New hydraulic insights into rapid sand filter bed backwashing using the Carman-Kozeny model.
Fluid flow through a bed of solid particles is an important process that occurs in full-scale water treatment operations. The Carman-Kozeny model remains highly popular for estimating the resistance across the bed. It is common practice to use particle shape factors in fixed bed state to match the predicted drag coefficient with experimentally obtained drag coefficients. In fluidised state, however, where the same particles are considered, this particle shape factor is usually simply omitted from the model without providing appropriate reasoning. In this research, it is shown that a shape factor is not a constant particle property but is dependent on the fluid properties as well. This dynamic shape factor for irregularly shaped grains increases from approximately 0.6 to 1.0 in fluidised state. We found that unstable packed beds in moderate up-flow conditions are pseudo-fixed and in a setting state. This results in a decreasing bed voidage and simultaneously in a decreasing drag coefficient, which seems quite contradictory. This can be explained by the collapse of local channels in the bed, leading to a more uniform flow distribution through the bed and improving the available surface for flow-through. Our experimental measurements show that the drag coefficient decreases considerably in the laminar and transition regions. This is most likely caused by particle orientation, realignment and rearrangement in particles' packing position. A thorough hydraulic analysis shows that up-flow filtration in rapid sand filters under backwash conditions causes the particle bed to collapse almost imperceptibly. In addition, an improved expression of the drag coefficient demonstrated that the Carman-Kozeny model constant, however often assumed to be constant, is in fact not constant for increasing flow rates. Furthermore, we propose a new pseudo-3D image analysis for particles with an irregular shape. In this way, we can explain the successful method using optimisation of the extended terminal sub-fluidisation wash (ETSW) filter backwashing procedure, in which turbidity and peaks in the number of particles are reduced with a positive effect on water quality.


The correlation between hematoma volume and outcome in ruptured posterior fossa arteriovenous malformations indicates the importance of surgical evacuation of hematomas.
The correlation between hematoma volume and outcome in ruptured arteriovenous malformations (AVM) with accompanying posterior fossa hematoma was retrospectively evaluated. Microsurgery operations were performed on 127 patients with intracranial AVM between January 1998 and January 2009 at our clinic. Fifteen (11.8%) patients were identified as suffering from posterior fossa AVM, and twelve of these patients presented with a cerebellar hematoma. All patients were clinically evaluated according to the following criteria: modified Rankin Scale (mRS) prior to surgery, Spetzler-Martin grade (SMG) of the AVMs, hematoma volume prior to surgery, and mRS following surgery. Postoperative mRS scores were significantly lower than preoperative scores (p=0.0001). Postoperative outcomes were concordant with the SMG of the AVMs (r=0.67, p=0.033), hematoma volume (r=0.537, p=0.072) and preoperative mRS scores (r=0.764, p=0.004). These analyses show that the postoperative mRS score is strongly correlated with a preoperative mRS score, hematoma volume and SMG. Posterior fossa AVMs present an increased risk for hemorrhage and for increased morbidity and mortality. Cases with hematoma should be operated on an urgent basis. We conclude that hematoma volume is a factor that impacts postoperative results and prognosis. SMG and preoperative mRS scores were also correlated with outcome.


Interleukin-8 expression in human nasal polyps.
The cytokine interleukin 8 (IL-8) has been shown to be a potent mediator of leukocyte recruitment and neovascularization in inflammatory and neoplastic diseases. In this study we hypothesize that IL-8 produced in the nasal polyp microenvironment is responsible for the leukocyte recruitment seen in nasal polyposis. To test this hypothesis we evaluated nasal polyps for distribution and content of IL-8 antigen with immunohistochemical techniques and radioimmunoassay to determine tissue levels of IL-8. The immunohistochemical results demonstrated that IL-8 antigen staining occurred predominantly within inflammatory cells and epithelium. IL-8 was detected in all nasal polyp tissue homogenates (a mean value of 1767 +/- 1633 pg/mg total protein (TP) with a range of 134 to 3668 pg/mg TP vs control specimens with a mean value of 77 pg/mg TP with a range of 0.09 to 255 pg/mg TP). These data demonstrate the presence and distribution and levels of IL-8 antigen in nasal polyps in vivo, supporting our hypothesis that local production of IL-8 could be an important factor in the sustained recruitment of leukocytes in nasal polyposis. Thus IL-8 likely plays a significant role in the pathogenesis of this disease process and therefore is a potential target for therapeutic intervention.


Subclinical Vitamin A Deficiency and Anemia among Women and Preschool Children from Northeast India.
Micronutrient deficiencies such as iron, Vitamin A, and iodine are important public health problems in India. The objective of the study was to assess subclinical Vitamin A deficiency (VAD) and anemia among women and preschool children from Northeast India. Methodology: A community-based cross-sectional study was carried out by adopting systematic sampling in Phek district of Nagaland. Data were collected from women on sociodemographic particulars, and finger prick blood was collected for hemoglobin and free-flowing drop for Vitamin A estimation on Whatman no. 1 filter paper. The overall prevalence of anemia was 27%, 40%, 44%, and 52% among preschool children, nonpregnant nonlactating women, lactating mothers, and pregnant women, respectively, whereas VAD was 37% among preschool children and 24%-32% among adult women. The prevalence of VAD was observed high among those living in kutcha house, illiteracy of head of households, big family size, and low per capita income. Anemia and VAD are important public health problems among tribal population in spite of the rich biodiversity.


Molecular characterization of a novel dipeptidyl peptidase like 2-short form (DPL2-s) that is highly expressed in the brain and lacks dipeptidyl peptidase activity.
DPL2 (DPP10) found at chromosome 2q14.1 is a member of the dipeptidyl peptidase IV (DPIV) gene family. Here we characterize a novel short DPL2 isoform (DPL2-s), a 789-amino acid protein, that differs from the previously described long DPL2 isoform (DPL2-l) at the N-terminal cytoplasmic domain by 13 amino acids. The two DPL2 isoforms use alternate first exons. DPL2 mRNA was expressed mainly in the brain and pancreas. Multiple forms of recombinant DPL2-s protein were observed in 293T cells, having mobilities 96 kDa, 100 kDa, and approximately 250 kDa which may represent soluble DPL2, transmembrane DPL2 and multimeric DPL2 respectively. DPL2 is glycosylated as a band shift is observed following PNGase F deglycosylation. DPL2-s was expressed primarily on the cell surface of transfected 293T and PC12 cells. DPL2-s exhibits high sequence homology with other DPIV peptidases, but lacks a catalytic serine residue and lacks dipeptidyl peptidase activity. Substitutions of Gly(644)-->Ser, Lys(643)Gly(644)-->TrpSer, or Asp(561)Lys(643)Gly(644)-->TyrTrpSer in the catalytic motif did not confer dipeptidyl peptidase activity upon DPL2-s. Thus, although DPL2 is similar in structure and sequence to the other dipeptidyl peptidases, it lacks vital residues required to confer dipeptidyl peptidase activity and has instead evolved features that enable it to act as an important component of voltage-gated potassium channels.


The effect of mitochondrial energization on cytochrome c oxidase kinetics as measured at low temperatures. II. The binding and reduction of dioxygen.
The effect of pre-energization of isolated mitochondria by ATP at room temperature upon the kinetics of oxygen intermediates (measured at very low temperatures) of cytochrome c oxidase has been studied. It was found that "energization" of mitochondria at room temperature had dramatic effects on several partial reactions of cytochrome aa3. Thus, in the "energized" frozen state, the rate of O2 binding to ferrous cytochrome a3 and the subsequent formation of the "peroxy" compound B are accelerated, while oxidation of cytochromes c and c1 is inhibited. These effects of ATP are abolished by oligomycin and uncoupling agents and may, therefore, be reflections of the coupling of the mitochondrial ATP synthetase to the respiratory chain at the level of cytochrome c oxidase, which is the basis of the mechanism of coupling respiration to ATP synthesis and respiratory control.


Local immune response in mice to Vibrio cholerae.
Cholera immunization schedules were investigated in mice, with emphasis placed on obtaining an immune response in the intestine. The most effective schedule for producing a good local response was found to be several orally-given priming doses of the organism followed after 14 days by an intravenous boosting dose. Major differences between the immune responses in the spleen and the intestine were noted.


Distinguishing Parotid Polymorphic Adenoma and Warthin Tumor Based on the CT Radiomics Nomogram: A Multicenter Study.
To develop, validate, and test a comprehensive radiomics prediction model to distinguish parotid polymorphic adenomas (PAs) and warthin tumors (WTs) using clinical data and enhanced computed tomography (CT) from a multicenter cohort. A total of 267 patients with PAs (n =172) or WTs (n = 95) from two hospitals were randomly divided into training (n =188) and validation (n =79) datasets. Radiomics features were extracted from the enhanced CT (arterial phase) followed by dimensionality reduction. Clinical and CT features were combined to establish a prediction model. A radiomics nomogram was constructed by combining RadScore and clinical factors. Moreover, an independent dataset of 31 patients from a third hospital was employed to test the model. Thus, the performance of the nomogram, radiomics signature, and clinical models was evaluated on the training, validation, and the independent testing datasets. Receiver operating characteristic (ROC) curves were used to compare the performance, and decision curve analysis (DCA) was used to evaluate the clinical effectiveness of the model. A total of 15 radiomics features were selected from CT data as the imaging markers to generate RadScores, and demographics or clinical data like age, sex, and smoking factors combined with RadScores were used to distinguish PAs and WTs based on multivariate logistic regression analyses. The results showed that radiomics nomograms combining clinical factors and RadScores provided satisfactory predictive values for distinguishing PAs from WTs, with areas under ROC curves (AUC) of 0.979, 0.922, and 0.903 for the training, validation, and the independent testing datasets, respectively. Decision curve analysis revealed that the radiomics nomogram outperformed the clinical factor models in terms of accuracy and effectiveness. CT-based radiomics nomograms combining RadScores and clinical factors can be used to identify PAs and WTs, which may help tumor management by clinicians.


Epigallocatechin 3-gallate: From green tea to cancer therapeutics.
Epigallocatechin 3-gallate (EGCG) possesses various biological functions, including anti-cancer and anti-inflammatory properties. EGCG is an abundant polyphenolic component originating from green tea extract that has exhibited versatile bioactivities in combating several cancers. This review highlights the pharmacological features of EGCG and its therapeutic implications in cancer and other metabolic diseases. It modulates numerous signaling pathways, regulating cells' undesired survival and proliferation, thus imparting strong tumor chemopreventive and therapeutic effects. EGCG initiates cell death through the intrinsic pathway and causes inhibition of EGFR, STAT3, and ERK pathways in several cancers. EGCG alters and inhibits ERK1/2, NF-κB, and Akt-mediated signaling, altering the Bcl-2 family proteins ratio and activating caspases in tumor cells. This review focuses on anti-cancer, anti-oxidant, anti-inflammatory, anti-angiogenesis, and apoptotic effects of EGCG. We further highlighted the potential of EGCG in different types of cancer, emphasizing clinical trials formulations that further improve our understanding of the therapeutic management of cancer and inflammatory diseases.


