Kinetic-Based Reactivity for Michael Acceptors: Structural Activity Relationships and Its Relationship to Excess Acute Fish Toxicity

Acute aquatic toxicity is divided into the “physical” mode governed by weak, non-covalent interactions and the “chemical” mode governed by covalent reactions. The potency of chemical interactions is typically expected to be greater than that for physical ones. This enhanced potency is called “excess” toxicity. As databases have become complex, substances thought to elicit a chemical mode reveal a lack of excess toxicity. One mechanism where the latter is prevalent is Michael-type addition. A series of α-β-unsaturated substances were evaluated for reactivity. Second order rate constants (k′) were calculated (M^?1 s^?1) and found to vary from >4000 to <0.0003. The electron-withdrawing capacity of the polar group impacts k′ values; the sequence is nitro > carbonyl or sulfone ? sulfoxide, nitrile or amide. When the α-carbon and/or the β-carbon of the π-system are substituted, the k′ value is sharply reduced. Excess toxicity is associated with k′ values >0.01 (M^?1 s^?1).     

Apoptosis and its relation with clinical course in patients with Crimean-Congo hemorrhagic fever

Crimean-Congo hemorrhagic fever (CCHF) is a tick-mediated viral infection. Patients with CCHF may show various clinical presentations. The cause of this difference in the clinical course is not completely understood. Apoptosis is programmed cell death and plays an important role in regulating the immune system. Our knowledge of the role of apoptosis in CCHF disease is limited. We investigated the role of apoptosis and their relationship with the severity of the disease in CCHF. Thus, in 30 patients with CCHF and 30 healthy individuals, we analyzed the serum levels of cytochrome C, apoptotic protease activating factor-1 (Apaf 1), caspase 3, caspase 8, caspase 9, sFas, sFasL, perforin, granzyme B, and CK18 by enzyme-linked immunosorbent assay. This is the first study that research the serum levels of the mentioned apoptosis markers in adult patients with CCHF. We found that the serum levels of sFasL, cytochrome C, Apaf 1, caspase 3, caspase 8, caspase 9, perforin, granzyme B, and M30 were statistically significantly different in the acute phase of the disease compared with healthy individuals and patients in convalescent period. There was no association between the clinical severity of the disease and apoptosis markers. In conclusion, the results of our study suggested that the extrinsic and intrinsic apoptosis pathway play an important role in CCHF.     

Flow diverter stents in the treatment of recanalized intracranial aneurysms

BackgroundWe assessed the safety and efficacy of flow diverter stents (FDSs) in the treatment of recanalized or residual intracranial aneurysms treated endovascularly.Materials & MethodsPatients whose recanalized or residual aneurysms were treated with FDSs in five tertiary hospitals were reviewed retrospectively. The patients’ demographic data, aneurysm characteristics, types of previous treatment, and clinical complications, or serious adverse events associated with FDSs, as well as the results of neurological and angiographic follow-up assessments, were recorded.ResultsEighty-six patients (37 males) with 87 aneurysms were included in this study. Eighty (91.9%) aneurysms were in the anterior and seven (8.1%) in the posterior circulation. The initial treatment methods were the primary coiling or balloon remodeling technique in 69 (79.3%) and stent-assisted coiling in 18 (20.7%) aneurysms. The endovascular procedure was successful in all patients. Complications occurred in four patients, for a total complication rate of 4.6%. A technical complication developed in one patient (1.2%). An in-stent thrombosis treated with tirofiban was seen in two cases. Late in-stent stenosis exceeding 50% was treated with balloon angioplasty in one patient. The mean length of follow-up was 21.0 months. The first angiographic follow-up (3–6 months) revealed the complete occlusion of 74 aneurysms (85.1%). While 76 aneurysms (87.4%) were occluded at the last angiographic follow-up (mean: 26.0 months), 11 aneurysms (12.6%) were still filling. Morbimortality was zero.ConclusionThe drawback of endovascular treatment is aneurysmal remnants or recurrences, which is safely and durably amenable to flow diversion.     

Role of magnetic resonance spectroscopy in differential diagnosis of solitary pulmonary lesions

PURPOSEThe aim of our study was to evaluate the availability of magnetic resonance spectroscopy (MRS) for the differentiation of benign or malignant pulmonary nodules and masses.METHODSA total of 59 patients (45 male, 14 female) with pulmonary nodules and masses were included in this prospective study. MRS was applied to the pulmonary lesions of the patients and choline levels were determined. Afterwards CT-guided percutaneous needle biopsy was performed. According to the biopsy results, pulmonary lesions were benign in 25 patients and malignant in 34 patients.RESULTSCholine levels were significantly higher in malignant lesions compared with benign lesions (p < 0.001). When the other conditions were kept constant, the probability of malignancy significantly increased by 17.38-fold (95% CI, 3.78–79.93) in those with choline levels >1.65 μmol/g compared to those with choline levels ≤1.65 μmol/g (p < 0.001).CONCLUSIONMRS is a noninvasive method that can be used in the differential diagnosis of pulmonary nodules and masses.

