Glycosyl imprinted mesoporous microspheres for the determination of glycopeptide antibiotics using ultra-high performance liquid chromatography coupled with tandem mass spectrometry.
Glycopeptide antibiotics are critical weapons against serious Gram-positive resistant bacteria, and therefore the development of analytical methods for their determination is essential. In this work, with the aim of extending the scope of molecularly imprinted mesoporous materials to the recognition of large molecules such as proteins and peptides, we selected the glycosyl moiety of glycopeptide antibiotics as a template and synthesised a boronic acid functional monomer by click chemistry reaction to prepare glycosyl imprinted mesoporous microspheres. On the basis of boronate affinity, the template and the functional monomer formed a self-assembly structure that was incorporated into the silica framework during polymerisation. The removal of the glycosyl moiety created cavities with boronic acid groups covalently anchored to the pore walls of the glycosyl imprinted mesoporous microspheres. The resultant microspheres showed regular spherical shape, narrow size distribution and porous structure and exhibited high adsorption capability and fast adsorption kinetics. The size exclusion effect of the mesoporous structure prevents large molecules from entering the cavities, while the glycosyl imprinted cavities provide selectivity for glycopeptide antibiotics. The glycosyl imprinted mesoporous microspheres were employed to separate six glycopeptide antibiotics in serum samples, which were then determined using ultra-high performance liquid chromatography tandem mass spectrometry. The proposed method exhibited satisfactory linearity in the range of 0.1 to 20.0 μg/L, demonstrating great potential for the determination of glycopeptide antibiotics in serum samples.


Nuclear GSK-3β segregation in desmoid-type fibromatosis.
Desmoid-type fibromatosis (DF) is a rare benign myofibroblastic neoplasm of the connective tissue that is unable to metastasize but is associated with a high local recurrence rate. Nuclear β-catenin is the most commonly used histological marker of DF; however, clinical and biological predictive markers guiding the treatment and follow-up of DF are still lacking. Normally, β-catenin is regulated by the cytoplasmic multiprotein complex of adenomatous polyposis coli (APC), axin, casein kinase 1α (CK1α), and glycogen synthase kinase 3β (GSK-3β); this phosphorylates and degrades β-catenin, which would otherwise translocate to the nucleus. The aim of this study was to analyse the expression and localization of the β-catenin-protein complex of the Wnt pathway in cells isolated from DF patients. We isolated cells from biopsies of DF patients, and demonstrated, by immunofluorescence and immunoblot analyses, that it is almost exclusively nuclear GSK-3β that colocalizes and interacts with β-catenin. The nuclear translocation of β-catenin and GSK-3β is not correlated with CTNNB1 mutations. In DF samples, the multiprotein complex is disrupted, as the cytoplasmic localization of APC and axin makes interaction with the nuclear β-catenin and GSK-3β impossible. Our data suggest that GSK-3β is an additional DF marker with an important role in the aetiopathogenesis of this entity.


Validation and precision of model-based radiostereometric analysis (MBRSA) for total ankle arthroplasty.
The goal of this study was to design a RSA marker insertion protocol to evaluate the stability of the bone-implant interface of a TAA prosthesis, and to validate that this marker insertion protocol can be combined with MBRSA technology to provide clinically adequate precision in assessing the micromotion of the TAA prosthesis. The Mobility™ Total Ankle System was used in this study. A marker placement protocol was developed with a Phantom Protocol. The Improved Marker Placement Protocol was used in 20 patients. Postoperative RSA double exams were taken. Condition Numbers (CN) were used to assess the marker distribution. The system precision was defined as the standard deviation of the double exams (MTE, MRE). MBRSA software was used to evaluate the double exams. The RSA marker insertion technique for the 20 {\it in vivo} cases provided satisfactory results. CNs in all subjects but one were below 50 mm(-1) and implied a desirable marker configuration. The tibial sphere MTE was 0.07 mm and the talar was 0.09 mm. The talar MRE was 0.51 degrees. The system precision for these {\it in vivo} TAA implants was within the normal range identified by RSA studies, and comparable to the existing TAA RSA studies. This study demonstrated a reliable RSA marker insertion technique in both the tibia and talus. The study confirms that the insertion and MBRSA technique allows the typical high precision demonstrated in other RSA studies (standard deviation less than or equal to 0.25 mm or 0.6 degrees). This method may allow more accurate assessment of prosthetic subsidence clinically.


Anaesthetic management for oophorectomy in pulmonary lymphangiomyomatosis.
Pulmonary lymphangiomyomatosis is an idiopathic disease, resulting in severe respiratory impairment. Bilateral oophorectomy has led to objective and subjective amelioration of the pulmonary pathology. In the anaesthetic management of such a patient, careful attention must be paid to pulmonary and systemic haemodynamics, and gas exchange. We describe the successful anaesthetic management of a 34-year-old female, using epidural anaesthesia, and pulmonary artery catheterization. Although the intraoperative and immediate postoperative courses were heralded by marked cardiorespiratory stability, refractory respiratory failure developed, and she died five months after surgery.


Haemagglutination inhibition and virus microneutralisation serology assays: use of harmonised protocols and biological standards in seasonal influenza serology testing and their impact on inter-laboratory variation and assay correlation: A FLUCOP collaborative study.
The haemagglutination inhibition assay (HAI) and the virus microneutralisation assay (MN) are long-established methods for quantifying antibodies against influenza viruses. Despite their widespread use, both assays require standardisation to improve inter-laboratory agreement in testing. The FLUCOP consortium aims to develop a toolbox of standardised serology assays for seasonal influenza. Building upon previous collaborative studies to harmonise the HAI, in this study the FLUCOP consortium carried out a head-to-head comparison of harmonised HAI and MN protocols to better understand the relationship between HAI and MN titres, and the impact of assay harmonisation and standardisation on inter-laboratory variability and agreement between these methods. In this paper, we present two large international collaborative studies testing harmonised HAI and MN protocols across 10 participating laboratories. In the first, we expanded on previously published work, carrying out HAI testing using egg and cell isolated and propagated wild-type (WT) viruses in addition to high-growth reassortants typically used influenza vaccines strains using HAI. In the second we tested two MN protocols: an overnight ELISA-based format and a 3-5 day format, using reassortant viruses and a WT H3N2 cell isolated virus. As serum panels tested in both studies included many overlapping samples, we were able to look at the correlation of HAI and MN titres across different methods and for different influenza subtypes. We showed that the overnight ELISA and 3-5 day MN formats are not comparable, with titre ratios varying across the dynamic range of the assay. However, the ELISA MN and HAI are comparable, and a conversion factor could possibly be calculated. In both studies, the impact of normalising using a study standard was investigated, and we showed that for almost every strain and assay format tested, normalisation significantly reduced inter-laboratory variation, supporting the continued development of antibody standards for seasonal influenza viruses. Normalisation had no impact on the correlation between overnight ELISA and 3-5 day MN formats.


Novel Treatments for Transient Ischemic Attack and Acute Ischemic Stroke.
The treatment of acute ischemic stroke is one of the most rapidly evolving areas in medicine. Like all ischemic vascular emergencies, the priority is reperfusion before irreversible infarction. The central nervous system is sensitive to brief periods of hypoperfusion, making stroke a golden hour diagnosis. Although the phrase "time is brain" is relevant today, emerging treatment strategies use more specific markers for consideration of reperfusion than time alone. Innovations in early stroke detection and individualized patient selection for reperfusion therapies have equipped the emergency medicine clinician with more opportunities to help stroke patients and minimize the impact of this disease.


Inhibition of stretching-evoked ATP release from bladder mucosa by anticholinergic agents.
To determine whether muscarinic receptor antagonism affects stretching-induced release of ATP. Mucosal strips, dissected from guinea pig (male, 450g; n = 10) urinary bladders, were placed in horizontal organ baths and superfused with Ca(2+) -free Tyrode's solution. Superfusate samples were taken pre- and post- intervention (rapid stretching or relaxation) and ATP concentration was quantified using a luciferin-luciferase assay. The effect of muscarinic acetylcholine receptor antagonism on ATP release was assessed by addition of methoctramine (1 µM) and 4-DAMP (10 nM). Rapid stretching (0 to 13.3 ± 1.2 mN; no. strips = 20) increased ATP in the superfusate to a median threefold increase over basal levels. After a period of equilibration, tension in the mucosal strips relaxed until it had reached a new steady-state after 60 min and stretching was repeated. In the presence of 4-DAMP (10 nM) or methoctramine (1 µM), ATP concentrations after stretching reduced to 61% or 20%, respectively. By contrast, ATP concentrations in mucosa-matched controls, perfused with vehicle, increased in response to stretching by 391% and 1500%, respectively. Rapid relaxation also stimulated ATP release. This release did not appear to be sensitive to 4-DAMP or methoctramine. An alteration of resting mucosal tension is the key determinant of ATP release, as ATP is released from the mucosa in response to both stretching and relaxation. Muscarinic receptor antagonism inhibits stretching-evoked ATP release from bladder mucosa, suggesting that anticholinergic agents used to treat human lower urinary tract pathologies act on urothelial muscarinic receptors.


In vitro evaluation of poly (vinyl alcohol)/collagen blended hydrogels for regulating human periodontal ligament fibroblasts and gingival fibroblasts.
Periodontitis is a chronic inflammatory disease that can destroy periodontal tissue. Guided tissue regeneration (GTR) is widely applied to treat periodontitis. However, the challenge is to develop a GTR membrane capable of simultaneously regenerating periodontal tissue and preventing epithelial downgrowth into the defect. Herein, blended hydrogels composed of polyvinyl alcohol (PVA) and fish collagen (Col) were prepared as GTR membranes. The morphology, Col release, and cellular behavior of the blended hydrogels were evaluated. The results showed that the surface porosity and Col release of the PVA/Col blended hydrogels were enhanced by increasing the Col concentration. The adhesion and proliferation of human periodontal ligament fibroblasts (HPDLFs) and human gingival fibroblasts (HGFs) on the PVA/Col blended hydrogels can be regulated by tuning the PVA/Col ratio. The PVA/Col (50:50) blended hydrogel exhibited the highest cell proliferation rate for HPDLFs with spread cell morphology; the lowest viability for HGFs was found on the PVA/Col (100:0) hydrogel. Thus, by controlling the ratio of PVA to Col, multifunctional PVA/Col blended hydrogels able to regulate the cellular behavior of HPDLFs and HGFs can be developed, demonstrating their potential as GTR membrances for guiding periodontal tissue regeneration.


