Evoking biphone neighborhoods with verbal transformations: illusory changes demonstrate both lexical competition and inhibition.
When a recorded verbal stimulus repeats over and over, perceptual changes occur and listeners hear competing forms. These verbal transformations (VTs) were obtained for a phonemically related set of 24 consonant-vowel syllables that varied widely in frequency-weighted neighborhood density (FWND). Listener's initial transformations involving substitution of consonants versus vowels were strongly correlated with the lexical substitution neighborhood [r=+0.82, p<0.0001]. Interestingly, as stimulus FWND increased, average time spent hearing illusory forms substantially decreased [r=-0.75, p<0.0001]. These results suggest that VTs not only reveal underlying competitors, but also provide a highly sensitive measure of lexical inhibition.


[Anatomy, diagnostics and therapy of diaphragmatic lacunae in infants and children (author's transl)].
The various forms of diaphragmatic lacunae and hernius find their explanation in the development of the diaphragm. The classification of Vos, Eijgelaar and Kuijjer should by used for typification of intraoperative findings and comparison of the therapeutic results. Own experiences are discussed concerning diagnostics, differential diagnostics and therapy.


Subjects' dissimilarity in the analysis of laser-tissue dose-response experiments: a potential cause for puzzling results.
The in vivo dose-response laser-tissue experiment is usually performed on several subjects, each exposed several times at different tissue sites. The collected data are then unified into a single statistical batch and analysed under the tacit assumption that the tolerances of all the subjects are similar. However, if this assumption is incorrect the data unification may lead to very biased results. This study reanalyses a raw data set measured by the US Army Medical Research Detachment Walter Reed Army Institute of Research (USAMRD-WRAIR), which was used to study the influence of the laser wavelength on the energy threshold of retinal injury. The USAMRD-WRAIR report reveals a significant variation of threshold with small changes in wavelength. Despite an extensive study, performed by the USAMRD-WRAIR researchers, which included possible lasers variations, many aspects of experimental technique and biological absorption properties of the eye, a cause for the threshold variation was not found. Our current results suggest that unaccounted specimen's dissimilarity might be the cause for this unclear threshold variations.


Intrinsic and extrinsic controls of the hypertrophic program of chondrocytes in the avian columella.
Immunohistochemical studies of the chick columella have shown that the extracellular matrix of this ossicular cartilage template is composed largely of type II collagen. As development proceeds, synthesis of type X collagen, a hypertrophic cartilage-specific molecule, is initiated by endochondral chondrocytes within the zone of cartilage cell hypertrophy. Subsequently, these cells and their surrounding extracellular matrix are removed, resulting in marrow cavity formation. We have examined which of these processes are programmed within the columella chondrocytes themselves, and which require involvement of exogenous factors. Prehypertrophic columella from 12-day chick embryos were grown either in organ culture on Nuclepore filters or as explants on the chorioallantoic membrane of host embryos. Chondrocytes from the same source were grown in monolayer cell cultures. In both organ culture and cell culture, chondrocytes developed to the stage at which some of them entered the hypertrophic program and initiated the production of type X collagen as determined by immunofluorescence histochemistry with a monoclonal antibody specific for that collagen type. The organ cultures, however, did not progress to the next stage, in which detectable removal of the type X collagen-containing matrix occurs. When identical columella were grown on the chorioallantoic membrane of host chicks, the type X collagen-containing matrix which formed was rapidly removed, resulting in the formation of a marrow cavity. Thus, progression of endochondral chondrocytes to the deposition of type X collagen-containing matrix seems to be programmed within the cells themselves. Subsequent removal of this matrix requires the involvement of exogenous factors.


Biotoxic effects and gene expression regulation of urban PM2.5 in southwestern China.
Atmospheric fine particulate matter (PM2.5) causes severe haze in China and is regarded as a threat to human health. The health effects of PM2.5 vary location by location due to the variation in size distribution, chemical composition, and sources. In this study, the cytotoxicity effect, oxidative stress, and gene expression regulation of PM2.5 in Chengdu and Chongqing, two typical urban areas in southern China, were evaluated. Urban PM2.5 in summer and winter significantly inhibited cell viability and increased reactive oxygen species (ROS) levels in A549 cells. Notably, PM2.5 in winter exhibited higher cytotoxicity and ROS level than summer. Moreover, in this study, PM2.5 commonly induced cancer-related gene expression such as cell adhesion molecule 1 (PECAM1), interleukin 24 (IL24), and cytochrome P450 (CYP1A1); meanwhile, PM2.5 commonly acted on cancer-related biological functions such as cell-substrate junction, cell-cell junction, and focal adhesion. In particular, PM2.5 in Chengdu in summer had the highest carcinogenic potential among PM2.5 at the two sites in summer and winter. Importantly, cancer-related genes were uniquely targeted by PM2.5, such as epithelial splicing regulatory protein 1 (ESRP1) and membrane-associated ring-CH-type finger 1 (1-Mar) by Chengdu summer PM2.5; collagen type IX alpha 3 chain (COL9A3) by Chengdu winter PM2.5; SH2 domain-containing 1B (SH2D1B) by Chongqing summer PM2.5; and interleukin 1 receptor-like 1 (IL1RL1) and zinc finger protein 42 (ZNF423) by Chongqing winter PM2.5. Meanwhile, important cancer-related biological functions were specially induced by PM2.5, such as cell cycle checkpoint by Chengdu summer PM2.5; macromolecule methylation by Chengdu winter PM2.5; endoplasmic reticulum-Golgi intermediate compartment membrane by Chongqing summer PM2.5; and cellular lipid catabolic process by Chongqing winter PM2.5. Conclusively, in the typical urban areas of southern China, both summer and winter PM2.5 illustrated significant gene regulation effects. This study contributes to evaluating the adverse health effects of PM2.5 in southern China and providing public health suggestions for policymakers.


Prey preference in stoneflies: a comparative analysis of prey vulnerability.
Laboratory feeding trials were conducted with the predaceous stonefly Hesperoperla pacifica and a number of mayfly and dipteran prey species to investigate the effects of predator size, and prey size and morphology, on the predator's success. Observations under dim red light permitted estimation of encounter rate (E/min), attack propensity (A/E), capture success (C/A) and handling time (HT). For prey of a particular species and size, HT decreased log-linearly with increasing predator size. Across all prey categories, HT increased log-linearly with increasing values of the ratio prey dry wt/predator dry wt, and differences among species appeared to be small. Overall, capture success was low, but C/A was higher for dipterans than for mayflies, especially with large H. pacifica. Predator size affected C/A when prey fell within a certain size range, but was not a detectable influence with very small or very large prey. Values of A/E of near 10% typified many predatorprey combinations; however, ephemerellid mayflies suffered markedly fewer attacks, and values of A/E up to 30% were obtained with some species-size combinations. We estimated benefit to the predator first as prey wt ingested per unit time (dry wt/HT), and second by mutliplying the former term by capture success. Values increased with increasing size of the predator, and inclusion of the C/A term indicated that predators would obtain greater reward from small relative to large prey, and from dipterans relative to mayflies. Howerver, there was little evidence that attacks were biased toward more profitable prey. We compare the relative contributions of E/min, A/E and C/A to prey choice, and discuss their applicability to predation events in nature.


Hemoglobin A1c (HbA1c) in children with long standing and newly diagnosed diabetes mellitus.
In 35 children with long-standing diabetes mellitus, a significant correlation was found between the hemoglobin A1c (HbA1c)--and the 24-hour urinary glucose excretion. By contrast, 11 newly diagnosed diabetic children had grossly elevated HbA1c-concentrations, but no correlations could be established between the levels of HbA1c and the duration of symptoms, blood glucose, glycosuria, ketonuria and the acid--base status. However, HbA1c and C-peptide were significantly correlated. The elevated HbA1c-concentrations decreased towards normal in all of these 11 children after 2--3 months following adequate therapy. The results suggest that the determination of HbA1c may serve as a valuable metabolic control index in children with long-standing diabetes mellitus, but adds little information in newly diagnosed patients. For the individual diabetic child during the early treatment period, HbA1c may be the index of choice for adequacy of metabolic control.


Laparoscopic Major Hepatectomy: Do Not Underestimate the Impact of Specimen Extraction Site.
In laparoscopic major hepatectomy, analysis of outcomes according to specimen extraction site remains poorly described. The aim was to compare postoperative outcomes according to specimen extraction site. From 2000 to 2017, all laparoscopic major hepatectomies were reviewed and postoperative outcomes were analyzed according to specimen extraction site: subcostal (Group 1), midline (Group 2), or suprapubic (Group 3) incision. Among 163 patients, 15 (9.2%) belonged to Group 1, 49 (30.1%) in Group 2, and 99 (60.7%) in Group 3. The proportion of right-sided, left-sided, or central hepatectomies, mortality, and overall and severe complications were comparable between groups. Group 1 had larger tumors (61 vs. 38 vs. 47 mm; P = 0.014), higher operative time (338 vs. 282 vs. 260 min; P < 0.008), higher adjacent organ resection rate (46.6 vs. 16.3 vs. 7.1%; P < 0.001), and tended to increase pulmonary complications (40.0 vs. 12.2 vs. 18.2%; P = 0.064). In Group 2, a previous midline incision scar was more frequently used for specimen extraction site (65.3 vs. 26.6 and 30.3%, Group 1 and 3; P < 0.001). Postoperative incisional hernia was observed in 16.4% (n = 23) and was more frequent in Group 2 (26.6 vs. 6.6% and 10.1%, Group 1 and Group 3; P = 0.030). Finally, Group 2 (HR 2.63, 95% CI 1.41-3.53; P = 0.032) was the only independent predictive factor of postoperative incisional hernia. While using a previous incision makes sense, the increased risk of postoperative incisional hernia after midline incision promotes the suprapubic incision.


Effect of two opaquing techniques and two metal surface conditions on metal-ceramic bond strength.
The optimal conditions for opaquing techniques during porcelain application have not been confirmed. In this study the metal-ceramic bond strength was measured among one porcelain and three dental alloys, namely a gold-platinum-palladium alloy, a silver-free gold-palladium alloy, and a base metal alloy, with two opaquing techniques (a single masking layer versus a thin overfired layer followed by a second masking layer). In addition, the opaque porcelain was fired over an oxidized and nonoxidized alloy surface for the silver-free gold-palladium alloy. No significant differences in bond strength were recorded between the two opaquing techniques with the gold-platinum-palladium and base metal alloys. There was no substantial differences between the two opaquing techniques when opaque was applied over an oxidized gold-palladium alloy surface and bond strengths were substantially greater over an oxidized surface. However, when the opaque was applied to a nonoxidized gold-palladium surface the two-layer technique created a significantly greater bond strength.


