Moderate or Severe Impairment in Pulmonary Function is Associated with Mortality in Sarcoidosis Patients Infected with SARS‑CoV‑2.
To investigate whether sarcoidosis patients infected with SARS-CoV-2 are at risk for adverse disease outcomes. This retrospective study was conducted in five hospitals within the Mount Sinai Health System during March 1, 2020 to July 29, 2020. All patients diagnosed with COVID-19 were included in the study. We identified sarcoidosis patients who met diagnostic criteria for sarcoidosis according to accepted guidelines. An adverse disease outcome was defined as the presence of intubation and mechanical ventilation or in-hospital mortality. In sarcoidosis patients, we reported (when available) the results of pulmonary function testing measured within 3 years prior to the time of SARS‑CoV‑2 infection. A multivariable logistic regression model was used to generate an adjusted odds ratio (aOR) to evaluate sarcoidosis as a risk factor for an adverse outcome. The same model was used to analyze sarcoidosis patients with moderate and/or severe impairment in pulmonary function. The study included 7337 patients, 37 of whom (0.5%) had sarcoidosis. The crude rate of developing an adverse outcome was significantly higher in patients with moderately and/or severely impaired pulmonary function (9/14 vs. 3/23, p = 0.003). While the diagnosis of sarcoidosis was not independently associated with risk of an adverse event, (aOR 1.8, 95% CI 0.9-3.6), the diagnosis of sarcoidosis in patients with moderately and/or severely impaired pulmonary function was associated with an adverse outcome (aOR 7.8, 95% CI 2.4-25.8). Moderate or severe impairment in pulmonary function is associated with mortality in sarcoidosis patients infected with SARS‑CoV‑2.


Amniotic membrane extract-enriched hydrogel augments the therapeutic effect of menstrual blood-derived stromal cells in a rat model of intrauterine adhesion.
We previously demonstrated that transplantation of menstrual blood-derived stromal cells (MenSCs) is a safe and effective therapy for treating intrauterine adhesions (IUA). However, improving the colonization and therapeutic efficiency of MenSCs is still needed before full clinical application. Here, we established an amniotic membrane extract (AME)-enriched RGD hydrogel, and evaluated the therapeutic effect of this adjuvant combined with MenSCs transplantation in an IUA rat model. Our results indicated that AME promoted the proliferation and secretion of MenSCs in vitro, up-regulated the expression of apoptosis-suppressing gene BCL2 and down-regulated the expression of apoptosis-related genes Caspase-3 and Caspase-8. The AME-enriched hydrogel was biocompatible, and improved the survival of MenSCs in vitro and in vivo. It also promoted the retention of MenSCs in IUA uterus and augmented the effects of MenSCs on improving uterus morphology, endometrial proliferation, endometrial receptivity and fibrosis suppression. In addition, co-transplantation of MenSCs with AME-enriched hydrogel markedly down-regulated the expressions of inflammation-related genes IL10 and TGFβ while up-regulated the IL4/IFN-γ ratio in the IUA endometrium, and improved the expressions of cell proliferation-related antigen, gland-regeneration-related marker leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), angiogenesis-related marker platelet and endothelial cell adhesion molecule 1 (PECAM1), endometrial receptivity related genes ITGα5 and ITGβ3. Our study suggested that AME and MenSCs had a synergistic effect. Co-transplantation of MenSCs with AME-enriched hydrogel provided a promising approach for stem cell-based IUA treatment.


Hematological cell findings in bone marrow and peripheral blood of rabbits after experimental acute exposure to Loxosceles intermedia (brown spider) venom.
The purpose of this work was to find out the cellular changes occurring in bone marrow and peripheral blood after acute exposure to the venom of Loxosceles intermedia. Doses of 40 microg of venom were injected intradermally into five rabbits, and five rabbits receiving only phosphate-buffered saline (PBS) were used as controls. Bone marrow and peripheral blood samples were obtained before the envenomation and 4, 8, 12, 24 and 48 h, and 5, 10, 15, 20 and 30 days after envenomation. In bone marrow samples we assessed cellularity, nucleated red cells, megakaryocytes and neutrophils, and in peripheral blood we assessed red cells (red cell concentration, hemoglobin and hematocrit), leukocytes, neutrophils and platelets. Our objective was to find out if the venom has a direct effect on bone marrow and peripheral blood or if changes in both of them are secondary to the needs of tissues, and if there is a good correlation between histopathological and hematological findings. We found that the red cell parameters were not affected by the venom, except for nucleated red cells which decreased after venom exposure. The depression of megakaryocyte numbers and thrombocytopenia showed a strong correlation with the histopathologic changes observed in skin biopsies obtained from the rabbits. The changes in cellularity and neutrophils of bone marrow were strongly correlated with those in peripheral blood and skin. The thrombocytopenia and neutropenia in peripheral blood are due to marrow depression, which may be a consequence of an extensive migration of platelets and neutrophils to the necrotic lesion or the marrow depression may be a transitory effect of evenoming by L. intermedia.


Work-related musculoskeletal disorders: design as a prevention strategy. A review.
Work-related musculoskeletal disorders are of serious concern to many organizations, including industry, insurance, and health care. They are also of immediate concern to the workers and their families who are adversely affected by these disorders. Work-related musculoskeletal disorders are a substantial source of economic drain to these organizations. Sources of this drain include economic losses incurred from lost or decreased productivity as well as medical treatment and indemnity costs. Therefore, it is within the best interest of these organizations to prevent work-related musculoskeletal disorders from occurring, before they manifest into serious issues of medical, social, and economic concern. The purpose of this paper is to review the concept of work-related musculoskeletal disorders and discuss the basis of their prevention as a primary means of occupational injury and illness management. The principal contributory role of ergonomics/human factors is presented as a viable means of prevention and an important contributor to the comprehensive management of these disorders.


Obesity is associated with impaired insulin-mediated potassium uptake.
The ability of insulin to promote extrarenal potassium uptake and to stimulate glucose uptake was examined in eight obese and ten normal weight control subjects. Insulin was infused at three rates to produced plasma insulin concentrations of approximately 100, 1,900, and 19,000 microU/mL. Insulin-mediated potassium, as well as glucose uptake, was diminished during the lowest dose insulin clamp study (100 microU/mL) but could be normalized at pharmacologic plasma insulin concentrations. These results indicate that obese subjects are resistant to the ability of insulin to stimulate potassium uptake by extrarenal tissues. Impaired potassium uptake at physiologic plasma insulin levels, with normalization at supraphysiologic insulin concentrations, is most consistent with a decrease in the number of insulin receptors on insulin target tissues.


Different concentrations of two small stress proteins, alphaB crystallin and HSP27 in human urological tumor tissues.
Concentrations of two small stress proteins, alphaB crystallin and the 27-kDa heat shock protein (HSP27) were quantitated in tissues of the human normal genitourinary system and their tumors. Levels of HSP27 in renal cell carcinomas (mean +/- SE: 1450+/-262 ng/mg protein, n = 15) were significantly higher than in normal kidney (the cortex: 540+/-99 ng/ mg protein, n = 13; the medulla: 600+/-106 ng/mg protein, n = 13) while those of alphaB crystallin tended to be increased without statistical significance. These findings were similar to those previously reported for renal cell tumors chemically induced in rats. Concentrations of alphaB crystallin in prostatic carcinoma tissues (410+/-129 ng/mg protein, n = 10) were also significantly higher than in benign prostatic hyperplasia (54+/-12 ng/mg protein, n = 14), whereas alphaB crystallin levels in testicular tumors including seminomas (2.1+/-0.8 ng/mg protein, n = 11) and non-seminomas (5.2+/-2.3 ng/mg protein, n = 9) were significantly lower than in normal testicular tissues (29.7+/-6.2 ng/mg protein, n = 5). Both alphaB crystallin and HSP27 could be immunohistochemically localized in the normal kidney and renal cell carcinoma tissues.


