Effect of cigarette smoking on extent of acid-secreting area and intestinal metaplasia in the stomach.
The association of cigarette smoking and other variables with the extent of the acid-secreting area and intestinal metaplasia were investigated by multivariate analysis. Studies were made by the endoscopic Congo red-methylene blue test developed in our hospital. In this test, acid-secreting areas and areas of intestinal metaplasia could be identified as discolored areas and areas staining blue with methylene blue, respectively. In multivariate analysis, the following variables were associated with a reduction in the size of the acid-secreting area in decreasing order of importance: the smoking index and age. The following factors had little or no influence on the size of the acid-secreting area: sex, and the consumption of aspirin and nonsteroidal, nonsalicylate, antiinflammatory drugs (NSNSAIDs). In general, in patients with a high smoking index, the acid-secreting area was small. Smoking had an influence in both younger and older patients and had more influence in females than in males. Multivariate analysis also shows that the following factors were associated with an increase in the area of intestinal metaplasia in decreasing order of importance: the extent of the acid-secreting area, age, and the smoking index. The following factors had little or no influence on the area of intestinal metaplasia: the consumption of aspirin and NSNSAIDs and sex. In general, in patients with little or no acid-secreting area, the area of intestinal metaplasia was extensive. These findings indicate that smoking is associated with reduction in the size of the acid-secreting area and so in development of intestinal metaplasia.


A Validated High-Throughput Fluorometric Method for Determination of Omeprazole in Quality Control Laboratory via Charge Transfer Sensitized Fluorescence.
A high-throughput 96-microwell plate fluorometric method was developed and validated to determine omeprazole (OMZ) in its dosage forms. The method was based on the charge-transfer (CT) sensitized fluorescence reaction of OMZ with 2, 3-dichloro-5, 6-dicyano-1, 4-benzoquinone (DDQ). This fluorescence reaction provided a new approach for simple, sensitive and selective determinations of OMZ in pharmaceutical preparations. In the present method, the fluorescence reaction was carried out in 96-microwell plates as reaction vessels in order to increase the automation of the methodology and the efficiency of its use in quality control laboratories. All factors affecting the fluorescence reaction were carefully studied and the conditions were optimized. The stoichiometry of the fluorescence reaction between OMZ and DDQ was determined and the reaction mechanism was suggested. Under the optimum conditions, the linear range was 100-6000 ng/ml with the lowest LOD of 33 ng/ml. Analytical performance of the proposed assay, in terms of accuracy and precision, was statistically validated and the results were satisfactory; RSD was <2.6 % and the accuracy was 98.6-101.6 %. The method was successfully applied to the analysis of OMZ in its dosage forms; the recovery values were 98.26-99.60 ± 0.95-2.22 %. The developed methodology may provide a safer, automated and economic tool for the analysis of OMZ in quality control laboratories.


Involvement of protein kinase C activation in regulation of acetylcholine release from rat hippocampal slices by minaprine.
Involvement of protein kinase C (PKC) activation in the regulation of acetylcholine (ACh) release from rat hippocampal slices by minaprine, [3(2-morpholinoethylamino)-4-methyl-6-phenylpyridazine] was investigated. Phorbol esters such as 4 beta-phorbol 12,13-dibutylate (PDBu) and 12-o-tetradecanoylphorbol 13-acetate (TPA) enhanced high K(+)-evoked [3H]ACh release from rat hippocampal slices. The enhancing effect of phorbol ester was attenuated by PKC inhibitors, staurosporine and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7). However, the inactive phorbol analogue, 4 alpha-phorbol 12,13-didecanoate (PDD) had no effect on [3H]ACh release. Minaprine and 4-aminopyridine (4-AP) attenuated the inhibitory effect of 5-hydroxytryptamine (5-HT) on high K(+)-evoked [3H]ACh release from rat hippocampal slices. The attenuating effect of minaprine on the inhibition of [3H]ACh release by 5-HT was prevented by staurosporine, while that of 4-AP was not influenced. Furthermore, PDBu blocked voltage-dependent, rapidly inactivating 42K efflux from rat brain synaptosomes. These results suggest that minaprine attenuates the inhibitory effect of 5-HT on ACh release via PKC activation in rat hippocampus, and that the blockade of the K+ channel with PKC activation might be involved in the action of minaprine.


Dose-dependent effects of intravitreal kainic acid on specific cell types in chicken retina.
In chicken retina, approximately two thirds of the bipolar cells and most amacrine cells are destroyed after intravitreal injection of from 20 to 60 nmoles of kainic acid. These cells, plus horizontal cells are destroyed after intravitreal injections of 120 nmoles of kainic acid. One third of the bipolar cells, Müller glial cells, photoreceptors and ganglion cells seem to be much more resistant. The resistance of the ganglion cells to intravitreal kainic acid is unusual and is not found in mammalian retinas. Dopaminergic amacrine cells may also be resistant to kainic acid. It is suggested that kainic acid interacts directly with bipolar cells and horizontal cells, depolarising the bipolar cells and horizontal cells and thereby killing them, while hyperpolarizing the ON-bipolar cells. The possibility that amacrine cell death may be an indirect result of kainic acid's effects on bipolar cells is discussed. Whatever the precise way in which kainic acid causes cell death, the technique of causing lesions is useful for defining the localization of retinal and particularly amacrine cell transmitter systems.


Risk of radial head arthroplasty revision is correlated with radial head diameter: a multicenter analysis of 405 cases.
Radial head arthroplasty (RHA) is commonly used for the treatment of comminuted radial head fractures. Indications as well as implant types continue to evolve. RHA has had good outcomes with midterm longevity. The literature is limited to small case series with varying implant types, and larger studies are needed to determine the optimal implant type and radial head diameter. A retrospective analysis of RHA cases performed by 75 surgeons at 14 medical centers in an integrated health care system between 2006 and 2017 was completed. Patient demographics, comorbidities, implant type and head diameter, and indications for revision were recorded. Patients' in-person clinical visit data were recorded. Patients were also contacted via telephone at a minimum of 2 years to obtain abbreviated Disabilities of the Arm, Shoulder, and Hand questionnaire and Oxford scores. Implant survivorship was also captured within our integrated system. 405 cases met our inclusion criteria. Mean age was 51.5 ± 15.5 years (range 16-88 years) and more common in females (62%). Chart review and telephone follow-up was performed at a mean of 68.9 ± 31.5 months (range 24-146 months). Our study found that revision rate was positively correlated with increasing radial head diameter. A 26-mm head had 7.7 odds of revision compared to a size 18-mm head (95% confidence interval 1.2-150.1). More than 95% of revision cases were performed within the first 36 months of the index procedure. Obese patients had a significantly lower mean postoperative Oxford score (35.5) compared to controls (38.3) (P = .02). There was a significantly higher overall reoperation rate for terrible triad (18.4%) vs. isolated injuries (10.4%) (P = .04). There was no difference between Acumed Anatomic and Evolve radial head implants in overall reoperation, implant revision, postoperative range of motion, or patient-reported outcomes. Risk of revision is directly correlated with implanted radial head diameter. There were no differences in outcomes and complications between the 2 main implants used. Individuals who did not undergo a revision by 3 years' time tend to retain the implant. Terrible triad injuries had a higher all-cause reoperation rate than isolated radial head fractures, but no difference in the rate of RHA revision. These data reinforce the practice of downsizing radial head implant diameter.


Agricultural crop waste materials - A potential reservoir of molecules.
Crop wastes are one of the agricultural wastes generated during the production and processing of food materials. Their generation is the other side of developmental activities. They are now becoming an alarming source of environmental pollution, leading to an unhealthy society. There is an urgent need to develop robust methods to utilize these types of wastes into beneficial compounds or materials. Many works are successfully done in these areas, and several strategies have been developed to produce biochemicals from biological wastes. In other words, value addition has been done to the crop waste materials. The chemicals like carbohydrates, minerals, proteins, and other compounds have been isolated from various crop residues. In this context, this article covers an overview of the crop wastes, chemicals isolated from them, their extraction methods, and the way forward to get the valuable chemicals.


Early postoperative hypoalbuminaemia is associated with pleural effusion after donor hepatectomy: A propensity score analysis of 2316 donors.
Pleural effusion and hypoalbuminaemia frequently occur after hepatectomy. Despite the emphasis on the safety of donors, little is known about the impact of postoperative albumin level on pleural effusion in liver donors. We retrospectively assessed 2316 consecutive liver donors from 2004 to 2014. The analysis of donors from 2004 to 2012 showed that postoperative pleural effusion occurred in 47.4% (970/2046), and serum albumin levels decreased until postoperative day 2 (POD2) and increased thereafter. In multivariable analysis, the lowest albumin level within POD2 (POD2ALB) was inversely associated with pleural effusion (OR 0.28, 95% CI 0.20-0.38; P < 0.001). POD2ALB ≤3.0 g/dL, the cutoff value at the 75th percentile, was associated with increased incidence of pleural effusion after propensity score (PS) matching (431 pairs; OR 1.69, 95% CI 1.30-2.21; P < 0.001). When we further analysed data from 2010 to 2014, intraoperative albumin infusion was associated with higher POD2ALB (P < 0.001) and lower incidence of pleural effusion (P = 0.024), compared with synthetic colloid infusion after PS matching (193 pairs). In conclusion, our data showed that POD2ALB is inversely associated with pleural effusion, and that intraoperative albumin infusion is associated with a lower incidence of pleural effusion when compared to synthetic colloid infusion in liver donors.


The HapMap: charting a course for genetic discovery in neurological diseases.
Whole-genome association analyses have begun to yield confirmed findings for genetic risk variants for complex disease. As the first reports of its application to neurological disease are described, we review this progress, explain the principles of the analysis, and discuss what the future is likely to be in this exciting area.


DNA logic circuits based amplification system for quencher-free and highly sensitive detection of DNA and adenosine triphosphate.
We fabricated a quencher-free and enzyme-free fluorescence detection system by employing the DNA logic circuits as signal amplifier and 2-aminopurine as signal indicator, and applied it to detect DNA and adenosine triphosphate (ATP). The assay system consisted of three hairpin probes with a sequestered 2-aminopurine molecule in each stem domain which was defined as inputs A, B and C of the logic operation. These three hairpin inputs kept stability and coexisted in reaction solution without target. However, adding target to the system would break the stability and initiate a dynamic assembly of the three inputs through toehold mediated displacement, resulting in the formation of three way junction and the liberation of 2-aminopurine from duplex structure. The structural circumstance changes from duplex to single stand switched the signal from "off" to "on" due to the disarming of base stack interaction, thus attaining amplified fluorescence detection without any extra quencher and avoiding the limitation of distance-independent signal conversion in conventional methods. A limit of detection of 0.46 pM was achieved for target DNA with high discrimination capability. Moreover, the sensing system was expandable for ATP detection. Importantly, the method was simple and easy-to-operate. These features make the DNA logic circuits adaptable as an enzyme-free and quencher-free amplifier, and thus the proposed method offers a powerful platform for DNA and ATP determination, and even other biotargets in clinical diagnosis.