Analysis of multidrug-resistance (MDR-1) glycoprotein and CD56 expression to separate monoclonal gammopathy from multiple myeloma.
Monoclonal gammopathy of undetermined significance (MGUS) is different from multiple myeloma (MM) by a low proliferation and by its indolent clinical course. In this study, two biological parameters were investigated which mark the transition from MGUS to MM, i.e. expression of the P-170 glycoprotein associated with the multidrug resistance phenotype (MDR-1) and expression of the natural killer cell antigen. CD56. Strong MDR-1 expression was found in plasma cells of 32/38 untreated MGUS as compared with 33/105 untreated MM stage I-III (84% v 32%, P < 0.001) and in 0/10 normal plasma cell samples. CD56 expression in high density was present in 43/57 analysed untreated MM but in none of 23 MGUS (78% v 0%, P < 0.0001). Plasma cells did characteristically show a low Ki-67 proliferation index in 14/15 MGUS patients (mean 0.05%, range 0-0.2%) and a higher index in 25 analysed MM patients (mean 2.31%, range 1-7%, P < 0.03). These data indicate that MDR-1 expression together with absence of CD56 expression and a low proliferation index can be used to separate MGUS from MM.


A case report of Kabuki make-up syndrome with cytomegalovirus infection.
An 8-month-male infant was admitted to our institute in order to investigate his developmental delay. He had facial features-long palpebral fissures with eversion of the lower lateral eyelids, arched eyebrows with lateral sparseness, depressed nasal tip, large, prominent and cupped ears. From these characteristical features, he was diagnosed as having Kabuki make-up syndrome (KS). When he was 2 months old, he was admitted to our institute because of intractable stridor and liver dysfunction associated with cytomegalovirus (CMV) infection. In KS, increased susceptibility to infection is described. We suspected persistent CMV infection because of an increased susceptibility to infection in KS. Recently acute idiopathic thrombocytopenic purpura (ITP) was diagnosed. According to the correlation between the number of CMV DNA copies and his platelet count, it is speculated that ITP would occur when the number of CMV DNA copies was elevated.


Characterization and identification of lysine crotonylation sites based on machine learning method on both plant and mammalian.
Lysine crotonylation (Kcr) is a type of protein post-translational modification (PTM), which plays important roles in a variety of cellular regulation and processes. Several methods have been proposed for the identification of crotonylation. However, most of these methods can predict efficiently only on histone or non-histone protein. Therefore, this work aims to give a more balanced performance in different species, here plant (non-histone) and mammalian (histone) are involved. SVM (support vector machine) and RF (random forest) were employed in this study. According to the results of cross-validations, the RF classifier based on EGAAC attribute achieved the best predictive performance which performs competitively good as existed methods, meanwhile more robust when dealing with imbalanced datasets. Moreover, an independent test was carried out, which compared the performance of this study and existed methods based on the same features or the same classifier. The classifiers of SVM and RF could achieve best performances with 92% sensitivity, 88% specificity, 90% accuracy, and an MCC of 0.80 in the mammalian dataset, and 77% sensitivity, 83% specificity, 70% accuracy and 0.54 MCC in a relatively small dataset of mammalian and a large-scaled plant dataset respectively. Moreover, a cross-species independent testing was also carried out in this study, which has proved the species diversity in plant and mammalian.


[Treatment practices in the management of patients with bipolar disorder in France. The TEMPPO study].
TEMPPO is an observational, cross-sectional and multicentre study, initiated in the French metropolitan territory in 2009. Set up from a random sample of 135 psychiatrists, it has observed the procedures for therapeutic management of a population (n=619) of their outpatients (respectively 197 and 422 in public and private practice) with bipolar disorder type I or II disorders (DSM-IV). The patients who were followed were mostly very sick. Every patient received a pharmacological treatment. The prescription included at least one mood stabilizer or an antipsychotic (71 % atypical) in 78 % and 56 % of cases respectively. Treatment regimen changes were frequent (61 % of patients had at least one change in treatment during the last 12 months). A single molecule by therapeutic class was generally prescribed. The presence of an antipsychotic in combination therapy was often associated with the severity or difficulty of care of the patient (mixed states, severity of the global functioning impairment, manic states, high number of hospitalizations and history of suicide attempt). The combination of two antipsychotics is found only in the difficult situations of manic states. Patients with severe depressive phase are those who benefit from the combination mood stabilizer+antipsychotic+antidepressant (16 % of the sample). In this study, the prescription of antidepressants significantly differs from recommendations for good prescribing practices. Indeed antidepressants were commonly prescribed in mixed-phase (63 %), particularly as a monotherapy in 5 % of cases. It was also found in patients in euthymic phase (48 %), manic phase (12 %) and hypomanic phase (29 %). The prescription of atypical antipsychotics (monotherapy or combination) is now fully established in the management of all phases of the disease. The importance of non-pharmacological treatment is acknowledged by psychiatrists and proposed whether a psychotherapeutic support, information about the disease and/or lifestyle changes. The data collected in this study allowed to demonstrate that the participant psychiatrists have a pharmacological management of patients with bipolar disorder mostly in line with national and international guidelines.


Echocardiography. Congenital heart disease.
Echocardiography can be used to identify malformations of the heart and to assess the degree of cardiac compensation that occurs with congenital heart disease. Integration of clinical and ultrasound data will generally allow a diagnosis to be made noninvasively. Contrast echocardiography may delineate intracardiac shunting.


Simple decompression versus anterior subcutaneous and submuscular transposition of the ulnar nerve for cubital tunnel syndrome: a meta-analysis.
Optimal surgical management of cubital tunnel syndrome remains uncertain despite the publication of numerous case series, observational studies, systematic reviews, and, in recent years, randomized controlled studies. The purpose of this meta-analysis was to compare simple decompression to anterior transposition of the ulnar nerve for the treatment of this condition, using comparative trials and randomized controlled trials. Computerized database searches of MEDLINE, EMBASE, Cochrane Central, and all relevant surgical archives were performed. Studies involving adults with cubital tunnel syndrome in whom surgical intervention was simple decompression or anterior transposition (subcutaneous or submuscular) were included. Analysis was limited to randomized controlled trials and comparative observational studies. Included studies were assessed for quality, heterogeneity, and publication bias. Odds ratios of clinical improvement comparing simple decompression to anterior transposition (submuscular or subcutaneous) were calculated for each study. Ten studies involving a total of 449 simple decompressions, 342 subcutaneous transpositions, and 115 submuscular transpositions were included. There was little evidence of publication bias or statistical study heterogeneity. Odds of improvement with simple decompression versus anterior transposition were 0.751, 95% confidence interval (0.542, 1.040). Subanalyses on the basis of transposition technique (subcutaneous or submuscular) and study quality did not render a statistically significant result. This report represents the best cumulative evidence to date examining the surgical management of cubital tunnel syndrome. In this study, we found no statistically significant difference, but rather a trend toward an improved clinical outcome with transposition of the ulnar nerve as opposed to simple decompression. Additional prospective, randomized studies that use reproducible preoperative and postoperative objective measures might add statistical power to this finding.


Palmatine ameliorates Helicobacter pylori-induced chronic atrophic gastritis by inhibiting MMP-10 through ADAM17/EGFR.
Palmatine (Pal), a plant-based isoquinoline alkaloid, was initially isolated from Coptidis Rhizoma (CR, Huanglian in Chinese) and considered to be a potential non-antibiotic therapeutic agent that can safely and effectively improve Helicobacter pylori (H. pylori) induced chronic atrophic gastritis (CAG). However, underlying mechanisms are unclear. In this study, we explored the protective effect of Pal on H. pylori induced CAG in vivo and in vitro. As a result, Pal alleviated the histological damage of gastric mucosa and the morphological changes of gastric epithelial cell (GES-1) caused by H. pylori. Furthermore, Pal significantly inhibited the expression of EGFR-activated ligand genes, including a disintegrin and metalloproteinase 17 (ADAM17) and heparin-binding epidermal growth factor-like growth factor (HB-EGF), and the proinflammatory factors, such as chemokine 16 (CXCL-16) and interleukin 8 (IL-8), were suppressed. In addition, Pal attenuated inflammatory infiltration of CD8+ T cells while promoted Reg3a expression to enhance host defense. Taken together, we concluded that Pal attenuated the MMP-10 dependent inflammatory response in the gastric mucosa by blocking ADAM17/EGFR signaling, which contributed to its gastrointestinal protective effect.


A first glimpse into the pattern and scale of gene transfer in Apicomplexa.
Reports of plant-like and bacterial-like genes for a number of parasitic organisms, most notably those within the Apicomplexa and Kinetoplastida, have appeared in the literature over the last few years. Among the apicomplexan organisms, following discovery of the apicomplexan plastid (apicoplast), the discovery of plant-like genes was less surprising although the extent of transfer and the relationship of transferred genes to the apicoplast remained unclear. We used new genome sequence data to begin a systematic examination of the extent and origin of transferred genes in the Apicomplexa combined with a phylogenomic approach to detect potential gene transfers in four apicomplexan genomes. We have detected genes of algal nuclear, chloroplast (cyanobacterial) and proteobacterial origin. Plant-like genes were detected in species not currently harbouring a plastid (e.g. Cryptosporidium parvum) and putatively transferred genes were detected that appear to be unrelated to the function of the apicoplast. While the mechanism of acquisition for many of the identified genes is not certain, it appears that some were most likely acquired via intracellular gene transfer from an algal endosymbiont while others may have been acquired via horizontal gene transfer.


Dynamic Pituitary-Adrenal Interactions in the Critically Ill after Cardiac Surgery.
Patients with critical illness are thought to be at risk of adrenal insufficiency. There are no models of dynamic hypothalamic-pituitary-adrenal (HPA) axis function in this group of patients and thus current methods of diagnosis are based on aggregated, static models. To characterize the secretory dynamics of the HPA axis in the critically ill (CI) after cardiac surgery. Mathematical modeling of cohorts. Cardiac critical care unit. 20 male patients CI at least 48 hours after cardiac surgery and 19 healthy (H) male volunteers. None. Measures of hormone secretory dynamics were generated from serum adrenocorticotrophic hormone (ACTH) sampled every hour and total cortisol every 10 min for 24 h. All CI patients had pulsatile ACTH and cortisol profiles. CI patients had similar ACTH secretion (1036.4 [737.6] pg/mL/24 h) compared to the H volunteers (1502.3 [1152.2] pg/mL/24 h; P = .20), but increased cortisol secretion (CI: 14 447.0 [5709.3] vs H: 5915.5 [1686.7)] nmol/L/24 h; P < .0001). This increase in cortisol was due to nonpulsatile (CI: 9253.4 [3348.8] vs H: 960 [589.0] nmol/L/24 h, P < .0001), rather than pulsatile cortisol secretion (CI: 5193.1 [3018.5] vs H: 4955.1 [1753.6] nmol/L/24 h; P = .43). Seven (35%) of the 20 CI patients had cortisol pulse nadirs below the current international guideline threshold for critical illness-related corticosteroid insufficiency, but an overall secretion that would not be considered deficient. This study supports the premise that current tests of HPA axis function are unhelpful in the diagnosis of adrenal insufficiency in the CI. The reduced ACTH and increase in nonpulsatile cortisol secretion imply that the secretion of cortisol is driven by factors outside the HPA axis in critical illness.