Classification of Cracks in Composite Structures Subjected to Low-Velocity Impact Using Distribution-Based Segmentation and Wavelet Analysis of X-ray Tomograms.
The problem of characterizing the structural residual life is one of the most challenging issues of the damage tolerance concept currently applied in modern aviation. Considering the complexity of the internal architecture of composite structures widely applied for aircraft components nowadays, as well as the additional complexity related to the appearance of barely visible impact damage, prediction of the structural residual life is a demanding task. In this paper, the authors proposed a method based on detection of structural damage after low-velocity impact loading and its classification with respect to types of acting stress on constituents of composite structures using the developed processing algorithm based on segmentation of 3D X-ray computed tomograms using the rebmix package, real-oriented dual-tree wavelet transform and supporting image processing procedures. The presented algorithm allowed for accurate distinguishing of defined types of damage from X-ray computed tomograms with strong robustness to noise and measurement artifacts. The processing was performed on experimental data obtained from X-ray computed tomography of a composite structure with barely visible impact damage, which allowed better understanding of fracture mechanisms in such conditions. The gained knowledge will allow for a more accurate simulation of structural damage in composite structures, which will provide higher accuracy in predicting structural residual life.


[Analyses of the patient knowledge about the medical report and its usefulness in neurology].
The medical report is a legal, written document issued by the physician, exposing the clinical history and the diagnostic and therapeutic protocols applied to the patient. To evaluate the patient knowledge about the medical report and its usefulness. We included consecutive first-visit patients attended in four general neurology offices. The descriptive analysis included: demographic data (age, sex, level of studies), degree of knowledge on the referring doctor (name, specialty, reason for referral), medical history (medical antecedents, treatment, dosage, reasons for its intake, reasons for not providing it) and the medical report (applications, reasons for not providing it and awarded usefulness). These data were compared between different sanitary areas and cultural levels. We included 378 patients (average age: 49.1 ± 20.6 years-old; 62.2% women; 40.2% with primary studies; 23.3% with secondary studies). 41.5% did not know the name of the referring doctor, 5.5% his specialty and 2.6% the reason for referral. 3.7% did not know their medical antecedents, 20.4% did not provide the treatment (49.3% did not know it was necessary), 4.8% did not know why they took it and 27.6% the dosage. 14.3% did not provide the medical report and 18.0% applied it (61.7% for bureaucratic reasons and 28.0% for information). Only 18.0% knew that the medical report included the medical information of the patient. The patient does not know the usefulness and importance of the medical report, despite being a legal document exposing the medical information of the patient disease.


Andropausal symptoms in men with Type 2 diabetes.
Serum androgen concentration is reported to be low in patients with Type 2 diabetes. There have been no studies comparing andropausal symptoms such as sleep disturbance, depression, erectile dysfunction and lower urinary tract symptoms simultaneously between men with Type 2 diabetes and subjects without diabetes. We compared andropausal symptom scores such as the Pittsburgh Sleep Quality Index, the Self-Rating Depression Scale, the International Index of Erectile Function and the International Prostate Symptom Score in 296 men with Type 2 diabetes and in 267 subjects without diabetes. Furthermore, we evaluated relationships of andropausal symptom scores to various anthropometric factors and compared andropausal symptom scores according to diabetic complications in men with Type 2 diabetes. Andropausal symptom scores such as the Pittsburgh Sleep Quality Index, the Self-Rating Depression Scale, the International Index of Erectile Function and the International Prostate Symptom Score were 4.2 ± 2.6 vs. 5.0 ± 3.3, P<0.01 by unpaired Student's t-test, 34.8 ± 8.2 vs. 38.4 ± 9.3, P<0.0001, 11.5 ± 6.4 vs. 9.9 ± 6.9, P<0.01 and 7.3 ± 6.7 vs. 9.0 ± 7.1, P<0.01 in subjects without diabetes and in patients with diabetes, respectively. The Pittsburgh Sleep Quality Index was higher in patients with neuropathy than without. The Self-Rating Depression Scale was higher in patients with advanced retinopathy. The International Index of Erectile Function was lower in patients with advanced retinopathy and nephropathy. The International Index of Erectile Function was lower and the International Prostate Symptom Score was higher in patients with cardiovascular disease than without. Our data demonstrated that men with Type 2 diabetes have higher prevalence of andropausal symptoms, especially those with diabetic complications.


Correlation between seroreactivity to HIV-1 V3 loop peptides and male-to-female heterosexual transmission.
To evaluate the correlation between seroreactivity to peptides corresponding to the V3 loop of the major envelope glycoprotein from different HIV-1 strains and the risk of heterosexual HIV-1 transmission. Sera from 39 infected individuals (16 transmitters and 23 non-transmitters) were tested for reactivity against synthetic peptides representing sequences of the V3 loop apex from HIV-1 strains MN, SC, WMJ2, RF and IIIB. A skewed distribution in seroreactivity to RF and IIIB peptides was observed between the two groups: reactivity was more prevalent in sera from non-transmitting than from transmitting individuals. Reactivity to the MN, SC and WMJ2 peptides was very frequent and there were no differences between the two groups. These data suggest that antibodies reactive with a larger set of V3 apex peptides (i.e., cross-reactive antibodies) could play a role in the prevention of heterosexual transmission.


Macrophage-derived Wnt signaling increases endothelial permeability during skeletal muscle injury.
The inflammatory response and the presence of macrophages are reported to be necessary for proper muscle regeneration. However, our understanding of the molecular mechanisms governing how macrophages signal to promote muscle regeneration is incomplete. Here we conditionally deleted Wls, which is required for Wnt secretion, from macrophages and examined the impact on endothelial permeability following muscle injury. The expression of Wnt ligands and Wls was increased in the tibialis anterior (TA) of mice 2 days following BaCl2 injury. Loss of macrophage Wls inhibited the loss of endothelial barrier function, as measured by transendothelial resistance and Evans blue dye permeability assays. Interestingly, the blockade in endothelial permeability correlated with reduced VEGF levels and pretreatment of wild type endothelial cells with a VEGFR2 blocking antibody was sufficient to reduce endothelial permeability induced by stimulated macrophage supernatant. We also found that macrophage Wls-null TAs had myocytes with reduced cross-sectional area 7 day post-injury suggesting a delay in muscle regeneration. Our results indicate that macrophage-derived Wnt signaling increases endothelial permeability in a VEGF-dependent fashion following muscle injury. Our findings implicate macrophages as a primary source of Wnt ligands following muscle injury and highlight the Wnt pathway as a therapeutic target following injury.


[Gender differences in career motivation: female doctors' ambitions benefit from family friendly work environment].
To determine gender differences in career motivation and the effect of a family friendly work environment. Cross-sectional pilot investigation. A web survey among male and female doctors (n = 107; 72 women and 35 men) in different specialties, including surgical, internal medicine and general practitioners, was used to gather information on different dimensions of career motivation and perceptions of the family friendliness of the work environment. Differences were analysed by means of t-tests and regression analyses. Male doctors had higher scores on career identity and on career planning than female doctors. However, male and female doctors did not differ in their willingness to achieve top positions. Female doctors were more determined concerning their career goals than their male counterparts. The family friendliness of the work environment had an overall positive effect on career motivation for both male and female doctors. However, a family friendly work environment had a negative effect on the career identity of male doctors. For male and female doctors alike, support to achieve career goals and elimination of career barriers lead to increased career identity. Male and female doctors differed in certain dimensions of career motivation. Offering support for career goals and taking away career barriers leads to a higher career motivation than offering a family friendly work environment.


The b-32 protein from maize endosperm: characterization of genomic sequences encoding two alternative central domains.
As derived from a cDNA clone, the structure of the b-32 protein of Zea mays, a putative regulatory factor of zein expression, has a central acidic region separated by two domains covered by secondary structure motifs. In this work, three b-32 genomic clones were selected from two genomic libraries obtained from the maize inbred lines W64A and A69Y. The nucleotide sequences of the complete coding region of each b-32 gene, as well as long stretches of their 5' and 3' flanking regions, were determined. Introns are not present in the b-32 genomic sequences. Minor variations among the three genes and an earlier reported b-32 cDNA indicates that they constitute a gene family showing a characteristic polymorphism. Such a polymorphism is highly evident in large segments of the upstream regulatory sequences. Interestingly, when compared with cDNA (W64A) or with gene b-32.120 (W64A), the genes b-32.129 (W64A) and b-32.152 (A69Y) show three jumps of the reading frame in the central part of the coding region, resulting in a completely different sequence of the b-32 protein central domain. In all cases, variations in the N- and C-terminal domains account only for microheterogeneity.


