Reaction pattern of xenografted human salivary glands in nude mice. An immunohistological and autoradiographical study.
35 specimens of human parotid gland and 37 of submandibular gland were transplanted into athymic nude mice. At distinct time intervals, from 1 day to 8 months the transplants were collected and examined. The transplanted glands were studied by light microscopy, immunohistology and autoradiography. The following changes were detectable: acute injury to the xenograft and inflammatory reaction (day 1-7), regeneration of the transplant and the beginning of adaptation to the "mouse milieu" (day 8-30), completion of adaptation (day 30 and later). The presence of the following substances was analysed: amylase, lactoferrin, secretory component, tissue polypeptide antigen (TPA). Amylase was only detected in the early transplants. Lactoferrin was seen only in the small duct system. TPA was present during all transplantation periods and was quantitatively correlated with the 3H thymidine labeling index. From our observations we can say that the salivary glands show two different reacting compartments: a large and a small duct system. The histogenesis of the xenografts, and the relationships of the changes observed to human salivary gland diseases were discussed.


A time function-based prediction model of mining subsidence: application to the Barapukuria coal mine, Bangla.
Coal mining may lead to ground subsidence in a long term and is widely distributed, which can cause environmental damage and other disasters. Predicting the dynamic process of ground subsidence in real time is very important for offering theoretical or technical guidance to deal with the consequences of mining. In this study, we developed a prediction method for dynamic ground subsidence using a time function model that considers two stages of surface subsidence and reflects the law of surface subsidence in goaf. We applied the model to the Barapukuria mine, and our simulation shows that the prediction results are in good agreement with the monitoring data. Our results suggest that the dynamic development of the ground subsidence basin may be an effective measure to assess the loss of ground and provide early warning of oncoming hazards.


Pectin-based composite film: Effect of corn husk fiber concentration on their properties.
Considering the polysaccharide composition and 32% of crystallinity of the water insoluble fiber extracted from corn husk (CHF) agricultural residue, its filler performance as water vapor permeability (WVP) and mechanical modifier in edible films based on commercial low methoxyl pectin (LMP) was evaluated (0, 1, 3, 5, 8% concentrations). The 53-μm-CHF carried phenolics and carotenes, and composites showed antioxidant capacity. Homogeneous films with a continuous LMP matrix were obtained. The 5%-CHF composite showed the highest surface contact angle (44°) and tensile strength, without change in elongation, while WVP was decreased in the 3-8% CHF-LMP-films. The latter was ascribed to the CHF-filler crystallinity whereas the improvement in mechanical performance and contact angle was attributed to a CHF-interconnected network formed at 5%-CHF critical concentration. Corn husk residue can be utilized as a source of fibers for material development. Composites with enhanced performance can be an antioxidant strategy at food interfaces.


Cyclic AMP mediated activity stimulation by metronidazole in rat liver.
In the homogenate of the liver biochemically examined 45 hrs after a single 250 mg dose of metronidazole administration, a 45% increase of c-AMP level was found as compared with controls. A marked proliferation of hepatic smooth endoplasmic reticulum was observed. In the light microscope numerous mitotic figures could be seen. No mitotic figures were present in the liver tissue of either treated or untreated animals examined 24, 72 and 120 hrs post administration of metronidazole. Two points seem of interest in the biologic properties of metronidazole: one is the participation of hepatic smooth endoplasmic reticulum in its metabolism, the other--the formation of active metabolites which may posses carcinogenous properties.


Appearance of lectin-binding sites during vascularization of the primordium of the central nervous system in 10 to 12-day-old mouse embryos.
In the present study lectin-binding sites were investigated for the lectins Ricinus communis agglutinin (RCA I), wheat germ agglutinin (WGA), soya bean agglutinin (SBA), concanavalin A (Con A), Lotus tetragonolobus-(LTA) and Limulus polyphemus agglutinin (LPA) during the initial stages of vasculogenesis of the CNS-anlage in 10 to 12-day-old NMRI mouse embryos. Specific binding sites for the lectins RCA I (sugar specificity: beta-D-galactose, N-acetylgalactosamine), WGA (sugar specificity: N-acetylglucosamine, sialic acid), and SBA (sugar specificity: N-acetylgalactosamine, beta-D-galactose) were detected in the newly formed capillaries within the neuroepithelial cell layer. In contrast, binding sites for Con A, LTA and LPA could not be observed at the start of the vascularization of the CNS-anlage. From these results, the conclusion can be drawn that glycoconjugates containing D-galactose, N-acetylgalactosamine and N-acetyl-glucosamine moieties are involved in the early vasculogenesis of the embryonic CNS-anlage of the mouse.


Structure-Property Relationship for Different Mesoporous Silica Nanoparticles and its Drug Delivery Applications: A Review.
Mesoporous silica nanoparticles (MSNs) are widely used as a promising candidate for drug delivery applications due to silica's favorable biocompatibility, thermal stability, and chemical properties. Silica's unique mesoporous structure allows for effective drug loading and controlled release at the target site. In this review, we have discussed various methods of MSNs' mechanism, properties, and its drug delivery applications. As a result, we came to the conclusion that more in vivo biocompatibility studies, toxicity studies, bio-distribution studies and clinical research are essential for MSN advancement.


Beta-lactamase activity in mycobacteria other than M. tuberculosis.
Beta-lactamase activity was studied in 142 non-tuberculosis mycobacterial strains. The distribution according to species was as follows: four M. avium, 14 M. chelonae, 10 M. fortuitum, 59 M. gordonae, 55 M. kansasii. The spectrum of hydrolysis of the beta-lactamases was screened using an acidimetric method and the characterization was performed by analytical isoelectric focusing.


A transitional cell carcinoma cell line.
A transitional cell carcinoma cell line, COLO 232, was derived from a primary urinary bladder tumor in a Caucasian male. In culture, COLO 232 retained distinct uroepithelial phenotypic traits and produced both carcinoembryonic antigen and adrenocorticotropic hormone. COLO 232 had a chromosome mode of 58 and retained the X and Y chromosomes. Ten marker chromosomes were identified. COLO 232 will be of value for biochemical and immunological studies.


Comparative study of the effects of laser photobiomodulation and extract of Brassica oleracea on skin wounds in wistar rats: A histomorphometric study.
The objective of this study was to investigate the effect of a photobiomodulation laser and Brassica oleracea on tissue morphology in skin wounds. The parameters analyzed were type I and III collagen fibers, and thickness and surface density of the epithelial tissue, as well as how quickly the wound closed. Five skin wounds 12mm in diameter were made on the backs of the animals, which were randomized into four groups (8 animals each). Saline Group: 0.9% saline solution; Ointment Group (extract of Cabbage, B. oleracea, 10% lanolin); Balsam Group (10% glycolic extract of B. oleracea emulsion oil); L60 Group (laser GaAsAl 60J/cm(2)). The applications were made daily during a 20-day treatment, and every 4 days tissue from different wounds was removed. The reduction in the size of the wounds on the 4th, 8th, 12th and 16th days was significantly greater in the treated groups compared to the control group. At all the time points analyzed, there was a greater proportion of collagen in the Balsam and L60 groups (p<0.05). There was also a greater proliferation of epithelial cells in the L60 and Balsam groups after 20 days of treatment (p<0.05). The healing extract and laser 60j/cm(2) exerted a great effect on collagen proliferation in stimulating scar tissue maturation.


[Rare case of incomplete Shone syndrome in adult man with marfanoid morphotype].
Shone syndrome is a rare and complex congenital heart disease. It is characterized in its complete form, by a constellation of the four potentially obstructive lesions of the left heart side. Incomplete Shone's complex includes 2 or 3 of the characteristic lesions which, include a supravalvular mitral membrane, valvular mitral stenosis (MS) by a parachute mitral valve (PMV), subaortic stenosis and aortic coarctation (Coa). We describe here, the case of a 35-year-old man, hospitalized for chronic dyspnea and in whom, the diagnosis of incomplete Shone's complex is retained by echocardiographic analysis. Observed lesions include a parachute mitral valve responsible for mild regurgitation and moderate mitral stenosis, bicuspid aortic valve, and pseudo interruption of the aorta with dilatation of the ascending aorta and a patent ductus arteriosus. This case is the 2nd on 3942 patients in Drighil congenital heart disease registry.


Cardiac event risk stratification in patients with end-stage renal disease: Sub-analysis of the B-SAFE study.
The aim of this study was to investigate whether 123I-labelled β-methyl iodophenyl-pentadecanoic acid (BMIPP) imaging as an abnormal myocardial fatty acid metabolism indicator better predicted fatal and non-fatal cardiac events than conventional predictors [e.g. peripheral artery disease (PAD) and diabetes mellitus (DM)] in haemodialysis patients. In a sub-analysis of the BMIPP SPECT Analysis for Decreasing Cardiac Events in Haemodialysis Patients (B-SAFE) study, 677 asymptomatic patients with ≥1 cardiovascular risk factor and without known coronary artery disease were followed for 3 years. The amount of radioactivity in each 17-left ventricular segment was graded visually and assigned a score from 0 (normal) to 4 (absent). Its total values were designated as baseline summed BMIPP scores. Outcome measures were composite cardiac events. Cardiac events correlated with age, PAD [hazard ratio (HR): 2.15; p=0.003], DM (HR: 1.76; p=0.006) and summed BMIPP scores (4-8, HR: 1.82; p<0.001; ≥9, HR: 3.49; p<0.001). Cardiac event-free rates decreased with increasing summed BMIPP scores, PAD and DM. Areas under the receiver operating curves (AUCs) indicated that a BMIPP-based model (AUC: 0.656) was more predictive than DM or PAD models (AUC: 0.591); a model with all three was most predictive (AUC: 0.708). The three-year cardiac event-free rates significantly decreased in patients with PAD and/or DM in all summed BMIPP score categories. Abnormal myocardial fatty acid metabolism strongly predicts cardiac events in haemodialysis patients; those with PAD or DM are at high risk for cardiac events.