Evaluation of D-dimer and factor VIII in cirrhotic patients with asymptomatic portal venous thrombosis.
D-dimer and factor VIII levels raise in advanced cirrhosis. We investigated the behavior and the diagnostic usefulness of D-dimer and factor VIII in cirrhotic patients with asymptomatic portal venous thrombosis. Factor VIII coagulant and D-dimer values were measured in 136 consecutive outpatients with stable cirrhosis divided according to Child-Pugh (CP) classification, who underwent color/power ultrasonography to detect portal thrombosis. Portal thrombosis was found in 33 patients (24.2%). In patients without thrombosis, factor VIII was significantly higher in CP class C compared with class A and B. Conversely, class C patients with portal thrombosis had lower factor VIII levels than those without thrombosis. In both groups, D-dimer was significantly increased in class C compared with class A and B. In class C, thrombotic patients showed higher D-dimer values than did patients without thrombosis. In class C, a D-dimer value > or = 0.55 microg/mL provided a sensitivity and a negative predictive value for portal thrombosis of 100%, and a factor VIII coagulant level < or = 80% showed a specificity and a negative predictive value of 76% and 84%, respectively. In class B, a D-dimer value > or = 0.225 microg/mL had a sensitivity of 89% and a negative predictive value of 82%. In conclusion, our study shows that factor VIII values increase in severe cirrhosis but significantly decrease in the presence of concomitant portal thrombosis, likely because of consumption during thrombosis; D-dimer is enhanced by both liver failure and portal thrombosis; in severe cirrhosis, normal D-dimer and factor VIII values may safely exclude the presence of asymptomatic portal thrombosis.


Effect of lysozyme solid-phase PEGylation on reaction kinetics and isoform distribution.
The combination of PEG-protein conjugation and chromatographic separation is generally known as solid-phase or on-column PEGylation and can provide advantages compared to commonly applied batch PEGylation. Even though the concept was already applied by several authors, changes in the isoform distribution compared to liquid-phase PEGylation due to sterically hindered PEGylation sites could not be confirmed. In this manuscript, a method for solid-phase PEGylation experiments in a 96-well plate format, using an automated liquid handling station is described. Applying size exclusion chromatography (SEC) and highly sensitive isoform analytics for mono-PEGylated lysozyme, we were able to investigate the differences in reaction kinetics and isoform distribution between adsorber-based PEGylation and modifications in free solution. Accordingly, solid-phase PEGylation with SP Sepharose FF and XL generally showed a reduced PEGylation reaction. In contrast to the predominant N-terminal PEGylation of lysozyme in liquid phase, a main modification of lys 97 and lys 116 was found for solid-phase experiments, which could be explained by binding orientations on corresponding adsorbent materials. Further experiments with varying amounts of bound protein additionally showed an influence on the isoform distribution of mono-PEGylated lysozyme.


Establishment of a highly metastatic buccal squamous cell carcinoma cell line from a Sprague-Dawley Rat.
The incidence of buccal squamous cell carcinoma (buccal SCC) is considered to be the second highest out of all oral cancers, but the unsatisfactory in vivo tumorigenicity and metastatic potential of the widely used cell lines have greatly delayed studies on the mechanisms of tumor progression. This study aimed to establish a highly metastatic buccal SCC cell line, which may serve a useful tool in buccal SCC research. Buccal SCC was induced by 4-nitroquinoline-1-oxide (4NQO) in Sprague-Dawley rats. The cancer samples were collected, and the tumor cells were purified in vitro. A highly aggressive cell line termed "Rca-B" was established by an invasion assay. Its proliferative ability, cell cycle distribution, baseline level of apoptosis, carcinogenicity and metastatic behavior in nude mice were investigated. To date, Rca-B cells have been stably cultured in vitro for more than 180 passages. These cells were polygonal or spindle-shaped, grew adhesively, and exhibited a stable epithelial phenotype as characterized by positive expression of cytokeratin. The population doubling time was 25.09 h. Cells in S-phase of the cell cycle accounted for 31.17% of the total number of cells, and the baseline level of apoptosis was 8.52%. The in vitro migration and invasion assays revealed highly aggressive features of Rca-B cells. In addition, the rate of xenograft formation was 100%, and the incidence of experimental lung metastasis was 81.8% in immunodeficient nude mice. The Rca-B cell line was established as a highly metastatic rat buccal SCC cell line, and its in-depth characterization, which includes malignant behaviors, allows for a wealth of functional studies on the molecular mechanisms of buccal SCC progression and targeted therapy.


Draft Genome Sequence of Methanol-Utilizing Methylophilus sp. Strain OH31, Isolated from Pond Sediment in Hokkaido, Japan.
Methylophilus sp. strain OH31 was isolated from the sediment of the Ohno pond at Hokkaido University. Strain OH31 utilizes methanol as its energy source. Here, we present the draft genome sequence of Methylophilus sp. strain OH31.


Mucinous and squamous metaplasia of the renal pelvis.
Mucinous and squamous cell metaplasia of the transitional cell epithelium occurs in response to chronic irritation and is predominantly found in the bladder. When the 2 forms of metaplasia occur simultaneously they usually are associated with malignancy. We report 2 cases of mucinous and squamous metaplasia of the epithelium of the renal pelvis that were not associated with malignancy. This is believed to be the fourth report of this divergent metaplasia. The mechanism for these changes is discussed.


The ecology of horse cyathostomin infective larvae (Nematoda-Cyathostominae) in tropical southeast Brazil.
Experimental studies about the recovery, survival and migration to pasture of cyathostomin infective larvae (L(3)) from fresh feces depositions were conducted from February 2005 to March 2007 in a tropical region of southeast Brazil. Grass and feces were collected weekly at 8 a.m., 1 and 5 p.m. and processed by the Baermann technique. Multivariate analysis (principal components method) showed the influence of time and environmental variables on the number of infective larvae recovered from the feces and pasture. In the rainy period (October-March), more infective larvae were recovered on the feces and grass apex. In contrast, in the dry period (April-September), the recovery was higher only on the grass base, as well as the L(3) survival on feces and grass. More larvae were recovered at 8 a.m., except from the grass apex, where the highest recovery was at 1 p.m. Few studies investigating the seasonal transmission of equine cyathostomin have been conducted in South American tropical climates. These results demonstrate that in tropical conditions L(3) are available on feces and pasture throughout the year. Knowledge of climatic influences on the development and survival of L(3) is crucial to designing integrated parasite control programs that provide effective protection while slowing the development of anthelmintic resistance.


Screening for cervical cancer in Africa: A proposal of a different combination of VIA test and cervical smear in Uganda.
To evaluate the efficacy of visual inspection with acetic acid (VIA) screening combined with a cervical smear in Uganda. Nine screening campaigns were held in Uganda between January 2011 and October 2019. In the last three campaigns, a new approach was used: the cervical smear was performed before the VIA test and, in case of a positive VIA test, the slide was sent for examination. The data collected were divided into two groups: the first six campaigns and the last three campaigns. During the study period, 10 520 women were screened, of whom 911 had a positive VIA test. The VIA test showed 84.2% false positives. In the first group, the VIA test was positive in 516 women, of whom 93% were referred for further examinations. In the second group, the VIA test was positive in 395 women, but the cervical smear was positive in only 65 women. Thus, only 16.5% women were referred for further examinations. Combining cervical smear, VIA test, and slide analysis in positive VIA tests may allow women who need treatment to be selected more effectively, while waiting for other more expensive solutions to become more affordable for this setting.


Nodular Human Lagochilascariasis Lesion in Hunter, Brazil.
Lagochilascariasis is a rare helminthic infection caused by Lagochilascaris minor nematodes and found in Latin America; most cases are reported in the Amazon region. We report on a case observed in a hunter in southern Brazil and describe scanning electron microscopy results for L. minor adult forms.


A biology-based approach for quantitative structure-activity relationships (QSARs) in ecotoxicity.
Quantitative structure-activity relationships (QSARs) for ecotoxicity can be used to fill data gaps and limit toxicity testing on animals. QSAR development may additionally reveal mechanistic information based on observed patterns in the data. However, the use of descriptive summary statistics for toxicity, such as the 4-day LC50 for fish, introduces bias and ignores valuable kinetic information in the data. Biology-based methods use all of the toxicity data in time to derive time-independent and unbiased parameter estimates. Such an approach offers whole new opportunities for mechanism-based QSAR development. In this paper, we apply the hazard model from DEBtox to analyse survival data for fathead minnows (Pimephales promelas). Different modes of action resulted in different patterns in the parameter estimates, and therefore, the toxicity data by themselves reveal insight into the actual mechanism of toxic action.


Differences in Overweight or Obesity, Changes in Dietary Habits after Studying Abroad and Sleep Quality by Acculturative Degree among Asian Foreign Students: A Cross Sectional Pilot Study.
The number of foreign students is increasing worldwide, and they suffer from acculturation to different environments or cultures. This pilot study examined the difference in overweight or obesity, changes in dietary habits after studying abroad and sleep quality according to acculturative degree among 225 Asian foreign students in South Korea. Most subjects (61.8%) experienced a low acculturative degree. The change in dietary habits after studying abroad showed a significant difference according to the acculturative degree (p < 0.001); however, there were no differences observed in sleep quality (p = 0.090) and prevalence of overweight or obesity according to acculturative degree (p = 0.101). Interestingly, a difference in the risk for being overweight or obese by sleep quality after being stratified into groups according to acculturative degree was observed. Among the groups with a low acculturative degree, subjects reporting poor sleep quality had a 2.875-fold (95% CI = 1.167−7.080) higher risk of being overweight or obese than those reporting good sleep quality. However, the risk of being overweight or obese was not different among the high acculturative group regardless of their sleep quality. The results showed that the degree of acculturation could influence the risk of being overweight or obese according to sleep quality among Asian foreign students.


Barriers to conducting clinical research in reproductive medicine: United States of America.
A decrease in National Institute of Health funding and an increase regulations are significant barriers in conducting research in the United States of America.


