Systematic assessment of surgical complications in laparoscopically assisted vaginal hysterectomy for pelvic organ prolapse.
To assess patient safety and complication rates in native tissue vaginal prolapse repair combined with laparoscopically assisted vaginal hysterectomy and prophylactic salpingectomy/salpingoophorectomy. This was a single-centre retrospective study conducted at the University Hospital, Urogynaecological Unit, with a certified urogynaecological surgeon. A cohort of 321 consecutive patients received laparoscopically assisted vaginal hysterectomy for pelvic organ prolapse grade II-IV combined with defect-specific vaginal native tissue repair. Analysis of the total cohort and subgroups according to prolapse grade and concomitant laparoscopic procedures was performed. Student's t-tests and chi-squared tests were used for descriptive statistical analysis. Surgical complications were classified using the Clavien-Dindo (CD) classification system of surgical complications. Complications were classified as CD I (1.87%), CD II (13.39%), CD IIIa (0.62%), and CD IIIb (1.87%); no CD IV or CD V complication occurred. One (0.31%) intraoperative bladder lesion, but no rectal lesion, ureter lesion, or intraoperative haemorrhage requiring blood transfusion, was noted. The overall morbidity rate, including the intraoperative bladder lesion and the CD I complication, was 18.06%. All (n=321) patients underwent prophylactic salpingectomy. Additional oophorectomy was performed in 222 post-menopausal patients. Pelvic adhesions were found in 123 (38.31%) patients and 148 (46%) patients presented grade IV prolapse. Operating time was longer for grade IV than for grade II/III prolapse (p<0.01), but CD III complication rates did not differ between these groups. Operating time was longer when laparoscopic adhesiolysis was performed (p=0.025), but this factor did not affect CD III complication rates. The combination of vaginal site-specific prolapse repair with laparoscopically assisted hysterectomy leads to low complication rates. Prophylactic salpingectomy or salpingoophorectomy can be performed safely in combination with hysterectomy for pelvic organ prolapse. In terms of surgical safety laparoscopy seems to be a meaningful addition to vaginal native tissue prolapse surgery.


Passive avoidance behavior in mice: interaction between age and genotype.
BALB/c (BALB) and C57BL/6 (C57) mice were tested in a passive avoidance apparatus at different ages (6, 12 and 24 months). Results showed a clear-cut retention decrease only in 24 month old BALB mice in comparison with younger animals. No significant age effect was evident in C57 mice.


Effects of waveform parameters on comfort during transcutaneous neuromuscular electrical stimulation.
Twenty-three females between the ages of 19 and 35 were studied in order to compare the effects of variations in pulse duration, waveform symmetry, and source regulation on comfort during quadriceps surface stimulation at amplitudes necessary to produce 27 Nm torque. Stimulation parameters compared were: 1) 50 and 300 microseconds pulse durations, 2) asymmetrical and symmetrical biphasic waveforms, and 3) current and voltage source regulation. Subjects overwhelmingly preferred the 300 microseconds pulse duration regardless of waveform or source regulation, strongly preferred the symmetrical biphasic waveform, and had inconsistent preference for either regulated voltage or regulated current sources.


The impact of symbolism on immunogenetics: an application to HLA.
The genes coding for the class I human lymphocyte antigens (HLA) are located on chromosome 6. These antigens are involved with the immunological interaction between cells. In some immunogenetic systems, such as HLA in humans, genes are defined by antibody/antigen reaction and are denoted by single symbolic identifiers. This symbolization assumes a one-to-one correspondence between antibodies, antigens and genes. Recent molecular studies, however, suggest that HLA antibody/antigen reaction is complex and most HLA class I specific antibodies may not uniquely identify a single allelic product. Where cross-reactivity is present in an immunogenetic system it is important to label each reagent with symbols corresponding to all genes coding for antigens with which the reagent will react. The problems of cross-reactive groups and unexplained linkage relations may be elucidated by the redefinition and clarification of certain HLA antigens. A computer program can suggest such labelling schemes using input given by phenotype reaction patterns with a panel of reagents. When this program was applied to data on the class I HLA antigens a genetic model was suggested that differs somewhat from the currently accepted model. The new model is able to predict what would appear as linkage relations in the accepted model. Our methodology can provide alternate models to guide in typing cloned genes in terms of the HLA locus and alleles.


Formation of Ca HPO4-2H2O from enamel mineral and its relationship to caries mechanism.
Tooth enamel, when treated with dilute H3P94 solutions, dissolved incongruently with formation of large CaHPO4-2HO2O crystals. Equilibrated solutions were saturated with respect to Ca5(PO4)3OH, probably an impure, defective apatite. The CaHPO4-2H2O crystals formed at considerably higher pH values than expected becuase of enhanced solubility of the apatitic phase in enamel. Pyolysis of carious enamel revealed the presence of acidic calcium phosphate presumed to be CaHPO4-2H2O.


DHA 12-LOX-derived oxylipins regulate platelet activation and thrombus formation through a PKA-dependent signaling pathway.
The effects of docosahexaenoic acid (DHA) on cardiovascular disease are controversial and a mechanistic understanding of how this omega-3 polyunsaturated fatty acid (ω-3 PUFA) regulates platelet reactivity and the subsequent risk of a thrombotic event is warranted. In platelets, DHA is oxidized by 12-lipoxygenase (12-LOX) producing the oxidized lipids (oxylipins) 11-HDHA and 14-HDHA. We hypothesized that 12-LOX DHA-oxylipins may be involved in the beneficial effects observed in dietary supplemental treatment with ω-3 PUFAs or DHA itself. To determine the effects of DHA, 11-HDHA, and 14-HDHA on platelet function and thrombus formation, and to elucidate the mechanism by which these ω-3 PUFAs regulate platelet activation. DHA, 11-HDHA, and 14-HDHA attenuated collagen-induced human platelet aggregation, but only the oxylipins inhibited ⍺IIbβ3 activation and decreased ⍺-granule secretion. Furthermore, treatment of whole blood with DHA and its oxylipins impaired platelet adhesion and accumulation to a collagen-coated surface. Interestingly, thrombus formation was only diminished in mice treated with 11-HDHA or 14-HDHA, and mouse platelet activation was inhibited following acute treatment with these oxylipins or chronic treatment with DHA, suggesting that under physiologic conditions, the effects of DHA are mediated through its oxylipins. Finally, the protective mechanism of DHA oxylipins was shown to be mediated via activation of protein kinase A. This study provides the first mechanistic evidence of how DHA and its 12-LOX oxylipins inhibit platelet activity and thrombus formation. These findings support the beneficial effects of DHA as therapeutic intervention in atherothrombotic diseases.


Transobturatory tension-free composite sling for urethral support in patients with stress urinary incontinence: favorable experience after 1 year follow up.
Symptomatic, anatomic and urodynamic results of a composite transobturatory tension-free sling with an absorbable middle part, in patients with stress urinary incontinence (SUI), were studied. A prospective study in 40 women with SUI was performed. Symptoms, urodynamics and anatomical improvements were evaluated separately. Surgery was performed with the transobturatory approach. All patients had both clinically and urodynamically confirmed SUI. Clinical outcome was favorable in 36/40 (90%) patients, after 1 year. Operation improved the position of the bladder neck (2.8 cm and 1.4 cm below the pubic bone, respectively) and significantly decreased mobility of the bladder neck during abdominal straining (3.3 cm and 1.7 cm, respectively). Both symptoms and quality of life were significantly improved 1 month after the surgery. Postoperative maximum flow was lower than the preoperative one but with borderline significance (25.8 and 23.7 mL/s; P = 0.05). Pressure flow study showed unobstructed voiding both preoperatively and postoperatively. Detrusor pressure at the maximum flow was increased (20, 4 and 22, 8 cmH(2)O, respectively) but not significantly. Our results confirmed a high objective cure rate, improvement of symptoms and quality of life, and at the same time, corrected position of the bladder neck and unobstructed voiding.


Biology and function of the aryl hydrocarbon receptor: report of an international and interdisciplinary conference.
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor present in many cells. The AhR links environmental chemical stimuli with adaptive responses, such as detoxification, cellular homoeostasis or immune responses. Furthermore, novel roles of AhR in physiological and genetic functions are being discovered. This is a report of a recent meeting in Düsseldorf. The meeting highlighted that AhR research has moved from its focus on toxic effects of dioxins and other environmental pollutants to its biological roles. For instance, it was recently discovered that AhR-responsive elements in retrotransposons contribute to the functional structure of the genome. Other exciting new reports concerned the way plant-derived compounds in our diet are necessary for a fully functioning immune system of the gut. Also, human brain tumours use the AhR system to gain growth advantages. Other aspects covered were neurotoxicology, the circadian rhythm, or the breadth of the adaptive and innate immune system (hematopoietic stem cells, dendritic cells, T cells, mast cells). Finally, the meeting dealt with the discovery of new xenobiotic and natural ligands and their use in translational medicine, or cancer biology and AhR.


Post-injury conditioning with lipopolysaccharide or lipooligosaccharide reduces inflammation in the brain.
Traumatic brain injury (TBI) is a leading cause of mortality and disability in the Western world. The first stage of TBI results from the mechanical damage from an impact or blast. A second stage occurs as an inflammatory response to the primary injury and presents an opportunity for clinical intervention. In this study, we investigated the effect of pre- and post-injury treatment with lipopolysaccharide (LPS) from Escherichia coli and lipooligosaccharide (LOS) from Neisseria meningitidis on levels of cerebral inflammatory cells, circulating blood cells, and pro- and anti-inflammatory cytokine levels in a rat model of neuroinflammation induced by intrastriatal injection of IL-1β to mimic the second stage of TBI. LPS or LOS was administered intravenously (IV) or intranasally (IN) 2h pre- or post-injection of IL-1β. The rats were euthanized 12h following IL-1β injection. Brain sections were immunostained with antibody to ED-1, a microglia cell marker. Cells in whole blood were assessed with a VetScan HM2 analyzer, and cytokine levels in sera were analyzed with a Bio-Plex system. Pre- and post-injury IV administration of LPS or LOS significantly reduced microglia in the brain, and IN pre-treatment with LPS or LOS showed a statistical trend towards reducing microglia. Pre- and post-treatment IV with LOS increased circulating levels of IL-2 and IL-4, whereas IN post-treatment with LPS reduced levels of the inflammatory cytokines, TNF-α and IFN-γ. The findings strongly support continued investigation of post-conditioning with LPS or LOS as potential neuroprotective treatments for neuroinflammation from TBI.