Single centre experience of 120 patients with non-infectious aortitis: Clinical features, treatment and complications.
Aortitis is an important form of vasculitis with significant risk of complications. Very few studies have provided detailed clinical phenotyping across the whole disease spectrum. Our primary aim was to look the clinical features, management strategies and complications associated with non-infectious aortitis. A retrospective review was performed on patients with diagnosis of noninfectious aortitis at the Oxford University hospitals NHS Foundation Trust. Clinicopathologic features were recorded including demographics, presentation, aetiology, laboratory, imaging findings, histopathology, complications, treatment, and outcome. We report the data on 120 patients (59% females). Systemic inflammatory response syndrome constituted the most common presentation (47.5%). 10.8% were diagnosed following a vascular complication (dissection or aneurysm). All patients (n = 120) had raised inflammatory markers (median ESR 70.0 mm/h and CRP 68.0 mg/L). Isolated aortitis subgroup (15%) had significantly higher likelihood of presenting with vascular complications and challenging to diagnose due to non-specific symptoms. Prednisolone (91.5%) and methotrexate (89.8%) were the most used treatment. 48.3% developed vascular complications during the disease course including ischaemic complications (25%), aortic dilatation and aneurysms (29.2%) and dissection (4.2%). Risk of dissection was higher in the isolated aortitis subgroup at 16.6% compared to all other types of aortitis at 1.96%. Risk of vascular complications is high in non-infectious aortitis patients during disease course, hence early diagnosis and appropriate management is key. DMARDs such as Methotrexate appear to be effective, nonetheless there remain gaps in evidence for longer-term management of relapsing disease. Dissection risk seems much higher for patients with isolated aortitis.


Online nephrology course replacing a face to face course in nursing schools' bachelor's program: a prospective, controlled trial, in four Israeli nursing schools.
Online learning is growing rapidly worldwide, especially in the health related sectors such as medicine and nursing. Our trial wished to measure the objective (i.e. final exam results, courseware usage patterns) and subjective (satisfaction) efficiency of online vs. face-to-face learning in a prospective, controlled trial, a first of its kind in Israel. The trial tested a blended online course, teaching introduction to clinical nephrology. The course was filmed and edited into a learning platform to fit computer based learning. 90 nursing students, from 4 bachelor's nursing programs in Israel participated in the study. The intervention group included 32 students who studied using the online course, accompanied by 3 frontal meetings dealing with technical and content issues. The reference group included 58 students from 3 nursing programs, studying in a traditional face-to-face course. The final exam results were significantly higher in the intervention group compared with the reference group (9.6 ± 2.57 vs. 8.4 ± 2.72; p<0.05). Student satisfaction was very high in the intervention group: 97% thought the course was well organized, 100% thought the teacher taught clearly and consistently, 90% thought the teacher encouraged self-thinking,100% thought the teacher used clarifying examples, 91% thought the teaching aids helped the learning process and 97% thought the teaching method contributed to the learning process. The average usage of the online course was 4:10h vs. 14 academic hours (10:30 h) in the traditional course. The daily usage habits of the courseware were also followed, indicating that most learning took place between 12 PM and 1 AM, peaking between 5 PM and 7 PM, and dipping between 3 AM and 10 AM. The online course had higher efficiency compared to the traditional face-to-face course. The subjective feedback of the intervention group proves high satisfaction with online learning.


Treatment of oroantral fistula:experience with 27 cases.
To review patients with chronic oroantral and oronasal fistula who underwent surgical correction. Twenty-seven patients with chronic oroantral and oral fistula who underwent surgical correction in the Hacettepe University Faculty of Medicine Department of Otorhinolaryngology Head and Neck Surgery between 1968 and 2001 were reviewed retrospectively. Local mucosal flaps were used for surgical correction. The underlying factors were tooth extraction in 13 patients (48%), tumor in 5 (18.5%), osteomyelitis in 3 (11%), Caldwell-Luc procedure in 2 (7.5%), trauma in 2 (7.5%), dentiginous cyst in 1(3.7%), and correction of septal perforation in 1 (3.7%). Among the fistulas, 23 were oroantral, 3 were oroantronasal, and 1 was oronasal, respectively. Two patients required revisional repairment. The surgical procedure failed in 1 diabetic patient and 3 patients with prior history of external radiotherapy. Tooth extraction was the most common etiologic factor, and malignancy should be excluded in all patients. The outcome may not be satisfactory in patients with systemic disease and in patients with history of radiotherapy. Multiple surgical interventions may be necessary only on rare occasions.


Cognitive impairment before and six months after cardiac surgery increase mortality risk at median 11 year follow-up: a cohort study.
The additive effects of cognitive impairment and depression on mortality risk after cardiac surgery are unknown. Patients were assessed on a battery of six neurocognitive measures before cardiac surgery (N = 521) and at six month follow up (N = 377/521, 72.4%). Cognitive impairment classification was based on cognitive test scores 1 SD below age and sex matched normative data, and classified according to amnestic, non-amnestic and mixed cognitive impairment subtypes. Survival analyses entered cognitive impairment subtypes and depression interactions terms adjusted for 12 common risk factors. There were 5407 person years for analysis (median 11.1 year survival, interquartile range of 7.9 to 13.1) and 176 deaths (33.8%) by the census date. Before cardiac surgery, patients with a mixed-cognitive impairment (adjusted hazard ratio (HR) = 2.53; 95% confidence interval (CI), 1.57-4.06, p<.001) and non-amnestic cognitive impairment (adjusted HR = 1.51; 95%, 1.00-2.32, p = .05) were at greater mortality risk. Six month analyses corroborated that the mixed-cognitive impairment group were at higher mortality risk (adjusted HR = 2.35; 95% CI, 1.30-4.25, p = .005). When change in neurocognitive functioning over time was analyzed, a higher mortality risk was evident only amongst patients with cognitive impairment evident at baseline and six months (adjusted HR = 1.83; 95% CI, 1.08-3.10, p = .03). No cognition by depression interaction term was significant. These data suggest that a mixed cognitive impairment subtype, and continuing cognitive impairment before and six months after cardiac surgery, is associated with long term mortality, independent of depression and common risk factors.


Disease Emergence in Multi-Patch Stochastic Epidemic Models with Demographic and Seasonal Variability.
Factors such as seasonality and spatial connectivity affect the spread of an infectious disease. Accounting for these factors in infectious disease models provides useful information on the times and locations of greatest risk for disease outbreaks. In this investigation, stochastic multi-patch epidemic models are formulated with seasonal and demographic variability. The stochastic models are used to investigate the probability of a disease outbreak when infected individuals are introduced into one or more of the patches. Seasonal variation is included through periodic transmission and dispersal rates. Multi-type branching process approximation and application of the backward Kolmogorov differential equation lead to an estimate for the probability of a disease outbreak. This estimate is also periodic and depends on the time, the location, and the number of initial infected individuals introduced into the patch system as well as the magnitude of the transmission and dispersal rates and the connectivity between patches. Examples are given for seasonal transmission and dispersal in two and three patches.


2,2',2''-[(2,4,6-Trimeth-oxy-benzene-1,3,5-tri-yl)tris-(methyl-ene)]tris-(isoindole-1,3-dione).
The title mol-ecule, C36H27N3O9, adopts an almost symmetric conformation in which the mean planes of the phthalimido units are inclined at dihedral angles of 81.1 (1), 85.3 (1) and 86.3 (1)° with respect to the plane of the central aromatic ring. The O atoms are involved in intra- and inter-molecular C-H⋯O hydrogen bonding. The crystal structure also features π-π arene inter-actions [minimum ring centroid separation = 3.683 (2) Å]. The present mode of non-covalent interactions leads to a three-dimensional supramolecular architecture.


Wahrnehmungen von Pflegenden im Bereich der Intensivpflege während der COVID-19-Pandemie.
Perceptions of intensive care nurses during the COVID-19 pandemic - A qualitative survey Abstract. Background: While at the beginning of the COVID-19 pandemic the need for intensive care is increasing, the specific care needs of patients are still largely unknown. This is a challenge for the work of intensive care staff. The aim of the study is to understand how intensive care nurses perceive their working conditions and the consequences for patient care. The study is a qualitative survey. Using a web-based questionnaire, narratives of n = 902 nurses were collected. This article reports the perceptions of n = 397 intensive care nurses. The evaluation is based on the qualitative content analysis according to 18-2Mayring (2015). The analysis of the data shows the following six categories: "The lack of staff is extremely noticeable" to "Waiting for something", "struggle for PPE (personal protective equipment)", "time to learn", "considerable discrepancy" in patient care, "attempts to compensate" and "constantly a bad feeling". The tension between the lack of knowledge and information on the one hand and the professional demand to do justice to the seriously ill and their relatives on the other hand, brings nurses to their professional limits. Conditions for ethical decision making have to be developed and concepts for a clear attribution of autonomy and responsibility for intensive care nurses must be introduced.


Percutaneous coronary angioscopy in patients with ischemic heart disease.
Percutaneous transluminal coronary angioscopy was performed during routine coronary angiography in seven patients and during PTCA in one patient with ischemic heart disease. A flexible fiberscope with an external diameter of 1.4 mm was introduced through an 8F or 9F guiding catheter used for PTCA into the coronary arteries. Warmed saline solution (15 to 20 ml) was injected through the guiding catheter into the coronary arteries for replacement of blood. Twenty-one of the 31 coronary segments were visualized and photographed on color cinefilms. The lumen of the atherosclerotic segment showed narrowing with smooth surface or with spiral folds. PTCA caused dilatation of the stenosed segment with scattered thin thrombi. These findings indicate the usefulness of angioscopy to observe luminal changes in the coronary arteries of patients with ischemic heart disease.


Two new species of Colobomatus Hesse, 1873 (Crustacea: Philichthyidae) parasitic in the interorbital canals of Holocentrus spp. (Holocentriformes: Holocentridae) in the South Atlantic Ocean.
Two new species of parasitic copepods of the genus Colobomatus Hesse, 1873 (Cyclopoida) are proposed based on specimens collected from the squirrelfishes (Holocentridae) off the coast of Rio de Janeiro, Brazil. Colobomatus luquei n. sp. from the interorbital canals of Holocentrus adscensionis (Osbeck) can be distinguished from its closest congeners by the following combination of characters in the adult female: first to fourth thoracic somites fused, two pairs of thoracic processes, fifth pedigerous somite without processes, and process in the third abdominal somite not transpassing the margins of the caudal rami; and in the adult male: antenna with two elements in the second endopodal segment, leg 1 with three spines and three setae in the second endopodal segment, and leg 2 with three spines and three setae in the second exopodal segment. Colobomatus freirei n. sp. from the interorbital canals of Holocentrus rufus (Walbaum) can be distinguished from its closest congeners through the possession of an anterior pair of thoracic processes four times longer than the posterior pair. The two new species described herein are the first representatives of the family Philichthyidae found to parasitize fish of the order Holocentriformes.


Comparing methodologies for the cost estimation of hospital services.
The aim of the study was to determine whether the total cost estimate of a hospital service remains reliable when the cost components of bottom-up microcosting were replaced by the cost components of top-down microcosting or gross costing. Total cost estimates were determined in representative general hospitals in the Netherlands for appendectomy, normal delivery, stroke and acute myocardial infarction for 2005. It was concluded that restricting the use of bottom-up microcosting to those cost components that have a great impact on the total costs (i.e., labour and inpatient stay) would likely result in reliable cost estimates.