Management guideline for Werner syndrome 2020. 6. Skin ulcers associated with Werner syndrome: Prevention and non-surgical and surgical treatment.
To provide guidelines on the diagnosis, treatment, and prevention of skin ulcers in Werner syndrome. This article was based on literature from 1996, when WRN was identified as a gene responsible for Werner syndrome, and we evaluated several authentic clinical cases of genetically diagnosed patients. There were 63 patients with Werner syndrome in the Japanese reports retrieved from Medical Online between January 1996 and December 2017. There were 56 patients with Werner syndrome in English reports written by Japanese authors and retrieved from PubMed during the same period. Records on skin ulcers were found in 27 (43%) out of 63 patients and 22 (40%) out of 56 patients from the Japanese and English reports, respectively. The reported ulcers were often located at the distal one-third of the lower legs. There were 8 patients with callosities in the foot in the Japanese reports and 9 patients in the English reports. A skin ulcer in Werner syndrome is generally intractable. Weight-bearing ulcers or callosity should be critically assessed in surgical procedures because they have effects on patient pain and gait. By adopting a recently advanced technique to facilitate wound healing, the cases of ulcers that were difficult to treat and those requiring major operations can be closed with minimally invasive surgery. Skin ulcers in Werner syndrome are refractory, and they lead to reduced quality of life of patients. A callosity in Werner syndrome is an important therapeutic target for the prevention of ulcers. Geriatr Gerontol Int 2021; 21: 153-159.


Self-assembly of heterobimetallic neutral macrocycles incorporating ferrocene spacer groups: spectroelectrochemical analysis of the double two-electron oxidation of a molecular rectangle.
Two Pt(4)-Fe(2) mixed-metal neutral assemblies, 4 and 5, incorporating four bis(triethylphosphine)platinum(II) centers, two flexible bridging 1,1'-ferrocenedicarboxylates, and two rigid 2,9-phenanthrenediyl (4) or 1,8-anthracenediyl (5) bridges, have been synthesized. X-ray characterization of 4 and 5 reveals the formation of discrete and highly symmetrical heterobimetallic neutral species possessing a rhomboidal and rectangular shape, respectively. The rectangular molecules, 5, could be reversibly oxidized in two two-electron steps, separated by 0.21 V. Spectroelectrochemistry in the UV-vis-NIR region confirms the ferrocene groups as primary oxidation sites; however, the intermediate 5(2+) is EPR silent even at 4 K due to enhanced EPR relaxation involving the oxidizable 1,8-anthracenediyl linkers.


Ultrastructure and stereology of leukocytes and platelets of normal foxes and a fox with a Chediak-Higashi-like syndrome.
Peripheral blood leukocytes and platelets from five normal foxes (Vulpes vulpes) and a fox with phenotypical characteristics of Chediak-Higashi syndrome (CHS) were examined by electron microscopy. Lymphocytes, monocytes, neutrophils, eosinophils, and platelets from the affected fox contained giant membrane-bound granules that resembled lysosomes. In eosinophils and neutrophils from the affected fox and a normal fox, relative cell volume occupied by granules and number of granules per unit area were calculated. Relative cell volume occupied by granules was the same in both foxes, but there were significantly fewer granules per unit area in the affected fox. This result is consistent with the idea that the giant granules arose from fusion of pre-existing, normal-sized granules, as occurs in CHS. In platelets from the affected fox, no osmiophilic granules were seen. Our findings agree with those from studies of CHS-affected blood cells in other species.


A statistical mechanical treatment of fatty acyl chain order in phospholipid bilayers and correlation with experimental data. B. Dipalmitoyl-3-sn-phosphatidylcholine.
In order to help bridge the conceptual gap between experimental data on chains of phospholipid molecules and their microscopic organization, a theoretical model has proposed in a preceding paper. The intentions associated with the new theory were to describe a model able to reproduce accurately the experimental data. This capability is essential to monitor some of the mechanisms behind the physical data. The results presented here show first that, provided a suitable fitting of the phenomenological parameters entailed in the model, the theory indeed gives good agreement with experimental data (2H-NMR, neutron scattering, calorimetry) obtained for a dipalmitoyl-3-sn-phosphatidylcholine bilayer. This property of the model is then specifically used to describe the nature of the perturbing effects of local anaesthetics and cholesterol on the organization of the acyl chains and to correlate these effects with the experimental data. Finally the theoretical model is used to supplement experimental data by describing the acyl chain organization in terms of the most probable spectrum of chain conformations. Predictions are made about the one-, two- and three-dimensional mean spatial characteristics of the acyl chains.


Developmental exposure to a brominated flame retardant: an assessment of effects on physiology, growth, and reproduction in a songbird, the zebra finch.
Mixtures of polybrominated diphenyl ethers (PBDEs) have been widely used as additive flame retardants, and BDE-99 is one of the most predominant congeners found in the environment. BDE-99 has been reported in avian samples worldwide, yet knowledge of its toxicity to birds is minimal. We assessed the short- and long-term effects of nestling exposure to environmentally relevant levels of BDE-99 in a model passerine, the zebra finch. Early exposure to BDE-99 did not affect hematocrit, oxidative stress, or thyroid hormones in either the juvenile or adult stages, and there were no effects on chick growth or survival. BDE-99 exposure caused a dose-dependent delay in timing of reproduction, but there were no other effects on reproductive success. In zebra finches, endpoints related to reproductive behavior appear to be the most sensitive to BDE-99. However, passerines overall appear to be less sensitive than birds of prey or mammals to PBDE exposure.


A dual shaping mechanism for postsynaptic ephrin-B3 as a receptor that sculpts dendrites and synapses.
As the neural network becomes wired, postsynaptic signaling molecules are thought to control the growth of dendrites and synapses. However, how these molecules are coordinated to sculpt postsynaptic structures is less well understood. We find that ephrin-B3, a transmembrane ligand for Eph receptors, functions postsynaptically as a receptor to transduce reverse signals into developing dendrites of mouse hippocampal neurons. Both tyrosine phosphorylation-dependent GRB4 SH2/SH3 adaptor-mediated signals and PSD-95-discs large-zona occludens-1 (PDZ) domain-dependent signals are required for inhibition of dendrite branching, whereas only PDZ interactions are necessary for spine formation and excitatory synaptic function. PICK1 and syntenin, two PDZ domain proteins, participate with ephrin-B3 in these postsynaptic activities. PICK1 has a specific role in spine and synapse formation, and syntenin promotes both dendrite pruning and synapse formation to build postsynaptic structures that are essential for neural circuits. The study thus dissects ephrin-B reverse signaling into three distinct intracellular pathways and protein-protein interactions that mediate the maturation of postsynaptic neurons.


Familial Mediterranean fever associated frosted branch angiitis, retinal vasculitis and vascular occlusion.
To analyse the entity of retinal vasculitis, including frosted branch angiitis (FBA), or retina vascular occlusion in patients with familial Mediterranean fever (FMF). Retrospective collaborative case series using invitation by email to uveitis specialists around the Mediterranean basin. This series was combined with a literature review. Exclusion criteria included infectious diseases, Behçet's disease or other autoimmune diseases. A total of 16 patients (21 eyes) had FMF and retinal vasculitis (FBA 11 patients, mild retinal vasculitis 5 patients). The mean age at onset of vasculitis was 29.5 ± 13.4 (range 9-62) with a female to male ratio of 9 to 7. In 19 eyes treated with various forms of corticosteroid and/or immunosuppression, the mean initial spectacle-corrected visual acuity improved from 6/194 to 6/10.5 at the last mean follow-up of 29.0 ± 34.9 months (p < 0.001). The most common FEVR mutations were M680I and M694V. In addition, retinal vascular occlusions included one case of central retinal artery occlusion and one case of branch retinal artery occlusion. FBA and milder forms of retinal vasculitis are associated with FMF. Therapy involves an increase in colchicine dosage in early cases, a long period of oral corticosteroid, intravitreal dexamethasone implant or periocular corticosteroid in select cases, and combination therapy with systemic immunosuppression in severe cases. FMF needs to be included in the differential diagnosis of retinal vasculitis.


[Effect of carbon disulfide on peripheral blood leukocytes. I. Effect of carbon disulfide on in vitro chromosome structure and division capability of leukocytes in man].
The peripheral blood leukocytes in normal subjects were cultured according to Moorhead with addition of CS2 (0,75 microliter/ml of culture). It has been found that CS2 decreases the mitotic index, and in some cultures inhibits totally the cell division. Moreover, it causes structural disturbances of chromosomes being of pre- and postreplicative character as well as their viscous degeneration, lesser spiralization and sometimes pulverization. The presence of greater amount of erythrocytes of the donor's blood in the culture markedly diminished the intensity of these changes.


An innate IL-25-ILC2-MDSC axis creates a cancer-permissive microenvironment for Apc mutation-driven intestinal tumorigenesis.
Interleukin-25 (IL-25) and group 2 innate lymphoid cells (ILC2s) defend the host against intestinal helminth infection and are associated with inappropriate allergic reactions. IL-33-activated ILC2s were previously found to augment protective tissue-specific pancreatic cancer immunity. Here, we showed that intestinal IL-25-activated ILC2s created an innate cancer-permissive microenvironment. Colorectal cancer (CRC) patients with higher tumor IL25 expression had reduced survival and increased IL-25R-expressing tumor-resident ILC2s and myeloid-derived suppressor cells (MDSCs) associated with impaired antitumor responses. Ablation of IL-25 signaling reduced tumors, virtually doubling life expectancy in an Apc mutation-driven model of spontaneous intestinal tumorigenesis. Mechanistically, IL-25 promoted intratumoral ILC2s, which sustained tumor-infiltrating MDSCs to suppress antitumor immunity. Therapeutic antibody-mediated blockade of IL-25 signaling decreased intratumoral ILC2s, MDSCs, and adenoma/adenocarcinoma while increasing antitumor adaptive T cell and interferon-γ (IFN-γ)-mediated immunity. Thus, the roles of innate epithelium-derived cytokines IL-25 and IL-33 as well as ILC2s in cancer cannot be generalized. The protumoral nature of the IL-25-ILC2 axis in CRC highlights this pathway as a potential therapeutic target against CRC.