Preoperative chemotherapy and the risk of hepatotoxicity and morbidity after liver resection for metastatic colorectal cancer: a single institution experience.
Patients undergoing liver resection for colorectal cancer liver metastasis (CRCLM) are often treated with chemotherapy before surgery. However, the associations between chemotherapy, liver injury, perioperative outcomes, and other confounding factors remain unclear. This study investigates the effect of preoperative chemotherapy for CRCLM on nontumoral liver histology and perioperative outcomes in a contemporary cohort. Five hundred six patients underwent hepatic resection for CRCLM between April 2003 and March 2007. Histologic evaluation of nontumoral liver parenchyma for sinusoidal dilatation, steatosis, and steatohepatitis was performed in 384 cases for which tissue was available. Patient factors, tumor characteristics, chemotherapy regimens, histology of nontumoral liver, and perioperative morbidity were analyzed. Two hundred fifty patients (65%) received preoperative chemotherapy for a median duration of 24 weeks. Irinotecan, increased body mass index (BMI), and diabetes mellitus (DM) were associated with hepatic steatosis and steatohepatitis. Sinusoidal dilatation was not associated with chemotherapy or any clinicopathologic factors. Perioperative blood transfusion was independently associated with an increased risk of any complication. Major postoperative complications were independently associated with major (≥ 3 segments) resections (57%) and perioperative blood transfusion. The use of any preoperative chemotherapy decreased the odds of major complications. Liver-related complications were independently associated with major resection and blood transfusion, but not with chemotherapy. Three postoperative deaths (0.8%) occurred, all in patients who were not treated with chemotherapy and had no evidence of liver injury. With appropriate patient selection, liver resection for CRCLM can be safely performed in patients treated with preoperative chemotherapy.


Contrasting subsurface denitrification characteristics under temperate pasture lands and its implications for nutrient management in agricultural catchments.
Subsurface denitrification plays a key role in the reduction or 'attenuation' of nitrate contamination of groundwater and surface waters. We investigated subsurface denitrification characteristics in the vadose zone and shallow groundwater at four sites under pastoral farming in the Manawatū River catchment, located in the lower part of North Island, New Zealand. The denitrification potential of the vadose zone was determined by the laboratory incubation assays measuring the denitrifying enzyme activity (DEA) in soil samples collected from different soil horizons (up to 2.1 m below ground surface), whereas denitrification rates in shallow groundwaters were measured in situ by single-well, push-pull tests conducted in piezometers installed at multiple depths at the study sites. Soils and underlying geology, defining hydrogeologic settings, appear to influence the spatial variability of subsurface denitrification characteristics at the study sites. Where the vadose zone is thin and composed of coarse-textured soils, percolation of nitrate was evident in observed high nitrate-nitrogen concentrations (>5 mg L-1) in oxic and young shallow groundwaters, but low nitrate-nitrogen concentrations (<0.05 mg L-1) were observed in the reduced shallow groundwater found underneath the fine textured soils and/or a thick vadose zone. This was confirmed by the push-pull tests measuring denitrification rates from 0.08 to 1.07 mg N L-1 h-1 in the reduced shallow groundwaters (dissolved oxygen or DO < 0.5 mg L-1), while negligible in the oxic groundwaters (DO > 5 mg L-1) found at the study sites. These contrasting subsurface denitrification characteristics determine the ultimate delivery of nitrate losses from agricultural soils to receiving waters, where the fine textured thick vadose zone and reducing groundwater conditions offer nitrate reduction in the subsurface environment.


Unusual Extensive Physiologic Pigmentation of the Tongue: A Case Report.
The deposition of colored endogenous or exogenous substances in the tissues of the tongue may result in pigmented lesions of the lingual mucosa. The accurate identification of the underlying condition can be difficult to achieve and relies mainly on patient history and clinical and histological evaluation. We present the case of a 30-year-old male referred to our hospital with a chief complaint of extensive pigmentation of the lingual dorsum. A diagnosis of physiologic pigmentation based on clinical and histological findings was made. Since some life-threatening diseases may present solely as pigmented lesions of the tongue, an early diagnosis is of utmost importance.


Irreversible inhibition of Ca2+ release in saponin-treated macrophages by the photoaffinity derivative of inositol-1, 4, 5-trisphosphate.
D-myo-inositol-1,4,5-trisphosphate (InsP3) is a putative intracellular second messenger for the mobilization of Ca2+ from intracellular stores, in particular, the endoplasmic reticulum. Specific binding sites on the endoplasmic reticulum may participate in the InsP3-induced release of Ca2+ from the Ca2+ pool. To examine the specific binding sites on the endoplasmic reticulum, we synthesized an arylazide derivative of InsP3 for photoaffinity labelling; InsP3 coupled to p-azidobenzoic acid (InsP3-pAB) using N,N'-carbonyldiimidazole (CDI) was obtained at a 9-11% yield. Here, we report that InsP3-pAB, but not an arylazide derivative of inositol-1,4-bisphophate (Ins(1,4)P2), causes the irreversible inhibition of InsP3-induced release of Ca2+ in saponin-permeabilized photo-irradiated macrophages. The irreversible inhibition by InsP3-pAB after photo-irradiation was prevented by a 10-fold excess of unmodified InsP3.


Liver transplantation for HCC: validation of prognostic power of the RETREAT score for recurrence in a UK cohort.
The Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score as a prognostic index for recurrence has been reported previously and has not been validated outside the USA. Our study has validated the score in a single center UK cohort of patients being transplanted for HCC. LT for HCC between 2008 and 2018 at our center were analyzed. Recurrence-free survival (RFS) was compared by the RETREAT score and validated using Net Reclassification Improvement (NRI) by comparing it to Milan criteria. 346 adult HCC patients were transplanted of whom 313 were included. 28 (8.9%) had a recurrence. Summation of largest diameter and total number of viable tumors (HR = 1.19, p < 0.001), micro-/macro-vascular invasion (HR = 3.74, p = 0.002) and AFP>20 ng/ml (HR = 3.03, p = 0.005) were associated with recurrence on multivariate analysis. RFS decreased with increasing RETREAT score (log-rank p = 0.016). RETREAT performed better than Milan with significant NRI at 1- and 2-years post-transplant (0.43 (p = 0.004) and 0.38 (p = 0.03) respectively). LT outcomes using the revised UK criteria are equivalent to Milan criteria. Further, RETREAT score was validated as a prognostic index for the first time in a UK cohort and may assist risk stratification, selection for adjuvant therapies and guide surveillance.


Respiratory syncytial virus infection in 406 hospitalized premature infants: results from a prospective German multicentre database.
Premature birth, chronic lung disease of prematurity (CLD), congenital heart disease and immunodeficiency predispose to a higher morbidity and mortality in respiratory syncytial virus (RSV) infection. This study describes the preterms hospitalised with RSV infection from the prospective German DSM RSV Paed database. The DMS RSV Paed database was designed for the prospective multicentre documentation and analysis of clinically relevant aspects of the management of inpatients with RSV infection. This study covers six consecutive RSV seasons (1999-2005); the surveillance took place in 14 paediatric hospitals in Germany. Of the 1,568 prospectively documented RSV infections, 26% (n=406) were observed in preterms [vs. 1,162 children born at term (74%)] and 3% (n=50) had CLD, of which 49 had received treatment in the last 6 months ('CLDplus'). A significantly higher proportion in the preterm group had congenital heart disease, nosocomial infection, and neuromuscular impairment. There were significantly more children older than 24 months in the preterm group. The attributable mortality was 0.2% (n=2) in children born at term vs. 1.2% (n=5) in the preterm group (p=0.015) [preterm plus CLD 8.0% (n=4 of 50); McIntosh grade 1, 8.6% (n=3 of 35) and McIntosh Grade 4, 15% (n=3 of 20)]. Eight patients were categorized as 'palivizumab failures'. In the multivariate analysis, premature birth, CLD(plus), and nosocomial infection were significantly and independently associated with the combined outcome 'complicated course of disease'. In conclusion, this is the first prospective multicentre study from Germany that confirms the increased risk for severe RSV disease in preterms, in particular in those with CLD treated in the last 6 months before the onset of the infection. From the perspective of our results, the statements of the German Society of Paediatric Infectious Diseases considering the use of passive immunisation (2003) seem reasonable.


Developmental change in red blood cell volume: implication in screening infants and children for iron deficiency and thalassemia trait.
The mean corpuscular volumen when determined by electronic counter is an accurate tool for identification of children with microcytosis due to either iron deficiency or thalassemia trait. The purpose of this report is to describe the normal developmental changes in MCV that occur in children afler 6 months of age. In 211 healthy infants and children screened to exclude those with borderline or overt iron deficiency, thalassemia trait, or hemoglobinopathy, we found that the lower limit of normal for MCV is 70 ft between 10 and 17 months of age and that there is a gradual increase of MCV with age; the lower limit is 74 between 1 1/2 and 4 years and 76 between 4 and 7 years. All of these values are well below the minimum adult level of 80 fl.


Finnish case-control and family studies support PTPN22 R620W polymorphism as a risk factor in rheumatoid arthritis, but suggest only minimal or no effect in juvenile idiopathic arthritis.
Several studies have identified the PTPN22 allelic variant 1858 C/T that encodes the R620W amino-acid change as a putative susceptibility factor in autoimmune diseases. The current study was undertaken to examine a large cohort of Finnish rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) subjects using both population control and, importantly, family-based association methods. The latter is particularly important when, as is the case for the 1858 C/T polymorphism, the frequency of the variant allele (T) differs in both major ancestral populations and in subpopulations. The analysis of rheumatoid factor-positive 1030 RA probands from Finland provides strong support for association of this variant in both population studies (allele specific odds ratio (OR)=1.47, 95% confidence interval (CI)=1.27-1.70, P=3 x 10(-7)) and in family studies (P<10(-6)). In contrast, no allelic association was seen with JIA (230 probands) and only weak evidence for a genotypic effect of 1858T homozygotes was observed in this population.