Ubiquitin-specific protease 14 promotes radio-resistance and suppresses autophagy in oral squamous cell carcinoma.
Oral squamous cell carcinoma (OSCC) is a common malignant tumor in the world. Radiotherapy is one of the standard therapies for patients with OSCC, but its clinical efficiency is limited due to radioresistance. In this study, we identified a mechanism of such resistance regulated by Ubiquitin-specific protease 14 (USP14). USP14 expression was significantly increased in clinical OSCC tissue samples and cell lines, and OSCC patients with high USP14 expression predicted poor overall survival rate. Additionally, a negative correlation between USP14 and LC3B was observed in patients with OSCC. We then found that irradiation (IR)-reduced cell survival of OSCC cells lines was further decreased when USP14 was knocked down. However, USP14 over-expression significantly promoted the cell viability of OSCC cells after IR treatment. Colony formation analysis confirmed thatafter IR treatment,USP14 knockdown markedly decreased the proliferation of OSCC cells, but over-expressing USP14 significantly up-regulated the proliferative activity of OSCC cells. Furthermore, DNA damage caused by IR was enhanced by USP14 knockdown, while been suppressed in OSCC cells with USP14 over-expression. Additionally, IR-inducedapoptosis was further promoted by USP14 knockdown in OSCC cells, which was, however, significantly abolished by USP14 over-expression.Moreover, our in vivo studies showed that IR-reduced tumor growth and tumor weight were further enhanced by USP14 knockdown in OSCC tumor-bearing nude mice. Finally, we found that USP14 knockdown could promote IR-induced autophagy by increasing LC3BII and γH2AX expression levels in IR-treated OSCC cells. However, this event was markedly abolished by ATG5 knockdown, subsequently restoring the cell proliferation in IR-incubated OSCC cells.Finally, we found that USP14-mediated apoptosis was autophagy-dependent in IR-treated OSCC cells. Taken together, these findings suggested that suppressing USP14 could alleviateradioresistancein OSCC both in vitro and in vivo by inducing apoptosis and autophagy, and thus could be served as a promising therapeutic strategy for OSCC treatment.


Rational design of dual-ligand Eu-MOF for ratiometric fluorescence sensing Cu2+ ions in human serum to diagnose Wilson's disease.
Copper levels in body fluids provide an important reference for the diagnosis of Wilson's disease, which associated with blood abnormalities, kidney and cardiovascular disease, and neuropathy. Metal-organic frameworks (MOF) can easily realize dual-emission from single excitation as ratiometric fluorescence sensing and visible detection platform with the intensity ratio of two emissions for simple, rapid, sensitive, and specific analysis of biological samples. Here, we rationally designed a dual-emission Eu-MOF with dual-ligand strategy, denoted as Eu-DATA/BDC. While terephthalic acid (H2BDC) was selected to sensitize Eu3+ ions for the antenna effect emission, 2,5-diaminoterephthalic acid (H2DATA) maintained its own emission and was used to identify Cu2+ ions. Thus, dual-emission from Eu-DATA/BDC and specific recognition of Cu2+ ions were realized for ratiometric sensing of Cu2+ ions. A wide linear concentration range (1-40 μM), low detection limit (0.15 μM), and fast response (less than 10 s) were realized. The color change also achieved the visible detection by naked eye. Copper levels were tested with human serum samples and compared to the ICP-OES results, confirmed the potential of Eu-DATA/BDC probe in the diagnosis of Wilson's disease. The response mechanism to Cu2+ ions was proposed as electron transfer between host and guest for fluorescence quenching. Thus, dual-ligand is a simple and efficient strategy to prepared dual-emission Eu-MOF for the ratiometric sensing and visible detection.


Risk factors, causes, and the economic implications of unplanned readmissions following total hip arthroplasty.
In order to identify risk factors for readmissions following total hip arthroplasty (THA) and the causes and financial implications of such readmissions, we analyzed clinical and administrative data on 1583 consecutive primary THAs performed at a single institution. The 30-day readmission rate was 6.51%. Increased age, length of stay, and body mass index were associated with significantly higher readmission rates. The most common re-admitting diagnoses were deep infection, pain, and hematoma. Average profit was lower for episodes of care with readmissions ($1548 vs. $2872, P=0.028). If Medicare stops reimbursing for THA readmissions, the institution under review would sustain an average net loss of $11,494 for episodes of care with readmissions and would need to maintain readmission rates below 23.6% in order to remain profitable.


Studies on cisternal and alveolar fractions & its composition and mammary health of Murrah buffaloes administered oxytocin.
The study was conducted on 18 lactating Murrah buffaloes in 83.72 +/- 14.75 days after calving. Group I buffaloes were not injected with oxytocin and served as control. Buffaloes of Group II were injected with oxytocin @ 2.5 IU per 0.5 ml intramuscularly at the hip region for a period of 1 month while Group III buffaloes received injection of oxytocin @ 5.0 IU per ml intramuscularly at the hip region for a period of 1 month. Milk samples from three groups of buffaloes were collected after oxytocin injections at 15 days interval on 0, 15, 30 and 45 days. Blood samples were collected in heparinized tubes at 0, 15, 30 and 45 days of experiment from all three groups of buffaloes. There was no significant change in cisternal, alveolar and total milk yield by exogenous oxytocin administration. Fat % in cisternal, alveolar and total milk decreased significantly (P < 0.01) by 11.8% and 21.3% in groups II and III buffaloes, respectively. Protein % increased significantly (P < 0.01) in group III. A significant increase was observed in somatic cell counts of milk by 5.36% and 6.22% in groups II and III, respectively as compared to control group.


Growth Differentiation Factor-15 as a Predictor of Functional Capacity, Frailty, and Ventricular Dysfunction in Patients With Aortic Stenosis and Preserved Left Ventricular Ejection Fraction.
In aortic stenosis (AS), left ventricular (LV) remodeling often occurs before symptom onset, and early intervention may be beneficial. Risk stratification remains challenging and identification of biomarkers may be useful. We evaluated the association between growth differentiation factor-15 (GDF-15) and soluble suppression of tumorigenicity 2 (sST2) and known markers of poor prognosis in AS. Baseline plasma GDF-15 and sST2 levels were measured in 70 patients with moderate-severe AS (aortic valve area <1.5 cm2) and preserved LV ejection fraction (>45%). Patients were categorized into "low GDF-15" versus "high GDF-15" and "low sST2" versus "high sST2" groups. Groups were compared for differences in cardiovascular risk factors, 6-minute walk test, 5 m gait speed, cognitive function (Montreal Cognitive Assessment), and echocardiographic parameters. Overall, 44% of patients were deemed asymptomatic by New York Heart Association class, 61% had severe AS (aortic valve area <1 cm2) and all patients had preserved LV ejection fraction. GDF-15 levels were not predictive of AS severity. However, high GDF-15 (>1,050 pg/ml) was associated with LV dysfunction as shown by lower indexed stroke volume (p <0.01), worse LV global longitudinal strain (p = 0.04), greater mean E/e' (p = 0.02) and indexed left atrial volume (p <0.01). It was also associated with decreased functional capacity with shorter 6-minute walk test (p = 0.01) and slower 5 m gait speed (p = 0.02). Associations between sST2 levels and markers of poor prognosis were less compelling. In this study of patients with moderate to severe AS, elevated GDF-15 levels are associated with impaired functional capacity, poorer performance on fragility testing, and LV dysfunction. In conclusion, GDF-15 may integrate these markers of adverse outcomes into a single biomarker of poor prognosis.


A rigid-body method for finding centers of rotation and angular displacements of planar joint motion.
A rigid-body method for determining the center of rotation (CR) and the angular displacement in a plane is developed. A comparison of this method to the graphical method of Reuleaux (Theoretische Kinematik: Grundzüge einer Theorie des Maschinenwerens, 1875) is found to have fewer constraints while meeting or exceeding the Reuleaux method in accuracy. The rigid-body method is not constrained by the location of the markers, as they can be placed radially or juxtapositioned about the CR. Magnitude of the rotation angle does not affect the accuracy in calculating the rotation angle. When applying both methods to locate the CR in a simulated knee joint, a substantial decrease in error is found with the new method. In a comparison of optimal marker angles used to locate the CR and find the angular displacement, the rigid-body method is found to be more accurate in both the mean and range of error. Effects of parameters specified by Panjabi (J. Biomechanics 12, 911-920, 1979) are applied to both methods. Results are then used in setting up guidelines for increasing accuracy with the rigid-body method.


Size and thickness effect on creep behavior in conventional and vitamin E-diffused highly crosslinked polyethylene for total hip arthroplasty.
Since the early 2000s, the use of large femoral heads is becoming increasingly popular in total hip arthroplasty (THA), which provides an improved range of motion and joint stability. Large femoral heads commonly necessitate to be coupled with thinner acetabular liners than the conventionally used because of the limited sizes of outer shells (especially for patients with small pelvic size). However, the influence of the liner thinning on the mechanical performance is still not clearly understood. The objective of this study was to experimentally clarify the size and thickness effect on the rates of compressive creep strain in conventional (virgin low-crosslinked) and vitamin E-diffused highly crosslinked, ultra-high molecular weight polyethylene (UHMWPE) acetabular liners. We applied uniaxial compression to these liners of various internal diameters (28, 32 and 36mm) and thicknesses (4.8, 6.8 and 8.9mm) up to 4320min under the constant load of 3000N. Vitamin E-diffused highly crosslinked UHMWPE components showed significantly greater creep resistance than the conventional ones. In the both types of UHMWPE, the rates of creep strain significantly decreased by increasing the internal diameter and thickness. Varying the component thickness contributed more largely to the creep behavior rather than the internal diameter. Our results suggest the positive mechanical advantage of using large femoral heads, but at the same time, a considerable liner thinning is not recommended for minimizing creep strain. Therefore, the further in-vitro as well as in-vivo research are necessary to conclude the optimal balance of head diameter and liner thickness within the limited sizes of outer shells.


Olfaction and smell identification tests: A novel test that may correlate with cochlear implant outcomes.
A cochlear implant (CI) is a prosthetic implantable device that is available for people who do not benefit from traditional, non-invasive means of amplification. Although many people receive significant improvement in their ability to understand speech with CI, there can be variability in patients' ability to understand open-set speech and some people may not get the expected degree of benefit after CI surgery. Currently, the patient-related factors that appear to correlate with CI outcomes are limited to age and duration of deafness. Recent work has suggested cognition, specifically, cognitive decline, may be an additional patient-related factor that contributes to poor CI outcomes. This work is based on the concept that processing of sound requires intact central processing and neurocognitive function. While the relationship between cognition and hearing is evolving, it is well-established that olfactory dysfunction is an early indicator of cognitive decline. Given this relationship, it stands to reason that olfaction may provide information regarding one's ability to process auditory information, which relies heavily on central functioning and cognition. We hypothesize that olfaction and smell identification scores on the University of Pennsylvania Smell Identification Test (UPSIT) may correlate with CI outcomes. More specifically, we hypothesize that olfactory dysfunction may serve as a potential predictor of poor CI outcomes. Evaluating this relationship has the potential to change the standard evaluation for CI candidates and may offer simple and efficient prognostic information for patients who are considering CI.