Complementation cell lines for viral vectors to be used in gene therapy.
Viral vectors provide a highly efficient method for the transfer of foreign genes into a variety of quiescent or dividing eukaryotic cells from many animal origins. While recombinant vectors derived from an increasing number of mammalian viruses (herpes simplex virus, autonomous and non-autonomous parvoviruses, poxviruses, retroviruses, adenoviruses available today, vectors based on murine retroviruses and human adenoviruses constitute preferential candidates for the delivery of marker or therapeutic genes into human somatic cells. The availability of such vectors has made possible the recent transition of human gene therapy from laboratory benches to clinical settings. Most current recombinant vectors have been generated by deleting essential viral genes in order to make space available for the introduction of passenger genes. Such vectors are therefore unable to replicate in the absence of these critical gene products and their production relies on the development of stable complementation cell lines providingin trans the missing viral functions. Although complementation (or packaging) cell lines are available for both adenovirus and retrovirus vectors, their respective drawbacks still limit their use to research applications and phase I clinical trials. The future success or failure of human gene therapy will therefore rely on the production of improved generations of packaging cell lines that can produce safer and more efficient vectors which are fully adapted to large scale production and clinical applications.


Influence of porosity and temperature on light non-aqueous phase liquid diffusion in soils.
Soil characteristics play an important role in distribution of light non-aqueous phase liquid (LNAPL) spilled from buried pipeline, and enhanced understanding of distribution is significant to the effective design of soil and groundwater remediation strategies. Therefore, distribution of diesel in soils with different porosity and temperature on the temporal evolution of the diesel migration following the saturation profiles of the two-phase flow in soils were investigated in this study. The diffusion ranges, areas and volumes in both the radial as well as in axial directions of leaked diesel in soils with different porosity and temperature increased with time. Soil porosities played an important role in the distributions when soil temperatures had no effect on distributions of diesel in soils. The distribution areas were 0.385 m2, 0.294 m2, 0.213 m2, and 0.170 m2 at 60 min when the soils porosities were 0.1, 0.2, 0.3, and 0.4, respectively. The distribution volumes were 0.177 m3, 0.125 m3, 0.082 m3, 0.060 m3 at 60 min when the soils porosities were 0.1, 0.2, 0.3, and 0.4, respectively. But the distribution areas were 0.213 m2 at 60 min when the soil temperatures were 286.15 K, 296.15 K, 306.15 K and 316.15 K, respectively. The distribution volumes were 0.082 m3 at 60 min when the soil temperatures were 286.15 K, 296.15 K, 306.15 K and 316.15 K, respectively. The calculation formulas of distribution areas and volumes of diesel in soils with different porosity and temperature for developing prevention and control strategies in the future were fitted. The seepage velocities of diesel changed sharply around the leakage port and decreased from about 4.9 m/s to 0 within a few millimeters in soils with different porosity. Additionally, the diffusion ranges of leaked diesel in soils with different porosity were different, indicating that soil porosity had a significant impact on seepage velocities and pressures. The seepage velocities fields and pressures fields of diesel in soils with different temperature were same at the leakage velocity of 4.9 m/s. And the study could provide some supports for determination of the safety zone and formulation of emergency response plans for LNAPL leakage accidents.


An Easy-to-Use Prehospital Indicator to Determine the Severity of Suspected Heat-Related Illness: An Observational Study in the Tokyo Metropolitan Area.
Rapid hospital arrival decreases mortality risk in heat-related illnesses. We investigated an easy-to-use indicator of life-threatening severity of heat-related illnesses in a community setting to enable quick hospitalization by using data extracted from prehospital transportation records of a database from 2016 that included information on the clinical severity of suspected heat-related illnesses in patients (n = 2528) upon hospital arrival. Patient-related risk factors (adjusted odds ratio, aOR [95% confidence interval, CI]) included age, vital signs, location of the patient, and illness severity, and respiratory rate (3.34 [1.80-6.22]), heart rate (2.88 [1.57-5.29]), axillary body temperature (7.79 [4.02-15.1]), and consciousness level (38.3 [5.22-281.1]) were independent risk factors for heat-related illness severity. On-site blood pressure was not an independent factor for illness severity. Heart rate > 120 beats/min, respiratory rate > 24 breaths/min, and temperature > 38.6 °C (highest areas under the receiver operating characteristic curves [95% CI]: 0.80 [0.75-0.87]; 0.73 [0.67-0.81]; and 0.83 [0.77-0.91], respectively) predicted life-threatening illness severity. Changes in the vital signs of patients with heat-related illnesses, particularly tachycardia and tachypnea, constitute sensitive, easy-to-use indicators that facilitate rapid identification of severity by laypersons and transport of patients before aggravation to a life-threatening situation.


Effects of the bioactive peptides Ile-Pro-Pro and Val-Pro-Pro upon autonomic neurotransmission and blood pressure in spontaneously hypertensive rats.
The bioactive peptides Ile-Pro-Pro (IPP) and Val-Pro-Pro (VPP) are believed to improve blood pressure and arterial function. To gain a better understanding of the mechanisms underlying the action of these peptides, we investigated their effects upon autonomic neurotransmission and blood pressure in spontaneously hypertensive rats (SHR). Both IPP and VPP caused a significant reduction in cutaneous arterial sympathetic nerve activity (CASNA) and reduced mean arterial pressure (MAP); however, both of these effects were eliminated following sub-diaphragmatic vagotomy. On the other hand, captopril, an angiotensin-converting enzyme inhibitor, reduced MAP without changing CASNA, and maintained this hypotensive effect following vagotomy. Moreover, the effects of IPP and VPP upon CASNA were observed following gastric administration but not by duodenal administration. These results suggest that IPP and VPP reduce CASNA via the stomach and afferent vagus nerve, thus causing reductions in MAP in SHR.


Colocalization of neurokinin-1, N-methyl-D-aspartate, and AMPA receptors on neurons of the rat nucleus tractus solitarii.
Substance P (SP) and glutamate are implicated in cardiovascular regulation by the nucleus tractus solitarii (NTS). Our earlier studies suggest that SP, which acts at neurokinin 1 (NK1) receptors, is not a baroreflex transmitter while glutamate is. On the other hand, our recent studies showed that loss of NTS neurons expressing NK1 receptors leads to loss of baroreflex responses and increased blood pressure lability. Furthermore, studies have suggested that SP may interact with glutamate in the NTS. In this study, we sought to test the hypothesis that NK1 receptors colocalize with glutamate receptors, either N-methyl-d-aspartate (NMDA) receptors or AMPA receptors or both in the NTS. We performed double-label immunofluorescent staining for NK1 receptors and either N-methyl-d-aspartate receptor subunit 1 (NMDAR1) or AMPA specific glutamate receptor subunit 2 (GluR2) in the rat NTS. Because vesicular glutamate transporter 2 (VGLUT2) containing fibers are prominent in portions of the NTS where cardiovascular afferent fibers terminate, we also performed double-label immunofluorescent staining for NK1 receptors and VGLUT2. Confocal microscopic images showed that NK1 receptors-immunoreactivity (IR) and NMDAR1-IR colocalized in the same neurons in many NTS subnuclei. Almost all NTS neurons positive for NK1 receptor-IR also contained NMDAR1-IR, but only 53.4% to 74.8% of NMDAR1-IR positive neurons contained NK1 receptors-IR. NK1 receptor-IR and GluR2-IR also colocalized in many neurons in NTS subnuclei. A majority of NK1 receptor-IR positive NTS neurons also contained GluR2-IR, but only 45.8% to 73.9% of GluR2-IR positive NTS neurons contained NK1 receptors-IR. Our results also showed that fibers labeled for VGLUT2-IR were in close apposition to fibers and neurons labeled for NK1 receptor-IR. The data support our hypothesis, provide an anatomical framework for glutamate and SP interactions, and may explain the loss of baroreflexes when NTS neurons, which could respond to glutamate as well as SP, are killed.


Effects of exercise interventions in Alzheimer's disease: A meta-analysis.
The aim of this study was to investigate the clinical efficacy of exercise intervention in the treatment of patients with Alzheimer's disease (AD) by meta-analysis. From January 2000 to January 2022, PubMed, Web of Science, Embase, CNKI, and WanFang databases were searched for all studies on the clinical efficacy of exercise intervention in the treatment of AD patients. Stata 17.0 statistical software was used for meta-analysis. Specifically, data of 983 patients were subjected to meta-analysis, including 463 patients in the control group (conventional drug therapy) and 520 patients in the treatment group (physical exercise on the basis of conventional therapy). The results of meta-analysis showed that Mini-Mental State Examination (MMSE) score and Activities of Daily Living Scale (ADL) score in the treatment group were significantly higher than those in the control group. Further subgroup analysis of exercise intervention >16 weeks found that MMSE and ADL scores in the treatment group were significantly higher than those in the control group. Subgroup analysis of exercise intervention ≤16 weeks demonstrated that MMSE and ADL in the treatment group were higher than those in the control group. In addition, the treatment group had a significant lower Neuropsychiatric Inventory (NPI) score compared with the control group (SMD = -0.76, 95% CI (-1.37, -0.16), p = .013); subgroup analysis showed that the NPI score in the treatment group were lower than that in the control group when exercise intervention was >16 weeks [SMD = -1.01, 95% CI (-1.99, -0.04), p = .042] and ≤16 weeks [SMD = 0.43, 95% CI (-0.82, -0.03), p = .034]. Exercise intervention can improve the neuropsychiatric symptoms, activities of daily living and cognitive function of AD patients, but the improvement is not significant in case of exercise intervention ≤16 weeks.


Effect of spinal versus epidural anaesthesia with 0.5% bupivacaine on lower limb blood flow.
Changes in the haemodynamics of the lower extremities, big toe temperature, blood pressure and heart rate were studied in 20 patients undergoing spinal or epidural anaesthesia for transurethral surgery. Calf blood flow was determined by strain gauge plethysmography (SGP) and Doppler ultrasound. Bupivacaine 0.5% was injected at the L3-L4 interspace, the dose being 3-4 ml (mean 3.6) in the spinal and 17-20 ml (mean 18.6) in the epidural group. The number of sensory blocked segments 30 min after anaesthesia was 12.7 +/- 0.7 (mean +/- s.e.mean) and 14.4 +/- 0.7, respectively. Only minor decreases in blood pressure were noted following the blocks. Heart rate remained virtually unchanged. The increase in skin temperature was more pronounced (P less than 0.01) following epidural (mean 8 degrees C) than spinal anaesthesia (mean 4 degrees C). In addition, the arterial blood flow was significantly higher (P less than 0.05) following epidural than spinal block (means 3.5 and 2.2 ml/100 ml/min, respectively). The venous capacity and maximum venous outflow remained practically unchanged in both groups. Obviously, epidural anaesthesia with bupivacaine causes a more intensive sympathetic block than does spinal anaesthesia. As probably no venous pooling occurred, when examined by SGP and Doppler ultrasound, neither of the blocks is likely to contribute to the initiation of deep vein thrombosis.


