In vivo detection of vascular adhesion protein-1 in experimental inflammation.
Vascular adhesion protein-1 (VAP-1) is an inflammation-inducible endothelial glycoprotein which mediates leukocyte-endothelial cell interactions. To study the pathogenetic significance of VAP-1 in inflammatory disorders, an in vivo immunodetection method was used to detect the regulation of luminally expressed VAP-1 in experimental skin and joint inflammation in the pig and dog. Moreover, VAP-1 was studied as a potential target to localize inflammation by radioimmunoscintigraphy. Up-regulation of VAP-1 in experimental dermatitis and arthritis could be visualized by specifically targeted immunoscintigraphy. Moreover, the translocation of VAP-1 to the functional position on the endothelial surface was only seen in inflamed tissues. These results suggest that VAP-1 is both an optimal candidate for anti-adhesive therapy and a potential target molecule for imaging inflammation.


The evolution of n-player cooperation-threshold games and ESS bifurcations.
An evolutionary game of individuals cooperating to obtain a collective benefit is here modelled as an n-player Prisoner's Dilemma game. With reference to biological situations, such as group foraging, we introduce a threshold condition in the number of cooperators required to obtain the collective benefit. In the simplest version, a three-player game, complex behaviour appears as the replicator dynamics exhibits a catastrophic event separating a parameter region allowing for coexistence of cooperators and defectors and a region of pure defection. Cooperation emerges through an ESS bifurcation, and cooperators only thrive beyond a critical point in cost-benefit space. Moreover, a repelling fixed point of the dynamics acts as a barrier to the introduction of cooperation in defecting populations. The results illustrate the qualitative difference between two-player games and multiple player games and thus the limitations to the generality of conclusions from two-player games. We present a procedure to find the evolutionarily stable strategies in any n-player game with cost and benefit depending on the number of cooperators. This was previously done by Motro [1991. Co-operation and defection: playing the field and the ESS. J. Theor. Biol. 151, 145-154] in the special cases of convex and concave benefit functions and constant cost.


Placental lesions attributed to shallow implantation, excess extravillous trophoblast and decidual hypoxia: Correlation with maternal vascular malperfusion and related obstetric conditions.
Maternal vascular malperfusion (MVM) is one of four main patterns of placental injury defined by the Amsterdam consensus statement and is associated with adverse fetal and maternal outcomes. Laminar decidual necrosis (DLN), extravillous trophoblast islands (ETIs), placental septa (PS), and basal plate multinucleate implantation-type trophoblasts (MNTs) are lesions attributed to decidual hypoxia, excess trophoblast, and shallow implantation, but are not included in the current MVM diagnostic criteria. We aimed to investigate the relationship between these lesions and MVM. A case-control model was used to evaluate for DLN, ETIs, PS, and MNTs. Placentas with MVM on pathologic examination (defined as ≥2 related lesions) constituted the case group, and maternal age- and GPA-status-matched placentas with less than 2 lesions constituted the control group. MVM-related obstetric morbidities were recorded, including hypertension, preeclampsia, and diabetes. These were correlated with the lesions of interest. 200 placentas were reviewed: 100 MVM cases and 100 controls. MNTs and PS showed significant enrichment in the MVM group (p < .05). Furthermore, larger foci of MNTs (>2 mm linear extent) were significantly associated with chronic or gestational hypertension (OR = 4.10; p < .05) and preeclampsia (OR = 8.14; p < .05). DLN extent correlated with placental infarction, but DLN and ETIs (including size and number) lacked association with MVM-related clinical conditions. As a marker of abnormally shallow placentation and related maternal morbidities, MNT merits inclusion within the MVM pathologic spectrum. Consistent reporting of MNTs >2 mm in size is recommended, as these lesions correlate with other MVM lesions and MVM-predisposing morbidities. Other lesions, particularly DLN and ETI, lacked such association questioning their diagnostic utility.


A chemical method for the labeling of fibrinogen with 99mTc.
A new method allowing the labelling of fibrinogen with 99mTcO4- is described. The 99mTcO4- is reduced by stannous chloride in an alkaline medium. After 1 h incubation with fibrinogen, the pH was brought down to 7.1. The study of (1) the pH of the solution, (2) the quantity of the reducer, and (3) the time of incubation allowed us to specify optimal conditions for labeling. The labeling yield varied from 91.68% plus or minus 6.05% to 95.18% plus or minus 2.13% according to the method of control used: the precipitation of fibrinogen by (NH4)2SO4 25% or thin-layer chromatography with methylethylketone as solvent. Clottable radioactivity averaged 72% plus or minus 4.43%. Column chromatography separated the tracer into two radioactive peaks. The first peak corresponded to the fibrinogen and carried 73.36% plus or minus 5.8% of the total radioactivity. The total recovered radioactivity amounted to 89.86% plus or minus 8.07%. Spectroscopic clottability was 88.23% plus or minus 2.42%. The in vivo stability of the labeling and the molecule was followed for 24 h after intravenous injection. If the radioactivity measured in the 5 min sample was considered to equal 100%, the 24 h sample averaged 32.71% plus or minus 3.25%, of which 85.68% plus or minus 2.92% was recovered in the clot. In conclusion, this method enabled us to obtain a stable tracer that we used for routine investigations in man.


Protective effect of residual splenic tissue after subtotal splenectomy.
Studies in animals and clinical experience in man have demonstrated that splenectomy leads to increased susceptibility to infection with encapsulated bacteria. Splenic tissue has an excellent ability to regenerate, even when implanted into subcutaneous tissue or the abdominal cavity. These implants, however, do not protect against bacterial challenge despite the fact that a number of other functions can be restored. We therefore studied the ability of residual splenic tissue to protect against challenge following subtotal splenectomy in Sprague-Dawley rats. Subtotal splenectomy was performed on 48 animals in which approximately 75% of the spleen was removed and left with a branch of its normal blood supply; 48 animals underwent total splenectomy and 48 had sham operations. Six months after surgery the groups were challenged intravenously with type 25 pneumococci to determine the LD50 for each group. Animals that had undergone subtotal splenectomy were more resistant to pneumococcal challenge than were asplenic animals, but they were not as resistant as normal animals. In addition, there was marked delay in death in the animals with subtotal splenectomy as compared with asplenic animals. Thus residual splenic tissue after subtotal splenectomy appears to confer some degree of protection against pneumococcal challenge.


Platelet-activating factor induced calcium mobilization and phosphoinositide metabolism in cultured bovine cerebral microvascular endothelial cells.
Platelet-activating factor (PAF) is a powerful lipid autacoid with a variety of biological activities. More and more evidence suggests that PAF might play an important role in modulation of cerebrovascular system function, particularly during ischemia-induced cerebrovascular damage. However, the mechanisms involved in PAF actions on cerebrovascular or other brain cells are virtually unknown. Therefore, this study was designed to investigate PAF receptor-mediated cellular signal transduction in bovine cerebral microvascular endothelial (CME) cells with the aid of a potent PAF antagonist, WEB 2086. PAF induced an immediate and concentration-dependent increase in [Ca2+]i with an EC50 of 4.75 nM. PAF-induced [Ca2+]i mobilization was inhibited by PAF antagonist WEB 2086, in a dose-dependent manner (IC50 = 15.53 nM). The calcium channel blockers diltiazem (10 microM) and verapamil (10 microM) had no effect on the PAF-induced increase in [Ca2+]i, but depletion of Ca2+ from the incubation buffer caused a 45.26% reduction of PAF-induced [Ca2+]i elevation. PAF stimulated phosphoinositide metabolism in a dose-dependent manner with an EC50 of 12.4 nM for IP3 formation, which was also inhibited by the PAF antagonist WEB 2086 in a dose-dependent manner with IC50 value of 16.97 nM for IP3 production. These data indicate that bovine CME cells respond to biologically relevant concentrations of PAF and this response involves activation of phospholipase C and increase in [Ca2+]i via specific PAF receptors. Our results may contribute to further understanding of the mechanism behind PAF actions on cerebrovascular cells.


Graphene/biofilm composites for enhancement of hexavalent chromium reduction and electricity production in a biocathode microbial fuel cell.
In this study, a simple method of biocathode fabrication in a Cr(VI)-reducing microbial fuel cell (MFC) is demonstrated. A self-assembling graphene was decorated onto the biocathode microbially, constructing a graphene/biofilm, in situ. The maximum power density of the MFC with a graphene biocathode is 5.7 times that of the MFC with a graphite felt biocathode. Cr(VI) reduction was also enhanced, resulting in 100% removal of Cr(VI) within 48h, at 40mg/L Cr(VI), compared with only 58.3% removal of Cr(VI) in the MFC with a graphite felt biocathode. Cyclic voltammogram analyses showed that the graphene biocathode had faster electron transfer kinetics than the graphite felt version. Energy dispersive spectrometer (EDS) and X-ray photoelectron spectra (XPS) analysis revealed a possible adsorption-reduction mechanism for Cr(VI) reduction via the graphene biocathode. This study attempts to improve the efficiency of the biocathode in the Cr(VI)-reducing MFC, and provides a useful candidate method for the treatment of Cr(VI) contaminated wastewater, under neutral conditions.


Short-period hypoxia increases mouse embryonic stem cell proliferation through cooperation of arachidonic acid and PI3K/Akt signalling pathways.
Hypoxia plays important roles in some early stages of mammalian embryonic development and in various physiological functions. This study examined the effect of arachidonic acid on short-period hypoxia-induced regulation of G(1) phase cell-cycle progression and inter-relationships among possible signalling molecules in mouse embryonic stem cells. Hypoxia increased the level of hypoxia-inducible factor-1alpha (HIF-1alpha) expression and H2O2 generation in a time-dependent manner. In addition, hypoxia increased the levels of cell-cycle regulatory proteins (cyclin D(1), cyclin E, cyclin-dependent kinase 2 (CDK2) and CDK4). Maximum increases in the level of these proteins and retinoblastoma phosphorylation were observed after 12-24 h of exposure to hypoxic conditions, and then decreased. Alternatively, the level of the CDK inhibitors, p21(Cip1) and p27(Kip1) were decreased. These results were consistent with the results of [3H]-thymidine incorporation and cell counting. Hypoxia also increased the level of [3H]-arachidonic acid release and inhibition of cPLA(2) reduced hypoxia-induced increase in levels of the cell-cycle regulatory proteins and [3H]-thymidine incorporation. The level of cyclooxygenase-2 (COX-2) was also increased by hypoxia and inhibition of COX-2 decreased the levels of cell-cycle regulatory proteins and [3H]-thymidine incorporation. Indeed, the percentage of cells in S phase, levels of cell cycle regulatory proteins, and [3H]-thymidine incorporation were further increased in hypoxic conditions with arachidonic acid treatment compared to normoxic conditions. Hypoxia-induced Akt and mitogen-activated protein kinase (MAPK) phosphorylation was inhibited by vitamin C (antioxidant, 10(-3) M). In addition, hypoxia-induced increase of cell-cycle regulatory protein expression and [(3)H]-thymidine incorporation were attenuated by LY294002 (PI3K inhibitor, 10(-6) M), Akt inhibitor (10(-6) M), rapamycin (mTOR inhibitor, 10(-9) M), PD98059 (p44/42 inhibitor, 10(-5) M), and SB203580 (p38 MAPK inhibitor, 10(-6) M). Furthermore, hypoxia-induced increase of [(3)H]-arachidonic acid release was blocked by PD98059 or SB203580, but not by LY294002 or Akt inhibitor. In conclusion, arachidonic acid up-regulates short time-period hypoxia-induced G(1) phase cyclins D(1) and E, and CDK 2 and 4, in mouse embryonic stem cells through the cooperation of PI3K/Akt/mTOR, MAPK and cPLA(2)-mediated signal pathways.