Heat-related cardiovascular mortality risk in Cyprus: a case-crossover study using a distributed lag non-linear model.
The frequency and intensity of heat waves is projected to increase in many parts of the world, particularly in regions such as the Eastern Mediterranean and Middle East (EMME), where the warming trends are much larger than the global average. The relationship between air temperature and premature mortality is widely recognized, however, it is not well defined in the aforementioned region. The objective of this study is to assess the relationship between cardiovascular mortality risk and air temperature in Cyprus, an island located centrally in the EMME. Daily cardiovascular mortality data and spatially aggregated daily mean, maximum, and minimum temperatures for the period 2004-2010 were analyzed using a case-crossover design combined with a distributed lag non-linear model. A relationship between high temperatures and cardiovascular mortality was observed for cerebrovascular diseases, ischaemic and other heart diseases; this relationship was exacerbated on days with high temperatures. The highest relative risk was observed on the day of the heat event and remained significantly elevated for another day. The results were consistent regardless whether the minimum, maximum, or mean temperatures were used, although the association seems to be more pronounced with the mean temperatures, which suggests that consecutive high day- and night-time temperatures are the most hazardous. The identification of a positive relationship between high temperatures and cardiovascular mortality in Cyprus raises concerns. In view of the projected climate changes and strong increases in extreme heat events in the region, appropriate interventions need to be developed.


Hairpin opening and overhang processing by an Artemis/DNA-dependent protein kinase complex in nonhomologous end joining and V(D)J recombination.
Mutations in the Artemis protein in humans result in hypersensitivity to DNA double-strand break-inducing agents and absence of B and T lymphocytes (radiosensitive severe combined immune deficiency [RS-SCID]). Here, we report that Artemis forms a complex with the 469 kDa DNA-dependent protein kinase (DNA-PKcs) in the absence of DNA. The purified Artemis protein alone possesses single-strand-specific 5' to 3' exonuclease activity. Upon complex formation, DNA-PKcs phosphorylates Artemis, and Artemis acquires endonucleolytic activity on 5' and 3' overhangs, as well as hairpins. Finally, the Artemis:DNA-PKcs complex can open hairpins generated by the RAG complex. Thus, DNA-PKcs regulates Artemis by both phosphorylation and complex formation to permit enzymatic activities that are critical for the hairpin-opening step of V(D)J recombination and for the 5' and 3' overhang processing in nonhomologous DNA end joining.


Influence of malonic acid and manganese dioxide on humic substance formation and inhibition of CO2 release during composting.
The aim of thisstudy was to explore the effects of malonic acid (MA), manganese dioxide (MnO2), malonic acid combined with manganese dioxide (MA + MnO2) additionon reducing CO2 emission and promoting humic substance (HS) formation during composting. The result showed that the addition of MA and MnO2 were an efficient way to reduce CO2 emission. Meanwhile, the CO2 emissions in the MA + MnO2 treatment was 36.8% less than that of the CK, and the amount of humic acid (HA) produced in the MnO2 treatment was 38.7% higher than that of the CK. Structural equation models demonstrated that the addition of exogenoussubstance promoted the conversion of amino acids and reducing sugars to HA. The addition of exogenous substances was the main reason for influencing the concentration of HA. In general, this research provided theoretical supports for the addition of exogenous substances to promote HA formation during composting.


Open and social leadership: a new paradigm in emergency management.
The world is changing and so are disasters. Citizens are leveraging emerging technology and social media communication tools to send, receive and process information. It is time for professional emergency management and disaster response to do the same. This paper presents an overview of these changing public patterns, and expectations must be met with a new leadership approach.


Influence of patient characteristics on chimeric antigen receptor T cell therapy in B-cell acute lymphoblastic leukemia.
CD19-specific chimeric antigen receptor T cell (CD19 CAR T) therapy has shown high remission rates in patients with refractory/relapsed B-cell acute lymphoblastic leukemia (r/r B-ALL). However, the long-term outcome and the factors that influence the efficacy need further exploration. Here we report the outcome of 51 r/r B-ALL patients from a non-randomized, Phase II clinical trial (ClinicalTrials.gov number: NCT02735291). The primary outcome shows that the overall remission rate (complete remission with or without incomplete hematologic recovery) is 80.9%. The secondary outcome reveals that the overall survival (OS) and relapse-free survival (RFS) rates at 1 year are 53.0 and 45.0%, respectively. The incidence of grade 4 adverse reactions is 6.4%. The trial meets pre-specified endpoints. Further analysis shows that patients with extramedullary diseases (EMDs) other than central nervous system (CNS) involvement have the lowest remission rate (28.6%). The OS and RFS in patients with any subtype of EMDs, higher Tregs, or high-risk genetic factors are all significantly lower than that in their corresponding control cohorts. EMDs and higher Tregs are independent high-risk factors respectively for poor OS and RFS. Thus, these patient characteristics may hinder the efficacy of CAR T therapy.


Operational diagnosis of epilepsy in children at undetermined risk: A meta-analysis of prognostic factors for seizure recurrence.
According to the operational epilepsy definition adopted by the International League Against Epilepsy (ILAE) in 2014, in patients with one unprovoked seizure, clinicians must stratify the recurrence risk to determine if the criteria for diagnosis of epilepsy have been met and if antiseizure medications (ASM) are required. A remote symptomatic etiology was considered to be one of the best predictors for seizure recurrence, also according to the available prediction tools, but in children with a previously negative history and a normal neurological examination, estimating the probability of seizure relapse remains less obvious. This meta-analysis aimed to fill this gap of knowledge. The PubMed, Embase, and Scopus databases were searched from January 2000 to December 2020. We selected studies reporting children (1 month-18 years old) presenting a first unprovoked seizure. The absence of a known remote neurological pathology had to be clearly stated in the paper or the idiopathic/cryptogenic group data were used; the finding of epileptogenic structural brain MRI abnormalities during the diagnostic workup at the moment of the first unprovoked seizure was not an exclusion criterion. Factors analyzed, as possible predictors of recurrence, included: age at onset, sex, family history of epilepsy, type of seizure (focal or generalized), epileptiform abnormalities on EEG, and epileptogenic structural brain MRI abnormalities. Four studies met the inclusion criteria and the sample size consisted of 741 children. The estimated recurrence rate within 3 years was 50% (95%CI:33.9%-66.0%). Among the predictors of recurrence, focal seizure (OR = 1.52; 95%CI = 1.05-2.19), epileptiform abnormalities on EEG (OR = 1.97; 95%CI = 1.31-2.96), and positive family history for epilepsy (OR = 2.37; 95%CI = 1.56-3.59) were associated with a statistically significant increased risk. The analysis of data available until now cannot adequately assess the risk of recurrence after a first unprovoked seizure in neurotypical children. Prospective and multicenter cohort studies are expected.


Central leptin gene delivery evokes persistent leptin signal transduction in young and aged-obese rats but physiological responses become attenuated over time in aged-obese rats.
The purpose of this study was to determine if long-term leptin treatment desensitizes leptin signal transduction and the subsequent downstream anorexic and thermogenic responses in normal and leptin-resistant age-related obese rats. To this end, we administered, i.c.v., recombinant adeno-associated virus encoding rat leptin cDNA (rAAV-leptin) or control virus into young and aged-obese rats and after 9 or 46 days, examined food intake, oxygen consumption, body weight, serum leptin, STAT3 phosphorylation, hypothalamic NPY and POMC mRNAs, and UCP1 expression and protein level in brown adipose tissue (BAT). In young rats, rAAV-leptin depleted body fat and both anorexic and thermogenic mechanisms contributed to this effect. Moreover, leptin signal transduction was not desensitized, and there were persistent physiological responses. Similarly, in the aged-obese rats, there was unabated leptin signal transduction, however, both the anorexic and thermogenic responses completely attenuated sometime after day 9. This attenuation, downstream of the leptin receptor, may be contributing to the leptin-resistance and age-related weight gain in these aged-obese rats. Finally, in young rats, although the initial responses to rAAV-leptin were dominated by anorexic responses, by 46 days, the predominant response was thermogenic rather than anorexic, suggesting that energy expenditure may be an important component of long-term weight maintenance.


Cost of Traveling to Follow-up Appointments at Kidney Transplant Clinics.
The number of kidney transplant (KT) recipients has increased in recent years, saturating kidney transplant visits at transplant centers (TCs). Furthermore, some patients live far from TCs, which adds displacement costs to their expenses. To solve these problems, joint follow-up of KT recipients has been initiated at TCs and referral hospitals. We performed a cross-sectional study in a cohort of 64 KT recipients during joint follow-up in TCs and the Hospital Arnau de Villanova (HAV) using a survey that evaluated the displacement costs as well as the advantages and disadvantages of each. Distance (320 km [IQR, 300-340 km] vs 15 km [IQR, 4-60 km]; P < .001), time (240 minutes [IQR, 210-240 minutes] vs 40 minutes [IQR, 30-68 minutes]; P < .001), total economic cost per visit (€60 [IQR, €50-90] vs €10 [IQR, €2-15]; P < .001), and annual CO2 emission (32.3 kg vs 1.4 kg; P < .05) were greater when patients traveled to TCs. Nephrologists at both TCs and HAV were rated positively by patients, while the displacement costs associated with travel to the TCs and the smaller size of the HAV were seen as negative aspects. Overall, 93.75% of the KT recipients preferred joint follow-up. This study suggests that joint follow-up between TCs and referral hospitals is an economic and ecological solution for follow-up in KT recipients living far away and visiting their referral hospital, which is the preferred choice for most patients.


Translational medicine in the field of ablative fractional laser (AFXL)-assisted drug delivery: A critical review from basics to current clinical status.
Ablative fractional lasers enhance uptake of topical therapeutics and the concept of fractional laser-assisted drug delivery has now been taken into clinical practice. We systematically reviewed preclinical data and clinical evidence for fractional lasers to enhance drug uptake and improve clinical efficacy. We searched PubMed and Embase databases; 34 articles met the inclusion criteria. Studies were categorized into experimental preclinical studies and clinical trials, the latter graded according to level of evidence. All preclinical trials (n = 16) documented enhanced topical drug uptake into skin after ablative fractional laser treatment. Clinical evidence encompassed 18 studies, of which 9 were randomized controlled trials and 2 were controlled trials, examining neoplastic lesions, photodamaged skin, scars, onychomycosis, and topical anesthetics. The highest level of evidence was reached for actinic keratoses treated with methylaminolevulinate for photodynamic therapy (level IB, 5 randomized controlled trials), substantiating superior and long-lasting efficacy versus conventional photodynamic therapy. No adverse events were reported, but ablative fractional laser-assisted drug delivery implies risks of systemic drug absorption, especially when performed over large skin areas. Fractional laser-assisted drug delivery is beneficial in enhancing preclinical and clinical outcomes for certain skin conditions.