Structure of lasso peptide epimerase MslH reveals metal-dependent acid/base catalytic mechanism.
The lasso peptide MS-271 is a ribosomally synthesized and post-translationally modified peptide (RiPP) consisting of 21 amino acids with D-tryptophan at the C-terminus, and is derived from the precursor peptide MslA. MslH, encoded in the MS-271 biosynthetic gene cluster (msl), catalyzes the epimerization at the Cα center of the MslA C-terminal Trp21, leading to epi-MslA. The detailed catalytic process, including the catalytic site and cofactors, has remained enigmatic. Herein, based on X-ray crystallographic studies in association with MslA core peptide analogues, we show that MslH is a metallo-dependent peptide epimerase with a calcineurin-like fold. The crystal structure analysis, followed by site-directed mutagenesis, docking simulation, and ICP-MS studies demonstrate that MslH employs acid/base chemistry to facilitate the reversible epimerization of the C-terminal Trp21 of MslA, by utilizing two pairs of His/Asp catalytic residues that are electrostatically tethered to a six-coordination motif with a Ca(II) ion via water molecules.


Defensive responses in invertebrates: Evolutionary and neural aspects.
Lower invertebrates exhibit both morphological and behavioral defensive responses to aversive stimuli, characterized by withdrawal. Typical immobility responses are "sinking" in Rotifers and "crumpling" in Cnidaria. They also display individual adaptation and phenotypic plasticity but not tonic immobility (TI). The higher phyla with a more organized nervous system have developed morphological and behavioral defensive strategies including TI, occurring both in natural and laboratory conditions. There are general but also specific prey-predator mechanisms, that have coevolved leading to reciprocal phenotypic plasticity. The evolution of traits differentiated in subpopulations has been described in many species (animal personality). In insects the variability in TI is heritable and inversely related to boldness. In two genetic lines of beetles with long and short TI duration, the long duration line has higher survival rate but lower mating success (behavioral syndromes). TI may have an adaptive significance also in intraspecific interactions in the context of sexual selection.


Effects of cellulose crystallinity, hemicellulose, and lignin on the enzymatic hydrolysis of Miscanthus sinensis to monosaccharides.
The effects of cellulose crystallinity, hemicellulose, and lignin on the enzymatic hydrolysis of Miscanthus sinensis to monosaccharides were investigated. A air-dried biomass was ground by ball-milling, and the powder was separated into four fractions by passage through a series of sieves with mesh sizes 250-355 microm, 150-250 microm, 63-150 microm, and <63 microm. Each fraction was hydrolyzed with commercially available cellulase and beta-glucosidase. The yield of monosaccharides increased as the crystallinity of the substrate decreased. The addition of xylanase increased the yield of both pentoses and glucose. Delignification by the sodium chlorite method improved the initial rate of hydrolysis by cellulolytic enzymes significantly, resulting in a higher yield of monosaccharides as compared with that for untreated samples. When delignified M. sinensis was hydrolyzed with cellulase, beta-glucosidase, and xylanase, hemicellulose was hydrolyzed completely into monosaccharides, and the conversion rate of glucan to glucose was 90.6%.


A high-resolution electron microscope study of synthetic and biological carbonated apatites.
A series of synthetic carbonated apatites and human dental enamels characterized by chemical analysis, infrared spectroscopy, and X-ray diffraction was studied using high-resolution transmission electron microscopy. Steps on the surfaces of apatite crystals, often only a few unit cells high and occasionally one unit cell high, were observed by their Fresnel diffraction contrast. Highly substituted synthetic carbonated apatites appeared to have more irregular and finer-textured surface features than materials with less carbonate substitution. The surface features of enamel apatite crystal were also irregular, but surface steps were less frequently aligned in crystallographic directions. Complex strain fields due to radiation damage centers were observed in some crystals and the fine structure of dislocations and grain boundaries in synthetic apatites was resolved at high magnification. Experimental lattice-image contrasts, in favorable circumstances, could be matched to computer-simulated images and were found to contain detail at near atomic resolution, around 2.0-2.5 A.


Import and assembly of Neurospora crassa Tom40 into mitochondria of Trypanosoma brucei in vivo.
The TOM complex (translocase of the mitochondrial outer membrane) is a dynamic, multisubunit protein complex. Tom40 is the major component of the complex and forms the preprotein conducting pore. To determine if a heterologous Tom40 could be properly targeted and assembled into the Trypanosoma brucei mitochondrial outer membrane, an ectopic copy of a gene encoding Neurospora crassa Tom40 (NcTom40) was expressed in procyclic trypanosomes from a tetracycline regulated procyclic acidic repetitive protein promoter. The level of NcTom40 expression was found to be maximal within 20-26 h of induction with tetracycline. Immunoblot analysis of subcellular fractions showed that NcTom40 was enriched in the mitochondrial fraction. Alkali extraction of isolated mitochondria revealed that NcTom40 was assembled as an integral membrane protein and limited proteolysis demonstrated that it was present in the outer membrane of the mitochondria. These data demonstrate that a heterologous mitochondrial protein containing internal targeting information can be correctly targeted to T. brucei mitochondria. Following blue native gel electrophoresis, the NcTom40 protein was found in a 370 kDa complex which may contain T. brucei Tom components. A 16 kDa protein was coimmunoprecipitated from T. brucei mitochondria containing NcTom40 using antisera developed against the N. crassa protein. The 16 kDa protein may represent a component of the T. brucei TOM complex that associates with NcTom40.


Steroid metabolism in human breast cancer cell lines.
The metabolism of 1,2-3H-androstenedione was studied in 2 cell lines, MCF-7 (estrogen responsive) and BT-20 (estrogen nonresponsive) over 48 hrs. Water soluble and unconjugated metabolites were separated by solvent partition and the former was submitted to chromatography on Sephadex LH-20 and enzyme hydrolysis. The resulting unconjugated steroids were separated by paper chromatography and identities were established by reverse isotope dilution. The unconjugated steroids initially obtained were separated by chromatography and identified by reverse isotope dilution. About 70% of the androstenedione was metabolized by both cell lines. However, the respective conversions to conjugates by MCF-7 and BT-20 were 31% and 0.32%. In the former, glucosiduronates predominated (94%) and consisted of androsterone (55%), etiocholanolone (9.4%) and androstanediol (5alpha-androstane-3alpha,17beta-diol) (9.3%). Androsterone comprised most of the unconjugated metabolites in both cell lines. Androstanediol was found in both cell lines, 2% in MCF-7 and 12% in BT-20. Testosterone, 5alpha-androstane-3,17-dione and 3beta-hydroxy-5alpha-androstan-17-one were isolated only from MCF-7. The metabolism of 3H-estriol was studied in a similar way. Both cell lines produced about equal amounts of estriol-3-sulfate (9%) and a compound with properties of estriol-3-glucosiduronate (0.15--0.5%). The results worthy of emphasis are: 1. The far greater conjugation of androgens exhibited by the MCF-7 cell lines as compared to the BT-20 cell lines; 2. In MCF-7, the high conversion of androstenedione to etiocholanolone (glucosiduronate form), a metabolite reported to form only in liver and sebaceous cysts; 3. The possible formation in both cell lines of estriol-3-glucosiduronate, normally a metabolite of the intestine.


Identification and characterization of extensive intra-molecular associations between 3'-UTRs and their ORFs.
During eukaryotic translation, mRNAs may form intra-molecular interactions between distant domains. The 5'-cap and the polyA tail were shown to interact through their associated proteins, and this can induce physical compaction of the mRNA in vitro. However, the stability of this intra-molecular association in translating mRNAs and whether additional contacts exist in vivo are largely unknown. To explore this, we applied a novel approach in which several endogenous polysomal mRNAs from Saccharomyces cerevisiae were cleaved near their stop codon and the resulting 3'-UTR fragments were tested either for co-sedimentation or co-immunoprecipitation (co-IP) with their ORFs. In all cases a significant fraction of the 3'-UTR fragments sedimented similarly to their ORF-containing fragments, yet the extent of co-sedimentation differed between mRNAs. Similar observations were obtained by a co-IP assay. Interestingly, various treatments that are expected to interfere with the cap to polyA interactions had no effect on the co-sedimentation pattern. Moreover, the 3'-UTR appeared to co-sediment with different regions from within the ORF. Taken together, these results indicate extensive physical associations between 3'-UTRs and their ORFs that vary between genes. This implies that polyribosomal mRNAs are in a compact configuration in vivo.


Nephritogenicity and immunocytochemical localization of the 70-kilodalton glycoprotein subunit (gp70) of Heymann antigen.
Heymann nephritis (HN) is an experimentally induced glomerulonephropathy of the rat characterized by subepithelial immune deposits and proteinuria. Immunization with a complex multimeric glycoprotein, gp600, comprising four subunits gp330, gp140, gp110, and gp70 has been shown to induce the complete form of the disease including proteinuria. Examination of three different batches of heterologous anti-gp600 antisera by immunoblot technique showed that the reactivity toward gp70 was dominant and common to all three antisera. gp70 was isolated from Triton X-100-solubilized Fx1A by lectin Lens culinaris affinity chromatography, and the purity was confirmed by SDS-PAGE. Ten rats were actively immunized with 200 micrograms of gp70. All 10 animals developed circulating brush border antibody and typical granular IgG deposits in the glomerulus but only 1/10 animals developed abnormal proteinuria. A potent antiserum against gp70 was prepared in the rabbit. It reacted strongly to the glomerular capillary wall and the proximal tubular brush border by immunofluorescence. By Protein A immunogold technique using anti-gp70, gold particles were found associated with the glomerular basement membrane (GBM)-endothelial region. By immunoblot analysis of rat GBM using the same anti-gp70 antiserum, a 70-kDa cross-reactive antigen was demonstrated in GBM preparations. These results show that the smallest subunit, gp70 of the complete HN antigen, gp600/Fx1A can independently induce the lesion of HN, but without proteinuria. The presence of gp70 on the endothelial side of the GBM is consistent with a role for in situ antigen-antibody reactions at sites other than the subepithelial region in the pathogenesis of HN.