Heritability and genome-wide association of swine gut microbiome features with growth and fatness parameters.
Despite recent efforts to characterize longitudinal variation in the swine gut microbiome, the extent to which a host's genome impacts the composition of its gut microbiome is not yet well understood in pigs. The objectives of this study were: i) to identify pig gut microbiome features associated with growth and fatness, ii) to estimate the heritability of those features, and, iii) to conduct a genome-wide association study exploring the relationship between those features and single nucleotide polymorphisms (SNP) in the pig genome. A total of 1,028 pigs were characterized. Animals were genotyped with the Illumina PorcineSNP60 Beadchip. Microbiome samples from fecal swabs were obtained at weaning (Wean), at mid-test during the growth trial (MidTest), and at the end of the growth trial (OffTest). Average daily gain was calculated from birth to week 14 of the growth trial, from weaning to week 14, from week 14 to week 22, and from week 14 to harvest. Backfat and loin depth were also measured at weeks 14 and 22. Heritability estimates (±SE) of Operational Taxonomic Units ranged from 0.025 (±0.0002) to 0.139 (±0.003), from 0.029 (±0.003) to 0.289 (±0.004), and from 0.025 (±0.003) to 0.545 (±0.034) at Wean, MidTest, and OffTest, respectively. Several SNP were significantly associated with taxa at the three time points. These SNP were located in genomic regions containing a total of 68 genes. This study provides new evidence linking gut microbiome composition with growth and carcass traits in swine, while also identifying putative host genetic markers associated with significant differences in the abundance of several prevalent microbiome features.


Complete mitochondrial genomes reveal robust phylogenetic signals and evidence of positive selection in horseshoe bats.
In genus Rhinolophus, species in the Rhinolophus philippinensis and R. macrotis groups are unique because the horseshoe bats in these group have relatively low echolocation frequencies and flight speeds compared with other horseshoe bats with similar body size. The different characteristics among bat species suggest particular evolutionary processes may have occurred in this genus. To study the adaptive evidence in the mitochondrial genomes (mitogenomes) of rhinolophids, especially the mitogenomes of the species with low echolocation frequencies, we sequenced eight mitogenomes and used them for comparative studies of molecular phylogeny and adaptive evolution. Phylogenetic analysis using whole mitogenome sequences produced robust results and provided phylogenetic signals that were better than those obtained using single genes. The results supported the recent establishment of the separate macrotis group. The signals of adaptive evolution discovered in the Rhinolophus species were tested for some of the codons in two genes (ND2 and ND6) that encode NADH dehydrogenases in oxidative phosphorylation system complex I. These genes have a background of widespread purifying selection. Signals of relaxed purifying selection and positive selection were found in ND2 and ND6, respectively, based on codon models and physicochemical profiles of amino acid replacements. However, no pronounced overlap was found for non-synonymous sites in the mitogenomes of all the species with low echolocation frequencies. A signal of positive selection for ND5 was found in the branch-site model when R. philippinensis was set as the foreground branch. The mitogenomes provided robust phylogenetic signals that were much more informative than the signals obtained using single mitochondrial genes. Two mitochondrial genes that encoding proteins in the oxidative phosphorylation system showed some evidence of adaptive evolution in genus Rhinolophus and the positive selection signals were tested for ND5 in R. philippinensis. These results indicate that mitochondrial protein-coding genes were targets of adaptive evolution during the evolution of Rhinolophus species, which might have contributed to a diverse range of acoustic adaptations in this genus.


Pregnancy and the Patient with Inflammatory Bowel Disease: Fertility, Treatment, Delivery, and Complications.
For many women with inflammatory bowel disease (IBD), the illness coincides with their childbearing years. IBD increases the risk of pregnancy complications and adverse pregnancy outcomes. The multidisciplinary care team should emphasize the importance of medication adherence to achieve preconception disease control and maintain corticosteroid-free remission throughout pregnancy. Medication adjustments to reduce fetal exposure may be considered on an individualized basis in quiescent disease; however, any benefits of such adjustments remain theoretic and there is risk of worsening disease activity. Mode of delivery is determined by obstetric indications, except for women with active perianal disease who should consider cesarean delivery.


Enhanced induction of heme oxygenase-1 suppresses thrombus formation and affects the protein C system in sepsis.
Heme oxygenase-1 (HO-1) displays anti-inflammatory and cytoprotective activities in sepsis. Here, we investigated the effects of HO-1 on thrombus formation and the protein C system in a septic C57BL/6 mouse model induced by cecal ligation and perforation (CLP). Septic mice were either preinjected with the vehicle, pretreated with hemin (an HO-1 inducer) or zinc protoporphyrin IX (ZnPP, an HO-1 inhibitor), or given a combination of hemin + ZnPP. CLP increased significantly the hepatic expression of HO-1; increased thrombosis in livers, kidneys, and lungs; shortened the prothrombin time (PT) and activated partial thromboplastin time (APTT); elevated the levels of tumor necrosis factor-1α (TNF-1α), interleukin-6 (IL-6), and thrombomodulin (TM); reduced the levels of protein C (PC) and activated protein C (aPC); and downregulated hepatic expression of PC and TM. The preadministration of hemin to septic mice increased the expression and activity of HO-1; inhibited thrombosis in the preceding 3 organs; prolonged PT and APTT; inhibited the production of TNF-α and IL-6; upregulated the expression of PC and TM in livers; elevated the plasma levels of PC and aPC; and reduced the plasma levels of TM. In contrast, ZnPP showed opposite effects to hemin and reversed the effects of hemin by inhibiting the activity of HO-1. The administration of tricarbonyl dichloro ruthenium (II) dimer (CORM-2), which is a CO-releasing molecule, had a similar effect to hemin on thrombosis and the protein C system. The data indicate that the enhanced induction of HO-1 inhibits thrombus formation and affects the protein C system in sepsis.


Lysine residues of Epstein-Barr virus-encoded nuclear antigen 2 do not confer secondary modifications via ubiquitin or SUMO-like proteins but modulate transcriptional activation.
Epstein-Barr virus nuclear antigen 2 (EBNA2) is essential for transformation through activation of viral and cellular genes. Within 487 residues, EBNA2 contains six lysine (K) residues (positions 335, 357, 359, 363, 366 and 480), which were mutated to arginine (R) residues, either individually or in combination, and tested for subcellular localization, mobility by SDS-PAGE and transactivation of three promoters. All mutants featuring the K(480)R mutation within the nuclear localization signal were partially cytoplasmic with a reduced level of transactivation of the latent membrane protein 1 (LMP1) promoter (-327 to +40). The K(366)R mutation also showed a decrease in transactivation of a promoter consisting only of 12 recombination signal-binding protein-Jkappa-binding sites, while all mutants with the K(335)R exchange showed a markedly elevated transactivation with the -327 to +40 construct and all mutants showed slightly reduced transactivation with a -634 to +40 LMP1 promoter. None of the mutants exhibited altered migration in SDS-PAGE, excluding secondary modification, i.e. through SUMO-like proteins.


Diagnosis of tuberculous lymphadenitis using fine needle aspiration biopsy.
Tuberculous lymphadenitis is the commonest form of extrapulmonary tuberculosis. However, the optimal approach to diagnosis, employing biopsy by either fine needle aspiration (FNA) or surgical excision, remains uncertain. To evaluate the diagnostic value of biopsy using each of the component diagnostic modalities of FNA (microscopy, cytology and culture), and compare these with excision biopsy in the diagnosis of tuberculous lymphadenitis in a predominantly migrant population in Melbourne. A retrospective examination of tuberculous lymphadenitis cases presenting to Western Health over 12 years was conducted. Using a reference method of positive culture of Mycobacterium tuberculosis, the diagnostic sensitivities of each modality employed in FNA were determined. Forty-two subjects having FNA and 30 having excision biopsy as the initial investigation were compared. Among specimens obtained by FNA, sensitivity of microscopy was 18% (95% confidence interval (CI): 5–40%) and sensitivity of cytology was 38% (95% CI: 20–59%). For specimens obtained by excision biopsies, sensitivities for microscopy and histology were 17% (95% CI: 2–32%) and 96% (95% CI: 88–100%) respectively. Sensitivity of culture performed on FNA specimens was 86% (95% CI: 65–97%). Given the relatively high sensitivity of mycobacterial cultures from FNA, this study supports its routine use as the initial investigation in most patients with suspected tuberculous lymphadenitis. Microscopy and cytology add relatively little to the clinical utility of FNA


Surgical Strategy and Outcome for Aortic Root in Patients Undergoing Repair of Acute Type A Aortic Dissection.
This study evaluated the relevance of our indication of aortic root operations for acute type A aortic dissection and compared early and long-term outcomes of emergency type A aortic dissection operations between patients who underwent aortic root operations and those who did not. We retrospectively reviewed 316 consecutive patients who underwent emergency aortic operations for acute type A aortic dissection between January 2009 and September 2013. We performed simultaneous aortic root operations when the aortic root diameter was greater than 45 mm or an intimal tear was present in the aortic root, or both. After this indication, we performed aortic repair involving the aortic root in 40 patients (aortic root replacement [ARR] group, 12.7%) and not involving the aortic root in 276 patients (non-ARR group, 87.3%). We analyzed early and long-term outcomes, including late aortic root events. In-hospital mortality was 12.5% (5 of 40) in the ARR group and 4.7% (13 of 276) in non-ARR group (p = 0.05). Overall survival at 3 and 5 years was 84.8% and 84.8%, respectively in ARR group and was 91.9% and 91.9%, respectively, in the non-ARR group (p = 0.078). Late aortic root events, defined as aortic root dilatation (≥ 3 mm/y), reoperation of the aortic root, aortic regurgitation (moderate or higher), and pseudoaneurysm, were observed in no patients in the ARR group and in 32 patients (11.6%) in the non-ARR group (p = 0.029). In the non-AAR group, dissection of 2 or more aortic sinuses was the only independent predictor of a late aortic root event (hazard ratio, 2.20; 95% confidence interval, 1.08 to 4.61; p = 0.03). Simultaneous aortic root operations significantly reduced the incidence of late aortic root events. The dissection of 2 or more sinuses of Valsalva was associated with a late aortic root event in patients who did not undergo aortic root operations.