Interchangeable utilization of metals: New perspectives on the impacts of metal ions employed in ancient and extant biomolecules.
Metal ions provide considerable functionality across biological systems, and their utilization within biomolecules has adapted through changes in the chemical environment to maintain the activity they facilitate. While ancient earth's atmosphere was rich in iron and manganese and low in oxygen, periods of atmospheric oxygenation significantly altered the availability of certain metal ions, resulting in ion replacement within biomolecules. This adaptation mechanism has given rise to the phenomenon of metal cofactor interchangeability, whereby contemporary proteins and nucleic acids interact with multiple metal ions interchangeably, with different coordinated metals influencing biological activity, stability, and toxic potential. The ability of extant organisms to adapt to fluctuating metal availability remains relevant in a number of crucial biomolecules, including the superoxide dismutases of the antioxidant defense systems and ribonucleotide reductases. These well-studied and ancient enzymes illustrate the potential for metal interchangeability and adaptive utilization. More recently, the ribosome has also been demonstrated to exhibit interchangeable interactions with metal ions with impacts on function, stability, and stress adaptation. Using these and other examples, here we review the biological significance of interchangeable metal ions from a new angle that combines both biochemical and evolutionary viewpoints. The geochemical pressures and chemical properties that underlie biological metal utilization are discussed in the context of their impact on modern disease states and treatments.


Comorbidity of poor sleep and primary headaches among nursing staff in north China.
Sleep disorders and primary headaches are both more prevalent among nursing staff than in the general population. However, there have been no reports about the comorbidity of poor sleep and primary headaches among nursing staff. Stratified random cluster sampling was used to select 1102 nurses from various departments in three hospitals in north China. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). The diagnosis of primary headaches including migraine, tension-type headache (TTH), and chronic daily headache (CDH) was based on the International Classification of Headache Disorders, 3rd edition (beta version) (ICHD-3-beta). The response rate was 93 %. Among 1023 nurses, the prevalence of poor sleep was 56.7 %. Of these, 315 nurses (34.13 %) had poor sleep comorbid with primary headaches. The prevalence of poor sleep in the groups with CDH (82.1 %), migraine (78.9 %), and TTH (59.0 %) was significantly higher than that in the group without headaches (47.3 %) (all P < 0.05). Multivariate logistic regression revealed that rotating shifts and suffering headache were independent risk factors for poor sleep. Also, the 1-year prevalence of the three types of primary headache was significantly increased in the poor sleep group (migraine: 21.2 % vs. 7.2 %; TTH: 27.9 % vs. 24.9 %; CDH: 4.1 % vs. 1.1 %; P < 0.05). Compared with normal sleepers, nurses with poor sleep were 1.72 times more likely to have severe headache (OR: 1.72, 95 % CI: 1.14-2.57). Comorbidity of poor sleep and primary headaches among nursing staff is common. Therefore, sleep quality should be carefully evaluated in nurses with primary headaches.


The complete mitochondrial genome of dhole Cuon alpinus: phylogenetic analysis and dating evolutionary divergence within Canidae.
The dhole (Cuon alpinus) is the only existent species in the genus Cuon (Carnivora: Canidae). In the present study, the complete mitochondrial genome of the dhole was sequenced. The total length is 16672 base pairs which is the shortest in Canidae. Sequence analysis revealed that most mitochondrial genomic functional regions were highly consistent among canid animals except the CSB domain of the control region. The difference in length among the Canidae mitochondrial genome sequences is mainly due to the number of short segments of tandem repeated in the CSB domain. Phylogenetic analysis was progressed based on the concatenated data set of 14 mitochondrial genes of 8 canid animals by using maximum parsimony (MP), maximum likelihood (ML) and Bayesian (BI) inference methods. The genera Vulpes and Nyctereutes formed a sister group and split first within Canidae, followed by that in the Cuon. The divergence in the genus Canis was the latest. The divarication of domestic dogs after that of the Canis lupus laniger is completely supported by all the three topologies. Pairwise sequence divergence data of different mitochondrial genes among canid animals were also determined. Except for the synonymous substitutions in protein-coding genes, the control region exhibits the highest sequence divergences. The synonymous rates are approximately two to six times higher than those of the non-synonymous sites except for a slightly higher rate in the non-synonymous substitution between Cuon alpinus and Vulpes vulpes. 16S rRNA genes have a slightly faster sequence divergence than 12S rRNA and tRNA genes. Based on nucleotide substitutions of tRNA genes and rRNA genes, the times since divergence between dhole and other canid animals, and between domestic dogs and three subspecies of wolves were evaluated. The result indicates that Vulpes and Nyctereutes have a close phylogenetic relationship and the divergence of Nyctereutes is a little earlier. The Tibetan wolf may be an archaic pedigree within wolf subspecies. The genetic distance between wolves and domestic dogs is less than that among different subspecies of wolves. The domestication of dogs was about 1.56-1.92 million years ago or even earlier.


From genome sequence to integrated bioprocess for succinic acid production by Mannheimia succiniciproducens.
Mannheimia succiniciproducens is a capnophilic gram-negative bacterium isolated from bovine rumen. Wild-type M. succiniciproducens can produce succinic acid as a major fermentation product with acetic, formic, and lactic acids as byproducts during the anaerobic cultivation using several different carbon sources. Succinic acid is an important C4 building block chemical for many applications. Here, we review the progress made with M. succiniciproducens for efficient succinic acid production; the approaches taken towards the development of an integrated process for succinic acid production are described, which include strain isolation and characterization, complete genome sequencing and annotation, development of genetic tools for metabolic engineering, strain development by systems approach of integrating omics and in silico metabolic analysis, and development of fermentation and recovery processes. We also describe our current effort on further improving the performance of M. succiniciproducens and optimizing the mid- and downstream processes. Finally, we finish this mini-review by discussing the issues that need to be addressed to make this process of fermentative succinic acid production employing M. succiniciproducens to reach the industrial-scale process.


Monoamine oxidase-inhibiting properties of SR 95191, a new pyridazine derivative, in the rat: evidence for selective and reversible inhibition of monoamine oxidase type A in vivo but not in vitro.
In rodents, SR 95191 [3-(2-morpholinoethylamino)-4-cyano-6-phenylpyridazine] has been shown to be active in animal models of depression. The profile of activity of SR 95191 suggests that the compound is a selective and short-acting type A monoamine oxidase (MAO) inhibitor (MAOI) in vivo. In the present study, the interaction of SR 95191 with MAO-A and MAO-B activity was further examined in vivo and in vitro. In brain, liver, and duodenum of pretreated rats, SR 95191 selectively inhibited MAO-A (ED50 = 3-5 mg/kg, p.o.), whereas MAO-B was only weakly inhibited for doses as high as 300 mg/kg, p.o. In vivo, SR 95191 (1-100 mg/kg, p.o.) antagonized, in a dose-dependent fashion, the irreversible inhibition of brain and liver MAO-A induced by phenelzine. Finally, dopamine and 5-hydroxytryptamine depleted from their striatal stores by tetrabenazine were able to displace SR 95191 from the active site of MAO-A. However, ex vivo, kinetic studies showed that the inhibitory effect of SR 95191 (1-10 mg/kg) towards MAO-A was noncompetitive and was unchanged after dilution or dialysis. In vitro, the inhibition of brain MAO-A, but not MAO-B, by SR 95191 was time dependent, with a 19-fold decrease in the IC50 values being observed over a 30-min incubation period (140 to 7.5 microM). At this time, the SR 95191-induced inhibition of MAO-A was not removed by repeated washings. When the reaction was started by adding the homogenate without prior preincubation with SR 95191, the inhibition of brain MAO-A was fully competitive (Ki = 68 microM).(ABSTRACT TRUNCATED AT 250 WORDS)


Predictors of Underlying Esophageal Motility Disorders in Patients Presenting with Esophageal Candidiasis.
Esophageal motility disorders (EMDs) are a known risk factor for esophageal candidiasis (EC), but this relation has not been described particularly well. We sought to evaluate the predictors of underlying EMDs in patients presenting with EC. Cases of EC at a single medical center between 2010 and 2021 were identified retrospectively based on the International Classification of Diseases, Ninth Revision code. Demographic, clinical, endoscopic, and manometric data were reviewed. The diagnosis of EC was based on typical endoscopic appearance. In total, 130 EC patients were identified (mean age 69.5 ± 14.6; 66.2% male). Of these, 12 (9.2%) had an underlying EMD (11 cases of achalasia; 1 case of esophagogastric junction outflow obstruction). Five (41.7%) of these patients had previously been diagnosed as having an EMD, whereas 7 were newly diagnosed only after their presentation with EC. No significant differences were noted between those with or without EMDs in terms of demographics, medical comorbidities, or medication use. Patients with an EMD, however, were more likely to complain of dysphagia (91.7% vs 30.5%, P < 0.001), and on endoscopy, they were more likely to have residual food in the esophagus, residual fluid in the esophagus, a dilated esophagus, and resistance to traversing the esophagogastric junction (all P < 0.001). Sixty-one (46.9%) patients with EC died during follow-up (mean 58 months). EMDs are present in approximately 10% of patients presenting with EC, with half being diagnosed only after presenting with EC. Similar to non-EC patients, patients with EC with dysphagia and the typical endoscopic findings of achalasia are more likely to have an EMD and warrant prompt manometric evaluation.