Numerical Model and Experimental Validation for Laser Sinterable Semi-Crystalline Polymer: Shrinkage and Warping.
Shrinkage and warping of additive manufacturing (AM) parts are two critical issues that adversely influence the dimensional accuracy especially in powder bed fusion processes such as selective laser sintering (SLS). Powder fusion, material solidification, and recrystallization are the key stages causing volumetric changes of polymeric materials during the abrupt heating-cooling process. In this work, the mechanisms of shrinkage and warping of semi-crystalline polyamide (PA) 12 in SLS are well investigated. Heat-transfer and thermo-mechanical models are established to predict the process-dependent shrinkage and warping. The influence of raw material- and laser-related parameters are considered in the heat-transfer and thermo-mechanical models. Such models are established considering the natural thermal gradient and dynamic recrystallization, which induce internal strain and volumetric change. Moreover, an experimental design via orthogonal approach is introduced to validate the feasibility and accuracy of the proposed models. Finally, the quantitative relationships of process parameters with product shrinkage and warping are established; the dimensional accuracy in part-scale can be well predicted and validated with printed parts in a real experiment.


Acute severe mitral regurgitation. Pathophysiology, clinical recognition, and management.
Acute severe mitral regurgitation often goes unrecognized as an emergency requiring prompt, lifesaving treatment. Its causes, physical signs, natural history, echocardiographic features, and findings on chest roentgenography, electrocardiography, and nuclear scintigraphic scanning are reviewed. Acute severe mitral insufficiency can be differentiated from chronic severe mitral insufficiency by noninvasive two-dimensional echocardiography. M-mode echocardiography is a valuable tool in evaluating mitral prosthetic paravalvular regurgitation.


Use and safety of anthroposophic medications for acute respiratory and ear infections: a prospective cohort study.
Anthroposophic medications (AMED) are widely used, but safety data on AMED from large prospective studies are sparse. The objective of this analysis was to determine the frequency of adverse drug reactions (ADR) to AMED in outpatients using AMED for acute respiratory and ear infections. A prospective four-week observational cohort study was conducted in 21 primary care practices in Europe and the U.S.A. The cohort comprised 715 consecutive outpatients aged ≥1 month, treated by anthroposophic physicians for acute otitis and respiratory infections. Physicians' prescription data and patient reports of adverse events were analyzed. Main outcome measures were use of AMED and ADR to AMED. two patients had confirmed ADR to AMED: 1) swelling and redness at the injection site after subcutaneous injections of Prunus spinosa 5%, 2) sleeplessness after intake of Pneumodoron(®) 2 liquid. These ADR lasted one and two days respectively; both subsided after dose reduction; none were unexpected; none were serious. The frequency of confirmed ADR to AMED was 0.61% (2/327) of all different AMED used, 0.28% (2/715) of patients, and 0.004% (3/73,443) of applications. In this prospective study, anthroposophic medications used by primary care patients with acute respiratory or ear infections were well tolerated.


Genetic modifiers and phenotypic variability in neuromuscular disorders.
Neuromuscular disorders are mostly rare diseases with autosomal dominant, recessive, or X-linked inheritance. Interestingly, among patients carrying the same mutations, a range of phenotypic severity is reported. This phenotypic variability in neuromuscular disorders is still not fully understood. This review will focus on genetic modifiers and will briefly describe metabolic pathways, in which they are involved. Genetic modifiers are variants in the same or other genes that modulate the phenotype. Proteins encoded by genetic modifiers in neuromuscular diseases are taking part in different metabolic processes, most commonly in inflammation, growth and regeneration, endoplasmic reticulum metabolism, and cytoskeletal activities. Recent advances in omics technologies, development of computational algorithms, and establishing large international consortia intensified discovery sped up investigation of genetic modifiers. As more individuals affected by neuromuscular disorders are tested, it is often suggested that classic models of genetic causation cannot explain phenotypic variability. There is a growing interest in their discovery and identifying shared metabolic pathways can contribute to design targeted therapies. We provide an update on variants acting as genetic modifiers in neuromuscular disorders and strategies used for their discovery.


Use of Computed Tomography of the Head in Patients With Acute Atraumatic Altered Mental Status: A Systematic Review and Meta-analysis.
The usefulness of computed tomography of the head (CTH) in patients with acute-onset atraumatic altered mental status (AMS) is poorly understood, but use in these patients remains high. To evaluate the use of CTH (event rate) in patients with AMS and the positive outcome event rate of the performed CTH studies. The PubMed/MEDLINE, PubMed Central, Embase, and CINAHL databases were searched using predefined Boolean parameters. All studies that met inclusion criteria until January 31, 2022, were included. Randomized clinical trials and observational, cohort, and case-control studies were included. Conference abstracts, reviews, letters, case reports, case series, systematic literature, and meta-analyses were excluded. The systematic literature review was performed per Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Data were independently extracted by 2 authors. Data were pooled using a random-effects method. Event rate of CTH use in patients with acute atraumatic AMS. The CTH event rates and positive CTH event rates were calculated with 95% CIs. Of 9338 studies identified, 26 qualified for the systematic review and 25 for the meta-analysis. The 25 studies in the meta-analysis included a total of 79 201 patients. The CTH event rate was 94% (proportion, 0.94; 95% CI, 0.76-1.00), and the positive CTH event rate was 11% (proportion, 0.11; 95% CI, 0.07-0.15). There was significant heterogeneity among the studies included (I2 > 50%, P < .001), for which a random-effects model was used. There was significant publication bias, as evident by an asymmetric funnel plot. There was no fluctuation of the results during the sensitivity analysis, which reassured the reliability of the data. In this meta-analysis, CTH use among patients with acute-onset atraumatic AMS was very high with a low yield. Large-scale studies are needed to guide clinical decision-making in such a situation.


Historical notes on the World Federation of Neurology Research Group on Aphasia and Cognitive Disorders (RGACD).
A brief history of the establishment and the activities of the WFN Research Group on Aphasia and Cognitive disorders is presented, based on the archives of the group. The purpose is to achieve continuity between the past and present and to document the collective memories of the activities of the group, hereby strengthening its future.


Low morbidity and mortality in children with diabetic ketoacidosis treated with isotonic fluids.
To assess current rates of complications of diabetic ketoacidosis (DKA), particularly cerebral edema, in a large tertiary-care pediatric hospital with a consistent management protocol. We report our single-center retrospective experience with 3712 admissions with DKA in 1999-2011. Our DKA protocol features a "3-bag" system using 2 bags of rehydration fluids, identical except for the presence in 1 bag of 10% dextrose, to allow rapid adjustment of glucose infusion rate. The third bag contains insulin. Fluids are administered at a total rate of 2-2.5 times "maintenance" fluid requirements. Total electrolyte concentration is kept approximately isotonic. Billing and medical records databases at Children's Medical Center Dallas were examined for cases of DKA, cerebral edema, other morbidities, and death. We ascertained 20 cases of cerebral edema (0.5%). Most presented early (median duration of treatment 2 hours). Only 10 of 20 computed tomography scans were graded as moderate edema or worse. Only 10 patients received treatment other than routine DKA management. There was 1 death in a patient with sickle cell trait who developed intravascular sickling. Two patients had neurologic sequelae at hospital discharge but both recovered fully. Compared with data in recent consensus statements, the Dallas protocol is associated with extremely low rates of death and disability (0.08% vs 0.3%) from DKA.


Recent research in organization and expression of immunoglobulin V region genes.
The first Jacques Monod Conference was held in Roscoff, Brittany on 1-5 June 1987 and dealt with the topic of 'Selection of Lymphocyte Repertoires' (organizers F. W. Alt, Columbia University, New York. P.-A. Cazenave, Institut Pasteur, Paris and A. Coutinho, Institut Pasteur, Paris). Much of the meeting was concerned with the recent developments in immunoglobulin and T-cell receptor V region organization and expression. This review is based on the contributions and discussions on Ig V genes, in particular their organization, rearrangements, allelic exclusion and somatic mutation. (Names without references indicate the conference speaker on that topic.)


Mirex and behavior in the Long-Evans rat.
In two experiments, adult male Long-Evans rats were fed chow containing mirex (1.78 ppm and 17.8 ppm in Experiment 1, 17.8 ppm in Experiment 2) over a several week period and were tested on a variety of behavioral tasks. No differences in behavior were seen between control and experimental animals tested in an open-field apparatus, on VI 30-sec and DRL 20-sec operant paradigms, or on a discrimination-reversal task motivated by escape from footshock.


Defying Expectations: How Neurons Compute Prediction Errors in Visual Cortex.
In this issue of Neuron, Jordan and Keller (2020) explore subthreshold computations underlying predictive coding using whole-cell recordings in mouse visual cortex. Their findings suggest that layer 2/3, but not layer 5/6, neurons compute prediction errors by subtracting predicted and actual visual flow inputs generated by locomotion.


Polycyclic aromatic hydrocarbon-DNA adduct formation in prostate carcinogenesis.
The evidence for polycyclic aromatic hydrocarbons (PAH) playing a role in prostate carcinogenesis comes mainly from associations between reported PAH exposures and prostate cancer in epidemiologic studies. Associations between prostate cancer and DNA repair genotypes and phenotypes have also been reported, lending further credence to a PAH-induced carcinogenesis pathway in prostate cancer. Recent work that demonstrates the human prostate has metabolic enzyme activity necessary for PAH activation and will form DNA adducts upon exposure to PAH further supports PAH carcinogenesis. We have demonstrated the presence of PAH-DNA adducts in prostate cancer cases, but further validation of this biomarker as a carcinogenic agent in human prostate is needed.


Management of intracranial pressure in tuberculous meningitis.
Tuberculous meningitis (TBM) remains a common serious neurological emergency especially in the developing world. Elevated intracranial pressure (ICP) is often a feature of severe TBM and is associated with high morbidity and mortality. The pathology associated with TBM, such as cerebral edema, hydrocephalus, tuberculoma(s), and infarcts related to arthritis, contribute to increase in intracranial volume and, therefore, elevated ICP. The three types of edema (vasogenic, cytotoxic, and interstitial) may contribute to cerebral edema. The molecular mechanisms underlying the events that ultimately lead to brain damage and cerebral edema during infection are complex. Similarly to bacterial meningitis, cerebral blood flow autoregulation is probably impaired in TBM, and the mechanisms are unclear. Although no universal guidelines are available to institute ICP monitoring in patients with severe TBM, it is be prudent to monitor patients at risk for increases in ICP. Such an approach helps to detect the secondary brain insults, allowing for a more informed approach to treatment. Treatment of elevated ICP involves a multipronged approach. The first step should be to identify focal brain lesions and hydrocephalus (which require surgical intervention) by brain imaging. Cerebral edema is treated with hyperosmolar agents. Mannitol is currently the most commonly used agent. It appears that use of hypertonic saline as an osmotic agent in infection-related cerebral edema has certain advantages. However, this needs to be established by well-designed trials. Use of steroids reduces not only cerebral edema but also the production of cytokines and other chemicals involved in the immunopathogenesis of TBM. Fever associated with TBM should be aggressively treated, because fever can worsen the impact of elevated ICP. Hyponatremia may complicate TBM and requires appropriate correction because it can aggravate cerebral edema.


