Protective effects of vitamin D3 (cholecalciferol) on vancomycin-induced oxidative nephrotoxic damage in rats.
Vancomycin (VCM), an important antibiotic against refractory infections, has been used to treat secondary infections in severe COVID-19 patients. Regrettably, VCM treatment has been associated with nephrotoxicity. Vitamin D3 can prevent nephrotoxicity through its antioxidant effect. This study tests the antioxidant effect of vitamin D3 in the prevention of VCM-induced nephrotoxicity. Wistar Albino rats (21) were randomly divided into 3 groups: (A) control; (B) VCM 300 mg/kg daily for 1 week; and (C) VCM plus vitamin D3 500 IU/kg daily for 2 weeks. All the rats were sacrificed and serum was separated to determine kidney function parameters. Their kidneys were also dissected for histological examination and for oxidative stress markers. Lipid peroxidation, creatinine, and urea levels decreased significantly (p < 0.0001) in the vitamin D3-treated group (14.46, 84.11, 36.17%, respectively) compared to the VCM group that was given VCM (MIC<2 μg/mL) only. A significant increase was observed in superoxide dismutase levels in the vitamin D3-treated group (p < 0.05) compared to rats without treatment. Furthermore, kidney histopathology of the rats treated with vitamin D3 showed that dilatation, vacuolization and necrosis tubules decreased significantly (p < 0.05) compared with those in the VCM group. Glomerular injury, hyaline dystrophy, and inflammation improved significantly in the vitamin D3 group (p < 0.001, p < 0.05, p < 0.05, respectively) compared with the VCM group. Vitamin D3 can prevent VCM nephrotoxicity. Therefore, the appropriate dose of this vitamin must be determined, especially for those infected with COVID-19 and receiving VCM, to manage their secondary infections.


Firearm injury-a preventable public health issue.
Firearm-related injury is a leading cause of death disproportionately affecting adolescents and young adults across the world, especially in the Americas. Little progress has been made over the past four decades, as inaction and the adoption of ineffective or unevidenced interventions have become commonplace. The COVID-19 pandemic reconfigured health systems towards prevention and harm reduction, sharpened public attention to the burden of preventable deaths, and inspired a fresh ambition of eliminating avertable deaths. In this Viewpoint, we argue that preventing firearm injury should garner bolder action in post-pandemic public health and we present a case for reducing the global burden of firearm injury supported by evidence and international examples. Crucially, we aim to guide policy making in directions that end the cycle of grief, anger, activism, deflection, and inaction and create more peaceful and fairer societies.


Hepatic and intestinal 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in genetically diabetic mice.
Cholesterol synthesis rate, as determined by 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, is characterized in the major organs of genetically diabetic mice. Both C57BL/Ks db+/db+ and C57BL/6 ob+/ob+ mice are hyperinsulinemic and insulin-resistant. These animals demonstrate loss of the circadian rhythm of hepatic reductase activity and a tendency for increased intestinal activity. As a result, proportionally more endogenous cholesterol synthesis occurs in intestinal mucosa than liver in genetically diabetic animals. Thus, the alterations in activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase which are observed in animal models of diabetes are the result of diminished insulin effect rather than insulin level.


Ultrasound Evaluation of the Lower Trapezius in Adolescent Baseball Pitchers.
Biomechanical studies have demonstrated that the lower trapezius (LT) facilitates normal shoulder function, and given its potential role in causing and/or perpetuating dysfunction, clinicians have begun to evaluate and rehabilitate the LT in the context of comprehensive shoulder rehabilitation programs. Although some studies have compared side-to-side differences in LT thickness among nonthrowers, no studies have been performed to examine the normal ultrasound appearance of the LT in the adolescent throwing population. To examine whether LT thickness and cross-sectional area (CSA) differ between dominant and nondominant sides in adolescent baseball pitchers and to determine the inter-rater and intrarater reliability of the sonographically measured parameters. Observational, repeated measures study. Hospital-based outpatient practice. Thirty asymptomatic male baseball pitchers aged 13-18 years with at least 3 years of pitching experience from a convenience sample in the Rochester, Minnesota, area. LT thickness and CSA were measured at the T8 and T5 vertebral levels at rest, and thickness was measured again in active prone T- and Y-pose positions by multiple investigators. Side-to-side differences in thickness and CSA were examined, and inter-rater and intrarater measurement reliability coefficients were estimated. Thickness and cross-sectional area were measured. For reliability, we calculated intraclass correlation coefficients along with the standard error of measurement and the minimal detectable change. Resting LT thickness was 0.064 cm greater on the dominant side than on the nondominant side (P = .001). During contraction, LT thickness was 0.084 and 0.097 cm greater on the dominant side in the T and Y poses (P = .036 and P = .001, respectively). The CSA at the T5 level was 0.36 cm(2) greater on the dominant side than on the nondominant side (P < .001). Inter-rater and intrarater reliability coefficients exceeded 0.898 across all levels of measurement. Asymptomatic adolescent pitchers have greater resting and contracted LT thickness and resting CSA on the dominant versus the nondominant side, although the quantitative differences are small. These differences suggest that structural changes and asymmetry can manifest at young ages; however, clinically, the nondominant arm can be used as a control in the adolescent pitching population. Ultrasound provides a noninvasive way to reliably evaluate LT thickness and CSA in adolescent pitchers.


Canonical Chinese medicine formula Danzhi-Xiaoyao-San for treating depression: A systematic review and meta-analysis.
Danzhi-Xiaoyao-San (DXS), as a canonical Chinese medicine formula, possessing the functions of the soothing liver, invigorating spleen, clearing heat, and cooling blood, has been widely used for the treatment of depression. This systematic review and meta-analysis of randomized controlled trials aimed to examine the efficacy of DXS in depression. We performed a literature search in several databases, e.g., PUBMED, until August 2021 and conducted the meta-analysis using Review Manager 5.3 software. The random-effects model and fixed-effects model were used to synthetize extracted data. Finally, this meta-analysis showed that comparing with antidepressants, DXS exhibited similar effect to antidepressants in the clinical comprehensive effect [RR = 1.04, 95% CI (0.77, 1.40); P = 0.81] and decrease in Self-Rating Depression Scale scores [WMD = 0.89, 95% CI (-6.33, 8.11); P = 0.81], while lower effect in Hamilton Depression Scale scores [SMD = -0.29, 95% CI (-0.55, -0.03); P = 0.03]; Furthermore, DXS plus antidepressants can significantly improve the clinical comprehensive effect [RR = 1.23, 95% CI (1.17, 1.29); P < 0.00001] and decrease the Hamilton Depression Scale scores [SMD = 1.04, 95% CI (0.51, 1.58); P = 0.0001] than pure antidepressants. This systematic review and meta-analysis approved an efficient role of DXS in improving depression in clinical randomized controlled trials. However, further evidence from large samples and high-quality randomized controlled trials is needed to be investigated for a reliable conclusion about DXS in the treatment of depression.


Antimicrobial resistance and genotypic characterization of coagulase-negative staphylococci over the dry period.
Coagulase-negative staphylococci (CNS) have become the most frequently isolated organisms from bovine intramammary infections in recent years. While antimicrobial resistance (AR) is not considered a major problem among mastitis pathogens, concerns over emerging AR in general are increasing worldwide. Little information exists about the association between AR and one of the most common mastitis control measures, antibiotic dry cow therapy. The primary objective of the current study was to determine the prevalence of AR in CNS isolated before and after antimicrobial dry cow therapy. An additional objective was to genotypically characterize selected CNS isolates using pulsed-field gel electrophoresis (PFGE), to assess diversity and persistence of organisms over the dry period. Resistance against 10 antimicrobials was determined using a broth microdilution method and compared between CNS isolates collected at dry-off and at calving and from cows treated or not treated with intramammary antimicrobial products at dry-off (752 cows in total). Results suggested that increasing age of a cow and dry cow treatment when combined with high milk somatic cell count at dry-off and positive clinical mastitis history, were associated with increased AR to most beta-lactam antimicrobials and sulfadimethoxine. PFGE results suggested considerable diversity among the tested isolates as well as some clusters within cows and herds. PFGE would be useful in distinguishing between potentially persisting infections and cures and reinfections with different CNS strains.


First Experience With Real-Time EPID-Based Delivery Verification During IMRT and VMAT Sessions.
Gantry-mounted megavoltage electronic portal imaging devices (EPIDs) have become ubiquitous on linear accelerators. WatchDog is a novel application of EPIDs, in which the image frames acquired during treatment are used to monitor treatment delivery in real time. We report on the preliminary use of WatchDog in a prospective study of cancer patients undergoing intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) and identify the challenges of clinical adoption. At the time of submission, 28 cancer patients (head and neck, pelvis, and prostate) undergoing fractionated external beam radiation therapy (24 IMRT, 4 VMAT) had ≥1 treatment fraction verified in real time (131 fractions or 881 fields). EPID images acquired continuously during treatment were synchronized and compared with model-generated transit EPID images within a frame time (∼0.1 s). A χ comparison was performed to cumulative frames to gauge the overall delivery quality, and the resulting pass rates were reported graphically during treatment delivery. Every frame acquired (500-1500 per fraction) was saved for postprocessing and analysis. The system reported the mean ± standard deviation in real time χ 91.1% ± 11.5% (83.6% ± 13.2%) for cumulative frame χ analysis with 4%, 4 mm (3%, 3 mm) criteria, global over the integrated image. A real-time EPID-based radiation delivery verification system for IMRT and VMAT has been demonstrated that aims to prevent major mistreatments in radiation therapy.


Antioxidant micronutrients in the critically ill: a systematic review and meta-analysis.
Critical illness is characterized by oxidative stress, which is a major promoter of systemic inflammation and organ failure due to excessive free radical production, depletion of antioxidant defenses, or both. We hypothesized that exogenous supplementation of trace elements and vitamins could restore antioxidant status, improving clinical outcomes. We searched computerized databases, reference lists of pertinent articles and personal files from 1980 to 2011. We included randomized controlled trials (RCTs) conducted in critically ill adult patients that evaluated relevant clinical outcomes with antioxidant micronutrients (vitamins and trace elements) supplementation versus placebo. A total of 21 RCTs met inclusion criteria. When the results of these studies were statistically aggregated (n = 20), combined antioxidants were associated with a significant reduction in mortality (risk ratio (RR) = 0.82, 95% confidence interval (CI) 0.72 to 0.93, P = 0.002); a significant reduction in duration of mechanical ventilation (weighed mean difference in days = -0.67, 95% CI -1.22 to -0.13, P = 0.02); a trend towards a reduction in infections (RR= 0.88, 95% CI 0.76 to 1.02, P = 0.08); and no overall effect on ICU or hospital length of stay (LOS). Furthermore, antioxidants were associated with a significant reduction in overall mortality among patients with higher risk of death (>10% mortality in control group) (RR 0.79, 95% CI 0.68 to 0.92, P = 0.003) whereas there was no significant effect observed for trials of patients with a lower mortality in the control group (RR = 1.14, 95% 0.72 to 1.82, P = 0.57). Trials using more than 500 μg per day of selenium showed a trend towards a lower mortality (RR = 0.80, 95% CI 0.63 to 1.02, P = 0.07) whereas trials using doses lower than 500 μg had no effect on mortality (RR 0.94, 95% CI 0.67 to 1.33, P = 0.75). Supplementation with high dose trace elements and vitamins may improve outcomes of critically ill patients, particularly those at high risk of death.