Calculation of Energy Diagram of Asymmetric Graded-Band-Gap Semiconductor Superlattices.
The paper theoretically investigates the peculiarities of energy diagram of asymmetric graded-band-gap superlattices with linear coordinate dependences of band gap and electron affinity. For calculating the energy diagram of asymmetric graded-band-gap superlattices, linearized Poisson's equation has been solved for the two layers forming a period of the superlattice. The obtained coordinate dependences of edges of the conduction and valence bands demonstrate substantial transformation of the shape of the energy diagram at changing the period of the lattice and the ratio of width of the adjacent layers. The most marked changes in the energy diagram take place when the period of lattice is comparable with the Debye screening length. In the case when the lattice period is much smaller that the Debye screening length, the energy diagram has the shape of a sawtooth-like pattern.


Impact of selenium on mood and quality of life: a randomized, controlled trial.
Selenium is known to be important to the brain. Three small, published studies have suggested an effect of selenium supplementation or deprivation on mood in healthy volunteers. We investigated these findings on a much larger scale. In this double-blind, placebo-controlled intervention, 501 UK participants aged 60-74 were randomly allocated to receive 100, 200 or 300 microg selenium/d as high-selenium yeast or placebo yeast. Mood (Profile of Moods States - Bipolar Form [POMS-BI] questionnaire), "quality of life" (Short Form 36 [SF-36] questionnaire) and plasma selenium were measured at baseline and six months. Supplementation significantly increased plasma selenium above baseline values: from an overall mean (SD) of 90(19) ng/g to 91(26), 144(27), 191(41) and 227(53) ng/g in the placebo, 100, 200, 300 microg selenium groups respectively (p < .001). Four hundred forty-eight participants completed the POMS-BI questionnaires at both time points, with no significant differences in total mood or mood-subscale scores seen between doses. After six months of supplementation, mean (SD) total mood scores for the four doses were 163(36), 161(37), 162(33), 162(34), F(3,443) = .25, p = .86. Quality of life was similarly unaffected. There was no evidence that selenium supplementation benefited mood or quality of life in these elderly volunteers. Though this is at odds with some previous results, our robust study design, much larger sample size and longer supplementation period, together with the evidence that the brain is a privileged site for selenium retention, suggest that this is a reliable finding.


Audiometric characteristics of a Dutch family linked to DFNA15 with a novel mutation (p.L289F) in POU4F3.
To report on the audiometric characteristics of a large Dutch family linked to DFNA15 with a novel mutation (p.L289F) in POU4F3 (OMIM 602460). Clinical investigation. Tertiary referral center. Family members from a large 5-generation pedigree with sensorineural hearing impairment segregating as an autosomal dominant trait. Cross-sectional and longitudinal analyses of pure-tone audiometric data, and cross-sectional analyses of speech audiometry data. Overall, a flat to gently downsloping audiometric configuration was observed with a progression rate of approximately 0.8 dB/y across most frequencies. Speech recognition scores remained fairly good in relation to age and hearing level compared with a group of patients with presbycusis. Interindividual variability was observed in terms of subjective onset age and audiometric configuration. Two mutation carriers, who reported vestibular symptoms, underwent vestibular examination and showed hypofunction of the vestibular labyrinth. The audiometric phenotype of the Dutch family linked to DFNA15 with a novel mutation in POU4F3 is comparable to that observed in the original Israeli family linked to DFNA15. Relatively good speech recognition scores suggest outer hair cell involvement. DFNA15 may represent a cochleovestibular disorder.


The relationship between poor sleep and inhibitory functions indicated by event-related potentials.
The present study focused on the relationship between normal variations of sleep and inhibitory functions as reflected in event-related potentials. For this reason one night of 21 healthy participants was analysed. After waking up all participants completed a visual Go/Nogo task. On the basis of a sleep disturbance index (SDI) the participants were separated into 8 SDI-good and 13 SDI-poor sleepers using a cluster analysis. The results showed that Nogo-N2 amplitude was smaller and Nogo-P3 latency longer in SDI-poor sleepers. Moreover, Go-P3 amplitude was smaller in SDI-poor sleepers. Performance parameters were not influenced by poor sleep. We concluded that poor sleep specifically affects the intensity of pre-motor inhibitory processes (Nogo-N2 amplitude), the speed to inhibit a motor response (Nogo-P3 latency) and the intensity of task-relevant information processing (Go-P3 amplitude). In further studies, it should be explored under which conditions such subliminal deficits also become relevant for overt behaviour.


Coordination Polymers Constructed from an Adaptable Pyridine-Dicarboxylic Acid Linker: Assembly, Diversity of Structures, and Catalysis.
4,4'-(Pyridine-3,5-diyl)dibenzoic acid (H2pdba) was explored as an adaptable linker for assembling a diversity of new manganese(II), cobalt(II/III), nickel(II), and copper(II) coordination polymers (CPs): [Mn(μ4-pdba)(H2O)]n (1), {[M(μ3-pdba)(phen)]·2H2O}n (M = Co (2), Ni (3)), {[Cu2(μ3-pdba)2(bipy)]·2H2O}n (4), {[Co(μ3-pdba)(bipy)]·2H2O}n (5), [Co2(μ3-pdba)(μ-Hbiim)2(Hbiim)]n (6), and [M(μ4-pdba)(py)]n (M = Co (7), Ni (8)). The CPs were hydrothermally synthesized using metal(II) chloride precursors, H2pdba, and different coligands functioning as crystallization mediators (phen: 1,10-phenanthroline; bipy: 2,2'-bipyridine, H2biim: 2,2'-biimidazole; py: pyridine). Structural networks of 1-8 range from two-dimensional (2D) metal-organic layers (1-3, 5-8) to three-dimensional (3D) metal-organic framework (MOF) (4) and disclose several types of topologies: sql (in 1), hcb (in 2, 3, 5), tfk (in 4), 3,5L66 (in 6), and SP 2-periodic net (6,3)Ia (in 7, 8). Apart from the characterization by standard methods, catalytic potential of the obtained CPs was also screened in the Knoevenagel condensation of benzaldehyde with propanedinitrile to give 2-benzylidenemalononitrile (model reaction). Several reaction parameters were optimized, and the substrate scope was explored, revealing the best catalytic performance for a 3D MOF 4. This catalyst is recyclable and can lead to substituted dinitrile products in up to 99% product yields. The present study widens the use of H2pdba as a still poorly studied linker toward designing novel functional coordination polymers.


On the emerging role of rabbit as human disease model and the instrumental role of novel transgenic tools.
The laboratory rabbit (Oryctolagus cuniculus) is widely used as a model for human diseases, because of its size, which permits non-lethal monitoring of physiological changes and similar disease characteristics. Novel transgenic tools such as, the zinc finger nuclease method and the sleeping beauty transposon mediated or BAC transgenesis were recently adapted to the laboratory rabbit and opened new opportunities in precise tissue and developmental stage specific gene expression/silencing, coupled with increased transgenic efficiencies. Many facets of human development and diseases cannot be investigated in rodents. This is especially true for early prenatal development, its long-lasting effects on health and complex disorders, and some economically important diseases such as atherosclerosis or cardiovascular diseases. The first transgenic rabbits models of arrhythmogenesis mimic human cardiac diseases much better than transgenic mice and hereby underline the importance of non-mouse models. Another emerging field is epigenetic reprogramming and pathogenic mechanisms in diabetic pregnancy, where rabbit models are indispensable. Beyond that rabbit is used for decades as major source of polyclonal antibodies and recently in monoclonal antibody production. Alteration of its genome to increase the efficiency and value of the antibodies by humanization of the immunoglobulin genes, or by increasing the expression of a special receptor (Fc receptor) that augments humoral immune response is a current demand.


The effects of hyperthyroidism on muscular dystrophy in the mdx mouse: greater dystrophy in cardiac and soleus muscle.
Muscle damage and repair were studied in mdx mice treated with triiodothyronine (T3) for 14 days. Hindlimb and cardiac muscles were examined for the severity of dystrophy, the degree of muscle centronucleation, and fiber size. In control and mdx mice, cardiac hypertrophy and skeletal muscle atrophy were present after T3 treatment. Both cardiac and soleus (but not fast-twitch) muscles had larger, more frequent dystrophic lesions in T3-treated mdx mice, and mdx soleus had an increased area of new myotubes after T3. Skeletal myogenesis in mdx mice may have been delayed by excess T3, possibly related to the general reduction in staining for basic fibroblast growth factor in hyperthyroid mice. These are the first observations of a metabolic perturbation which worsens mdx dystrophy and possibly repair in a muscle-specific manner, and are likely related to T3-induced changes in myosin heavy chain expression, and to increased mechanical strain on dystrophin-deficient muscles.


[Patients' Use of Digital Innovations in the Care Process: A Scoping Review].
Digital innovations in healthcare continue to be extensively researched and publicly discussed. The research perspective is often indication-specific or process-oriented and focuses on an application by health professionals in care settings. From the patient's perspective, there are additional digital innovations and opportunities for use that take place privately in addition to sectoral care services. The aim of this scoping review was to map digital innovations currently available for patients and their possible applications in the care process by exploring the following question: Which digital innovations are currently available for patients in health care? A systematic literature search in four databases helped identify 44 international publications as relevant for our analysis. They were categorized and analyzed according to the types of digital innovations, their use by patients, and their location within the care process. In addition, the intentions whereby digital innovations can be applied were discussed. We found that current research was focused on patient-applied digital innovations in the therapeutic field, and a broad application spectrum of interfaces for digital care was emerging. These included apps, smart devices, teleconsultation, patient portals, games, implants, robotics, intelligent information and communication systems, and ambient assisted living environments. Many digitally supported health applications are designed to be used exclusively by patients themselves, or are performed in only partial interaction with providers. In this respect, the active participation and personal responsibility of patients in the treatment process could be strengthened with the help of digital innovations.


The evaluation analysis on the airborne dust regional pollution of the anchor drilling operation in the tunnel.
The anchor drilling operations generate massive airborne dust particles in the tunnel heading face that raises the pneumoconiosis morbidity and explosion risk. In this paper, a full-scale tunnel physical model is constructed to study the effect of the wind velocity and drilling site position on the airborne dust regional pollution scope based on the actual anchor drilling craft. The research indicates that the four extensive vortex areas keep the dust suspension at 14 m from the heading face and make the deposition dust particle refloat. The average respirable dust rate reaches the maximum value at section 5 m and presents a gradual decline as the dust particle migrates along the outlet direction. Raising the wind velocity contributes to alleviating the airborne dust pollution in the anchor drilling operation. As the wind velocity increases from 3 to 24 m/s, the high dust concentration area and number higher than 200 mg/m3 pose overall decrease trends, and the average dust concentration displays a linear decrease until 26.14-58.65 mg/m3 around the anchor worker head. Moving the drilling site positions closer to the exhaust air duct aggravates the airborne dust pollution in the front breathing zone. As the anchor drilling operation switches from the return air side to the supply air side, the dust concentration area ascends by 59.4-84.4% in the personnel respiratory space.