Modeling of Chronic Lung Inflammation in Rats by Repeated Intratracheal Administration of LPS.
A model of a chronic lung inflammation in SPF Sprague-Dawley rats was developed by repeated intratracheal administration of LPS in a dose of 0.4 mg/kg. On day 22 of the study, male rats treated with LPS have relative monocytopenia and reduced mean concentration of hemoglobin in the erythrocyte and the mean platelet volume in comparison with the control animals (saline). Intratracheal administration of LPS induced an inflammatory process in the lungs characterized by focal atelectasis, compensatory emphysematous expansion of subpleural pulmonary acini, focal mononuclear and neutrophilic perivascular and peribronchial infiltration, and minor focal mononuclear and neutrophilic infiltration of the alveolar walls. Against the background of LPS administration, germinal centers appeared in the lymphoid follicles of the white pulp of the spleen, and focal mononuclear infiltration of the tracheal mucosa and/or submucosa was observed in some animals.


Ethylene Signaling Controls Fast Oxygen Sensing in Plants.
When plants are submerged by water they suffer from hypoxia. Although it has long been known that ethylene accumulates in submerged plants, its role in plant tolerance to hypoxia remained elusive. Recently, Hartman et al. described a mechanism that explains the role of ethylene in oxygen sensing and signaling.


Outlier-response pattern checks to improve measurement with the Montgomery-Asberg depression rating scale (MADRS).
Symptom manifestations in affective disorders can be subtle. Small imprecisions in measurement can lead to incorrect estimation of change. Previously, expert-derived scoring inconsistency flags were developed for MADRS. Currently, we derive empirically based outlier-pattern flags, to further detect imprecisions in ratings. NEWMEDS data repository of almost 25,000 MADRS administrations from 11 registration trials of antidepressants was used to identify outlier response patterns reflecting potentially careless responses. Coverage of these flags was compared to previously published expert derived flags. Both sets of flags were also further tested in Monte Carlo simulated data as a proxy to applying flags under conditions of known inconsistency. The outlier flags derived provide cutting points to identify: (1) under and overuse of values (e.g., Scoring "1″ on 6 or more items), (2) disproportionate use of even or odd response choices (e.g., 8 or more odd values), (3) longest consecutive use of value (e.g., more than 5 items in a row scored with same value), (4) high variability within administration (standard deviation greater than 1.8), (5) outlier responses on multiple items (i.e., multivariate outliers), and (6) outlier scoring (e.g., scoring 4,5 or 6 on item 1). Outlier response flags were raised in 26% of the MADRS administration and in 97% of the Monte Carlo data. Of administrations with no expert flag, 21.7% had an outlier flag and of administrations with at least one expert flag, 27.7% also had an outlier flag. Outlier-pattern flags appear to be a useful adjunct to expert derived flags in the quest to improve measurement in clinical trials.


Association of polychlorinated biphenyls with vitamin D in female subjects.
Polychlorinated biphenyls (PCBs) are known endocrine disrupters. A potentially causal association of PCBs with vitamin D has been reported. Higher body mass index (BMI) is associated with lower PCB levels whilst the strongest association of PCBs with BMI is in non-obese individuals. Therefore, this study examined the association of PCBs with vitamin D3 (25(OH)D3) and the active 1,25-dihydrovitamin D3 (1,25(OH)2D3) in a cohort of non-obese women. 58 female participants (age 31.9 ± 4.6 years; BMI 25.7 ± 3.7 kg/m2) had seven indicator PCBs [PCB28, PCB52, PCB101, PCB118, PCB138, PCB153 and PCB180] measured using high resolution gas chromatography, with total PCB level calculated. 25(OH)D3 and 1,25(OH)2D3 levels were determined by isotope-dilution liquid chromatography tandem mass spectrometry. In this cohort, vitamin D3 (25(OH)D3) and 1,25(OH)2D3 levels were 50.7 ± 25.3 nmol/L and 0.05 ± 0.02 ng/ml, respectively. Of those, 28 had vitamin D deficiency [25(OH)D3 level <20 ng/ml (<50nmol/)]. Total PCBs correlated positively with total group 25(OH)D3 (r = 0.22, p = 0.04) as did PCB118 (r = 0.25, p = 0.03). Total PCBs did not correlate with total group 1,25(OH)2D3; however, PCB180 did correlate positively with 1,25(OH)2D3 (r = 0.34, p = 0.03) as did PCB153 (r = 0.33, p < 0.03), with PCB 28 correlating negatively (r = -0.29, p < 0.04). In the vitamin D deficient subgroup, total PCBs, PCB153 and PCB180 positively correlated with 25(OH)D3 (p < 0.05). Multilinear regression analysis indicated all associations could be accounted for by BMI. Though certain PCBs associated with 25(OH)D3 and 1,25(OH)2D3, all associations could be accounted for by BMI. This study therefore indicates that the deleterious effects from PCB accumulation are not mediated by effects on 25(OH)D3 or 1,25(OH)2D3.


How do authors of systematic reviews deal with research malpractice and misconduct in original studies? A cross-sectional analysis of systematic reviews and survey of their authors.
To study whether systematic reviewers apply procedures to counter-balance some common forms of research malpractice such as not publishing completed research, duplicate publications, or selective reporting of outcomes, and to see whether they identify and report misconduct. Cross-sectional analysis of systematic reviews and survey of their authors. 118 systematic reviews published in four journals (Ann Int Med, BMJ, JAMA, Lancet), and the Cochrane Library, in 2013. Number (%) of reviews that applied procedures to reduce the impact of: (1) publication bias (through searching of unpublished trials), (2) selective outcome reporting (by contacting the authors of the original studies), (3) duplicate publications, (4) sponsors' and (5) authors' conflicts of interest, on the conclusions of the review, and (6) looked for ethical approval of the studies. Number (%) of reviewers who suspected misconduct are reported. The procedures applied were compared across journals. 80 (68%) reviewers confirmed their data. 59 (50%) reviews applied three or more procedures; 11 (9%) applied none. Unpublished trials were searched in 79 (66%) reviews. Authors of original studies were contacted in 73 (62%). Duplicate publications were searched in 81 (69%). 27 reviews (23%) reported sponsors of the included studies; 6 (5%) analysed their impact on the conclusions of the review. Five reviews (4%) looked at conflicts of interest of study authors; none of them analysed their impact. Three reviews (2.5%) looked at ethical approval of the studies. Seven reviews (6%) suspected misconduct; only 2 (2%) reported it explicitly. Procedures applied differed across the journals. Only half of the systematic reviews applied three or more of the six procedures examined. Sponsors, conflicts of interest of authors and ethical approval remain overlooked. Research misconduct is sometimes identified, but rarely reported. Guidance on when, and how, to report suspected misconduct is needed.


Survival after resection of colorectal liver metastases in octogenarians and sexagenarians compared to their respective age-matched national population.
The aim of the current study was to investigate survival after resection of colorectal liver metastases (CLM) in octogenarians. The survival of octogenarian patients was compared to the survival of the national population of octogenarians and the survival of sexagenarians, the latter representing the average-age patient undergoing resection of CLM. Octogenarian and sexagenarian were defined as person 80-89 and 60-69 years of age, respectively. Survival analyses of patients who underwent resection of CLM between 2002 and 2014 were performed. Data from Statistics Norway were used to estimate the survival of the age-matched national population of octogenarians (ageM-Octo) and the age-matched national population of sexagenarians (ageM-Sexa). During the study period, 59 octogenarians underwent resection of CLM. The majority of patients underwent a minor liver resection (n=50). In octogenarians, the 5-year survival was 32.5% and 66.3% [difference, 33.8 percentage points (pp)] in patients and ageM-Octo, respectively. The 10-year survival was 14.1% and 31.2% (difference, 17.1 pp) in patients and ageM-Octo, respectively. In sexagenarians, the 5-year survival was 50.9% and 96.2% (difference, 45.3 pp) in patients and ageM-Sexa, respectively. The 10-year survival was 35.7% and 90.3% (difference, 54.6 pp) in patients and ageM-Sexa, respectively. The 5-year cancer-specific survival and 5-year recurrence-free survival (RFS) after resection of CLM in octogenarians were 43.1% and 32.9%, respectively. After resection of CLM, the survival was poorer in octogenarians than in sexagenarians. However, the difference between the survival curves of patients and their age-matched population was smaller in octogenarians. In practice, this finding may indicate a greater benefit of resection in the elderly than the survival rates alone would suggest.


[Diagnostic ability of ultrasonography for the rotator cuff tear: comparison with ultrasonography and MRI findings].
Ultrasonography (US) is a non-invasive method which can assess not only solid tissue organs but also soft tissues such as tendons and nerves. However, it has not been fully understood that US is a useful tool for the depiction of periarticular structure. We compared the diagnostic accuracies between US and magnetic resonance imaging (MRI) in the patients with rotator cuff tear (RCT). Seventy patients, who underwent arthroscopic surgery, preoperative US and MRI examinations at Gifu University Hospital from January 2010 to April 2013 (49 male, 21 female, mean age 59.7 +/- 15.9) were included in this study. The diagnostic accuracy, sensitivity and specificity of US and MRI were 94.3% and 94.3%, 95.8% and 97.9%, 90.9% and 84.6%, respectively, when the intraoperative finding was regarded as a gold standard. These results suggest that US is useful for the diagnosis of RCT as equal as MRI.


Early regionalisation of the neocortex and the medial ganglionic eminence.
The two major functional classes of neurons that build the cerebral cortex are generated in two distinct parts of the telencephalon. Excitatory long distance projecting neurons are produced dorsally in the pallium, whereas local inhibitory interneurons are mainly produced in the medial ridge of the ventral telencephalon. These two parts of the telencephalon are molecularly regionalized from early embryonic stages, but cellular indices of regionalisation are observed only at later stages of development. We have looked for cellular indices of regionalisation in the cortical anlage at early embryonic stages, when the first efferent cortical neurons are generated. Similarly, we have looked for functional regionalisation of the medial ganglionic eminence at the same stages, when the future cortical interneurones are generated. Here, we summarize data showing that two regions in the mouse cortex embryo, the lateral and dorsal cortex, differ strongly in their early neurogenesis. Moreover, the two domains differ in their capacity to produce GABAergic neurons in vitro; this capacity is only observed in the dorsal cortex. The differentiation of the two domains appears to be independent of the laterorostral to mediocaudal gradient of maturation of the cortex. In the basal telencephalon too, the capacity to differentiate GABAergic neurons is not uniformly distributed across the medial ganglionic eminence. The neurogenesis of future cortical interneurons is seen to be highly active in a small area located in the rostral MGE, at mid dorso-ventral level.