Measurement of the fast neutron sensitivities of Geiger-Mueller counter gamma dosemeters.
An associated-particle coincidence technique was used to measure the sensitivity of 14-7 MeV neutrons of three types of energy-compensated Geiger--Mueller counters used in mixed field dosimetry. These were then used to measure the gamma-dose component of a 14-7 MeV neutron flux. The thermal neutron sensitivities were also measured.


Study on the metabolic process of synthetic cannabinoids 4F-MDMB-BINACA and 4F-MDMB-BICA in human liver microsome and zebrafish model via UHPLC-QE Orbitrap MS.
In order to address the increasing abuse of synthetic cannabinoids, on July 1, 2021, China listed the whole category of synthetic cannabinoids in the Supplementary Catalog for the Control of Non-medicinal Narcotic Drugs and Psychotropic Substances. Because synthetic cannabinoids metabolize rapidly, techniques are urgently needed to identify the phase I metabolites of new synthetic cannabinoids, as well as the symbol metabolites, which can be used for detection in real cases. In this study, we used pooled human liver microsome (pHLM) and zebrafish combined with ultra-high-performance liquid chromatography (UHPLC) Q Exactive Orbitrap MS to identify the phase I metabolites of two new synthetic cannabinoids 4F-MDMB-BICA and 4F-MDMB-BINACA in vitro and in vivo, respectively. We studied the toxicokinetics of 4F-MDMB-BICA and 4F-MDMB-BINACA by sampling from a pHLM incubation system at different time points to study the change in metabolites over time. We detected a total of 14 metabolites of 4F-MDMB-BINACA and 16 metabolites of 4F-MDMB-BICA in this study. Metabolites of 4F-MDMB-BICA were detected in vitro for the first time. One metabolite of 4F-MDMB-BINACA, M05, was discovered for the first time. Based on the toxicokinetics results, we recommend three metabolites (M03, M11, M12) of 4F-MDMB-BINACA and three metabolites (M10, M12, M14) of 4F-MDMB-BICA as their symbol metabolites. The results showed that these two structurally similar synthetic cannabinoids 4F-MDMB-BINACA and 4F-MDMB-BICA had similar metabolic processes, as well as similar structures of their main symbol metabolites.


A caucasoid pedigree demonstrating the transmission of a Gm 1,2,17;5,13,14 haplotype.
Data illustrating the inheritance of a Gm1,2,17,5,13,14 haplotype in a Caucasian family are presented. The mother and two children are heterozygous for this unusual haplotype. The possible origin of the haplotype is discussed.


Proteogenomic analysis of chemo-refractory high-grade serous ovarian cancer.
To improve the understanding of chemo-refractory high-grade serous ovarian cancers (HGSOCs), we characterized the proteogenomic landscape of 242 (refractory and sensitive) HGSOCs, representing one discovery and two validation cohorts across two biospecimen types (formalin-fixed paraffin-embedded and frozen). We identified a 64-protein signature that predicts with high specificity a subset of HGSOCs refractory to initial platinum-based therapy and is validated in two independent patient cohorts. We detected significant association between lack of Ch17 loss of heterozygosity (LOH) and chemo-refractoriness. Based on pathway protein expression, we identified 5 clusters of HGSOC, which validated across two independent patient cohorts and patient-derived xenograft (PDX) models. These clusters may represent different mechanisms of refractoriness and implicate putative therapeutic vulnerabilities.


1-year retention rates and performance ratings: comparing associate degree, baccalaureate, and accelerated baccalaureate degree nurses.
The purpose of this study was to examine 1-year retention and managerial performance ratings of newly licensed RNs (NLRNs) according to nursing education program types (associate degree, traditional baccalaureate, and accelerated 2nd degree baccalaureate). Findings revealed retention and performance differences, suggesting the possibility of tradeoffs related to educational program type when selecting NLRNs for open positions.


Childhood parental loss and adult hypothalamic-pituitary-adrenal function.
Several decades of research link childhood parental loss with risk for major depression and other forms of psychopathology. A large body of preclinical work on maternal separation and some recent studies of humans with childhood parental loss have demonstrated alterations of hypothalamic-pituitary-adrenal (HPA) axis function that could predispose to the development of psychiatric disorders. Eighty-eight healthy adults with no current Axis I psychiatric disorder participated in this study. Forty-four participants experienced parental loss during childhood, including 19 with a history of parental death and 25 with a history of prolonged parental separation. The loss group was compared with a matched group of individuals who reported no history of childhood parental separation or childhood maltreatment. Participants completed diagnostic interviews and questionnaires and the dexamethasone/corticotropin-releasing hormone (Dex/CRH) test. Repeated measures general linear models were used to test the effects of parental loss, parental care, gender, and age on the hormone responses to the Dex/CRH test. Parental loss was associated with increased cortisol responses to the test, particularly in men. The effect of loss was moderated by levels of parental care; participants with parental desertion and very low levels of care had attenuated cortisol responses. Adrenocorticotropic hormone responses to the Dex/CRH test did not differ significantly as a function of parental loss. These findings are consistent with the hypothesis that early parental loss induces enduring changes in neuroendocrine function.


Performance evaluation of MRI-based PAGAT polymer gel dosimeter in an inhomogeneous phantom using EGSnrc code on a Co-60 machine.
Relative isodose curves were obtained using PAGAT gel dosimeter on homogeneous and inhomogeneous phantoms. Distance-to-agreement (DTA) was calculated between simulated and measured values for both the homogeneous and inhomogeneous phantoms. All DTAs except one passed the acceptance criterion (+/-5 dose variation for selected isodose levels). Results of this study also showed the ability of the Monte Carlo modeling to provide accurate dosimetry, and revealed that the dose response of PAGAT polymer gel is dependent on the method of fabrication.


Implications of postneurosurgical meningitis caused by carbapenem-resistant Acinetobacter baumannii.
Acinetobacter baumannii is an important cause of postneurosurgical meningitis. The emergence of carbapenem-resistant strains in this setting has caused a therapeutic challenge. We investigated the clinical implications of postneurosurgical meningitis caused by carbapenem-resistant A. baumannii. In this study, we retrospectively reviewed the medical records of patients more than 16 years of age with A. baumannii meningitis that developed after a neurosurgical procedure at five university-affiliated hospitals between January 2005 and May 2011. Of 40 cases identified, 22 (55.0%) were caused by carbapenem-resistant strains. Of those evaluable 36 patients with A. baumannii meningitis, 14 (38.9%) died of meningitis. Meningitis-related mortality was significantly related to carbapenem resistance (59.1% versus 7.1%; P = 0.002). In patients with meningitis caused by carbapenem-resistant A. baumannii, colistimethate-containing regimens (4/13 versus 7/9; P = 0.040), intrathecal or intraventricular (IT/IVR) administration of antibiotics (2/13 versus 8/9; P = 0.001), and combined intravenous and IT/IVR therapy (2/13 versus 6/9; P = 0.026) were significantly associated with cure. This study shows that use of colistimethate and combined systemic and local administration of antibiotics should be considered for the treatment of meningitis caused by carbapenem-resistant A. baumannii.


A hospital based epidemiological study of snakebite in Western Development Region, Nepal.
Snakebite is an important and serious medical problem throughout the entire terai region of Nepal. But comprehensive study of snakebite epidemiology in Western Development Region of Nepal is scarce. We described the status of snakebite situation in the region based on retrospective data retrieved from 10 snakebite treatment centers during June 2011 to February 2012. We reported six thousand and nine hundred ninety three snakebites in 2008-2010. Of all, we found 640 (9%) cases envenomed and received anti-venom therapy. We recorded the highest number of snakebites in July, August and September, which account 57% of all snakebite victims, during 15.00 and 21.00 h. People aged 11-20 years were mostly victimized by snakebite as compared to other age groups. Female suffered more than male. The average requirement of polyvalent snake anti-venom was 16 vials. Overall, case fatality rate was 13%.


Primary Headaches in an Elderly Population Seeking Medical Care for Cognitive Decline.
To assess the prevalence of specific headache disorders in a population older than 65 years seeking consultation due to memory problems or cognitive impairment. We verified the occurrence of headache symptoms and the impact of headaches on daily life. Headaches were classified as per the International Classification of Headache Disorders, 2nd edition (ICHD-2). All patients were screened with the Mini-Mental State Examination (MMSE), followed by the Selective Reminding Test and neuroimaging. Participants with severe cognitive impairment or dementia were excluded. A total of 1,237 patients (51.6% women), with mean age of 75.6 years (SD = 6.9) were screened from January 2006 to December 2014. Of them, 302 (24.4%) patients suffered from headaches. Most common individual diagnoses were probable migraine (13.8%), episodic tension-type headache (3.4%), and episodic migraine (3.0%). Chronic migraine or probable chronic migraine happened in 3.5%, while chronic tension-type headache affected 0.6%. Most patients with headaches routinely used symptomatic medications (55.6%). Mean MMSE scores were similar in patients with or without headaches, or with different headache diagnoses. Headache disorders overall, frequent headaches, and headaches requiring treatment are commonly seen in the elderly seeking care for cognitive decline and should be properly assessed and managed.


Digital Phenotyping: A Game Changer for the Broiler Industry.
In response to escalating global demand for poultry, the industry grapples with an array of intricate challenges, from enhancing productivity to improving animal welfare and attenuating environmental impacts. This comprehensive review explores the transformative potential of digital phenotyping, an emergent technological innovation at the cusp of dramatically reshaping broiler production. The central aim of this study is to critically examine digital phenotyping as a pivotal solution to these multidimensional industry conundrums. Our investigation spotlights the profound implications of 'digital twins' in the burgeoning field of broiler genomics, where the production of exact digital counterparts of physical entities accelerates genomics research and its practical applications. Further, this review probes into the ongoing advancements in the research and development of a context-sensitive, multimodal digital phenotyping platform, custom-built to monitor broiler health. This paper critically evaluates this platform's potential in revolutionizing health monitoring, fortifying the resilience of broiler production, and fostering a harmonious balance between productivity and sustainability. Subsequently, the paper provides a rigorous assessment of the unique challenges that may surface during the integration of digital phenotyping within the industry. These span from technical and economic impediments to ethical deliberations, thus offering a comprehensive perspective. The paper concludes by highlighting the game-changing potential of digital phenotyping in the broiler industry and identifying potential future directions for the field, underlining the significance of continued research and development in unlocking digital phenotyping's full potential. In doing so, it charts a course towards a more robust, sustainable, and productive broiler industry. The insights garnered from this study hold substantial value for a broad spectrum of stakeholders in the broiler industry, setting the stage for an imminent technological evolution in poultry production.