Impact estimates of nosocomial bloodstream infection: looking from a different angle.
Mortality associated with nosocomial bloodstream infection is multifactorial. Source of infection, etiology, age, underlying disease, acute illness, and appropriateness of antimicrobial therapy all contribute to the final outcome. As such, estimates of mortality attributable to bloodstream infection may differ largely according to the presence or absence of risk factors in distinct patient populations. The adverse effect of nosocomial bloodstream infection for the individual patient is substantial, with about a doubling of the risk of death. Yet, in settings with a high standard of care in terms of infection prevention and control, the occurrence rate of bloodstream infection is relatively low and therefore its impact on overall ICU mortality rather limited. As a consequence, untargeted interventional studies focused on infection prevention should use occurrence rate of infection rather than mortality as outcome variable.


The prognostic significance of Nectin-2 and Nectin-4 expression in glial tumors.
Glial tumors are the most frequent neoplasms of the central nervous system in adults and despite recent advances in diagnosis and treatment of the disease, the prognosis of glioma is poor. Therefore, there is a great need to identify new prognostic factors and potential immunotherapeutic targets. Members of the Nectin family of proteins are gaining significant attention as possible diagnostic and immunotherapeutic targets in many solid tumors, but they have not been extensively investigated in glial tumors. The aim of the present study was to evaluate the expression of Nectin-2 and Nectin-4 in glial tumors of different grades, and to assess their prognostic value. The results showed heterogeneous expression of Nectin-2 and Nectin-4 in tumor cells and neuropil, with significantly higher Nectin-2 expression compared to Nectin-4, but without differences among tumor grades. In addition, the expression of Nectin-2 and Nectin-4 was associated with shorter survival times in patients with grade II/III gliomas. These results suggest that Nectin-2 and Nectin-4 expression may be used as an independent prognostic indicator for patients with II/III gliomas. This study contributes to the development of personalized care for patients with glioma and provides a basis for further research on nectin-based immunotherapy for brain tumors.


Subclavian steal syndrome presenting as recurrent pulmonary oedema associated with acute left ventricular diastolic dysfunction.
Subclavian steal syndrome typically presents as angina in patients with internal mammary artery grafts. Atypical clinical presentations have been rarely described. We report an unusual case of subclavian steal syndrome presenting as pulmonary oedema with acute left ventricular diastolic dysfunction and preserved ejection fraction in a patient with internal mammary artery graft and severe stenosis of the proximal left subclavian artery. After successful angioplasty and stenting of subclavian artery, the patient remained asymptomatic for six months, but then experienced acute diastolic dysfunction and recurrent pulmonary oedema associated with critical subclavian in-stent restenosis with stent deformation. This report points out that, in patients with internal mammary-to-LAD grafts, subclavian steal syndrome may present as acute left ventricular diastolic dysfunction and pulmonary oedema even in the presence of normal ejection fraction.


Defense response of a pepper cultivar cv. Sy-2 is induced at temperatures below 24°C.
Temperature is one of the most important environmental factors that influence plant growth and development. Recent studies imply that plants show various responses to non-extreme ambient temperatures. Previously, we have found that a pepper cultivar cv. Sy-2 (Capsicum chinense) shows developmental defects at temperatures below 24°C. In this study, to gain new insights into the temperature sensitivity of cv. Sy-2, temperature-sensitive genes were screened using microarray techniques. At restrictive temperature of 20°C, almost one-fourth of the 411 up-regulated genes were defense related or predicted to be defense related. Further expression analyses of several defense-related genes showed that defense-related genes in cv. Sy-2 were constitutively expressed at temperatures below 24°C. Moreover, accumulation of high level of salicylic acid (SA) in cv. Sy-2 grown at 20°C suggests that the defense response is activated in the absence of pathogens. To confirm that the defense response is induced in cv. Sy-2 below 24°C, we evaluated the resistance to biotrophic bacterial pathogen Xanthomonas campestris pv. vesicatoria and necrotrophic fungal pathogen Cercospora capsici. Cv. Sy-2 showed enhanced resistance to X. campestris pv. vesicatoria, but not to C. capsici.


Detection of exercise-induced ischemia by changes in B-type natriuretic peptides.
The purpose of this study was to examine the effect of exercise-induced ischemia on levels of B-type natriuretic peptide (BNP) and its inactive N-terminal fragment (NT-pro-BNP)and to determine whether measurement of these peptides can improve the diagnostic accuracy of exercise testing. The ability of exercise testing to detect coronary artery disease (CAD) is limited by modest sensitivity and specificity. B-type natriuretic peptides (NT-pro-BNP and BNP) are released by ventricular myocytes in response to wall stress. We hypothesized that exercise-induced ischemia results in increased wall stress and triggers release of NT-pro-BNP and BNP. A total of 74 patients with known CAD, normal left ventricular function, and normal resting levels of NT-pro-BNP and BNP who were referred for exercise testing with radionuclide imaging, and 21 healthy volunteers, were enrolled. Blood was drawn before and after maximal exercise and analyzed for NT-pro-BNP and BNP. Of the patients with CAD, 40 had ischemia on perfusion images and 34 did not. Median post-exercise increases in NT-pro-BNP and BNP (DeltaNT-pro-BNP and DeltaBNP) were approximately four-fold higher in the ischemic group than in the nonischemic group (DeltaNT-pro-BNP 14.5 vs. 4 pg/ml, p < 0.0001; DeltaBNP 36.5 vs. 7.5 pg/ml, p < 0.0001). In volunteers, median DeltaNT-pro-BNP was almost identical to that of the nonischemic patient group. At equal specificity to the electrocardiogram (ECG) (58.8%), the sensitivities of DeltaNT-pro-BNP and DeltaBNP for detecting ischemia were 90% and 80%, respectively; in contrast, the sensitivity of the exercise ECG was 37.5%. Measurement of exercise-induced increases in BNPs more than doubles the sensitivity of the exercise test for detecting ischemia with no loss of specificity.


Post-fixation horseradish peroxidase tracing in rat fetus and pups.
Horseradish peroxidase (HRP) has been shown to be applicable to fixed tissue in tracing projections in adult animals. This technique has several advantages in studying short projections in difficult attainable brain areas, especially with fetuses in utero. We have used this method to trace developing fibers (e.g., vestibulo-cerebellar connections) in rat fetuses and pups. It has been possible to make discrete and precise injections in any location. The quality of labeling by this method is distinctly related to the grade of fixation. Fixation grade determines how well HRP is anchored inside fibers and cell bodies. In optimally fixed preparations fibers and cell bodies are intensively stained with HRP up to over 3 mm from the center of an injection site. HRP is probably only taken up by damaged fibers so that the amount of fibers labeled is determined by the extent of the lesion caused by the injection pipette.


Investigation of ultra-low insertion speeds in an inelastic artificial cochlear model using custom-made cochlear implant electrodes.
Latest research on cochlear implantations focuses on hearing preservation during insertion of the implant's electrode array by reducing insertion trauma. One parameter which may influence trauma is insertion speed. The objective of this study was to extend the range of examined insertion speeds to include ultra-low velocities, being lower than manually feasible, and investigate whether these reduce insertion forces. 24 custom-made cochlear implant test samples were fabricated and inserted into an artificial scala tympani model using 12 different insertion speeds while measuring the resulting insertion forces. Three commercially available slim straight electrode carriers were inserted using the same setup to analyze whether the results are comparable. Insertions of the test samples using high insertion speeds (2.0/2.8 mm/s) showed significantly higher insertion forces than insertions done with low insertion speeds (0.2 mm/s) or ultra-low insertion speeds (< 0.1 mm/s). The insertions with commercial slim straight electrode arrays showed significantly reduced insertion forces when using a low insertion speed as well. Slow insertions showed significantly reduced insertion forces. Insertion speeds which are lower than manually feasible showed even lower insertion forces.


Personal values among undergraduate nursing students: A cross-sectional study.
Personal values influence nursing students' development of professional values, which affect professional outcomes, and how nursing students react to different situations. Personal values can be shaped by different factors, including culture, gender, and age. To explore personal values held by nursing students, and to verify if and how gender and year of study affect nursing students' personal values. A multicenter, cross-sectional study was used. The whole population of nursing undergraduate students available at the time was recruited from eight centers of two Universities, composing a sample of 947 students. Demographic data were collected and it was administered the Portrait Values Questionnaire. Ethical approval was obtained from the Institutional Review Boards of the University of the participating centers. The study sample was mainly composed of young (92.6%, n = 877), female (77.3%, n = 732), Italian (95.8%, n = 907), and unmarried (98.6%, n = 934) nursing students. The most important value for nursing students, consistently through the years of nursing school, was Self-transcendence, which has the motivational emphasis on helping others and selflessness. Then, we found that male students had higher levels of Power (p < 0.001) and Achievement (p = 0.031), while female students outscored male students in Benevolence (p = 0.005) and Security (p = 0.006). Year of study showed no statistically significant difference. Nursing students express high levels in hetero-directed values. Male nursing students, although they choose a stereotypically feminine profession, outscored females in stereotypical masculine values such as dominance and success. This is the first study that describes the personal value profile of undergraduate nursing students, according to the Theory of Basic Human Values, and it is a starting point for future research. Nursing educators might want to consider the findings from this study while guiding students in developing awareness for their personal values.


Telephone Consultation in Otorhinolaryngology During the Coronavirus Disease 2019 Pandemic: a Cross-sectional Analysis of Effectiveness and Satisfaction for Patients and Clinicians.
The COVID-19 pandemic has necessitated measures to minimise face-to-face interaction. We assessed the efficacy of teleconsultation and patient satisfaction in adult otorhinolaryngology clinic. A prospective review of telephone consultations over 6 months in a single district general hospital was conducted. Data was collected on the characteristics and outcomes of teleconsultations by clinicians, and a questionnaire was sent to patients. Of 304 telephone consultations, 115 were new and 189 were follow-up. Five percent of patients were listed for surgery. The discharge rate was 31%, largely comprising of patients with otorhinolaryngological symptoms. High clinician and patient satisfaction were reported by 90% and 96%, respectively. Telephone consultation was a good one-stop treat and discharge service for a number of otorhinolaryngological complaints such as hearing loss, tinnitus and recurrent tonsillitis. Patient and clinician satisfaction was high. Careful triaging of referrals for telephone consultation can potentially reduce the number of face-to-face clinic appointments.