A glycoproteomic approach to identify novel glycomarkers for cancer stem cells.
Most cancers consist of heterogeneous populations of cells with substantial differences in tumorigenicity. Cells that possess self-renewal and tumor-initiating properties are often called cancer stem cells (CSCs). Since CSCs underlie tumor recurrence and metastasis and are resistant to current anti-cancer therapies, novel therapeutic strategies to efficiently target this subset of cells are needed. Aberrant glycosylation is one of the hallmarks of cancer. Many cancer-associated glycans have been reported to be involved in tumor progression and metastasis, and are used as tumor markers. Over the past several years, we have identified characteristic glycans on CSCs by utilizing recent advances in glycoproteomic technologies. In this review, we would like to summarize a series of our recent studies and discuss possible applications of glycomarkers for CSCs.


Correlation of T1- to T2-weighted signal intensity ratio with T1- and T2-relaxation time and IDH mutation status in glioma.
The current study aimed to test whether the ratio of T1-weighted to T2-weighted signal intensity (T1W/T2W ratio: rT1/T2) derived from conventional MRI could act as a surrogate relaxation time predictive of IDH mutation status in histologically lower-grade gliomas. Strong exponential correlations were found between rT1/T2 and each of T1- and T2-relaxation times in eight subjects (rT1/T2 = 1.63exp-0.0005T1-relax + 0.30 and rT1/T2 = 1.27exp-0.0081T2-relax + 0.48; R2 = 0.64 and 0.59, respectively). In a test cohort of 25 patients, mean rT1/T2 (mrT1/T2) was significantly higher in IDHwt tumors than in IDHmt tumors (p < 0.05) and the optimal cut-off of mrT1/T2 for discriminating IDHmt was 0.666-0.677, (AUC = 0.75, p < 0.05), which was validated in an external domestic cohort of 29 patients (AUC = 0.75, p = 0.02). However, this result was not validated in an external international cohort derived from TCIA/TCGA (AUC = 0.63, p = 0.08). The t-Distributed Stochastic Neighbor Embedding analysis revealed a greater diversity in image characteristics within the TCIA/TCGA cohort than in the two domestic cohorts. The failure of external validation in the TCIA/TCGA cohort could be attributed to its wider variety of original imaging characteristics.


Lgl1 controls NG2 endocytic pathway to regulate oligodendrocyte differentiation and asymmetric cell division and gliomagenesis.
Oligodendrocyte progenitor cells (OPC) undergo asymmetric cell division (ACD) to generate one OPC and one differentiating oligodendrocyte (OL) progeny. Loss of pro-mitotic proteoglycan and OPC marker NG2 in the OL progeny is the earliest immunophenotypic change of unknown mechanism that indicates differentiation commitment. Here, we report that expression of the mouse homolog of Drosophila tumor suppressor Lethal giant larvae 1 (Lgl1) is induced during OL differentiation. Lgl1 conditional knockout OPC progeny retain NG2 and show reduced OL differentiation, while undergoing more symmetric self-renewing divisions at the expense of asymmetric divisions. Moreover, Lgl1 and hemizygous Ink4a/Arf knockouts in OPC synergistically induce gliomagenesis. Time lapse and total internal reflection microscopy reveals a critical role for Lgl1 in NG2 endocytic routing and links aberrant NG2 recycling to failed differentiation. These data establish Lgl1 as a suppressor of gliomagenesis and positive regulator of asymmetric division and differentiation in the healthy and demyelinated murine brain.


Automatic Segmentation of the Fetus in 3D Magnetic Resonance Images Using Deep Learning: Accurate and Fast Fetal Volume Quantification for Clinical Use.
Magnetic resonance imaging (MRI) provides images for estimating fetal volume and weight, but manual delineations are time consuming. The aims were to (1) validate an algorithm to automatically quantify fetal volume by MRI; (2) compare fetal weight by Hadlock's formulas to that of MRI; and (3) quantify fetal blood flow and index flow to fetal weight by MRI. Forty-two fetuses at 36 (29-39) weeks gestation underwent MRI. A neural network was trained to segment the fetus, with 20 datasets for training and validation, and 22 for testing. Hadlock's formulas 1-4 with biometric parameters from MRI were compared with weight by MRI. Blood flow was measured using phase-contrast MRI and indexed to fetal weight. Bland-Altman analysis assessed the agreement between automatic and manual fetal segmentation and the agreement between Hadlock's formulas and fetal segmentation for fetal weight. Bias and 95% limits of agreement were for automatic versus manual measurements 4.5 ± 351 ml (0.01% ± 11%), and for Hadlock 1-4 vs MRI 108 ± 435 g (3% ± 14%), 211 ± 468 g (7% ± 15%), 106 ± 425 g (4% ± 14%), and 179 ± 472 g (6% ± 15%), respectively. Umbilical venous flow was 406 (range 151-650) ml/min (indexed 162 (range 52-220) ml/min/kg), and descending aortic flow was 763 (range 481-1160) ml/min (indexed 276 (range 189-386) ml/min/kg). The automatic method showed good agreement with manual measurements and saves considerable analysis time. Hadlock 1-4 generally agree with MRI. This study also illustrates the confounding effects of fetal weight on absolute blood flow, and emphasizes the benefit of indexed measurements for physiological assessment.


pH-dependent stability and membrane interaction of the pore-forming domain of colicin A.
Thermal stability of the pore-forming domain of colicin A was studied by high sensitivity differential scanning calorimetry and circular dichroism spectroscopy. In the pH range between 8 and 5, the thermal denaturation of the protein in solution occurs at 66-69 degrees C and is characterized by the calorimetric enthalpy of approximately 90 kcal/M. At pH below 5, there is a rapid pH-dependent destabilization of the pore-forming domain resulting in the lowering of the midpoint denaturation temperature and a decrease in the calorimetric enthalpy of denaturation. Circular dichroism spectra in the near and far ultraviolet show that the thermotropic transition is associated with collapse of the native tertiary structure of the pore-forming domain, although a large proportion of the helical secondary structure remains preserved. The present data indicate some similarity also between acid-induced and temperature-induced denaturation of the pore-forming domain of colicin A. Association of the pore-forming domain with phospholipid vesicles of dioleoylphosphatidylglycerol results in total disappearance of the calorimetric transition, even at pH values as high as 7. Since lipid binding also induces collapse of the near ultraviolet circular dichroism spectrum, these data indicate that interaction with the membrane facilitates a conformational change within the pore-forming domain to a looser (denaturated-like) state. These findings are discussed in relation to the recent model (van der Goot, F. G., Gonzalez-Manas, J. M., Lakey, J. H., Pattus, F. (1991) Nature 354, 408-410) which postulates that a flexible "molten globule" state is an intermediate on the pathway to membrane insertion of colicin A.