Thyroxine preferentially stimulates transcription by isolated neuronal nuclei in the developing rat brain cortex.
The administration of thyroxine to neonatal rats stimulates RNA synthesis by neuronal nuclei isolated from the developing rat brain cortex. Glial nuclei are relatively resistant to thyroxine treatment. The activity of neuronal RNA polymerase II is particularly stimulated by the hormone. Thyroxine also affects neuronal chromatin structure as shown by changes in the relative proportion of different subnuclear fractions obtained by gentle micrococcal nuclease digestion of nuclei from hormone-treated rats.


Diagnosis of retro-esophageal right aortic arch by computed tomography.
A case of retro-esophageal right aortic arch was clearly demonstrated by computed tomography and confirmed by arch aortography.


Efficacy, Safety, and Tolerability of Centanafadine Sustained-Release Tablets in Adults With Attention-Deficit/Hyperactivity Disorder: Results of 2 Phase 3, Randomized, Double-blind, Multicenter, Placebo-Controlled Trials.
Centanafadine is an inhibitor of norepinephrine, dopamine, and serotonin reuptake transporters under investigation for the treatment of attention-deficit/hyperactivity disorder (ADHD). Two phase 3 randomized, double-blind, placebo-controlled, parallel-group studies of 200 mg/d or 400 mg/d centanafadine sustained-release tablets versus placebo included adults (18-55 years of age) with a diagnosis of ADHD. The primary and key secondary efficacy endpoints were the change from baseline at day 42 in the Adult ADHD Investigator Symptom Rating Scale (AISRS) total score and the Clinical Global Impression-Severity of Illness Scale, respectively. Subjects randomized in study 1 (centanafadine 200 mg/d, n = 149; centanafadine 400 mg/d, n = 149; placebo, n = 148) and study 2 (centanafadine 200 mg/d, n = 145; centanafadine 400 mg/d, n = 143; placebo, n = 142) had moderate to severe ADHD (mean AISRS total score, 38.7 [SD, 6.8] across both studies). At day 42, statistically significant least-squares mean differences in AISRS total score were observed in favor of centanafadine versus placebo in study 1 (200 mg/d: -3.16, P = 0.019; 400 mg/d: -2.74, P = 0.039) and study 2 (200 mg/d: -4.01, P = 0.002; 400 mg/d: -4.47, P = 0.001). Effect sizes versus placebo were -0.28 for 200 mg/d and -0.24 for 400 mg/d in study 1 and -0.37 for 200 mg/d and -0.40 for 400 mg/d in study 2. The overall rate of treatment-emergent adverse events (TEAEs) was low, but there was a small increase in TEAE occurrence with increasing dose. Incidences of serious TEAEs and abuse potential-related AEs were low. These are the first large-scale studies to demonstrate the efficacy and safety profiles of 200 mg/d and 400 mg/d centanafadine in adults with ADHD.


IL-1 gene polymorphisms and genetic susceptibility of gallbladder cancer in a north Indian population.
Long-standing gallstones are generally present in 65-80% patients of gallbladder cancer (GBC). It has also been suggested that inflammation caused by gallstones may be involved in the development of GBC. Interleukin-1 receptor antagonist (IL-1RN) and interleukin-1 beta (IL-1B) are proinflammatory cytokine genes at the interleukin-1 locus, and polymorphisms of these genes have been associated with various inflammatory diseases. The aim of this study was to investigate whether polymorphism in the IL-1RN and IL-1B genes are associated with GBC patients with and without gallstones. Polymorphisms within the IL-1RN 86-base pair VNTR (variable number tandem repeat) and IL-1B (-511C --> T) were genotyped using polymerase chain reaction (PCR) and PCR restriction fragment length polymorphism in 166 healthy subjects and 124 GBC patients. The frequency of the IL-1RN, VNTR 2/2 genotype was significantly higher in GBC patients [P = 0.017; odds ratio (OR) = 3.25; 95% confidence interval (CI) = 1.23-8.58]. CC genotype and 'C' allele of the -511IL-1B C --> T polymorphism also showed high risk for GBC (P = 0.033; OR = 3.36; 95%CI = 1.52-7.43, P = 0.047, OR = 1.41; 95%CI = 1.00-1.98, respectively). The higher cancer risk due to the IL-1RN, 2/2 genotype was observed in GBC patients with or without stones (P = 0.038; OR = 3.58; 95%CI = 1.08-11.65, P = 0.035; OR = 3.33; 95%CI = 1.08-10.61). Risk due to the CC genotype of IL-1B, however, was confined to GBC patients harboring gallstones (P = 0.0003; OR = 6.92; 95%CI = 2.65-18.03). The haplotype 1/C of IL-1RN and IL-1B was found to confer a significantly enhanced risk of GBC in cancer patients with gallstones (P = 0.022; OR = 2.19; 95%CI = 1.12-4.27), while higher risk resulting from 2/C haplotype was of borderline significance (P = 0.061; OR = 3.04; 95%CI = 0.95-9.70). Individuals with 1/C and 2/C haplotypes of IL-1RN VNTR and -511IL-1B C --> T polymorphisms were more susceptible to develop GBC with gallstones compared to healthy controls in north India.


Evaluation of the reported data linkage process and associated quality issues for linked routinely collected healthcare data in multimorbidity research: a systematic methodology review.
The objective of this systematic review was to examine how the record linkage process is reported in multimorbidity research. A systematic search was conducted in Medline, Web of Science and Embase using predefined search terms, and inclusion and exclusion criteria. Published studies from 2010 to 2020 using linked routinely collected data for multimorbidity research were included. Information was extracted on how the linkage process was reported, which conditions were studied together, which data sources were used, as well as challenges encountered during the linkage process or with the linked dataset. Twenty studies were included. Fourteen studies received the linked dataset from a trusted third party. Eight studies reported variables used for the data linkage, while only two studies reported conducting prelinkage checks. The quality of the linkage was only reported by three studies, where two reported linkage rate and one raw linkage figures. Only one study checked for bias by comparing patient characteristics of linked and non-linked records. The linkage process was poorly reported in multimorbidity research, even though this might introduce bias and potentially lead to inaccurate inferences drawn from the results. There is therefore a need for increased awareness of linkage bias and transparency of the linkage processes, which could be achieved through better adherence to reporting guidelines. CRD42021243188.


Atomistic molecular simulations of protein folding.
Theory and experiment have provided answers to many of the fundamental questions of protein folding; a remaining challenge is an accurate, high-resolution picture of folding mechanism. Atomistic molecular simulations with explicit solvent are the most promising method for providing this information, by accounting more directly for the physical interactions that stabilize proteins. Although simulations of folding with such force fields are extremely challenging, they have become feasible as a result of recent advances in computational power, accuracy of the energy functions or 'force fields', and methods for improving sampling of folding events. I review the recent progress in these areas, and highlight future challenges and questions that we may hope to address with these methods. I also attempt to place atomistic models into the context of the energy landscape view of protein folding, and coarse-grained simulations.


Shame among unemployed men.
Explicit criteria for rating feelings of shame were applied in a group of 80 unemployed men. Shame was prominent in 15% of the sample and milder features were present in a further 10%. It was strongly associated with the presence of minor affective disorder and with some, but not all, of the vulnerability factors associated with the latter. Possible explanations for these associations are discussed.


Modulation of aromatase activity by testosterone in transplants of fetal rat hypothalamus-preoptic area.
Conversion of androgens to estrogens by neural aromatase appears to be a prerequisite for a variety of effects of androgens on brain function, including sexual differentiation. Activity of aromatase is modulated by its substrate testosterone (T) in adult hypothalamus-preoptic area (HPOA), resulting in significantly higher levels in the male. Perinatal sex differences in activity have also been observed in hypothalamus, POA and/or amygdala. However, it is not known if higher levels in the perinatal male occur in response to circulating androgens, nor whether early exposure to gonadal steroids is necessary to establish either basal levels or the androgen sensitivity of aromatase activity in the adult brain. In order to investigate the influence of early steroid exposure on the development of neural aromatase activity, embryonic day (E)17 fetal HPOA was transplanted onto the choroidal pia overlying the superior colliculus of adult ovariectomized-adrenalectomized (OVX-ADX) Holtzman female hosts. In the first experiment, the effect of androgen exposure on aromatase activity in mature HPOA transplants was determined. Hosts received T-filled silastic capsules or underwent sham surgery 7 weeks after transplantation and were sacrificed 7 days later. Aromatase activity was determined in vitro using the stereospecific production of 3H2O from [1 beta-3H]androstenedione as an index of estrogen formation. Aromatase activity was significantly greater in T-treated HPOA versus controls (P less than 0.005). Activity was not affected by the sex of the donor fetus. In the second experiment, the effect of androgen exposure during the first 6 days following transplantation of E17 HPOA (corresponding to the last gestational week) was determined.(ABSTRACT TRUNCATED AT 250 WORDS)


The pattern of evolution of smaller-scale gene duplicates in mammalian genomes is more consistent with neo- than subfunctionalisation.
Gene duplication and the accompanying release of negative selective pressure on the duplicate pair is thought to be the key process that makes functional change in the coding and regulatory regions of genomes possible. However, the nature of these changes remains unresolved. There are a number of models for the fate of gene duplicates, the two most prominent of which are neofunctionalisation and subfunctionalisation, but it is still unclear which is the dominant fate. Using a dataset consisting of smaller-scale (tandem and segmental) duplications identified from the genomes of four fully sequenced mammalian genomes, we characterise two key features of smaller-scale duplicate evolution: the rate of pseudogenisation and the rate of accumulation of replacement substitutions in the coding sequence. We show that the best fitting model for gene duplicate survival is a Weibull function with a downward sloping convex hazard function which implies that the rate of pseudogenisation of a gene declines rapidly with time since duplication. Our analysis of the accumulation of replacement substitutions per replacement site shows that they accumulate on average at 64% of the neutral expectation immediately following duplication and as high as 73% in the human lineage. Although this rate declines with time since duplication, it takes several tens of millions of years before it has declined to half its initial value. We show that the properties of the gene death rate and of the accumulation of replacement substitutions are more consistent with neofunctionalisation (or subfunctionalisation followed by neofunctionalisation) than they are with subfunctionalisation alone or any of the other alternative modes of evolution of smaller-scale duplicates.


[Use of ultrasonics in the fixation of autologous skin transplants].
Based upon his clinical experience the author proves advantages of the ultrasonic welding for the transplant fixation in skin plasty with using cyacrine as joining material.


Erratum: Mobile phone use while driving and the risk of collision: A study among preparatory year students at King Saud University, Riyadh, Saudi Arabia.
[This corrects the article on p. 102 in vol. 25, PMID: 29922110.].