A Comprehensive Review of Continuous-/Discontinuous-Time Fractional-Order Multidimensional Neural Networks.
The dynamical study of continuous-/discontinuous-time fractional-order neural networks (FONNs) has been thoroughly explored, and several publications have been made available. This study is designed to give an exhaustive review of the dynamical studies of multidimensional FONNs in continuous/discontinuous time, including Hopfield NNs (HNNs), Cohen-Grossberg NNs, and bidirectional associative memory NNs, and similar models are considered in real ( [Formula: see text]), complex ( [Formula: see text]), quaternion ( [Formula: see text]), and octonion ( [Formula: see text]) fields. Since, in practice, delays are unavoidable, theoretical findings from multidimensional FONNs with various types of delays are thoroughly evaluated. Some required and adequate stability and synchronization requirements are also mentioned for fractional-order NNs without delays.


The activity of leukocyte NADPH oxidase: regulation by p47PHOX cysteine and serine residues.
The leukocyte NADPH oxidase is regulated chiefly by phosphorylation of the serines of p47(PHOX), one of its cytosolic subunits. Its activity is also regulated, however, by the four cysteines of the same subunit, as indicated by the replacement of those cysteines by alanines.


Glycine N-methylation in NGR-Tagged Nanocarriers Prevents Isoaspartate formation and Integrin Binding without Impairing CD13 Recognition and Tumor Homing.
NGR (asparagine-glycine-arginine) is a tumor vasculature-homing peptide motif widely used for the functionalization of drugs, nanomaterials and imaging compounds for cancer treatment and diagnosis. Unfortunately, this motif has a strong propensity to undergo rapid deamidation. This reaction, which converts NGR into isoDGR, is associated with receptor switching from CD13 to integrins, with potentially important manufacturing, pharmacological and toxicological implications. It is found that glycine N-methylation of NGR-tagged nanocarriers completely prevents asparagine deamidation without impairing CD13 recognition. Studies in animal models have shown that the methylated NGR motif can be exploited for delivering radiolabeled compounds and nanocarriers, such as tumor necrosis factor-α (TNF)-bearing nanogold and liposomal doxorubicin, to tumors with improved selectivity. These findings suggest that this NGR derivative is a stable and efficient tumor-homing ligand that can be used for delivering functional nanomaterials to tumor vasculature.


Allelic dropout in the ENG gene, affecting the results of genetic testing in hereditary hemorrhagic telangiectasia.
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant vascular disorder with three disease-causing genes identified to date: ENG, ACVRL1, and SMAD4. We report an HHT patient with allelic dropout that on routine sequence analysis for a known mutation in the family (c.817-3T>G in ENG) initially seemed to be homozygous for the mutation. To explore the possibility of allelic dropout causing a false result in this patient. Mutation analysis of additional family members was performed and haplotype analysis carried out. New primers were designed to reveal the presence of a possible sequence variant, which could explain the presumed allelic dropout. Allelic dropout caused by a six-nucleotide duplication close to the standard reverse primer was the assumed cause of a false homozygous diagnosis. Sequence variants outside of the primer regions can be the cause of allelic dropout, creating unforeseen errors in genotyping. Our finding emphasizes the need for careful quality control in all molecular genetic studies.


Corrigendum: Proteomic analysis reveals proteins and pathways associated with declined testosterone production in male obese mice after chronic high-altitude exposure.
[This corrects the article DOI: 10.3389/fendo.2022.1046901.].


Optimal electrode design: Straight versus perimodiolar.
The electrode in a cochlear implant (CI) system is a key factor in hearing performance as it is the interface between the device and the auditory pathway of the recipient. The first CI electrodes were straight and thus adopted a lateral wall position. Subsequent innovations include: perimodiolar electrodes designed to lie adjacent to the modiolar wall and thus to provide more spatially-focused stimulation of the spiral ganglion cells; shorter atraumatic straight electrodes for combined electric and acoustic (hybrid) stimulation. This paper explores the relative merits of straight and perimodiolar electrodes in the search for the optimal electrode design with reference to electrodes from Cochlear(®).


Running to win or to be thin? An evaluation of body dissatisfaction and eating disorder symptoms among adult runners.
The current study evaluated associations between sport-performance-related body dissatisfaction (BD), general-appearance-related BD, and their relation to EAT-26 scores among a sample of adult runners who participated in middle- and long-distance races in the northeastern United States (N=400, 46.5% male). Women reported elevated BD and eating disorder symptoms, as compared to men. Ridge regression was used to analyze correlations between appearance- and performance-related BD with EAT-26 scores. Results demonstrated that appearance- and performance-related BD positively correlated with EAT-26 scores in women (βs=0.18 and 0.13, respectively). Race length was a significant covariate for women, such that those who ran middle-distance race events were more likely to report higher EAT-26 scores (β=-3.12). These associations were not demonstrated in men. Results suggest that it is beneficial to address sport-specific body image concerns, in addition to more general appearance-related body image concerns in female runners.


The influence of two photobiomodulation protocols on orthodontically induced inflammatory root resorption (a randomized controlled clinical trial).
Controversial results have been reported regarding the impact of photobiomodulation (PBM) on orthodontically induced inflammatory root resorption (OIIRR). The aim of this study was to evaluate the influence of two PBM protocols, one of them requiring a high application frequency (on days 0, 3, 7, 14, then every 2 weeks), while the second requires less frequent applications (every 3 weeks), on OIIRR accompanying orthodontic treatment. Twenty female patients were recruited for this randomized controlled trial, requiring the therapeutic extraction of maxillary first premolars, and they were randomly divided into 2 equal groups. In Group A, one side of the maxillary arch randomly received PBM on days 0, 3, 7, 14, and every 2 weeks thereafter, while in Group B, one side was randomly chosen to receive PBM every 3 weeks. The laser applied was a Diode laser with a wavelength of 980 nm, in a continuous mode. Canine retraction in both groups was carried out using closed-coil springs, delivering 150 g of force, and the force level was checked every 3 weeks, over a 12-week study period. Pre-retraction and post-retraction cone-beam computed tomography (CBCT) was done for the evaluation of OIIRR. No significant differences in the amount of OIIRR have been reported between the laser and control sides in both groups A and B. Also, no significant differences have been reported between the laser sides in both groups. Photobiomodulation does not affect OIIRR, whether by increasing or decreasing its occurrence, with both laser application protocols. Therefore, it can be stated that PBM does not result in root resorption less than the commonly observed range elicited with conventional orthodontic treatment, and that it has no effect on OIIRR. Trial registration Two Low-level Laser Irradiation Protocols on the Rate of Canine Retraction (NCT04926389), 15/06/2021-retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT04926389 .


Identification of GIMAP7 and Rabl3 as Putative Biomarkers for Oral Squamous Cell Carcinoma Through Comparative Proteomic Approach.
Oral squamous cell carcinoma (OSCC) accounts for more than 90% of all oral cancers and has been listed as sixth most common human cancer. Due to late diagnosis and insufficient therapeutic response among patients, the survival rate remains very low accentuating the importance of early diagnostic markers. The study aimed to identify differentially expressed proteins in search for putative serum biomarkers and drug targets. Serum samples (n = 45) were depleted and resolved on two dimensional gel electrophoresis. Among differentially expressed proteins, two were identified using MALDI-TOF mass spectrometry. Gene expression levels of identified proteins were quantified in malignant and normal tissue using RT-qPCR. To validate serum Rabl3 expression, sandwich ELISA was performed. Proteomics analysis revealed two proteins which were found to be associated with oral cancer. The expression of GIMAP7 was found to be down regulated in serum of patients suffering from oral cancer while the expression of Rabl3 was found to be up-regulated. Gene expression analysis in malignant tissue and adjacent normal tissue revealed the same pattern. Quantitative ELISA was used to validate expression of Rabl3 in serum from oral cancer patients and healthy subjects which demonstrated significant up-regulation in cancer patients. Findings in current study demonstrate differential expression of novel putative biomarkers GIMAP7 and Rabl3 in oral cancer which suggests their potential role in oral cancer pathology and can be considered as predictive biomarkers.


Neonatal STZ model of type II diabetes mellitus in the Fischer 344 rat: characteristics and assessment of the status of the hepatic adrenergic receptors.
The Fischer 344 rat was found to be extremely sensitive to the diabetogenic effects of neonatally injected streptozotocin (STZ): injection of 40-100 mg/kg STZ at 1.5 days postnatal produced in the adult graded levels of hyperglycemia in males but not the females. The optimal dose in the 1.5 day old male was 80 mg/kg: it produced hyperglycemia without affecting growth or thyroid status in the adult. The neonatally STZ-injected adult rat displayed characteristics consistent with type II diabetes: mild hyperglycemia accentuated by fasting or consumption of a high fat diet; little change in insulin levels; slight elevation in glucagon levels; no alterations in ketones. Using radioligand binding techniques to isolated rat liver plasma membranes, compared to the control state, the type II diabetic state was found to have: no effect on either alpha(2)- or beta-adrenergic receptor binding; a decrease in the major dominant alpha(1)-adrenergic receptor, reflecting a decrease in receptor numbers but not their affinity; an increase in the plasma membrane calcium transport system, potentially depleting intracellular calcium stores essential for producing an alpha(1)-adrenergic receptor response. Since the alpha(1)-adrenergic receptor-calcium effector system is critical for the actions of catecholamines in the rat, these results suggest that the liver in the type II diabetic state may be refractory to the actions of catecholamines. We propose that the diabetes-evoked decrease in the dominant adrenergic receptor-effector system through which catecholamines act may be the cellular expression of defective glucocounterregulation in the diabetic state.