Quantifying cannabis problems among college students from English and Spanish speaking countries: Cross-cultural validation of the Cannabis Use Disorders Identification Test-Revised (CUDIT-R).
The Cannabis Use Disorders Identification Test - Revised (CUDIT-R) is a broadly employed measure of cannabis-related problems. However, minimal research has tested the measurement invariance of the CUDIT-R among youths from different countries, hindering cross-national comparisons. Thus, the present study aimed to test the measurement invariance of the CUDIT-R between seven countries and gender groups, and provide different sources of reliability and validity evidence of the scale. A sample of 4,712 college student lifetime cannabis users (mean age = 20.57, SD = 3.97; 70.4% females) from seven countries completed the CUDIT-R. Last 30-day cannabis users (n = 2402; mean age = 20.09, SD = 3.18; 67.7% females) additionally completed another measure of cannabis-related problems, and measures of cannabis frequency, quantity and motives. Multigroup analysis showed configural (equal number of factors and pattern of factor-indicator relationships), metric (equal factor loadings) and scalar (equal thresholds) invariance of the CUDIT-R across five countries and across gender in the sample of lifetime cannabis users. Cronbach's alphas and ordinal omegas ranked from .72 and .85. Large correlations were found between the CUDIT-R and another cannabis-related problem scale. Small to large associations were found between the CUDIT-R and other criterion variables (frequency and quantity of consumption and cannabis-related motives) providing convergent and discriminant validity evidence. Only a few differences in the magnitude of the correlations across countries were found. The results suggest that the CUDIT-R is a suitable measure to assess cannabis-related problems among college student from the U.S., Canada, South Africa, Spain, and Argentina and across gender groups.


The scopolamine model as a pharmacodynamic marker in early drug development.
Drug development is a high-risk and high failure enterprise, and studies that provide an early read on the pharmacodynamic activity of novel compounds could save time and money, increasing the efficiency of the drug development process. Preclinical and clinical experiments were designed to examine the utility of the scopolamine-induced cognitive impairment model in predicting pharmacodynamic signals of putatively procognitive compounds, utilizing the acetylcholinesterase inhibitor donepezil for illustration. In normal healthy rats, scopolamine (0.3 mg/kg) significantly impaired performance on the two-platform water maze and on the T-maze. The deficits in water maze performance were reversed by donepezil at 0.5 and 1.0 mg/kg. There was a trend towards reversal of scopolamine-induced deficits in performance on the T-maze with 1.0 mg/kg donepezil. In normal healthy humans, scopolamine (0.3 and 0.5 mg) reliably impaired performance on the Cognitive Drug Research test battery composite scores (power of attention, continuity of attention, quality of working memory, quality of episodic secondary memory, and speed of memory) in a dose- and time-dependent manner. Donepezil (10 mg) significantly attenuated the scopolamine-induced impairment in cognition on power of attention, continuity of attention, quality of working memory, and speed of memory. These findings suggest that reversal of scopolamine-induced cognitive impairment is a viable model for predicting pharmacodynamic signals of procognitive compounds in both animals and humans. The utility of the scopolamine-induced cognitive impairment model is discussed and illustrated at various decision points in drug development, with a focus on Go/No Go decisions.


Diagnosis and management of jejunoileal diverticular haemorrhage: An update on the experience in a single centre.
Jejunoileal diverticular haemorrhage is a rare disease that is difficult to diagnose and treat. Despite advances in endoscopic technology, recommendations on diagnosis and management for jejunoileal diverticular haemorrhage have remained unchanged and these new options have not been compared against traditional surgical management. We retrospectively reviewed the diagnosis, management, and outcome for jejunoileal diverticular haemorrhage cases at our institution over the past 20 years. Data were organized and analysed by chi-square test, student t-test and Kaplan-Meier survival analysis. The most utilised diagnostic procedure was computed tomography, followed by enteroscopy, angiography, small bowel flow-through and surgery. Primary treatments included, in a decreasing order, medical therapy, surgery, endoscopy and radiology. Surgical treatment was not associated with rebleeding, but it did result in longer hospital stays and larger blood transfusions than non-surgical treatments. The bleeding-related mortality rate was very low. Notably, there was also little change in the diagnosis and treatment between decades. We presented our experience with the diagnosis and management of jejunoileal diverticular haemorrhage, as well as long-term follow-up after treatments that have not been reported previously. Surgical treatment continues to dominate management for jejunoileal diverticular haemorrhage, but we support increasing the role of endoscopy for select patient groups.


The impact of nucleoside base modification in mRNA vaccine is influenced by the chemistry of its lipid nanoparticle delivery system.
The use of modified nucleosides is an important approach to mitigate the intrinsic immunostimulatory activity of exogenous mRNA and to increase its translation for mRNA therapeutic applications. However, for vaccine applications, the intrinsic immunostimulatory nature of unmodified mRNA could help induce productive immunity. Additionally, the ionizable lipid nanoparticles (LNPs) used to deliver mRNA vaccines can possess immunostimulatory properties that may influence the impact of nucleoside modification. Here we show that uridine replacement with N1-methylpseudouridine in an mRNA vaccine encoding influenza hemagglutinin had a significant impact on the induction of innate chemokines/cytokines and a positive impact on the induction of functional antibody titers in mice and macaques when MC3 or KC2 LNPs were used as delivery systems, while it impacted only minimally the titers obtained with L319 LNPs, indicating that the impact of nucleoside modification on mRNA vaccine efficacy varies with LNP composition. In line with previous observations, we noticed an inverse correlation between the induction of high innate IFN-α titers in the macaques and antigen-specific immune responses. Furthermore, and consistent with the species specificity of pathogen recognition receptors, we found that the effect of uridine replacement did not strictly translate from mice to non-human primates.


Environmental mycological studies on the causative agent of summer-type hypersensitivity pneumonitis.
Environmental mycological studies were carried out in 22 homes of patients with summer-type hypersensitivity pneumonitis and in 195 homes of control subjects. In 10 patients' homes, indoor sampling was performed by open-plate culture, house dust culture, and swab culture (group 1), but in the other 12 patients' homes, sampling was only by house dust culture (group 2). We isolated 302 strains of yeasts from the 22 patients' homes and 962 strains of yeasts from the homes of control subjects. The incidence of yeasts, except genera Trichosporon, was not significantly different between homes of patients and control subjects when homes were assessed by three culture methods. T. cutaneum was isolated from seven of 10 patients' homes in group 1, and their colonizing places were revealed by the swab culture method. In group 2, the cells were isolated from four of 12 patients' homes. No T. cutaneum, however, was isolated from the control subjects' homes. Among the isolated yeasts from patients' homes, 23 strains were reactive to the patients' sera at 1:128 or higher in indirect fluorescent antibody titers; 10 yeasts were T. cutaneum, isolated from 10 homes of 14 patients, but the other 13 yeasts were each a different species isolated from 10 different homes. Furthermore, inhalation challenge with the culture-filtrate antigen prepared from T. cutaneum was performed on the nine patients of six homes in group 1 and the two asymptomatic family members. Of the nine patients, six were positive, one was probable, and two patients were negative. Neither of the two asymptomatic family members responded. These results suggest that T. cutaneum is a major causative agent of summer-type hypersensitivity pneumonitis.


Novel LaBO3 hollow nanospheres of size 34±2 nm templated by polymeric micelles.
Novel lanthanum borate (LaBO(3)) hollow nanospheres of size 34±2 nm have been reported for the first time by soft-template self-assembly process. Poly(styrene-b-acrylic acid-b-ethylene oxide) (PS-PAA-PEO) micelle with core-shell-corona architecture serves as an efficient soft template for fabrication of LaBO(3) hollow particles using sodium borohydride (NaBH(4)) and LaCl(3)⋅7H(2)O as the precursors. In this template, the PS block (core) acts as a template of the void space of hollow particle, the anionic PAA block (shell) serves as reaction field for metal ion interactions, and the PEO block (corona) stabilizes the polymer/lanthana composite particles. The PS-PAA-PEO micelles and the resulting LaBO(3) hollow nanospheres were thoroughly characterized by dynamic light scattering (DLS), transmission electron microscope (TEM), X-ray diffraction, magic angle spinning-nuclear magnetic resonance ((11)B MAS NMR), energy dispersive X-ray analysis, thermal analyses, Fourier transform infra red spectroscopy, and nitrogen adsorption/desorption analyses. The nitrogen adsorption/desorption analyses and TEM observation of the hollow particles confirmed the presence of disordered mesopores in the LaBO(3) shell domain. The solid state (11)B MAS NMR spectra of LaBO(3) hollow nanospheres revealed that the shell part contains both trigonal and tetrahedral boron species. The LaBO(3) hollow particles were applied to anode materials in lithium-ion rechargeable batteries (LIBs). The hollow particles exhibited high coulombic efficiency and charge-discharge cycling capacities of up to 100 cycles in the LIBs.


Microarrays--identifying molecular portraits for prostate tumors with different Gleason patterns.
We present in this chapter the combined use of several recently introduced methodologies for the analysis of microarray datasets. These computational techniques are varied in type and very powerful when combined. We have selected a prostate cancer dataset which is available in the public domain to allow for further comparisons with existing methods. The task is to identify biomarkers that correlate with the clinical phenotype of interest, i.e., Gleason patterns 3, 4, and 5. A supervised method, based on the mathematical formalism of (alpha, beta)-k-feature sets (1), is used to select differentially expressed genes. After these "molecular signatures" are identified, we applied an unsupervised method (a memetic algorithm) to order the samples (2). The objective is to maximize a global measure of correlation in the two-dimensional display of gene expression profiles. With the resulting ordering and taxonomy we are able to identify samples that have been assigned a certain Gleason pattern, and have gene expression patterns different from most of the other samples in the group. We reiterate the approach to obtain molecular signatures that produce coherent patterns of gene expression in each of the three Gleason pattern groups, and we analyze the statistically significant patterns of gene expression that seem to be implicated in these different stages of disease.


Are fluorescence-detected sedimentation velocity data reliable?
Sedimentation velocity analytical ultracentrifugation is a classical biophysical technique that is commonly used to analyze the size, shape, and interactions of biological macromolecules in solution. Fluorescence detection provides enhanced sensitivity and selectivity relative to the standard absorption and refractrometric detectors, but data acquisition is more complex and can be subject to interference from several photophysical effects. Here, we describe methods to configure sedimentation velocity measurements using fluorescence detection and evaluate the performance of the fluorescence optical system. The fluorescence detector output is linear over a concentration range of at least 1 to 500nM fluorescein and Alexa Fluor 488. At high concentrations, deviations from linearity can be attributed to the inner filter effect. A duplex DNA labeled with Alexa Fluor 488 was used as a standard to compare sedimentation coefficients obtained using fluorescence and absorbance detectors. Within error, the sedimentation coefficients agree. Thus, the fluorescence detector is capable of providing precise and accurate sedimentation velocity results that are consistent with measurements performed using conventional absorption optics, provided the data are collected at appropriate sample concentrations and the optics are configured correctly.