Race and ethnic variation in college students' allostatic regulation of racism-related stress.
Racism-related stress is thought to contribute to widespread race/ethnic health inequities via negative emotion and allostatic stress process up-regulation. Although prior studies document race-related stress and health correlations, due to methodological and technical limitations, they have been unable to directly test the stress-reactivity hypothesis in situ. Guided by theories of constructed emotion and allostasis, we developed a protocol using wearable sensors and daily surveys that allowed us to operationalize and time-couple self-reported racism-related experiences, negative emotions, and an independent biosignal of emotional arousal. We used data from 100 diverse young adults at a predominantly White college campus to assess racism-related stress reactivity using electrodermal activity (EDA), a biosignal of sympathetic nervous system activity. We find that racism-related experiences predict both increased negative emotion risk and heightened EDA, consistent with the proposed allostatic model of health and disease. Specific patterns varied across race/ethnic groups. For example, discrimination and rumination were associated with negative emotion for African American students, but only interpersonal discrimination predicted increased arousal via EDA. The pattern of results was more general for Latinx students, for whom interpersonal discrimination, vicarious racism exposure, and rumination significantly modulated arousal. As with Latinx students, African students were particularly responsive to vicarious racism while 1.5 generation Black students were generally not responsive to racism-related experiences. Overall, these findings provide support for allostasis-based theories of mental and physical health via a naturalistic assessment of the emotional and sympathetic nervous system responding to real-life social experiences.


The rate and pattern of otic epithelial migration: systematic review.
Epithelial migration has been associated with the self-cleansing mechanism of the ear. The rate and pattern of epithelial migration in healthy and pathological ears are reviewed. Two authors independently screened articles over one month using the following search terms: epithelial migration, epithelial, tympanic membrane, external auditory canal and mastoidectomy cavity. Ten studies were included. The fastest rate of epithelial migration was observed in the external auditory canal, with a mean of 144.75 μm per day, whereas the slowest epithelial migration was seen in post-mastoidectomy cavities, with a rate of 20 μm per day. Epithelial migration was present in both studies involving post-mastoidectomy cavities. Epithelial migration is faster in healthy tympanic membrane than in pathological tympanic membrane. The rate of epithelial migration in the external auditory canal was higher in the pathological group than in the healthy group. Epithelial migration is present in post-mastoidectomy cavities.


Examining Secondary Trauma as a Result of Clients' Reports of Discrimination.
In the current study, we examined the extent to which 86 American clinicians heard reports of discrimination from their clients of color. Findings indicated that 96.5% of clinicians heard at least one report of discrimination from clients of color at least occasionally in counseling. The acts of discrimination most frequently reported by clients of color were: a) being made to feel like outsiders, b) treated unfairly by coworkers and classmates, and c) treated unfairly by teachers and principals. Additionally, we investigated the predictive nature of reports of discrimination from clients of color on clinicians' compassion satisfaction, burnout, and secondary traumatic stress. The three predictor variables (clinicians' age, years counseling, and clients of color's reports of discrimination) did not significantly predict compassion satisfaction or burnout, yet significantly predicted secondary traumatic stress. These results revealed that as reports of discrimination from clients of color increased, so too did clinicians' secondary traumatic stress.


Diclofenac-associated hepatotoxicity: analysis of 180 cases reported to the Food and Drug Administration as adverse reactions.
Diclofenac is a nonsteroidal anti-inflammatory drug approved in the United States in 1988 for the treatment of patients with osteoarthritis, rheumatoid arthritis, or ankylosing spondylitis. To characterize the clinical, biochemical, and histological features and possible mechanisms of hepatic injury associated with its use, a retrospective analysis was undertaken of 180 patients whose cases were reported to the Food and Drug Administration from November 1988 through June 1991, as having had possible adverse reactions to diclofenac. Of the reported 180 cases, 79% were female, 71% were 60 years of age or older, and 77% had osteoarthritis. Sixty-seven percent of the cases were detected by symptoms and the remainder by abnormal laboratory tests. Seventy-five percent of the symptomatic patients (90 of 120) were jaundiced. Seven of the 90 icteric patients died. The biochemical pattern of injury was hepatocellular or mixed hepatocellular in 66% of cases. Only 8% had a pattern of cholestatic injury. The remainder, with modestly increased values of both transaminases and alkaline phosphatase, were considered "indeterminate," i.e., either mild hepatocellular or anicteric "cholestatic" injury. Sections of liver from 21 cases were available for study. Hepatic injury was apparent by 1 month after starting the drug in 24%, by 3 months in 63%, and by 6 months in 85% of cases. The latent period in 12% was 6 to 12 months, whereas in 3% it was greater than 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)


IoT Sensing Platform as a Driver for Digital Farming in Rural Africa.
Small-scale farming can benefit from the usage of information and communication technology (ICT) to improve crop and soil management and increase yield. However, in order to introduce digital farming in rural areas, related ICT solutions must be viable, seamless and easy to use, since most farmers are not acquainted with technology. With that in mind, this paper proposes an Internet of Things (IoT) sensing platform that provides information on the state of the soil and surrounding environment in terms of pH, moisture, texture, colour, air temperature, and light. This platform is coupled with computer vision to further analyze and understand soil characteristics. Moreover, the platform hardware is housed in a specifically designed robust casing to allow easy assembly, transport, and protection from the deployment environment. To achieve requirements of usability and reproducibility, the architecture of the IoT sensing platform is based on low-cost, off-the-shelf hardware and software modularity, following a do-it-yourself approach and supporting further extension. In-lab validations of the platform were carried out to finetune its components, showing the platform's potential for application in rural areas by introducing digital farming to small-scale farmers, and help them delivering better produce and increasing income.


Chronic leg ulcerations resembling vasculitis in two siblings with prolidase deficiency.
Two cases of prolidase deficiency in two siblings are presented. The patients complained of the typical clinical symptoms of the disease, including chronic leg ulcerations resembling vasculitis. They were mentally retarded, had typical facial characteristics, splenomegaly, and haematologic anomalies. Biochemical and morphological investigations confirmed the diagnosis. In these cases, alterations of the peripheral nervous system and decreased IgA levels were demonstrated for the first time.


Antimicrobials in dog-to-dog bite wounds: A retrospective study of 1526 dog bite events (1999-2019).
Although dog-to-dog bite wounds (DBW) are common, few studies worldwide have evaluated antimicrobial usage patterns or appropriateness of use. Report frequency and results of DBW cultures, including antimicrobial susceptibility patterns. Determine the most commonly prescribed antimicrobials and their appropriateness for the treatment of DBW, and if antimicrobial importance is associated with wound severity, clinic type or year. One thousand five hundred twenty-six dog bite events involving 1436 dogs presenting with DBW from 3 Australian university clinics from 1999 to 2019. Retrospective study. Medical records were reviewed for presenting signs, culture and susceptibility testing, antimicrobial treatment, and outcome. A partial proportional odds model was used to determine if use of higher importance antimicrobials was associated with wound severity, clinic, or year. Antimicrobials were prescribed in 88.1% (1344/1526) of DBW. Amoxicillin-clavulanic acid was prescribed in 73.4% (1121/1526) of dogs, followed by first-generation cephalosporins, 18.1% (277/1526). Of a total of 1647 antimicrobial prescriptions, underdosing occurred in 13.4% for AMC (220/1647) and 26.1% (81/310) of dogs prescribed first generation cephalosporins. There was an association between the increased use of high-importance antimicrobials and wound severity (P < .001), antimicrobial polytherapy (P < .001) and year (P < .001). The odds of the clinic with specialists prescribing high-importance antimicrobials compared to those of medium importance for DBW was 82% less than that of a semi-rural, mixed and general practice. Culture and susceptibility (C&S) testing was performed in 1.8% of dogs. Empirical use of amoxicillin-clavulanic acid was common for DBW. Increasing wound severity was associated with greater use of high-importance antimicrobials. While C&S testing was rarely performed, routine susceptibility profiles are recommended to optimize antimicrobial stewardship.


Behavioral effects of exposure to nuclear magnetic resonance imaging: I. Open-field behavior and passive avoidance learning in rats.
The effect of exposure to the magnetic and radio-frequency fields associated with Nuclear Magnetic Resonance Imaging (MRI) on two standard animal behavior tests, was examined in rats. In the first experiment male rats were given a baseline open-field test and 48 hrs later exposed for 22.5 min to a MRI procedure, a sham imaging procedure, or a control condition. Immediately after this exposure period a second open-field test was administered. All animals were given 4 more daily exposures to their respective treatment conditions and after the last exposure period a third open-field test was given. Analysis of open-field ambulation, rearing, and defecation responses indicated no significant effect of exposure to MRI on these behaviours. In a second experiment rats were conditioned in a step-down passive avoidance task and then exposed for 23.2 min (48 hrs later) to MRI, sham imaging, or control conditions. Retention tests for the passive avoidance response were administered after the first and fifth daily exposure to the experimental treatment conditions. No significant effects of the treatment conditions on retention of the avoidance response were obtained and a third retention test 3 months after the second test, also failed to provide any evidence for treatment effects. These results fail to provide any evidence for short or long term behavioral changes in animals exposed to MRI.


Adrenergic mechanism in cold stored taenia caecum after rewarming.
After cold storage of guinea-pig taenia strips for 4 days at 2 degrees C, structures with specific catecholamine fluorescence were not observed. Upon incubation in Krebs Ringer medium (37 degrees C) the fluorescence in the cold stored tissue reappeared and the density of fluorescence was comparable to that of fresh preparations. The specific fluorescence was affected following reserpine or 6-hydroxydopamine treatment; however, the rewarming process restored fluorescence only in the reserpine-treated tissue. The cold storage treatment (4 and 7 days) also decreased the tissue noradrenaline and dopamine contents and dopamine-beta-hydroxylase activity and inhibited the [3H-noradrenaline release from the tissue, all of which were not restored by the incubation procedure. Moreover, in these cold stored taenia the inhibitory effect to nicotine and perivascular nerve stimulation were not manifested. Therefore, the reappearance of specific fluorescence in the cold stored taenia strips after rewarming does not assure functional recovery of adrenergic nerve activity.