Obstructive sleep apnea reduces functional capacity and impairs cardiac autonomic modulation during submaximal exercise in patients with chronic obstructive pulmonary disease: A follow-up study.
Functional capacity and heart rate variability (HRV) are important prognostic markers in chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea syndrome (OSA). However, the impact of the overlap of these diseases and the one-year clinical follow-up has not yet been evaluated. To assess whether the presence of OSA can impair functional performance and cardiac autonomic control during exercise in patients with COPD; and to verify whether the overlap of these diseases could lead to worse clinical outcomes during the one-year follow-up. Thirty-four patients underwent pulmonary function tests, echocardiography and polysomnography for diagnostic confirmation, disease staging, exclusion of any cardiac changes, and allocation between groups. The patients underwent the six-minute walk test (6MWT) to assess functional capacity and HRV during exercise. Subsequently, patients were followed up for 12 months to record outcomes such as exacerbation, hospitalization, and deaths. At the end of this period, the patients were revaluated to verify the hypotheses of the study. The OSA-COPD group showed greater functional impairment when compared to the COPD group (p=0.003) and showed worse cardiac autonomic responses during the 6MWT with greater parasympathetic activation (p=0.03) and less complexity of the autonomic nervous system, in addition to being more likely to exacerbate (p=0.03) during one year of follow-up. OSA-COPD produces deleterious effects on functional performance and a greater autonomic imbalance that impairs clinical outcomes.


Directly revealing the geometric phase effect of dissociative D2+ by two-color strong field photodissociation.
We study the geometric phase (GP) effect of D2+ produced by the encirclement of the dissociated nuclear wavefunction around the light-induced conical intersection (LICI) using a linearly polarized two-color (800 nm and its third harmonic at 266 nm) synthesized laser field. We calculate the photofragment momentum distribution of D2+ with the random orientation by solving the time-dependent Schrödinger equation. We reveal the GP effect that manifests as the Aharonov-Bohm-like interference in the photofragment angular distribution along the direction perpendicular to the linear polarization axis. Our work deepens the understanding of the physical mechanisms of the molecular dynamics when driven by the synthesized strong laser field.


Effect of Patellar Resurfacing on Patellofemoral Crepitus in Posterior-Stabilized Total Knee Arthroplasty.
Patellofemoral crepitus (PC) is a complication of total knee arthroplasty (TKA). Although patellar resurfacing (PR) directly influences the kinematics of the patellofemoral joint, the influence of PR on PC is unclear. The purpose of this study was to investigate the influence of PR on the incidence of PC. This study included 84 knees from 69 patients who underwent TKA using the Vanguard Complete Total Knee System, with or without PR (n = 42 each). Clinical evaluation of the incidence of PC; Knee Society Score; and radiographic measurements of patellar tilt, patellar distance, patellar shift, Insall-Salvati ratio, patellar flexion, femorotibial angle; and rotation of the femoral component was performed. Parameters were evaluated preoperatively and at postoperative months 2, 6, 12, and 24. Logistic regression analysis was conducted to investigate the effect of PR on the risk of PC. The incidence of PC was significantly higher in the non-PR group than the PR group (33.3% vs 4.8%). The knees of the PR group displayed a significantly increased patellar tilt, medially shifted patella, and decreased patella flexion angle compared with those of the non-PR group. There were no significant differences in the other radiographic parameters or Knee Society Score. The absence of PR was associated with a much higher risk of PC (odds ratio, 10.37; 95% confidence interval, 2.18-10.37). PR may decrease the incidence of PC by increasing the patellar tilt and medial shift and positioning the patella more closely parallel to the femur. PR is recommended during TKA with this prosthesis.


Developmental aspects of atrioventricular septal defects.
Three human embryos with an atrioventricular septal defect were studied. Their morphology was compared with that of 67 autopsy specimens, in which particular attention was paid to the septal attachments of the bridging leaflets. The malformed embryos showed deficiency of the inlet component of the ventricular septum. They had distinct superior and inferior bridging leaflets, which were nearly completely muscular. Myocardial undermining had taken place at two independent sites but had not been able to lead to the formation of a valve of mitral morphology. Normal delamination of myocardium to form the leaflets could not continue directly below the aortic root because the rim of the inlet septum had a more apical position. From this, we conclude that the deficiency of the inlet septum is the cause of the typical morphology of the left valve in these hearts. The role of endocardial cushion tissue is probably restricted to glueing together myocardial structures, thus determining the variable septal attachment of the bridging leaflets in atrioventricular septal defect.


Environmental contaminants modulate transport activity of zebrafish (Danio rerio) multidrug and toxin extrusion protein 3 (Mate3/Slc47a2.1).
Zebrafish Mate3 is one of six co-orthologs of human multidrug and toxin extrusion proteins. It is highly expressed in the kidneys, intestine, testes, and brain of males. Initial interaction studies showed its interaction with xenobiotic compounds, suggesting a role in the efflux of toxic compounds. In this study, we aimed to test various environmental contaminants for their interaction with zebrafish Mate3. We developed a stable zebrafish Mate3 cell line and optimized a high-throughput screening assay using DAPI and ASP+ as fluorescent model substrates. To gain insight into the structure and function of the Mate3 protein and relate these to the results of the DAPI and ASP+ transport measurements, we predicted its 3D structure using the AlphaFold2 algorithm. A 3D structure with high per residue confidence scores with 13 transmembrane segments (TMs) was obtained, with topology and mutual positioning characteristic of the Mate protein family in a shape open to the extracellular part. Molecular docking methods were used to identify DAPI and ASP+ binding sites on the surface and in the center of the protein cavity. Because our kinetics experiments combined with molecular docking indicated that there may be additional active sites in zebrafish Mate3, additional cytotoxicity experiments were performed and highly potent Mate3 interactors were identified from a set of 55 different environmental contaminants. Our results suggest that some of the identified interactors may be of environmental concern, as their interaction with Mate3 could lead to an impairment of its normal efflux function, making fish more sensitive to harmful substances commonly released into the aquatic environment. Finally, the quality of zebrafish Mate3 structures predicted by the AlphaFold2 algorithm opens up the possibility of successfully using this tool for in silico research on transport preferences of other Mate proteins.


Social competence is defined as the ability of an animal to optimize the expression of social behaviour as a function of the available social information. The social environment encountered early in life can affect the expression of various social behaviours later in life. We investigated whether early social experience can affect social competence. In the cooperatively breeding cichlid Neolamprologus pulcher, we tested whether individuals reared with older brood-caring conspecifics persistently perform better in a series of tasks (1) simulating different social contexts, (2) assigning individuals different social roles and (3) exposing them to an unknown social situation. Fish that had been reared together with older conspecifics showed more appropriate behaviours both as winners (more aggressive displays) and as losers (more submissive displays) when aggressively competing with peers over a resource, and when trying to be accepted as subordinate group member and prospective brood care helper by an unfamiliar dominant pair (more submissive displays near shelters), a situation they had never encountered before. In both tasks fish that had grown up with older fish were tolerated better by conspecifics than fish reared with same-age siblings only. We detected effects of the early environment on social behaviour in the juvenile and adult stages of the test fish. Our results suggest that growing up in more complex social groups fosters a general social ability (i.e. social competence) in N. pulcher that improves their performance across different social roles and contexts, and which may provide fitness benefits.


A head-mounted device for measurement of pointing to visual targets without seeing the pointing arm.
A mobile, head-mounted device is introduced, which allows the presentation of visual targets and the measurement of pointing movements to these targets in visual open loop (i.e. blind pointing without seeing the pointing arm). This microcomputer-controlled, easy-to-operate device offers a variety of applications both in basic research and for clinical diagnosis in ophthalmology, neurology, and otolaryngology.


Comparative safety of infliximab and adalimumab on pregnancy outcomes of women with inflammatory bowel diseases: a systematic review & meta-analysis.
Inflammatory bowel disease (IBD) is a condition that affects most of the digestive tract. There is no report of fertility reduction in medically managed IBD women compared with the general population. On the other hand, active IBD can lead to significantly decreased fertility. Over the previous 2 decades, anti-tumor necrosis factor (anti-TNF) has been an effective treatment for managing patients with IBD, increasing the use of infliximab and adalimumab in clinical practice. However, it is unclear which biologics are better for pregnant women with IBD. We conducted a systematic review and meta-analysis for the risk of adverse pregnancy outcomes following treatment with infliximab and adalimumab in women with IBD. Bibliographic databases were retrieved from their inception to July 2022. The results were adverse pregnancy outcomes, including congenital malformations and spontaneous abortion. A total of 8 studies included 527 pregnant women with IBD. Of these, 343 received infliximab, and 184 received adalimumab therapy. Compared to adalimumab, adverse pregnancy outcomes were not increased in infliximab therapy including congenital malformations and spontaneous abortion. Infliximab and adalimumab therapy did not show the difference of risk in adverse pregnancy outcomes in women with IBD. http://www.crd.york.ac.uk/PROSPERO , identifier: CRD 42,021,277,869.


QT dispersion at rest and during adenosine stress myocardial perfusion imaging correlation with Myocardial Jeopardy Score.
The usefulness of QT dispersion (QTd) during adenosine myocardial perfusion imaging (MPI) to predict severity of coronary artery disease (CAD) has not been studied. Eighty-eight patients referred for diagnostic cardiac catheterization after abnormal MPI were included. Thirty-four patients with no stenosis (Duke Score = 0) were included in Group 1, and 54 patients with significant CAD (Duke Score > or = 2) formed Group 2. Resting and stress QTd and prolongation in QTd (delta QTd) were measured and evaluated as independent predictors for severity of CAD. Resting QTd was higher in Group 2 as compared with Group 1. During peak infusion of adenosine, QTd was significantly prolonged in Group 1 but remained unchanged, or fixed, in Group 2. In addition, in patients with significant CAD, resting QTd positively correlated with the Duke Score. On multiple regression analysis; independent predictors for significant CAD (odds ratio [OR], 95% confidence interval [CI], p-value) were resting QTd (4.9, 95% CI 1.1-21.6, < 0.05 for fourth Quartile compared with first Quartile) and delta QTd (4.0, 1.4-11.2, < 0.01 for first and second Quartiles compared with third and fourth Quartiles). In patients with abnormal stress MPI, prolonged resting QTd, and fixation of QTd during stress are independent predictors of significant CAD. In addition, resting QTd correlate with the Duke Jeopardy Score and therefore, may have independent prognostic value.