Self-reported symptoms of social anxiety in a sample of combat veterans with posttraumatic stress disorder.
The relationship between posttraumatic stress disorder (PTSD) and self-reported levels of social anxiety among combat veterans was assessed using the Social Phobia and Anxiety inventory (SPAI). Participants were 45 veterans with combat-related PTSD assessed using a multimeasure assessment package. The veterans reported a high level of social anxiety and agoraphobia-like symptoms. Agoraphobia scores were predicted by PTSD severity and elevated by Minnesota Multiphasic Personality Inventory-2 (MMPI-2) scales of acute distress and psychopathology. Social phobia scores were predicted by severity of depression. The relationship between social anxiety, depression, and PTSD is discussed. Implications for the assessment and treatment of PTSD are also discussed.


[Heart rate variability: analysis of time-domain indices in patients with chronic Chagas disease before and after an exercise program].
Chagas disease (CD) is an infection caused by the protozoan flagellate Trypanosoma cruzi, and transmitted by insects of the genera Triatoma, Rhodnius and Panstrongylus. The heart is affected to varying degrees by inflammatory and destructive lesions in atrial and ventricular myocardial fibers. Several studies have demonstrated the benefits of exercise in patients with congestive heart failure (CHF), including reduced sympathetic tone and increased parasympathetic tone, the result of reduced epinephrine and norepinephrine levels, both at rest and during exercise, including at submaximal levels. It has been hypothesized that the increase in sympathetic arousal during exercise improves peripheral muscle metabolism. The objectives of this study were to select patients with chronic Chagas cardiomyopathy (CCC) with dysautonomia on 24-h Holter monitoring, assess autonomic function after rehabilitation, and determine whether it resulted in reduced daytime levels of SDNN and increased daytime and nighttime levels of pNN50 and rMSSD. We analyzed time-domain indices of heart rate variability through 24-h Holter monitoring before and after a supervised exercise program. We studied 18 CCC patients (five men), mean age 57.33±9.73 years, followed at the CD outpatient clinic of the National Institute of Cardiology and IPEC/Fiocruz in Rio de Janeiro, Brazil, between April 2009 and November 2010. The following tests were used to assess the severity of CCC: clinical examination, functional evaluation by cardiopulmonary stress testing, electrocardiogram and conventional Doppler echocardiography. The exams were performed within a month of the start and end of the exercise program, which consisted of 60-min sessions of aerobic exercise on a treadmill and resistance training three times a week for six months. The goal was to reach the patients' heart rate target zone during training, and their rating of perceived exertion was assessed by the modified Borg scale. There were no statistically significant differences (p>0.05) in SDNN, pNN50 and rMSSD, probably due to the large standard deviation observed, patients' poor adherence to the program and their low socioeconomic status, resulting in a small sample, and the short duration of the program. Heart rate variability parameters in patients with CCC did not undergo statistically significant changes after a six-month cardiac rehabilitation program.


The original experimental model in rats to study gastric banding surgery.
A new bariatric surgical experimental model in rats for aspects of investigation was created. In 121 male Wistar rats with body mass 250-270 g, the original gastric banding (GB) operation was performed. Sixty days after the surgical procedure, we measured body mass and upper part of the alimentary tract patency (radiography with contrast medium). One hundred twenty one rats were operated on. In the study group, the mortality was 0%. A complication (incisional hernia) was found in only three cases. The average weight of the rat in the GB group on the 60th day after the surgery was 355.0 +/- 4.12 g, and that in the sham-operation group was 394.0 +/- 4.80 g (t test, t = 6,073, p < 0.001). The daily weight gain in sham-operated rats was 2.23 +/- 0.07 g, whereas in the GB group, it was 1.60 +/- 0.07 g (p < 0.02). Complete inhibition of weight gain was not observed. The rat model of GB surgery that we created is easy to perform, repeatable, long-lasting, relatively cheap, and can be used in various experimental trials of diverse aspects of surgery in the field of obesity.


The role of preoperative blood parameters to predict the risk of surgical site infection.
Routine preoperative blood work is not recommended but selected biochemical markers may predict the risk of surgical site infection (SSI). This study examines the association between preoperative biochemical markers and the risk of SSI. This observational cohort study, nested in a randomized controlled trial, was conducted at two tertiary referral centers in Switzerland. 122 (5.8%) of 2093 patients experienced SSI. Preoperative increasing levels of albumin (OR 0.93), CRP (OR 1.34), hemoglobin (OR 0.87) and eGFR (OR 0.90) were significantly associated with the odds of SSI. The same accounts for categorized parameters. The highest area under the curve from ROC curves was 0.62 for albumin. Positive predictive values ranged from 6.4% to 9.5% and negative predictive values from 94.8% to 95.7%. The association of CRP, mildly and moderately decreased eGFR and hemoglobin with the odds of SSI remained significant on multivariate analysis. Our results do not support generally delaying elective surgery based on preoperative blood results. However, it may be considered in situations with potentially severe sequelae of SSI.


Dense anatomical annotation of slit-lamp images improves the performance of deep learning for the diagnosis of ophthalmic disorders.
The development of artificial intelligence algorithms typically demands abundant high-quality data. In medicine, the datasets that are required to train the algorithms are often collected for a single task, such as image-level classification. Here, we report a workflow for the segmentation of anatomical structures and the annotation of pathological features in slit-lamp images, and the use of the workflow to improve the performance of a deep-learning algorithm for diagnosing ophthalmic disorders. We used the workflow to generate 1,772 general classification labels, 13,404 segmented anatomical structures and 8,329 pathological features from 1,772 slit-lamp images. The algorithm that was trained with the image-level classification labels and the anatomical and pathological labels showed better diagnostic performance than the algorithm that was trained with only the image-level classification labels, performed similar to three ophthalmologists across four clinically relevant retrospective scenarios and correctly diagnosed most of the consensus outcomes of 615 clinical reports in prospective datasets for the same four scenarios. The dense anatomical annotation of medical images may improve their use for automated classification and detection tasks.


Impedance plethysmography as a screening procedure for asymptomatic deep venous thrombosis in a rehabilitation hospital.
Patients admitted for an inpatient rehabilitation treatment program almost uniformly have an elevated risk of deep venous thrombosis (DVT) and pulmonary embolism (PE). We assessed the value of impedance plethysmography (IPG) as a screening procedure for asymptomatic deep venous thrombosis in a series of patients admitted to our institution. Using a prospective observational study design, consecutive admissions to our facility for a period of almost one year were subjected to IPG within several days of admission. The study site was a 60-bed hospital-based rehabilitation center. Four hundred eighty-three consecutive patients were studied prospectively within several days of admission. Diagnoses included a variety of neurological disorders that resulted in significant weakness, intracranial surgery, orthopedic surgical procedures and fractures, joint replacements, and nonorthopedic postsurgical deconditioning. Three hundred eighteen patients were available for three-month follow-up. IPG was successfully completed in 301 patients. If IPG was positive, DVT was further assessed by duplex ultrasound (DU). When IPG and DU confirmed the presence of a DVT, administration of heparin and Coumadin was begun. Thirteen of 416 attempted IPG studies were positive for DVT, whereas DU confirmed the diagnosis in only 3 patients. Follow-up found that six patients developed DVT or PE before discharge from our institution; five patients developed DVT or PE after discharge. IPG has a poor yield as a screening tool for asymptomatic DVT on admission to an inpatient rehabilitation facility. The sensitivity and positive predictive value of IPG was too low to advocate its routine use in this setting.


Psychometric evaluation of the Swedish version of the Hypoglycaemia Fear Survey.
The objective of this study was to evaluate the psychometric properties of the Swedish version of the Hypoglycaemia Fear Survey (Swe-HFS) for use among Swedish-speaking patients with type 1 diabetes. The HFS was translated using the forward-backward translation method and was thereafter answered by 325 type 1 patients. The psychometric properties were investigated using exploratory factor analysis, Cronbach's alpha, content and convergent validity. The factor analysis showed that a three-factor solution was reasonable with the subscales Behaviour/Avoidance (10 items), Worry (6 items) and Aloneness (4 items). Cronbach's alpha coefficient for the total score was 0.85. The result also supports the instrument's content validity and convergent validity. The Swedish version of the HFS appears to be a reliable and valid instrument for measuring fear of hypoglycaemia (FoH) in type 1 patients. The results from this study suggest that the Swe-HFS, an instrument that is brief and easy to administer, may be valuable in clinically assessing FoH among patients with type 1 diabetes.


The components of executive functioning in traumatic brain injury.
Theorists have proposed models of executive functioning, and functional neuroimaging and factor analytic studies have attempted to examine the components of executive functioning. These studies have arrived at different conclusions and many empirical studies are wrought with methodological confounds. The purpose of this exploratory study was to investigate the subcomponents of executive abilities while addressing some of the limitations common in previous studies. Neuropsychological test data were obtained from a sample of individuals with a history of TBI seen at one-year follow-up (n=104). Principal components factor analysis was conducted and yielded three factors that accounted for 52.7% of the variance. The first factor included higher-order executive functions with two components: self-generative behavior and cognitive flexibility/set shifting. The second factor appeared to represent mental control, particularly of ongoing working memory. The third factor consisted of memory errors, representing failure to inhibit reporting of inaccurate information. Although the results are not entirely consistent with any of the current theoretical models of executive function, they appear to be most consistent with the 1986 model of Stuss and Benson.


Case report 716. Soft-tissue metastasis in synovial sarcoma.
We describe the case of a 21-year-old woman with a synovial sarcoma of the thigh, who exhibited a soft-tissue metastasis to the shoulder approximately 3 months after her initial presentation. Due to its increasing availability and the recognized importance of MRI in the preoperative evaluation of patients with soft-tissue masses, it is important to be aware of even the uncommon manifestations of frequently encountered soft-tissue sarcomas.