MCC950/CRID3 potently targets the NACHT domain of wild-type NLRP3 but not disease-associated mutants for inflammasome inhibition.
The nucleotide-binding-domain (NBD)-and leucine-rich repeat (LRR)-containing (NLR) family, pyrin-domain-containing 3 (NLRP3) inflammasome drives pathological inflammation in a suite of autoimmune, metabolic, malignant, and neurodegenerative diseases. Additionally, NLRP3 gain-of-function point mutations cause systemic periodic fever syndromes that are collectively known as cryopyrin-associated periodic syndrome (CAPS). There is significant interest in the discovery and development of diarylsulfonylurea Cytokine Release Inhibitory Drugs (CRIDs) such as MCC950/CRID3, a potent and selective inhibitor of the NLRP3 inflammasome pathway, for the treatment of CAPS and other diseases. However, drug discovery efforts have been constrained by the lack of insight into the molecular target and mechanism by which these CRIDs inhibit the NLRP3 inflammasome pathway. Here, we show that the NAIP, CIITA, HET-E, and TP1 (NACHT) domain of NLRP3 is the molecular target of diarylsulfonylurea inhibitors. Interestingly, we find photoaffinity labeling (PAL) of the NACHT domain requires an intact (d)ATP-binding pocket and is substantially reduced for most CAPS-associated NLRP3 mutants. In concordance with this finding, MCC950/CRID3 failed to inhibit NLRP3-driven inflammatory pathology in two mouse models of CAPS. Moreover, it abolished circulating levels of interleukin (IL)-1β and IL-18 in lipopolysaccharide (LPS)-challenged wild-type mice but not in Nlrp3L351P knock-in mice and ex vivo-stimulated mutant macrophages. These results identify wild-type NLRP3 as the molecular target of MCC950/CRID3 and show that CAPS-related NLRP3 mutants escape efficient MCC950/CRID3 inhibition. Collectively, this work suggests that MCC950/CRID3-based therapies may effectively treat inflammation driven by wild-type NLRP3 but not CAPS-associated mutants.


A vibrational spectroscopic study of the borate mineral takedaite Ca3(BO3)2.
We have studied the mineral takedaite Ca3(BO3)2, a borate mineral of calcium using SEM with EDX and vibrational spectroscopy. Chemical analysis shows a homogeneous phase, composed of Ca. Boron was not detected. A very intense Raman band at 1087 cm(-1) is assigned to the BO stretching vibration of BO3 units. Additional Raman bands may be due to isotopic splitting. In the infrared spectrum, bands at 1218 cm(-1) and at 1163, 1262 and 1295 cm(-1) are assigned to the trigonal borate stretching modes. Raman bands at 712 and 715 cm(-1) are assigned to the in-plane bending modes of the BO3 units. Vibrational spectroscopy enables aspects of the molecular structure of takedaite to be assessed.


A Case of Exacerbation of Subclinical Hyperthyroidism after First Administration of BNT162b2 mRNA COVID-19 Vaccine.
COVID-19 vaccines are the most critical measure for controlling the COVID-19 pandemic; however, we have little information on their complications. We experienced a case of a patient who developed hyperthyroidism complicated with atrial fibrillation and heart failure on the sixth day after the first dose of COVID-19 vaccination. This case report shows the importance of considering hyperthyroidism as a possible complication after COVID-19 vaccination.


Dissecting the understanding of students about our teaching methods: A single institute, analytical cross-sectional study.
To measure the perception of medical students regarding different methods of active learning, and its association with the year of study. The analytical cross-sectional study was conducted at Shalamar Medical and Dental College, Lahore, Pakistan, from May to September 2020, and comprised medical students of either gender from first to final year of studies. Data was collected using an online questionnaire regarding different methods of active learning and e-learning. Perceptions and their association with the year of study were worked out. Data was analysed using SPSS 16. Of the 270 subjects, 155(57.4%) were females and 115(42.5%) were males. Overall, 39(14.4%) students were from the first year of studies, 32(11.9%) second, 47(17.4%) third, 120(44.4%) fourth and 32(11.9%) were from the final year of medical studies. Most students preferred class lectures as the teaching method of choice 240(89%), followed by small group discussions 156(58%). Students showed positive perception of different learning methods except e-learning 78(28.89%). The association between perceptions and the year of study was statistically significant (p< 0.05). Students apparently enjoyed using different interactive methods, but were apprehensive about online learning.


Microbial biotransformations of a synthetic immunomodulating agent, HR325.
The microbial biotransformation of HR325 [2-cyano-3-cyclopropyl-3-hydroxy-N-(4'-trifluoromethyl-3'-methylphenyl)- propenamide], a synthetic immunomodulating agent, has been investigated in order to be compared with animal metabolism and to prepare some metabolites which are difficult to obtain by chemical methods. Several fungal strains are able to completely metabolize this drug. Mortierella isabellina NRRL 1757 only achieves a benzylic hydroxylation on the aromatic methyl group, affording in high yield the corresponding hydroxymethyl derivative. In addition, other strains, such as Cunninghamella elegans ATCC 26269 or Beauveria bassiana ATCC 7159 can cleave both cyclopropyl and cyano groups in a new unknown oxidative biochemical reaction, which can be mimicked by m-chloroperbenzoate oxidation. The resulting cyanohydrin is hydrolyzed and reduced to a primary alcohol. In B. bassiana, the final incubation product is a beta-4-O-methylglucoside derivative of this alcohol, and has been fully characterized by independent synthesis. The different metabolic patterns of HR325 in the three fungal strains are discussed, and a mechanistic hypothesis about the oxidative cleavage of the right part of the molecule is proposed. The production of microbial metabolites is compared to animal metabolism in terms of structure and efficiency.


Negative pressure-induced hyperemia, a new modality in the monitoring of skin paddle containing free flaps.
In free tissue transfer, monitoring is paramount to timely detect vascular complications. Although various technical methods have been introduced, clinical flap monitoring and, particularly, capillary refill test (CRT) remain the gold standard. In pale flaps, CRT is challenging as it relies on the color difference between blanched and perfused skin. We proposed a new method of negative pressure-induced hyperemia (NPIH) using handheld electrical negative pressure devices to improve flap monitoring. Forty consecutive patients who received 42 free flaps in our institution were included in the study. Postoperatively, digital photographs were taken during CRT and NPIH, and the color difference (ΔE) was calculated based on the images. Additionally, three surgeons and three nurses evaluated the ease of assessment of capillary refill and NPIH on each flap using five grades. NPIH yielded a significantly higher color difference than CRT with a mean ΔE of 10.3 ± 3.3 versus 6.8 ± 4.2. Although for CRT, ΔE of 14 flaps was <5 and of seven flaps <3, all flaps had a ΔE of >5 for NPIH. Subjectively, both surgeons and nurses found NPIH in all flaps to be easier to assess with a mean score of 1.1 ± 0.3 versus 1.8 ± 1.1 for CRT. However, some flaps were found to be challenging or not assessable by CRT. NPIH represents a safe, easily applicable, and cheap addition to the established clinical and technical examination methods and may offer advantages over conventional CRT in detecting arterial complications in pale flaps.


Total Knee Arthroplasty Without Reduction of the Patella for Genu Valgum With Permanent Dislocation of the Patella: A Case of Nail Patella Syndrome.
A 75-year-old woman presented with progressive bilateral knee pain and severe genu valgum. She could walk utilizing braces and T-canes, with a 20° flexion contracture and 150° of maximum flexion. During knee flexion, the patella laterally dislocated. Radiographs demonstrated severe bilateral lateral tibiofemoral osteoarthritis and patellar dislocation. She underwent posterior-stabilized total knee arthroplasty without patellar reduction. After implantation, the knee range of motion was 0°-120°. Intraoperative findings revealed that the affected patella was too small, low articular cartilage volume resulted in the diagnosis of nail patella syndrome with the tetrad of nail dysplasia, patella dysplasia, elbow dysplasia, and iliac horn. At the 5-year follow-up visit, she could walk without a brace and had a knee range of motion (10°-135°) with clinically favorable results.


The efficacy of neoadjuvant EGFR-TKI therapy combined with radical surgery for stage IIIB lung adenocarcinoma harboring EGFR mutations: A retrospective analysis based on single center.
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) could provide survival benefits for locally advanced EGFR-mutant (EGFRm) non-small cell lung cancer (NSCLC). However, the role of radical surgery for EGFR-TKI treated stage IIIB EGFRm NSCLC remains controversial. This study attempted to assess the feasibility of neoadjuvant EGFR-TKI followed by radical surgery for stage IIIB EGFRm NSCLC. Between 2013 and 2020, EGFRm lung adenocarcinoma (LUAD) patients in clinical stage IIIB undergoing neoadjuvant EGFR-TKI followed by surgery (T-S-Arm) and EGFR-TKI alone (T-Arm) were reviewed retrospectively in Shanghai Pulmonary Hospital (SPH). The chi-square test, Student's t-test or Fisher's exact test was performed for analysis of baseline characteristics. Progression-free survival (PFS) was estimated using the Kaplan-Meier analysis. Multivariate Cox regression analysis was used to identify independent predictors of progression. A total of 43 patients were divided into T-S-Arm (n = 21) and T-Arm (n = 22). Patients were well-balanced between the two arms. The majority of patients were female (n = 25, 58.1%), non-smokers (n = 35, 81.4%), first-generation of EGFR-TKI treatment (n = 39, 90.7%), and exon 19 deletions (19-DEL) (n = 26, 60.5%). The median diagnostic age was 63.0 years [interquartile range (IQR), 54.0-67.5 years). At the cut-off date with June 30th 2022, median follow-up time was 28 months (IQR, 20-39 months). Neoadjuvant EGFR-TKI treatment followed by radical surgery could significantly improve the median PFS compared with patients underwent EGFR-TKI alone (23.0 months vs 14.5 months, P = 0.002). Multivariate Cox regression analysis demonstrated that radical surgery (T-S-Arm vs. T-Arm, HR: 0.406; 95% CI: 0.207-0.793, P = 0.027) was the only independent predictor for disease progression. The stratified analysis demonstrated patients with N2 disease could benefit from radical surgery (HR, 0.258; 95% CI, 0.107-0.618), especially for patients harboring L858R mutation (HR, 0.188; 95% CI, 0.059-0.604). For stage IIIB EGFRm NSCLC patients, the prognosis might be improved by neoadjuvant EGFR-TKI followed by radical surgery versus EGFR-TKI alone, especially for those with N2 disease and harboring L858R mutation.