The relationship between microRNAs and bladder cancer: are microRNAs useful to predict bladder cancer in suspicious patients?
Recent studies indicate that circulating micro RNAs (miRNAs) are novel class of non-invasive biomarkers with diagnostic and prognostic information. We evaluated the miRNA expressions in bladder cancer (BC) and their associations with disease diagnosis. We profiled the expressions of 379 miRNAs in the plasma samples from patients with non-muscle invasive bladder cancer (NMIBC) (n = 34) and non-malignant urological diseases as a control group (n = 32). Patients were evaluated regarding with age, miRNA expressions, by using descriptive statistics. miRNA expression in extracted RNA was quantified using the NanoString nCounter Digital Analyzer. The analysis of plasma miRNA levels in the marker identification cohort indicated that plasma (miR-1260a, let-7a-3p miR-196b-5p, miR-196a-5p, miR-99a-5p, miR-615-5p, miR-4301, miR-28-3p, miR-4538, miR-1233-3p, miR-4732-5p, miR-1913, miR-1280) levels were increased in NMIBC patients compared to control subjects. There were no significant differences other parameters studied between groups. The analysis of serum plasma miRNA (miR-1260a, let-7a-3p miR-196b-5p, miR-196a-5p, miR-99a-5p, miR-615-5p, miR-4301, miR-28-3p, miR-4538, miR-1233-3p, miR-4732-5p, miR-1913, miR-1280) levels could be useful plasma biomarkers for BC.


CCR 20th Anniversary Commentary: Molecular Pathology of ALK-Rearranged Lung Tumors.
The article by Rodig and colleagues, which was published in the August 15, 2009, issue of Clinical Cancer Research, helped detail the clinicopathologic profile of ALK-positive tumors and initiated the development of ALK diagnostics. Subsequent clinical trials utilized these findings, resulting in the approval of effective targeted therapies. The ALK story is a model for the development of therapies in the genomic era.


Human bone marrow adiposity is linked with serum lipid levels not T1-diabetes.
Increased marrow adiposity is often associated with bone loss. Little is known about the regulation of marrow adiposity in humans. Marrow adiposity is increased in several mouse models including type I (T1)-diabetic mice, which also display bone loss. However, the impact of metabolic disease on marrow adiposity in humans has yet to be examined. This study measured bone marrow adiposity levels with iterative decomposition of water and fat with echo asymmetry and least-squares estimation magnetic resonance imaging and determined their relationship with T1-diabetes, bone mineral density (BMD), and serum lipid levels. Participants were adult T1-diabetic patients (glycosylated hemoglobin averaging 7.70%±0.4%) and age- and body-mass-index-matched nondiabetic subjects. Consistent with previous reports, serum osteocalcin levels were lower in subjects with T1-diabetes compared to controls (reaching statistical significance in females) and negatively correlated with disease duration (r=-0.50, P<.01). Furthermore, femur neck BMD inversely correlated with diabetes severity (r=-0.417, P<.05). While marrow adiposity was not altered by T1-diabetes, there was a striking positive correlation between vertebral, femur, and tibia marrow adiposity and serum lipid levels (low-density lipoprotein, total cholesterol, cholesterol:high-density lipoprotein ratio, and triglyceride; r≥0.383), reaching a significance of P<.001 in some comparisons. Marrow adiposity also displayed strong intrasubject correlations at multiple bone sites (r≥0.411, P<.05), increased with age (r=0.410, P<.05 at vertebral sites), and was reciprocally related to bone density (r≥-0.378, P<.05). Taken together, our data suggest that marrow adiposity may be an indicator of elevated serum lipid levels and decreased bone density.


The HAT Score: a simple grading scale for predicting hemorrhage after thrombolysis.
To develop a grading scale to predict the risk of intracerebral hemorrhage (ICH) and prognosis after treatment with IV tissue-plasminogen activator (t-PA) in patients with ischemic stroke. We constructed a five-point scale based on NIH Stroke Scale score, extent of hypodensity on CT scan, serum glucose at baseline, and history of diabetes to predict the risk of hemorrhage after thrombolysis (HAT score). We evaluated the predictive ability of this scale, using c-statistics, in two independent cohorts: the t-PA treated group in the National Institute of Neurological Disorders and Stroke study, and consecutive patients treated with IV t-PA at our institution. The percentage of patients who developed any ICH after t-PA increased with higher scores in both cohorts. Collectively, the rate of any symptomatic ICH was 2% (0 point), 5% (1 point), 10% (2 points), 15% (3 points), and 44% (>3 points). The c-statistic was 0.72 (95% CI 0.65-0.79; p < 0.001) for all hemorrhages; 0.74 (0.63-0.84; p < 0.001) for symptomatic hemorrhages; and 0.79 (0.70-0.88; p < 0.001) for hemorrhages with final fatal outcome. Similar results were obtained when each cohort was analyzed separately. The score also reasonably predicted good (mRS < or = 2) (c-statistic 0.75; 0.69-0.80; p < 0.001) and catastrophic (mRS > or = 5) (0.78; 0.72-0.84; p < 0.001) functional outcomes on day 90 in the National Institute of Neurological Disorders and Stroke t-PA-treated patients. The hemorrhage after thrombolysis (HAT) score is a practical, quick, and easy-to-perform scale that allows reasonable risk stratification of intracerebral hemorrhage after IV tissue-plasminogen activator (t-PA). However, the prognostic value of this scale and its use to predict the net benefit from t-PA needs to be refined and prospectively confirmed in a larger cohort of patients before it can be used in clinical decision-making.


Phosphodiesterase inhibition and positive inotropy in failing human myocardium.
Positive inotropic effects of phosphodiesterase inhibitors like 3-isobutyl-1-methylxanthine (IBMX), pimobendan, adibendan, milrinone, saterinone, and enoximone are greatly diminished in isolated heart muscle preparations from human failing myocardium as compared to nonfailing myocardium. This is accompanied by a reduced increase in cAMP content in intact isometrically contracting human trabeculae. With anion exchange chromatography four peaks of phosphodiesterase activities (PDE I-IV) could be separated from both nonfailing and failing human myocardium. Substrate specificity, Km, and Vmax were similar in nonfailing and failing myocardium. Furthermore, the PDE inhibitors investigated exhibited similar IC50-values in both tissues, indicating that the sensitivity of the enzymes from nonfailing and failing tissue was unchanged. Thus, changes in PDE are probably not responsible for the reduced positive inotropic and cAMP-increasing effects of PDE inhibitors in human failing heart muscle preparations. Instead, an increase in signal transducing inhibitory G-proteins may keep the adenylyl cyclase at reduced activity, resulting in an attenuated formation of cAMP, even in the presence of PDE inhibitors.


Role of whole abdominal radiation therapy in the management of endometrial cancer; prognostic importance of factors indicating peritoneal metastases.
From 1973 through 1983, 27 women received postoperative open-field external beam abdominal radiotherapy as primary treatment of endometrial carcinoma. The 5-year survival rate was 71%. Two distinct prognostic groups were demonstrated. Patients with spread to the adnexa, peritoneal fluid, or both, had a 5-year relapse-free rate of 90%. Patients with macroscopic spread of cancer beyond the adnexa had a 5-year relapse-free rate of 0%. Guidelines are suggested for the radiotherapeutic management of endometrial cancer metastatic to the peritoneal cavity.


Seizure secondary to citalopram overdose.
Selective serotonin reuptake inhibitors (SSRIs) are widely used in the community for treating many forms of mental illness. Citalopram, a newer generation SSRI, is commonly prescribed but, despite its low toxicity profile, has a danger of seizure and dysrhythmias in overdose. This case report documents the key aspects in treatment of a citalopram overdose resulting in a seizure and an episode of supraventricular tachycardia (SVT). The seizure was successfully treated with benzodiazepines. The SVT was terminated with administration of adenosine. We review the literature and make recommendations on treatment of citalopram overdose.


Competition between adsorbed fibrinogen and high-molecular-weight kininogen on solid surfaces incubated in human plasma (the Vroman effect): influence of solid surface wettability.
The influence of the surface energy on the competition between fibrinogen and high-molecular-weight kininogen has been studied with the use of a recently described wettability gradient method. One finding is that the decrease in the antifibrinogen binding on plasma incubated gradient surfaces was not associated with an increase in anti-HMWK binding at all parts of the gradient surfaces.


Shell biomass material supported nano-zero valent iron to remove Pb2+ and Cd2+ in water.
Nanoscale zero-valent iron (NZVI) has a high adsorption capacity for heavy metals, but easily forms aggregates. Herein, preprocessed undulating venus shell (UVS) is used as support material to prevent NZVI from reuniting. The SEM and TEM results show that UVS had a porous layered structure and NZVI particles were evenly distributed on the UVS surface. A large number of adsorption sites on the surface of UVS-NZVI are confirmed by IR and XRD. UVS-NZVI is used for adsorption of Pb2+ and Cd2+ at pH = 6.00 in aqueous solution, and the experimental adsorption capacities are 29.91 and 38.99 mg g-1 at optimal pH, respectively. Thermodynamic studies indicate that the adsorption of ions by UVS-NZVI is more in line with the Langmuir model when Pb2+ or Cd2+ existed alone. For the mixed solution of Pb2+ and Cd2+, only the adsorption of Pb2+ by UVS-NZVI conforms to the Langmuir model. In addition, the maximum adsorption capacities of UVS-NZVI for Pb2+ and Cd2+ are 93.01 and 46.07 mg g-1, respectively. Kinetic studies demonstrate that the determination coefficients (R 2) of the pseudo first-order kinetic model for UVS-NZVI adsorption of Cd2+ and Pb2+ are higher than those of the pseudo second-order kinetic model and Elovich kinetic model. Highly efficient performance for metal removal makes UVS-NZVI show potential application to heavy metal ion adsorption.


Understanding the Relationship Between State Forgiveness and Psychological Wellbeing: A Qualitative Study.
Over the last 20 years, increasing attention has been given to associations between dispositional forgiveness and specific mental health problems. However, few studies have assessed whether forgiving real-life interpersonal hurts may be related to diverse psychological health outcomes. The present study addresses this gap by investigating, in depth, relationships between perceptions about state forgiveness and a variety of mental wellbeing outcomes as well as exploring perceptions about the factors that may modify such effects. Developing an understanding of a forgiveness wellbeing relationship is of relevance to healthcare workers, researchers and policy makers with an interest in improving public health. In-depth semi-structured interviews were conducted, and data were analysed using grounded theory methods. From England and Ireland, eleven adults who were affiliated with religious/spiritual and secular/atheist groups were recruited using purposive and convenience sampling methods. Key themes that appeared to be related to the effects of unforgiveness were: increases in negative affect; reduction in cognitive abilities and barriers to psychological and social growth. For the majority of participants, state forgiveness had strong ties to participants perceived sense of mental wellbeing, including reductions in negative affect, feeling positive emotions, positive relations with others, spiritual growth, a sense of meaning and purpose in life as well as a greater sense of empowerment. The data also revealed a number of factors that may positively or negatively influence a forgiveness-wellbeing link such as: viewing an offender as spiritually similar or different, responsibility/karma, blaming, wanting restitution/apology as well as practices such as meditation and prayer. The findings suggest that forgiving a range of real-life interpersonal offences may be an important determinant of psychological wellbeing, particularly among religious/spiritual populations. Further research is, however, needed.