Virus-like particles and α-galactosylceramide form a self-adjuvanting composite particle that elicits anti-tumor responses.
Virus-like particles (VLP) are effective vehicles for delivery of heterologous antigen to antigen-presenting cells. However VLP alone are insufficiently stimulatory to generate the signals required to facilitate effective priming of naïve T cells. We show that the VLP derived from rabbit hemorrhagic disease virus can bind the galactose-containing adjuvant α-galactosylceramide to form a composite particle for co-delivery of antigen and adjuvant to the same antigen-presenting cell. Vaccination with VLP and α-galactosylceramide activated splenic iNKT cells to produce IFN-γ and IL-4, led to the generation of antigen-specific T cells that protected prophylactically against subcutaneous tumor challenge, and was more effective at generating anti-tumor immune responses than either component individually. These data demonstrate a novel method for immunopotentiating VLP to increase their efficacy in the generation of anti-tumor responses via the innate ligand recognition properties of calicivirus-derived nanoparticles.


Exploiting the UMLS Metathesaurus for extracting and categorizing concepts representing signs and symptoms to anatomically related organ systems.
To develop a method to exploit the UMLS Metathesaurus for extracting and categorizing concepts found in clinical text representing signs and symptoms to anatomically related organ systems. The overarching goal is to classify patient reported symptoms to organ systems for population health and epidemiological analyses. Using the concepts' semantic types and the inter-concept relationships as guidance, a selective portion of the concepts within the UMLS Metathesaurus was traversed starting from the concepts representing the highest level organ systems. The traversed concepts were chosen, filtered, and reviewed to obtain the concepts representing clinical signs and symptoms by blocking deviations, pruning superfluous concepts, and manual review. The mapping process was applied to signs and symptoms annotated in a corpus of 750 clinical notes. The mapping process yielded a total of 91,000 UMLS concepts (with approximately 300,000 descriptions) possibly representing physical and mental signs and symptoms that were extracted and categorized to the anatomically related organ systems. Of 1864 distinct descriptions of signs and symptoms found in the 750 document corpus, 1635 of these (88%) were successfully mapped to the set of concepts extracted from the UMLS. Of 668 unique concepts mapped, 603 (90%) were correctly categorized to their organ systems. We present a process that facilitates mapping of signs and symptoms to their organ systems. By providing a smaller set of UMLS concepts to use for comparing and matching patient records, this method has the potential to increase efficiency of information extraction pipelines.


Fishery resource management with migratory prey harvesting in two zones- delay and stochastic approach.
In this work, we looked at a two-zone aquatic habitat where both prey and predators can access the zones. The prey alternates between two zones at random. The growth of prey in the absence of a predator is believed to be logistic in each zone. The inner steady state is determined. Around the interior steady state, the deterministic model's local and global stability is investigated. Furthermore, a stochastic stability study is performed in the neighbourhood of a positive steady state, using analytical estimates of population mean square fluctuations to investigate the system's dynamics in the presence of Gaussian white noise.


Loyalty of hospital patients: a vital marketing objective.
Hospitals must strive for patient loyalty as a top priority objective in their marketing strategies. Loyal patients are sources of repeat business, potential users of new services, and positive spokespersons in word-of-mouth advertising.


Changes in the susceptibility of red blood cells to oxidative and osmotic stress following submaximal exercise.
Red blood cell (RBC) susceptibility to oxidative and osmotic stress in vitro was investigated in cells from trained and untrained men before and after submaximal exercise. Whilst no significant change in peroxidative haemolysis occurred immediately after 1 h of cycling at 60% of maximal aerobic capacity (VO2max), a 20% increase was found 6h later in both groups (P < 0.05). The RBC osmotic fragility decreased by 15% immediately after exercise (P < 0.001) and this was maintained for 6h (P < 0.001). There was an associated decrease in mean cell volume (P < 0.05). Training decreased RBC susceptibility to peroxidative haemolysis (P < 0.025) but it did not influence any other parameter. These exercise-induced changes were smaller in magnitude but qualitatively similar to those found in haemopathological states involving haem-iron incorporation into membrane lipids and the short-circuiting of antioxidant protection. To explore this similarity, a more strenuous and mechanically stressful exercise test was used. Running at 75% VO2max for 45 min reduced the induction time of O2 uptake (peroxidation), consistent with reduced antioxidation capacity, and increased the maximal rate of O2 uptake in RBC challenged with cumene hydroperoxide (P < 0.001). The proportion of high-density RBC increased by 10% immediately after running (P < 0.001) but no change in membrane-incorporated haem-iron occurred. In contrast, treatment of RBC with oxidants (20-50 mumol.l-1) in vitro increased cell density and membrane incorporation of haem-iron substantially. These results showed that single episodes of submaximal exercise caused significant changes in RBC susceptibility to oxidative and osmotic stress. Such responses may account for the increase in RBC turnover found in athletes undertaking strenuous endurance training.


Heavy metals in agricultural soils and crops and their health risks in Swat District, northern Pakistan.
This study assessed the concentrations of heavy metals such as cadmium (Cd), chromium (Cr), copper (Cu), manganese (Mn), nickel (Ni) and zinc (Zn) in agricultural soils and crops (fruits, grains and vegetable) and their possible human health risk in Swat District, northern Pakistan. Cd concentration was found higher than the limit (0.05 mg/kg) set by world health organization in 95% fruit and 100% vegetable samples. Moreover, the concentrations of Cr, Cu, Mn, Ni and Zn in the soils were shown significant correlations with those in the crops. The metal transfer factor (MTF) was found highest for Cd followed by Cr>Ni>Zn>Cu>Mn, while the health risk assessment revealed that there was no health risk for most of the heavy metals except Cd, which showed a high level of health risk index (HRI⩾10E-1) that would pose a potential health risk to the consumers.


Correlates of retention on the South Australian Methadone Program 1981-91.
To investigate correlates of retention on the South Australian Methadone Program during 1981-91. Retrospective study of a nonstratified random sample of 229 HIV-negative clients who received methadone between January 1981 and June 1991. Data were collected from clinical records of the 229 HIV-negative clients and also from the 40 clients known to be infected with HIV during the decade. Being HIV positive, receiving larger maximum doses of methadone, receiving methadone from a private pharmacy and enrolling later in the decade were all associated with longer retention times on the program. This study supports the findings of previous studies, that maximum dose of methadone is crucial to retention in methadone programs, But even allowing for maximum dose, obtaining methadone from a private pharmacy was also strongly associated with retention on the program. The more 'humane' clinic policy later in the decade is likely to have increased retention and reduced illicit drug use also.


ab initio study of Mn-based systems for oxidative degradation.
Organic contaminants can be removed from water/wastewater by oxidative degradation using oxidants such as manganese oxides and/or aqueous manganese ions. The Mn species show a wide range of activity, which is related to the oxidation state of Mn. Here, we use ab initio molecular dynamics simulations to address Mn oxidation states in these systems. We first develop a correlation between Mn partial atomic charge and the oxidation state based on results of 31 simulations on known Mn aqueous complexes. The results collapse to a master curve; the dependence of partial atomic charge on oxidation state weakens with increasing oxidation state, which concurs with a previously proposed feedback effect. This correlation is then used to address oxidation states in Mn systems used as oxidants. Simulations of MnO2 polymorphs immersed in water give average oxidation states (AOS) in excellent agreement with experimental results, in that β-MnO2 has the highest AOS, α-MnO2 has an intermediate AOS, and δ-MnO2 has the lowest AOS. Furthermore, the oxidation state varies substantially with the atom's environment, and these structures include Mn(III) and Mn(V) species that are expected to be active. In regard to the MnO4-/HSO3-/O2 system that has been shown to be a highly effective oxidant, we propose a novel Mn complex that could give rise to the oxidative activity, where Mn(III) is stabilized by sulfite and dissolved O2 ligands. Our simulations also show that the O2 would be activated to O22- in this complex under acidic conditions, and could lead to the formation of OH radicals that serve as oxidants.


Plasma vitronectin levels in patients with coronary atherosclerosis are increased and correlate with extent of disease.
Acute thrombosis after atherosclerotic plaques disruption is a major complication of primary atherosclerosis, leading to acute ischemic syndromes and atherosclerotic progression. Vitronectin (VN) is multifunctional glycoprotein in blood and in the extracellular matrix. It binds glycosaminoglycans, collagen, plasminogen and urokinase receptor. VN stabilizes the inhibitory confirmation of plasminogen activation inhibitor-1 (PAI-1). Vitronectin may control the clearance of vascular thrombi by binding and stabilizing PAI-1, a key regulator of fibrinolysis. Therefore, VN is generally regarded as a cofactor for PAI-1 activity. On the other hand vitronectin binds to platelet glycoproteins may mediate platelet adhesion and aggregation at sites of vascular injury. Previous studies showed that anti-VN antibodies inhibit platelet aggregation in vitro, suggesting that vitronectin contributes to platelet accumulation at sites of vascular injury. In this study; we investigated the levels of plasma vitronectin in patients with Coronary Artery Disease (CAD) and control group. The patient group was divided into four subgroups: patients with no, single, double and triple vessel disease according to their angiography results. ELISA procedure (Technoclone) was used to determine the plasma vitronectin levels. Plasma vitronectin levels in patient with CAD (% 125.87 +/- 58.38) were found to be significantly higher than control group (% 89.47 +/- 25.3) (p:0.000). In addition, in patients with double vessel disease (% 146.03 +/- 71.69) plasma vitronectin levels were significantly higher than no vessel disease (% 87.84 +/- 22.30) and control group, triple vessel disease (% 160.81 +/- 57.02) significantly higher as compare with no, single vessel disease (% 111.68 +/- 45.34) and control group (p < 0.05). There was no correlation between vitronectin and lipid parameters. These findings suggested that vitronectin is a marker of CAD. Elevated levels may indicate its role in the genesis and/or progression of CAD or may be the results of a compensatory mechanism.


Percutaneous treatment of focal vs. diffuse in-stent restenosis: a prospective randomized comparison of conventional therapies.
Few randomized studies compare outcomes for focal vs. diffuse in-stent restenosis (ISR) using conventional treatments. The purpose of this study was to compare the rates of major adverse cardiac events (MACEs) for focal vs. diffuse ISR using conventional techniques. One hundred thirteen patients with ISR were prospectively classified as focal (< 10 mm) or diffuse (> 10 mm). Focal ISR was randomized to balloon angioplasty (n = 29) or restenting (n = 29) and diffuse ISR randomized to rotational atherectomy (n = 30) or restenting (n = 25). At 9 months, patients with focal ISR had higher survival free of MACEs than patients with diffuse ISR (86% vs. 63%; P < 0.005), with no difference between techniques. Only the presence of diffuse ISR was an independent predictor of MACE at 9 months. Thus, focal ISR has a low rate of MACE compared to diffuse ISR, which carries a high event rate regardless of treatment employed.


