散光在术后6mo末次检查时由术前-6.94±2.79 DS和-4.24±1.42 DC分别变为术后-0.23±0.43 DS和-1.05±0.49 DC。术前平均Snellen视力为0.18±0.10。6mo内未矫正视力和最佳矫正视力平均值分别为0.13±0.10和0.05±0.15。平均安全指数为1.11。所有眼视力均无降低,其中22眼视力提高超过1行。20眼(71.4%)屈光度在0.50 D以内,27眼(96.42%)在±1.00 D以内。术后1wk至6mo,屈光度变化为-0.23±0.43(范围： -1.00至+0.75)。6mo内角膜内皮细胞(ECL)丢失率小于5%。术后6mo眼压(IOP)为11.32±2.28 mmHg。

结论：Toric植入式Phakic角膜接触镜在矫正与稳定圆锥角膜相关的近视和近视散光方面具有有效性、安全性和可预测性。     

中国非高碘地区人群膳食碘摄入量评估

目的评估中国非高碘地区(水碘含量<150μg/L)人群膳食碘摄入量不足的潜在风险。方法利用中国营养与健康状况调查资料、食盐消费量数据和饮用水推荐摄入量,以及中国食物成分表及盐碘和水碘监测数据,估计我国非高碘地区13个性别-年龄组人群在食用加碘食盐和不加碘食盐情形下的膳食碘摄入量,并与我国的膳食碘摄入量推荐标准进行比较。结果在非高碘地区食用加碘盐情况下,虽然人群的平均碘摄入量均高于推荐摄入量(RNI),但碘摄入量超过最高耐受摄入量(UL)的比例平均为5.8%,而低于RNI的比例平均为13.4%,并且18岁以上成人(含孕妇和乳母)低于平均需要量(EAR)的比例为9.4%,且食盐对膳食碘的贡献率远高于饮用水和各类食物;在非高碘地区食用不加碘盐的情况下,虽然多数性别-年龄组人群的平均碘摄入量高于RNI,但摄入量低于RNI的平均比例高达97.6%,其中18岁以上成人(含孕妇和乳母)低于EAR的比例为97.4%,且各类食物合并的平均碘贡献率高于饮用水。结论中国非高碘地区居民碘缺乏的健康风险大于碘过量的健康风险,这在食用不加碘食盐的情况下尤为明显;加碘食盐应当是非高碘地区居民膳食碘的最主要来源。     

A novel,highly sensitive electrochemical 1,4-dioxane sensor based on reduced graphene oxide–curcumin nanocomposite

1,4-Dioxane is a carcinogenic, non-biodegradable, organic water pollutant which is used as a solvent in various industries. It is also formed as an undesired by-product in the cosmetic and pharmaceutical industry. Given its carcinogenicity and ability to pollute, it is desirable to develop a sensitive and selective sensor to detect it in drinking water and other water bodies. Current works on this sensor are very few and involve complex metal oxide composite systems. A sensitive electrochemical sensor for 1,4-dioxane was developed by modifying a glassy carbon electrode (GCE) with a reduced graphene oxide–curcumin (rGO–CM) nanocomposite synthesized by a simple solution approach. The prepared rGO–CM was characterized by X-ray Diffraction (XRD), Fourier Transform Infrared (FTIR) Spectroscopy, Raman spectroscopy, UV-Vis spectroscopy, and Scanning Electron Microscopy (SEM). The rGO–CM/GCE sensor was employed for the detection of 1,4-dioxane in the range of 0.1–100 μM. Although, the detection range is narrower compared to reported literature, the sensitivity obtained for the proposed sensor is far superior. Moreover, the limit of detection (0.13 μM) is lower than the dioxane detection target defined by the World Health Organization (0.56 μM). The proposed rGO–CM/GCE also showed excellent stability and good recovery values in real sample (tap water and drinking water) analysis.

Reduced graphene oxide–curcumin (rGO–CM) nanocomposite was prepared from graphite oxide using curcumin. The rGO–CM/GCE was used for highly sensitive 1,4-dioxane detection. The LOD obtained (0.13 μM) was lower than the WHO guideline value.     

A survey of current practice patterns in prophylaxis against venous thromboembolism (VTE) and gastrointestinal (GI) ulceration among Canadian burn centers

Prospective data on efficacy of routine thromboprophylaxis in burn population remains limited. We believe that this uncertainty has lead to diverse management practices across Canada. Similarly, despite data supporting effectiveness of early enteral nutrition (EEN) for gastrointestinal (GI) ulcer prophylaxis, we hypothesize that many burn centers continue to use additional medical prophylaxis. A questionnaire was sent to 16 Canadian burn units regarding their practices of venous thromboembolism (VTE) and GI ulcer prophylaxis. We had 50% response rate. Fifty percent of respondents reported routine use of VTE prophylaxis in all their burn patients regardless of risk factors, 75% of these were among the largest burn centers in Canada. Only 1 center reported use of low molecular weight heparin, Enoxaparin, as their only mode of prophylaxis. With regards to GI ulcer prophylaxis, 62.5% of respondents indicated limiting use of ulcer prophylactic medications to ICU patients. Three (37.5%) centers reported practicing EEN for prophylaxis, 1 of which administered it as the sole modality. 7 of 8 centers used additional pharmacologic prophylaxis, most commonly an H2-blocker, ranitidine. There remains lack of consensus among Canadian burn centers in areas of VTE and GI ulcer prophylaxis, reflecting the limited prospective data in these fields.