Burden of Disease in Patients with Mild or Mild-to-Moderate Chronic Obstructive Pulmonary Disease (Global Initiative for Chronic Obstructive Lung Disease Group A or B): A Systematic Literature Review.
Patients with mild or mild-to-moderate chronic obstructive pulmonary disease (COPD), defined as Global Initiative for Chronic Obstructive Lung Disease (GOLD) group A/B, are regarded as having a lower risk of experiencing multiple or severe exacerbations compared with patients classified as GOLD group C/D. Current guidelines suggest that patients in GOLD A/B should commence treatment with a bronchodilator; however, some patients within this population who have a higher disease burden may benefit from earlier introduction of dual bronchodilator or inhaled corticosteroid-containing therapies. This study aimed to provide research-based insights into the burden of disease experienced by patients classified as GOLD A/B, and to identify characteristics associated with poorer outcomes. A systematic literature review (SLR) was conducted to identify evidence (burden of disease and prevalence data) relating to the population of interest (patients with COPD classified as GOLD A/B). A total of 79 full-text publications and four conference abstracts were included. In general, the rates of moderate and severe exacerbations were higher among patients in GOLD group B than among those in group A. Among patients classified as GOLD A/B, the risk of exacerbation was higher in those with more symptoms (modified Medical Research Council or COPD Assessment Test scales) and more severe airflow limitation (forced expiratory volume in 1 second % predicted). Data from this SLR provide clear evidence of a heavier burden of disease for patients in GOLD B, compared with those in GOLD A, and highlight factors associated with worse outcomes for patients in GOLD A/B.


Rivers as a source of marine litter--a study from the SE Pacific.
Composition and abundance of persistent buoyant litter (plastics, polystyrene and manufactured wood) were investigated at riversides and on adjacent coastal beaches of four rivers flowing into the SE Pacific Ocean. Persistent buoyant litter made up the main share of litter at riversides (36-82%) and on coastal beaches near the river mouths (67-86%). The characteristic litter composition of each river is attributable to human influences along its course. Riverine litter items were deposited to both sides of the river mouths on coastal beaches, and their abundance generally declined with distance from the river mouth. However, maximum litter accumulations were often found on beaches north of the river mouth, suggesting a long-term influence of the prevailing equatorward low-level jet along the Chilean coast. The results confirm that riverine transport has an important impact on litter abundances on coastal beaches.


1H-NMR relaxation times and water compartmentalization in experimental tumor models.
The present studies were conducted with RIF-1, M5076 and Panc02 subcutaneous tumor models to assess the relationship between tissue-free water compartmentalization and observed tissue T1 and T2 changes at 10 MHz. Observed T1 was shown to correlate directly with total extracellular water and interstitial water volumes. T1 and T2 were also inversely related to intracellular water volumes. T1 and T2 decreases after dexamethasone treatment were, however, most closely correlated with changes in tumor extracellular water and not changes in cell or total water volumes. Studies to assess Gd-DTPA-dimeg dose dependent T1 and T2 modification in model serum protein solutions indicated that although the Gd concentration that reduced T2 by 50% was about 2.5 fold greater than that required to reduce T1 equally, the of the concentration dependent T1 and T2 modifications were similar. In studies with tumor models, the injected dose of Gd-DTPA-dimeg that reduced T1 by 50% was inversely correlated with tumor extracellular water volumes. The slopes for dose dependent T1 modification in all tumors were similar and similar to that observed for model protein solutions. Gd-DTPA-dimeg had a different effect on observed T2 values for the 3 tumor models. Exponential slopes were about twice that observed for T2 modification of serum protein solutions, and Gd-DTPA-dimeg doses that reduced observed tumor T2 ranged from 9 to 50 times that necessary to similarly reduce T1. The results from these studies indicate that the observed T1, for these tumors, was dominated by relaxation of water protons in interstitial water but that the observed T2 was most strongly influenced by proton relaxation in water compartments that were unavailable to the Gd labeled probe.


Avian thrombocyte thrombospondin.
A high molecular weight glycoprotein (450,000) was obtained from thrombin-treated duck thrombocytes by barium citrate adsorption technique followed by heparin-agarose affinity chromatography. Amino acid composition (high number of acidic amino acids and cystine) as well as carbohydrate contents (1.3 per cent hexosamine, 0.9 per cent sialic acid and 1.5 per cent hexose) showed similarity to mammalian platelet thrombospondin.


The predictive and prognostic significance of cell-free DNA concentration in melanoma.
Melanoma is the leading cause of skin cancer-related deaths worldwide. While there have been significant improvements in the treatment of advanced melanoma in the past decade, biomarker development lagged behind. The majority of liquid biopsy biomarkers rely on the analyses of oncogenic mutations; however, about 20% of melanoma patients are wild type. Therefore, validation of universal predictive and prognostic biomarkers is urgently needed. We analysed plasma samples in a discovery cohort (n = 20) and expansion cohort (n = 166) of metastatic melanoma patients and healthy donors (n = 116). Total plasma circulating cell-free DNA (cfDNA) concentrations were measured on the Qubit® platform using assays for single-(ss) and double (ds)-stranded DNA, DNA spectrophotometry and RNase P qPCR. We explored the diagnostic, predictive and prognostic potential of cfDNA concentration by bio-statistical methods and established a cfDNA threshold for risk stratification. Our selected best method was Qubit® dsDNA assay which quantified higher plasma cfDNA concentrations in melanoma patients than in healthy controls (AUC 72%). Measurement of baseline cfDNA concentration revealed that high cfDNA was associated with presence of metastases and higher AJCC stage (P < 0.05). Furthermore, high baseline cfDNA was an indicator of shorter overall survival in patients with oncogenic mutations (HR 2.12, P = 0.0008), and in wild-type patients (HR 5.55, P < 0.0001). We provide evidence that total cfDNA can be used as a biomarker for melanoma irrespective of the tumour genotype and can provide information on tumour load, risk of progression and risk of death.


Osteochondral plate angiogenesis: a new treatment target in osteoarthritis.
Healthy adult joint cartilage contains neither blood vessels nor nerves. Osteoarthritic cartilage, in contrast, may be invaded by blood vessels from the subchondral bone. The mechanisms underlying cartilage angiogenesis in osteoarthritis are unclear but may involve hypertrophic chondrocyte differentiation. Active research is under way to identify the factors involved in cartilage angiogenesis. Here, we discuss the pathophysiological mechanisms of osteoarthritic cartilage angiogenesis based on evidence from a systematic literature review of articles retrieved via PubMed and ISI Web of Knowledge. Our conclusions suggest new research perspectives and treatment options.


A Time of Healing: Can Social Engagement After Bereavement Reduce Trajectories of Depression After the Death of a Child?
We work from a stress and life-course perspective to examine the mental health of parents who experienced the death of their child. We examine whether mental health eventually returns to pre-bereavement levels and how social engagement after bereavement may shape the recovery process of depressive symptoms. We analyze discontinuous growth curve models to assess the association between a child's death and trajectories of parents' depressive symptoms from the 1998-2016 Health and Retirement Study. The sample includes 16,182 parents aged 50 years and older. Those who transitioned to bereavement experienced an elevation in depressive symptoms and a relatively long recovery time (e.g., 7 years) to their pre-bereavement mental health in our findings. However, when engaging in volunteer work after their loss, depressive symptoms reduce more quickly to their pre-bereavement levels. Volunteering offsets up to 3 years of the negative consequences of child loss. The death of a child is a traumatic event with extensive health consequences, but research should more fully examine the dynamic nature and potential mitigation of these health consequences over time. Our findings expand the temporal lens to encompass healing processes after bereavement, incorporating the importance of social engagement.


Organometallic Half-Sandwich Dichloridoruthenium(II) Complexes with 7-Azaindoles: Synthesis, Characterization and Elucidation of Their Anticancer Inactivity against A2780 Cell Line.
A series of organometallic half-sandwich dichloridoruthenium(II) complexes of the general formula [Ru(η6-p-cym)(naza)Cl2] (1-8; p-cym = p-cymene; naza = 7-azaindole or its derivatives) was synthesised and fully characterized by elemental analysis, mass spectrometry, and infrared and multinuclear NMR spectroscopy. A single-crystal X-ray structural analysis of [Ru(η6-p-cym)(2Me4Claza)Cl2] (6) revealed a typical piano-stool geometry with an N7-coordination mode of 2-methyl-4-chloro-7-azaindole (2Me4Claza). The complexes have been found to be inactive against human ovarian cancer cell line A2780 up to the highest applied concentration (IC50 > 50.0 μM). An inactivity of the complexes is caused by their instability in water-containing solvents connected with a release of the naza N-donor ligand, as proved by the detailed 1H NMR, mass spectrometry and fluorescence experiments.