Trypsin is the culprit of multiple organ injury with severe acute pancreatitis.
The consistently high proportion of early deaths in patients with severe acute pancreatitis (SAP) has been associated mainly with the development of multiple organ dysfunction syndromes (MODS). So far, scholars believed that the main reasons of MODS with SAP are systemic microcirculation dysfunction and inflammatory mediator induced cascading effect on the basis of pancreas digesting itself. However, there is some special pathological phenomenon in the process of SAP which could not be explained by current theories. First, it has been evident that the pancreatic tissue bleeding and necrosis is special pathological change in pancreas autodigestive effect from digestive enzymes such as trypsin in SAP. However, we found that the liver, the lung, the intestine, the brain and the kidney have the same pathological changes in experimental animal models of SAP. Secondly, unlike the general inflammatory response, a significantly amount of bloody ascites and pleural effusion was often in patients with SAP and in experimental SAP animal models. It indicates that the vascular permeability significantly increased leading to the red blood cells extravasation. Thirdly, apart from dual blood supply, liver bears a strong compensatory function. However, liver has the highest incidence of injury in SAP when compared with other organs. In addition, we found a very interesting phenomenon after reading texts and clinical records. From the pancreatic venous drainage from the point of view, the farther the organ from the pancreas, the lower injury incidence rate observed. How to explain these mysteries? We postulate that the trypsin is the culprit of multiple organs dysfunction in SAP. The activated trypsin destroy the pancreas itself, causing pancreatic tissue bleeding and necrosis, at the same time, through venous flow it flow into the blood circulation and destroy the vascular endothelial barrier, leading to highly increased vascular permeability. So, a large number of bloody exudates leakages from the vessels, resulting in patients early circulatory disorders, multiple organ bleeding, bloody pleural effusion and ascites. This pathological change is the most apparent in the liver because the liver is the first organ to receive the pancreatic venous flow having the highest concentration of trypsin. Thus, if the quantity of trypsin decreases in blood, its ability to damage other organs also shows a trend of gradually reducing. These mysteries can be explained by this hypothesis and might help us to understand more clearly about the mechanism of SAP-associated MODS.


Golimumab in inflammatory bowel diseases: present and future scenarios.
Golimumab is the third anti-TNF agent approved for the treatment of ulcerative colitis. Despite initial success demonstrated by PURSUIT trials, only few real-life studies have been published evaluating its efficacy and safety in clinical practice. Its subcutaneous route and monthly administration represent an advantage in patient compliance, respectively, vs infliximab (intravenous) and adalimumab (two doses per month). The most important weakness of the molecule which often leads clinicians to choose another anti-TNF is the impossibility to dose escalate or reduce the frequency of administrations in case of secondary failure; ongoing studies are trying to solve this problem by monitoring drug levels and the eventual presence of neutralizing anti-drug antibodies. No advantage has still been demonstrated for combination therapy of golimumab with immunosuppressants and further studies are necessary to evaluate this aspect. Preliminary data also report golimumab efficacy in Crohn's disease with higher doses than in ulcerative colitis with an acceptable safety profile. Additional studies are needed in this field to confirm the initial findings.


A 7-year-old girl with subcutaneous emphysema, pneumomediastinum, pneumothorax, and pneumoretroperitoneum caused by Mycoplasma pneumoniae pneumonia.
A 7-year-old girl presented with subcutaneous emphysema, pneumomediastinum (PM), pneumoretroperitoneum, and pneumothorax caused by Mycoplasma pneumoniae (MP). The patient had been treated with clarithromycin for pneumonia at another hospital; however, her condition deteriorated and complications developed. Soon after admission to our hospital, we started the patient on minocycline and prednisolone, and the complications improved promptly. Laboratory data showed serum ferritin and urinary beta-2-microglobulin levels were greatly elevated. We therefore speculated that the patient might have underlying hypercytokinemia. Prednisolone is an effective treatment for hypercytokinemia. We therefore recommend prednisolone treatment for cases of severe M. pneumoniae pneumonia that do not respond to antimicrobial agents.


Recycled fibers from pre- and post-consumer textile waste as blend constituents in manufacturing 100% cotton yarns in ring spinning: A sustainable and eco-friendly approach.
The usage of recycled fibers has achieved enormous importance in the textile sector due to growing environmental awareness, legal requirements for more sustainability and the cost of raw materials. Recycled cotton fibers derived from mechanical shredding of textile waste possess lower quality values and therefore they are spun through blending with other fibers in rotor spinning system for the production of coarse yarns (10-20 Ne) to make denim, towel and home furnishing. Owing to low fiber migration, rotor yarns require high twist during spinning which makes them stiffer and poorly moisture absorbent. Rotor yarns also feel harsh in skin contact due to the presence of wrapper fibers in the yarn surface. Intending to make knit top garments like T-shirts and polo shirts, apparel manufacturers nowadays demand recycled fiber-contained soft and high moisture absorbent yarn that can be produced in ring spinning system. In the current endeavor, cotton fibers reclaimed from pre- and post-consumer textile waste were blended with virgin cotton and soft-twisted 30 Ne yarns were manufactured in ring spinning frame on an industrial scale in a spinning mill. A thorough analysis of the structure and properties of the yarns revealed that up to 25% recycled cotton fibers can be used as an alternative to virgin cotton to manufacture medium count (30 Ne) yarn in ring spinning suitable to produce knit top garments.


The Accuracy of Computerized Adaptive Testing in Heterogeneous Populations: A Mixture Item-Response Theory Analysis.
Computerized adaptive testing (CAT) utilizes latent variable measurement model parameters that are typically assumed to be equivalently applicable to all people. Biased latent variable scores may be obtained in samples that are heterogeneous with respect to a specified measurement model. We examined the implications of sample heterogeneity with respect to CAT-predicted patient-reported outcomes (PRO) scores for the measurement of pain. A latent variable mixture modeling (LVMM) analysis was conducted using data collected from a heterogeneous sample of people in British Columbia, Canada, who were administered the 36 pain domain items of the CAT-5D-QOL. The fitted LVMM was then used to produce data for a simulation analysis. We evaluated bias by comparing the referent PRO scores of the LVMM with PRO scores predicted by a "conventional" CAT (ignoring heterogeneity) and a LVMM-based "mixture" CAT (accommodating heterogeneity). The LVMM analysis indicated support for three latent classes with class proportions of 0.25, 0.30 and 0.45, which suggests that the sample was heterogeneous. The simulation analyses revealed differences between the referent PRO scores and the PRO scores produced by the "conventional" CAT. The "mixture" CAT produced PRO scores that were nearly equivalent to the referent scores. Bias in PRO scores based on latent variable models may result when population heterogeneity is ignored. Improved accuracy could be obtained by using CATs that are parameterized using LVMM.


Impaired specific CD8 T cell response with aging is not due to decreased expression of CD90 on TCR transgenic T cells.
CD90 (Thy-1) is a small glycoprotein that is particularly abundant on the surface of mouse thymocytes and peripheral T cells, and is often used as a marker in adoptive transfer experiments to distinguish donor and recipient T cells with different CD90 subtypes. We have performed adoptive transfer experiments with T cell receptor transgenic (TCR Tg) mice to study the impaired CD8 T cell response with aging. After stimulation with a CD8 T cell epitope, HA518-524, the response of TCR Tg CD8 T cells from aged mice was decreased compared to the response of TCR Tg T cells from young mice. CD90 expression was also substantially decreased on the TCR Tg CD8 T cells of aged mice. However, the responses of CD90hi and CD90low CD8 T cells of the aged mice were similar in both early activation and proliferation, demonstrating that the impaired Tg T cell response with aging is not associated with the altered CD90 expression on CD8 T cells. The impaired Tg CD8 T cell response in aged mice is not due to age-associated changes in CD90 expression on Tg CD8 T cells.


Association of lipid metabolism with pneumonia risk in under-five children in China.
The relationship between lipid metabolism and pneumonia in under-five children remains unclear. The aim of the study was to explore the association of several lipids, lipoproteins and apolipoproteins with the risk of childhood pneumonia, and to initially reveal the mechanisms involved. There were 1000 children with confirmed severe pneumonia and 1000 healthy controls (18-59 months old) in the study. Serum levels of several lipids, lipoproteins and apolipoproteins were measured. The occurrence of hypoxaemia and serum level of C-reactive protein were recorded. Multivariate logistic regression and spearman correlation analysis were adopted to assess the correlation between these variables to achieve the research objective. First, higher triglycerides, total cholesterol, LDL cholesterol, VLDL cholesterol and apolipoprotein B levels were associated with the elevated risk of severe pneumonia (OR: 1.407, 95%CI: 1.336∼1.480; OR: 1.947, 95%CI: 1.741∼2.175; OR: 1.153, 95%CI: 1.116∼1.189; OR: 1.310, 95%CI: 1.222∼1.404; OR: 1.075, 95%CI: 1.003∼1.151). Higher HDL cholesterol and apolipoprotein A1 levels were associated with a decreased risk of the disease (OR: 0.903, 95%CI: 0.873∼0.933; OR: 0.921, 95%CI: 0.891∼0.952). Second, higher triglycerides level was associated with an increased risk of hypoxemia in these children (OR: 1.142, 95%CI: 1.072∼1.215). Third, serum HDL cholesterol level was linearly associated with C-reactive protein level in these children (ρ = -0.343, P < 0.001). Abnormal levels of several lipids, lipoproteins and apolipoproteins were related to severe childhood pneumonia. The findings that triglycerides and HDL cholesterol were respectively implicated in hypoxaemia and inflammation might partly explain the mechanisms linking lipid metabolism to severe pneumonia.


Ultrasonographic study on changes in axial eye dimensions after encircling procedure in retinal detachment surgery.
The pre- and postoperative results of ultrasonographic measurements on the axial ocular components in 10 phakic eyes with retinal detachment treated with encircling silicone rubber band are presented. A significant increase (P less than 0.001) in axial eye length from 0.62 to 1.24 mm (average: 0.98 mm) was found. The elongation of the eye was caused by a corresponding increase in the length of the vitreous cavity. No significant changes were found in the anterior segment of the eyes. These data demonstrate that the postoperative refractive change in a myopic direction, which an encircling procedure with moderate indentation often produces, is caused by an axial elongation of the eye.