Deoxycytidine and Deoxythymidine Treatment for Thymidine Kinase 2 Deficiency.
Thymidine kinase 2 (TK2), a critical enzyme in the mitochondrial pyrimidine salvage pathway, is essential for mitochondrial DNA (mtDNA) maintenance. Mutations in the nuclear gene, TK2, cause TK2 deficiency, which manifests predominantly in children as myopathy with mtDNA depletion. Molecular bypass therapy with the TK2 products, deoxycytidine monophosphate (dCMP) and deoxythymidine monophosphate (dTMP), prolongs the life span of Tk2-deficient (Tk2-/- ) mice by 2- to 3-fold. Because we observed rapid catabolism of the deoxynucleoside monophosphates to deoxythymidine (dT) and deoxycytidine (dC), we hypothesized that: (1) deoxynucleosides might be the major active agents and (2) inhibition of deoxycytidine deamination might enhance dTMP+dCMP therapy. To test these hypotheses, we assessed two therapies in Tk2-/- mice: (1) dT+dC and (2) coadministration of the deaminase inhibitor, tetrahydrouridine (THU), with dTMP+dCMP. We observed that dC+dT delayed disease onset, prolonged life span of Tk2-deficient mice and restored mtDNA copy number as well as respiratory chain enzyme activities and levels. In contrast, dCMP+dTMP+THU therapy decreased life span of Tk2-/- animals compared to dCMP+dTMP. Our studies demonstrate that deoxynucleoside substrate enhancement is a novel therapy, which may ameliorate TK2 deficiency in patients. Ann Neurol 2017;81:641-652.


Characterization of glucose transport system in Drosophila Kc cells.
We have characterized the glucose transport system in the Kc cells of Drosophila melanogaster. The transporter is stereospecific and can be inhibited by both cytochalasin B and phloretin, with ki values of 4 microM and 30 microM for cytochalasin B and phloretin, respectively. Moreover, phlordzin does not affect uptake of glucose by Kc cells. Thus, on the basis of inhibitor studies, it appears that this insect cell line contains glucose transporters similar to those of the mammalian cells. However, probes prepared from rat transporter cDNAs showed no cross-hybridization with Drosophila RNA under moderately stringent conditions. Sugar selectively has also been investigated by competition assay. The km values for D-glucose, 2-deoxy-D-glucose, D-fructose and D-galactose are 2 mM, 6 mM, 17 mM and 16 mM, respectively. The results indicate that this transporter prefers D-glucose and that it does not discriminate between D-galactose and D-fructose.


Ferritin concentrations correlate to outcome of hematopoietic stem cell transplantation but do not serve as biomarker of graft-versus-host disease.
Clinical presentation and laboratory data are often too unspecific to distinguish the onset or activity of graft-versus-host disease (GvHD) from infections or toxicity. Antigen-presenting cells such as monocytes/macrophages and dendritic cells are involved in GvHD pathogenesis after allogeneic hematopoietic stem cell transplantation (HSCT). To test whether ferritin, an iron storage marker and macrophage activation-linked acute-phase protein, represents a candidate biomarker for acute or chronic GvHD in pediatric HSCT, we retrospectively evaluated a 2-year follow-up data from 131 eligible consecutive patients with different malignant and nonmalignant diseases who underwent allogeneic HSCT. Thirteen patients (10 %) suffered from acute GvHD II-IV°, 18 (14 %) had limited, and 14 (11 %) had extensive chronic GvHD. In extension of previous studies in adults investigating pre-transplant ferritin, our data show that post-HSCT hyperferritinemia (analyzed on days 0, +30, +60, +100, +180, +360, and +720) was significantly associated with decreased long-term survival (p < 0.001-0.03) in children and adolescents. Increased ferritin concentrations were associated with number and timing of red blood cell transfusions and toxic or infectious multi-organ failure but did not show significant differences between patients without GvHD and with acute grades II-IV, limited, or extensive chronic GvHD. Thus, our data do not identify ferritin as specifically GvHD-linked biomarker; however, they support the prognostic value of ferritin levels for outcome after HSCT in children.


Resistance to antimicrobial agents among enterococci isolated from fecal samples of wild marine species in the southern coast of Brazil.
The purpose of this study was to evaluate species distribution, antimicrobial resistance profiles, and presence of resistance genes in enterococci isolated from fecal samples of wild marine species, including seabirds (n=12), sea turtles (n=8), and mammals (n=3) found alive or dead in southern coast of Brazil. Enterococci were classified based on phenotypic and genotypic characteristics, tested for antibiotic susceptibility, and the presence of tet(S), tet(M), tet(L), mrsC, and erm(B) genes by PCR. Enterococcus faecalis and Enterococcus faecium were the most common species. Single (37.09%), double (25.80%), and multiple (16.12%) antibiotic resistance patterns were observed. Resistance to rifampicin occurred most frequently. The msrC, tet(M), and/or tet(L) genes were detected in 60.15%, 73.07%, and 23.07% of the resistant strains, respectively. In conclusion, the presence of antibiotic resistant strains in these species could be related to food web interactions and aquatic pollutants or linked to environmental resistome.


Targeting the glucocorticoid receptor in breast and prostate cancers.
Steroid receptors for androgens and estrogens have essential roles in prostate and breast cancers. Recently, glucocorticoid receptor (GR) activity has also been proposed as having an important role in these cancers. Underscoring the cooperative nature of nuclear receptor activity, data now suggest that GR function in prostate and breast cancers is dependent on the tumor's concomitant androgen or estrogen receptor activity.


Defining window-boundaries for genomic analyses using smoothing spline techniques.
High-density genomic data is often analyzed by combining information over windows of adjacent markers. Interpretation of data grouped in windows versus at individual locations may increase statistical power, simplify computation, reduce sampling noise, and reduce the total number of tests performed. However, use of adjacent marker information can result in over- or under-smoothing, undesirable window boundary specifications, or highly correlated test statistics. We introduce a method for defining windows based on statistically guided breakpoints in the data, as a foundation for the analysis of multiple adjacent data points. This method involves first fitting a cubic smoothing spline to the data and then identifying the inflection points of the fitted spline, which serve as the boundaries of adjacent windows. This technique does not require prior knowledge of linkage disequilibrium, and therefore can be applied to data collected from individual or pooled sequencing experiments. Moreover, in contrast to existing methods, an arbitrary choice of window size is not necessary, since these are determined empirically and allowed to vary along the genome. Simulations applying this method were performed to identify selection signatures from pooled sequencing FST data, for which allele frequencies were estimated from a pool of individuals. The relative ratio of true to false positives was twice that generated by existing techniques. A comparison of the approach to a previous study that involved pooled sequencing FST data from maize suggested that outlying windows were more clearly separated from their neighbors than when using a standard sliding window approach. We have developed a novel technique to identify window boundaries for subsequent analysis protocols. When applied to selection studies based on F ST data, this method provides a high discovery rate and minimizes false positives. The method is implemented in the R package GenWin, which is publicly available from CRAN.


Vascular ring in interruption of the aortic arch with bilateral patent ductus arteriosi.
The previously unreported occurrence of a true vascular ring in association with interruption of the aortic arch resulting from bilateral persistence of the ductus arteriosi is described. Division of both ductus is necessary to minimize the potential for tracheobronchial compression. This should be accomplished either during definitive (one-stage) repair of the interrupted aortic arch and associated anomalies or at the initial procedure of a staged repair.


Ontogenic study of lithium-pilocarpine-induced status epilepticus in rats.
Lithium is known to potentiate the ability of pilocarpine to induce status epilepticus in rats. The goal of this study was to determine whether lithium could potentiate pilocarpine-induced seizures in developing animals. Behavioral, electroencephalographic (EEG), and histopathological changes induced by systemic administration of lithium (3 meq/kg) followed 20 h later by pilocarpine (3, 10, 30, 60 mg/kg) were studied in 3-30-day-old rats. Lithium followed by pilocarpine (30 and 60 mg/kg) induced hyperactivity, tremor, loss of postural control and scratching but no electrographic seizures in 3-8-day-old rats. In the 7-10-day-old animals pretreatment with lithium and pilocarpine 60 mg/kg induced status epilepticus with sustained myoclonus and continuous bilateral synchronous spike and sharp wave, but doses of pilocarpine lower than 60 mg/kg had no effect. The susceptibility to lithium-pilocarpine-induced status epilepticus increased markedly during the third postnatal week of life. During this time period, rats treated with lithium (3 meq/kg) plus pilocarpine 10 mg/kg exhibited behavioral and EEG manifestations of status epilepticus. The same combination of lithium and pilocarpine failed to induce status epilepticus either before or after the third week of life. Histopathological analysis of the brains of the animals used in these studies failed to demonstrate the widespread damage reported in adult rats that have undergone lithium-pilocarpine-induced status epilepticus.


Biomarker discovery for neuroendocrine cervical cancer.
Neuroendocrine cervical cancer is an aggressive but rare form of cervical cancer. The majority of neuroendocrine cervical cancer patients present with advanced-stage diseases. However, the limited numbers of neuroendocrine tumor markers are insufficient for clinical purposes. Thus, we used a proteomic approach combining lysine labeling 2D-DIGE and MALDI-TOF MS to investigate the biomarkers for neuroendocrine cervical cancer. By analyzing the global proteome alteration between the neuroendocrine cervical cancer line (HM-1) and non-neuroendocrine cervical cancer lines (CaSki cells, ME-180 cells, and Hela cells), we identified 82 proteins exhibiting marked changes between HM-1 and CaSki cells, and between ME-180 and Hela cells. Several proteins involved in protein folding, cytoskeleton, transcription control, signal transduction, glycolysis, and redox regulation exhibited significant changes in abundance. Proteomic and immunoblot analyses indicated respective 49.88-fold and 25-fold increased levels of transgelin in HM-1 cells compared with that in other non-neuroendocrine cervical cancer cell lines, implying that transgelin is a biomarker for neuroendocrine cervical cancer. In summary, we used a comprehensive neuroendocrine/non-neuroendocrine cervical cancer model based proteomic approach for identifying neuroendocrine cervical cancer markers, which might contribute to the prognosis and diagnosis of neuroendocrine cervical cancer.


[Treatment of ureteral calculi with ballistic lithoclast].
To evaluate the availability of ballistic lithoclast in treatment of ureteral calculi. Totally 625 patients with ureteral calculi were treated with ballistic lithoclast by rigid ureteroscopy. Totally 610 patients were treated successfully by ballistic lithoclast with a cure rate of 97.6% (90.3% in upper ureter, 96.8% in middle ureter, 100% in lower ureter). The average time of lithoclast was (5.0 +/- 2.8) minutes and the stone-free rate was 99.2%. Ballistic lithoclast combined with rigid ureteroscopy is safe and effective in treating ureteral calculi.


Valorization of Rhizoclonium sp. algae via pyrolysis and catalytic pyrolysis.
The valorization of Rhizoclonium sp. algae through pyrolysis for obtaining bio-oils is studied in this work. The reaction is carried out at 400°C, at high contact time. The bio-oil has a practical yield of 35% and is rich in phytol. Besides, it is simpler than the corresponding to lignocellulosic biomass due to the absence of phenolic compounds. This property leads to a bio-oil relatively stable to storage. In addition, heterogeneous catalysts (Al-Fe/MCM-41, SBA-15 and Cu/SBA-15), in contact with algae during pyrolysis, are analyzed. The general trend is that the catalysts decrease the concentration of fatty alcohols and other high molecular weight products, since their mild acidity sites promote degradation reactions. Thus, the amount of light products increases upon the use of the catalysts. Particularly, acetol concentration in the bio-oils obtained from the catalytic pyrolysis with SBA-15 and Cu/SBA-15 is notably high.