Gunshot wounds then and now.
This review is a study of the development of the bullet and its effects, and the surgical treatment of gunshot wounds from John Hunter's time to the present day.


Anorexia-cachexia and obesity treatment may be two sides of the same coin: role of the TGF-b superfamily cytokine MIC-1/GDF15.
Anorexia-cachexia associated with cancer and other diseases is a common and often fatal condition representing a large area of unmet medical need. It occurs most commonly in advanced cancer and is probably a consequence of molecules released by tumour cells, or tumour-associated interstitial or immune cells. These may then act directly on muscle to cause atrophy and/or may cause anorexia, which then leads to loss of both fat and lean mass. Although the aetiological triggers for this syndrome are not well characterized, recent data suggest that MIC-1/GDF15, a transforming growth factor-beta superfamily cytokine produced in large amounts by cancer cells and as a part of other disease processes, may be an important trigger. This cytokine acts on feeding centres in the hypothalamus and brainstem to cause anorexia leading to loss of lean and fat mass and eventually cachexia. In animal studies, the circulating concentrations of MIC-1/GDF15 required to cause this syndrome are similar to those seen in patients with advanced cancer, and at least some epidemiological studies support an association between MIC-1/GDF15 serum levels and measures of nutrition. This article will discuss its mechanisms of central appetite regulation, and the available data linking this action to anorexia-cachexia syndromes that suggest it is a potential target for therapy of cancer anorexia-cachexia and conversely may also be useful for the treatment of severe obesity.


Quality improvement: single-field sterile scrub, prep, and dwell for laparoscopic hysterectomy.
The vulva and vaginal interior are considered a contaminated surgical area, and current OR guidelines require surgeons who are gloved and gowned at the abdominal field to avoid contact with the urethral catheter, the uterine manipulator, and the introitus or to change their gloves and even regown if contact occurs. It is our belief that the perception of the vaginal field as contaminated reflects a lack of specific standards for the preoperative cleansing of the deeper vagina and a lack of preoperative prep instructions for the combined fields. We developed a comprehensive single-field prep technique designed to improve surgical efficiency and prevent contamination of the sterile field. Combining a methodical scrub, prep, and dwell, this technique allows the entire abdomino-perineovaginal field to be treated as a single sterile field for laparoscopic procedures. Our surgical site infection rate of 1.8% when using this single-field prep technique and the subsequent surgical treatment of the abdominal, vaginal, and perineal fields as a single sterile field is well within reported norms.


Immunocytochemical localization of glucocorticoid receptors in cells, cytoplasts, and nucleoplasts.
A monoclonal antibody has been used to assess the intracellular localization of the glucocorticoid receptor in rodent L-929 fibroblasts and GH3 pituitary tumor cells. Whole cells from both cell lines showed immunoreactivity in the cytoplasm and nucleus. However, when cytoplasts and nucleoplasts of these cells were examined, only L-cells showed strong antibody binding in both fractions; in contrast, GH3 cells exhibited nuclear staining and slight cytoplasmic staining. These results are discussed in terms of the current findings regarding the intracellular location of steroid hormone receptors.


Use of the Bárány Society criteria to diagnose benign paroxysmal positional vertigo.
Benign paroxysmal positional vertigo (BPPV) is the most common vestibular disorder affecting about 20% of dizzy patients. Early diagnosis and treatment can improve the quality of life for patients. We reviewed the classifications of different subtypes of benign paroxysmal positional vertigo and the problems we encountered using the diagnostic criteria of the Bárány Society. Both the Dix-Hallpike maneuver and supine roll test were performed on 568 patients, and diagnoses were made based on patient history and the type of provoked nystagmus (if any). Next, the numbers of patients with each subtype and other parameters, including age and sex, were analyzed. Posterior semicircular canal BPPV (pc-BPPV) accounted for the largest proportion, followed by horizontal semicircular canal BPPV (hc-BPPV). Both anterior canal BPPV and multiple canal lithiasis BPPV were rare, and no patient was diagnosed with cupulolithiasis of the posterior canal. pc-BPPV, hc-BPPV, and cupulolithiasis of the horizontal canal (hc-BPPV-cu) were the three major subtypes that could be definitively diagnosed, whereas the diagnoses of possible benign paroxysmal positional vertigo (pBPPV) and probable benign paroxysmal positional vertigo [spontaneously resolved] (pBPPVsr) require further investigation, with special attention being paid to appropriate differentiation and repositioning maneuvers.


Legume seeds and colorectal cancer revisited: Protease inhibitors reduce MMP-9 activity and colon cancer cell migration.
MMP-9 activity is strongly related to cancer growth and metastization. This study aimed at assessing the inhibitory potential of the major seed protein fractions from eight selected legume species towards MMP-9 activity in colon carcinoma cells. Albumin and globulin fractions were screened for MMP-9 inhibitors, using a fluorometric assay and gelatin zymography. Their effect on HT29 cell proliferation and cell migration was tested, as well as on the corresponding intrinsic cellular MMP-9 activities. Seed proteins include potent inhibitors of MMP-9, particularly low molecular mass proteins. Their effectiveness differs greatly among species, with a positive correlation detected between their inhibitory activity and the reduction in cell migration. Lupin seeds contain the most efficient MMP-9 inhibitors of all legume seeds analyzed, inhibiting both gelatinases and HT29 migration and growth, while pea seeds showed no effect. Results reveal legume protein MMPIs as novel metalloproteinase inhibitors with possible pharmacological interest. This may be important for selecting leguminous species with potential use in anti-cancer diets.


Effectiveness of vitamin D2 supplementation on high-sensitivity C-reactive protein and other metabolic indices in menopausal Thai women: a randomized-controlled trial.
To investigate the effectiveness of vitamin D2 supplementation with ergocalciferol on high-sensitivity C-reactive protein (hsCRP) level and other cardio-metabolic indices in menopausal Thai women. A double-blind, randomized, placebo-controlled trial was conducted at the menopause clinic of a university hospital in Thailand from May 2017 to 2018. Participants were 80 postmenopausal women randomly assigned to treatment (N = 40, receiving vitamin D2 40,000 IU/week) or control (N = 40, receiving placebo) for 12 weeks. The primary outcome was hsCRP level, and secondary outcomes were cardio-metabolic profiles and 10-year risk of developing cardiovascular disease using the Framingham risk score. The changes from baseline to week-12 (Δ) of all outcomes were analyzed using a modified intention-to-treat (ITT) population. The vitamin D2 (N = 39) and placebo (N = 37) groups were comparable in all baseline characteristics. The hsCRP level was significantly reduced in the vitamin D2 group (Δ of -0.39 ± 1.30 mg/L, p = .024) but not in the placebo group (Δ of -0.15 ± 1.15 mg/L, p = .521). However, the Δ of hsCRP had no statistical difference between groups; neither did the Δ of other cardio-metabolic parameters. In menopausal Thai women, vitamin D2 supplementation with ergocalciferol 40,000 IU/week for 12 weeks can reduce hsCRP level; and the treatment might be superior to placebo. However, the hsCRP levels after 12 weeks between both groups were not statistically different. Clinical Trial Registration: Thai Clinical Trials Registry (TCTR20161216001).


Individualized Choice of Simultaneous Cholecystectomy in Patients with Gastric Cancer: A Systematic Review and Meta-analysis.
Patients undergoing gastrectomy for gastric cancer are more likely to develop gallstones than the general population. Prophylactic cholecystectomy remains controversial. Studies from 2000-2022 were systematically searched in the PubMed, EMBASE, and Cochrane Library databases. The search included simultaneous cholecystectomy or risk factors for gallstone formation with gastrectomy alone. Major prognostic factors included complications and mortality, and risk factor analyses included age, sex, TNM stage, gastrectomy type, lymph node dissection, diabetes, and duodenal exclusion. Random effects regression models were used to analyze risk estimates and data were presented as odds ratios (ORs) with corresponding 95% confidence intervals (CIs). There were no significant differences in postoperative morbidity (OR 1.12, 95% CI 0.90-1.39; p = 0.33, I2 = 11%) and mortality (OR 1.23, 95% CI 0.62-2.43; p = 0.56, I2 = 0%) between gastrectomy alone and simultaneous cholecystectomy. Older age (OR 1.48, 95% CI 1.36-1.59; p < 0.001, I2 = 59%), male sex (OR 1.38, 95% CI 1.10-1.71; p = 0.004, I2 = 77%), total gastrectomy (OR 1.50, 95% CI 1.25-1.81; p < 0.001, I2 = 72%), diabetes mellitus (OR 1.38, 95% CI 1.17-1.63; p < 0.001, I2 = 8%), and duodenal exclusion (OR 1.77, 95% CI 1.47-2.15; p < 0.001, I2 = 30%) were risk factors for cholecystolithiasis. Simultaneous cholecystectomy did not increase the incidence of postoperative complications or mortality. Older age, male sex, total gastrectomy, duodenal exclusion, and diabetes were risk factors for gallstone development after gastrectomy.


Gastric insufflation during IAC-CPR and standard CPR in a canine model.
This study was undertaken to determine the effect of interposed abdominal compressions (IAC) during cardiopulmonary resuscitation (CPR) on gastric insufflation when the airway is not secured with an endotracheal tube. A canine model was used in which a common ventilation pressure was applied to separate cuffed esophageal and tracheal tubes. Gas entering the stomach was collected by a pre-placed gastrostomy tube leading to a bell spirometer. Gas entering the lungs was measured with a Wright Respirometer in series with the endotracheal tube. During standard CPR, measurable gastric gas volume was collected in 28 of 30 trials (mean 215 +/- 93 ml/ventilation). During IAC-CPR, in which abdominal pressure was maintained during ventilation after every 5th chest compression, measurable gastric gas was collected in 15 of 30 trials (mean 40 +/- 11 ml/ventilation). Interposed abdominal compressions as an adjunct to standard CPR may not only be of hemodynamic benefit, but may also reduce the incidence of gastric insufflation and attendant complications.


A high-energy and long-cycling lithium-sulfur pouch cell via a macroporous catalytic cathode with double-end binding sites.
Lithium-sulfur batteries are attractive alternatives to lithium-ion batteries because of their high theoretical specific energy and natural abundance of sulfur. However, the practical specific energy and cycle life of Li-S pouch cells are significantly limited by the use of thin sulfur electrodes, flooded electrolytes and Li metal degradation. Here we propose a cathode design concept to achieve good Li-S pouch cell performances. The cathode is composed of uniformly embedded ZnS nanoparticles and Co-N-C single-atom catalyst to form double-end binding sites inside a highly oriented macroporous host, which can effectively immobilize and catalytically convert polysulfide intermediates during cycling, thus eliminating the shuttle effect and lithium metal corrosion. The ordered macropores enhance ionic transport under high sulfur loading by forming sufficient triple-phase boundaries between catalyst, conductive support and electrolyte. This design prevents the formation of inactive sulfur (dead sulfur). Our cathode structure shows improved performances in a pouch cell configuration under high sulfur loading and lean electrolyte operation. A 1-A-h-level pouch cell with only 100% lithium excess can deliver a cell specific energy of >300 W h kg-1 with a Coulombic efficiency >95% for 80 cycles.