De novo trisomy 4pter leads to q21.
Clinical and cytogenetic findings in an infant girl with multiple congenital anomalies, principally anophthalmia, are presented. The patient's karyotype was 47,XX,+del(4)(pter leads to q21), the largest partial trisomy of chromosome 4 reported. The possible mechanism of the origin of this abnormality is discussed.


Sexual offenses and the brain.
Sexual offenses are a great concern worldwide due to the devastating physical and psychological consequences the victims of such crimes often experience. It is an important task to investigate potential mechanisms that may underlie sexual offending and predispose an individual for such antisocial behavior. Advanced techniques in neuroscience are increasingly used to uncover biomarkers in psychiatric disorders and organic brain disease. As this type of research is flourishing, preliminary studies with the aim to explore the neural basis of sex offenders have started to appear. To this purpose, researchers began to study the brain's structural and functional changes and the neurocognitive profiles of sex offenders, in comparison to nonoffenders and nonsex offenders, or among different subtypes of sex offenders. Most of the research to date has focused on pedophilia, with some inconsistent findings, which hampers the translation of the results into the forensic and clinical context. Any attempt to increase convergent evidence may profit from the harmonization of data analysis and avoidance of methodological inconsistencies, which can account for the different results across studies. Today, uncovering the neural basis of sex offences has to become a priority, not only for clinical interventions, but might also be important knowledge for crime prevention.


CX3CL1 promotes M1 macrophage polarization and osteoclast differentiation through NF-κB signaling pathway in ankylosing spondylitis in vitro.
Ankylosing spondylitis (AS) is an autoimmune disease with a genetic correlation and is characterized by inflammation in the axial skeleton and sacroiliac joints. Many AS patients also have inflammatory bowel diseases (IBD), but the underlying causes of intestinal inflammation and osteoporosis in AS are not well understood. CX3CL1, a protein involved in inflammation, has been found to be up-regulated in AS patients and AS-model mice. The authors investigated the effects of CX3CL1 on AS by studying its impact on macrophage polarization, inflammation factors, and osteoclast differentiation. Furthermore, the effects of inhibiting the NF-κB pathway and blocking CX3CL1 were assessed using BAY-117082 and anti-CX3CL1 mAb, respectively. AS model mice were used to evaluate the effects of anti-CX3CL1 mAb on limb thickness, spine rupture, and intestinal tissue damage. The authors found that CX3CL1 increased the expression of M1-type macrophage markers and inflammation factors, and promoted osteoclast differentiation. This effect was mediated through the NF-κB signaling pathway. Inhibition of the NF-κB pathway prevented M1-type macrophage polarization, reduced inflammation levels, and inhibited osteoclast differentiation. Injection of anti-CX3CL1 mAb alleviated limb thickness, spine rupture, and intestinal tissue damage in AS model mice by inhibiting M1-type macrophage polarization and reducing intestinal tissue inflammation. The study demonstrated that up-regulated CX3CL1 promotes M1-type macrophage polarization and osteoclast differentiation through the NF-κB signaling pathway. Inhibition of this pathway and blocking CX3CL1 can alleviate inflammation and bone destruction in AS. These findings contribute to a better understanding of the pathogenesis of AS and provide a basis for clinical diagnosis and treatment.


Female sperm limitation in natural populations of a sexual/asexual mating complex (Poecilia latipinna, Poecilia formosa).
In sperm-dependent sexual/asexual mating systems, male mate choice is critical for understanding the mechanisms behind apparent stability observed in natural populations. The gynogenetic Amazon molly (Poecilia formosa) requires sperm from sexual males (e.g. Poecilia latipinna) to trigger embryogenesis, but inheritance is strictly maternal. Consequently, males should try to avoid or reduce the cost of mating with asexuals. We investigated male mate choice by documenting the presence of sperm in natural populations and found that a higher proportion of sexual females had sperm than asexuals. In addition, among those females that had sperm, sexuals had more sperm than asexuals. Our results hint at a role for male mate choice as a stabilizing factor in such systems.


Determinants of Longitudinal Measure Pulse Rate of Chronic Heart Failure Patients at Felege Hiwot Referral Hospital, Ethiopia: A Longitudinal Modeling Data Analysis.
Heart rate is a significant modifiable factor in lowering mortality in heart failure patients. The heart rate, often known as the pulse rate, is the number of times the heart beats in a given amount of time. Irregular pulse rate or heart block are all measured using heart rate data. A higher heart rate has been associated with worse clinical outcomes. The main purpose of this study was to identify factors associated with the longitudinal pulse rate of congestive heart failure patients. Hospital-based retrospective studies were conducted among 249 congestive heart failure patients who were 18 years old or older and who were on treatment follow-up from first February 2016 to thirty-one December 2017 in Felege Hiwot Referral Hospital, Bahir Dar, Ethiopia. Data were explored using descriptive statistics, individual and mean profile plots, and analyzed using linear mixed models. Out of the total 249 patients, 139 (55.8%) were females. The majority 179 (71.9%) of the CHF patients were rural residents. 65 (26.1%) patients had Hypertension, 30 (12.5%) patients had Diabetes Mellitus, 58 (23.3%) patients had Pneumonia. Thus age, LVEF, follow-up time in a month had a negative significant effect whereas NYHA class, male gender, pneumonia had a positive significant effect on the average evaluation of pulse rate of patients. The time interaction effect of NYHA Class (Time* NYHA Class), and LVEF (Time*LVEF) had a significant effect on average pulse rate evolution. The variables age, LVEF, and follow-up time were negatively associated whereas, male gender, NYHA class, and presence of pneumonia were positively associated with the progression change of pulse rate of patients rate of progression of pulse rate decreases over time. Furthermore, health professionals give more attention to patients who are NYHA class IV, had low LVEF, pneumonic patients to reduce pulse rate during the follow-up time.


A single-institution experience with the AneuRx Stent Graft for endovascular repair of abdominal aortic aneurysm.
We report our experience of endovascular repair of infrarenal abdominal aortic aneurysms (EVAR) using the modular AneuRx Stent Graft System. We retrospectively reviewed the outcomes of 113 patients who underwent EVAR with the AneuRx system performed at our institution between October 1999 and August 2003. The mean age of this group was 72.5 years, with 71% (n = 80) over the age of 70 years and 95% (n = 107) males. Aneurysm diameter ranged 4.0-9.0 cm, with 33% (n = 37) >6.0 cm. The average duration of late follow-up was 32.6 +/- 24.8 months (median = 37). Successful deployment of the modular AneuRx system was noted in all patients. There were no immediate operative conversions, deaths within 24 hr of operation, or type I or III endoleaks observed at the completion of the procedure. Thirty-day mortality was 3.5% (n = 4). Acute deployment-related complications occurred in 10% (n = 13) of patients and included misdeployment, operative bleeding, arterial perforation/dissection, and access site complications. Acute systemic complications were present in nine patients, predominantly renal and cardiac complications. An endoleak noted at any time occurred in 25% of patients, with 40% of those requiring a secondary intervention. Two patients suffered late aneurysm rupture due to a type I endoleak and graft infection. Kaplan-Meier analysis revealed 5-year freedom from secondary intervention of 72.4%; freedom from aneurysm-related death of 93.9%; and probability of survival based on all-cause mortality of 60.1%. Endovascular treatment with the modular AneuRx Stent Graft System is safe and effective, producing acceptable rates of disease-free survival and mid-term clinical outcome.


The utility and limitations of B- and T-cell gene rearrangement studies in evaluating lymphoproliferative disorders.
A hallmark of lymphoid malignancies is the presence of a monoclonal lymphocyte population. Monoclonality of B- and T-cell populations can be established through immunoglobulin (IG) or T-cell receptor (TCR) gene rearrangement analysis, respectively. The biological rationale of IG and TCR gene rearrangement analysis is that due to the extensive combinatorial repertoire made possible by V(D)J recombination in lymphocytes, it is unlikely that any substantive lymphocyte population would share the same IG or TCR gene rearrangement pattern unless there is an underlying neoplastic or reactive origin. Modern IG and TCR gene rearrangement analysis is typically performed by polymerase chain reaction (PCR) using commercially available primer sets followed by gel capillary electrophoresis. This process is highly sensitive in the detection of nearly all lymphoid malignancies. Several pitfalls and limitations, both biological and technical, apply to IG/TCR gene rearrangement analysis, but these can be minimised with high quality controls, performance of assays in duplicate, and adherence to strict criteria for interpreting and reporting results. Next generation sequencing (NGS) will likely replace PCR based methods of IG/TCR gene rearrangement analysis but is not yet widespread due to the absence of standardised protocols and multicentre validation.


Rice protein concentrate as a fish meal substitute in Oreochromis niloticus: Effects on immune response, intestinal cytokines, Aeromonas veronii resistance, and gut microbiota composition.
The potential of rice protein concentrate (RPC) to substitute fishmeal (FM) protein in the diet of Oreochromis niloticus was assessed in a five-month-long feeding trial. Fishmeal protein was replaced by RPC at rates of 0% (control), 25%, 50%, and 75% (RPC0, RPC25, RPC50, and RPC75, respectively). RPC25 had no significant effect on antioxidant capacity (total antioxidant capacity; superoxide dismutase, catalase, and glutathione peroxidase activities) and immune indices (lysozyme, nitric oxide, antiprotease, and bactericidal activities) after one, two, and five months of feeding, while the values for these parameters were significantly lower in the RPC75 group compared to those in the RPC0 group. The RPC25 group showed higher mRNA levels of the intestinal cytokines IL-1β, IL-10β, TGF-β, and TNF-α than the control group. In fish affected by Aeromonas veronii, the highest significant cumulative mortality was recorded in the RPC75 group, followed by the RPC50, RPC25, and control groups. Gut microbiome analyses showed a reduction in microbial diversity in response to the addition of RPC, regardless of the RPC content, and the composition of the community of the RPC samples differed from that of the control. RPC-enriched diets resulted in higher relative abundances of Bacteroidetes and Fusobacteria in the gut compared to that in the gut of the control fish. In summary, RPC can be used to replace up to 25% of the FM protein in the diet of O. niloticus, while improving the antioxidant capacity, immunocompetence, and disease resistance of the fish.