Journal club: "Racial disparities in catheter related urinary tract infections among elderly trauma patients in the US".
In this article for Journal Club commentary entitled "Racial Disparities in Catheter Related Urinary Tract Infections Among Elderly Trauma Patients in the US", Keneally et al, conducted a study with the goal of assessing the role of social disparities in catheter associated urinary tract infections (CAUTIs). This cross-sectional study utilized secondary data to determine the possible CAUTI risk in ventilated, older (≥ 65 years of age) trauma patients exploring possible racial structural bias in healthcare. The analysis addressed the following questions in this specific population:While this study does consider race and discusses structural biases, which are important and sparsely researched in healthcare-associated infection (HAI) outcomes, the practice implementations are somewhat limited due to study design and analysis. Therefore, the focus of this Journal Club commentary will be reviewing basic steps Infection Preventionists (IPs) can take to critically appraise the literature for application in their facility's patient population.


Visible light sensitive Ag/TiO2/graphene composite as a potential coating material for control of Campylobacter jejuni.
Infectious diarrhea caused by the food borne pathogen, Campylobacter jejuni, is a major threat to public health worldwide leads high incidence of child mortality each year. In the present study, hydrothermal synthesis of Silver-Graphene-TiO2 nanocomposites along with TiO2, TiO2-Graphene and TiO2-silver nanocomposites was done and the samples were characterized using X-ray diffraction (XRD), tunneling electron microscopy (TEM) and UV-Vis Spectroscopy. Effect of silver and graphene addition on the broad spectrum antibacterial ability of TiO2 was studied under visible light. Moreover, the effects on bacterial survival, membrane integrity, cellular motiltiy and biofilm formation of C. jejuni were also evaluated. A synergetic effect of silver and graphene on Silver-Graphene-TiO2 nanocomposites was observed as indicated by its increased visible light sensitivity and enhanced antibacterial activity under visible light compared to its parent derivatives. Silver-Graphene-TiO2 composites effectively reduced growth and caused leakage of protein and DNA from C. jejuni cell. Atomic Force Microscopy was used to confirm bacterial cell damage. Besides, it also reduced motillity, hydrophobicity and autoaggregation of C. jejuni and showed excellent inhibition of biofilm formation. Furthermore, no significant cytotoxicity of synthesized nanoparticles was observed in human cell lines. We propose that Silver-Graphene-TiO2 composites can be used as effective antimicrobial agents to control the spread of C. jejuni by preventing both bacterial growth and biofilm formation.


1-Oleoyl-lysophosphatidylethanolamine stimulates RORγt activity in TH17 cells.
Metabolic fluxes involving fatty acid biosynthesis play essential roles in controlling the differentiation of T helper 17 (TH17) cells. However, the exact enzymes and lipid metabolites involved, as well as their link to promoting the core gene transcriptional signature required for the differentiation of TH17 cells, remain largely unknown. From a pooled CRISPR-based screen and unbiased lipidomics analyses, we identified that 1-oleoyl-lysophosphatidylethanolamine could act as a lipid modulator of retinoid-related orphan receptor gamma t (RORγt) activity in TH17 cells. In addition, we specified five enzymes, including Gpam, Gpat3, Lplat1, Pla2g12a, and Scd2, suggestive of the requirement of glycerophospholipids with monounsaturated fatty acids being required for the transcription of Il17a. 1-Oleoyl-lysophosphatidylethanolamine was reduced in Pla2g12a-deficient TH17 cells, leading to the abolition of interleukin-17 (IL-17) production and disruption to the core transcriptional program required for the differentiation of TH17 cells. Furthermore, mice with T cell-specific deficiency of Pla2g12a failed to develop disease in an experimental autoimmune encephalomyelitis model of multiple sclerosis. Thus, our data indicate that 1-oleoyl-lysophosphatidylethanolamine is a lipid metabolite that promotes RORγt-induced TH17 cell differentiation and the pathogenicity of TH17 cells.


Oncogenic structural aberration landscape in gastric cancer genomes.
Structural variants (SVs) are responsible for driver events in gastric cancer (GC); however, their patterns and processes remain poorly understood. Here, we examine 170 GC whole genomes to unravel the oncogenic structural aberration landscape in GC genomes and identify six rearrangement signatures (RSs). Non-random combinations of RSs elucidate distinctive GC subtypes comprising one or a few dominant RS that are associated with specific driver events (BRCA1/2 defects, mismatch repair deficiency, and TP53 mutation) and epidemiological backgrounds. Twenty-seven SV hotspots are identified as GC driver candidates. SV hotspots frequently constitute complexly clustered SVs involved in driver gene amplification, such as ERBB2, CCNE1, and FGFR2. Further deconstruction of the locally clustered SVs uncovers amplicon-generating profiles characterized by super-large SVs and intensive segmental amplifications, contributing to the extensive amplification of GC oncogenes. Comprehensive analyses using adjusted SV allele frequencies indicate the significant involvement of extra-chromosomal DNA in processes linked to specific RSs.


Glucose Intolerance after a Recent History of Gestational Diabetes Based on the 2013 WHO Criteria.
Uncertainty exists on the prevalence of glucose intolerance in women with a recent diagnosis of gestational diabetes (GDM) based on a two-step screening strategy and the 2013 World Health Organization (WHO) criteria. Our aim was to evaluate the uptake of postpartum screening, the prevalence and the risk factors for glucose intolerance in women with a recent history of GDM. Retrospective analysis of the medical records of women with a recent history of GDM diagnosed in a universal two-step screening strategy with the 2013 WHO criteria. All women with a history of GDM are advised to undergo a 75g oral glucose tolerance test (OGTT) around 12 weeks postpartum. Indices of insulin sensitivity (the Matsuda index and the reciprocal of the homeostasis model assessment of insulin resistance, 1/HOMA-IR) and an index of beta-cell function, the Insulin Secretion-Sensitivity Index-2 (ISSI-2) were calculated based on the OGTT postpartum. Multivariable logistic regression was used to adjust for confounders such as age, BMI, ethnicity and breastfeeding. Of the 191 women with GDM, 29.3% (56) did not attend the scheduled postpartum OGTT. These women had a higher BMI (28.6 ±6.8 vs. 26.2 ± 5.6, p = 0.015), were more often from an ethnic minority (EM) background (41.1% vs. 25.2%, p = 0.029) and smoked more often during pregnancy (14.3% vs. 2.2%, p = 0.001) than women who attended the OGTT postpartum. Of all women (135) who received an OGTT postpartum, 42.2% (57) had prediabetes (11.9% impaired fasting glucose, 24.4% impaired glucose tolerance and 5.9% both impaired fasting and impaired glucose tolerance) and 1.5% (2) had overt diabetes. Compared to women with a normal OGTT postpartum, women with glucose intolerance were older (32.5±4.3 vs. 30.8±4.8 years, p = 0.049), were more often obese (34.5% vs. 17.3%, p = 0.023), were more often from an EM background (33.9% vs. 18.4%, p = 0.040), less often breastfed (69.5% vs. 84.2%, p = 0.041) and had more often an abnormal fasting glycaemia at the time of the OGTT in pregnancy (55.6% vs. 37.3%, p = 0.040). In the multivariable logistic regression, an EM background [OR = 2.76 (1.15-6.62), p = 0.023] and the HbA1c level at the time of the OGTT in pregnancy [OR = 4.78 (1.19-19.20), p = 0.028] remained significant predictors for glucose intolerance postpartum. Women with glucose intolerance postpartum had a similar insulin sensitivity [Matsuda index 0.656 (0.386-1.224) vs. 0.778 (0.532-1.067), p = 0.709; 1/HOMA-IR 0.004 (0.002-0.009) vs. (0.004-0.003-0.007), p = 0.384] but a lower beta-cell function compared to women with a normal OGTT postpartum, remaining significant after adjustment for confounders [ISSI-2 1.6 (1.2-2.1) vs. 1.9 (1.7-2.4),p = 0.002]. Glucose intolerance is very frequent in early postpartum in women with GDM based on the 2013 WHO criteria in a two-step screening strategy and these women have an impaired beta-cell function. Nearly one third of women did not attend the scheduled OGTT postpartum and these women have an adverse risk profile. More efforts are needed to engage and stimulate women with GDM to attend the postpartum OGTT.


Characterization of nanoemulsion of Nigella sativa oil and its application in ice cream.
The aim of this study was to develop ice-cream product fortified with a Nigella sativa oil (NSO) nanoemulsion at four ratios (0% control, 3%, 5% and 10%). The NSO nanoemulsion stabilized by combinations of gum arabic, sodium caseinate, and Tween-20 at three ratios (5%, 10%, and 15%) of emulsifiers. The results showed that 10% nanoemulsion has the highest stability and zeta potential (-31.92), and lowest change of PDI (0.182). The 5% nanoemulsion showed the lowest particle size (175.83 µm). The result demonstrated that NSO nanoemulsion improved the ice-cream physical properties and consumer acceptability. Among the different samples, sensory evaluation revealed that ice-cream sample of 5% nanoemulsion received more acceptability from the panelist. This results demonstrated ice cream can be fortified with NSO nanoemulsion. This means it could be used as a functional ice cream with manifold NSO health benefits.


Clinical Impact of Stump Closure Reinforced With Hemopatch on the Prevention of Clinically Relevant Pancreatic Fistula After Distal Pancreatectomy: A Multicenter Randomized Trial.
Postoperative pancreatic fistula (POPF) is the most dreaded complication after distal pancreatectomy (DP). This multicenter randomized trial evaluated the efficacy, safety, and tolerance of Hemopatch in preventing clinically relevant (grades B/C according to the ISGPS classification) POPF after DP. After stump closure, patients were randomized to affix Hemopatch to the stump or not. Statistical significance was set at 0.025. Clinical significance was defined as the number of patients needed to treat (NNT) to avoid 1 B/C POPF. Of 631 eligible patients, 360 were randomized and 315 analyzed per protocol (155 in the standard closure group; 160 in the Hemopatch group). The rates of B/C POPF (the primary endpoint) were 23.2% and 16.3% (P = 0.120), while the number of patients with 1 or more complications (including patients with B/C POPF) was 34.8% and 24.4% (P = 0.049) in the standard and Hemopatch groups, respectively. In patients with hand-sewn stump and main duct closure, the rates were 26.2% versus 10.0% (P = 0.014) and 23.3% versus 7.7% (P = 0.015) in the standard and Hemopatch groups, respectively. The NNT in these 2 subgroups was 6 and 6.4, respectively. The results of the first randomized trial evaluating Hemopatch-reinforced pancreatic stump after DP to prevent type B/C POPF do not allow us to conclude that the risk of B/C POPF was lower. Based on the NNT, however, routine use of Hemopatch after DP may result in fewer complications (including POPF) overall, especially in cases with hand-sewn closure of the pancreatic stump or main pancreatic duct.