Copper hexacyanoferrate nanocrystal as a highly efficient non-noble metal catalyst for reduction of 4-nitrophenol in water.
As Prussian Blue analogues (PBAs) represent one of the most classical families of coordination compounds and exhibit versatile catalytic activities, PBAs have been considered as useful heterogeneous catalysts for reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP). Nevertheless, while Cu has been a well-proven transition metal for 4-NP reduction, especially, due to their ability to attain pronounced conversions of reactants under mild conditions, environmental friendliness and great stability. Nevertheless, while Cu has been a well-proven transition metal for 4-NP reduction, Cu-based PBA has never been developed and thoroughly investigated for 4-NP reduction. Thus, in this study, copper hexacyanoferrate, CuII3[Fe(CN)6]2 (CuFeCN) is particularly synthesized and proposed for the first time as a catalyst for reduction of 4-NP in the presence of NaBH4. CuFeCN exhibits a very high catalytic activity towards reduction of 4-NP to 4-AP with 100% conversion within 4 min. The activity factor (AF) at room temperature, 8057.14 s-1 g-1, is between 1 and 2 orders higher than all other MFeCN Prussian blue analogues (M = Co, Fe, Ni, Zn, and Mn). In addition, CuFeCN shows excellent reusability to achieve 100% conversion of 4-NP to 4-AP with highly stable rate constants over successive 7 cycles. The activation energy (Ea) and turn over frequency (TOF) for the reduction of 4-NP to 4-AP catalyzed by CuFeCN system are determined as 24.6 kJ mol-1 and 36.93 min-1, respectively, which are both significantly more superior than most of reported catalysts in literatures. These advantageous properties make CuFeCN ideal to be developed into a promising catalyst for elimination of nitroaromatic contaminants in water.


Nuclear-Targeting MSNs-Based Drug Delivery System: Global Gene Expression Analysis on the MDR-Overcoming Mechanisms.
The biological mechanisms of nuclear-targeting mesoporous silica nanoparticles (MSNs)-based DDSs (DOX@NT-MSNs) in overcoming multidrug resistance of cancer cells are studied. It is interesting to find for the first time that DOX@NT-MSNs down-regulate the expression of apoptosis suppressor genes and inhibit DNA repair process by disturbing the p53 pathway.


Region-specific saturation germline mutagenesis in mice using the Sleeping Beauty transposon system.
Recent consolidation of the whole-genome sequence with genome-wide transcriptome profiling revealed the existence of functional units within the genome in specific chromosomal regions, as seen in the coordinated expression of gene clusters and colocalization of functionally related genes. An efficient region-specific mutagenesis screen would greatly facilitate research in addressing the importance of these clusters. Here we use the 'local hopping' phenomenon of a DNA-type transposon, Sleeping Beauty (SB), for region-specific saturation mutagenesis. A transgenic mouse containing both transposon (acts as a mutagen) and transposase (recognizes and mobilizes the transposon) was bred for germ-cell transposition events, allowing us to generate many mutant mice. All genes within a 4-Mb region of the original donor site were mutated by SB, indicating the potential of this system for functional genomic studies within a specific chromosomal region.


Executive system dysfunction occurs as early as middle-age in the rhesus monkey.
As our understanding of age-related cognitive decline advances, studies are now focusing on identification of those areas of cognitive function that undergo the first changes with age. In the present study, in order to determine whether executive function is sensitive to the aging process, we assessed the performance of 16 monkeys of middle-age (12-19 years of age) on the conceptual set-shifting task, an analogue of the Wisconsin Card Sorting Test (WCST). We compared their performance to that of seven young adult (5-9 years of age) and 18 aged monkeys (20-30). The findings showed that middle-aged monkeys, like those of advanced age, were significantly impaired on the conceptual set-shifting task (CSST). These findings parallel those of recent studies in humans demonstrating an increase in perseverative errors on the WCST by middle-aged as well as aged individuals and, in turn, support the notion that disruption of executive function is one of the earliest changes in cognition to occur in normal aging.


DCX+ neuronal progenitors contribute to new oligodendrocytes during remyelination in the hippocampus.
A pool of different types of neural progenitor cells resides in the adult hippocampus. Apart from doublecortin-expressing (DCX+) neuronal progenitor cells (NPCs), the hippocampal parenchyma also contains oligodendrocyte precursor cells (OPCs), which can differentiate into myelinating oligodendrocytes. It is not clear yet to what extent the functions of these different progenitor cell types overlap and how plastic these cells are in response to pathological processes. The aim of this study was to investigate whether hippocampal DCX+ NPCs can generate new oligodendrocytes under conditions in which myelin repair is required. For this, the cell fate of DCX-expressing NPCs was analyzed during cuprizone-induced demyelination and subsequent remyelination in two regions of the hippocampal dentate gyrus of DCX-CreERT2/Flox-EGFP transgenic mice. In this DCX reporter model, the number of GFP+ NPCs co-expressing Olig2 and CC1, a combination of markers typically found in mature oligodendrocytes, was significantly increased in the hippocampal DG during remyelination. In contrast, the numbers of GFP+PDGFRα+ cells, as well as their proliferation, were unaffected by de- or remyelination. During remyelination, a higher portion of newly generated BrdU-labeled cells were GFP+ NPCs and there was an increase in new oligodendrocytes derived from these proliferating cells (GFP+Olig2+BrdU+). These results suggest that DCX-expressing NPCs were able to contribute to the generation of mature oligodendrocytes during remyelination in the adult hippocampus.


Prospective randomized clinical trial comparing the effects of a masticatory bite wafer and avoidance of hard food on pain associated with initial orthodontic tooth movement.
The purpose of this prospective, randomized clinical trial was to compare the use of masticatory bite wafers with the avoidance of mastication in reducing pain and discomfort associated with initial orthodontic tooth movement. Eighty-four subjects (mean age, 14.1 years), randomly allocated to a bite-wafer group (BWG) or a reduced-mastication group (RMG), completed the study. In each subject, 1 arch was bonded and ligated with a round austenitic active 0.016-in nickel-titanium wire, and placebo instructions were given. The subjects in the BWG then performed immediate supervised mastication of the wafers for 10 minutes, and they were instructed thereafter to bite on the wafers to prevent pain for the next 7 days. The subjects in the RMG were instructed not to masticate for 3 hours after placement of the fixed appliance and to avoid masticating hard food for 7 days. Each patient's level of anxiety was assessed before treatment with standard psychometric questionnaires. Each patient recorded the level of pain immediately after archwire ligation on a 100-mm visual analogue scale (VAS) and used a pain diary with a verbal rating scale for the next 7 days. No statistically significant differences in the VAS immediately after ligation of the archwires were observed between the 2 groups. The median pain score for the BWG was higher for the first 4 days. The median peak difference was reached on the evening of the first day. At this maximum value, the median pain score of the BWG was higher and statistically significant (P = .006). Although the amount of pain and discomfort reported by the patients undergoing fixed orthodontic therapy varied, more pain was reported by those using bite wafers than by those who avoided masticatory activity after placement of fixed appliances.).


The incidence, clinical outcome, and protective factors of mixed chimerism following hematopoietic stem cell transplantation for severe aplastic anemia.
The aim of our study was to determine possible predictors and clinical course of mixed chimerism (MC) in aplastic anemia after transplantation. A total of 207 transplants were obtained from haploidentical donors (HID) using busulfan (Bu), cyclophosphamide (Cy), and anti-thymocyte globulin (ATG) regimens, and 69 transplants from matched related donors (MRD) and 29 transplants from unrelated donors (URD) using Cy/ATG regimens were obtained. Incidences of MC were 1.93 ± 0.01%, 20.29 ± 0.01%, and 35.71 ± 0.01% in HID, MRD, and URD transplantation (p < .001). In multivariate analysis, incidence of MC was significantly higher in patients without adding Bu in conditioning (p < .001) and receiving a lower number of CD3 + cells in graft (p = .042). MC was associated with significantly lower II-IV aGvHD (3.70% vs. 27.7%, p = .007), but higher secondary graft rejection rates (14.8% vs. 0.4%, p < .001) and poorer overall survival (72.7 ± 8.9% vs. 89.6 ± 2.0%, p = .011) than those of donor chimerism cohort. Mixed chimerism was an unsettling status even in non-malignancy. Haploidentical transplantation with more intense regimen by adding Bu to Cy and ATG was associated with reduced MC following HSCT for SAA. An intensified regimen should be explored in matched related or unrelated donors.


Accuracy evaluation of the 'Cardiette BP one' ambulatory blood pressure monitor.
Blood pressure (BP) 'Cardiette BP one' system (BP one) is an oscillometric ambulatory BP monitor manufactured in Italy in conformity to current regulations for medical devices. We decided to determine the accuracy of measures made with BP one, using the protocol of the British Hypertension Society published in 1990, and revised in 1993, for evaluating the accuracy of BP measurement devices. The evaluation included before-use calibration, in-use assessment, after-use calibration, and static device validation that involved 85 participants. The mean difference between manual readings with sphygmomanometer and automatic ones with the device were -0.36+/-5.74 (mean+/-SD) for systolic values and 2.52+/-4.87 for diastolic values. On the basis of the percentages of measurements differing from the mercury sphygmomanometer standard by <or=5, <or=10, and <or=15 mmHg, the device was graded 'A' for systolic and diastolic BP, for low, median, and high BP values. On the basis of the standards indicated by the 1993 modified British Hypertension Society protocol, the BP one recorder can be classified as 'A' grade both for systolic and diastolic pressure.


Transient focal ischemia in hyperglycemic rats is associated with increased cerebral infarction.
To study whether transient ischemia is influenced by hyperglycemia, the middle cerebral artery was occluded for 5, 10 and 15 min in normo- and hyperglycemic rats. Five-minute ischemia induced minor lesions in both groups. After 10-min ischemia a significant greater infarct volume was found in hyperglycemia compared with normoglycemia (29 +/- 9 mm3 vs 4 +/- 4 mm3, P less than 0.001). Fifteen-minute artery occlusion induced even more damage in both hyper- and normoglycemia (63 +/- 20 mm3 vs 13 +/- 12 mm3, P less than 0.006). The lateral part of striatum was infarcted in all hyperglycemic animals exposed to 10 or 15 min of ischemia. In the same area selective neuronal injury occurred in 6 out of 9 normoglycemic animals. The findings show that hyperglycemia increases brain damage during transient ischemia by conversion of selective neuronal injury into cerebral infarction.