Clinical characteristics and outcome of patients with acute mesenteric ischemia: a retrospective cohort analysis.
Acute mesenteric ischemia (AMI) is an uncommon, but life-threatening clinical entity due to late diagnosis resulting in irreversible ischemic bowel necrosis. The most common causes of AMI are the embolic occlusion and the acute thrombosis of the mesenteric circulation. Typical treatment is composed of an early revascularization of the mesenteric circulation followed by abdominal surgery for resection of nonviable intestine and restoration of the intestinal continuity, but the mortality rates remain high. A retrospective cohort analysis was conducted, aiming to evaluate clinical characteristics, performed surgical procedures and outcomes of patients with acute mesenteric ischemia who underwent emergency abdominal surgery at a high volume surgical center in Germany. Overall, 53 patients were identified with the intraoperatively proven diagnosis of AMI. Overall hospital mortality was with 62% comparable to the literature. Nineteen patients presented with an intraoperatively verified complete and non-reversible intestinal infarction without any angiographic or surgical option for a revascularization of the mesenteric circulation or an option for intestinal resection. From the rest of the patients, 14 underwent intestinal resection of the ischemic area without restoration of intestinal continuity; the other 20 underwent resection with a primary anastomosis to restore intestinal continuity. The mortality rate of these patients with curative-intended surgery remained high (41% of patients died). Pre- and postoperative hyperlactatemia were associated with lower survival of these patients. AMI remains a life-threatening abdominal emergency. Therapeutic approaches are highly depended on acting surgeon's decision, being affected by subjectively rated bowel viability and physical condition of the affected patient. Only selected patients with good bowel viability appear to be suitable for receiving primary anastomosis. The results clearly indicate the need for further research to develop therapeutic approaches for a better management of AMI and to improve outcome of affected patients.


Rare human mitochondrial HV lineages spread from the Near East and Caucasus during post-LGM and Neolithic expansions.
Of particular significance to human population history in Eurasia are the migratory events that connected the Near East to Europe after the Last Glacial Maximum (LGM). Utilizing 315 HV*(xH,V) mitogenomes, including 27 contemporary lineages first reported here, we found the genetic signatures for distinctive movements out of the Near East and South Caucasus both westward into Europe and eastward into South Asia. The parallel phylogeographies of rare, yet widely distributed HV*(xH,V) subclades reveal a connection between the Italian Peninsula and South Caucasus, resulting from at least two (post-LGM, Neolithic) waves of migration. Many of these subclades originated in a population ancestral to contemporary Armenians and Assyrians. One such subclade, HV1b-152, supports a postexilic, northern Mesopotamian origin for the Ashkenazi HV1b2 lineages. In agreement with ancient DNA findings, our phylogenetic analysis of HV12 and HV14, the two exclusively Asian subclades of HV*(xH,V), point to the migration of lineages originating in Iran to South Asia before and during the Neolithic period. With HV12 being one of the oldest HV subclades, our results support an origin of HV haplogroup in the region defined by Western Iran, Mesopotamia, and the South Caucasus, where the highest prevalence of HV has been found.


Antioxidant properties of Amaranthus hypochondriacus seeds and their effect on the liver of alcohol-treated rats.
Amaranth constitutes a valuable pseudocereal, due to its nutritional quality and its nutraceutical properties, which contribute to improve human health. This work evaluated the effect of a diet based on Amaranthus hypochondriacus (Ah) seed on oxidative stress and antioxidant status in the liver of rats sub-chronically exposed to ethanol. The seed extract was investigated for antioxidant capacity in vitro, showing an adequate content of total phenols and antioxidant activity elevated. For in vivo assays, four groups of six rats each were fed with an AIN-93 M diet for 28 days. In groups III and IV casein was replaced by Ah as the protein source; groups II and IV were received ethanol in the drinking water (20% v/v). When comparing groups IV and II, the following was observed: significant decrease in the activity of aspartate aminotransferase and content of malondialdehyde (p<0.001) in serum; decrease of malondialdehyde and increase in the activity and gene expression of Cu,Zn-superoxide dismutase, also, decrease in the NADPH oxidase transcript levels (p<0.05) in liver. Our data suggest that Ah is a good source of total phenols and exerts a protective effect in serum and in liver of rats intoxicated with ethanol.


Eight weeks of citicoline treatment does not perturb sleep/wake cycles in cocaine-dependent adults.
Citicoline (cytidine-5'-diphosphate) is a mononucleotide composed of ribose, cytosine, pyrophosphate, and choline, and is involved in the biosynthesis of the structural phosopholipids of cell membranes. Treatment with citicoline, improves memory in patients with dementia, and reduces damage to the brain after traumatic brain injury or stroke. Recent research has been conducted to assess whether citicoline is an effective treatment for cocaine dependence. In cocaine-dependent individuals, withdrawal from cocaine is associated with disturbed sleep, which may contribute to the high rate of relapse to cocaine use. Therefore, it is important to know the impact of citicoline on the sleep/wake cycle in these individuals in order to rate its overall efficacy. In this double-blind, placebo-controlled trial, the effects of citicoline treatment on the sleep/wake cycles of cocaine dependent participants were assessed. The results of the current study are reported as part of a larger study, consisting of an eight-week treatment period to assess the efficacy of longer-term treatment with citicoline at decreasing cocaine consumption in cocaine-dependent polydrug using participants. In this non-abstinent, cocaine-dependent population, citicoline had no effect on any of the sleep parameters measured including sleep efficiency, sleep latency, total sleep time, number of waking episodes, time awake per episode, amount of time in bed spent moving, number of sleep episodes, time asleep per episode, and amount of time in bed spent immobile. These data suggest that eight weeks of citicoline administration does not disturb sleep/wake cycles of cocaine-dependent individuals.


Electromyographic activity and rate of muscle fatigue of the quadriceps femoris during cycling exercise in the severe domain.
This study compared the activation pattern and the fatigue rate among the superficial muscles of the quadriceps femoris (QF) during severe cycling exercise. Peak oxygen consumption (VO(2)peak) and maximal accumulated oxygen Deficit (MAOD) were established by 10 well-trained male cyclists (27.5 ± 4.1 years, 71.0 ± 10.3 kg, 173.4 ± 6.6 cm, mean VO(2)peak 56.7 ± 4.4 ml·kg·min(-1), mean MAOD 5.7 ± 1.1 L). Muscle activity (electromyographic [EMG] signals) was obtained during the supramaximal constant workload test (MAOD) and expressed by root mean square (RMS) and median frequency (MF slope). The RMS of the QF, vastus lateralis (VL) and vastus medialis (VM) muscles were significantly higher than at the beginning after 75% of exercise duration, whereas for the rectus femoris (RF), this was observed after 50% of exercise duration (p ≤ 0.05). The slope of the MF was significantly higher in the RF, followed by the VL and VM (-3.13 ± 0.52 vs. -2.61 ± 0.62 vs. -1.81 ±0.56, respectively; p < 0.05). We conclude that RF may play an important role in limiting performance during severe cycling exercise.


Identity of alanine:glyoxylate aminotransferase with alanine:2-oxoglutarate aminotransferase in rat liver cytosol.
Rat liver soluble fraction contained 3 forms of alanine: glyoxylate aminotransferase. One with a pI of 5.2 and an Mr of approx. 110,000 was found to be identical with cytosolic alanine:2-oxoglutarate aminotransferase. The pI 6.0 enzyme with an Mr of approx. 220,000 was suggested to be from broken mitochondrial alanine:glyoxylate aminotransferase 2 and the pI 8.0 enzyme with an Mr of approx. 80,000 enzyme from broken peroxisomal and mitochondrial alanine:glyoxylate aminotransferase 1. These results suggest that the cytosolic alanine: glyoxylate aminotransferase activity is due to cytosolic alanine: 2-oxoglutarate aminotransferase.


Multi-mode non-Gaussian variational autoencoder network with missing sources for anomaly detection of complex electromechanical equipment.
Anomaly detection is crucial to the safety of complex electromechanical equipment. With the rapid accumulation of industrial data, intelligent methods without human intervention have become the mainstream of anomaly detection. Among them, variational autoencoder (VAE) performs well in anomaly detection with missing fault samples due to the self-supervised learning paradigm. However, the data from electromechanical equipment is usually non-Gaussian, making it difficult for the standard VAE based on Gaussian distribution to recognize the abnormal states. To solve the above problems, we proposed multi-mode non-Gaussian VAE (MNVAE) to detect anomalies from unknown distribution vibration signals without fault samples or prior knowledge. Firstly, the encoder maps the input to a Gaussian mixture distribution in latent space and samples a latent variable from it, after which the Householder Flow is applied to the latent variable to capture more abundant features. Finally, to describe the non-Gaussianity of the signal, Weibull distribution serves as the likelihood function of the reconstructed signal output from the decoder and as the basis for anomaly discrimination. In comparison to 6 related methods, our method yields the best results across various datasets. Through further experiments, the robustness of our method is proved and the proposed improvements are effective.


Toxic and mutagenic effects of carcinogens on the mitochondria of Saccharomyces cerevisiae.
Nineteen haploid yeast (Saccharomyces cerevisiae) strains were used to assess the relative growth inhibitory potencies on fermentable vs. non-fermentable media of a collection of carcinogenic and non-carcinogenic chemicals. The majority of carcinogens were distinctly more potent on the non-fermentable (glycerol) medium, where mitochrondrial function is required for growth, than on the fermentable medium, where it is not. The anti-mitochondrial selectivity indicated by these growth tests was much slighter for the non-carcinogens. Similarly most carcinogens induced the cytoplasmic petite mutation whereas the non-carcinogens did not. Five carcinogens which were tested impaired the development of cytochromes aa3 and b in glucose cultures. Six carcinogens, when tested, inhibited growth on three fermentable sugars, the utilisation of which requires mitochondrial function. Out of five carcinogens which were examined, four suppressed the surface-dependent phenomenon of fluocculence in a flocculating strain of yeast, at concentrations primarily affecting the mitochondrial system; the fifth had a similar but less pronounced effect.


Evaluation of the mechanical behaviour and estimation of the elastic properties of porcine zonular fibres.
The mechanical behaviour of zonular fibres greatly affects the accommodation process in mammalian eyes. This paper introduces a detailed measurement procedure for the purpose of obtaining the force-displacement diagram necessary to evaluate the mechanical properties of porcine zonular fibres in situ. It is a complex technique, keeping the integrity of the zonular bundles between the crystalline lens and the ciliary muscle cells. We present a brief description of the measurement procedure both in theory and in practice, along with the force-displacement diagrams acquired from a porcine sample group. The strengths of this newly developed method are the unequivocal force transmission between the sample and the transducer, and the intact connection between the ciliary body and the crystalline lens via zonular fibres. With the aid of these measurements, we define an estimated material model for the zonular apparatus both analytically and using the finite element method. The two different evaluation methods show close agreement in the calculated Young's modulus for the zonular fibres. The range of the calculated elastic modulus is 200-250 kPa. This new measuring method is adaptable to human specimens. Despite its complexity, the entire procedure and the evaluation part are reproducible. The constitutive model aims to shed light on the mechanics of the accommodation process.