Anticoagulation Choice and Timing in Stroke Due to Atrial Fibrillation: A Survey of US Stroke Specialists (ACT-SAFe).
Risk of early recurrent ischemic stroke in patients with atrial fibrillation may be high. ASA/AHA guidelines provide imprecise recommendations on the timing and anticoagulant choice for this indication. We assessed current opinions of stroke neurologists. Case scenarios describing patients with acute ischemic stroke (AIS) due to paroxysmal atrial fibrillation (AF) were presented to US board-certified stroke neurologists in an internet-based questionnaire. Questions assessed timing and choice of anticoagulation for secondary stroke prevention, factors prompting earlier anticoagulation, reasons for specific anticoagulant choice, and alternatives to anticoagulation in ineligible patients. Open-ended comments were also solicited. Responses were available from 238/1239 stroke neurologists surveyed. In patients with small AIS without hemorrhagic transformation (HT), 51% elected to start anticoagulation within 96 hours. With increased stroke severity and asymptomatic HT, only 29% and 26% respectively chose to anticoagulate within 7 days. Few requested stability imaging before starting anticoagulation. With symptomatic HT the majority (79%) waited >14 days. 93% would anticoagulate earlier if left atrium/left atrial appendage or acute left ventricular thrombi, or mechanical heart valve were present. Direct oral anticoagulants (DOACs) were the preferred anticoagulation strategy (64%), and the remaining 38% preferred Warfarin. Aspirin was preferred by 57% in anticoagulation ineligible. Apart from AIS with symptomatic HT, there is a remarkable lack of consensus among stroke neurologists regarding the timing of anticoagulation for secondary stroke prevention in patients with AIS due to PAF. DOACs are the preferred anticoagulation strategy. More studies are required to clarify anticoagulant management in this patient population.


Small airways disease in asthma.
A mounting body of physiologic and pathologic evidence indicates that asthma involves the central and the more distal airways. In patients with asthma, the peripheral lung accounts for a significant portion of airway resistance and, similar to the large airways, the small airways have been shown to be hyperresponsive to nonspecific stimuli, such as methacholine. Cellular inflammation, consisting of an infiltrate rich with lymphocytes and eosinophils, is present in the small airways of patients with asthma and may be more intense than that observed in the large airways. Clinical assessment of the peripheral airways continues to be a challenge, and new techniques, such as quantitative analysis of chest CT images, have proven to be useful research tools. The recognition of small airways involvement in asthma has clinical relevance, as new formulations of inhaled corticosteroids with smaller particle aerosols may be more effective in addressing this component of asthma.


A sensitive colorimetric strategy for monitoring cerebral β-amyloid peptides in AD based on dual-functionalized gold nanoplasmonic particles.
A sensitive and selective strategy for the colorimetric visualization of the total monomeric Aβ down to 40 pg mL(-1) based on dual-functionalized gold nanoplasmonic particles (GNPs) is developed and applied to evaluate Aβ levels in the AD cerebral system.


Synthesis of 1-Aryltetralins via Re2O7/HReO4 Mediated Intramolecular Hydroarylations.
Here, we describe highly efficient intramolecular hydroarylations mediated by Re2O7/HReO4. Styrene derivatives of different electronic properties have been activated to effect a challenging intramolecular hydroarylation for the facile access to various substituted 1-aryltetralin structures. This method is characterized by mild reaction conditions, broad substrate scope, high chemical yields, and 100% atom economy. The potential synthetic application of this methodology was exemplified by the efficient total synthesis of an isoCA-4 analogue.


"Eat me" and "don't eat me" signals govern the innate immune response and tissue repair in the CNS: emphasis on the critical role of the complement system.
A full innate immune system (e.g. complement system, scavenger receptors, Toll-like receptors (TLR)) has been described in the CNS and is thought to be an extremely efficient army designed to fight against invading pathogens and toxic cell debris such as apoptotic cells and amyloid fibrils. The binding of soluble or secreted innate immune molecules on pathogen-associated molecular patterns (PAMPs) as well as apoptotic cell-associated molecular patterns (ACAMPs) provide several "eat me" signals to promote the safe disposal of the intruders by professional and amateur phagocytes. These patterns are deciphered by receptors (pattern recognition receptors, PRRs; e.g. CR3) that control phagocytosis and associated inflammatory response depending on the meaning of these signals. Importantly, in order to avoid excessive collateral damage of surrounding cells, it is increasingly evident that "don't eat me" signals (coined herein as self-associated molecular patterns, SAMPs; e.g. complement regulatory proteins, CD200) are of paramount importance to signal a robust anti-inflammatory response and promote tissue repair. Further knowledge of the innate immune response in the CNS will greatly help to delineate the novel therapeutic routes to protect from CNS inflammation and neurodegeneration.


Regulation of gonadotropin secretion in Turner's syndrome.
To determine the role of body fat in regulating secretion of luteinizing hormone and follicle-stimulating hormone, we measured both at 20-minute intervals for 24 hours in eight children with Turner's syndrome. The 24-hour mean luteinizing hormone levels varied from 20.2 to 70.5 mlU per milliliter. Total body weight, total body fat and percentage of body fat showed a significant negative correlation with the 24-hour mean luteinizing hormone concentrations (P less than 0.01). The 24-hour mean follicle-stimulating hormone concentrations ranged from 60.4 to 229 mlU per milliliter, with a significant negative correlation between total body fat and percentage body fat and the 24-hour mean concentrations (P less than 0.05). These negative correlations were not mediated by estrogens or androgens.


In response to "The Knowledge of Our Knowledge": a reflection on McAndrews' view of epistemology.
This commentary considers one of the articles published in the first volume of this journal and reflects on the status of research and knowledge at that time. The chiropractic profession has witnessed advancement in the use of the scientific method in the past several decades, and scholarly journals have helped support this substantial growth.


A 5-year study of the prevalence and genetic diversity of human caliciviruses associated with sporadic cases of acute gastroenteritis in young children admitted to hospital in Melbourne, Australia (1998-2002).
The prevalence and genetic diversity of human caliciviruses causing sporadic cases of acute gastroenteritis in young children hospitalized in a large pediatric hospital in Melbourne, Australia over 5 years (incorporating January 1998-December 2002) was studied by reverse transcription and sequence analysis of part of the polymerase gene. The overall prevalence of calicivirus infection in children aged <5 years during the 5 year study was 9.2% (113/1,233), with 95% of the strains belonging to the Norovirus genera. Strains of the norovirus G11-4 cluster were the most common type identified in 4 of the 5 years studied (1998, 1999, 2001, and 2002), with strains of norovirus cluster G11-5 the most common type during 2000. Additional norovirus genetic clusters GI-3, GII-1, GII-2, GII-3, GII-6, and GII-7, were also identified, but comprised only 17/94 of norovirus genogroup II strains. Five sapovirus strains were also identified. These results highlight the divergence of norovirus strains identified in a pediatric population.


Occurrence and distribution of micro(meso)plastic-sorbed heavy metals and metalloids in sediments, Gulf of Guinea coast (SE Atlantic).
The pervasive existence of microplastics (MPs) and toxic metals is raising environmental and health concerns. Plastics are essentially a complex mixture of chemicals, but exposure to the aquatic environment increases their complexity through contaminant desorption/sorption. The aim of this study was to establish baseline data on the elemental occurrence and distribution of potentially toxic and geochemical metals/metalloids in microplastics 1-5 mm and mesoplastics (> 5 mm - 1 cm) along designated coastlines of the Gulf of Guinea (Nigeria) in addition to enabling more comprehensive ecotoxicological risk assessment. The concentrations of twenty-six metals: aluminium (Al), antimony (Sb), arsenic (As), barium (Ba), boron (B), cadmium (Cd), calcium (Ca), chromium (Cr), cobalt (Co), copper (Cu), iron (Fe), lead (Pb), magnesium (Mg), manganese (Mn), molybdenum (Mo), nickel (Ni), potassium (K), selenium (Se), sodium (Na), silicon (Si), silver (Ag), strontium (Sr), thallium (Tl), titanium (Ti), vanadium (V), and zinc (Zn), associated with beach MPs, pristine, and lagoon plastics were determined after extraction in 10% nitric acid and analysis using inductively coupled plasma-optical emission spectroscopy (ICP-OES). The distribution of MPs was variable, with 3680 particles identified along the drift and high waterlines across designated shoreline locations. The beach MPs were dominated by polyethylene (PE), polypropylene (PP), and polystyrene (PS), whereas lagoon-sourced plastics were characterized by polyethylene terephthalate (PET), polystyrene (PS), and polyurethane (PUR). Metal concentration was higher when associated with foam plastic (PS, PUR, PEVA) compared to hard plastic (PE, PP, PET) samples. The results showed that all samples had slightly elevated Al, Fe, Mn, and Zn concentrations, suggesting potential sorption interactions and plastic additive influences. Notably, foam MPs had a stronger affinity for metals. This study emphasizes the critical role of microplastics in serving as vectors for toxic metals. Except for Cd, pollution indices such as the potential contamination index (PCI), hazard quotient (HQ), and modified hazard quotient (mHQ) indicated low severity contamination of beach and lagoon MPs by heavy metals. However, considering long-term accumulation of sorbed metals, their potential toxicity to marine biota may be considerable.