Discovering and differentiating new and emerging clonal populations of Chlamydia trachomatis with a novel shotgun cell culture harvest assay.
Chlamydia trachomatis is the leading cause of preventable blindness and bacterial sexually transmitted diseases worldwide. Plaque assays have been used to clonally segregate laboratory-adapted C. trachomatis strains from mixed infections, but no assays have been reported to segregate clones from recent clinical samples. We developed a novel shotgun cell culture harvest assay for this purpose because we found that recent clinical samples do not form plaques. Clones were strain-typed by using outer membrane protein A and 16S rRNA sequences. Surprisingly, ocular trachoma reference strain A/SA-1 contained clones of Chlamydophila abortus. C. abortus primarily infects ruminants and pigs and has never been identified in populations where trachoma is endemic. Three clonal variants of reference strain Ba/Apache-2 were also identified. Our findings reflect the importance of clonal isolation in identifying constituents of mixed infections containing new or emerging strains and of viable clones for research to more fully understand the dynamics of in vivo strain-mixing, evolution, and disease pathogenesis.


Regulation of placental glucose transfer and consumption by fetal glucose production.
We studied ten normoglycemic [maternal glucose (GA) = 70 mg/dL] and six insulin-induced hypoglycemic (GA = 22 mg/dL) pregnant sheep to test the hypothesis that development of fetal glucose production (GPR) could help maintain fetal glucose concentration, limit uteroplacental-fetal glucose transfer (UPGT), and sustain uteroplacental glucose consumption (UPGC). Compared with the normoglycemic group, the hypoglycemic group demonstrated the following values: fetal glucose concentration (Ga) was 9.8 +/- 0.8 mg/dL (51% lower, p less than 0.01), uterine glucose uptake (UtGU) was 16.7 +/- 1.4 mg/min (54% lower, p less than 0.01), UPGT was 3.1 +/- 0.6 mg/min (81% lower, p less than 0.001), and UPGC was 13.6 +/- 1.4 mg/min (30% lower, p less than 0.05). The reduction in UPGC was significantly less (p less than 0.05) than the reductions in UPGT and UtGU. Fetal glucose utilization rate (GUR) was decreased 20% (p less than 0.05) to 3.99 +/- 0.35 mg/min/kg. A further decrease in GUR was prevented by the appearance of fetal GPR of 2.82 +/- 0.32 mg/min/kg (p less than 0.05) compared with negligible GPR in the normoglycemic group. UPGT and UPGC in both groups were not influenced by maternal or fetal insulin infusions as long as Ga did not change; however, fetal glucose infusion that increased Ga increased UPGC in both groups. We conclude that, during chronic maternal hypoglycemia, increased fetal GPR limits the simultaneous decrease in fetal GUR and glucose concentration. By sustaining Ga fetal GPR limits UPGT to a significantly greater extent than UtGU, diverting UtGU to UPGC. Thus, fetal GPR promotes placental as well as fetal metabolic autonomy when the maternal supply of glucose is reduced.


Superovulation and embryo transfer in Holstein cattle using sexed sperm.
The use of sexed bull sperm in multiple ovulation and embryo transfer (MOET) programs for Holsteins was evaluated for (1) heifers housed at a commercial embryo transfer (ET) facility (Experiments 1 and 2), and (2) heifers and cows on dairy farms (Experiment 3). In Experiment 1, superstimulated heifers were inseminated with 5 x10(6) sexed (X-sorted; n=5) or unsexed (n=5) frozen-thawed sperm from one bull at 12 and 24h after estrus detection. No difference was observed in the rates of transferable embryos (53.4% vs 68.1%), degenerate embryos (24.8% vs 26.6%) and unfertilized ova (21.8% vs 5.3%) between sexed and unsexed sperm, respectively, except for the percent of female transferable embryos diagnosed by embryo sexing (100% vs 49.3%, P<0.0001). In Experiment 2, donors were inseminated twice with 5 x10(6) sexed unfrozen sperm (n=10) or sexed frozen-thawed sperm (n=9). Embryo production rates for both treatments were similar to that observed on a commercial ET facility using unsexed sperm. Pregnancy rates for frozen-thawed embryos were similar for sexed and unsexed sperm (70.4% vs 72.4%, respectively). In Experiment 3, 99 flushes were conducted using sexed frozen-thawed sperm from nine bulls but an overall statistical analysis was not completed because the use of bulls was not balanced. However, for one bull with balanced usage, the rate of transferable embryos was higher in heifers than in cows (P<0.05) inseminated twice with 5 x10(6) sperm/dose (10 x10(6) total). We concluded that the use of sexed frozen-thawed sperm (> or =90% X-sperm biased and 10 x10(6) total sperm) may be economically viable for commercial MOET programs in Holstein heifers.


Impact of ganga canal on thermal comfort in the city of Roorkee, India.
The rise in urban air temperature has forced the researchers to look for nature-based solutions to resolve the problem sustainably. Urban waterbody plays a multidimensional role in the well-being of the city by catering to its economical, ecological, and socio-cultural needs. It can offer a potential solution for urban heat attenuation, but its effect on outdoor thermal comfort is contentious in humid subtropical climate. This study investigates the thermal impact of waterbody on its surroundings in humid subtropical climate by adopting a human centric approach. Waterbody impact on ambient air temperature, PET, and UTCI are evaluated and compared for a better understanding of its thermal impact on nearby surroundings. This study employs a CFD-based simulation model Envi-met for microclimate analysis. The results show that a dynamic waterbody lowers the ambient air temperature during daytime in summer of its nearby surroundings in humid subtropical climate. Maximum cooling is observed in open mid-rise LCZ where the cooling impact range is 140 m with the amplitude of 2.59 °C and compact low-rise LCZ exhibits minimum cooling of the identified LCZs with the cooling impact ending 24 m from waterbody edge with amplitude being 0.131 °C in the study area. Air temperature, UTCI, and PET do reflect the same trend when moving away from the waterbody in large low-rise LCZ, but it decreases drastically in open mid-rise LCZ and is non-existent in compact low-rise. This result provides an insight on the impact of waterbody on thermal comfort in its surroundings in humid subtropical climate, thus assisting urban planners and designers in making context-specific holistic decision.


Interaction of tubulin with the macromolecular apolar probe, octyl sepharose.
Binding of the microtubule protein, tubulin, to hydrophobic groups immobilized on octyl sepharose has been investigated. The results indicate that tubulin binds to octyl sepharose in a time-, temperature-, and concentration-dependent manner. Binding is multiphasic, with one fast phase and at least two slow phases, and is influenced by the presence of antimitotic drugs. Colchicine, vinblastine and podophyllotoxin enhance the fast binding of tubulin with very little effect on the slow binding. Pre-incubation of tubulin with the apolar probe, bis(1,8-anilinonaphthalenesulfonate) (BisANS) enhances both the rapid and slow phases of binding of tubulin to octyl sepharose. 1,8-Anilinonaphthalenesulfonate, the monomer of BisANS, has no effect. These results are consistent with a model for tubulin decay which involves the appearance of hydrophobic sites with time.


Pulmonary hypertension in mitral valve disease: 56 surgical patients reviewed.
A total of 392 patients have undergone prosthetic valve surgery including the mitral valve over a four-year period (1972-76). Of these patients 56 (14%) had a pulmonary artery systolic pressure of 70 mmHg or more during preoperative cardiac catheterisation and the hospital mortality of this group was 5.4%. Similarly, the hospital mortality of the remaining 336 patients with a pulmonary artery pressure below 70 mmHg was 5.4%. The presence of pulmonary hypertension in patients with valve disease including the mitral valve does not therefore indicate that the risk of dying in hospital as a consequence of corrective surgery is increased. The absence of a raised hospital mortality in this recent series may be attributed to improved surgical techniques and materials, while the use of droperidol and pentolinium which may reduce pulmonary vascular resistance as well as systemic resistance during surgery could be contributory.


Surfactant treatment of an infant with acute idiopathic pulmonary hemorrhage.
To describe the successful use of surfactant for treatment of respiratory distress refractory to conventional mechanical ventilation in a 4-wk-old with pulmonary hemorrhage. Case report. Tertiary care center pediatric intensive care unit. Four-week-old infant. Clinical improvement of respiratory distress as evidenced by 50% reduction in oxygenation index and subsequent extubation. Pulmonary hemorrhage is a rare but potentially fatal condition in children. Previously described therapeutic approaches include high-frequency oscillation ventilation and extracorporeal membrane oxygenation. Infants with pulmonary hemorrhage and respiratory distress may benefit from a trial of surfactant before escalating care.


Key stakeholder perspectives on expert-by-experience involvement in the values-based recruitment of student mental health nurses: A co-produced qualitative study.
Values-based recruitment is a mandatory process for nursing programmes within UK higher education, with the Nursing Midwifery Council expecting that experts-by-experience are engaged in these recruitment and selection processes. The wider involvement of experts-by-experience in healthcare education is gaining momentum internationally with calls for engagement in all aspects of design and delivery; however, the impact of such involvement in recruitment of nursing students has received little attention, particularly in mental health nursing. To understand the impact of expert-by-experience involvement in the values-based recruitment of mental health nursing students from the perspective of candidates, experts-by-experience, and academic staff. This qualitative approach was co-designed and implemented by a research team comprised of academics, experts-by-experience, and student mental health nurses. Focus groups and an on-line survey were used to collect data, with Burnard's thematic analysis providing a framework for data analysis. This study took place at one UK university. Participants included nurse academics, experts-by-experience, and student nurses with experience of a values-based recruitment process. Thematic analysis identified four themes: starting out, collaboration, rich assessment, and stakeholder gains. Whilst not without its challenges, the involvement of experts-by-experience in the recruitment of mental health nursing students was identified as delivering a robust recruitment process, encompassing academic abilities alongside the personal qualities required to make a 'good nurse'. Personal benefits for experts-by-experience, candidates, and academics were also reported. This study provides insights into the impact of experts-by-experience in supporting values-based recruitment. The approach is identified as enhancing the selection process by drawing from academic and lived experience perspectives and highlights to potential candidates, at the outset of their career, the value of meaningful engagement. These findings support the Nursing Midwifery Council's position that experts-by-experience should be engaged in the recruitment and selection of student nurses.