Association of Pediatric Buccal Epigenetic Age Acceleration With Adverse Neonatal Brain Growth and Neurodevelopmental Outcomes Among Children Born Very Preterm With a Neonatal Infection.
Very preterm neonates (24-32 weeks' gestation) remain at a higher risk of morbidity and neurodevelopmental adversity throughout their lifespan. Because the extent of prematurity alone does not fully explain the risk of adverse neonatal brain growth or neurodevelopmental outcomes, there is a need for neonatal biomarkers to help estimate these risks in this population. To characterize the pediatric buccal epigenetic (PedBE) clock-a recently developed tool to measure biological aging-among very preterm neonates and to assess its association with the extent of prematurity, neonatal comorbidities, neonatal brain growth, and neurodevelopmental outcomes at 18 months of age. This prospective cohort study was conducted in 2 neonatal intensive care units of 2 hospitals in Toronto, Ontario, Canada. A total of 35 very preterm neonates (24-32 weeks' gestation) were recruited in 2017 and 2018, and neuroimaging was performed and buccal swab samples were acquired at 2 time points: the first in early life (median postmenstrual age, 32.9 weeks [IQR, 32.0-35.0 weeks]) and the second at term-equivalent age (TEA) at a median postmenstrual age of 43.0 weeks (IQR, 41.0-46.0 weeks). Follow-ups for neurodevelopmental assessments were completed in 2019 and 2020. All neonates in this cohort had at least 1 infection because they were originally enrolled to assess the association of neonatal infection with neurodevelopment. Neonates with congenital malformations, genetic syndromes, or congenital TORCH (toxoplasmosis, rubella, cytomegalovirus, herpes and other agents) infection were excluded. The extent of prematurity was measured by gestational age at birth and PedBE age difference. PedBE age was computed using DNA methylation obtained from 94 age-informative CpG (cytosine-phosphate-guanosine) sites. PedBE age difference (weeks) was calculated by subtracting PedBE age at each time point from the corresponding postmenstrual age. Total cerebral volumes and cerebral growth during the neonatal intensive care unit period were obtained from magnetic resonance imaging scans at 2 time points: approximately the first 2 weeks of life and at TEA. Bayley Scales of Infant and Toddler Development, Third Edition, were used to assess neurodevelopmental outcomes at 18 months. Among 35 very preterm neonates (21 boys [60.0%]; median gestational age, 27.0 weeks [IQR, 25.9-29.9 weeks]; 23 [65.7%] born extremely preterm [<28 weeks' gestation]), extremely preterm neonates had an accelerated PedBE age compared with neonates born at a later gestational age (β = 9.0; 95% CI, 2.7-15.3; P = .01). An accelerated PedBE age was also associated with smaller cerebral volumes (β = -5356.8; 95% CI, -6899.3 to -2961.7; P = .01) and slower cerebral growth (β = -2651.5; 95% CI, -5301.2 to -1164.1; P = .04); these associations remained significant after adjusting for clinical neonatal factors. These findings were significant at TEA but not earlier in life. Similarly, an accelerated PedBE age at TEA was associated with lower cognitive (β = -0.4; 95% CI, -0.8 to -0.03; P = .04) and language (β = -0.6; 95% CI, -1.1 to -0.06; P = .02) scores at 18 months. This cohort study of very preterm neonates suggests that biological aging may be associated with impaired brain growth and neurodevelopmental outcomes. The associations between epigenetic aging and adverse neonatal brain health warrant further attention.


Properties of oligomycin-induced occlusion of Na+ by detergent-solubilized Na,K-ATPase from pig kidney or shark rectal gland.
Oligomycin induces occlusion of Na+ in membrane-bound Na,K-ATPase. Here it is shown that Na,K-ATPase from pig kidney or shark rectal gland solubilized in the nonionic detergent C12E8 is capable of occluding Na+ in the presence of oligomycin. The apparent affinity for Na+ is reduced for both enzymes upon solubilization, and there is an increase in the sigmoidicity of binding curves, which indicates a change in the cooperativity between the occluded ions. A high detergent/protein ratio leads to a decreased occlusion capacity. De-occlusion of Na+ by addition of K+ is slow for solubilized Na,K-ATPase, with a rate constant of about 0.1 s-1 at 6 degrees C. Stopped-flow fluorescence experiments with 6-carboxyeosin, which can be used to monitor the E1Na-form in detergent solution, show that the K(+)-induced de-occlusion of Na+ correlates well with the fluorescence decrease which follows the transition from the E1Na-form to the E2-form. There is a marked increase in the rate of fluorescence change at high detergent/protein ratios, indicating that the properties of solubilized enzyme are subject to modification by detergent in other respects than mere solubilization of the membrane-bound enzyme. The temperature dependence of the rate of de-occlusion in the range 2 degrees C to 12 degrees C is changed slightly upon solubilization, with activation energies in the range 20-23 kcal/mol for membrane-bound enzyme, increasing to 26-30 kcal/mol for solubilized enzyme. Titrations of the rate of transition from E1Na to E2K with oligomycin can be interpreted in a model with oligomycin having an apparent dissociation constant of about 2.5 microM for C12E8-solubilized shark Na,K-ATPase and 0.2 microM for solubilized pig kidney Na,K-ATPase.


[Evaluation of the relationships between abrasion and surface alterations after professional tooth cleaning].
The effects of mechanical plaque removal on the enamel are compared in vitro by quantifying roughness and abrasion. The abrasion values after cleaning with ultrasound devices, polishing paste and abrasive blast units correlate with the roughness values measured.


Isomeric methoxy analogs of nimesulide for development of brain cyclooxygense-2 (COX-2)-targeted imaging agents: Synthesis, in vitro COX-2-inhibitory potency, and cellular transport properties.
Nimesulide analogs bearing a methoxy substituent either at the ortho-, meta- or para-position on the phenyl ring, were designed, synthesized, and evaluated for potential as radioligands for brain cyclooxygenase-2 (COX-2) imaging. The synthesis of nimesulide and regioisomeric methoxy analogs was based on the copper-mediated arylation of phenolic derivatives for the construction of diaryl ethers. These isomeric methoxy analogs displayed lipophilicity similar to that of nimesulide itself, as evidenced by their HPLC logP7.4 values. In vitro inhibition studies using a colorimetric COX (ovine) inhibitor-screening assay demonstrated that the para-methoxy substituted analog retains the inhibition ability and selectivity observed for parent nimesulide toward COX-2 enzyme, whereas the meta- and ortho-methoxy substituents detrimentally affected COX-2-inhibition activity, which was further supported by molecular docking studies. Bidirectional transport cellular studies using Caco-2 cell culture model in the presence of the P-glycoprotein (P-gp) inhibitor, verapamil, showed that P-gp did not have a significant effect on the efflux of the para-methoxy substituted analog. Further investigations using the radiolabeled form of the para-methoxy substituted analog is warranted for in vivo characterization.


ATP is required for the binding of precursor proteins to chloroplasts.
One of the first steps in the transport of nuclear-encoded, cytoplasmically synthesized precursor proteins into chloroplasts is a specific binding interaction between precursor proteins and the surface of the organelle. Although protein translocation into chloroplasts requires ATP hydrolysis, binding is generally thought to be energy independent. A more detailed investigation of precursor binding to the surface of chloroplasts showed that ATP was required for efficient binding. Protein translocation is known to require relatively high levels (1 mM or more) of ATP. As little as 50-100 microM ATP caused significant stimulation of precursor binding over controls with no ATP. Several different precursors were tested and all showed increased binding upon addition of low levels of ATP. Nonhydrolyzable analogs of ATP did not substitute for ATP, indicating that ATP hydrolysis was required for binding. A protonmotive force was not involved in the energy requirement for binding. Other (hydrolyzable) nucleotides could substitute for ATP but were less effective at stimulating binding. Binding was stimulated by ATP generated inside chloroplasts even when an ATP trap was present to destroy external ATP. We conclude that internal ATP is required for stimulation of precursor binding to chloroplasts.


Identification of new members within suites of amphiphilic marine siderophores.
Marine bacterial isolates Vibrio sp. HC0601C5 and Halomonas meridiana str. HC4321C1 were isolated off the coast of southern California and were found to produce an expanded suite of previously identified amphiphilic siderophores. Specifically two new members of the amphibactin family, amphibactins S and T, which have a C14:1 ω-7 fatty acid and a saturated C12 fatty acid, respectively, were produced by Vibrio sp. HC0601C5. These siderophores are produced in addition to a number of previously described amphibactins and are excreted into the culture supernatant. Two new members of the aquachelin family of siderophores, aquachelins I and J, which have an hydroxylated C12 fatty acid and a saturated C10 fatty acid, respectively, were produced by Halomonas meridiana str. HC4321C1. These four new siderophores are more hydrophilic than their previously reported relatives, aquachelins A-D and the amphibactin suite of siderophores.


Correspondence between thermal biology and locomotor performance in a liolaemid lizard from the southeastern coastal Pampas of Argentina.
The behavioral and physiological mechanisms of thermoregulation and the morphological traits of lizards result in a particular range of body temperatures, which influence performance and ultimately fitness. We studied the thermal biology and locomotor performance of the lizard Liolaemus wiegmannii from the coastal dunes in the southeastern Pampas of Argentina. During the austral summer, we examined the link between thermoregulation and optimal locomotor performance. Liolaemus wiegmannii faced a stressful environment due to high risk of overheating; despite this, the species was able to achieve field body temperatures (Mean Tb ± SD = 35.58 ± 2.86 °C) than expected by chance (i.e., the null model) and suitable for sustaining its physiological performance. Locomotion in this species was thermally-sensitive, with lizards showing high-performance bouts at a relatively wide range of body temperatures (30-38 °C). Lizards exhibited a mean maximum running speed of 1.30 m/s at 37.3 °C (i.e., optimal temperature for locomotion) which was within the set point range of preferred temperature (Tset = 35.4-37.5 °C). Therefore, we found a correspondence between thermal optimum and preferred temperature. Our findings suggest that L. wiegmannii, like other lizard species with a broad distribution, is capable of performing well across a wide range of temperatures despite the spatiotemporal thermal fluctuations of the environment.


Histopathological analysis and the immune related gene expression profiles of mandarin fish (Siniperca chuatsi) infected with Aeromonas hydrophila.
Hemorrhagic septicemia of mandarin fish (Siniperca chuatsi) was mainly caused by Aeromonas hydrophila which was an opportunistic pathogen. In recent years, the disease has caused tremendous economic loss with high morbidity and mass mortality in the mandarin fish breeding industry. Histopathological analysis and the immune related gene expression profiles of mandarin fish (S. chuatsi) infected with A. hydrophila were investigated in this study. Transmission electron microscopy (TEM) images showed that the cells of A. hydrophila densely covered with a mass of fimbriae. Histopathological analysis revealed that inflammation, vacuolization and extensive necrosis existed in the gill, liver, spleen and head kidney of the diseased fish. Quantitative real-time PCR was performed to measure mRNA expression levels for six immune related genes in mandarin fish after A. hydrophila infection. The transcriptional analysis of these immune related genes demonstrated that the expression levels of major histocompatibility complex class II (MHC II), T cell receptor α (TCRα), tumor necrosis factor α (TNFα), CC chemokine 3, interleukin 8 (IL-8) and Hepcidin were strongly up-regulated in spleen and head kidney of mandarin fish post-infection. These results will contribute to further study on the pathogenesis and host defensive system in A. hydrophila infection.