Uncoupling protein 1 inhibits mitochondrial reactive oxygen species generation and alleviates acute kidney injury.
Uncoupling protein 1 (UCP1) is predominantly found in brown adipose tissue mitochondria, and mediates energy dissipation to generate heat rather than ATP via functional mitochondrial uncoupling. However, little is known about its expression and function in kidney. We carried out a mRNA microarray analysis in mice kidneys with ischemia reperfusion (IR) injury. The most dramatically downregulated gene UCP1 after IR was identified, and its role in generation of mitochondrial reactive oxygen species (ROS) and oxidative stress injury was assessed both in vitro and in vivo. Genetic deletion of UCP1 was used to investigate the effects of UCP1 on ischemia or cisplatin-indued acute kidney injury (AKI) in mice. UCP1 was located in renal tubular epithelial cells in kidney and downregulated in a time-dependent manner during renal IR. Deletion of UCP1 increased oxidative stress in kidneys and aggravated ischemia or cisplatin induced AKI in mice.Viral-based overexpression of UCP1 reduced mitochondrial ROS generation and apoptosis in hypoxia-treated tubular epithelial cells. Furthermore, UCP1 expression was regulated by peroxisome proliferator-activator receptor (PPAR) γ in kidneys during renal IR. Overexpression of PPAR-γ resembled UCP1-overexpression phenotype in vitro. Treatment with PPAR-γ agonist could induce UCP1 upregulation and provide protective effect against renal IR injury in UCP1+/+mice, but not in UCP1-/-mice. UCP1 protects against AKI likely by suppressing oxidative stress, and activation of UCP1 represents a potential therapeutic strategy for AKI. FUND: National Natural Science Foundation of China grants, Science and Technology Commission of Shanghai.


Potential of montmorillonite modified by an organosulfur surfactant for reducing aflatoxin B1 toxicity and ruminal methanogenesis in vitro.
Montmorillonite clay modified by organosulfur surfactants possesses high cation exchange capacity (CEC) and adsorption capacity than their unmodified form (UM), therefore they may elevate the adverse impact of aflatoxin B1 (AFB1) on ruminal fermentation and methanogenesis. Chemical and mechanical modifications were used to innovate the organically modified nano montmorillonite (MNM). The UM was modified using sodium dodecyl sulfate (SDS) and grounded to obtain the nanoscale particle size form. The dose-response effects of the MNM supplementation to a basal diet contaminated or not with AFB1 (20 ppb) were evaluated in vitro using the gas production (GP) system. The following treatments were tested: control (basal diet without supplementations), UM diet [UM supplemented at 5000 mg /kg dry matter (DM)], and MNM diets at low (500 mg/ kg DM) and high doses (1000 mg/ kg DM). Results of the Fourier Transform Infra-Red Spectroscopy analysis showed shifts of bands of the OH-group occurred from lower frequencies to higher frequencies in MNM, also an extra band at the lower frequency range only appeared in MNM compared to UM. Increasing the dose of the MNM resulted in linear and quadratic decreasing effects (P < 0.05) on GP and pH values. Diets supplemented with the low dose of MNM either with or without AFB1 supplementation resulted in lower (P = 0.015) methane (CH4) production, ruminal pH (P = 0.002), and ammonia concentration (P = 0.002) compared to the control with AFB1. Neither the treatments nor the AFB1 addition affected the organic matter or natural detergent fiber degradability. Contamination of AFB1 reduced (P = 0.032) CH4 production, while increased (P < 0.05) the ruminal pH and ammonia concentrations. Quadratic increases (P = 0.012) in total short-chain fatty acids and propionate by MNM supplementations were observed. These results highlighted the positive effects of MNM on reducing the adverse effects of AFB1 contaminated diets with a recommended dose of 500 mg/ kg DM under the conditions of this study.


Rerefinement of the crystal structure of tri-chlorido-sulfonium-(IV) hexa-chlorido-uranate(V), (SCl3)[UCl6].
Single crystals of tri-chlorido-sulfonium-(IV) hexa-chlorido-uranate(V) were obtained from the reaction of uranium(IV) chloride with an excess of disulfur dichloride and studied by single-crystal X-ray diffraction. In comparison with the structure model reported previously [Sawodny et al. (1983 ▸). Z. Anorg. Allg. Chem. 499, 81-88.], the lattice parameters and fractional atomic coordinates were determined to a much higher precision, leading overall to an improved structure model. The ionic compound contains trigonal-pyramidal (SCl3)+ cations and slightly distorted octa-hedral [UCl6]- anions. The structure was refined as an inversion twin with a twin ratio of 4.4:1.


Antimicrobial susceptibility profile of contemporary clinical strains of Stenotrophomonas maltophilia isolates: can moxifloxacin activity be predicted by levofloxacin MIC results?
The susceptibility profile of 763 Stenotrophomonas maltophilia isolates was evaluated against 16 antimicrobials by the CLSI reference broth microdilution method. Minocycline (MIC(90), 1 microg/ml; 100.0% susceptible) was the most active compound, followed by doxycycline (MIC(90), 4 microg/ml; 99.6% susceptible), trimethoprim/sulfamethoxazole (MIC(90), 1 microg/ml; 97.8% susceptible), and tigecycline (MIC(90), 2 microg/ml). An excellent correlation between levofloxacin (MIC(90), 4 microg/ml; 86.5% susceptible by published breakpoint criteria) and moxifloxacin (MIC(90), 2 micro g/ml) MIC results was observed indicating that moxifloxacin could be further evaluated as a therapeutic option for S. maltophilia infections.


Simplified population data analysis using gamma distribution for nutritional requirements and its application to the estimation of iron requirements for women of child-bearing age.
Estimation of nutritional requirements is a difficult task, especially for nutrients whose requirements have skewed distribution like iron in menstruating women. To mathematically develop a simplified population data analysis using gamma distribution for the estimation of nutritional requirements, not depending on extensive numerical calculation. The required equations for the estimation of requirements were devised and solved. Existing data of iron intakes and iron losses in literature were fitted to cumulative distribution curves including gamma distribution. The proposed method was applied to the estimation of iron requirements in women using the National Health and Nutrition Survey data from 2003 to 2007 in Japan. The type 2 equation of nutritional state is first introduced: prevalence of inadequate nutritional state = Σ(individuals with intake/requirement <1)/(total number of individuals). The prevalence of inadequate nutritional status is determined by F-distribution with positive real number parameters, if the intake and the requirement have independent gamma distributions. The sum of basal and menstrual iron losses is well approximated by gamma distribution, if the basal and menstrual iron losses have independent gamma distributions. Using these relationships, an approximate estimate of iron requirements was determined. Iron intakes and losses were found to be well approximated by gamma distribution. The median of the coefficient of variation (CV) of basal iron loss was 34 %. A new correction method for intra-individual variation in gamma distribution under constant CV is presented also. The median of the estimated median iron requirement was 8.12 mg, 8.15 mg and 8.18 mg for women aged 18-29 years, respectively, as the exact numerical estimate, the approximate estimate using BETA.INV in Excel and the approximate estimate using F.INV in Excel. For women aged 30-49 years, it was 9.15 mg, 9.17 mg and 9.14 mg. The intake covering the needs of 97.7 % women was 14.55 mg, 14.44 mg and 14.49 mg for women aged 18-29 years, and 15.70 mg, 15.77 mg and 15.60 mg for women aged 30-49 years. The approximate estimates of iron requirements agreed well with the exact numerical estimate. The proposed method is useful for the estimation of iron requirements in menstruating women that usually requires extensive numerical calculations.


Halothane inhibits hypoxic pulmonary vasoconstriction in the presence of cyclooxygenase blockade.
Using an isolated lung the effects of halothane on hypoxic pulmonary vasoconstriction (HPV) were studied in the presence of cyclooxygenase blockade. The pulmonary vasculature can be divided into arterial, middle and venous segment resistances. Analysis of the vascular pressure-flow relationship further separates resistance into a flow dependent resistance (1/slope) and a zero-flow pressure intercept (PCRIT). We ventilated six lobes with control (35 per cent O2) and hypoxic (three per cent O2) gas mixtures with the addition of either 0, 0.5, 1.0, or 2.0 per cent halothane. We found that after addition of indomethacin (5 mg.kg-1), ventilation with three per cent O2 increased total resistance by 87 per cent over baseline with the increase primarily in the middle vascular segment. During normoxic ventilation PCRIT was 7.9 cm H2O and this increased significantly with hypoxia to 11.5 cm H2O). Only 2.0 per cent halothane blocked the increases in middle segment resistance and in PCRIT. We conclude that following cyclooxygenase blockade, halothane inhibits HPV by acting on middle segment vessels.


Cisplatin induces lung cell cilia disruption and lung damage via oxidative stress.
Cisplatin (cis-diamminedichloroplatinum II) is widely used for the treatment of cancer, but its cellular toxicity, especially in the form of oxidative stress, limits its use in multiple organs including the lungs. As a cellular organelle, cilia play an important role in cellular function and can be damaged by oxidative stress. However, the effect of cisplatin-induced lung toxicity on cilia has not yet been defined. Herein, we investigated the association of cilia and oxidative stress with cisplatin-induced lung damage. Mice were administered with cisplatin. Some mice were treated with 2-(2,2,6,6-Tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl) triphenylphosphonium chloride (Mito-TEMPO, a mitochondria-specific antioxidant) before the administration of cisplatin. Disruption of cilia was evaluated by the detection of ciliary proteins and fragments in the bronchoalveolar lavage fluid (BALF). Cisplatin caused the thickening of interalveolar septa, infiltration of immune cells into the interalveolar septa, and increased protein concentration and total cell number in the BALF. Cisplatin also increased ciliary fragments and proteins in the BALF. In the lungs, cisplatin increased the production of hydrogen peroxide, lipid peroxidation, and apoptosis, while decreasing manganese superoxide dismutase, isocitrate dehydrogenase 2, and catalase expression. Treatment with Mito-TEMPO prevented cisplatin-induced lung damage, ciliary fragmentation, oxidative stress, and apoptosis. By increasing oxidative stress in the lung, cisplatin induces lung cell damage, disruption of cilia, and release of disrupted cilia into the BALF. This suggests that cisplatin-induced lung damage can damage the cilia, manifesting as increased ciliary proteins in the BALF.


Managing Low Back Pain: Exercise, Manual Therapy, and Education.
Many people experience low back pain during their lives. Low back pain usually resolves within a couple of weeks or months; however, for some people, it can last for several months or years. Recently, experts developed a guideline for physical therapists to use when treating low back pain. This guideline aims to improve treatment and outcomes for people with back pain, and help you and your physical therapist make decisions that work best for you. J Orthop Sports Phys Ther 2021;51(11):535. doi:10.2519/jospt.2021.0508.