Biomechanical effects of internal fixation with self-lock compression anti-rotation blade for Pauwels type III femoral neck fractures: a comparative finite element analysis.
Self-lock compression anti-rotation blade (SCAB) is a novel internal fixation implant for femoral neck fractures (FNF). We conducted this finite element analysis study to evaluate the biomechanical performances of SCAB combined with a cannulated screw for fixation of Pauwels type III FNF. Three finite element models of Pauwels type III FNF treated with various internal fixations were established: a: the inverted triangular parallel cannulated screw (3CS) model, b: the biplane double-supported screw fixation (BDSF) model, c: the SCAB combined with a cannulated screw model. Displacement and Von Mises stress of femurs and internal fixations under increasing loads as well as the average stress on fracture surfaces and maximum displacements on the X and Z axis of proximal fracture fragments at maximum load were measured and compared. The SCAB-based internal fixation exhibited superior biomechanical performances compared with 3CS and BDSF configurations, as the former resulted in lower parameters including displacement of the femur, Von Mises stress of internal fixation, stress on fracture surfaces as well as X and Z axis displacement of fracture fragments. Internal fixation using SCAB combined with a cannulated screw for Pauwels type III FNFs shows enough stability, with satisfied resistance to varus and shearing forces, which may provide a new option for the treatment of FNFs.


Recovery from lead induced biochemical and immunological alterations following combined treatment with DMSA and calcium disodium EDTA in rats.
The therapeutic potential of meso 2,3-dimercaptosuccinic acid (DMSA) and calcium disodium ethylenediamine tetraacetic acid (CaNa(2)EDTA) alone or in combination in reducing levels of lead in blood and other soft organs and reversing lead induced biochemical and immunological alterations were investigated after chronic low level lead exposure. Lead exposure produced a significant adverse effect on few selected haematopoietic, nervous, testicular and immunological variables. Conventional 5-day treatment with both DMSA and CaNa(2)EDTA individually was effective in inducing elimination of lead but the recovery of the altered biochemical and clinical indices was moderate. When given in combination for 5 days, (DMSA was administered orally twice daily before intraperitoneal CaNa(2)EDTA administration) they were more effective in depleting body lead burden and providing recoveries in the altered biochemical parameters. Along with the rapid removal of lead from body stores after combined treatment, the immunological variables also recovered spontaneously. However, the altered CNS disorders remained practically unchanged following 5 days of chelation therapy. Lead induced testicular alterations also showed some recoveries after combined treatment. The results indicate that combined DMSA and CaNa(2)EDTA treatment could be more beneficial than individual treatment with any of these agents.


Monitoring the effects of chronic alcohol consumption and abstinence on brain metabolism: a longitudinal proton magnetic resonance spectroscopy study.
This study focused on metabolic brain alterations in recently detoxified alcohol-dependent patients (S1) and their possible reversibility after 3 (S2) and 6 months (S3) of abstinence. Thirty-three alcohol-dependent patients and 30 healthy control subjects were studied with multislice proton magnetic resonance spectroscopic imaging (echo time = 135 msec at 1.5 T at three time points). In the patient group, we found that choline-containing compounds (Ch) in three frontal and cerebellar subregions at S1 were significantly below normal, whereas N-acetyl aspartate (NAA) differences did not reach significance but showed a trend toward below-normal values in frontal white matter. Abstinent patients showed a significant increase of Ch in all subregions at S2. At S3, no further significant metabolite changes in abstinent patients compared with S2 could be detected. No significant increase of NAA could be detected at follow-up. The increase of the Ch signal in the follow-up measurement after 3 months in abstinent alcohol-dependent patients supports the hypotheses of an alcohol- or alcohol detoxification-induced altered cerebral metabolism of lipids in membranes or myelin, which seems to be reversible with duration of alcohol abstinence.


Implementation and evaluation of STOPP/START criteria to address polypharmacy in older adults in an inpatient psychiatric setting.
There is a scarcity of research in applying the Screening Tool of Older Person's Prescriptions/Screening Tool to Alert to Right Treatment (STOPP/START) criteria to older adults admitted to a psychiatric hospital. The primary aim of this study was to determine the extent of polypharmacy in older adults admitted to a psychiatric hospital and to assess the number of STOPP/START triggers detected and recommended by pharmacists. Secondary objectives include evaluating if the STOPP/START criteria is a useful tool to improve prescribing in this setting by assessing the implementation rates of STOPP/START triggers. This was a prospective, longitudinal study in a psychiatry inpatient setting. Data were collected over a 7-week period. Explicit informed consent was obtained from participants. Medication reconciliation was completed and participants' medications were reviewed using STOPP/START criteria. The number of STOPP/START triggers detected, recommended and implemented was recorded. Sixty-two patients were included in the study. Ninety-four percent were prescribed ≥5 medications and 55% were prescribed ≥10 medications on admission. The mean number of medications prescribed per patient increased from 10 on admission to 12 at follow-up. Of 174 Potential Inappropriate Medications (PIMs) detected, 41% were recommended for review and, of these only 31% were implemented. 27% of the 77 Potential Prescribing Omissions (PPOs) detected were recommended for review and only 23% of those were implemented. STOPP/START did not reduce the prevalence of polypharmacy in this setting. The implementation rates observed in this study were much lower than those observed in non-psychiatric settings.


Comparison of Manual and Semi-Automatic [18F]PSMA-1007 PET Based Contouring Techniques for Intraprostatic Tumor Delineation in Patients With Primary Prostate Cancer and Validation With Histopathology as Standard of Reference.
Accurate contouring of intraprostatic gross tumor volume (GTV) is pivotal for successful delivery of focal therapies and for biopsy guidance in patients with primary prostate cancer (PCa). Contouring of GTVs, using 18-Fluor labeled tracer prostate specific membrane antigen positron emission tomography ([18F]PSMA-1007/PET) has not been examined yet. Ten Patients with primary PCa who underwent [18F]PSMA-1007 PET followed by radical prostatectomy were prospectively enrolled. Coregistered histopathological gross tumor volume (GTV-Histo) was used as standard of reference. PSMA-PET images were contoured on two ways: (1) manual contouring with PET scaling SUVmin-max: 0-10 was performed by three teams with different levels of experience. Team 1 repeated contouring at a different time point, resulting in n = 4 manual contours. (2) Semi-automatic contouring approaches using SUVmax thresholds of 20-50% were performed. Interobserver agreement was assessed for manual contouring by calculating the Dice Similarity Coefficient (DSC) and for all approaches sensitivity, specificity were calculated by dividing the prostate in each CT slice into four equal quadrants under consideration of histopathology as standard of reference. Manual contouring yielded an excellent interobserver agreement with a median DSC of 0.90 (range 0.87-0.94). Volumes derived from scaling SUVmin-max 0-10 showed no statistically significant difference from GTV-Histo and high sensitivities (median 87%, range 84-90%) and specificities (median 96%, range 96-100%). GTVs using semi-automatic segmentation applying a threshold of 20-40% of SUVmax showed no significant difference in absolute volumes to GTV-Histo, GTV-SUV50% was significantly smaller. Best performing semi-automatic contour (GTV-SUV20%) achieved high sensitivity (median 93%) and specificity (median 96%). There was no statistically significant difference to SUVmin-max 0-10. Manual contouring with PET scaling SUVmin-max 0-10 and semi-automatic contouring applying a threshold of 20% of SUVmax achieved high sensitivities and very high specificities and are recommended for [18F]PSMA-1007 PET based focal therapy approaches. Providing high specificities, semi-automatic approaches applying thresholds of 30-40% of SUVmax are recommend for biopsy guidance.


Nonlinear relationship between mycophenolate mofetil dose and mycophenolic acid exposure: implications for therapeutic drug monitoring.
Mycophenolate mofetil (MMF) is an immunosuppressive drug used in renal transplant patients. Upon oral administration it is hydrolyzed to the active agent mycophenolic acid (MPA). In renal transplant recipients, MMF therapy is optimal when the area under the curve of MPA is 30 to 60 mg·h/L. When MMF doses are adjusted, a linear relationship between dose and MPA exposure is assumed. In this study, the linearity of MMF pharmacokinetics was investigated. MPA concentration-time profiles from renal transplant recipients cotreated with cyclosporine (n = 140) or tacrolimus (n = 101) were analyzed retrospectively using nonlinear mixed-effects modeling. The correlation between the MMF dose and the pharmacokinetics parameters was evaluated. In the developed population pharmacokinetics model MPA clearance and the central volume of distribution were correlated with cyclosporine coadministration and time posttransplantation. The pharmacokinetics of MPA were not linear. Bioavailability decreased with increasing MMF doses. Compared with an MMF dose of 1000 mg (=100%), relative bioavailability was 123%, 111%, 94%, and 90% in patients receiving MMF doses of 250, 500, 1500, and 2000 mg in combination with cyclosporine (P < 0.001); respective values in tacrolimus-cotreated patients were 176%, 133%, 85%, and 76% (P < 0.001). Because of the decreasing relative bioavailability, MPA exposure will increase less than proportionally with increasing MMF doses. MMF exhibits nonlinear pharmacokinetics. This should be taken into account when performing therapeutic drug monitoring.


Triazole GHS-R1a antagonists JMV4208 and JMV3002 attenuate food intake, body weight, and adipose tissue mass in mice.
The only peripherally released orexigenic hormone, ghrelin, plays a key role in food intake and body weight regulation. Antagonizing the ghrelin receptor, GHS-R1a, represents a promising approach for anti-obesity therapy. In our study, two novel GHS-R1a antagonists JMV4208 and JMV3002, which are trisubstituted 1,2,4-triazoles, decreased food intake in fasted lean mice in a dose-dependent manner, with ED50 values of 5.25 and 2.05 mg/kg, respectively. Both compounds were stable in mouse blood, with half-lives of 90 min (JMV4208) and 60 min (JMV3002), and disappeared from the blood 8h after administration. Fourteen days of treatment with the ghrelin antagonists (20 mg/kg twice a day) decreased food intake, body weight and adipose tissue mass in mice with diet-induced obesity (DIO). These results are likely attributable to an impact on food intake reduction and an attenuated expression of the lipogenesis-promoting enzymes (acetyl-CoA carboxylase 1 in subcutaneous fat and fatty acid synthase in subcutaneous and intraperitoneal fat). The decrease in fat mass negatively impacted circulating leptin levels. These data suggest that JMV4208 and JMV3002 could be useful therapeutic agents for the treatment of obesity.