Model of topographic map development guided by a transiently expressed repulsion molecule.
The projection from the retina develops into a precise map of the visual world on the surface of the tectum. The search for molecular position cues that mediate map formation has recently yielded a tectal molecule that exerts a repulsion to fibers from the entire temporal half retina. This molecule appears not to function in the generally accepted gradient manner but instead provides only binary position information, and it is only expressed transiently during early development. Here we describe modeling results that compare the efficacy of binary versus graded position cues in topographic map formation; the model also includes an activity dependent process. We find that binary repulsion is more efficient than graded chemoaffinity in the rapid establishment of map polarity, and transient expression of either cue provides sufficient guidance for precise map formation.


Respiratory neurons of the pneumotaxic center during sleep and wakefulness.
Extracellular recordings were made from respiratory related units (RRUs) in the pneumotaxic center (PNC) of unanesthetized cats across states of consciousness: wakefulness, NREM and REM sleep. Contrary to expectations from results in acute preparations, well-modulated respiratory activity was detected in chronic animals with vagi intact. Pontine RRU activity decreased during sleep in 75% of the cells studied. The greatest reduction occurred during REM sleep.


Lysine malonylation and propionylation are prevalent in human lens proteins.
Acylated lysine residues represent major chemical modifications in proteins. We investigated the malonylation and propionylation of lysine residues (MalK, PropK) in the proteins of aging human lenses. Western blot results showed that the two modifications are present in human lens proteins. Liquid chromatography-mass spectrometry (LC-MS/MS) results showed 4-18 and 4-32 pmol/mg protein of MalK and PropK, respectively, in human lens proteins with no apparent changes related to aging. Mass spectrometry results revealed that MalK- and PropK-modified lysine residues are present in all major crystallins, other cytosolic proteins, and membrane and cytoskeletal proteins of the lens. Several mitochondrial and cytosolic proteins in cultured human lens epithelial cells showed MalK and PropK modifications. Sirtuin 3 (SIRT3) and sirtuin 5 (SIRT5) were present in human lens epithelial and fiber cells. Moreover, lens epithelial cell lysate deacylated propionylated and malonylated lysozyme. The absence of SIRT3 and SIRT5 led to higher PropK and MalK levels in mouse lenses. Together, these data suggest that MalK and PropK are widespread modifications in lens and SIRT3 and SIRT5 could regulate their levels in lens epithelial cells.


The corpus callosum: normal fetal development as shown by transvaginal sonography.
Detection of the corpus callosum in the developing fetus on sonograms usually is difficult. We determined the normal appearance and development of this structure during the second half of pregnancy, as shown on transvaginal sonograms. One hundred one fetuses were evaluated with transvaginal sonography between 18 and 42 weeks' gestation. The length of the corpus callosum and the thicknesses of the genu, body, and splenium were measured, and growth tables were produced. The corpus callosum was detected in 95% of cases and showed gradual enlargement during pregnancy; growth was linear, from nearly 17 mm in length at 18 weeks' gestation to 44 mm at term. The ratios of the length of the corpus callosum to the anteroposterior diameter of the brain remained relatively constant from 20 to 21 weeks' gestation to term. Transvaginal sonography can be used to visualize and measure the corpus callosum in the developing fetus. Data from this study may be useful as a reference for normal development of the corpus callosum.


Self-initiated coping with Tourette's syndrome: Effect of tic suppression on QOL.
Because of the semi-voluntary nature of tics, patients with Tourette' syndrome (TS) often report self-initiated coping with tics. Our goals were to understand the experiences of self-initiated coping with tics by individuals with TS (e.g., suppression frequency, suppression ability, and side effects of tic suppression), and investigate the effects of tic control on quality of life (QOL). One hundred participants with TS (38 children and 62 adults) answered a questionnaire concerning tic control, QOL, and other clinical characteristics. Fifty-eight percent of the participants always or frequently tried to suppress tics daily. In contrast, over 90% felt uncomfortable or incomplete when they suppressed tics and needed concentration or extra effort to suppress them. Thirty-four percent could suppress tics for less than one minute and 65% could suppress tics for less than 10min. Higher subjective satisfaction with tic control was positively correlated with life satisfaction and QOL. Individuals with TS often attempt self-initiated coping in their daily lives, especially through tic suppression, despite experiencing subjective discomfort and being aware that the duration of tic suppression is often limited. Moreover, it was found that their subjective satisfaction with tic control and effective tic suppression might have a positive influence on their life satisfaction and QOL. Thus, self-initiated coping with tics is vital for improving the QOL of individuals with TS and intervention aimed at enhancing subjective satisfaction with tic control could help manage TS.


Mediation of smoking-associated postoperative mortality by perioperative complications in veterans undergoing elective surgery: data from Veterans Affairs Surgical Quality Improvement Program (VASQIP)--a cohort study.
To assess the mediation of smoking-associated postoperative mortality by postoperative complications. Observational cohort study. Using data from the Veterans Affairs (VA) Surgical Quality Improvement Programme, a quality assurance programme for major surgical procedures in the VA healthcare system, we assessed the association of current smoking at the time of the surgery with 6-month and 1-year mortality. Using mediation analyses, we calculated the relative contribution of each smoking-associated complication to smoking-associated postoperative mortality, both unadjusted and adjusted for age, race/ethnicity, work relative value unit of the operation, surgeon specialty, American Society of Anesthesiologists class and year of surgery. Smoking-associated complications included surgical site infection (SSI), cardiovascular complications (myocardial infarction, cardiac arrest and/or stroke) and pulmonary complications (pneumonia, failure to wean and/or reintubation). There were 186 632 never smokers and 135 741 current smokers. The association of smoking and mortality was mediated by smoking-related complications with varying effects. In unadjusted analyses, the proportions of mediation of smoking to 6-month mortality explained by the complications were as follows: SSIs 22%, cardiovascular complications 12% and pulmonary complications 89%. In adjusted analyses, the per cents mediated by each complication were as follows: SSIs 2%, cardiovascular complications 4% and pulmonary complications 22%. In adjusted analyses for 1-year mortality, respective per cents mediated were 2%, 3% and 16%. Pulmonary complications, followed by cardiovascular complications and SSIs were mediators of smoking-associated 6-month and 1-year mortality. Interventions targeting smoking cessation and prevention and early treatment of pulmonary complications has the likelihood of reducing postoperative mortality after elective surgery.


[Chronic meningococcal meningitis in an adult].
A 46-year-old woman was admitted for a four-month history of progressive cognitive and behavioral disorders. MRI revealed hydrocephalus with meningeal enhancement after gadolinium infusion. The lumbar puncture found a purulent CSF containing 305 nucleate elements per cubic millimeter including 84% altered polymorphonuclear neutrophils, protein at 4.88 g/L, and glucose at 0.5 mmol/L (for a glycemia at 6 mmol/L); there was no germ on direct examination. High dose IV cefotaxime was started together with anti-tuberculous treatment. After nine days CSF cultures were positive for Neisseria meningitidis group B. The patient improved dramatically. Only three cases of chronic N. meningitidis meningitis have been previously reported in the literature. It is important to recall that the clinical presentation of N. meningitis can be misleading, sometimes pseudo-psychiatric, without frank infectious syndrome, and may follow a chronic course.


STAT: Superior Vena Cava Syndrome.
Superior vena cava syndrome is the obstruction of blood flow through the superior vena cava.