[Contributions to mechanical dishwashing. III. Dynamics of removal of protein residue from glass surfaces (author's transl)].
Using tracer technique the removal of protein soil--dried casein resp. skin milk--from glass plates by mechanical dishwashing was investigated. Prerinsing for 2 min with cold tap water removes 91.25 percent of the quantity of casein originally present. When this prerinse is followed by 20 min main wash, the residual casein can be removed if at least 30g of detergent has been added to 131 water. Optimum inter-relation-ships of quantity of detergent added with time and temperature of the washing and rinse cycles are given. Dry protein residues from skim milk are more easily removed than casein residues, probably because the salts and lactose dried together with the proteins facilitate the cleaning.


Magnetic resonance image (MRI) of an acquired aorto-pulmonary fistula, associated with cerebral and paradoxical embolism.
Aorto-pulmonary fistula has been described in Marfan's syndrome, with severe degeneration of connective tissue, particularly severe at the aortic site. Rarely, the chronic evolution of this condition could determine the formation of a fistula between the aorta and the adjacent anatomic structures [Ann Thorac Surg 59 (1995) 1563; J Cardiovasc Surg 29 (1988) 403; Thorax 28 (1973) 521]. Here, we describe the first case of aorto-pulmonary fistula, with cerebral and paradoxical embolism, described with angio-nuclear magnetic resonance (MRI) of the heart.


Exercise tolerance in asymptomatic elderly men with fluoroscopically detected coronary artery calcification.
The value of detecting coronary artery calcification (CAC), by cardiac imaging, for the diagnosis of coronary artery disease (CAD) in asymptomatic middle-aged men has been demonstrated. However, the incidence of CAC increases with age. The functional significance of CAC remains unknown in asymptomatic elderly men. The purpose of this study is to explore whether CAC in asymptomatic aging men signifies the presence of cardiovascular dysfunction during exercise. This study was designed to address whether elderly asymptomatic men, selected because they have CAC, have reduced exercise tolerance due to functionally significant CAD. Thirty-eight asymptomatic male volunteers (ages 50 to 75 years, mean [+/-SD] 64+/-7 years) with a normal resting ECG and at least one coronary risk factor, in a population study. Nineteen subjects had CAC detected by digital subtraction fluoroscopy in at least two major coronary arteries, and 19 subjects had no identifiable CAC. Each subject underwent a symptom-limited incremental exercise test with 12-lead ECG monitoring and respiratory gas analysis. Four indexes of exercise oxygen transport were evaluated: peak oxygen uptake (VO2), lactic acidosis threshold, peak VO2/heart rate ratio, and VO2 relative to a work rate increase. Eleven of 38 subjects (28%) were found to have reduced oxygen transport, which was defined as an abnormal reduction in more than two of the above four indexes of oxygen transport. Five of the 11 subjects with reduced oxygen transport had CAC, and 6 subjects did not (not significant). Only one subject with CAC had exercise ST depression. Significant CAC in asymptomatic men over age 50 does not signify exercise limitation due to CAD.


Natto: A medicinal and edible food with health function.
Natto is a soybean product fermented by natto bacteria. It is rich in a variety of amino acids, vitamins, proteins and active enzymes. It has a number of biological activities, such as thrombolysis, prevention of osteoporosis, antibacterial, anticancer, antioxidant and so on. It is widely used in medicine, health-care food, biocatalysis and other fields. Natto is rich in many pharmacological active substances and has significant medicinal research value. This paper summarizes the pharmacological activities and applications of natto in and outside China, so as to provide references for further research and development of natto.


Analysis of chromosome breakpoints in neuroblastoma at sub-kilobase resolution using fine-tiling oligonucleotide array CGH.
Understanding the genes and genetic pathways targeted by recurrent chromosomal imbalances in malignancy, along with the molecular mechanisms that generate the imbalances, are important problems in cancer biology. In this report, we demonstrate that oligonucleotide array CGH (oaCGH) analysis can routinely map chromosomal imbalance breakpoints at exon-level resolution, including imbalances that are single copy number genomic alterations. Different tiling-path array designs were used in this study: a whole-genome array with a 6-kb median probe spacing and fine-tiling arrays for selected genomic regions with either 50- or 140-bp median probe spacing. In both array formats, oligonucleotide probes were of isothermal design and were tiled through genic and inter-genic regions. Whole-genome oaCGH analysis of two neuroblastoma cell lines and three primary tumors led to the identification of 58 chromosomal breakpoints that generated 45 large-scale partial chromosomal imbalances (> 2 Mb). An unexpectedly high proportion (34%) of these breakpoint intervals mapped to regions containing segmental duplications. In addition, 88 smaller-sized regions (< 2 Mb) of imbalance were detected, the majority of which mapped to segmentally duplicated regions and may reflect constitutional copy number polymorphisms. The chromosomal breakpoints for 12 recurrent abnormalities exhibited in neuroblastoma tumors and cell lines, including MYCN amplicon boundaries, loss of 3p, loss of 11q, and gain of 17q, could be mapped to intervals ranging from 50 bp to 10 kb in size using high-density fine-tiling oligonucleotide microarrays. Fine-tiling oaCGH analysis provides an unprecedented level of resolution, allowing detailed mapping of recurrent unbalanced chromosomal abnormalities. Supplementary material for this article can be found on the Genes, Chromosomes, and Cancer website at http://www.interscience.wiley.com/jpages/1045-2257/suppmat/index.html.


Real-Life Barriers to Diagnosis of Early Mycosis Fungoides: An International Expert Panel Discussion.
Mycosis fungoides (MF) is a rare, primary cutaneous T-cell lymphoma that is challenging to diagnose due to its heterogeneous clinical presentation and complex histology. The subtlety of the initial clinical appearance of MF can result in diagnostic delays and hesitancy to refer suspected cases to specialist clinics. An unmet need remains for greater awareness and education. Therefore, an international expert panel of dermatologists, oncologists, hematologists, and dermatopathologists convened to discuss and identify barriers to early and accurate MF diagnosis that could guide clinicians toward making a correct diagnosis. Confirmation of MF requires accurate assessment of symptoms and clinical signs, and subsequent correlation with dermatopathological findings. This review summarizes the expert panel's guidance, based on the literature and real-life experience, for dermatologists to help include MF in their list of differential diagnoses, along with simple clinical and histopathologic checklists that may help clinicians to suspect and identify potential MF lesions and reduce diagnostic delays.


Abnormal platelet function in a case of megakaryoblastic leukaemia.
A platelet function study in a patient with megakaryoblastic leukaemia is reported. The abnormalities of the platelet function suggest a probable platelet membrane injury and a platelet release defect. The reduced platelet half-life and the non changing splenohepatic ratio confirm the clinical and histological features of the systemic disease.


Comparative genomic analysis of Flavobacteriaceae: insights into carbohydrate metabolism, gliding motility and secondary metabolite biosynthesis.
Members of the bacterial family Flavobacteriaceae are widely distributed in the marine environment and often found associated with algae, fish, detritus or marine invertebrates. Yet, little is known about the characteristics that drive their ubiquity in diverse ecological niches. Here, we provide an overview of functional traits common to taxonomically diverse members of the family Flavobacteriaceae from different environmental sources, with a focus on the Marine clade. We include seven newly sequenced marine sponge-derived strains that were also tested for gliding motility and antimicrobial activity. Comparative genomics revealed that genome similarities appeared to be correlated to 16S rRNA gene- and genome-based phylogeny, while differences were mostly associated with nutrient acquisition, such as carbohydrate metabolism and gliding motility. The high frequency and diversity of genes encoding polymer-degrading enzymes, often arranged in polysaccharide utilization loci (PULs), support the capacity of marine Flavobacteriaceae to utilize diverse carbon sources. Homologs of gliding proteins were widespread among all studied Flavobacteriaceae in contrast to members of other phyla, highlighting the particular presence of this feature within the Bacteroidetes. Notably, not all bacteria predicted to glide formed spreading colonies. Genome mining uncovered a diverse secondary metabolite biosynthesis arsenal of Flavobacteriaceae with high prevalence of gene clusters encoding pathways for the production of antimicrobial, antioxidant and cytotoxic compounds. Antimicrobial activity tests showed, however, that the phenotype differed from the genome-derived predictions for the seven tested strains. Our study elucidates the functional repertoire of marine Flavobacteriaceae and highlights the need to combine genomic and experimental data while using the appropriate stimuli to unlock their uncharted metabolic potential.


The plight of loneliness in Parkinson's disease: New opportunities.
The human phenomenon of loneliness has been increasing in prominence across societies, with precipitous increase since COVID-19, and individuals with Parkinson's disease are not unscathed. Loneliness is of clinical relevance as it is cross-sectionally related to, and longitudinally precedes, mortality and other health risks, including worse motor, cognitive, and behavioral-psychological functioning. Relatively few studies have evaluated loneliness, or associated social experiences, in the context of Parkinson's, but the existing data is provocative. The authors advocate for clinicians' awareness and researchers' investigational focus.


A perspex grid for localization of non-palpable mammographic lesions in breast biopsies.
The examination of excised, non-palpable mammographic lesions in breast biopsies is a recognized problem for the pathologist. There may be difficulties in identifying the lesion macroscopically and in subsequent sampling. This paper describes a simple method for resolving these problems. The breast biopsy is attached to a perspex grid and then radiographed. Use of the grid co-ordinates assists appropriate sampling of the specimen. Advantages over previously described methods are discussed.


Parent-child correlation for various indices of adiposity in an endogamous Indian population.
The study was conducted on 1,042 Punjabi adults and adolescent boys and girls (11-17 years) belonging to middle class families residing in Delhi, India. To study the relative influence of genetic and environmental factors on various fat measures, a set of 7 body measurements namely weight, stature and skinfold thickness at biceps, triceps, subscapular, suprailiac and medial calf measurements was taken on each subject. There was a redistribution of fat away from extremity towards the trunk, a rapid occurring process in males than in females. Increase in body mass index (BMI) with age was more pronounced in females than in males, both at adolescence and adult stage. There was an increase in grand mean thickness (GMT) calculated as mean of all five skinfold thicknesses, in adolescent girls where as in adolescent boys it fluctuated with age. The trunk/extremity ratios reflected a trend in favor of increase in trunk fat, more marked in boys than in girls. The correlations were of low magnitude, however, some skin folds displayed relatively higher value of correlation indicating that these could be determinant of adult obesity.