Laparoscopic cholecystectomy injury: an unusual indication for liver transplantation.
The introduction of laparoscopic cholecystectomy has been associated with a rise in the number of reported bile duct injuries (0.3%-0.8%). Significant vascular injuries are rare (0.16%), but may lead to life-threatening complications. We present a case report of a patient undergoing transplantation for a laparoscopic cholecystectomy injury.


Distinct structural requirements for clustering and immobilization of K+ channels by PSD-95.
PDZ-domain-containing proteins such as PSD-95 have been implicated in the targeting and clustering of membrane proteins. Biochemical and immunohistochemical studies indicate that PSD-95 recognizes COOH-terminal S/TXV sequences present in Kv1 K+ channels. However, the effect of binding a PDZ domain on a target protein has not been studied in live cells. In the present study, a green fluorescent protein-Kv1.4 fusion protein is used to study the effect of PSD-95 on channel movement. Fluorescence recovery after photobleaching showed that PSD-95 can immobilize K+ channels in the plasma membrane in an all-or-none manner. Furthermore, time lapse imaging showed that channel clusters formed in the presence of PSD-95 are stable in size, shape, and position. As expected from previous reports, two green fluorescent protein-tagged COOH-terminal variants of Kv1.4, Delta15 and V655A, are not clustered by PSD-95. However, coexpression of PSD-95 with V655A, but not Delta15, leads to the appearance of PSD-95 immunoreactivity in the plasma membrane. Furthermore, fluorescence recovery after photobleaching studies show that V655A channels are immobilized by PSD-95. Thus, V655A channels can interact with PSD-95 in a manner that leads to channel immobilization, but not clustering. These experiments document for the first time that PSD-95 immobilizes target proteins. Additionally, the data presented here demonstrate that the structural requirements for protein clustering and immobilization by PSD-95 are distinct.


Inter- and intra-individual variation in the metabolism of methaqualone in man after a single oral dose.
The urinary excretion of five C-monohydroxy metabolites and the N-oxide metabolite of methaqualone in the 24 h period immediately after oral dosing with 250 mg methaqualone (Melsed) has been measured in ninteen healthy adults (13 male, 6 female) to assess interindividual variations and in five adults (3 male, 2 female) on five separate occasions to assess intraindividual variation. The overall importance of the six metabolites was 4'-hydroxy greater than N-oxide greater than 2'-hydroxymethyl greater than 3'-hydroxy greater than 6-hydroxy = 2-hydroxymethyl. Variations in this order both within the 24 h period and within each of the three eight-hour periods constituting the 24 hours were minor and variations in the absolute amount of each metabolie excreted ranged from two to three-fold. Intraindividual variations were generally smaller than interindividual variations and for each individual the pattern of metabolism was similar on the five occasions. There is evidence that the C-oxidation of methaqualone may be more sensitive to cyclical variations in hormone levels than is N-oxidation.


Gingival Squamous Cell Carcinoma Predicted to Originate From the Gingival Sulcular Epithelium in a Young Female: A Report of a Rare Case.
Oral cancer is a disease primarily in older adults and extremely rare in young adults. Risk factors for oral cancer are irritants such as tobacco smoke and alcohol and chronic mechanical irritants but mechanisms involved in carcinogenesis in young adults are unclear because of less exposure to their risk factors. Herein, we report a rare case of gingival squamous cell carcinoma in a 19-year-old female patient, in whom the tumor predictably originated in the gingival sulcular epithelium. Histopathological examination of the resected tissue showed a cancer cell nest invading from the gingival sulcular epithelium without a breakdown of the basement membrane of the marginal gingival epithelium. Six years after the surgery, no recurrence or metastasis has been detected.


Receptors for substance P. II. Classification by agonist fragments and homologues.
Substance P (SP), a series of C-terminal fragments, SP-(2-11), SP-(3-11), SP-(4-11), SP-(5-11), SP-(6-11), SP-(7-11) and the homologues physalaemin, eledoisin and kassinin were used to measure the order of potency of agonists in five pharmacological preparations. These are: the guinea pig ileum, the guinea pig trachea, the rabbit mesenteric vein, the dog common carotid artery and the rabbit aorta. Apparent affinities (pD2) and relative activities of SP-related peptides were measured in the absence and presence of antagonists (a mixture of atropine, indomethacin and diphenhydramine) in the guinea pig ileum and the rabbit mesenteric vein, in the absence and presence of indomethacin in the guinea pig trachea and in tissues with intact endothelium (the dog carotid artery and the rabbit aorta). The orders of potency measured in the absence and presence of antagonists in the guinea pig ileum were different, while no major changes were noted in two other preparations, namely the guinea pig trachea and the rabbit mesenteric vein. The order of potency of agonists determined with homologues revealed the existence of three major patterns namely: kassinin greater than eledoisin greater than physalaemin = SP in the guinea pig trachea and the rabbit mesenteric vein, SP = physalaemin greater than eledoisin greater than kassinin in the arterial smooth muscle of the dog carotid artery and the rabbit aorta and physalaemin greater than kassinin greater than eledoisin greater than SP in the guinea pig ileum treated with antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)


Tactile neurons of the superior colliculus of the cat: input and physiological properties.
Neurons in the strata intermediale and profundum of the cat superior colliculus (SC) previously have been shown to be organized somatotopically and to respond to tactile stimuli. The stimulus properties required for neuronal activation suggest that these neurons are excited by inputs from selected classes of high-velocity, sensitive cutaneous mechanoreceptors, and that stimulus-response relationships indicate only a narrow range of information concerning stimulus magnitude. The properties of these neurons have been interpreted as serving a role in stimulus detection that recovers slowly and may be best suited for directed attention and orientation behavior. The input to the SC was studied by injection of horseradish peroxidase (HRP) for retrograde labeling of neurons projecting to this region. The main inputs subserving the tactile pathway are the principal trigeminal nucleus and the rostral portion of the spinal V subnucleus oralis and the main cuneate nucleus. Sparser labeling was found in other somatic relays, including the gracile and lateral cervical nuclei and posterior portion of the spinal trigeminal complex. Several other projections relating to visual mechanisms are also described.


Congenital heart disease and ocular hypertelorism--a new case and a summary of the literature.
A case of patent ductus arteriosus coinciding with ocular hypertelorism (Greig's syndrome) is reported for the first time. The literature regarding association of congenital cardiac malformations and ocular hypertelorism is reviewed.


Further observations on the effects of 1-thiocarbamoyl-2-imidazolidinone (TCI) on cell-mediated immunity.
1-Thiocarbamoyl-2-imidazolidinone (TCI) affected several cell-mediated immune responses, including two under suppressor control. In the cutaneous delayed hypersensitivity reaction of C57BL/6J (B6) mice to 2,4-dinitro-1-fluorobenzene (DNFB). TCI produced different effects depending on when it was given relative to hapten sensitization and challenge. When given 2 days before initial sensitization, TCI (10(-9)g/kg) caused inhibition of the 24 hr ear swelling response elicited 5 days after sensitization and slight enhancement of the response elicited at 10 days. Given 2 days after sensitization, the same dose of TCI produced little effect on the day 5 elicited response but appreciable enhancement of the day 10 elicited reaction. At doses of 10(-4) to 10(-1)g/kg, TCI given to B6 mice 1 day before tolerogen decreased 2,4-dinitrobenzenesulfonic acid sodium salt (DNB SO 3NA)-induced tolerance to DNFB sensitization initiated 10 days later. In vitro, TCI at concentrations of 10(-12), 10(-12) to 10(-3), and 10(-9) to 10(-1) g/liter was demonstrated to suppress, respectively, concanavalin A (Con A)-stimulated proliferation of B6 mouse spleen cells, the one way mixed lymphocyte reaction between mitomycin-inactivated AKR mouse spleen stimulator cells and B6 mouse spleen responder cells, and the generation of cytotoxic B6 spleen cells directed against 51Cr-labeled Con A splenic lymphoblasts from AKR mice. The results indicate that TCI can affect immunological reactions under suppressor control and mimic the immunosuppressive effects of either niridazole itself in vivo or immunoactive niridazole metabolite preparations in vitro.


Augmented reality-assisted navigation system contributes to better intraoperative and short-time outcomes of laparoscopic pancreaticoduodenectomy: a retrospective cohort study.
Augmented reality (AR)-assisted navigation system are currently good techniques for hepatectomy; however, its application and efficacy for laparoscopic pancreatoduodenectomy have not been reported. This study sought to focus on and evaluate the advantages of laparoscopic pancreatoduodenectomy guided by the AR-assisted navigation system in intraoperative and short-time outcomes. Eighty-two patients who underwent laparoscopic pancreatoduodenectomy from January 2018 to May 2022 were enrolled and divided into the AR and non-AR groups. Clinical baseline features, operation time, intraoperative blood loss, blood transfusion rate, perioperative complications, and mortality were analyzed. AR-guided laparoscopic pancreaticoduodenectomy was performed in the AR group ( n =41), whereas laparoscopic pancreatoduodenectomy was carried out routinely in the non-AR group ( n =41). There was no significant difference in baseline data between the two groups ( P >0.05); Although the operation time of the AR group was longer than that of the non-AR group (420.15±94.38 vs. 348.98±76.15, P <0.001), the AR group had a less intraoperative blood loss (219.51±167.03 vs. 312.20±195.51, P =0.023), lower blood transfusion rate (24.4 vs. 65.9%, P <0.001), lower occurrence rates of postoperative pancreatic fistula (12.2 vs. 46.3%, P =0.002) and bile leakage (0 vs. 14.6%, P =0.026), and shorter postoperative hospital stay (11.29±2.78 vs. 20.04±11.22, P <0.001) compared with the non-AR group. AR-guided laparoscopic pancreatoduodenectomy has significant advantages in identifying important vascular structures, minimizing intraoperative damage, and reducing postoperative complications, suggesting that it is a safe, feasible method with a bright future in the clinical setting.