Mitochondrial NADP-dependent malic enzyme of cod heart. Rate of forward and reverse reaction.
The mitochondrial NADP-dependent malic enzyme (EC 184.108.40.206) was purified about 300-fold from cod Gadus morhua heart to a specific activity of 48 units (mumol/min)/mg at 30 degrees C. The possibility of the reductive carboxylation of pyruvate to malate was studied by determination of the respective enzyme properties. The reverse reaction was found to proceed at about five times the velocity of the forward rate at a pH 6.5. The Km values determined at pH 7.0 for pyruvate, NADPH and bicarbonate in the carboxylation reaction were 4.1 mM, 15 microM and 13.5 mM, respectively. The Km values for malate, NADP and Mn2+ in the decarboxylation reaction were 0.1 mM, 25 microM and 5 microM, respectively. The enzyme showed substrate inhibition at high malate concentrations for the oxidative decarboxylation reaction at pH 7.0. Malate inhibition suggests a possible modulation of cod heart mitochondrial NADP-malic enzyme by its own substrate. High NADP-dependent malic enzyme activity found in mitochondria from cod heart supports the possibility of malate formation under conditions facilitating carboxylation of pyruvate.


RNA interference: roles in fungal biology.
The discovery of RNA interference (RNAi) has been the major recent breakthrough in biology. Only a few years after its discovery, RNAi has rapidly become a powerful reverse genetic tool, especially in organisms where gene targeting is inefficient and/or time-consuming. In filamentous fungi, RNAi is not currently used as widely as is gene targeting by homologous recombination that works with practical efficiencies in most model fungal species. However, to explore gene function in filamentous fungi, RNAi has the potential to offer new, efficient tools that gene disruption methods cannot provide. In this review, possible advantages and disadvantages of RNAi for fungal biology in the postgenomics era will be discussed. In addition, we will briefly review recent discoveries on RNAi-related biological phenomena (RNA silencing) in fungi.


Human papillomavirus type 16 E7 oncoprotein-induced upregulation of lysine-specific demethylase 5A promotes cervical cancer progression by regulating the microRNA-424-5p/suppressor of zeste 12 pathway.
Human papillomavirus (HPV) infection and viral protein expression cause several epigenetic alterations that lead to cervical carcinogenesis. Our previous study identified that upregulated lysine-specific demethylase (KDM) 2 A promotes cervical cancer progression by inhibiting mircoRNA (miR)-132 function. However, the roles of histone methylation modifiers in HPV-related cervical cancer remain unclear. In the present study, changes in the expression of 48 histone methylation modifiers were assessed following knockdown of HPV16 E6/E7 in CaSki cells. The dysregulated expression of KDM5A was identified, and its function in cervical cancer was investigated in vitro and in vivo. E7 oncoprotein-induced upregulation of KDM5A promoted cervical cancer cell proliferation and invasiveness in vitro and in vivo, which was correlated with poor prognosis in patients with cervical cancer. KDM5A was found to physically interact with the promoter region of miR-424-5p, and to suppress its expression by removing the tri- and di-methyl groups from H3K4 at the miR-424-5p locus. Furthermore, miR-424-5p repressed cancer cell proliferation and invasiveness by targeting suppressor of zeste 12 (Suz12). KDM5A upregulation promoted cervical cancer progression by repressing miR-424-5p, which resulted in a decrease in Suz12. Therefore, KDM5A functions as a tumor activator in cervical cancer pathogenesis by binding to the miR-424-5p promoter and inhibiting its tumor-suppressive function. These results indicate a function for KDM5A in cervical cancer progression and suggest its candidacy as a novel prognostic biomarker and target for the clinical management of this malignancy.


Combined Hepatic Arterial Infusion Pump and Systemic Chemotherapy in the Modern Era for Chemotherapy-Naive Patients with Unresectable Colorectal Liver Metastases.
Chemotherapy-naive patients with unresectable colorectal liver metastases (CRLM) have been the best responders to hepatic arterial infusion (HAI) therapy. The current treatment paradigm has drifted away from HAI in the first-line setting. We aimed to analyze outcomes of combined first-line systemic therapy with HAI therapy (HAI+SYS) in the modern era. We conducted a retrospective study of consecutive chemotherapy-naive patients with unresectable CRLM who received HAI+SYS between 2003 and 2019. Patients were selected from a prospectively maintained database. Outcomes included radiological response rate, conversion to resection (CTR) rate, and overall survival (OS). Fifty-eight chemotherapy-naive patients were identified out of 546 patients with unresectable CRLM managed with HAI. After induction treatment, 4 patients (7%) had a complete radiological response, including two durable responses. In total, 32 patients (55%) underwent CTR. CTR or complete response without resection was achieved after seven cycles of systemic therapy and four cycles of HAI therapy. Median OS for the whole cohort was 53.0 months (95% confidence interval 23.0-82.9). Three- and 5-year OS in patients who achieved CTR or complete response versus patients who did not was 88% and 72% versus 27% and 0% respectively. Of patients who underwent CTR, complete and major pathological response (no and <10% viable tumor cells, respectively) was observed in 7 (22%) and 12 patients (38%). Combined HAI+SYS in chemotherapy-naive patients resulted in durable and substantial response in a large proportion of patients. Nearly two-thirds of patients achieved a complete response or proceeded to conversion surgery, which was associated with prolonged survival.


Functional Chest Pain and Esophageal Hypersensitivity: A Clinical Approach.
Functional chest pain, functional heartburn, and reflux hypersensitivity are 3 functional esophageal disorders defined by the Rome IV criteria. Specific criteria, combining symptoms and the results of objective testing, allow for an accurate diagnosis of these conditions. Management may include medications targeted at optimizing acid suppression or neuromodulation, as well as a host of complementary or alternative treatment options. Psychological and behavioral interventions, such as cognitive behavioral therapy and hypnotherapy, have displayed substantial benefits in the treatment of functional chest pain and functional heartburn. Acid suppression and focused neuromodulation are key evidence-based treatment options for reflux hypersensitivity.


Benefits and Safety of Periprocedural Heparin During Thrombectomy in Patients Contra-Indicated for Alteplase.
Role of peri-procedural heparin as an adjuvant treatment during mechanical thrombectomy (MT) for patients contra-indicated for alteplase remains a source of debate. We included patients from the multicenter French register ETIS that underwent MT without administration of alteplase, and compared patients who received heparin during MT with patients who did not. Heparin impact on outcome were analyzed regarding final TICI score, NIHSS at day one, modified rankin scale (mRS) and intracranial hemorrhagic transformation on imaging at day one. Over 1031 patients, 751 were included between January 2015 and June 2018 in 6 different centers, and 223 (26.69%) received heparin. Heparin administration was associated with a significant deleterious effect on NIHSS at 24h [adjusted OR = 1.2; p = 0.02], mRS at 3 months [adjusted OR 1.58; p = 0.03], and on complete reperfusion [TICI 3 adjusted OR 0.68; p = 0.02]. Heparin administration was associated with a significant reduction of hemorrhagic transformation [adjusted OR 0.48; p = 0.00005]. Heparin administration during MT seems deleterious for reperfusion and functional outcome. Randomized trials are needed to identify the role of antithrombotic treatments, such as heparin, in the setting of acute ischemic stroke management.


A new single band variant of the Gc subtypes determined by isoelectric focusing.
A new single band variant (Gc Ta) of the Gc subtypes which does not correspond with the known Gc variants has been detected in a healthy blood donor by isoelectric focusing. Using this technique the variant is represented by a single band, which is more cathodically located than the 1A8(fast) band and more anodically located than the 1A3(fast) band. It is well known that the single band Gc phenotypes remain unaltered after neuraminidase treatment. Nevertheless, the new single band variant (Gc Ta) is altered after neuraminidase treatment. In this case the new single band Gc variant also contained N-acetylneuraminic acid (NANA).


Immobilization After Rotator Cuff Repair: What Evidence Do We Have Now?
Recurrent tears after rotator cuff repair are common. Postoperative rehabilitation after rotator cuff repair is a modifiable factor controlled by the surgeon that can affect re-tear rates. Some surgeons prefer early mobilization after rotator cuff repair, whereas others prefer a period of immobilization to protect the repair site. The tendon-healing process incorporates biochemical and biomechanical responses to mechanical loading. Healing can be optimized with controlled loading. Complete load removal and chronic overload can be deleterious to the process. Several randomized clinical studies have also characterized the role of postoperative mobilization after rotator cuff repair.


Comprehensive metabolomic analysis of first-trimester serum identifies biomarkers of early-onset hypertensive disorder of pregnancy.
Hypertensive disorders of pregnancy (HDP) lead to the death of approximately 30,000 women annually, and the identification of biomarkers to predict their onset before symptom occurrence is crucial. Here, we aimed to identify the first-trimester maternal serum biomarkers for predicting early-onset HDP via a comprehensive metabolomic analysis. This study was conducted by the Fukushima Regional Center as an adjunct study to the Japan Environment and Children's Study. The study comprised 12 patients with early-onset HDP and 12 control subjects with healthy pregnancy whose medical background information was matched with that of the patients by propensity-score matching. Capillary electrophoresis and mass spectrometry-based quantitative analysis of charged metabolites were performed with the first-trimester maternal serum samples. Welch's t-test was used to analyse metabolite peak areas in the two groups. A total of 166 charged metabolites were identified. The peak area of N-dimethylglycine and S-methylcysteine was significantly higher in the first-trimester serum of patients with early-onset HDP than in the controls. Conversely, the peak area of munic acid was significantly decreased in the serum of patients with early-onset HDP. Although we identified potential biomarkers for the prediction and diagnosis of early-onset HDP, no clear marker was identified because of a low statistical power.