BCR expression is decreased in meningiomas showing loss of heterozygosity of 22q within a new minimal deletion region.
Neurofibromin 2 (NF2), located on chromosome arm 22q, has been established as a tumor suppressor gene involved in meningioma pathogenesis. In our study, we investigated 149 meningiomas to determine whether there are additional tumor suppressor genes localized on chromosome 22q, apart from NF2, that might be involved in meningioma pathogenesis. The LOH analysis on chromosome 22q identified two regions of deletion: the first one, which is limited to the NF2 gene locus, and the second one, which is outside this location. The new minimal deletion region (MDR) included the following genes: BCR (breakpoint cluster region), RAB36 (a member of RAS oncogene family), GNAZ [guanine nucleotide binding protein (G protein), alpha-z polypeptide], and RTDR1 (rhabdoid tumor deletion region gene 1). The expression levels of all these genes, including NF2, were subsequently analyzed by quantitative real-time polymerase chain reaction. We observed a significantly lowered expression level of NF2 in meningiomas with 22q loss of heterozygosity (LOH) within NF2 region compared to the one in meningiomas with 22q retention of heterozygosity (ROH, P<0.05). Similarly, BCR showed a significantly lowered expression in meningiomas with 22q LOH within the new MDR compared to cases with 22q ROH (P<0.05). Our data, together with the already published information considering BCR function suggest that BCR can be considered as a candidate tumor suppressor gene localized on chromosome 22q which may be involved in meningioma pathogenesis.


Genomic landscape of T-large granular lymphocyte leukemia and chronic lymphoproliferative disorder of NK cells: a single institution experience.
LGLL is a rare and chronic lymphoproliferative disorder including T-LGLL and CLPD-NK. Here, we investigated the genomic profiles of LGLL with a focus on STAT3 and STAT5B mutations in a cohort of 49 patients (41 T-LGLL, 8 CLPD-NK). Our study indicated that STAT3 was identified in 38.8% (19/49) of all patients, while STAT5B occurred in only 8.2% (4/49) of patients. We found that STAT3 mutations were associated with lower ANC in T-LGLL patients. The average number of pathogenic/likely pathogenic mutations in STAT3/STAT5B-mutated patients was significantly higher than that in WT patients (1.78 ± 1.17 vs 0.65 ± 1.36, p = 0.0032). Additionally, TET2-only mutated T-LGLL (n = 5) had a significant reduction in platelet values compared with the WT (n = 16) or STAT3-only mutated T-LGLL (n = 12) (p < 0.05). In conclusion, we compared the somatic mutational landscape between STAT3/STAT5B WT and mutated patients and correlate with their distinct clinical characteristics.


Auditory cortex mapmaking: principles, projections, and plasticity.
Maps of sensory receptor epithelia and computed features of the sensory environment are common elements of auditory, visual, and somatic sensory representations from the periphery to the cerebral cortex. Maps enhance the understanding of normal neural organization and its modification by pathology and experience. They underlie the derivation of the computational principles that govern sensory processing and the generation of perception. Despite their intuitive explanatory power, the functions of and rules for organizing maps and their plasticity are not well understood. Some puzzles of auditory cortical map organization are that few complete receptor maps are available and that even fewer computational maps are known beyond primary cortical areas. Neuroanatomical evidence suggests equally organized connectional patterns throughout the cortical hierarchy that might underlie map stability. Here, we consider the implications of auditory cortical map organization and its plasticity and evaluate the complementary role of maps in representation and computation from an auditory perspective.


The effect of locational disadvantage on hospital utilisation and outcomes in Western Australia.
This study analyses the effect of location of residence on hospital utilisation and outcomes using geocoded hospital morbidity and mortality data for the Western Australian population from 1994 to 1999. Compared to highly accessible areas, the overall hospital admission rate ratio was 2.27 (95% CI 2.19-2.36) for those in moderately accessible areas and 2.35 (95% CI 2.23-2.47) for those in remote areas. The corresponding ratios for total length of stay were 1.19 (95% CI 1.17-1.20) and 1.25 (95% CI 1.23-1.27) and the hazard ratios for risk of readmission at 30 days were 1.06 (95% CI 1.04-1.07) and 1.17 (95% CI 1.15-1.19). This study represents an important advance in describing the effects of remoteness on health service utilisation and outcomes.


Assembling and maintaining the Photosystem II complex in chloroplasts and cyanobacteria.
Plants, algae and cyanobacteria grow because of their ability to use sunlight to extract electrons from water. This vital reaction is catalysed by the Photosystem II (PSII) complex, a large multi-subunit pigment-protein complex embedded in the thylakoid membrane. Recent results show that assembly of PSII occurs in a step-wise fashion in defined regions of the membrane system, involves conserved auxiliary factors and is closely coupled to chlorophyll biosynthesis. PSII is also repaired following damage by light. FtsH proteases play an important role in selectively removing damaged proteins from the complex, both in chloroplasts and cyanobacteria, whilst undamaged subunits and pigments are recycled. The chloroplastic Deg proteases play a supplementary role in PSII repair.


Simultaneous analyses of clutch coupling and actin polymerization in dendritic spines of rodent hippocampal neurons during chemical LTP.
Dendritic spine enlargement by synaptic activation is thought to increase synaptic efficacy underlying learning and memory. This process requires forces generated by actin polymerization and actin-adhesion coupling (clutch coupling). Here, we describe a protocol to monitor actin filament retrograde flow and actin polymerization within spines using a standard epi-fluorescence microscope. In combination with chemical long-term potentiation, this protocol allows us to quantify clutch coupling efficiency and actin polymerization rate, which are essential variables for generating forces for activity-dependent spine enlargement. For complete details on the use and execution of this protocol, please refer to Kastian et al. (2021).


Differential analysis of Orientia tsutsugamushi genomes for therapeutic target identification and possible intervention through natural product inhibitor screening.
Orientia tsutsugamushi (Ott) is a causative agent of scrub typhus, and one of the emerging pathogens that could affect a large human population. It is one of the misdiagnosed and under-reported, febrile illnesses that infects various body organs (skin, heart, lung, kidney, and brain). The control of this infection is hampered due to the lack of drugs or vaccine against it. This study was undertaken to identify potential drug targets from the core genome of Ott and investigate novel natural product inhibitors against them. Hence, the available genomes for 22 strains of Ott were downloaded from the PATRIC database, and pan-genomic analysis was performed. Only 202 genes were present in the core region. Among these, 94 were identified as essential, 32 non-homologous to humans, nine non-homologous to useful gut flora and a single gene dapD as a drug target. Product of this gene (2,3,4,5-tetrahydropyridine-2-carboxylate N-succinyltransferase) was modeled and docked against traditional Indian (Ayurvedic) and Chinese phytochemical libraries, with best hits selected for docking, based on multiple target-drug/s interactions and minimum energy scores. ADMET profiling and molecular dynamics simulation was performed for top three compounds from each library to assess the toxicity and stability, respectively. We presume that these compounds (ZINC8214635, ZINC32793028, ZINC08101133, ZINC85625167, ZINC06018678, and ZINC13377938) could be successful inhibitors of Ott. However, in-depth experimental and clinical research is needed for further validation.


Peroxisome biogenesis: advances and conundrums.
Investigations of peroxisome biogenesis in diverse organisms reveal new details of this unique process and its evolutionary conservation. Interactions among soluble receptors and the membrane peroxins that catalyze protein translocation are being mapped. Ubiquitination is observed. A receptor enters the organelle carrying folded cargo and recycles back to the cytosol. Tiny peroxisome remnants - vesicles and tubules - are discovered in pex3 mutants that lack the organelle. When the mutant is transfected with a good PEX3 gene, these protoperoxisomes acquire additional membrane peroxins and then import the matrix enzymes to reform peroxisomes. Thus, de novo formation need not be postulated. Dynamic imaging of yeast reveals dynamin-dependent peroxisome division and regulated actin-dependent segregation of the organelle before cell division. These results are consistent with biogenesis by growth and division of pre-existing peroxisomes.


Post-mortem water uptake by sheep lenses left in situ.
Human lenses are generally obtained from eye bank eyes, which have been stored in the cold for extended periods. It is not known what effect the storage has on the lens. In this study, we examine the effects of post mortem time on the weights of sheep lenses left in the eye. Lenses were removed from 299 ex vivo sheep eyes (200-day-old), which had been kept on ice for various times up to 76 h. Wet and dry weights were then determined. In addition, wet and dry weights were obtained from 147,414-day-old and 149,660-day-old lenses removed within one hour of death. After about 30 h in the eye, lens wet weights started to increase. By 76 h, the water content had increased by 25%. Uptake of water by lenses while stored in the eye at low temperature can significantly alter lens properties. It is suggested that caution is needed when interpreting data obtained with lenses from eye bank eyes unless it can be demonstrated that there has been no water uptake.


July effect in clinical outcomes of esophagogastroduodenoscopy performed at teaching hospitals in the United States.
Esophagogastroduodenoscopy (EGD) is a common procedure used for both diagnosis and treatment, but carries risks such as bleeding and perforation. The "July effect"-described as increased complication rates during the transition of new trainees-has been studied in other procedures, but has not been thoroughly evaluated for EGD. We used the National Inpatient Sample database for 2016 to 2018 to compare outcomes in EGD performed between July to September and April to June. Approximately 0.91 million patients in the study received EGD between July to September (49.35%) and April to June (50.65%), with no significant differences between the two groups in terms of age, gender, race, income, or insurance status. Of the 911,235 patients, 19,280 died during the study period following EGD, 2.14% (July-September) vs 1.95% (April-June), with an adjusted odds ratio of 1.09 (P < 0.01). The adjusted total hospitalization charge was $2052 higher in July-September ($81,597) vs April to June ($79,023) (P < 0.005). The mean length of stay was 6.8 days (July-September) vs 6.6 days (April-June) (P < 0.001). The results of this study are reassuring as the July effect on inpatient outcomes for EGDs was not significantly different according to our study. We recommend seeking prompt treatment and improving new trainee training and interspecialty communication for better patient outcomes.


Variations induced by different methodologies in Trypanosoma cruzi surface antigen profiles.
An attempt was made to reconcile published data on the cell surface profile of Trypanosoma cruzi epimastigotes. Cloned parasites were used to compare the effects of centrifugal forces, radioiodination catalyst and protein solubilization methods on the autoradiographic profile of putative surface antigens. Harvesting and washing procedures, and antigen extraction methods, greatly influenced the results obtained, whilst the iodination catalyst was not of critical importance. Mobility in different gel electrophoresis systems, Western blots and partial proteolysis maps indicated that two previously described epimastigote-specific surface antigens (GP72 and Mr 75,000) possibly are distinct molecules.