Ta2O5-incorporated in photoinduced electrocatalyst of TiO2-RuO2 decorated by PPy-NrGO nanocomposite for boosting overall water splitting.
In the current work, the heterostructures highly PEC activity photoelectrodes composed of mixed metal oxides (TiO2-RuO2-Ta2O5 (TRT)), polypyrrole- N doped reduced graphene oxide (PPy-NrGO) were prepared by electrodeposition of PPy-NrGO films on the TRT- coated titanium (Ti) plates as substrates. The TRT coatings were deposited on Ti plates via the sol-gel technique. The effects of the Ta2O5 molar ratios were followed using physical and PEC measurements. Morphology studies showed that the surface structure of photoelectrodes alters remarkably by changing the Ta2O5 content in the mixture of metal oxides. TRT/PPy-NrGO photoelectrodes indicated to have a decreasing impact on the charge transfer resistance at the photoelectrode/electrolyte interfaces. The overall PEC water splitting performances of photoelectrodes were compared by measuring photocurrent density at 0 and 1.23 V vs. RHE, Tafel slopes, charge carrier density, stability, hydrogen evaluation reaction (HER) and oxygen evaluation reaction (OER) efficiencies. The highest HER (43.68% at -0.4 V) and OER (17.51% at 0.45 V) efficiencies were obtained in photoelectrodes comprising of 20 mol% Ta2O5 which possessed charge carrier density (5.9 × 1018) of about 1.7 times higher than that considered for TRT (0%)/PPy-NrGO with no Ta2O5 in the mixture of metal oxides.


Evaluation of MealSense©: A Sensory Integration-Based Feeding Support Program for Parents.
Children with autism spectrum disorder (ASD) often experience feeding challenges related to difficulties with sensory integration. To evaluate the content, acceptability, and usefulness of MealSense©, an online parent education program for children with ASD who have feeding challenges related to poor sensory integration. A descriptive study in which experts reviewed and rated MealSense content for consistency with Ayres Sensory Integration® (ASI) principles and evidence-based practices in feeding. A convenience sample of expert reviewers (n = 5) and parents of children with ASD and feeding challenges (n = 5). Expert ratings (n = 5) met criteria showing that MealSense is consistent with ASI and evidence-based practices in feeding. Parent ratings (n = 5) met criteria showing that MealSense is acceptable and useful. MealSense is acceptable and useful to parents of children with ASD and is consistent with ASI and evidence-based practices in feeding. What This Article Adds: This study provides preliminary support for MealSense as an evidence-based tool to supplement direct intervention for children with ASD and feeding difficulties. Further research is needed to determine its efficacy in improving the transfer of feeding skills into the home environment.


Effect of phosphate omission on glucose-induced insulin release in vitro.
In the isolated perfused rat pancreas, omission of extracellular phosphate (H2PO-4) significantly reduces the insulin secretion in response to 16.7 mM glucose.


Pattern recognition of rat behavior.
Analysis of animal behavior has been an arduous task requiring a human observer to record and classify individual motor acts. A computer pattern recognition system is introduced which simplifies this task by minimizing the need for human intervention. This system uses two video cameras with horizontal and vertical views of the behavior of a control and an experimental rat as they explore a simple environment for 15 minutes. Their behavior is sampled at a rate of one frame/second. Data from the video cameras are then converted into a form acceptable to Micro Vax I and VAX 11/750 computers. Each video picture is reduced to a 256 by 256 array, and ultimately each 15 minute observation session generates 28,800 blocks of information at 512 bytes each. Using a mathematically complete set of moments to the fourth order and the associated scalar invariants, the computer is programmed to identify the five major body positions of the rat including standing, sitting, rearing, walking and lying down. The computer also is programmed to identify the behaviors of grooming, head turning, whole body turning, looking, smelling, sniffing and washing face. This computer pattern recognition system not only speeds up behavioral classification, it alleviates the much criticized subjectivity introduced by human observers.


Three-dimensional geometry of the normal shoulder: a software analysis.
Three-dimensional (3D) geometry of the normal glenohumeral bone anatomy and relations is poorly documented. Our aims were (1) to determine the 3D geometry of the normal glenohumeral joint (GHJ) with reference to the scapular body plane and (2) to identify spatial correlations between the orientation and direction of the humeral head and the glenoid. Computed tomographies (CTs) of the normal, noninjured GHJ were collected from patients who had undergone CTs in the setting of (1) polytrauma, (2) traumatic head injury, (3) chronic acromioclavicular joint dislocations, and (4) unilateral trauma with a contralateral normal shoulder. We performed 3D segmentation and measurements with a fully automatic software (Glenosys; Imascap). Measurements were made in reference to the scapular body plane and its transverse axis. Geometric measurements included version, inclination, direction, orientation, best-fit sphere radius (BFSR), humeral subluxation, critical shoulder angle, reverse shoulder angle, glenoid area, and glenohumeral distance. Statistical correlations were sought between glenoid and humeral 3D measurements (Pearson correlation). A total of 122 normal GHJs (64 men, 58 women, age: 52 ± 17 years) were studied. The glenoid BFSR was always larger than the humerus BFSR (constant factor of 1.5, standard deviation = 0.2). The mean glenoid version and inclination were -6° ± 4° and 7° ± 5°, respectively. Men and women were found to have significantly different values for inclination (6° vs. 9°, P = .02), but not for version. Humeral subluxation was 59% ± 7%, with a linear correlation with glenoid retroversion (r = -0.70, P < .001) regardless of age. There was a significant and linear correlation between glenoid and humeral orientation and direction (r = 0.72 and r = 0.70, P < .001). The 3D geometry of the glenoid and humeral head present distinct limits in normal shoulders that can be set as references in daily practice: version and inclination are -6° and 7°, respectively, and humeral posterior subluxation is 59%; interindividual variations, regardless of the size, are relative to the scapular plane. There exists a strong correlation between the position of the humeral head and the glenoid orientation and direction.


Additive manufacturing of laminar flow cells for single-molecule experiments.
A microfluidic laminar flow cell (LFC) forms an indispensable component in single-molecule experiments, enabling different substances to be delivered directly to the point under observation and thereby tightly controlling the biochemical environment immediately surrounding single molecules. Despite substantial progress in the production of such components, the process remains relatively inefficient, inaccurate and time-consuming. Here we address challenges and limitations in the routines, materials and the designs that have been commonly employed in the field, and introduce a new generation of LFCs designed for single-molecule experiments and assembled using additive manufacturing. We present single- and multi-channel, as well as reservoir-based LFCs produced by 3D printing to perform single-molecule experiments. Using these flow cells along with optical tweezers, we show compatibility with single-molecule experiments including the isolation and manipulation of single DNA molecules either attached to the surface of a coverslip or as freely movable DNA dumbbells, as well as direct observation of protein-DNA interactions. Using additive manufacturing to produce LFCs with versatility of design and ease of production allow experimentalists to optimize the flow cells to their biological experiments and provide considerable potential for performing multi-component single-molecule experiments.


Prerequisites for Effective Implementation of Telemedicine: Focusing on Current Situations in Korea.
The practice of telemedicine requires social interventions and systems for efficient implementation. Further, it requires sufficient discussions among related parties because the purpose of telemedicine is diagnosis and treatment, and the participation of medical specialists is essential. Based on the characteristics of the healthcare structure of Korea, which has a low proportion of public healthcare and most patients are taken care of by a few large tertiary care hospitals, the fundamental issues need to be discussed. A comparison was conducted with overseas cases to discuss the prerequisites for the effective implementation of telemedicine in South Korea under the current situation. We also examined the structural characteristics of the Korean medical community. The current paper recommends that an in-depth analysis and studies are conducted on the following aspects: a search for telemedicine services focused on public healthcare, a search of services for illnesses that impose high levels of burden on households, and the development and implementation of a telemedicine system for follow-up management at primary and secondary care hospitals after the patient undergoes surgery or treatment at tertiary care hospitals. As the technology develops, the focus should also be on factors such as safety, usefulness, availability, and how the functions will be realized in order to enable user communication. A clear system should be established to regulate and manage the lack of sufficient discussions. In addition, seeking projects and systems that reflect the characteristics of each country will facilitate the efficient implementation of telemedicine.


Challenges of diabetes in elderly TB patients.
Diabetes mellitus (DM) and tuberculosis (TB) are worldwide health burdens post-COVID-19. TB is the second-leading cause of death by a single infectious microbe. There is much evidence around the world about the responsibility of TB-DM co-morbidity. Both TB and DM prevalence is high in low- and middle-income countries. Especially the elderly with diabetes are more prone to TB infection due to compromised immune systems. Diabetic patients are three times as likely to develop tuberculosis as non-diabetic patients. DM interferes with the status of TB and leads to undesirable outcomes in the treatment of TB. This may later lead to the development of multidrug-resistant tuberculosis (MDR-TB). The coexistence of TB and DM leads to a high mortality rate and therefore becomes an enormous challenge for the medical field. This viewpoint includes the most current information about TB and DM, disease complications, treatment strategies, challenges to be faced in disease management and the importance of TB-DM bidirectional screening in older adults, which helps in early detection and better treatment programme.


Anomeric preferences of D-glucose uptake and utilization by cerebral cortex slices of rats.
On aerobic incubation of rat cerebral cortex slices with anomers of D-glucose and with 2-deoxy-D-glucose (2DG) for 5 min, the disappearance of beta-D-glucose from the incubation mixture was greater than that of alpha-D-glucose and both anomers had a greater rate of disappearance than that of 2DG. In addition, there were significantly greater consumption of oxygen and production of lactate with the beta-anomer than with the alpha-anomer. In similar experiments with 3H-labeled D-glucose anomers and [1-3H]-3-O-methyl-D-glucose (3MG), the accumulation of [1-3H]-beta-D-glucose (up to 5 min) by rat cerebral cortex slices was greater than that of [1-3H]-alpha-D-glucose. Although initially lower than that of the anomers, the accumulation of [1-3H]-3MG increased at a greater rate and, by 5 min of incubation, was greater than that of both glucose anomers. This preferential accumulation was seen to disappear when the slices were preincubated with 2DG (hexokinase inhibitor) or when the temperature of incubation was reduced to 20 degrees C. Under those conditions the data with the glucose anomers were similar to those obtained with 3MG. Our data then suggested that the greater accumulation of beta-D-glucose than of alpha-D-glucose by the slices was probably not due to differences in transport through brain cell membranes but rather to the preferential metabolism of the beta-D-glucose.


Inhibition of carcinogenicities of 1,2-dimethylhydrazine and azoxymethane by pyrazole.
Inhibitory effects of pyrazole on the carcinogenicities of 2 large-bowel carcinogens, 1,2-dimethylhydrazine (DMH) and azoxymethane (AOM), were examined, because our previous study revealed that pyrazole completely inhibited the induction of mutations by these carcinogens in the host-mediated mutation assay. ICR male mice were treated subcutaneously once a week for 20 weeks either with DMH or with AOM. Pyrazole was given orally to mice 2 h before treatment with the carcinogen. Pathological examinations were conducted 36 weeks after the first treatment. Treatment with DMH or AOM alone induced colorectal and/or anal tumorigenic lesions in 92% (23/25) mice of the DMH group and 100% (22/22) mice of the AOM group. By contrast, none of the animals in the combined treatment groups (carcinogen + pyrazole) developed those tumors. On the other hand, 50% (13/26) of mice treated with DMH alone and 78% (18/23) of mice treated with AOM alone developed vascular tumors. Pretreatment of mice with pyrazole reduced the percentage of mice bearing this type of tumor to about 30% of that in the carcinogen group with either carcinogen. These results clearly show that pyrazole has the ability to inhibit carcinogenicities of DMH and AOM, especially for the colorectum and anus, and indicate that the inhibition studies of mutation induction in vivo provide a useful tool for the screening for inhibitors of the carcinogenicities of DMH and AOM.