Development of Machine Learning Algorithms to Predict Patient Dissatisfaction After Primary Total Knee Arthroplasty.
Postoperative dissatisfaction after primary total knee arthroplasty (TKA) that requires additional care or readmission may impose a significant financial burden to healthcare systems. The purpose of the current study is to develop machine learning algorithms to predict dissatisfaction after TKA. A retrospective review of consecutive TKA patients between 2014 and 2016 from 1 large academic and 2 community hospitals was performed. Preoperative variables considered for prediction included demographics, medical history, flexion contracture, knee flexion, and outcome scores (patient-reported health state, Knee Society Score [KSS], and KSS-Function [KSS-F]). Recursive feature elimination was used to select features that optimized algorithm performance. Five supervised machine learning algorithms were developed by training with 10-fold cross-validation 3 times. These algorithms were subsequently applied to an independent testing set of patients and assessed by discrimination, calibration, Brier score, and decision curve analysis. Of 430 patients, a total of 40 (9.0%) were dissatisfied with their outcome after primary TKA at a minimum of 2 years postoperatively. The random forest algorithm achieved the best performance in the independent testing set not used for algorithm development (c-statistic: 0.77, calibration intercept: 0.087, calibration slope: 0.74, Brier score: 0.082). The most important factors for predicting dissatisfaction were age, number of medical comorbidities, presence of one or more drug allergies, preoperative patient-reported health state score, and preoperative KSS. The current study developed machine learning algorithms based on partially modifiable risk factors for predicting dissatisfaction after TKA. This model demonstrates good discriminative capacity for identifying those at greatest risk for dissatisfaction and may allow for preoperative health optimization.


Nanoscale imaging and hydrophobicity mapping of the antimicrobial effect of copper on bacterial surfaces.
Copper has a long historical role in the arena of materials with antimicrobial properties. Various forms of copper ranging from surfaces to impregnation in textiles and particles, have attracted considerable interest owing to their versatility, potency, chemical stability, and low cost. However, the effects and mechanisms of their antimicrobial action is still unclear. In this study, the effect of copper particles on Escherichia coli was studied at the nanoscale using atomic force microscopy (AFM). Time-lapse AFM images at the single cell level show the morphological changes on live E. coli during antimicrobial treatment, in which for the first time, this process was followed in situ on the same cell over time. AFM-based hydrophobicity mapping further showed that incubating cells with Cu decreased the surface hydrophobicity with an increase of incubation time. Specifically, we are able to visualize both morphology and physico-chemical nature of the bacterial cell surface change in response to copper treatment, leading to the membrane damage and cytoplasm leakage. Overall, the time-lapse AFM imaging combined with hydrophobicity mapping approach presented here provides spatio-temporal insight into the antimicrobial mechanisms of copper at the single cell level, and can be applied to design of better metallic antimicrobial materials as well as investigate different microorganisms.


Use of aspirin to intentionally induce gastrointestinal tract barrier dysfunction in feedlot cattle.
Stress negatively affects the gastrointestinal tract (GIT) barrier function, resulting in compromised animal health. A deeper understanding of how diet and stress impacts the GIT barrier function in feedlot cattle is needed. Aspirin decreases mucus production and mucosal repair in the GIT and could be used as a model for GIT barrier dysfunction research. The objective of this study was to evaluate the effectiveness of aspirin to induce GIT barrier dysfunction in beef cattle. In experiment 1, sixteen crossbred heifers (425.0 ± 8.6 kg) were allotted to 0, 50, 100, or 200 mg/kg body weight (BW) aspirin doses based on BW. Experiment 1 consisted of two periods separated by 4 wk where four heifers per treatment received the same aspirin dose during each period. Heifers were fed a 49.4% corn silage and 50.6% concentrate diet. The 200 mg/kg BW aspirin treatment was dosed as a 100 mg/kg BW aspirin oral bolus 36 and 24 h prior to Cr-ethylenediaminetetraacetic acid (EDTA) dosing (1 liter; 180 mM). The 50 and 100 mg/kg BW aspirin treatments were dosed as an oral bolus 24 h prior to Cr-EDTA dosing. Urine was collected every 3 h for 48 h and analyzed for Cr. Serum was collected at 0 and 48 h and analyzed for lipopolysaccharide-binding protein (LBP), interleukin-6, serum amyloid A (SAA), haptoglobin, and aspartate aminotransferase. In experiment 2, sixteen crossbred steers (576.0 ± 14.2 kg) fed a similar diet were allotted by BW to the 0 and 200 mg/kg BW aspirin treatments (eight steers/treatment) and were slaughtered 24 h after the last dose. Jejunal tissues were collected, and claudin (CLDN) 1, 2, and 3, occludin, and zonula occludens tight junction messenger ribonucleic acid (mRNA) expression was determined. Data were analyzed using the MIXED procedure of SAS. Urinary Cr excretion increased linearly at hours 3, 6, 9, and 12 (P ≤ 0.04) as aspirin dose increased from 0 to 200 mg/kg. Aspirin linearly increased Cr absorption (P = 0.02) and elimination (P = 0.04) rates and linearly decreased mean retention time of Cr (P = 0.02). Aspirin increased SAA (P = 0.04) and tended to increase LBP (P = 0.09) in serum but did not affect any other serum inflammatory marker (P ≥ 0.19). Aspirin tended to increase jejunal CLDN-1 mRNA expression (P = 0.10) but did not affect the mRNA expression of other genes regulating tight junction function (P ≥ 0.20). Results from this study indicate that aspirin disrupts the GIT barrier function in beef cattle and has a potential as a model in GIT permeability research.


Automatic analysis of cardiac repolarization morphology using Gaussian mesa function modeling.
A novel fully automated method for wave identification and extraction from electrocardiogram (ECG) waveforms is presented. This approach implements the combined use of a new machine-learning algorithm and of specified parameterized functions called Gaussian mesa functions (GMFs). Individual cardiac cycle waveforms are broken up into GMFs using a generalized orthogonal forward regression algorithm; each individual GMF is subsequently identified (wave labeling) and analyzed for feature and morphologic extraction. The GMF associated with the repolarization waveform of the main vector lead, based on principal components analysis, was analyzed, and a set of morphologic parameters were derived under 2 experimental settings: first, in 100 digital 12-lead ECG Holter recordings acquired during three 24-hour periods (baseline and after 160 and 320 mg of sotalol) from 38 healthy subjects; second, in drug-free 12-lead resting ECGs from 100 genotyped long QT syndrome (LQTS) patients (50 each with LQT1 and LQT2). QT-interval duration was measured using an on-screen method applied to the global representative beats and reviewed by a senior cardiologist. QTci (individual correction) was used for analysis. All parameters in the sotalol test showed highly significant differences between the time of peak plasma concentration (Tmax) and baseline ECGs; however, the dynamic pattern of individual parameters followed different patterns. The LQTS test confirmed the results of the sotalol test, showing that GMF-based repolarization parameters were strongly modified as compared with healthy controls. In particular, T-wave width and descending phase of repolarization were more prolonged in LQT2 compared to LQT1.


Effects of [N-(2-oxo-3,5,7-cycloheptatrien-1-yl)] aminooxoacetic acid ethyl ester (AY-25,674) on cyclic 3',5'-nucleotide formation and phosphodiesterase activity.
The orally-effective antiallergic compound [N-(2-oxo-3,5,7-cycloheptatrien-1-yl)] aminooxoacetic acid ethyl ester (AY-25,674) exhibited a potency equivalent to or 3 times less than theophylline in inhibiting guinea-pig lung and beef heart PDE, respectively, AY-25,674 did not affect the basal activity of guinea-pig lung adenyl cyclase. Although part of the antiallergic activity of AY-25,674 may be due to the ability to elevate cyclic AMP levels by PDE inhibition, other modes of action appear to be of greater relevance.


Solute carriers (SLCs) identified and characterized from kidney transcriptome of golden mahseer (Tor putitora) (Fam: Cyprinidae).
The solute carriers (SLC) are trans-membrane proteins, those regulate the transport of various substances (sugars, amino acids, nucleotides, inorganic cations/anions, metals, drugs etc.) across the cell membrane. There are more than 338 solute carriers (slc) reported in fishes that play crucial role in cellular influx and efflux. The study of solute carrier families may reveal many answers regarding the function of transporter genes in the species and their effect in the existing environment. Therefore, we performed RNA sequencing of kidney tissue of the golden mahseer (Tor putitora) using Illumina platform to identify the solute carrier families and characterized 24 putative functional genes under 15 solute carrier families. Out of 24 putative functional genes, 11 genes were differentially expressed in different tissues (head kidney, trunk kidney, spleen, liver, gill, muscle, intestine and brain) using qRT-PCR assay. The slc5a1, slc5a12, slc12a3, slc13a3, slc22a13 and slc26a6 were highly expressed in kidney. The slc15a2, slc25a47, slc33a1 and slc38a2 were highly expressed in brain and slc30a5 was over-expressed in gill. The unrooted phylogenetic trees of slc2, slc5, slc13 and slc33 were constructed using amino acid sequences of Homo sapiens, Salmo salar, Danio rerio, Cyprinus carpio and Tor putitora. It appears that all the putative solute carrier families are very much conserved in human and fish species including the present fish, golden mahseer. This study provides the first hand database of solute carrier families particularly transporter encoding proteins in the species.


Hashimoto's thyroiditis impairs embryo implantation by compromising endometrial morphology and receptivity markers in euthyroid mice.
Although thyroid dysfunction caused by Hashimoto's thyroiditis (HT) is believed to be related to implantation failure due to the underdevelopment of the receptive uterus, it is unknown whether HT itself, even in the euthyroid state, impairs embryo implantation associated with endometrial receptivity defects. To address whether HT itself can affect endometrial receptivity accompanied by implantation alterations, a euthyroid HT model was established in mice. Female NOD mice were immunized twice with thyroglobulin and adjuvant to induce the experimental HT model. Four weeks after the second treatment, the mice were normally mated, and pregnant ones were sacrificed in implantation window for thyroid-related parameter and steroid hormones measurements by electrochemiluminescence immunoassay and enzyme-linked immunosorbent assay and implantation site number calculation by uptake of Chicago Blue dye. In addition, certain morphological features of endometrial receptivity were observed by hematoxylin-eosin staining and scanning electron microscopy, and the expression of other receptivity markers were analyzed by immunohistochemistry, RT-qPCR or Western Blot. HT mice displayed intrathyroidal monocyte infiltration and elevated serum thyroid autoantibody levels without thyroid dysfunction, defined as euthyroid HT in humans. Euthyroid HT resulted in implantation failure, fewer pinopodes, retarded pinopode maturation, and inhibited expression of receptivity markers: estrogen receptor α (ERα), integrin β3, leukemia inhibitory factor (LIF), and cell adhesion molecule-1 (ICAM-1). Interestingly, despite this compromised endometrial receptivity response, no statistical differences in serum estradiol or progesterone level between groups were found. These findings are the first to indicate that HT induces a nonreceptive endometrial milieu in the euthyroid state, which may underlie the detrimental effects of HT itself on embryo implantation.