Cervical elastography during pregnancy: a critical review of current approaches with a focus on controversies and limitations.
In normal pregnancy, the cervix functions as a protective mechanical barrier that must remain tight and closed. Premature remodeling and consecutive shortening occur in many cases of spontaneous preterm birth. Although the complex underlying physiology of normal and abnormal cervical remodeling is not fully understood, it is clear that cervical softening occurs prior to delivery, and inappropriate timing seems to be associated with preterm delivery. Also, degree of cervical softness is a component of the Bishop score currently used clinically to predict successful induction of labor. Therefore, the assessment of changes in cervical stiffness with ultrasound elastography techniques might be useful in the prediction of preterm delivery or successful induction of labor. Two different approaches for cervical elastography for quantitative determination of the physical properties of the pregnant cervix have been developed: strain elastography and shear wave elastography. Recently, several feasibility studies showed the reliability of these cervical elastography techniques for the prediction of preterm delivery and successful labor induction. In this review, we contrast strain elastography, which determines only relative values of tissue stiffness because the applied transducer pressure is unknown, with shear wave elastography, which provides, in principle at least, a more objective description of tissue softness. While more promising preliminary results involving these approaches to assessing cervical softness have been recently published, current limitations in technical implementation need to be addressed before elastography techniques will become clinically useful. We discuss these limitations and present challenges for future studies and equipment development.


The Phenotype of Elderly Patients with Type 2 Diabetes Mellitus and Poor Sleep Quality.
Sleep disturbances are a common problem among patients with Type 2 diabetes mellitus (T2DM). The aim of the study was to identify the phenotype of T2DM patients with poor sleep quality. An observational, cross-sectional study was conducted between May 2013 and August 2015. One hundred and sixty consecutive patients with T2DM: 74 women and 86 men, with a median age of 69.50 years (59.00; 79.50 years) were enrolled in the study. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Poor sleep quality was noted in 85 (53%) patients. Sleep disorders were associated with older age, as well as female gender, longer duration of diabetes, lower level of fasting plasma glucose, glycated hemoglobin A1c, estimated glomerular filtration rate, triglycerides, waist-to-hip ratio, and the presence of nephropathy. A multivariate logistic regression revealed that sleep disorders were associated with older age (Odd Ratio (OR) = 1.11, 95% Confidence Interval (CI) 1.07-1.15). Fifty-one patients (31.87%) were treated with sleeping pills. We found that older age, female gender, longer duration of diabetes, lower level of fasting plasma glucose, glycated hemoglobin A1c, estimated glomerular filtration rate, triglycerides, and the presence of nephropathy were linked with more frequent usage of hypnotics. A multivariate logistic regression demonstrated that older age (OR = 1.09, 95% CI 1.05-1.14) and nephropathy (OR = 2.79, 95% CI 1.24-6.28) were associated with a more frequent receiving the hypnotics, whereas male gender (OR = 0.30, 95% CI 0.13-0.71) has less frequent hypnotics usage. Although, we assessed a wide range of patients' characteristics, age had the most negative impact on the quality of sleep in patients with T2DM. We detected more frequent use of hypnotics in older females, with coexisting nephropathy.


[Carcinoma of the bladder. Clinical stage classification and therapy (author's transl)].
The therapeutic management of bladder tumors at the Zurich University Hospital is pointed out. It is to emphasize the important rank of the TNM-classification, which is introduced in the European Association of Urology, for comparing the results of therapy.


Frequency of D222G and Q223R hemagglutinin mutants of pandemic (H1N1) 2009 influenza virus in Japan between 2009 and 2010.
In April 2009, a novel swine-derived influenza A virus (H1N1pdm) emerged and rapidly spread around the world, including Japan. It has been suggested that the virus can bind to both 2,3- and 2,6-linked sialic acid receptors in infected mammals, in contrast to contemporary seasonal H1N1 viruses, which have a predilection for 2,6-linked sialic acid. To elucidate the existence and transmissibility of α2,3 sialic acid-specific viruses in H1N1pdm, amino acid substitutions within viral hemagglutinin molecules were investigated, especially D187E, D222G, and Q223R, which are related to a shift from human to avian receptor specificity. Samples from individuals infected during the first and second waves of the outbreak in Japan were examined using a high-throughput sequencing approach. In May 2009, three specimens from mild cases showed D222G and/or Q223R substitutions in a minor subpopulation of viruses infecting these individuals. However, the substitutions almost disappeared in the samples from five mild cases in December 2010. The D187E substitution was not widespread in specimens, even in May 2009. These results suggest that α2,3 sialic acid-specific viruses, including G222 and R223, existed in humans as a minor population in the early phase of the pandemic, and that D222 and Q223 became more dominant through human-to-human transmission during the first and second waves of the epidemic. These results are consistent with the low substitution rates identified in seasonal H1N1 viruses in 2008.


The diagnostic performance of ultrasound elastography for biliary atresia: A meta-analysis.
Biliary atresia (BA) is a severe inflammatory obliterative cholangiopathy of infancy that requires early diagnosis and prompt surgical intervention. In this study, we aimed to obtain comprehensive evidence on the diagnostic performance of liver stiffness measurement by ultrasound elastography in the detection of BA through a meta-analysis. The PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched for studies that investigated the diagnostic performance of ultrasound elastography in the detection of BA up to January 10, 2022. In this study, in order to summarize the diagnostic performance of ultrasound elastography, the summary receiver operating characteristic (SROC) modeling was constructed. Heterogeneity was estimated with the I 2 statistic. Multiple subgroup analyses were also performed. Fourteen studies from eleven articles, including 774 BA patients, 850 non-BA patients, and 173 controls were included in the present meta-analysis. The summary sensitivity and specificity of ultrasound elastography for liver stiffness were 85% [95% confidence interval (CI): 79-89%] and 82% (95% CI: 73-88%) with the I 2 value of 82.90 and 84.33%, respectively. The area under the SROC curve (AUROC) using ultrasound elastography for diagnosing BA was 0.90 (95% CI: 0.87-0.92). In addition, a subgroup analysis of 9 two-dimensional shear wave elastography studies was also performed. Subgroup analysis revealed that the summary sensitivity and specificity were 85% (95% CI: 77-91%) and 79% (95% CI: 71-86%), respectively, and the summary AUROC was 0.89 (95% CI: 0.86-0.92). Ultrasound elastography exhibits good diagnostic accuracy for BA and can be served as a non-invasive tool to facilitate the differential diagnosis of BA.


DISC1 association, heterogeneity and interplay in schizophrenia and bipolar disorder.
Disrupted in schizophrenia 1 (DISC1) has been associated with risk of schizophrenia, schizoaffective disorder, bipolar disorder, major depression, autism and Asperger syndrome, but apart from in the original translocation family, true causal variants have yet to be confirmed. Here we report a harmonized association study for DISC1 in European cohorts of schizophrenia and bipolar disorder. We identify regions of significant association, demonstrate allele frequency heterogeneity and provide preliminary evidence for modifying interplay between variants. Whereas no associations survived permutation analysis in the combined data set, significant corrected associations were observed for bipolar disorder at rs1538979 in the Finnish cohorts (uncorrected P=0.00020; corrected P=0.016; odds ratio=2.73+/-95% confidence interval (CI) 1.42-5.27) and at rs821577 in the London cohort (uncorrected P=0.00070; corrected P=0.040; odds ratio=1.64+/-95% CI 1.23-2.19). The rs821577 single nucleotide polymorphism (SNP) showed evidence for increased risk within the combined European cohorts (odds ratio=1.27+/-95% CI 1.07-1.51), even though significant corrected association was not detected (uncorrected P=0.0058; corrected P=0.28). After conditioning the European data set on the two risk alleles, reanalysis revealed a third significant SNP association (uncorrected P=0.00050; corrected P=0.025). This SNP showed evidence for interplay, either increasing or decreasing risk, dependent upon the presence or absence of rs1538979 or rs821577. These findings provide further support for the role of DISC1 in psychiatric illness and demonstrate the presence of locus heterogeneity, with the effect that clinically relevant genetic variants may go undetected by standard analysis of combined cohorts.


Serological survey of Q fever in Crete, southern Greece.
Coxiella burnetii, the causative agent of Q fever, is an obligatory intracellular bacterium with worldwide distribution. The aim of this study was to determine the prevalence of C. burnetii phase II antibodies in two different groups (high and low risk) of healthy human population and investigate the epidemiological characteristics of the infection in the island of Crete (southern Greece). Collection and testing by IFA of 493 sample sera for IgG and IgM antibodies against C. bumetii phase II antigen indicated a prevalence of IgG antibodies of 48.7%. Of the seropositive individuals, 34% also revealed IgM seropositive antibody titers. Analysis of 225 sample sera by IFA from high risk population presented a prevalence for C. burnetii of 62.2%. Our findings revealed that C. burnetii is highly endemic in Crete, indicating a high exposure of the population to the pathogen regardless of occupation or place of residence.


Alternate Restacking of 2 D CoNi Hydroxide and Graphene Oxide Nanosheets for Energetic Oxygen Evolution.
Morphology and composition tuning of layered materials is evaluated to influence their electrochemical performance for energy storage and conversion applications. Layered Co1-x Nix hydroxides (x=0, 1/2, 1/3, 1/4, 1) of three different morphologies-nanocones, 2 D nanosheets obtained by the rapid exfoliation of nanoconical counterparts, and 2 D superlattice-like nanostructures alternately restacked by the oppositely charged hydroxide and graphene oxide (GO) nanosheets-have been systematically investigated for electrocatalytic oxygen oxidation. High activity is obtained with the 2 D Co2/3 Ni1/3 hydroxide nanosheets/GO superlattice (Co2/3 Ni1/3 NS-GO), achieving a current density of 10 mA cm-2 at a low overpotential of 259 mV accompanied by a small Tafel slope of 35.7 mV dec-1 , surpassing nanocones and 2 D nanosheets, as well as the congeneric heterostructured Co1-x Nix hydroxide nanosheets/GO nanoarchitectures (Co1-x Nix NS-GO; x=0, 1/2, 1/4, 1) and the commercial RuO2 electrocatalyst. The outstanding activity of Co2/3 Ni1/3 NS-GO superlattice uncovers the combined merits of 2 D superlattice-like structure and composition optimization for electrocatalysis, providing a strategy for developing high-performance electrochemical materials by rational morphology and composition design.