Effects of Brazilin on induction of immunological tolerance by sheep red blood cells in C57BL/6 female mice.
Brazilin was examined for its effects on the induction of immunological tolerance. Brazilin was administered to C57BL/6 female mice for 2 consecutive days before the immunization with high dose SRBC (10(9) cells) which can produce immunological tolerance. Delayed type hypersensitivity, IgM plaque forming cells, ConA induced IL-2 production and mitogen- or antigen-induced proliferation of lymphocytes were measured as evaluation parameters. Administration of brazilin prior to immunization could keep the DTH and IL-2 production almost optimally immunized levels. Brazilin also inhibited the elevation of non-specific suppressor cell activity. ConA induced proliferation of splenocytes in high dose SRBC immunized mice was significantly decreased by pretreatment of brazilin. And this might be one of the reason for augmentation of DTH by brazilin. However, IgM plaque forming cells were not affected by the treatment of brazilin. These results indicate that brazilin prevents the induction of immunological tolerance caused by high dose SRBC by suppressing the elevation of suppressor cell activity and by inhibiting the decrease in IL-2 production in C57BL/6 female mice.


Association between harm reduction intervention uptake and skin and soft tissue infections among people who inject drugs.
Bacterial skin and soft tissue infections (SSTIs) are a health issue for people who inject drugs (PWID). There is a lack of evidence on the associations between harm reduction (HR) uptake and SSTIs. This paper examines the associations between the uptake of injecting equipment (IE) and opiate substitution treatment (OST) on SSTIs among PWID, and the injecting behaviours associated with having had an SSTI. This is the first large-scale, national study to examine the association between IE uptake and SSTIs. A cross-sectional, voluntary and anonymous survey was undertaken with PWID recruited from pharmacies/agencies providing IE across mainland Scotland during 2013-2014. Participants were asked: if they had an SSTI within the past year; about their uptake of HR within the past 6 months (including needle/syringes (N/S), paraphernalia and OST); and about their frequency of injecting, sharing of IE and re-use of own N/S. Data from 1876 PWID who had reported injecting within the past 6 months were analysed. In multivariate logistic regression, those with high combined IE-OST uptake (adjusted odds ratio [AOR] 0.614, 95% CI 0.458-0.823, p=0.001) and medium combined IE-OST uptake (AOR 0.725, 95% CI 0.546-0.962, p=0.026) had lower odds of having had an SSTI compared to those with low combined IE-OST uptake. IE and OST uptake may reduce the level of SSTIs among PWID, suggesting increasing combined uptake may be beneficial. Nevertheless, a sizeable proportion of PWID with high HR uptake experienced SSTIs, suggesting the importance of other interventions.


A double commutant theorem for Murray-von Neumann algebras.
Murray-von Neumann algebras are algebras of operators affiliated with finite von Neumann algebras. In this article, we study commutativity and affiliation of self-adjoint operators (possibly unbounded). We show that a maximal abelian self-adjoint subalgebra A of the Murray-von Neumann algebra A(f)(R) associated with a finite von Neumann algebra R is the Murray-von Neumann algebra A(f)(A(0)), where A(0) is a maximal abelian self-adjoint subalgebra of R and, in addition, A(0) is A Π R. We also prove that the Murray-von Neumann algebra A(f)(C) with C the center of R is the center of the Murray-von Neumann algebra A(f)(R). Von Neumann's celebrated double commutant theorem characterizes von Neumann algebras R as those for which R'' = R, where R', the commutant of R, is the set of bounded operators on the Hilbert space that commute with all operators in R. At the end of this article, we present a double commutant theorem for Murray-von Neumann algebras.


Development of a four-body statistical pseudo-potential to discriminate native from non-native protein conformations.
Most scoring functions used in protein fold recognition employ two-body (pseudo) potential energies. The use of higher-order terms may improve the performance of current algorithms. Proteins are represented by the side chain centroids of amino acids. Delaunay tessellation of this representation defines all sets of nearest neighbor quadruplets of amino acids. Four-body contact scoring function (log likelihoods of residue quadruplet compositions) is derived by the analysis of a diverse set of proteins with known structures. A test protein is characterized by the total score calculated as the sum of the individual log likelihoods of composing amino acid quadruplets. The scoring function distinguishes native from partially unfolded or deliberately misfolded structures. It also discriminates between pre- and post-transition state and native structures in the folding simulations trajectory of Chymotrypsin Inhibitor 2 (CI2).


Weighing the QT intervals with the slope or the amplitude of the T wave.
The reproducibility of QT interval measurements is low, even for the mean QT interval based on the standard ECG. In this study we analyzed whether the reproducibility of the mean weighed QT interval was better than the simple mean QT interval. The weighing was based on the amplitude of the T wave or the slope of the steepest tangent on the terminal part of the T wave. 12-lead ECGs of 130 postmyocardial infarction patients were obtained. The QT intervals were measured by the tangent-method on two occasions by the same observer Mismatch QT intervals were defined as QT intervals that were measured at only one occasion. Sixteen ECGs were rejected. The data were split into 34 and 80 ECGs for optimization and validation of the weighing, respectively. The weighed QT dispersion was calculated as the weighed mean of the three longest minus the weighed mean of the three shortest QT intervals. Weighing with the slope increased the reproducibility by 41% (P = 3 10(-6)), but weighing with the amplitude reduced it by 20% (P = 0.02). However, if measurements with errors above 75 ms were rejected, weighing with the slope or the amplitude increased the reproducibility with 26% and 20% (P = 0.02), respectively. Weighing did not change the reproducibility of the weighed QT dispersion. Weighing with the slope improved the reproducibility of the mean weighed QT interval. However, if measurements with errors above 75 ms were rejected, weighing with the amplitude also increased the reproducibility. Weighing did not change the reproducibility of the weighed QT dispersion. Weighing is particularly efficient at reducing the negative impact of mismatch QT intervals on the reproducibility.


Characterisation of vaccine-induced, broadly cross-reactive IFN-γ secreting T cell responses that correlate with rapid protection against classical swine fever virus.
Live attenuated C-strain classical swine fever viruses (CSFV) provide a rapid onset of protection, but the lack of a serological test that can differentiate vaccinated from infected animals limits their application in CSF outbreaks. Since immunity may precede antibody responses, we examined the kinetics and specificity of peripheral blood T cell responses from pigs vaccinated with a C-strain vaccine and challenged after five days with a genotypically divergent CSFV isolate. Vaccinated animals displayed virus-specific IFN-γ responses from day 3 post-challenge, whereas, unvaccinated challenge control animals failed to mount a detectable response. Both CD4(+) and cytotoxic CD8(+) T cells were identified as the cellular source of IFN-γ. IFN-γ responses showed extensive cross-reactivity when T cells were stimulated with CSFV isolates spanning the major genotypes. To determine the specificity of these responses, T cells were stimulated with recombinant CSFV proteins and a proteome-wide peptide library from a related virus, BVDV. Major cross-reactive peptides were mapped on the E2 and NS3 proteins. Finally, IFN-γ was shown to exert potent antiviral effects on CSFV in vitro. These data support the involvement of broadly cross-reactive T cell IFN-γ responses in the rapid protection conferred by the C-strain vaccine and this information should aid the development of the next generation of CSFV vaccines.


Head and neck mucoepidermoid carcinoma: does AFIP histological grading correlate with rate of nodal metastases?
The aim of this study is to retrospectively evaluate the presentation of head and neck mucoepidermoid carcinoma at the Royal Melbourne Hospital and identify the significance of AFIP histological grading on the risk of neck metastasis and cancer free survival. This study is a retrospective cohort analysis of patients treated for head and neck mucoepidermoid carcinoma at the RMH between 2005 and 2022. Patient demographics, treatment, pathology, in particular the AFIP histological grading of the primary tumour, and outcomes were collected and tabulated. Time to recurrence was recorded, and survival outcomes were calculated with Kaplan-Meier method. Comparisons were made on different histological grading and regional metastases. Thirty-three patients were identified and thirty met the inclusion criteria. There was an age range of 18-77 years (median 54 years) with no significant sex difference. Our patients had a 94% 5-year survival and an 86% 10-year survival. Thirteen patients had elective neck dissection and 2 out of 13 (15%) of the patients had positive neck disease. Of the two patients with regional metastasis, the primary tumour was graded as intermediate and low grade. No high-grade MEC patients had regional metastasis. Mucoepidermoid carcinoma of the head and neck is associated with a good disease-specific and overall survival despite the presence of regional metastasis. The AFIP histological grading system did not have a statistically significant correlation to the incidence of nodal metastasis.


Photosynthesis of Littorella uniflora grown under two PAR regimes: C3 and CAM gas exchange and the regulation of internal CO2 and O2 concentrations.
The submersed aquatic macrophyte Littorella uniflora was grown under 50 and 300 μmol m-2 s-1 photosynthetically active radiation (PAR) (low and high PAR regimes) but identical sediment CO2 supply (1.0 mol m-3). The interactions between plant morphology, whole plant CO2 and O2 exchange, CAM activity, [CO2] i and [O2] i have been investigated in comparison with in vitro CO2 and PAR response characteristics (using 1 mm leaf sections). In terms of morphology, high-PAR-grown plants were smaller and leaves contained less chlorophyll, although root growth was proportionally larger. Gas exchange fluxes over roots and shoots of intact plants were similar in direction under the two PAR regimes, with the majority of CO2 uptake via the roots. Photosynthetic O2 evolution from intact plants was greater in high-PAR-grown L. uniflora (2.18 compared with 1.49 μmol O2g-1 fresh weight h-1 for the low PAR regime). Although net daytime CO2 uptake was similar for both PAR regimes (0.79 and 0.75 μmol g-1 fwt h-1), net dark CO2 uptake was at a higher rate (0.92 compared with 0.52 μmol CO2 g-1 fwt h-1), and dark fixation (as malic acid) was threefold greater in high PAR plants (ΔH+ 117 compared with 42 μmol H+ g-1 fwt). Comparison of dark CO2 uptake with dark fixation suggested that much of the CO2 fixed at night and regenerated during the day may be respiratory in origin (60% low PAR plants, 71% high PAR plants). Regeneration of CO2 from CAM could account for 62% of daytime CO2 supply in low PAR plants and 81% in high PAR plants. [CO2] i values (ranging from 0.42 to 1.03 mol m-3) were close to or above the concentration required to saturate photosynthesis in vitro (0.5 mol m-3) under both PAR regimes, and combined with the low [O2] i (2.6-4.3 mol m-3) should have suppressed photorespiration. However, PAR inside leaves would have been well below the in vitro light saturation requirement (850-1000 μmol m-2 s-1 for both treatments). Thus PAR rather than CO2 supply appeared to limit photosynthesis even in high PAR grown plants, and CAM appears to have an important role in the regulation of CO2 supply for photosynthesis in response to variation in light regime.