Massive right atrial myxoma: an unusual presentation in an elderly patient.
Primary heart tumors are rare with an estimated incidence ranging 0.0017-0.19%. Myxoma is the most prevalent primary heart tumor. The right atrium is an unusual location, occurring only in the 15-20% of myxoma cases. We describe the case of a massive right atrial myxoma causing right ventricular inflow and tricuspid valve obstruction. The tumor was detected by echocardiography and confirmed by abdomen-thoracic tomography. It was resected along with a section of tricuspid septal leaflet, followed by primary repair. In 2-year follow-up the patient is asymptomatic.


The primary sequence of the PFK-1 inactivating zinc-binding protein as deduced from cDNA sequencing. Identity of the zinc-binding protein with rat parathymosin.
We have recently described the sequence of the Zn2+-binding domain (43 amino acid residues) of a newly detected Zn2+-binding protein which reversibly inactivates phosphofructokinase-1 in a Zn2+-dependent manner [(1986) J. Biol. Chem. 269, 5895-5900; (1988) Eur. J. Biochem. 177, 561-568]. Here, we describe the primary sequence of this protein based on a full-length cDNA. A sequence comparison reveals the identity of the Zn2+-binding protein with a protein called parathymosin-alpha.


Cerebral arteritis associated with heroin abuse.
A twenty-year-old man suffered a left homonymous hemianopia after self-administration of heroin. Investigations revealed right occipital infarction with angiographic changes of arteritis in the posterior cerebral arteries.


Lead-induced cardiac and hematological alterations in aging Wistar male rats: alleviating effects of nutrient metal mixture.
Age related mitochondrial impairments are considered to be contributors of cardiovascular disease. This study was designed to examine whether early life exposure to lead (Pb) would lead to the Pb induced age related hematological and cardiac mitochondrial changes in rats, and to further examine the protective effect of nutrient metal mixture containing zinc, iron and calcium. Male albino rats were lactationally exposed to 0.2 % Pb-acetate or 0.2 % Pb-acetate together nutrient metal mixture (0.02 %) in drinking water of the mother from postnatal day 1 (PND1) to PND 21. The hemoglobin level, the activities of serum ceruloplasmin oxidase, cardiac mitochondrial enzymes catalase, manganese superoxide dismutase, copper zinc superoxide dismutase, glutathione peroxidase, succinate dehydrogenase, lipid peroxidation and Pb levels were analyzed at PND 45, 12 and 24 months age. The hematological parameters, and the cardiac TCA cycle and antioxidant enzyme markers and lipid peroxidation levels were significantly altered following Pb exposure in young rats (PND 45). These Pb induced changes persisted, though at much lower level in the aged rats. The Pb levels in blood and heart were also significantly higher in PND 45 and remained at detectable levels in older rats. The nutrient metal mixture containing iron, calcium and zinc significantly reversed these changes in all the chosen markers except lipid peroxidation in which the reversal effect was not significant. These data are supportive of age-related cardiac mitochondrial impairments and further provide evidence for the protective efficacy of nutrient metal mixture against Pb-toxicity.


Computerised tomography and intravenous pyelography in urinary tuberculosis: a retrospective descriptive study.
To assess the radiological findings of urinary tuberculosis (TB) in patients from multiple centres to improve understanding of this disease among urologists and radiologists. A total of 192 consecutive patients (98 males and 94 females) with urinary TB underwent computed tomography; 28 of the 192 also underwent contrast agent-enhanced intravenous pyelography of the kidney, ureter and bladder (KUB/IVP). The most common finding was hydronephrosis, observed in 79.1% of the patients, with 81.4% of the destructive renal lesions identified in the medulla. The numbers of lesions in the dorsal medulla and the lower pole of the renal medulla were greater than those in the ventral, middle and upper poles (P = 0.0361). Hydronephrosis is a frequently observed radiological finding among patients with urinary TB. Most TB lesions were observed in the renal medulla, especially the dorsal and lower poles of the medulla.


Screening of methicillin-resistant Staphylococcus aureus in healthcare workers and students and its susceptibility to mupirocin in a tertiary care teaching hospital in South India.
Staphylococcus is the most common pathogen causing infection in hospitals. They also colonize the healthcare workers who serve as reservoir of infection. Emergence of methicillin-resistant Staphylococcus aureus (MRSA) is a burning issue throughout the world contributing to significant morbidity and mortality. Use of mupirocin to eradicate the carrier state is the need of the hour. To screen healthcare workers (HCWs) and medical students for MRSA and to know the susceptibility of mupirocin in this group. A total of 432 students, nursing staff, doctors and house-keeping staff were screened for MRSA for 4 months. The MRSA and methicillin-resistant coagulase-negative Staphylococcus (MRCoNS) isolates were then tested for mupirocin resistance. Out of 432 samples, 24 (5.55%) were MRSA and 104 (24.07%) were MRCoNS. Only 4.16% (n = 1) showed high-level resistance to mupirocin among the MRSA isolates, while resistance among MRCoNS was higher at 6.7% (n = 7) for low-level resistance and 17.30% (n = 18) for high-level resistance. MRSA colonization of HCWs may serve as a source of infection and mupirocin resistance should be screened for all whether working in Intensive Care Units or not and if detected, alternative treatment should be used which will result in appropriate use of this antibiotic for decolonization.


Effects of syndecan-4 gene silencing by micro RNA interference in anoikis resistant endothelial cells: Syndecan-4 silencing and anoikis resistance.
The cell's resistance to cell death by adhesion loss to extracellular matrix (anoikis), contributes to tumor progression and metastasis. Various adhesion molecules are involved in the anoikis resistance, including the syndecan-4 (SDC4), a heparan sulfate proteoglycan (HSPG) present on the cell surface. Changes in the expression of SDC4 have been observed in tumor and transformed cells, indicating its involvement in cancer. In previous works, we demonstrated that acquisition of anoikis resistance resistance by blocking adhesion to the substrate up-regulates syndecan-4 expression in endothelial cells. This study investigates the role of SDC4 in the transformed phenotype of anoikis resistant endothelial cells. Anoikis-resistant endothelial cells (Adh1-EC) were transfected with micro RNA interference (miR RNAi) targeted against syndecan-4. The effect of SDC4 silencing was analyzed by real-time PCR, western blotting and immunofluorescence. Transfection with miRNA-SDC4 resulted in a sequence-specific decrease in syndecan-4 mRNA and protein levels. Furthermore, we observed a reduction in the number of heparan and chondroitin sulfate chains in the cell extract and culture medium. The SDC4 silencing led to downregulation of proliferative and invasive capacity and angiogenic abilities of anoikis-resistant endothelial cells. Compared with the parental cells (Adh1-EC), SDC4 silenced cells (SDC4 miR-Syn-4-1-Adh1-EC e miR-Syn-4-2-Adh1-EC) exhibited an increase in adhesion to collagen and laminin and also in the apoptosis rate. Moreover, transfection with miRNA-SDC4 caused a decrease in the number of cells in the S phase of the cell cycle. This is accompanied by an increase in the heparan sulfate synthesis after 12 h of simulation with fetal calf serum (FCS). SDC4 silencing cells are more dependent of growth factors present in the FCS to synthesize heparan sulfate than parental cells. Similar data were obtained for the wild-type cell line (EC). Our results indicated that downregulation of SDC4 expression reverses the transformed phenotype of anoikis resistant endothelial cells. These and other findings suggest that syndecan-4 is suitable for pharmacological intervention, making it an attractive target for cancer therapy.


Treatment and prophylaxis of cardiac allograft vasculopathy.
Cardiac allograft vasculopathy (CAV) remains a life-threatening complication after heart transplantation (HT). Recipients with severe intimal thickening are 10-fold more likely to suffer cardiac events than those without severe hyperplasia. From July 1987 to July 2007, we performed 323 HTs with 5-year actuarial freedom from CAV of 69%, similar to the data reported by the International Society for Heart and Lung Transplantation, namely, 68% at 5 years. Therefore, CAV is not uncommon in Asia. The pathogenesis of CAV is initial endothelial injury followed by intimal hyperplasia and proliferation of vascular smooth muscle cells. It may be caused by both immunological events (involving T or B cells in response to donor major histocompatibility antigens, or natural killer [NK] cell-triggered recruitment of T cells not responsive to donor alloantigen) and nonimmunologic factors, such as older age, ischemia-reperfusion injury, viral infection (particularly cytomegalovirus [CMV] infection), immunosuppressive drugs, and classic risk factors, such as hyperlipidemia, insulin resistance, and hypertension. The therapy for CAV has been disappointing, despite prescriptions of statin lipid-lowering agents, calcium-channel blockers, angiotensin-converting enzyme inhibitors, and antiproliferative drugs. Patients with CAV are often not amenable to successful revascularization (medical or surgical) because of the diffuse obliterative process. Prophylaxis of CAV starts with modification of risk factors: hypertension, hyperlipemia, hyperglycemia, obesity, and smoking, as well as promotion of exercise programs. The HMG-CoA reductase inhibitors and antiproliferative drugs may slow the progression of CAV by various immunologic and nonimmunologic effects. Prevention of CMV infection reduces CAV. Mycophenolate mofetil and signal transduction inhibitors, such as everolimus, reduce intimal thickening and CAV.


The cardiovascular actions of centrally administered neuropeptide Y.
The cardiovascular actions of intracerebroventricular (i.c.v.) administration of neuropeptide Y (NPY) were examined in conscious, unrestrained rats. A prolonged decrease in heart rate (HR) and a fall in mean arterial pressure (MAP) were obtained following i.c.v. administration of NPY (1 and 10 micrograms). Passive immunization with an antiserum directed against NPY confirmed that the slowing of HR following i.c.v. administration of NPY was mediated via a central nervous mechanism and not from leakage of NPY out of the brain. Administration of NPY into different brain parenchymal regions identified a putative site of action in the rostral region of the solitary tract. The mechanism of the decrease in HR caused by centrally administered NPY was investigated by i.c.v. administration of NPY to animals that were pretreated with agents that altered autonomic tone. Administration of NPY to atropine-treated animals produced a reversal of the atropine-induced tachycardia, suggesting that the NPY-induced decrease in HR was not due to augmented vagal tone. However, administration of NPY to animals pretreated with propranolol did not significantly lower HR below that obtained with propranolol alone. These data suggest that i.c.v. administration of NPY may cause a decrease in cardiac sympathetic outflow. The effects of centrally administered NPY on baroreflex function were studied. The changes in HR caused by NPY did not significantly alter baroreflex set-point or gain. These studies provide evidence that NPY acted within a brainstem region to decrease sympathetic nervous outflow, resulting in a decrease in HR and MAP.