Retracted: FOXD1 Regulates the Sensitivity of Cetuximab by Regulating the Expression of EGFR in Head and Neck Squamous Cell Cancer.
[This retracts the article DOI: 10.1155/2022/6108241.].


The influence of obesity on functional outcomes and patient satisfaction 8 weeks after total knee arthroplasty: results of the prospective FInGK study.
To investigate obese versus non-obese subjects´ knee joint function, stiffness, pain, expectations, and outcome satisfaction before and two months after total knee arthroplasty (TKA). This study is a secondary analysis of data retrieved via a prospective single-centre cohort study investigating knee joint function and health care services utilization in patients undergoing TKA (FInGK Study). For the primary study, elective TKA patients were consecutively recruited between December 2019 and May 2021. Preoperative expectations, Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC), surgery outcome satisfaction, and sociodemographic variables were assessed via self-reported questionnaires. In the current study, obese (Body Mass Index (BMI) ≥ 30 kg/m²) versus non-obese (BMI < 30 kg/m²) subjects' data were exploratively compared before and two months after TKA. Multivariable logistic regression assessed factors associated with TKA satisfaction two months postoperatively. Linear regression evaluated factors associated with higher WOMAC change two months postoperatively. A total of 241 subjects participated (response: 85.2%). Eighty-seven were non-obese (mean age: 70.7 years, 63.2% female) and 154 were obese (mean age: 67.1 years, 57.8% female). Obese subjects reported inferior pre- and postoperative pain and knee joint function compared to non-obese subjects. Yet, WOMAC scores of obese and non-obese subjects significantly improved from preoperative means of 52.6 and 46.8 to 32.3 and 24.4 after surgery, respectively. The only significant TKA satisfaction predictor was subjects' smoking status. Non-obesity and worse preoperative WOMAC scores were predictive of higher WOMAC change scores after two months. Both obese and non-obese subjects reported significant symptom improvements. However, as obese subjects' short-term outcomes were still inferior, more research on TKA rehabilitation measures adapted to the needs of this growing patient group is warranted to maximize their benefits from TKA.


[Evaluation of dietary pattern and nutritional status of residents in southeast coastal area].
To evaluate the dietary pattern and nutritional status of urban residents in southeast coastal area. A dietary survey concerning 1332 persons aged 18 and over was carried out with dietary inquiry and 24-hour recall methods from August to December in 2009. The intakes of cereal, meat, eggs, seafood were enough. The consumption of milk and dairy products, vegetables, fruits was insufficient while the amount of oil was too high. Among them, the intake of milk and dairy products was only 1/3 of suggested values in Dietary Guideline and Balanced Diet Pagoda for Chinese Residents. The intakes of protein, retinol, iron and selenium were sufficient, while those of calcium, thiamine, riboflavin, ascorbic acid were too less than the dietary reference intakes (DRIs). The dietary pattern of urban residents in Ningbo was not reasonable. Nutrition education should be strengthened to guide residents for planning reasonable and balanced diets.


Cochlear motion across the reticular lamina implies that it is not a stiff plate.
Within the cochlea, the basilar membrane (BM) is coupled to the reticular lamina (RL) through three rows of piezo-like outer hair cells (OHCs) and supporting cells that endow mammals with sensitive hearing. Anatomical differences across OHC rows suggest differences in their motion. Using optical coherence tomography, we measured in vivo and postmortem displacements through the gerbil round-window membrane from approximately the 40-47 kHz best-frequency (BF) regions. Our high spatial resolution allowed measurements across the RL surface at the tops of the three rows of individual OHCs and their bottoms, and across the BM. RL motion varied radially; the third-row gain was more than 3 times greater than that of the first row near BF, whereas the OHC-bottom motions remained similar. This implies that the RL mosaic, comprised of OHC and phalangeal-process tops joined together by adhesion molecules, is much more flexible than the Deiters' cells connected to the OHCs at their bottom surfaces. Postmortem, the measured points moved together approximately in phase. These imply that in vivo, the RL does not move as a stiff plate hinging around the pillar-cell heads near the first row as has been assumed, but that its mosaic-like structure may instead bend and/or stretch.


Functional insights to the development of bioactive material for combating bacterial infections.
The emergence of antibiotic-resistant "superbugs" poses a serious threat to human health. Nanomaterials and cationic polymers have shown unprecedented advantages as effective antimicrobial therapies due to their flexibility and ability to interact with biological macromolecules. They can incorporate a variety of antimicrobial substances, achieving multifunctional effects without easily developing drug resistance. Herein, this article discusses recent advances in cationic polymers and nano-antibacterial materials, including material options, fabrication techniques, structural characteristics, and activity performance, with a focus on their fundamental active elements.


Preparation and evaluation of naringenin-loaded sulfobutylether-β-cyclodextrin/chitosan nanoparticles for ocular drug delivery.
The aim of this study was to prepare and characterize the naringenin-loaded sulfobutylether-β-cyclodextrin/chitosan nanoparticles (Nag-CD/CS-NPs) and evaluate their potential for the topical ophthalmic delivery. Naringenin was first complexed with sulfobutylether-β-cyclodextrin (SBE-β-CD), which can significantly enhance the solubility of poorly soluble drugs. Then, nanoparticles were prepared by ionic gelation of chitosan with SBE-β-CD, and their in vitro and vivo properties were investigated, respectively. The resulting nanoparticles showed an average size of 446.4±112.8nm and zeta potential of +22.5±4.91mV with predominant spherical in shape. The FT-IR and DSC confirmed the formation of Nag-CD/CS-NPs. The in vitro release study indicated that Nag-CD/CS-NPs achieved moderate sustained-release effect, and the in vivo study revealed that the prepared nanoparticles was nonirritating to rabbit's eye and had better ability to prolong the residence time than the naringenin suspension, which can significantly increase naringenin bioavailability in the aqueous humor. In conclusion, the developed CD/CS nanoparticles offer a potential alternative for the ocular administration of poorly soluble drugs.


Accelerated development of arthritis in mice lacking endothelial selectins.
The selectins, along with very late antigen-4 and CD44, have been implicated in mediating leukocyte rolling interactions that lead to joint recruitment and inflammation during the pathogenesis of rheumatoid arthritis. Previously, we showed that P-selectin deficiency in mice resulted in accelerated onset of joint inflammation in the murine collagen-immunized arthritis model. Here, we report that mice deficient either in E-selectin or in E-selectin and P-selectin (E/P-selectin mutant) also exhibit accelerated development of arthritis compared with wild type mice in the CIA model, suggesting that these adhesion molecules perform overlapping functions in regulating joint disease. Analyses of cytokine and chemokine expression in joint tissue from E/P-selectin mutant mice before the onset of joint swelling revealed significantly higher joint levels of macrophage inflammatory protein-1alpha and IL-1beta compared to wild-type mice. IL-1beta remained significantly increased in E/P-selectin mutant joint tissue during the early and chronic phases of arthritis. Overall, these data illustrate the novel finding that E-selectin and P-selectin expression can significantly influence cytokine and chemokine production in joint tissue, and suggest that these adhesion molecules play important regulatory roles in the development of arthritis in E/P-selectin mutant mice.


Role of calcium in the analgesic action of tetrahydroisoxazolepyridinol and muscimol.
The role of calcium in the analgesic activity of 4,5,6,7-tetrahydroisoxazole-(5,4-c) pyridin-2-ol (THIP) and muscimol has been investigated using the acetic acid assay procedure. THIP and muscimol produced significant analgesic response. Whilst neither calcium chloride nor nifedipine in the doses employed significantly altered the number of writhings, calcium chloride antagonized the analgesic responses of THIP and muscimol while nifedipine potentiated them. Similar responses were recorded for morphine. These findings suggest that THIP and muscimol, like morphine, might alter the calcium movements across the plasma membrane to elicit the analgesic response.


Serial cultivation of normal rat bladder epithelial cells in vitro.
Recent advances in culture techniques for human urothelial cells have led to the development of an improved method for growing primary rat bladder epithelial cells. We report here the conditions developed for large-scale in vitro growth and serial cultivation of normal diploid rat bladder epithelial cells. Primary cultures were initiated by attachment of bladder mucosal explants to type I collagen gels. A rapid outgrowth of epithelial cells from the explants occurred when cultured in a hormone-supplemented medium with epidermal growth factor. These primary outgrowths were passaged by nonenzymatic dispersion with 0.1 per cent ethylenediaminetetracetic acid and replating onto new gels. The capacity for routine serial passaging and maintenance of rat bladder epithelial cells required the presence of epidermal growth factor, a requirement not observed with human urothelial cells. The characteristics of the cultured rat bladder epithelial cells were similar to human urothelial cells in: ultrastructural and phase-contrast morphologic properties, showing junctional complexes, desmosomes, stratification and an apical glycocalyx; the absence of stromal cell contamination; and the ability to be serially passaged. Spontaneous cell-line formation was observed with the rat bladder epithelial cells, but has not been found with the human urothelial cells. With the method that we have developed, the number of rat bladder epithelial cells generated from a single bladder of a 4 to 6 week old rat was increased 100-fold from about 7 X 10(5) cells to 7 X 10(7) viable cells within 3 weeks of culture. The capability of culturing normal, primary rat bladder epithelial cells on this scale has not been reported previously and will facilitate comparative studies of the biological and molecular characteristics of the mammalian urothelium. Furthermore, this culture system will be useful for carcinogenesis studies, including metabolic activation of carcinogens and cellular transformation in vitro.


Dramatic volume reduction of a large GH/TSH secreting pituitary tumor with short term Octreotide therapy.
A case is presented of a huge GH/TSH secreting tumor and marked volumetric reduction in size with only one week of Octreotide therapy. To our knowledge, this is the first reported case of such a dramatic volumetric response to short-term Octreotide therapy.