Gastrobronchial fistula: an unusual complication of Nissen fundoplication.
Gastrobronchial fistula is a rare complication of antireflux surgery. Presentation can be subacute, with only productive cough. Endoscopy often fails to visualize these fistulae. Barium in the bronchial tree during postoperative upper gastrointestinal series is diagnostic, but can be confused with that appearing due to aspiration. Every case reported after antireflux surgery has followed intrathoracic Nissen fundoplication.


Using 3dRPC for RNA-protein complex structure prediction.
3dRPC is a computational method designed for three-dimensional RNA-protein complex structure prediction. Starting from a protein structure and a RNA structure, 3dRPC first generates presumptive complex structures by RPDOCK and then evaluates the structures by RPRANK. RPDOCK is an FFT-based docking algorithm that takes features of RNA-protein interactions into consideration, and RPRANK is a knowledge-based potential using root mean square deviation as a measure. Here we give a detailed description of the usage of 3dRPC. The source code is available at http://biophy.hust.edu.cn/3dRPC.html.


Capillary perfusion patterns in reperfused ischemic subendocardial myocardium: experimental study using fluorescent dextran.
The relationship between functional capillary perfusion patterns and sarcolemmal membrane permeability in localized acute myocardial ischemia was investigated in the rat model. The macromolecule dextran (MW 150,000) labeled with fluorescein (FITC) was intravenously injected. In histological sections, the label fluorescence showed those capillaries which had been perfused by the stained plasma; the blood-tissue barrier could be explored by detection of fluorescein in interstitial spaces and/or within the myocardial cells. Morphological parameters were calculated by semiautomatic image analysis. The data obtained indicate that (1) there is a great heterogeneity in the pattern of capillary perfusion within the reperfused ischemic myocardium; (2) as early as 20 min after coronary artery clamping followed by short reperfusion, the macromolecular tracer can be seen in the cytoplasm of muscle cells randomly distributed in subendocardial areas; (3) only the underperfused areas display permeated myocardial cells. It is suggested that capillary perfusion varies from site to site depending on the difference in cellular membrane permeability changes. The ischemia-induced cell changes can lead to capillary filling defects and an increase in coronary flow resistance. Whether the inadequate blood flow upon reperfusion contributes to further myocyte damage remains a matter of debate.


[Epidemiological and clinical profile childhood cancers with pleural and pulmonary lesions in the pediatric oncology unit of Treichville University Hospital (Abidjan, Côte d'Ivoire)].
Pediatric cancers are a major public health problem in sub-Saharan Africa. However, they are seldom studied, especially as regards in their extensive forms. An eight-year retrospective and descriptive study was carried out so as to specify the epidemiological and clinical characteristics of cancers with pleural and pulmonary involvement in children of 0 to 14years of age in the pediatric oncology unit at the University Hospital of Treichville, Côte d'Ivoire (Ivory Coast). The frequency of pleural and pulmonary involvement in pediatric cancers was 13.8%. Children's average age was 7.2years, with sex ratio at 2.11. Solid tumors were predominant, with a predominance of Burkitt's lymphoma (39.3%) and nephroblastoma (35.7%). The most affected age groups were 10 to 15years (Burkitt's lymphoma) and 0 to 5years (nephroblastoma). Time to diagnosis ranged from 31 and 60days in 40.4% of cases, and time to treatment was at most 30 days, for the overwhelming majority (97.1%) of the children. Chemotherapy was initiated in 67.9% of patients. Hospital mortality was 73.2%. Through this study, the authors established the profile of childhood cancers with pleural and pulmonary involvement. Comparative studies of mortality in pediatric cancers with and without pleural and pulmonary involvement could further underline the importance of early management before dissemination.


Interference of Notch1 inhibits the growth of glioma cancer cells by inducing cell autophagy and down-regulation of Notch1-Hes-1 signaling pathway.
Glioma is the most common malignant tumors in adult brains, and Notch signaling pathway plays an important role in cell differentiation. The aim of the present study is to investigate the role of Notch1 in the progression of glioma cancers and clarify the mechanism of Notch1 silencing on inhibiting the proliferation of glioma cancer cells. First, endogenous Notch1 expression was interfered with a lentiviral vector of Notch1 shRNA. RT-PCR and western blotting were used for detecting the expression of Notch1 mRNA and protein, respectively. MTT assay results demonstrated that transfection with Notch1 shRNA and treatment with MRK003, a Notch1 inhibitor, both inhibited the proliferation of glioma cancer cells (p < 0.01). The lentiviral vector of Notch1 shRNA transfected into U251 cells induced cell cycle arrest at G0/G1 phase by FACS with PI staining analysis. Meanwhile, the expression levels of LC3-II and Beclin1 significantly increase in Notch1 shRNA-transfected U251 cells, suggesting that cell autophagy was induced when interfering with Notch1 in glioma cells. The downstream transcription factors were also detected by RT-PCR and western blotting analysis, and the data showed that interference with Notch1 increased the expression level of Hes-1, but not Hes-5. Taken together, all the data obviously revealed that Notch1 played an important role in the progression of glioma cancers. The clarification of the mechanism will be helpful for the diagnosis of glioma cancer and would provide new clues to molecular targets for cancer therapy.


Anticancer effect of novel luteolin capped gold nanoparticles selectively cytotoxic towards human cervical adenocarcinoma HeLa cells: An in vitro approach.
Although luteolin has been confirmed as potent anticancer agent, its potential application as therapeutic is limited by its water solubility. To overcome this shortcoming nanoparticle technology approach was applied. Owing to their proven low toxicity and the possibility to be easily functionalized gold nanoparticles (AuNP) were the nanosystem of choice used in this study. Novel luteolin capped gold nanoparticles (AuNPL) were synthesized and their anticancer effect towards human cervical adenocarcinoma HeLa cells was investigated in vitro. AuNPL were synthesized by reducing chloroauric acid by trisodium citrate with subsequent addition of luteoline during synthesis and their physicochemical characterization was done. AuNPL cytotoxicity against HeLa, human malignant melanoma A375, and normal human keratinocytes HaCaT cells was tested by MTT cell survival assay, and their IC50 values were determined. The capability of AuNPL to induce cell cycle arrest and apoptosis in HeLa cells were demonstrated by flow cytometry. The antioxidant activity of AuNPL was assessed by DPPH· and ABTS·+ scavenging assays. Cytoprotective properties of AuNPL towards HaCaT cells were examined by measuring the physiological and H2O2 induced intracellular reactive oxygen species (ROS) levels using flow cytometry. Also, genotoxicity of AuNPL in HaCaT cells was investigated by the single cell alkaline comet assay. Spherical AuNPL, stable in aqueous solution up to six months at 4 °C were obtained in the synthesis. The selectivity in the cytotoxic action of AuNPL on HeLa and A375 cancer cells compared with their cytotoxicity on normal keratinocytes HaCaT was observed. AuNPL exerted their cytotoxic activity against HeLa cells through accumulation of the cells in the subG1 phase of the cell cycle, inducing the apoptotic cell death mediated by the activation of caspase-3 - 8, and - 9. AuNPL antioxidative potential was confirmed by DPPH· and ABTS·+ scavenging assays. IC50 concentration of AuNPL exerted cytoprotective effect against HaCaT cells by the significant reduction of the physiological intracellular ROS level. Additionally, AuNPL were shown as more cytoprotective towards HaCaT cells then luteolin due to the more successful elimination of H2O2 induced intracellular ROS. Moreover, nontoxic concentrations of AuNPL did not cause considerable DNA damage of HaCaT cells, indicating low genotoxicity of the nanoparticles. Synthesized AuNPL showed selective cytotoxic activity against HeLa cells, while being nontoxic and cytoprotective against HaCaT cells. The observed findings encourage further investigation of AuNPL as a promising novel anticancer agent.


Proteomic and Phosphoproteomic Analysis Reveals Differential Immune Response to Hirame Novirhabdovirus (HIRRV) Infection in the Flounder (Paralichthys olivaceus) under Different Temperature.
Hirame novirhabdovirus (HIRRV) is one of most serious viral pathogens causing significant economic losses to the flounder (Paralichthys olivaceus)-farming industry. Previous studies have shown that the outbreak of HIRRV is highly temperature-dependent, and revealed the viral replication was significantly affected by the antiviral response of flounders under different temperatures. In the present study, the proteome and phosphoproteome was used to analyze the different antiviral responses in the HIRRV-infected flounder under 10 °C and 20 °C. Post viral infection, 472 differentially expressed proteins (DEPs) were identified in the spleen of flounder under 10 °C, which related to NOD-like receptor signaling pathway, RIG-I-like receptor signaling pathway, RNA transport and so on. Under 20 °C, 652 DEPs were identified and involved in focal adhesion, regulation of actin cytoskeleton, phagosome, NOD-like receptor signaling pathway and RIG-I-like receptor signaling pathway. Phosphoproteome analysis showed that 675 differentially expressed phosphoproteins (DEPPs) were identified in the viral infected spleen under 10 °C and significantly enriched in Spliceosome, signaling pathway, necroptosis and RNA transport. Under 20 °C, 1304 DEPPs were identified and significantly enriched to Proteasome, VEGF signaling pathway, apoptosis, Spliceosome, mTOR signaling pathway, mRNA surveillance pathway, and RNA transport. To be noted, the proteins and phosphoproteins involved in interferon production and signaling showed significant upregulations in the viral infected flounder under 20 °C compared with that under 10 °C. Furthermore, the temporal expression profiles of eight selected antiviral-related mRNA including IRF3, IRF7, IKKβ, TBK1, IFIT1, IFI44, MX1 and ISG15 were detected by qRT-PCR, which showed a significantly stronger response at early infection under 20 °C. These results provided fundamental resources for subsequent in-depth research on the HIRRV infection mechanism and the antiviral immunity of flounder, and also gives evidences for the high mortality of HIRRV-infected flounder under low temperature.


Observations of clear air turbulence by high power radar.
Clear air turbulence is a hazard to aviation and is thought to have important effects on atmospheric dynamics. This article describes the structure and evolution of clear air turbulence at high altitudes as revealed by a high power radar and vertical soundings of wind and temperature.