Potential methane emission reductions for two manure treatment technologies.
The effect of two dairy manure treatments, solid-liquid separation (SLS) and anaerobic digestion (AD), on methane potential and the speed of production was evaluated. Assays were performed in the lab to measure methane (CH4) production over 202 d from dairy manure samples taken before and after each treatment. Compared to raw manure, CH4 emissions on a per-L basis were reduced 81% by SLS and 59% by AD, on average. The mean (SD) ultimate CH4 emission potential (B0) per kg of volatile solids (VS) was 247 (8) L CH4 kg-1 VS for raw manure, 221 (9) L CH4 kg-1 VS for separated liquid, and 160 (4) L CH4 kg-1 VS for anaerobic digestate. Thus, SLS reduced the B0 of the liquid fraction by 11% and AD reduced B0 by up to 35% compared to raw manure. Manure treatment affected the speed of CH4 production: SLS increased the CH4 production rate and thus separated liquid manure was the fastest to produce 90% of the ultimate CH4 production. Therefore, both the speed of degradation and B0 should be considered when assessing these techniques for farm-scale manure storages, because actual emission reductions will depend on storage conditions.


Effectiveness of antiepileptic drug tapering in the pediatric epilepsy monitoring unit.
Limited evidence on the relationship between antiepileptic drug (AED) tapering and the likelihood of a seizure during an Epilepsy Monitoring Unit (EMU) admission is available, and no evidence specific to the pediatric population has been published. Our study sought to determine whether AED tapering leads to increased seizure likelihood in a pediatric EMU setting. We performed a retrospective chart review of children admitted to the pediatric EMU at the Hospital for Sick Children in Toronto between June 1, 2014 and June 1, 2016. Data collected included demographics, reason for EMU referral, and epilepsy and medical characteristics. Among those with nondaily seizures, Kaplan-Meier curves were fit to compare probability of EMU seizure in those who were tapered fully from at least one AED to those not tapered. A Cox proportional hazards model was fit to evaluate this relationship after adjustment for subject sex, distance traveled to hospital, epilepsy duration, seizure frequency, time since last seizure, whether EMU referral was part of presurgical planning, magnetic resonance imaging (MRI) findings, and number of prescribed AEDs. An interaction between medication taper and number of prescribed AEDs was also included. Terms not significant at p < 0.3 were removed from the model, and the reduced model was recomputed. Of the 281 children included in the study, 159 had nondaily seizures. Kaplan-Meier curves indicated fully tapering at least one AED was associated with increased likelihood of seizure during EMU; however, after adjustment for confounding variables, this association was not preserved. Abnormal MRI findings, referral for presurgical evaluation, and shorter (≤3 months) time since last seizure were associated with increased likelihood of seizure during EMU. Short-term AED tapering in pediatric patients may not be effective for increasing seizure likelihood in the EMU.


Rationale and methods of the integrated biomarker and imaging study (IBIS): combining invasive and non-invasive imaging with biomarkers to detect subclinical atherosclerosis and assess coronary lesion biology.
Death or myocardial infarction, the most serious clinical consequences of atherosclerosis, often result from plaque rupture at non-flow limiting lesions. Current diagnostic imaging with coronary angiography only detects large plaques that already impinge on the lumen and cannot accurately identify those that have a propensity to cause unheralded events. Accurate evaluation of the composition or of the biomechanical characteristics of plaques with invasive or non-invasive methods, alone or in conjunction with assessment of circulating biomarkers, could help identify high-risk patients, thus providing the rationale for aggressive treatments in order to reduce future clinical events. The IBIS (Integrated Biomarker and Imaging Study) study is a prospective, single-center, non-randomized, observational study conducted in Rotterdam. The aim of the IBIS study is to evaluate both invasive (quantitative coronary angiography, intravascular ultrasound (IVUS) and palpography) and non-invasive (multislice spiral computed tomography) imaging techniques to characterize non-flow limiting coronary lesions. In addition, multiple classical and novel biomarkers will be measured and their levels correlated with the results of the different imaging techniques. A minimum of 85 patients up to a maximum of 120 patients will be included. This paper describes the study protocol and methodological solutions that have been devised for the purpose of comparisons among several imaging modalities. It outlines the analyses that will be performed to compare invasive and non-invasive imaging techniques in conjunction with multiple biomarkers to characterize non-flow limiting subclinical coronary lesions.


Concentrated polymer brushes do not induce the expression of inflammatory and angiogeneic genes in human umbilical vein endothelial cells.
When polymer brushes are applied as the inner coating for artificial blood vessels, they may induce unwanted responses in vascular endothelial cells continuously exposed to the polymer surface. Accordingly, we have examined the in vitro effect of non-biofouling concentrated polymer brushes (CPBs) on pro-inflammatory and angiogenic responses of human umbilical vein endothelial cells (HUVECs). Micro-patterned CPBs were prepared on silicon wafers using biocompatible polymers, poly(poly(ethylene glycol)methyl ether methacrylate) (PPEGMA) and poly(2-hydroxyethyl methacrylate) (PHEMA). HUVECs were cultured on PPEGMA-CPBs and PHEMA-CPBs with different channel widths (20, 50, and 80 µm) and analyzed for mRNA expression of the pro-inflammatory cytokines IL-6 and IL-8 and angiogeneic vascular endothelial growth factor (VEGF). Irrespective of channel width, PHEMA-CPBs reduced the expression of all target genes, whereas PPEGMA-CPBs reduced VEGF and did not affect IL-6 and IL-8 levels. Micro-patterned CPBs, irrespective of chemical structure or adhesion area, do not induce the expression of important pro-inflammatory and angiogenic mediators in endothelial cells.


Electronic properties and behavior of carbon network based on graphene and single-walled carbon nanotubes in strong electrical fields: quantum molecular dynamics study.
Using the self-consistent-charge density-functional tight-binding method (SCC-DFTB) and extended lagrangian DFTB-based molecular dynamics, we performedin silicostudies of the behavior of graphene-nanotube hybrid structures that are part of a branched 3D carbon network in strong electrical fields. It has been established that strong fields with strength ranging from 5 to 10 V nm-1cause oscillating deformations of the atomic framework with a frequency in the range from 1.22 to 1.38 THz. It has been revealed that the oscillation frequency is determined primarily by the topology of the atomic framework of graphene-nanotube hybrid, while the electric field strength has an effect within 1%-2%. A further increase in electric field strength reduces the oscillation frequency to 0.7 THz, which accompanies the partial destruction of the atomic framework. The critical value of the electric field strength when the graphene is detached from the nanotube is ∼20 V nm-1.


Role of pharmacokinetic consideration for the development of drug delivery systems: A historical overview.
Drug delivery system is defined as a system or technology to achieve optimum therapeutic effects of drugs through precise control of their movements in the body. In order to optimize function of drug delivery systems aiming at targeting, their whole-body distribution profiles should be systematically evaluated and analyzed, where pharmacokinetic analysis based on the clearance concepts plays important role. Organ perfusion experiments combined with statistical moment analysis further supply detailed information on drug disposition at organ and cellular levels. Based on general relationship between physicochemical properties and distribution profile, macromolecular prodrugs or polymer conjugates of proteins are rationally designed and further introduction of ligand structure brings cell-specific delivery for them. These approaches are also applicable for particulate carriers such as liposomes and offer various opportunities for biological drugs such as nucleic acid drugs for their delivery. Mechanistic approach for dermal absorption analysis based on physiological skin model offers another opportunity in rational design of drug delivery. Potential of drug delivery technology in future medicines such as cell therapy and nanomaterial platform application is further discussed in relation to pharmacokinetic consideration.


Endothelium-derived relaxing factor released from cultured cells: differentiation from nitric oxide.
1. Endothelium-derived relaxing factor (EDRF) is an extremely labile mediator thought to be identical to nitric oxide (NO). 2. A cascade superfusion technique was used to bioassay EDRF released from bovine aortic endothelial cells grown to confluence on microcarrier beads. 3. Bradykinin (1-100 nmol/l), infused through a 1 cm column of endothelial cells on microcarriers, released an EDRF-like substance that caused relaxations of de-endothelialized strips of rabbit aorta (precontracted with phenylephrine). These relaxations diminished on successive tissues in the cascade, when compared with those produced by glyceryl trinitrate as a stable standard. 4. Haemoglobin (1 mumol/l), infused directly over the bioassay tissues, abolished bradykinin-induced relaxations and these were restored within 5 min after removal of haemoglobin. The infusion did not affect the relaxations produced by glyceryl trinitrate in this system. 5. Methylene blue (20 mumol/l) inhibited bradykinin-induced relaxations when infused over the rabbit aortae, and reduced those relaxations produced by glyceryl trinitrate. The effects of bradykinin, but not glyceryl trinitrate, were partially restored after removing methylene blue. 6. These data are consistent with the known effects of these compounds on the activity of NO, and on EDRF in isolated blood vessels. 7. The activity of EDRF (released by bradykinin) was compared directly with NO on strips of guinea-pig trachea (de-epithelialized) interposed in cascade between two rabbit aortae; all strips were precontracted with histamine and phenylephrine. 8. A submaximal dose of NO that matched the relaxation produced by EDRF on the uppermost aorta, caused relaxation of the trachea, but EDRF had no effect on this tissue. In addition, the NO-induced relaxation of the lower aorta was greater than that produced by EDRF. 9. These data indicate that EDRF does not have identical biological activity to NO. EDRF could contain an NO moiety attached to a carrier molecule that is bound and stabilized in tracheal tissue.


Mitochondria transfer can enhance the murine embryo development.
To evaluate the effect of mitochondrial transfer on embryonic development. Mitochondria concentrates were collected from murine hepatocytes and fertilized murine zygotes from young and older mice in the 2PN stage were subjected to mitochondrial transfer and cultured in vitro to evaluate the embryonic development. After extended in vitro culture, 37.65% and 20.91% embryos from the young mice developed to the blastocyst stage in the injected and control groups respectively, which is statistically significant. There was no difference in terms of hatching rates (1.76% and 1.82% respectively). Zygotes from the older mice (>20 weeks old) that received mitochondrial transfer also had a better developmental outcome than the control group (54.35% and 18.92% developed to morula stage, 43.48% and 8.11% developed to the blastocyst stage respectively), which is statistically significant. Our results for the murine model provide direct scientific evidence that mitochondrial transfer improves embryonic development. However, potential risks such as mitochondrial heteroplasmy, nuclear-mitochondrial interaction and epigenetic aspects all deserve further evaluation before mitochondrial transfer is applied clinically.