Anticoagulation alone as an effective and safe antithrombotic therapy in LVAD: When less is more.
To evaluate the safety and effectiveness of anticoagulation alone in HeartMate3 patients. According to antithrombotic regimen, patients were divided into 2 groups: Group-1(warfarin+aspirin) and Group-2(warfarin). A comparison of hemocompatibility-related adverse events (HRAEs), hemocompatibility score (HCS), and hemocoagulative laboratory markers, both qualitative and quantitative, between the 2 groups were performed. Fifty patients were enrolled, 28 (56%) in Group-1 and 22 in Group-2 (44%), without statistical differences at baseline. Median time of follow-up was 590 days (IQR: 410.25-1007.50). Eighteen HRAEs (36.0%) occurred: 17 in Group-1 (34%) and 1 in Group-2 (2%) (P < 0.001). The net HCS for Group-1 versus Group-2 was 24 points and 1 point (OR 12.116[2.034-233.226], P = 0.023), respectively. Hemocoagulative values turned into the normality and remained stable during follow-up, without differences between groups, except for ASPI-test (P = 0.003). HeartMate3 showed a high hemocompatibility independently from antithrombotic therapy. Aspirin avoidance resulted a safe and effective strategy since it reduced hemorrhagic events, without increasing thrombotic risk.


Nonspecific immunity in pregnancy: monocyte surface Fcgamma receptor expression and function.
The state of pregnancy is an immunological enigma during which the body must prevent rejection of the antigenically foreign fetus while at the same time maintain sufficient maternal host defense mechanisms to combat infection. Although most studies on the immunology of pregnancy focus on immune suppression, several studies have shown an increase in nonspecific host defense, which is postulated to be a compensatory mechanism for decreased specific immunity during pregnancy. Studies in this laboratory have shown that monocyte surface FcgammaRI (CD64) and FcgammaRII (CD32) expression progressively increase throughout pregnancy, while surface MHC class II expression remains unchanged. Functional studies revealed that the number of phagocytic monocytes which could be isolated from pregnant women was increased. These cells exhibited an increased capacity to ingest IgG-opsonized human erythrocytes. This study shows for the first time that monocyte surface FcgammaR expression and FcgammaR-mediated functions are increased during pregnancy. These results support the hypothesis that nonspecific immunity as represented by FcgammaR expression and function is increased during pregnancy.


The day when the echocardiographist went mushrooming….
We report a case of partial congenital absence of the pericardium associated with severe aortic stenosis on a bicuspid valve in a 72-year-old man. Diagnosis was based on echocardiography and confirmed with magnetic resonance imaging, and the patient benefited from pericardioplasty and aortic valve replacement.


In Vivo Effects of Orally Administered Different Concentrations of Silver Oxide Nanoparticles in Hyperuricemic Mice.
Silver oxide nanoparticles (AgO-NPs) antioxidant, anti-cancer, anti-microbial, and tissue repair properties. Gouty arthritis is the inflammation of tissues and joints caused by the deposition of monosodium urate crystals. In this experiment, we investigated the anti-hyperuricemic effectiveness of different concentrations of AgO-NPs in mice. The present study aimed to investigate the effect of administration of AgO-NPs in monosodium urate (MSU)-induced gouty mice for the very first time. Monosodium urate (MSU) crystals were administered intraperitoneal for gout induction, followed by 5, 10, and 20 µg/mL doses of AgO-NPs for 2 weeks. The positive control was provided with the commercially available drug allopurinol to compare the effects of AgO-NPs and allopurinol. The main purpose of the study was to investigate the effectiveness of the nanoparticles in comparison with commercially available drugs. AgO-NPs have been shown to improve the condition of gouty arthritis by reducing significantly (P ˂ 0.001) increased levels of ALT, AST, and total bilirubin. The total protein estimation results showed significant improvement at concentration of 20 µg/mL of AgO-NPs. The lipid profile results showed that high concentration (20 µg/mL) of AgO-NPs decrease the lipid content significantly as compared to control. It was concluded from this study that the antioxidant, anti-inflammatory, and antilipidemic properties of AgO-NPs may improve the hyperuricemic condition in gouty arthritis mice.


Rethinking the paradigm: How comparative studies on fatty acid oxidation inform our understanding of T cell metabolism.
The classic paradigm of T cell metabolism posits that activated Teff cells utilize glycolysis to keep pace with increased energetic demands, while resting and Tmem cells rely on the oxidation of fat. In contrast, Teff cells during graft-versus-host disease (GVHD) increase their reliance on oxidative metabolism and, in particular, on fatty acid oxidation (FAO). To explore the potential mechanisms driving adoption of this alternative metabolism, we first review key pathways regulating FAO across a variety of disparate tissue types, including liver, heart, and skeletal muscle. Based upon these comparative studies, we then outline a consensus network of transcriptional and signaling pathways that predict a model for regulating FAO in Teff cells during GVHD. This model raises important implications about the dynamic nature of metabolic reprogramming in T cells and suggests exciting future directions for further study of in vivo T cell metabolism.


[Update on lymphatic resorption of cerebrospinal fluid after review of the literature].
The intention of this article is to review and to comment some of the historic and recent informations regarding the lymphatic drainage of brain and cerebrospinal fluid, and to try to specify the different pathways of this drainage.


The frequency of microbial invasion of the amniotic cavity and histologic chorioamnionitis in women at term with intact membranes in the presence or absence of labor.
The amniotic cavity is normally sterile for bacteria. However, experimental evidence indicates that regular uterine contractions exert a suction-like effect whereby vaginal fluid ascends into the uterine cavity with contractions (demonstrated by sonohysterography contrast media). Consequently, this study was conducted to determine whether the presence and progress of labor are associated with an increased risk of microbial invasion of the amniotic cavity (MIAC), intraamniotic inflammation, and histologic chorioamnionitis in women with term pregnancies with intact membranes. Amniotic fluid (AF) was obtained from term singleton pregnant women with intact membranes at the time of cesarean delivery. AF was cultured for aerobic and anaerobic bacteria and genital mycoplasmas, and white blood cell (WBC) count was determined. Patients were divided into 3 groups according to the presence or absence of labor and the progress of labor. Nonparametric statistics were used for analysis. Results included: (1) a total of 884 pregnant women were enrolled and divided into 3 groups: group 1, not in labor (n = 775); group 2, in early labor (cervical dilatation less than 4 cm) (n = 86); and group 3, in active labor (cervical dilatation 4 cm or greater) (n = 23); (2) the frequency of MIAC was 1% (6 of 775) in women not in labor, 3.5% (3 of 86) in patients with early labor, and 13% (3 of 23) in patients with active labor; and (3) the median AF WBC count and the frequency of histologic chorioamnionitis were also higher in the presence of labor than in the absence of labor. We came to the following conclusions: (1) labor is associated with an increased risk of MIAC, a higher median AF WBC count, and histologic chorioamnionitis in term pregnancy with intact membranes; (2) the more advanced the cervical dilatation, the greater the risk of MIAC, a higher median AF WBC count, and histologic chorioamnionitis; and (3) in contrast, fetal inflammation (funisitis) did not increase with the presence of labor or as a function of cervical dilatation. We propose that labor predisposes to MIAC, a higher median AF WBC count, and histologic chorioamnionitis.


Reduction of Colles' fractures without anaesthesia using a new dynamic bone alignment system.
Two techniques for reduction of Colles' fractures were compared in a prospective, randomized study. With use of a newly designed dynamic bone alignment device, reduction manoeuvres were performed on 62 patients with Colles' fractures (group A) without any form of anaesthesia. In a control group of 54 patients (group B) Colles' fractures were reduced manually in the traditional way using local infiltration anaesthesia. In each group the pain experienced by the patients was recorded. Severe pain during the reduction was reported by 8 per cent of the patients in group A and by 35 per cent of those in group B. No complications occurred during or after dynamic reduction without anaesthesia. This method of treatment seems to be a very gentle one for the patients, with the advantage of causing less pain than treatment under local anaesthesia.


CMOS-Compatible Memristor for Optoelectronic Neuromorphic Computing.
Optoelectronic memristor is a promising candidate for future light-controllable high-density storage and neuromorphic computing. In this work, light-tunable resistive switching (RS) characteristics are demonstrated in the CMOS process-compatible ITO/HfO2/TiO2/ITO optoelectronic memristor. The device shows an average of 79.24% transmittance under visible light. After electroforming, stable bipolar analog switching, data retention beyond 104 s, and endurance of 106 cycles are realized. An obvious current increase is observed under 405 nm wavelength light irradiation both in high and in low resistance states. The long-term potentiation of synaptic property can be achieved by both electrical and optical stimulation. Moreover, based on the optical potentiation and electrical depression of conductances, the simulated Hopfield neural network (HNN) is trained for learning the 10 × 10 pixels size image. The HNN can be successfully trained to recognize the input image with a training accuracy of 100% in 13 iterations. These results suggest that this optoelectronic memristor has a high potential for neuromorphic application.


Performance evaluation of two different software programs for automated ASPECTS scoring in patients with suspected stroke.
The range of software available to radiologists has increased enormously with the advancement of AI. A good example of this is software to determine ASPECTS in the treatment of potential stroke patients. In this study, two software packages (eASPECTS from Brainomix and VIA_ASPECTS from Siemens) were tested and compared for their performance in the daily clinical routine of a maximum care provider with a 24/7 stroke unit. A total of 637 noncontrast CT images were obtained from consecutive patients with suspected stroke, of whom 73 were finally diagnosed with MCA infarction. Differences in agreement and quantification of agreement were analysed, as well as the correlation and sensitivity, specificity and accuracy compared to raters. Compared to VIA_ASPECTS, eASPECTS shows good agreement and strong correlation with the raters. VIA_ASPECTS has lower accuracy and low specificity than eASPECTS but a higher sensitivity. Both software products have the potential to be decision support tools for radiologists. There are, however, differences between the two software products in terms of their intended use.


The desire to gamble: the influence of outcomes on the priming effects of a gambling episode.
The influence of gambling outcomes on the efficacy of a short gambling episode to prime motivation to continue gambling was determined in two experiments in which desire to gamble was evaluated while participants played a slot machine located in a virtual reality casino. In experiment 1, 38 high-risk [>3 Problem Gambling Severity Index (PGSI)] [Ferris and Wynne (The Canadian problem gambling index: final report, 2001)] and 36 non-problem gamblers (0 PGSI) either won or lost a modest amount. Among high-risk gamblers, winning resulted in a greater increase in the desire to continue gambling than did losing. In experiment 2, 39 high-risk, 33 low-risk (0 < PGSI < 3), and 31 non-problem gamblers experienced either a single large win or a series of small wins (equivalent monetary gain). Participants were permitted to continue playing as long as they wanted (all subsequent spins being losses) thus permitting evaluation of persistence (resistance to extinction). Throughout, desire to gamble was assessed using a single item measure. High-risk gamblers who experienced a large win reported significantly greater desire to gamble upon voluntary cessation than those who experienced a series of small wins. It seems that the priming effects of a short gambling episode are contingent on the pattern of outcomes experienced by the gambler. The data were related to motivational factors associated with gambling, gambling persistence, and chasing losses.