Combined experimental and computational investigations of the fluorosolvatochromism of chromeno[4,3-b]pyridine derivatives: Effect of the methoxy substitution.
Extensive research has been conducted on the spectral properties of chromeno[4,3-b]pyridine derivatives, owing to their potential applications in sensing, optoelectronic devices, and drug discovery. This study presents a comprehensive investigation into the fluorosolvatochromism of selected chromeno[4,3-b]pyridine derivatives, with a particular emphasis on the impact of methoxy substitution. Three derivatives were synthesized and subjected to spectral analysis: chromeno[4,3-b]pyridine-3-carboxylate (I) as the parent compound, and its 7-methoxy (II) and 8-methoxy (III) substituted derivatives.The UV-Vis absorption spectra of all derivatives exhibited a broad band with a maximum absorption wavelength that remained unaffected by the surrounding medium. However, distinct fluorescence properties were observed among them. Specifically, derivative II displayed notable fluorescence, while derivatives I and III exhibited no fluorescence properties. Furthermore, derivative II exhibited a fluorescence spectrum that is significantly influenced by the polarity of the medium. To investigate the fluorosolvatochromic behavior in depth, we conducted a comprehensive analysis using various neat solvents with different polarities and hydrogen bonding capabilities. The results obtained revealed a significant positive fluorosolvatochromism, with a bathochromic shift in the fluorescence spectrum as the solvent polarity increased. To understand how specific and non-specific interactions between the solute and the solvent affected the fluorosolvatochromism of II, we employed the four empirical scales model of Catalán. The obtained results demonstrated that intramolecular charge transfer played a crucial role in the fluorescence behavior of II. To provide a molecular-level explanation for the experimental spectral properties, we utilized the DFT and TD-DFT/B3LYP/6-31 + G(d) computational methods with the IEFPCM implicit solvation approach. The spectral differences between II and III were rationalized in terms of the frontier molecular orbitals (FMOs: the HOMO and LUMO), where distinct natures were observed among the examined derivatives. This study offers valuable insights into the impact of methoxy substitution on the physical and chemical properties of chromeno[4,3-b]pyridine derivatives, specifically concerning their spectral properties as elucidated by their fluorosolvatochromic behavior.


Management of cerebrospinal fluid leaks after vestibular schwannoma surgery.
To evaluate the incidence and treatment of cerebrospinal fluid (CSF) leaks after resection of vestibular schwannomas and to propose a treatment algorithm for their management. Retrospective chart review. Tertiary referral center. Review of 1,922 subjects who underwent resection of vestibular schwannomas from 1970 to 2010. Surgical resection of vestibular schwannoma. Patient demographics, surgical approach used, CSF leak incidence, meningitis, treatment, and success in the management of CSF leaks. Postoperative CSF leaks were observed in 12.9% of our patients. There was no significant difference between the type of approach and the presence of CSF leak with translabyrinthine, suboccipital and middle fossa CSF leak rates of 12%, 12%, and 13%, respectively (p = 0.07). Patients presented with a wound leak or rhinorrhea almost equally. Ultimately, 92% of patients with rhinorrhea underwent surgical intervention. The probability of a patient with rhinorrhea requiring a second intervention was higher when the initial intervention was conservative rather than surgical. However, the probability of a patient with a wound leak requiring a second intervention was essentially the same when initially treated conservatively or surgically. Our data suggests that there is no difference in CSF leak rates between the different surgical approaches. The appropriate treatment strategy is dependent on the presentation of the CSF. Although conservative treatment is effective for managing wound leaks, it is less effective in managing patients with rhinorrhea. Therefore, surgical treatments should play an early role in the treatment algorithm of patients with CSF rhinorrhea.


Response of extrapyramidal and limbic neurotensin systems to phencyclidine treatment.
Although phencyclidine (PCP) has several neurochemical effects, the most pharmacologically relevant are thought to be its ability to antagonize the activity of N-methyl-D-aspartate (NMDA)-type glutamate receptors and to increase extracellular dopamine concentrations. In order to elucidate the nature and consequence of PCP actions on glutamatergic and dopaminergic pathways, this study examined the response of extrapyramidal and limbic neurotensin systems to this drug. Multiple, but not single, doses of PCP caused increases in striatal neurotensin-like immunoreactivity content of 150-200% of control. These effects were blocked by the dopamine D1 receptor antagonist, SCH 23390, suggesting they were caused by PCP-mediated enhanced dopamine activity at dopamine D1 receptors. In contrast, MK-801 (dizocilpine), a selective NMDA receptor antagonist that acts at the same site as PCP, had no effect on neurotensin-like immunoreactivity content when given alone. In addition, coadministration of MK-801 with PCP did not alter the effect of PCP on striatal neurotensin-like immunoreactivity content. This lack of effect suggests that the actions of PCP on NMDA receptors was not involved in the neurotensin response. The PCP effect on neurotensin striatal pathways also appeared not to be associated with the dopamine D2 or gamma-aminobutyric acid (GABA) systems: a possible role for the sigma receptor in this effect could not be eliminated. Administration of multiple doses of PCP also affected neurotensin-like immunoreactivity content in the nucleus accumbens (160% compared to control) and frontal cortex (40% compared to control), but not the substantia nigra. The neurotensin effects of PCP are compared to those of another psychotomimetic drug of abuse, methamphetamine.


Evaluating the Chase Utley Rule: The Association Between a Rule Change and Collision-Related Injuries in Major League Baseball.
Major League Baseball (MLB) adopted a rule change in 2016 to reduce the number of collisions that occur when a player slides into a base. The effect of rule 6.01(j) has not been quantified, and it remains unknown if this rule change has led to improved player safety. Rule 6.01(j) would be associated with a reduction in the number of collision-related injuries at second base. Cohort study; Level of evidence, 3. Using data from the MLB Health and Injury Tracking System, we quantified the number of collision-related injuries for defensive (ie, fielding) players in the infield at the major and minor league levels between the 2010 and 2019 seasons. We compared the median number of collision-related injuries for defensive players in the infield from before (2010-2015) to after (2016-2019) the implementation of rule 6.01(j) and also calculated the difference in location of the median from the seasons before versus after the rule change. An additional 3 analyses were performed to support or contradict a conclusion that any observed reduction in injuries at the start of the 2016 season was likely caused by the adoption of rule 6.01(j). The median number of collision-related injuries for defensive players at second base decreased from 58.5 to 37.5 injuries per season after the rule change, which was a 36% decrease (difference in location, 19.5 [95% CI, 5.0 to 31.0]; P = .019). In contrast, the median number of collision-related injuries at first base decreased by only 14.1%, from 49.5 before to 42.5 after the rule change (difference in location, -9.0 [95% CI, -4.0 to 18.0]; P = .16), and the median number of collision-related injuries per season at third base was unchanged at 15 per season. This rule change was associated with a decrease in the number of collision-related injuries, with the largest effect observed at second base, as expected.


Life-threatening hyperkalemia in severe heart failure.
The therapeutic course of patients with severe heart failure can be complicated by disturbances in potassium homeostasis. Although hypokalemia in more prevalent, hyperkalemia may occur. Among 730 consecutive patients admitted to the hospital because of heart failure, nine episodes of acute, life-threatening hyperkalemia (mean serum potassium level: 7.2 +/- 0.5 mEq/L) were diagnosed in six patients (0.8%) with severe chronic heart failure during maintenance oral potassium therapy and exacerbation of heart failure and/or after additional oral doses had been administered for correction of hypokalemia. Of nine hyperkalemic episodes observed, one was fatal, seven episodes were successfully treated, and one resolved spontaneously. Only one patient was receiving an angiotensin-converting enzyme inhibitor. An awareness of this complication and the clinical setting in which it is likely to occur could lead to earlier recognition and successful management.


Effect of coprophagy on bioavailability of iron from plant foods fed to anemic rats.
Effects of coprophagy and coprophagy preventing device on iron bioavailability were evaluated in two experiments. In Experiment 1, rats were fed diets with FeSO4, spinach, bran cereal or cornmeal as the iron source. The rats in each diet group were fitted with collars, sham-collars or not fitted with collars (control). In Experiment 2, rats were fed diets with FeSO4 or green peas as the iron source and were fitted with collars, tail cups, sham-collars or not fitted with any device (control). Preventing coprophagy reduced hemoglobin regeneration efficiency (HRE) of rats fed bran cereal, green peas, spinach or cornmeal diets by 26 (P less than .05), 24(P less than .05), 22(P less than .05) and 11% (not significant), respectively. Preventing coprophagy in rats fed FeSO4 diet did not significantly reduce HRE. Sham-collaring reduced (P less than .05) HRE of rats fed the FeSO4 diet by 12 and 13% but did not significantly affect HRE in rats fed food iron sources. It was more convenient and effective to prevent coprophagy with collars than with tail cups. Differences in bioavailability between food and FeSO4 iron due to coprophagy may be explained based on two gastrointestinal nonheme iron pools, complexed and highly soluble.


[Assessment of microcirculation in critically ill patients].
Adequate organ supply of oxygen and of nutrients depends on microcirculation. Impaired microcirculation may result in temporary or irreversible loss of function. Therefore, critically ill patients require early diagnosis and therapy of microcirculatory disorders. Besides surrogate parameters of microcirculation like urine production or serum lactate levels, direct visualization became possible with sidestream darkfield intravital microscopy. This technique has been evaluated in clinical studies focusing on early diagnosis and therapy in cardiogenic shock like vasopressors, nitrates, or circulatory assist devices. Further studies evaluating measurements of microcirculation are necessary before a general recommendation for its routine use can be made.


Structural characterization of two Hericium erinaceus polysaccharides and their protective effects on the alcohol-induced gastric mucosal injury.
Hericium erinaceus, a traditional edible mushroom, is known as a medicine food homology to ameliorate gastrointestinal diseases. However, the relationship between the structural characteristics of Hericium erinaceus and its stomach-protecting activity remains unclear. Here, the structural properties of two polysaccharides from Hericium erinaceus, mycelium polysaccharide (HMP) and fruiting body polysaccharide (HFP) were investigated by spectral approaches. The results showed that the distribution of HMP was more uniform compared to HFP. Both HMP and HFP have triple helix structures, but the HMP conformation showed greater stability. Subsequently, the preventive effect of HMP and HFP on ethanol-induced gastric mucosal injury was also evaluated in rats and GES-1 cells, and it showed that both HMP and HFP had significant protective activity against gastric mucosal injury, but HMP showed better activity than HFP. These results suggested that conformational stability polysaccharide in Hericium erinaceus is more related to its gastric-protecting activity.


Evidence for stereospecific phospholipid-cholesterol interaction in lipid bilayers.
The CH2 proton NMR linewidths of sn-3 and sn-1 dipalmitoyl phosphatidylcholine respond differently to the addition of cholesterol to the lipid vesicles. This result points to a stereospecific phospholipid-cholesterol interaction in the "hydrogen belt" region.


Transplantation of brain tissue in the brain of adult rats.
Brain tissues obtained from rat embryos were transplanted in the forebrain and/or cerebellum of the adult rats. The transplants survived, grew and achieved normal cellular and cytoarchitectural differentiation. They had become anatomically integrated with the host brain. The animals did not show any obviously detectable abnormal behavior or pathology of the brain. The transplants survived as long as the animals did suggesting that they had become a part and parcel of the host brain.