Performance and antioxidant traits of broiler chickens fed with diets containing rapeseed or flaxseed oil and optimized quercetin.
This study evaluated the effect of quercetin (Q) added to feed mixtures, at concentrations directly optimized for the peroxidability of dietary rapeseed (RO) and flaxseed oil (FLO), on performance and selected biomarkers of oxidative stress of broiler chickens. Ninety-six one-day-old Ross 308 broiler chicken males were randomly assigned to four groups (six replicates per treatment, four birds per cage, n = 24 per group): Group RO received diets containing rapeseed oil (RO) and group FLO received diets containing flaxseed oil (FLO); Group RO_Q and group FLO_Q received these same diets containing RO or FLO oils, supplemented with optimized quercetin (Q). Blood, pectoral muscles, and liver samples of chickens were collected after 35 days to determine: (1) the global indicators of antioxidant capacity: ferric reducing antioxidant power (FRAP), antiradical activity (DPPH·/ABTS·+), total antioxidant status (TAS), and glutathione peroxidase (GSH-Px); (2) the activity of the antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD); and (3) the concentration of malondialdehyde (MDA). Data showed that the FLO diet did not affect the final performance parameters in relation to RO, but the optimized Q tended to improve the total body weight gain and the final body weight of broiler chickens (P = 0.10). The antioxidant traces analyzed in the blood (GSH-Px), plasma (FRAP, ABTS·+, DPPH·, TAS), serum (DPPH·), and pectoral muscles (SOD, CAT) of chickens were not altered by either Oil or Q factor. FLO supplementation increased MDA content in the liver of chickens (P < 0.05) and increased liver CAT activity, which was not improved by optimized Q. Meanwhile, the Oil × Q interaction suggests that optimized Q could reduce the liver burden and negative effects of oxidized lipid by-products associated with FLO diets. Our results indicate that optimizing the addition of natural polyphenols to feed may be a valuable alternative to the application of polyphenolic antioxidants in animal nutrition, allowing for an economical use of the antioxidant additives when customized to the peroxidability of fat sources, which is line to the conception of sustainable development covering 'The European Green Deal' and 'Farm to Fork Strategy'.


Unilocular cystic lymphangioma of thigh-an extremely rare clinical entity.
Majority of cystic lymphangiomas are multilocular and occur in neck and axilla. The cystic lymphangioma is also known as cystic hygroma. Unilocular cystic hygroma of neck and breast have been reported in literature and have been termed hydrocele of neck and breast respectively. However unilocular cystic hygroma of thigh is probably being reported for the first time.


Prostacyclin: a potent stimulator of adrenal steroidogenesis.
The relative potencies of various prostaglandins were investigated in trypsin-dispersed cat adrenocortical cells. Prostacyclin proved to be the most potent steroidogenic prostaglandin, being 100-1000 times more potent than PGE2. This stimulant effect of prostacyclin was only partially dependent upon the presence of extracellular calcium and was associated with increased levels of cyclic AMP. These data suggest a possible role for prostacyclin in corticosteroidogenesis.


Reappraisal of Hydatigera taeniaeformis (Batsch, 1786) (Cestoda: Taeniidae) sensu lato with description of Hydatigera kamiyai n. sp.
The common cat tapeworm Hydatigera taeniaeformis is a complex of three morphologically cryptic entities, which can be differentiated genetically. To clarify the biogeography and the host spectrum of the cryptic lineages, 150 specimens of H. taeniaeformis in various definitive and intermediate hosts from Eurasia, Africa and Australia were identified with DNA barcoding using partial mitochondrial cytochrome c oxidase subunit 1 gene sequences and compared with previously published data. Additional phylogenetic analyses of selected isolates were performed using nuclear DNA and mitochondrial genome sequences. Based on molecular data and morphological analysis, Hydatigera kamiyai n. sp. Iwaki is proposed for a cryptic lineage, which is predominantly northern Eurasian and uses mainly arvicoline rodents (voles) and mice of the genus Apodemus as intermediate hosts. Hydatigera taeniaeformis sensu stricto (s.s.) is restricted to murine rodents (rats and mice) as intermediate hosts. It probably originates from Asia but has spread worldwide. Despite remarkable genetic divergence between H. taeniaeformis s.s. and H. kamiyai, interspecific morphological differences are evident only in dimensions of rostellar hooks. The third cryptic lineage is closely related to H. kamiyai, but its taxonomic status remains unresolved due to limited morphological, molecular, biogeographical and ecological data. This Hydatigera sp. is confined to the Mediterranean and its intermediate hosts are unknown. Further studies are needed to classify Hydatigera sp. either as a distinct species or a variant of H. kamiyai. According to previously published limited data, all three entities occur in the Americas, probably due to human-mediated introductions.


Hepatitis B virus DNA forms in the liver of chronically infected individuals. Relation to replication profile.
To analyze the profile of HBV-DNA forms in the liver in relation to different levels of virus replication, liver biopsies from 52 chronic HBsAg carriers were studied by Southern blot analysis. Quantitative evaluation of the major HBV-DNA molecules was carried out by densitometry in 27 patients with ongoing hepatitis B virus (HBV) replication in the liver. Significant variations in the intensity of the different bands were noted in individual cases, but statistical correlation between the amount of single stranded forms and levels of serum HBV-DNA was not observed. In contrast, the amount of linear 3.2 kb HBV-DNA appeared to have an inverse correlation with levels of circulating virions. Only the 3.2 kb form was detected in three patients negative for serum HBV-DNA. In these cases with 'inactive' state of episomic HBV genome seroconversion to anti-HBe occurred from 12 months before to 4 months after the time of liver biopsy testing. This 3.2 kb form can therefore be interpreted as a pattern of transition from the replicative to the non-replicative state of the virus.


A Case of Novel Lamin A/C Mutation Manifesting as Atypical Progeroid Syndrome and Cardiomyopathy.
Mutations in the gene LMNA cause a wide spectrum of diseases that selectively affect different tissues and organ systems. The clinical features of these disorders can overlap but be generally categorized into 2 groups: cardiomyopathy and neuromuscular disorders; premature aging and lipodystrophy disorders. It is significant for a single patient who harbours the 2 sets of diseases simultaneously. We present a female patient with a unique phenotype including rare atypical progeroid syndrome and dilated cardiomyopathy. Genetic mutation detection in the gene LMNA revealed a novel heterozygous de novo mutation p.Leu59Val located in the first exon of gene LMNA c.175C>CG.


Quantitative non-targeted analysis: Bridging the gap between contaminant discovery and risk characterization.
Chemical risk assessments follow a long-standing paradigm that integrates hazard, dose-response, and exposure information to facilitate quantitative risk characterization. Targeted analytical measurement data directly support risk assessment activities, as well as downstream risk management and compliance monitoring efforts. Yet, targeted methods have struggled to keep pace with the demands for data regarding the vast, and growing, number of known chemicals. Many contemporary monitoring studies therefore utilize non-targeted analysis (NTA) methods to screen for known chemicals with limited risk information. Qualitative NTA data has enabled identification of previously unknown compounds and characterization of data-poor compounds in support of hazard identification and exposure assessment efforts. In spite of this, NTA data have seen limited use in risk-based decision making due to uncertainties surrounding their quantitative interpretation. Significant efforts have been made in recent years to bridge this quantitative gap. Based on these advancements, quantitative NTA data, when coupled with other high-throughput data streams and predictive models, are poised to directly support 21st-century risk-based decisions. This article highlights components of the chemical risk assessment process that are influenced by NTA data, surveys the existing literature for approaches to derive quantitative estimates of chemicals from NTA measurements, and presents a conceptual framework for incorporating NTA data into contemporary risk assessment frameworks.


Characterization of DNA polymerase I*, a form of DNA polymerase I found in Escherichia coli expressing SOS functions.
DNA polymerase I* is a form of the DNA polymerase I isolated from Escherichia coli which are expressing recA/lexA (SOS) functions. Induction of recA or polA1 cells by nalidixic acid does not result in the appearance of pol I*, but lexA or recA mutants that are constitutive for SOS functions constitutively express pol I* and mutants which lack functional recA protein produce pol I* when they carry a lexA mutation which renders the lexA repressor inoperative. Pol I* has been induced by nalidixic acid in dinA, dinD, dinF, and umuC mutants. Polymerase I* has a lower affinity for single-stranded DNA-agarose than polymerase I and it sediments through sucrose gradients in a dispersed manner between 6.6-10.5 S, whereas polymerase I sediments at 5 S. Whereas pol I* migrates significantly faster than pol I in nondenaturing polyacrylamide gels, the active polypeptide of both forms migrates at the same rate in denaturing polyacrylamide gels. Compared with polymerase I, polymerase I* has an enhanced capacity to incorporate the adenine analog, 2-amino-purine, into activated salmon sperm DNA and a relatively low fidelity in replicating synthetic polydeoxyribonucleotides. Both the 3'----5' (proofreading) and 5'----3' (nick-translational) exonuclease activities of pol I* and pol I are indistinguishable. Estimates of processivity give a value of approximately 6 for both forms of the enzyme.


Health-Related Quality of Life in Patients with the Bladder Exstrophy-Epispadias Complex and Relationship to Incontinence and Sexual Factors: A Review of the Recent Literature.
The bladder exstrophy-epispadia complex (BEEC) includes malformations with midline closing defects of the lower abdomen and external genitalia. Long-term consequences with urinary incontinence and sexual dysfunction, in spite of multiple surgical interventions, are common and expected to affect the patient's health-related quality of life (HRQOL). The extent and the predictive factors are, however, not known. New patient-reported outcome research is emerging, but valid and reliable condition-specific HRQOL are still missing. The aim of this review is to summarize and discuss the latest published reports (2015-2019) on HRQOL in patients with the BEEC and its relationship to incontinence and sexual factors.


Effects of beta-lactam antibiotics on eukaryotic cells.
A symposium on effects of beta-lactam antibiotics on eukaryotic cells was held as part of the 9th International Congress of Infectious and Parasitic Diseases (Munich, Germany, July 1986). This symposium provided an opportunity to review recent work on the effect of beta-lactam structures on mammalian cells in culture and to speculate on possible clinical implications. This paper is a comment on the subject matter covered by the symposium papers which follow.


Innate immunity and the lung: defense at the interface between host and environment.
The lung serves as a major interface between the host and the external environment. As such, numerous lines of defense protect the host from inhaled potential pathogens. A breach in pulmonary innate immunity can lead to deleterious outcomes, such as pneumonia and disseminated infection. Pulmonary innate immunity, the first line of defense, is mediated by airway and alveolar epithelial cells as well as resident and recruited leukocytes. This article will discuss the key cellular and secreted components of the pulmonary innate immune system.