Combined use of WEPS and Models-3/CMAQ for simulating wind erosion source emission and its environmental impact.
The wind erosion source is the greatest contributor of PM₁₀ in Tianjin, China. It is difficult to establish a PM₁₀ emission inventory for the wind erosion source because of the complicated conditions affecting PM₁₀ emissions from wind erosion. In this study, a novel method is developed to establish a PM₁₀ emission inventory for the wind erosion source by using the Wind Erosion Prediction System (WEPS) model with 1 × 1 km spatial resolution. In 2011, the average annual emission of PM₁₀ in Tianjin was 0.373 tons km(-2) (1.113 tons km(-2) in the heating period, 0.237 tons km(-2) in the sand period, and 0.013 tons km(-2) in the non-heating period), and the total PM₁₀ emission was 904,871.6 tons (221,080.7 tons in the heating period, 52,977.8 tons in the sand period, and 1953.2 tons in the non-heating period). After establishing the PM₁₀ emission inventory for the wind erosion source in this manner, the data were input into Model-3/SMOKE. The contribution of the PM₁₀ concentration from the wind erosion source was estimated using the Community Multi-scale Air Quality (Model-3/CMAQ) model and was compared with the monitoring value and the source apportionment results using the chemical mass balance (CMB) method. For this comparison, over the entire year, the R(2) was 0.711. More specifically, R(2) was 0.664, 0.733, and 0.679 in the heating, non-heating, and sand periods, respectively. Thus, we have obtained a reliable method for estimating the source of PM₁₀ from wind erosion.


Suppressive effect of corn bran hemicellulose on liver injury induced by D-galactosamine in rats.
It is well known that the indigestible oligo- and polysaccharides including dietary fiber are important food components and that they have many physiologic functions. This study examined the effect of water-soluble corn bran hemicellulose (CBH) on the development of D-galactosamine (GalN) hepatitis in rats to obtain some knowledge about new functions of dietary fiber. Male Wistar rats were fed diets containing 5% CBH for various days (1 to 14 d). On the final day of feeding rats were treated with GalN (400 mg/kg), and their plasma transaminase (aspartate and alanine aminotransferases) activity (6 or 24 h later) and liver glutathione concentration (6 h later) were determined. Ingested CBH suppressed the increase in plasma aspartate and alanine aminotransferase activities 24 h after GalN treatment. Such suppressive effect was observed only 7 d after CBH ingestion and not after 1 or 3 d. In the early phase of the liver injury, at 6 h after GalN treatment, the liver glutathione concentration in the CBH group was significantly higher than that in the control group, and the concentration in the CBH group after GalN injection was almost the same as that in the control group without GalN treatment. Results suggest that dietary CBH suppresses the development of hepatic injury by GalN in rats and that this phenomenon is partly attributable to the increase in hepatic glutathione concentration by CBH.


Perspectives on barriers to treatment engagement of people with eating disorder symptoms who have not undergone treatment: a qualitative study.
Many people with an eating disorder (ED) never engage with an evidence-based ED treatment. Of the few studies that have qualitatively explored barriers to receiving treatment, some do so in relation to mental health conditions in general, and others focus on participants who have already undergone treatment. This study aims to address this gap in the literature by exploring the barriers to ED treatment engagement from the perspectives of individuals in the community with an ED (either self-identified or professionally diagnosed) and had not received ED treatment/s. Fifty-six of 772 participants in an online Eating Disorders Treatment Experience survey had self-identified as having symptoms consistent with an ED, or had received a diagnosis of an ED and indicated that they had never undergone treatment for an ED. They were asked to share the reasons for which they did not receive treatment with an open-ended question. Qualitative analysis of survey responses was completed using the Framework Method to generate overarching themes that encapsulated the diverse participant accounts. The thematic analysis generated two main themes, each with two subthemes. The first theme was the negotiation of the need for treatment within oneself (intrapersonal factors; theme 1). The second theme explored interpersonal contexts that shaped the participant's decision not to seek treatment (interpersonal/external factors; theme 2). Two cross-cutting subthemes of fear and health literacy were also generated that demonstrated a high degree of overlap with the aforementioned main themes. The process by which individuals decide whether or not to engage with ED treatment services is complex and involves intra- and interpersonal negotiations intertwined with health literacy and fear. A factor not prominent in previous research was negative self-perceptions and the belief of being undeserving of treatment. These factors have implications for ongoing community and clinical interventions to further address barriers to ED treatment engagement.


Radioiodinated peanut lectin: a potential radiopharmaceutical for immunodetection of carcinoma expressing the T antigen.
The Thomsen-Friedenreich (T) antigen, beta-D-Gal-(1 leads to 3)-alpha-D-GalNAc, is exposed in reactive form on many human adenocarcinomata, but not on corresponding benign tissues. Peanut lectin (PNA) has a strong binding affinity for the T antigen and reportedly binds preferentially to certain malignant tissues. We investigated the potential of radiolabelled PNA as a tumour localising agent in an animal model system using a mouse lymphoma (RI) shown to bind fluorescein-labelled PNA in vitro. The radioiodinated lectin showed good tumour localization and rapid blood clearance. Clear images of tumours were obtained, in serial scintigraphic imaging, by 24 and 48 h. No blood background subtraction was necessary. Biodistribution studies revealed tumour to blood ratios in mice were 6:1 (at 24 h) and 17:1 (at 48 h), and tumour to muscle ratios were 34:1 (at 24 h) and 40:1 (at 48 h). Rapid in vivo breakdown of 125I-PNA led to some localization of free iodide in the kidneys, stomach, thyroid and salivary glands.


Lateral automatic landing guidance law based on risk-state model predictive control.
A lateral automatic carrier landing system (ACLS) control law is proposed for carrier-based aircraft, which could suppress the landing risk and increase the control precision. The nonlinear lateral landing equation is transformed into a polytopic model with a serial of state bounds. The landing risk including approach and arresting risks is proposed, and a Kalman filter is used to integrate both risks to construct the landing risk model. The concept of virtual state deviations is adopted by the output augment, which is estimated by an observer. The risk-state model predictive control (MPC) is established on the basis of the landing risk gradient composed of virtual states and time-varying weights. A compared simulation is tested on a semi-physical platform, which verifies excellent performance of the proposed method.


Biophysical aspects of Am-241 and Pu-241 in the environment.
Most of plutonium released by nuclear explosions is Pu-241 which decays to Am-241. We have studied the deposition of Pu-241 and Am-241 in lichens collected since 1958 in the central part of Sweden (62.3 degrees N, 12. 4 degrees E). Comparative studies with Pu-isotopes, Pu-239 + 240 and Pu-238 were also performed. In 1972 the total accumulated deposition of Pu-241 was 8 mCi/km2 of Pu-239 + 240 1 mCi/km2 and of Am-241 0.2 mCi/km2. About 80% of the Am-241 activity has been formed in situ from decay of Pu-241. The biological mean-residence time for all Pu-isotopes were about 6 years and for Am-241 4 years. The spatial distribution of Am-241 in the lichen carpet is quite different from that of Pu-241. The activity concentrations of Am-241 and Pu-241 have been studied in reindeer liver and bone. The average concentrations found were in liver 0.6 and 40 pCi/kg, in bone 0.2 and 6 pCi per kg for Am-241 and Pu-241 respectively. The activity content of Am-241 and Pu-241 in the Lapps due to their reindeer diet was estimated to be in liver 1.0 E-4 and 1.0 E-2 pCi/kg, in bone (3-9) E-5 and 1.0 E-2 pCi/kg for Am-241 and Pu-241 respectively. The estimated values for the fractions of ingested activity retained were in liver 7 E-6 and 14 E-6, in bone 20 E-6 for Am-241 and Pu-241 respectively. The fraction of ingested activity of Pu retained in reindeer liver is about 2-3 times higher than that of Am.


Exploring the origin of sentencing disparities in the Crown Court: Using text mining techniques to differentiate between court and judge disparities.
Research on sentence consistency in England and Wales has focused on disparities between courts, with differences between judges generally ignored. This is largely due to the limitations in official data. Using text mining techniques from Crown Court sentence records available online we generate a sample of 7,212 violent and sexual offences where both court and judge are captured. Multilevel time-to-event analyses of sentence length demonstrate that most disparities originate at the judge, not the court-level. Two important implications follow: i) the extent of sentencing consistency in England and Wales has been underestimated; and ii) the importance attributed to the location in which sentences are passed - in England and Wales and elsewhere - needs to be revisited. Further analysis of the judge level disparities identifies judicial rotation across courts as a practice conducive of sentence consistency, which suggests that sentencing guidelines could be complemented with other, less intrusive, changes in judicial practice to promote consistency.


Late asthmatic responses: inquiry into mechanisms and significance.
Late asthmatic responses are common, simulate a chronic phase of asthma, and are associated with an influx of inflammatory cells. The precise sequence of events leading to late inflammatory responses and increased hyperresponsiveness of the airways is uncertain, but likely begins with the triggering of mediator release from local (luminal or interstitial) mast cells or, conceivably, alveolar macrophages. Consequent influx and activation of granulocytes, including eosinophils and neutrophils, possibly T lymphocytes, basophils, and platelets, and subsequently later-arriving monocytes and macrophages, may be responsible for a continuing inflammatory reaction, airways hyperresponsiveness, and continuing active bronchial asthma. Identification of the relative importance of responsible cells and mediators will help clarify pathogenesis of bronchial asthma and should lead to a better understanding and design of therapeutic regimens and preventive measures in the management of this common and important disease.


A prospective, randomized, double-blind, multicenter comparative study on the safety and efficacy of Celecoxib and GCSB-5, dried extracts of six herbs, for the treatment of osteoarthritis of knee joint.
This prospective, randomized, double-blind, multicenter study compared the efficacy and safety of Celecoxib and GCSB-5, a new product from extracts of six herbs, for the treatment of knee osteoarthritis. A total of 198 eligible patients were randomly assigned to the Celecoxib group (n=99 patients) or the GCSB-5 group (n=99 patients) for the 12-week study. The amount of change and percentage of the change in Western Ontario and McMaster Universities (WOMAC) Arthritis Index from the baseline, the change in pain on walking by visual analogue scale (VAS), physician's global assessment on response to therapy (PGART) by five point Likert scale, and the amount of rescue medicine taken were used as parameters for efficacy. Adverse drug reactions (ADRs) were carefully investigated. The WOMAC score improved in both the Celecoxib group and GCSB-5 group by 20.5 and 21.3 (P=0.79). The percentage of the change in WOMAC score were -42.0% and -38.9% (P=0.54). The pain VAS score decreased by 29.9 and 27.9 (P=0.58). The responders by PGART were 95.3% and 93.8% (P= 0.66), and the median amount of rescue medicine taken were 2.0 and 6.5 tablets (P=0.06). The incidence of ADRs were 31.3% and 21.2% (P=0.11). The most common ADRs were gastrointestinal system related; 17.2% in GCSB-5 group and 22.2% in Celecoxib group. Any severe ADR was not observed in either group. The result of this study supports that GCSB-5 is comparable to Celecoxib in terms of the efficacy and safety for the treatment of osteoarthritis of knee joint.