Brain mechanisms of mammalian fluid homeostasis: insights from use of immediate early gene mapping.
A comprehensive review of the literature through mid-1997 is presented on the application of immediate early gene mapping to problems related to brain mechanisms of fluid homeostasis and cardiovascular regulation in mammals. First, the basic mechanisms of fluid intake and the principles and pitfalls of immediate early gene mapping are briefly introduced. Then, data from several principal paradigms are reviewed. These include fluid deprivation and intracellular dehydration, both of which are associated with thirst and water intake. The contributions of peripheral sodium receptors, and of both hindbrain and forebrain integrative mechanisms are evaluated. Extracellular dehydration, and associated aspects of both thirst and sodium appetite are then reviewed. The contributions of both structures along the lamina terminalis and the hypothalamic magnocellular neurosecretory groups figure prominently in most of these paradigms. Effects of hypotension and hypertension are discussed, including data from the endogenous generation and the exogenous application of angiotensin II. Lastly, we summarize the contribution of the early gene mapping technique and consider briefly the prospects for new advances using this method.


Discovery of novel pyrazolo[1,5-a]pyrimidines as potent pan-Pim inhibitors by structure- and property-based drug design.
Pim kinases are promising targets for the development of cancer therapeutics. Among the three Pim isoforms, Pim-2 is particularly important in multiple myeloma, yet is the most difficult to inhibit due to its high affinity for ATP. We identified compound 1 via high throughput screening. Using property-based drug design and co-crystal structures with Pim-1 kinase to guide analog design, we were able to improve potency against all three Pim isoforms including a significant 10,000-fold gain against Pim-2. Compound 17 is a novel lead with low picomolar potency on all three Pim kinase isoforms.


Regulation of an enzyme cascade reaction by a DNA machine.
A strategy for the regulation of enzyme cascade reaction efficiency by a DNA machine in vitro is presented. Two cascade enzymes (GOx and HRP) are attached to the DNA machine, and the enzyme cascade reaction shows much higher efficiency when the two enzymes are brought closer by the DNA machine than when they are distant.


Bilirubin release induced by tumor necrosis factor in combination with galactosamine is toxic to mice.
Application of tumor necrosis factor (TNF) in combination with galactosamine (GalN) in mice causes severe apoptosis of hepatocytes, resulting in complete destruction of the liver. Administration of high levels of unconjugated bilirubin and abnormally high production of unconjugated bilirubin have been reported to cause liver damage and are associated with several human pathologies. Serum alanine aminotransferase as well as total and direct bilirubin levels in mice were determined. Bilirubin levels are shown to significantly increase after a challenge with TNF/GalN in mice. Pretreatment with a heme oxygenase-1 inhibitor significantly prevents this release in bilirubin and offers significant protection against TNF/GalN-induced lethality. A correlation between the release of unconjugated bilirubin and the toxicity accompanied with this release is provided.


Thiolated sodium alginate conjugates for mucoadhesive and controlled release behavior of metformin microspheres.
The absorption of BCS III drugs can be improved by inhibiting the P-glycoprotein (P-gp) efflux and by increasing the mucoadhesion of natural polymers. In the present study, an esterification of sodium alginate (SA) with thioglycolic acid (TGA) was applied for the preparation of thiolated sodium alginate (TSA). The Ellman's test was applied to quantify the thiol group and a di-sulphide bond test was performed to confirm any SS linkages. The FTIR, DSC, XRD, 1H NMR and charring point determinations were confirmed the thiol group of TSA. The gel like rheological properties with porcine mucous was confirmed by viscoelasticity properties and the mucoadhesion with the rabbit intestine was carried out after compression of 30 mg tablets of TSA. The content of thiol group was in the range of 320-730 μmoL/g of the polymer. The FTIR spectrum showed a characteristic peak of sulfhydryl group at 2557 cm-1 in TSA and the reduction of the charring point from 220 °C to 178 °C was confirmed the thiolation of TSA. A direct relationship of mucoadhesion and swelling was observed with the concentration of TGA and SA, respectively. The prepared microspheres were 2-7 μm in size, excellent rheological properties and non-fickian drug release behavior was observed.


Lacosamide cardiac safety: clinical trials in patients with partial-onset seizures.
To evaluate the cardiac safety of adjunctive lacosamide in a large pool of adults with partial-onset seizures (POS). Post-randomization changes from baseline for electrocardiographic (ECG) measurements, diagnostic findings, and relevant adverse events (AEs) were compared for pooled data from three randomized, placebo-controlled trials of adjunctive lacosamide for the treatment of POS. Lacosamide did not prolong the QTc interval or affect heart rate as determined by an analysis of data from patients randomized to lacosamide 200, 400, or 600 mg/day (n = 944) compared with placebo (n = 364). After 12-week maintenance treatment, mean changes from baseline for QRS duration were similar between the placebo and lacosamide 200 and 400 mg/day groups (0.0, -0.2, and 0.4 ms), but slightly increased for lacosamide 600 mg/day (2.3 ms). A small, dose-related mean increase in PR interval was observed (-0.3, 1.4, 4.4, and 6.6 ms for the placebo and lacosamide 200, 400, and 600 mg/day groups, respectively). First-degree atrioventricular (AV) block was reported as a non-serious AE in 0.0%, 0.7%, 0.2%, and 0.5% of patients in the same respective groups. Second- or higher degree AV block was not observed. There was no evidence of a PR-interval-related pharmacodynamic interaction of lacosamide with either carbamazepine or lamotrigine. Evaluation of the pooled cardiac safety data from patients with POS showed that adjunctive lacosamide at the maximum recommended dose (400 mg/day) was not clearly associated with any cardiac effect other than a small, dose-related increase in PR interval that had no evident symptomatic consequence.


Drug-resistant epilepsy in adults: Outcome trajectories after failure of two medications.
To examine the seizure trajectories of adults with epilepsy developing drug-resistant epilepsy (DRE) and to identify the predictors of seizure trajectory outcome. Adult patients failing two antiepileptic drugs (AEDs) due to inefficacy and starting their third AED at a tertiary epilepsy center were followed for seizure trajectory outcome during medical management. Seizure trajectories were categorized into one of four patterns: (1) course with constant seizures; (2) fluctuating course; (3) delayed attainment of seizure freedom (seizure freedom delayed for >12 months after start of the study, but patient stayed in seizure freedom); and (4) early attainment of seizure freedom (within 12 months of starting study). Multiple ordinal logistic regression models were used to estimate the association between trajectory categories and clinical factors. Four hundred three adult patients met the eligibility criteria. Of these, 212 (53%) never achieved a seizure-free period of a year or more. The trajectories of 63 patients (16%) had a complex fluctuating trajectory, 62 (15%) had delayed onset of seizure freedom, and 66 (16%) had an early seizure freedom. Independent predictors associated with more favorable outcome trajectories were epilepsy type and length of follow-up. Specifically, compared to patients with focal epilepsy of temporal lobe, patients with focal epilepsy of occipital lobe (OR 3.80, 95% confidence interval [CI] 1.00-14.51, p = 0.04), generalized genetic (OR 3.23, 95% CI 1.88-5.57, p < 0.0001), unclear epilepsy type (OR 3.82, 95% CI 1.53-9.52, p < 0.005), and both focal and generalized epilepsy(OR 11.73, 95% CI 1.69-81.34, p = 0.01) were significantly more likely to experience a better trajectory pattern. Examination of patterns of seizure trajectory of patients with incident DRE showed that 31% were in continuous seizure freedom at the end of the observation period.


Regulation of endothelial tissue plasminogen activator and plasminogen activator inhibitor type 1 synthesis by diacylglycerol, phorbol ester, and thrombin.
The influence of diacylglycerols, which are physiological activators of protein kinase C, on the production of tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor type 1 (PAI-1) by human umbilical vein endothelial cells (HUVEC) was studied in order to gain insight into the regulation of fibrinolysis by these cells. 1,2-dioctanoyl-sn-glycerol (diC8) stimulated tPA production in a dose- and time-dependent manner. The tPA antigen in cell supernatants increased from 0.9 ng/10(6) cells in unstimulated cells to 12.4 ng (10(6) cells after incubation with 400 microM diC8 for 24 hours. In contrast, PAI-1 production was not influenced by diC8, whereas phorbol 12-myristate 13-acetate (PMA) or thrombin stimulated both, tPA and PAI-1 production by HUVEC. Staurosporine and H7, which are inhibitors of protein kinase C, inhibited tPA synthesis by HUVEC. The degree of inhibition was dependent on the agonist used. While diC8-induced tPA production was inhibited to more than 80% by H7 (10 microM) and staurosporine (10 nM), higher doses of inhibitors were required to inhibit thrombin- and PMA-induced tPA production. Thrombin-induced PAI-1 production was inhibited to more than 80% by H7 (10 microM) and to about 50% by staurosporine, whereas PMA-induced PAI-1 production was not inhibited by staurosporine, and only to about 50% by higher doses of H7 (30 microM). These data suggest that activation of protein kinase C is a common intracellular trigger mechanism for the induction of tPA synthesis by HUVEC. Protein kinase C is most likely also involved in the regulation of PAI-1 synthesis by HUVEC.


Copper nanoparticle-embellished Zr-based metal-organic framework for electrocatalytic hydrogen evolution reaction.
Copper nanoparticles (Cu NPs) have gained immense popularity in catalysis by virtue of their impressive properties and earth abundance. Herein, we incorporated small-sized copper nanoparticles into the amine-functionalized NU-1000 MOF and used this composite material as an effective catalyst for electrocatalytic Hydrogen Evolution Reaction (HER) studies.


Heat- and cold-shock responses in Fusarium graminearum 3 acetyl- and 15 acetyl-deoxynivalenol chemotypes.
Fusarium graminearum Schwabe is the primary cause of Fusarium head blight (FHB) in North America. Chemically distinct F. graminearum sub-populations can be identified based on the type or composition of deoxynivalenol (DON) mycotoxin derivatives, including 3-acetyl (3-ADON) and 15-acetyl (15-ADON). The evaluation of randomly selected 3-ADON and 15-ADON isolates, collected from spring wheat throughout Canada, was performed using thin layer chromatography (TLC), high-performance liquid chromatography (HPLC), ice-nucleation activity (INA), and heat and cold tolerance tests conducted within a temperature range of -70°C to 65°C. The results indicated that the 3-ADON sub-population, which is responsible for the highest disease severity and has rapidly displaced the 15-ADON sub-population, produces more DON and zearalenone (ZEA) than the 15-ADON sub-population when exposed to heat and cold. Following exposures (1 and 2 h) to extremely high or low temperatures, 3-ADON isolates exhibited faster mycelial growth than 15-ADON isolates. In addition, the warmest temperature at which INA activity occurred was in 3-ADON (-3.6°C) vs. 15-ADON (-5.1°C). Taken together, these features suggest that the newly emerging 3-ADON sub-population is more resilient than the resident 15-ADON sub-population. Overall, the differences between the two sub-populations could provide new insights into FHB epidemiology and if validated under field conditions, may provide important information for predicting future FHB epidemics.