Basic symptoms influence real-life functioning and symptoms in individuals at high risk for psychosis.
To investigate potential clinical differences in high-risk profiles presenting with and without basic symptoms, and additionally investigate the association between basic symptoms and clinical symptoms, functioning, and cognition. High-risk individuals (n = 133) were stratified into individuals fulfilling ultra-high-risk (UHR) criteria (n = 59) and individuals fulfilling UHR+ basic symptoms criteria (BS) (n = 74). Group differences were assessed on clinical symptoms, real-life functioning, and cognition. Regression analyses were conducted to elucidate on the relationship between BS and clinical symptoms, functioning, neurocognition, and social cognition. The group fulfilling both UHR+ BS criteria had significantly more symptoms and lower real-life functioning and quality of life but not more cognitive deficits. BS influenced on attenuated psychotic, depressive, and general symptoms, but only modestly on negative symptoms. No relationship between BS and neuro- and social cognition was established except for an association with emotion recognition processing speed. BS influenced real-life functioning, and this finding was sustained when controlling for the effect of negative symptoms. Our findings indicate that BS contribute highly to the distress and symptom load of clinical high-risk individuals. Longitudinal findings are needed to establish the predictive validity of BS on high-risk individuals' clinical and functional prognosis.


H2 S donor improves heart function and vascular relaxation in diabetes.
Diabetes dramatically increases the risk of cardiovascular complications and mortality. Hydrogen sulphide plays an important role in reducing oxidative stress. Several studies demonstrated that hydrogen sulphide protects islet beta cells from oxidant stress damage and decreases apoptosis. The aim of the work is to investigate the effect of hydrogen sulphide donor on heart functions and endothelium-dependent relaxation of aortic smooth muscle in diabetes. Rats were divided into control and diabetic groups. Diabetes mellitus was induced with a single intraperitoneally injection of streptozotocin (60 mg kg-1 ). The functional cardiohemodynamic indicators were registered via microcatheter and Pressure-Volume System. The sodium hydrosulphide NaHS (15.8 mg kg-1 ) was administered intraperitoneally. The contractile activity of the muscle preparations of the thoracic aorta was recorded using a strain gauge. We demonstrate that the NaHS improves pumping function and restores diastolic heart function in streptozotocin-induced (STZ) diabetes rats. We show that pretreatment with NaHS increased the stroke volume by 43.1%, and the ejection fraction increased by 48.64%. NaHS improves the ventriculo-arterial coupling and increases by 3.4 times acetylcholine-induced relaxation of the aorta in diabetic rats. The inhibition of NOS activity by blocker L-NAME abolished NaHS-mediated vasodilatation in the intact endothelium of the aorta in diabetes. It indicates that the NaHS caused vasodilatation by a NOS-dependent mechanism. The exogenous hydrogen sulphide can improve pumping function and restore diastolic heart function in diabetes. The pretreatment with NaHS can prevent endothelial dysfunction in diabetes due to the NOS-dependent mechanism.


[Illustrations of visceral referred pain. "Head-less" Head's zones].
Reviewing anatomical, physiological and neurological standard literature for illustrations of referred visceral pain only one type of illustration can frequently be found, which is referred to as Treves and Keith. In fact, the original illustration as a model for most current pictures stems from the German edition of Sir Frederick Treves' famous book "Surgical Applied Anatomy" from 1914, which was reillustrated for didactical reasons for the German readership. While neither Treves and Keith nor the German illustrator Otto Kleinschmidt ever published any work on referred pain this illustration must have been adapted or copied from older sources by the illustrator. Therefore the comprehensive systematic original works before 1914 were reviewed, namely those of Sir Henry Head and Sir James Mackenzie. Due to the name of the phenomenon in the German literature of Head's zones, the illustrations were expected to be based mainly on Head's work. However, a comparison of all available illustrations led to the conclusion that Kleinschmidt chiefly used information from Mackenzie as a model for his illustration. Due to the inexact reproduction of Mackenzie's work by the illustrator some important features were lost that had been reported by the original authors. These include the phenomenon of Head's maximum points, which nowadays has fallen into oblivion.Therefore current charts, based on the illustration by Kleinschmidt from 1914, lack experimental evidence and appear to be a simplification of the observational results of both Head's and Mackenzie's original systematic works.


Analysis of risk factors and establishment of a risk prediction model for post-transplant diabetes mellitus after kidney transplantation.
Post-transplant diabetes mellitus (PTDM) is a known side effect in transplant recipients administered immunosuppressant drugs, such as tacrolimus. This study aimed to investigate the risk factors related to PTDM, and establish a risk prediction model for PTDM. In addition, we explored the effect of PTDM on the graft survival rate of kidney transplantation recipients. Patients with pre-diabetes mellitus before kidney transplant were excluded, and 495 kidney transplant recipients were included in our study, who were assigned to the non-PTDM and PTDM groups. The cumulative incidence was calculated at 3 months, 6 months, 1 year, 2 years, and 3 years post-transplantation. Laboratory tests were performed and the tacrolimus concentration, clinical prognosis, and adverse reactions were analyzed. Furthermore, binary logistic regression analysis was used to identify the independent risk factors of PTDM. Age ≥ 45 years (adjusted odds ratio [aOR] 2.25, 95% confidence interval [CI] 1.14-3.92; P = 0.015), body mass index (BMI) > 25 kg/m2 (aOR 3.12, 95% CI 2.29-5.43, P < 0.001), tacrolimus concentration > 10 ng/mL during the first 3 months post-transplantation (aOR 2.46, 95%CI 1.41-7.38; P < 0.001), transient hyperglycemia (aOR 4.53, 95% CI 1.86-8.03; P < 0.001), delayed graft function (DGF) (aOR 1.31, 95% CI 1.05-2.39; P = 0.019) and acute rejection (aOR 2.16, 95% CI 1.79-4.69; P = 0.005) were identified as independent risk factors of PTDM. The PTDM risk prediction model was developed by including the above six risk factors, and the area under the receiver operating characteristic curve was 0.916 (95% CI 0.862-0.954, P < 0.001). Furthermore, the cumulative graft survival rate was significantly higher in the non- PTDM group than in the PTDM group. Risk factors related to PTDM were age ≥ 45 years, BMI > 25 kg/m2, tacrolimus concentration > 10 ng/mL during the first 3 months post-transplantation, transient hyperglycemia, DGF and acute rejection.


Pulmonary fibrosis from molecular mechanisms to therapeutic interventions: lessons from post-COVID-19 patients.
Pulmonary fibrosis (PF) is characterised by several grades of chronic inflammation and collagen deposition in the interalveolar space and is a hallmark of interstitial lung diseases (ILDs). Recently, infectious agents have emerged as driving causes for PF development; however, the role of viral/bacterial infections in the initiation and propagation of PF is still debated. In this context, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the current coronavirus disease 2019 (COVID-19) pandemic, has been associated with acute respiratory distress syndrome (ARDS) and PF development. Although the infection by SARS-CoV-2 can be eradicated in most cases, the development of fibrotic lesions cannot be precluded; furthermore, whether these lesions are stable or progressive fibrotic events is still unknown. Herein, an overview of the main molecular mechanisms driving the fibrotic process together with the currently approved and newly proposed therapeutic solutions was given. Then, the most recent data that emerged from post-COVID-19 patients was discussed, in order to compare PF and COVID-19-dependent PF, highlighting shared and specific mechanisms. A better understanding of PF aetiology is certainly needed, also to develop effective therapeutic strategies and COVID-19 pathology is offering one more chance to do it. Overall, the work reported here could help to define new approaches for therapeutic intervention in the diversity of the ILD spectrum.


Erratum: In vitro and in vivo antiangiogenic activity of desacetylvinblastine monohydrazide through inhibition of VEGFR2 and Axl pathways.
[This corrects the article on p. 843 in vol. 6, PMID: 27186435.].


Thick slices from tomosynthesis data sets: phantom study for the evaluation of different algorithms.
Tomosynthesis is a 3-dimensional mammography technique that generates thin slices separated one to the other by typically 1 mm from source data sets. The relatively high image noise in these thin slices raises the value of 1-cm thick slices computed from the set of reconstructed slices for image interpretation. In an initial evaluation, we investigated the potential of different algorithms for generating thick slices from tomosynthesis source data (maximum intensity projection-MIP; average algorithm-AV, and image generation by means of a new algorithm, so-called softMip). The three postprocessing techniques were evaluated using a homogeneous phantom with one textured slab with a total thickness of about 5 cm in which two 0.5-cm-thick slabs contained objects to simulate microcalcifications, spiculated masses, and round masses. The phantom was examined by tomosynthesis (GE Healthcare). Microcalcifications were simulated by inclusion of calcium particles of four different sizes. The slabs containing the inclusions were examined in two different configurations: adjacent to each other and close to the detector and with the two slabs separated by two 1-cm thick breast equivalent material slabs. The reconstructed tomosynthesis slices were postprocessed using MIP, AV, and softMip to generate 1-cm thick slices with a lower noise level. The three postprocessing algorithms were assessed by calculating the resulting contrast versus background for the simulated microcalcifications and contrast-to-noise ratios (CNR) for the other objects. The CNRs of the simulated round and spiculated masses were most favorable for the thick slices generated with the average algorithm, followed by softMip and MIP. Contrast of the simulated microcalcifications was best for MIP, followed by softMip and average projections. Our results suggest that the additional generation of thick slices may improve the visualization of objects in tomosynthesis. This improvement differs from the different algorithms for microcalcifications, speculated objects, and round masses. SoftMip is a new approach combining features of MIP and average showing image properties in between MIP and AV.


Neighborhood socioeconomic deprivation and psychiatric medication purchases. Different neighborhood delineations, different results? A nationwide register-based multilevel study.
Previous studies of neighborhood socioeconomic deprivation and mental health treatment have shown mixed results. Multiple reviews have highlighted that the definition and measurement of neighborhoods can lead to different results, providing one explanation for these mixed findings. This study compares the use of micro-areas created using an automated redistricting algorithm and divided by physical barriers with the use of two administrative units, Danish parishes and postal codes. The geographical data are linked to Danish register data of the Danish population from age 16 in 2017, N = 4,347,001, to measure the association between the purchase of psychiatric medication and neighborhood socioeconomic deprivation using logistic multilevel models. Neighborhood socioeconomic deprivation is associated with a slightly increased probability of redeeming prescriptions for psychiatric medication after controlling for individual sociodemographic composition. However, this association was present only for micro-areas and not for parishes or postal codes. The results indicate that neighborhood effects on psychiatric medication purchases are affected by the neighborhood delineations used and that future studies should carefully consider how neighborhoods are defined and measured.