The majority of the solitary pulmonary nodules have a benign character (1). However, all pulmonary nodules should be considered as malignant lesions unless proven otherwise (2). The differential diagnosis of these lesions may be an important problem in routine medical practice. Computed tomography (CT) is the standard method for the examination of the nodules and mass lesions (3). CT imaging of morphological features like size, margins, and calcification enables the investigation of malignancy (4). However, there is some overlap so that some malignant lesions may appear benign, while some benign nodules may show morphological features typical for malignancy (5). CT imaging for differantial diagnosis have problems like false-negative and false-positive results, over-diagnosis, benign nodule resections, and exposure to radiation (6). Biopsy is the most reliable and effective method for the diagnosis of the pulmonary nodules and mass lesions. However, it may cause serious complications such as pneumothorax, hemoptysis, air embolism, tumor cell seeding and death (7, 8). In addition, the tolerability of this invasive intervention is rather low among patients.Magnetic resonance imaging (MRI) provides information about the tumor morphology and magnetic resonance spectroscopy (MRS) provides biochemical information about the physiology and metabolism of the disease (9). MRS enables molecular analysis of the tissues based on the display of different chemical shifts of certain nuclei in the magnetic field (10). MRS was initially used in neuroradiology for characterization of tumor, stroke, epilepsy, infection, and neurodegenerative diseases. In recent years, it was also introduced in the evaluation of lesions in other organs like breast (11), liver (12), pancreas (13), and prostate (14). There are some in vitro studies in the literature on the use of MRS in lung cancer showing higher lactate and total choline peaks compared with normal tissues (15, 16). Also there is one case report in the literature regarding the feasibility of using MRS in lung cancer (17).The objective of this study was to demonstrate the value of MRS, which is a noninvasive method and does not require a contrast agent, in the differential diagnosis of pulmonary nodules and mass lesions.     

Is the Yedikule-solitary pulmonary nodule malignancy risk score sufficient to predict malignancy? An internal validation study

Open in a separate window OBJECTIVESWe aimed to develop a malignancy risk score model for solitary pulmonary nodules (SPNs) using the demographic, radiological and clinical characteristics of patients in our centre. The model was then internally validated for malignancy risk estimation. METHODSA total of 270 consecutive patients who underwent surgery for SPN between June 2017 and May 2019 were retrospectively analysed. Using the receiver operating characteristic curve analysis, cut-off values were determined for radiological tumour diameter, maximum standardized uptake value and the Brock University probability of malignancy (BU-PM) model. The Yedikule-SPN malignancy risk model was developed using these cut-off values and demographic, radiological and clinical criteria in the first 180 patients (study cohort) and internally validated with the next 90 patients (validation cohort). The Yedikule-SPN model was then compared with the BU-PM model in terms of malignancy prediction.RESULTSMalignancy was reported in 171 patients (63.3%). Maximum standardized uptake value and BU-PM scores were sufficient to predict malignancy (P < 0.001 for both), while the effectiveness of nodule size determined on thoracic computed tomography did not reach statistical significance (P = 0.09). When the Yedikule-SPN model developed with the study cohort was applied to the validation cohort, it significantly predicted malignancy (area under the receiver operating characteristic curve: 0.883, 95% confidence interval: 0.827–0.957, P < 0.001). Comparison of patients in the validation group with Yedikule-SPN scores above (n = 53) and below (n = 37) the cut-off value of 65.75 showed that the malignancy rate was significantly higher among patients with Yedikule-SPN score over 65.75 (86.8% vs 21.6%, P < 0.001, odds ratio = 23.821, 95% confidence interval: 7.805–72.701). When compared with the BU-PM model in all patients, the Yedikule-SPN model tended to be a better predictor of malignancy (P = 0.06).CONCLUSIONSThe internally validated Yedikule-SPN model is also a good predictor of the malignancy of SPN(s). Prospective and multicentre external validation studies with large patients’ cohorts are needed.     