Adaptation of the Workflow Integration Survey to Turkey: A Validity and Reliability Study.
Background and Purpose: Electronic health record systems (EHRSs) are widely used to record patients' data and should be compatible with nurses' workflow. The purpose of this study was to adapt the Workflow Integration Survey (WIS) to the Turkish language and examine the reliability and validity measures of the Turkish version of the scale. Methods: In this methodological study, data were collected between December 2019 and February 2020 from 120 nurses. This study included the following phases: translation and evaluation of the content validity; explanatory and confirmatory factor analyses (CFAs) and reliability analysis. The intraclass correlation coefficient (ICC) was used for the test-retest reliability with 30 nurses. Results: The results of CFA revealed a two factors' structure, and these two factors explained 50.57% of the total variance. This was confirmed (χ2/df = 1.673, goodness-of-fit index [GFI] = 0.948, incremental fit index [IFI] = 0.923, comparative fit index [CFI] = 0.918, root mean square error of approximation [RMSEA] = 0.075, and standardized root mean square residual [SRMR] = 0.0604) using structural equation modeling. The total Cronbach's alpha value was found to be .702, .636, and .649 for the subscales. The intraclass correlation coefficient (ICC) was calculated for test-retest reliability and was found to be 0.871. Conclusions: The validity and reliability of the WIS have been found to be sufficient. It is recommended that the validity and reliability studies on the WIS be conducted in different hospitals with a larger number of participants. Furthermore, the use of the scale in cross-cultural studies to evaluate the compatibility of EHRSs with nurses' workflow in different cultures is also suggested.


Action Africa!
In Sub-Saharan Africa because of the prevailing economy, the equipping of neurological and neurosurgical services, as well the training of younger colleagues remains a recurrent problem. Therefore, all currently available resources ought to be mobilized and put together to obtain very rapid, short-term results. This is not a dream. The forces of the improvement of development lie in our hands.


Detection of circulating cancer cells with K-ras oncogene using membrane array.
K-ras oncogene is frequently found in human cancers and thus may serve as a potential diagnostic marker for cancer cells in circulation. So far, there is no reliable method for detecting cancer cells with K-ras oncogene in peripheral blood. The objective of this study was to develop a diagnostic membrane array using activated K-ras oncogene-associated molecules as detection targets. In our previous study, cDNA microarray analysis showed that there were 94 genes differentially expressed in K-ras mutant stably transfected adrenocortical cells. In the present study, we obtained 22 up-regulated genes in the closest relation to K-ras oncogene through bioinformatic analysis. At first, we carried out membrane array analysis by using in vitro culture cells. We demonstrated that this diagnostic technique was feasible and highly sensitive. A number as low as 5 cancer cells bearing K-ras oncogene in 1 ml of blood could be distinctively detected. Then, we collected blood specimens from 76 cancer patients. Direct sequencing analysis of these 76 samples showed that K-ras mutation was present in 43 patients with mutation sites mainly at codons 13, 15 and 61, which have been commonly established to be activated sites. We subsequently analyzed these 76 specimens with our diagnostic membrane array. Thirty-nine specimens were detected as positive for activated K-ras oncogene. Eighty percent (12/15) of mutations occurred at codon 13, 72.7% (8/11) at codon 61, and 88.9% (8/9) at codon 15 were accurately detected by our diagnostic membrane. Finally, through a series of biostatistical analyses, the sensitivity, specificity and accuracy of the diagnostic membrane array were 83.7, 90.9 and 86.8%, respectively. These findings suggest that the K-ras oncogene membrane array has a great potential for further investigation and clinical application.


Laparoscopic retroperitoneal splenopexy for wandering spleen: A novel technique using a three-incision retroperitoneal pouch.
Wandering spleen is a rare condition for which splenopexy is indicated to prevent splenic torsion. We present a novel laparoscopic splenopexy technique for wandering spleen based on creation of a three-incision retroperitoneal pouch. A 12-year-old male patient with abdominal distention and vomiting was transferred to our institution. Contrast-enhanced CT revealed a swollen wandering spleen with associated gastric volvulus, and the patient underwent laparoscopic surgery. A 5-mm camera port was inserted through an umbilical incision with two additional ports, one in the right upper abdomen and one in the left flank. Normal saline was injected into the retroperitoneal space from the left flank with a 23-G needle to create a retroperitoneal pouch. Three ventrodorsal peritoneal incisions were created at the same site in the peritoneum. The swollen spleen was inserted into the retroperitoneal pouch from the central incision, and the upper and lower poles of the spleen were exposed to the abdominal cavity from the cranial and caudal incisions to prevent splenic torsion. Finally, anterior gastropexy was performed. The postoperative period was uneventful. The patient was discharged on postoperative day 11 without complaints. As of 10 months after surgery, the patient had no recurrences of splenic torsion or gastric volvulus. In the present method, the retroperitoneal pouch was created without difficulty by injection of normal saline. Even in a patient with a swollen spleen, this novel method could prevent splenic torsion without using artificial materials or extensively dissecting the retroperitoneal space.


Clinical and genetic risk factors for aromatase inhibitor-associated arthralgia in breast cancer survivors.
Arthralgia is a common and debilitating toxicity of aromatase inhibitors (AI) that leads to premature drug discontinuation. We sought to evaluate the clinical and genetic risk factors associated with AI-associated arthralgia (AIAA). We performed a cross-sectional study among postmenopausal women with stage 0-III breast cancer who were prescribed a third-generation AI for adjuvant therapy. The primary outcome was patient-reported AIAA occurrence. We extracted and assayed germline DNA for single nucleotide polymorphisms (SNPs) of genes implicated in estrogen and inflammation pathways. Multivariable logistic regression models examined the association between demographic, clinical, and genetic factors and AIAA. Analyses were restricted to White participants. Among 1049 White participants, 543 (52%) reported AIAA. In multivariable analyses, women who had a college education [Adjusted Odds Ratio (AOR) 1.49, 95% Confidence Interval (CI) 1.00-2.20], had a more recent transition into menopause (<10 years) (5-10 years AOR 1.55, 95% CI 1.09-2.22; <5 years AOR 1.78, 95% CI 1.18-2.67), were within one year of starting AIs (AOR 1.61, 95% CI 1.08-2.40), and those who received chemotherapy (AOR 1.38, 95% CI 1.02-1.88) were significantly more likely to report AIAA. Additionally, SNP rs11648233 (HSD17B2) was significantly associated with higher odds of AIAA (AOR 2.21, 95% CI 1.55-3.16). Time since menopause and start of AIs, prior chemotherapy, and SNP rs11648233 within the HSD17B2 gene in the estrogen pathway were significantly associated with patient-reported AIAA. These findings suggest that clinical and genetic factors involved in estrogen withdrawal increase the risk of AIAA in postmenopausal breast cancer survivors.


Zea mays chloroplast ribosomal RNA genes are part of a 22,000 base pair inverted repeat.
Zea mays chloroplast rDNA exists in two identical units. Each unit contains one sequence for the 16, 23 and 5S rRNAs in the order given. The 16 and 23S sequences in each unit are separated by a 2100 base pair (bp) spacer. The DNA sequence for 5S RNA is closely linked to that for the 23S RNA. Within the above unit, the three RNAs are transcribed from a single DNA strand. The two rDNA units on the circular chloroplast DNA molecule are separated from each other by 18,500 bp in one direction and by 106,100 bp in the other direction. The two rDNA units have an inverted orientation with respect to each other. Each rDNA unit is part of a 22,000 bp sequence which is repeated with inverted orientation.


Length-tension relation of cat heart muscle studied by a segment-control method.
We studied the effects of the damaged ends on the length-tension relationship of the cat right ventricular papillary muscle during twitch contraction (30/min) using a newly developed segment-control system. The segment length (SL), defined as the distance between two thin black films attached to the central surface of the muscle with silicone grease, was measured by a Hamamatsu Photonics Width Analyzer (C1170) and Camera (C1000) and controlled with a servoactuator. The marker distance was determined to be either the central 24%-30% (short marker distance) or 47%-56% (long marker distance) of the muscle length (ML) at which the maximum developed twitch tension was observed (MLmax). The muscle was lengthened and shortened in a triangular fashion under both ML and SL isometric twitch modes over a period of 250s. The relationship between ML or SL and developed tension (DT, total minus resting tension) was obtained from the twitch tension data during the lengthening. The DT in the SL isometric twitch was always greater than that in the ML isometric twitch over the range of lengths studied. The slope of the SL-DT relation curve was much less steep than that of the ascending limb of the ML-DT relation curve. The gradient of the SL-DT relationship curve was greater for the long marker than for the short marker distance. The percentage shortening of SL in the ML isometric twitch increased with decreasing ML; it was greater for the short marker than for the long marker distance, particularly at shorter MLs.(ABSTRACT TRUNCATED AT 250 WORDS)


Passive Muscular Insufficiency: The Etiology of Gastrocnemius Equinus.
The current understanding is that gastrocnemius equinus is caused by a pathologic tightening of the muscle leading to decreased ankle joint dorsiflexion. However, an alternative hypothesis is that it is a normal limitation of available muscle length. Passive muscular insufficiency of the gastrocnemius muscle acts on a pathologic foot, which is poorly prepared to accept the forces from the gastrocnemius-soleus complex. In this manner, a normal gastrocnemius muscle exerts abnormal forces across the foot. This alternative hypothesis leads to a different interpretation of the current research literature and a potential new area of biomechanical research.


Rotational alignment of the lower extremity in the presence of total knee endoprosthesis: Reproducibility of torsion analyses using ultra-low-dose photon-counting CT.
Leg torsion analysis can provide valuable information in symptomatic patients after total knee arthroplasty. However, extensive beam-hardening and photon-starvation artifacts limit diagnostic assessability and dose reduction potential. For this study, we investigated the reproducibility of rotational measurements in ultra-low-dose photon-counting CT with spectral shaping via tin prefiltration. Employing a first-generation photon-counting CT, eight cadaveric specimens were examined with an established three-level scan protocol (hip: Sn 140, knee: Sn 100, ankle: Sn 100 kVp). In three body donors with unilateral knee endoprostheses, additional modified settings were applied (Sn 140 kVp at knee level). Protocols were executed with three dose levels (hip-knee-ankle, high-quality: 5.0-3.0-2.0 mGy, low-dose: 0.80-0.30-0.26 mGy, ultra-low-dose: 0.25-0.06-0.06 mGy). Six radiologists performed torsion analyses, additionally reporting their diagnostic confidence. Intraclass correlation coefficients (ICC) were calculated to assess interrater reliability. No significant differences were ascertained for femoral (p = 0.330), tibial (p = 0.177), and overall leg rotation measurements (p = 0.358) among high-quality, low-dose, and ultra-low-dose protocols. Interrater reliability was excellent for torsion of the femur (ICC 0.915, 95% confidence interval 0.871-0.947), tibia (0.960, 0.938-0.976), and overall leg (0.967, 0.945-0.981). In specimens with total knee endoprostheses, absolute rotational measurements were unaffected by dose level and tube voltage despite superior diagnostic confidence on the ipsilateral and contralateral sides with modified settings (p < 0.001). Combining the advantages of photon-counting CT and spectral shaping, reliable leg torsion analyses are feasible with ultra-low radiation exposure even in the presence of total knee endoprostheses.