On the primary site of control in the spontaneous development of small-intestinal sucrase-isomaltase after birth.
We have compared the appearance in the small intestine of baby rabbits, of sucrase and isomaltase activities and of the sucrase-isomaltase mRNA. For the latter we used a cDNA probe encompassing approximately 4.1 kb from the 5'-end of pro-sucrase-isomaltase cDNA [(1986) Cell 46, 227-234]. Sucrase-isomaltase mRNA and the enzyme activities developed simultaneously from the 15th day after birth onwards. Over two orders of magnitude the enzymatic activities and sucrase-isomaltase mRNA matched one another closely, thus ruling out translation as the main site of biosynthetic control during spontaneous development, while rendering very probable transcription as the primary site of control. However, we cannot rule out the possibility that, prior to day 15, sucrase-isomaltase mRNA might be degraded so rapidly that it is not translated.


Expression of S100B protein levels in serum and cerebrospinal fluid with different forms of neuropsychiatric systemic lupus erythematosus.
The aim of this study is to determine S100B protein levels in serum and cerebrospinal fluid (CSF) in patients with different forms of neruopsychiatric systemic lupus erythematosus (NPSLE). There were 157 SLE patients (65 with and 92 without NPSLE, and 20 patients without rheumatic diseases served as controls) recruited in the present study. Serum and CSF S100B protein levels were measured by ELISA assay. Serum S100B protein levels in patients with NPSLE (0.179 +/- 0.095 microg/l) were significantly higher than the levels in patients without NPSLE (0.110 +/- 0.091 microg/l; p < 0.001) and in controls (0.103 +/- 0.065 microg/l; p = 0.005). Thus, the differences in serum levels between non-NPSLE patients and controls had no statistical significance. The serum and CSF S100B protein contents in patients with organic brain syndrome, seizures, cerebral vascular accident, and psychosis were significantly higher than those in controls (all p < 0.001). However, there was no significant difference in serum and CSF S100B protein levels among patients with headache, patients with neuropathy, and controls. In conclusion, serum and CSF S100B levels were raised in NPSLE, especially concerning patients with organic brain syndrome, seizures, cerebral vascular accident, and psychosis. The results obtained imply that S100B protein is possibly an available and complementary biochemical marker within evaluation of NPSLE and deserves further study.


The Atmospheric Pressure and Temperature Seem to Have No Effect on the Incidence of Rupture of Abdominal Aortic Aneurysm in a Mid-European Region.
This study aims to examine the relationship between weather changes (atmospheric pressure and temperature) and incidence of rupture of abdominal aortic aneurysm (AAA). All patients with ruptured infrarenal AAA and who were referred to our institution between August 1998 and August 2015 were prospectively entered into a database of which a retrospective review of a ruptured AAA was performed. The needed information about the daily atmospheric pressure and air temperature could be extracted from the meteorological unit in Cologne. During the study period (6,225 days), a total number of 154 patients with confirmed ruptured AAA were identified. Basic patients' characteristics are tabulated. The mean daily atmospheric pressure during the study was 1,004.04 ± 8.79 mBar ranging from 965.40-1031.80 mBar. The mean atmospheric pressure on the days of rupture was 1,004.03 vs. 1,004.68 on those days when no rupture occurred (P = 0.34). The mean atmospheric pressure on the day of rupture and that on the preceding day was not significantly different (1,004.78 vs. 1,005.44 with P = 0.13). The air temperature (10.62 ± 6.25 vs. 10.77 ± 6.83°C, P = 0.787) was equally distributed between days of rupture events and control days. The present study could not show a significant association between the monthly and seasonal difference in atmospheric pressure and the prevalence of AAA rupture as it has been supposed by previous studies.


Feature and motion-based gaze cuing is linked with reduced social competence.
Gaze following is a fundamental ability that plays an important role in human social function. However, the link between these two processes remains elusive. On the one hand, typically developing persons show robust gaze following in laboratory cuing tasks. On the other hand, investigations with individuals with autism suggest that reduced social competence in this population may partly reflect an atypical access to social information through attending to perceptual changes that normally accompany gaze shifts, like luminance or motion transients. Here we investigated if gaze cuing in typically developing individuals was modulated by similar task-irrelevant perceptual changes. In Experiment 1, a social gaze cue was presented with or without a luminance change. In Experiment 2, a social gaze cue was presented together with a motion cue. Both experiments indicated reduced magnitudes of gaze cuing in persons with low social competence on trials containing an irrelevant perceptual change. This suggests that similarly to individuals with autism, typically developing persons with low social competence also utilize idiosyncratic perceptual changes in the environment to access social content, revealing strong links between basic gaze following abilities and a range of social competence within typical individuals.


History of cystometry.
Looking back on the changes in the conceptualization of micturition and the development of cystometry, it is reasonable to arrive at several conclusions. Considering their poor technical equipment, Budge's and Goltz's neurophysiologic observations in the 19th century were impressive. The pontine center for micturition, found by Budge, was later confirmed, by Barrington, to have a facilitating and coordinating function. Goltz's demonstration that micturition could be partially accomplished by a spinal reflex was unfortunately given too little attention by clinicians practicing cystometry in the beginning of this century. Dubois' careful pioneering investigations of bladder pressure, and Mosso and Pellacani's studies in bladder motility were outstanding. From Born's and Genouville's contributions, continuously recordable filling cystometry was developed as early as the end of the last century. However, due to a fixation on "bladder tone" and the concept of "crossed innervation" by succeeding investigators, development of cystometry was at a standstill for almost forty years before gradually attaining its modern interpretation. Compared to our century, it is striking how carefully all investigators from the 19th century cited each other and knew about each other's work. This was possible, in spite of poor communication, because of the small number of investigators involved in studies of bladder function. Although cystometry today is quite informative in many cases, two main points, the presence of detrusor contraction reflex and the patient's capacity to suppress its occurrence, are still highly dependent on the technique used and the subject's cooperation. The more complicated urodynamic investigations flourishing during the last fifteen years have been met with the same uncertainty as the preceding ones since they are partially or completely dependent on patient compliance. Frequently, findings in the laboratory do not relate to the clinical situation. Hopefully, future development of monitoring of bladder-urethral function and the use of neurophysiologic electrodiagnostic methods will reduce these difficulties. The authors believe that modern cystometry began in the 1950s, and that discussion of this period and up to the present is more appropriately the subject of a review on modern methodologies. Further, it is difficult to place modern technology and investigators in historical perspective when events are evolving.


Evaluation of an assay for serum 1,5-anhydroglucitol (GlycoMark) and determination of reference intervals on the Hitachi 917 analyzer.
1,5-Anhydroglucitol (1,5-AG) is a glucose analogue, which is decreased in hyperglycemic individuals. We report the technical performance of an assay (GlycoMark) on a chemistry analyzer, evaluation of analyte stability and determination of reference intervals for 1,5-AG in a non-diabetic US population. NCCLS protocols were followed to evaluate the reagent on a Hitachi 917 chemistry analyzer. Intra- and interassay imprecision ranged from 1.3% to 3.8% and 0.79% to 3.7%, respectively. The assay was linear to 110 microg/ml. Interference from triglyceride, hemoglobin and bilirubin was <10% to concentrations of 12.6 mmol/l, 12.1 and 911.4 micromol/l, respectively. Correlation coefficients between lot numbers on the Hitachi 917 and between analyses on the Hitachi 917 and the Hitachi 7170 analyzers were >0.99. The lowest limit of detection was 0.49 microg/ml (mean+/-2 S.D.). 1,5-AG was stable at 4 degrees C for 7 days, at 22 degrees C for 5 days, at -80 degrees C for 14 days and for three freeze-thaw cycles at -80 degrees C. The US reference intervals (nonparametric 2.5th-97.5th percentiles) were 10.2-33.8 microg/ml (males) and 5.9-31.8 microg/ml (females). The performance of the GlycoMark assay for the measurement of 1,5-AG was acceptable on the Hitachi 917 analyzer.


Measuring radiofrequency field-induced temperature variations in brain MRI exams with motion compensated MR thermometry and field monitoring.
An MR thermometry (MRT) method with motion and field fluctuation compensation is proposed to measure non-invasively sub-degree brain temperature variations occurring through radiofrequency (RF) power deposition during MR exams. MRT at 7T with a multi-slice echo planar imaging (EPI) sequence and concurrent field monitoring was first tested in vitro to assess accuracy in the presence of external field perturbations, an optical probe being used for ground truth. In vivo, this strategy was complemented by a motion compensation scheme based on a dictionary pre-scan, as reported in some previous work, and was adapted to the human brain. Precision reached with this scheme was assessed on eight volunteers with a 5 minute-long low specific absorption rate (SAR) scan. Finally, temperature rise in the brain was measured twice on the same volunteers and with the same strategy, this time by employing a 20-minutes scan at the maximum SAR delivered with a commercial volume head coil. In vitro, the root mean square (RMS) error between optical probe and MRT measurements was 0.02°C with field sensor correction. In vivo, the low SAR scan returned a precision in temperature change measurement with field monitoring and motion compensation of 0.05°C. The 20-minutes maximum SAR scan returned a temperature rise throughout the inner-brain in the range of 0-0.2°C. Brain periphery remained too sensitive with respect to motion to lead to equally conclusive results. Sub-degree temperature rise in the inner human brain was characterized experimentally throughout RF exposure. Potential applications include improvement of human thermal models and revision of safety margins.


Cell-autonomous role for NF-kappa B in immature bone marrow B cells.
The NF-kappaB transcription factors have many essential functions in B cells, such as during differentiation and proliferation of Ag-challenged mature B cells, but also during final maturation of developing B cells in the spleen. Among the various specific functions NF-kappaB factors carry out in these biologic contexts, their ability to assure the survival of mature and maturing B cells in the periphery stands out. Less clear is what if any roles NF-kappaB factors play during earlier stages of B cell development in the bone marrow. Using mice deficient in both NF-kappaB1 and NF-kappaB2, which are thus partially compromised in both the classical and alternative activation pathways, we demonstrate a B cell-autonomous contribution of NF-kappaB to the survival of immature B cells in the bone marrow. NF-kappaB1 and NF-kappaB2 also play a role during the earlier transition from proB to late preB cells; however, in this context these factors do not act in a B cell-autonomous fashion. Although NF-kappaB1 and NF-kappaB2 are not absolutely required for survival and progression of immature B cells in the bone marrow, they nevertheless make a significant contribution that marks the beginning of the profound cell-autonomous control these factors exert during all subsequent stages of B cell development. Therefore, the lifelong dependency of B cells on NF-kappaB-mediated survival functions is set in motion at the time of first expression of a full BCR.