Migraine and associated comorbidities are three times more frequent in children with ADHD and their mothers

Objective

Attention deficit and hyperactivity disorder (ADHD) is a neuro-developmental disorder related to internalizing and externalizing disorders as well as somatic complaints and disorders. This study was conducted to evaluate the prevalence of headache subtypes, epilepsy, atopic disorders, motion sickness and recurrent abdominal pain among children and adolescents with ADHD and their parents.

No significant difference in clinically relevant findings between Pillcam~? SB3 and Pillcam~? SB2 capsules in a United States veteran population

BACKGROUND Capsule endoscopy(CE) allows for a non-invasive small bowel evaluation for a wide range of gastrointestinal(GI) symptoms and diseases. Capsule technology has been rapidly advancing over recent years, often improving image frequency and quality. The Pillcam~? SB3(SB3) capsule is one such technology that offers an adaptive frame rate advantage over the previous versions of the capsule the Pillcam~? SB2(SB2). Some have proposed that this improvement in capsule technology may lead to increased diagnostic yields; however, real world clinical data is currently lacking.AIM To evaluate the clinically relevant findings of SB3 and SB2 capsules in a population of United States veterans.METHODS A retrospective analysis of 260 consecutive CE studies was performed including130 SB3 and 130 SB2 capsule studies. Recorded variables included: age, gender,type of capsule, body mass index, exam completion, inpatient status, opioid use,diabetes, quality of preparation, gastric transit time, small bowel transit time,indication, finding, and if the exam resulted in a change in clinical management.The primary outcome measured was the detection of clinically relevant findings between SB3 and SB2 capsules.RESULTS Mean age of the study population was 67.1 ± 10.4 years and 94.2% of patients were male. Of these 28.1% were on opioid users. The most common indications for capsule procedure were occult GI bleeding(74.6%) and overt GI bleeding(14.6%). Rates of incomplete exam were similar between SB3 and SB2 groups(16.9% vs 9.2%, P = 0.066). The overall rate of clinically relevant finding was48.9% in our study. No significant difference was observed in SB3 vs SB2 capsules for clinically relevant findings(46.2% vs 51.5%, P = 0.385) or change in clinical management(40.8% vs 50.0%, P = 0.135).CONCLUSION Our study found no significant difference in clinically relevant findings between SB3 and SB2 capsules.     

MLVA用于新疆部分地区结核分枝杆菌基因分型的初步研究

目的探讨结核菌株进行多位点可变数目串联重复序列分析(the multiple locus VNTR analysis,MLVA)。方法选择2010年至2011年新疆维吾尔自治区第五次结核病流行病学抽样调查资料,采用经典24位点方法进行基因分型。并采用Bio Numerics5.0数据库进行基因聚类分析。将结核分枝杆菌原始株,取一菌环溶于400μl TE中悬菌,80℃1 h灭活,12 000 r/min离心10 min,弃上清,600μl TE重新悬菌,进行多位点串联重复序列分析。结果新疆99株结核分枝杆菌分为2个基因群:分别为基因群Ⅰ和基因群Ⅱ,基因群Ⅰ66株(66.7%),基因株Ⅱ33株(33.3%);基因群Ⅰ是北京家族,基因群Ⅰ的66株结核分枝杆菌有65种不同的基因型,有2株结核分枝杆菌属于同一簇,成簇率为1.5%,基因群II33株结核分枝杆菌菌株的MLVA图谱不同,成簇率为0。结论新疆结核分枝杆菌菌株存在明显的基因多态性,以北京基因型菌株为主,同时还存在一定比例的非北京基因型,应加强对主要流行菌株流行的监控及管理。     

Bronchial Hyper‐Reactivity in Migraine Without Aura: Is It a New Clue for Inflammation?

Objective.— We attempted to investigate the relationship between migraine without aura (MwoA) and bronchial hyper‐reactivity to postulate inflammation as an underlying mechanism in migraine. Background.— Comorbidity of migraine and atopic diseases such as asthma has been an argument for suspected immune system dysfunction in migraineurs. Methods.— Twenty patients with MwoA and 5 control subjects without history of atophy and asthma were included in study. Subjects with abnormal physical examination and chest radiographs were excluded. After a normal spirometry, methacholine bronchoprovocation test was performed in all subjects and controls according to 5 breath dosimeter methods. Results.— Sixteen of 20 patients and 2 of 5 control subjects were women. Mean ages were 37.5 (19‐56) and 33.8 (26‐43) years, respectively. Methacholine bronchoprovocation test was positive in 3 patients (15%) but was normal in all controls (0%). Conclusions.— The relationship between MwoA and bronchial hyper‐reactivity may help to postulate the inflammation in migraine as an underlying mechanism.