Natural antioxidant formula ameliorates lipopolysaccharide-induced impairment of hippocampal neurogenesis and contextual fear memory through suppression of neuroinflammation in rats.
This study investigated the ameliorating effects of a natural antioxidant formula (NAF) consisting of Ginkgo biloba leaf extract, docosahexaenoic acid/eicosapentaenoic acid, ferulic acid, flaxseed oil, vitamin E, and vitamin B12 on a lipopolysaccharide (LPS)-induced cognitive dysfunction model in rats. Six-week-old rats received a diet containing 0.5% (w/w) NAF for 38 days from Day 1, and LPS (1 mg/kg body weight) was administered intraperitoneally once daily on Days 8 and 10. On Day 11, LPS alone increased interleukin-1β and tumor necrosis factor-α in the hippocampus and cerebral cortex and the numbers of M1-type microglia/macrophages and GFAP+ reactive astrocytes in the hilus of the hippocampal dentate gyrus. NAF treatment decreased brain proinflammatory cytokine levels and increased the number of M2-type microglia/macrophages. During Days 34-38, LPS alone impaired fear memory acquisition and the extinction learning process, and NAF facilitated fear extinction learning. On Day 38, LPS alone decreased the number of type-3 neural progenitor cells in the hippocampal neurogenic niche, and NAF restored the number of type-3 neural progenitor cells and increased the numbers of both immature granule cells in the neurogenic niche and reelin+ hilar interneurons. Thus, NAF exhibited anti-inflammatory effects and ameliorated LPS-induced adverse effects on hippocampal neurogenesis and fear memory learning, possibly through amplification of reelin signaling by hilar interneurons. These results suggest that neuroinflammation is a key factor in the development of LPS-induced impairment of fear memory learning, and supplementation with NAF in the present study helped to prevent hippocampal neurogenesis and disruptive neurobehaviors caused by neuroinflammation.


Chronic calcific pancreatitis in association with celiac disease.
Painless pancreatitis with extensive calcification and villous atrophy of the small intestine was observed in a nonalcoholic female patient. The etiology of villous atrophy could not be established. The pathophysiological significance of this association is discussed.


Retraction note to: Can fresh embryo transfers be replaced by cryopreserved-thawed embryo transfers in assisted reproductive cycles? A randomized controlled trial.
This article has been retracted at the request of the Editor and the ASRM Publications Committee, based on the results of an investigation which found serious methodological flaws in the study.


The immediate effect of streptokinase on serum lipoprotein(a) concentration and the effect of myocardial infarction on serum lipoprotein(a), apolipoproteins A1 and B, lipids and C-reactive protein.
Lipoprotein(a) (Lp(a)) has close structural homology with plasminogen and, at least in vitro, may interfere with fibrinolysis. Any changes in the serum Lp(a) concentration during and following myocardial infarction (MI) and whether the serum Lp(a) level is affected by streptokinase (SK) are therefore of interest. Serum Lp(a) levels immediately before and 3 h after completion of an intravenous infusion of SK in 39 patients with acute MI were not significantly different (median 31.3 mg/dl before and 35.9 mg/dl after). Furthermore, SK added during the serum Lp(a) assay did not affect the result, except at very high concentrations of SK (1000 units/ml). Serum Lp(a) and fasting lipids were measured daily for 3 days following definite MI in 13 patients and then after 14 and 42 days. There was no significant change in serum Lp(a) following MI. In marked contrast, C-reactive protein levels in these patients increased steeply immediately following MI. Thus, there was no early 'acute-phase response' in serum Lp(a) levels after MI. However, greater variation in its concentration was observed at day 14 than at other times. Serum cholesterol, apolipoprotein B and apolipoprotein A1 concentrations decreased significantly following MI, whereas a significant transient increase in serum triglycerides occurred. Forty-two days after MI all lipid and lipoprotein values had regained their day 1 levels, except for apo A1, which remained depressed.


Factors affecting the spatial distributions of thinly encrusting sponges from temperate waters.
Interactions along borders between pairs of species of abundant thinly encrusting sponges from a hard substratum subtidal community were investigated. Over a nine month study period the majority of borders between species did not shift in position. Several different forms of overgrowth were found but none lead to the death of the underlying species or subsequent attainment by the overgrower of the space occupied by the underlying sponge. Overgrowth in these types of sponges may be a defensive strategy aimed at maintaining presently occupied space. Only one species, Aplysilla rosea, gained space along borders and this occurred without any overgrowth of the space-losing species. This Dictyoceratid sponge was found to be very toxic toward a variety of indicator organisms and it is possible that these toxins form the basis of the mechanism behind its success in maintaining and obtaining space. In this community free space (unoccupied primary space) was available over 16% of the substratum due primarily to the grazing activities of an abundant echinoid Evechinus chloroticus. The encrusting sponges were damaged experimentally to investigate the influence of their different rates of regeneration on the outcome of competitive interactions. Again, Aplysilla rosea gained the most space but some species which did not gain space along borders gained space from neighbouring sponges in this experiment. Aplysilla rosea might be expected to be the dominant species in this community but this sponge was one of the least abundant species in this community. Although competitive interactions along sponge borders and clearings are useful to predict some aspects of sponge spatial patterns, other life history processes such as recruitment may be more important.


Cephalosporin antibiotics: molecules that respond to different needs.
Since the introduction of cephalothin in 1964, there has been a large number of cephalosporins synthesized and used clinically. Modification of the beta-acyl side chain has yielded compounds with stability against attack by plasmid and chromosomal beta-lactamases. The presence of methoxy groups at C-7 of the bicyclic cephalosporin nucleus has provided excellent activity against many anaerobic species. Changes in structure have also provided agents with extended half-lives, permitting twice a day dosing or single-dose prophylaxis. Cephalosporins clearly have come of age as agents to meet many different infectious needs.


A novel fluorometric assay for quantitative analysis of dihydrofolate reductase activity in biological samples.
In an effort to study the level of dihydrofolate reductase (DHFR), the main molecular target of antifolate drugs, in healthy and malignant tissues of human origin, a new and convenient fluorometric enzymatic assay has been developed. The technique measures the overall decrease in fluorescence emission at 454 nm (lambda ex = 342 nm) due to the contributions from coenzyme oxidation and substrate reduction. This technique was developed by using an enzyme purified from beef liver. All criteria of quality were checked: sensitivity, reproducibility and specificity made it suitable for low activity measurements. It was successfully applied to human tissue crude extracts.


Multiple chromatographic peaks of phenylalanyl-tRNA associated with spontaneous hydrolysis of Y base during isolation.
In contrast to the single phenylalanyl-tRNA found in normal cells, some tumours are known to have more than one phenylalanine isoacceptor. However, during certain steps in tRNA isolation from normal or tumour tissue, additional chromatographic peaks can be artificially produced which may be confused with the tumour-specific Phe-tRNA. Such procedures as extraction with unbuffered phenol and unbuffered gel filtration chromatography appear to produce adventitious isoacceptors by hydrolysis of Y base.


Inducible production of macrophage colony-stimulating factor (CSF-1) by malignant and normal human T cells.
The CEM-ON malignant T cell line and long-term cultured normal T cells can be induced to release CSF-1 in their culture supernatants. Chemical inducers (PMA + A23187) and, more interestingly, cytokines (tumor necrosis factor alpha (TNF alpha) and interleukin-1 alpha (IL-1 alpha)), as well as physiological (antigen + IL-2) or specific (anti-CD3 + IL-2 or PMA) stimuli, lead to rapid transient colony-stimulating factor-1 (CSF-1) gene expression and production of biologically active CSF-1. These data suggest that CSF-1 may play a role in the early phases of immune response.


qPCR assays to quantify genes and gene expression associated with microbial perchlorate reduction.
Quantitative PCR (qPCR) assays targeting cld (developed in this work) and pcrA (previously described) were used to quantify these perchlorate-related genes in a perchlorate-reducing enrichment culture. Transcript copies were quantified in perchlorate-reducing Rhodocyclaceae strain JDS4. Oxygen and nitrate inhibited expression of cld and pcrA.


Characterization of immune response induced against catalytic domain of botulinum neurotoxin type E.
Botulinum neurotoxins (BoNTs) represent a family of bacterial toxins responsible for neuroparalytic disease 'botulism' in human and animals. Their potential use as biological weapon led to their classification in category 'A' biowarfare agent by Centers for Disease Control and Prevention (CDC), USA. In present study, gene encoding full length catalytic domain of BoNT/E-LC was cloned, expressed and protein was purified using Ni-NTA chromatography. Humoral immune response was confirmed by Ig isotyping and cell-mediated immunity by cytokine profiling and intracellular staining for enumeration of IFN-γ secreting CD4+ and CD8+ T cells. Increased antibody titer with the predominance of IgG subtype was observed. An interaction between antibodies produced against rBoNT/E-LC was established that showed the specificity against BoNT/E in SPR assay. Animal protection with rBoNT/E-LC was conferred through both humoral and cellular immune responses. These findings were supported by cytokine profiling and flow cytometric analysis. Splenocytes stimulated with rBoNT/E-LC showed a 3.27 and 2.8 times increase in the IFN-γ secreting CD4+ and CD8+ T cells, respectively; in immunized group (P < 0.05). Protection against BoNT/E challenge tended to relate with increase in the percentage of rBoNT/E-LC specific IL-2 in the splenocytes supernatant (P = 0.034) and with IFN-γ-producing CD4+ T cell responses (P = 0.045). We have immunologically evaluated catalytically active rBoNT/E-LC. Our results provide valuable investigational report for immunoprophylactic role of catalytic domain of BoNT/E.


Circulating concentrations of fetal fibronectin do not reflect reduced trophoblastic invasion in preeclamptic pregnancies.
This prospective, nested, case-control study investigated whether maternal plasma fetal fibronectin reflects reduced trophoblastic invasion at 16 to 20 weeks in women who later have preeclampsia. Concentrations of fetal fibronectin were 8.7 +/- 2.6 micrograms/ml in women with preeclampsia and 8.1 +/- 2.5 micrograms/ml in matched controls (p greater than 0.5). These results are discussed.