Blockade of adipocyte differentiation by cordycepin.
Cordyceps militaris has the potential to suppress differentiation of pre-adipocytes. However, the active entities in the extract and the underlying mechanisms of its action are not known. Hence, we investigated whether and how cordycepin (3'-deoxyadenosine), a constituent of C. militaris, inhibits adipogenesis. Differentiation of 3T3-L1 pre-adipocytes and pre-adipocytes in primary cultures was induced by Insulin, dexamethasone and IBMX, and these were used as in vitro models of adipogenesis. The effects of cordycepin on adipogenesis were examined with particular focus on the regulation of CCAAT/enhancer-binding protein β (C/EBPβ) and PPARγ. Cordycepin suppressed the lipid accumulation and induction of adipogenic markers that occurred on differentiation of pre-adipocytes and also blocked the down-regulation of a pre-adipocyte marker. This anti-adipogenic effect was reversible and mediated by an adenosine transporter, but not A₁, A₂ or A₃ adenosine receptors. This effect of cordycepin was not reproduced by other adenosine-related substances, including ATP, ADP and adenosine. Early induction of the adipogenic C/EBPβ-PPARγ pathway was suppressed by cordycepin. Blockade of mTORC1 via inhibition of PKB (Akt) and activation of AMP kinase was identified as the crucial upstream event targeted by cordycepin. In addition to its negative effect on adipogenesis, cordycepin suppressed lipid accumulation in mature adipocytes. These results suggest that the anti-adipogenic effects of cordycepin occur through its intervention in the mTORC1-C/EBPβ-PPARγ pathway. Cordycepin, by blocking both adipogenesis and lipid accumulation, may have potential as a therapeutic agent for effective treatment of obesity and obesity-related disorders.


The influence of nutritional status on skin anergy in experimental cancer.
Malignant tumours as well as severe malnutrition can interfere with carcass weight, serum albumin and delayed hypersensitivity tests. In order to identify the separate effects of these two phenomena, Wistar rats were submitted to various nutritional manipulations prior to Walker-256 carcinosarcoma inoculation (TU). Six groups of well-nourished rats with positive response to the Keyhole Limpet Haemocyanin (KLH) test were studied. Three TU-bearing groups were established, [1] protein-deprived before and after TU (group DDT), [2] protein deprived before TU and later brought back to normal chow (group DNT), and [3] those receiving a complete diet throughout the experiment (group NNT). Identical control groups without TU, sham-injected, were called DDC, DNC and NNC. Tumour size and body weight were measured daily. KLH tests were done sequentially and serum albumin was determined at sacrifice. Results indicated that cancer produced marked changes in immune response. Malnutrition was responsible for anergy and weight loss, and further aberrations tended to occur when both conditions were present. Feeding was able to restore body weight and KLH response in tumour-bearing as well as in control rats, but subsequent deterioration occurred in cancer bearing rats after the first week of tumour development. It is concluded that cancer potentiates the effects of malnutrition, on body weight and immune response, but temporary recovery could be demonstrated after adequate refeeding.


Polyphenols of Cassia tora leaves prevents lenticular apoptosis and modulates cataract pathology in Sprague-Dawley rat pups.
Cataract is a leading cause of visual impairment worldwide with multifactorial etiology and is a significant global health problem with increasing prevalence with age. Currently, no pharmacological measures are discovered to prevent and treat cataract and a significant number of epidemiological studies have suggested the potential role of antioxidants in the prevention of cataract by scavenging free radicals and preventing lens protein derangement and lenticular cell damage. The main goal of the present study is to evaluate Cassia tora leaves; an edible leafy vegetable employed in Ayurvedic and Chinese system of medicine for eye rejuvenation in preventing selenite-induced cataract in rat pups and to identify the active components that produce the effect. ECT pre-treatment effectively restored both enzymatic and metabolic antioxidant levels, membrane integrity and reduced metal accumulation and thus down-regulate epithelial cell death. Gene expression studies also confirmed these findings. ESI-MS analysis of ECT revealed the presence of chrysophanol, emodin, kaemferol, quercetin, stigmasterol and isoquercetin. The study suggests the possible role of C. tora in alleviating cataract pathology and presence of many anthraquinones and flavonoids. As it is an edible plant, the incorporation of these leaves in daily vegetables might prevent or delay the onset and maturation of cataract.


Clinical outcome and prognosis of dogs with histopathological features consistent with epitheliotropic lymphoma: a retrospective study of 148 cases (2003-2015).
Limited information is available regarding the treatment and outcome of dogs with epitheliotropic lymphoma. The disease typically has a poor prognosis. To characterize the clinical signs, identify prognostic factors and evaluate the treatment outcome of dogs with epitheliotropic lymphoma. A retrospective review of medical records from 2003 to 2015. Treatment details, tumour response and survival time were recorded for 148 dogs. Potential prognostic factors were evaluated for their statistical effect on median survival time. The overall median survival time for dogs was 264 days (cutaneous: 130 days; mucocutaneous/mucosal: 491 days). On multivariate analysis, a shorter median survival time was associated with the cutaneous form (P < 0.001) and the presence of multiple lesions (P < 0.001). Among 80 dogs with cutaneous lesions, chemotherapy treatment (P < 0.001) and having a solitary lesion (P < 0.001) were associated with longer median survival. In 72 dogs with multiple cutaneous lesions, chemotherapy intervention (P < 0.001), retinoid treatment (P = 0.001) and complete remission (P = 0.001) were associated with longer median survival. In 68 dogs with mucocutaneous/mucosal lesions, decreasing age (P = 0.020) and a solitary lesion (P = 0.015) were associated with longer median survival. Canine epitheliotropic lymphoma may be divided into cutaneous and mucocutaneous/mucosal forms. Solitary lesions have a better prognosis. Dogs with multiple lesions appear to benefit from chemotherapy and retinoid treatment, with those attaining complete remission having longer survival times. Multi-agent chemotherapy could be considered in dogs with cutaneous lesions that fail to respond to single-agent chemotherapy.


Decision-Making on Recommended Age of Spay/Neuter for a Specific Dog: General Principles and Cultural Complexities.
Many dogs and cats were euthanized in US animal shelters through the 1940s, sharply declining in the 1980s. Early age neutering of young cats and dogs grew frequent in the 1990s; adoptions from shelters increased, leading to a decline in shelter euthanasia of dogs. Several publications, beginning in 2013, revealed heightened risks of joint disorders and some cancers for some dog breeds when neutered at young ages. These risks are breed-, gender-, and body-size specific and related to neutering age. Current guidelines suggest making a personalized decision for each dog's neutering age. Recommendations are presented for 40 breeds and mixed-breed weight classes.


Exclusion of lung metastases in placental site trophoblastic tumor using [18F]fluorodeoxyglucose positron emission tomography: a case report.
We present the first case using [18F]fluorodeoxyglucose positron emission tomography (PET) for the evaluation of multiple lung nodules in a woman with placental site trophoblastic tumor (PSTT) and history of pulmonary tuberculosis. PSTT was diagnosed by endometrial biopsy in a 38-year-old female, 11 months after an abortion. She had received medical treatment for pulmonary tuberculosis 8 years ago. Nodular lung lesions in upper and lower lung fields were noted on the chest X-ray and computed tomography, which was not shown on PET. She then received hysterectomy and complete remission of serum beta-hCG titer with stationary lung lesions in follow-up images were noticed thereafter. PET, as adjuvant study to conventional images, may help in the differentiation of chest lesions in PSTT.


No impact of NOD2/CARD15 on outcome after SCT.
Recent studies have pointed towards an association between certain single nucleotide polymorphisms (SNPs) in the NOD2/CARD15 gene, and negative outcome of Allo-SCT. In this study, 198 patients and their corresponding donors were analyzed retrospectively for the occurrence of NOD2/CARD15 mutations to evaluate the impact on clinical results after Allo-SCT. In all, 7.6% of the patients and 11% of the donors were heterozygous for one of three SNPs 8, 12 or 13. Contrary to earlier findings, we found no significant impact on incidence of acute GVHD or TRM following Allo-SCT. These differences in results could be due to a lower mutation frequency in the studied population and/or a lower overall incidence of severe GVHD. On the basis of these findings we conclude that a consideration to NOD2/CARD15 mutation status is not pertinent when selecting a donor for Allo-SCT at our centre.


[Study of temperature of composite resins during polymerization].
Temperature was measured during polymerization of 24 composite materials within 5 minutes (up to 10 minutes) after starting polymerization. A sudden rise (10 K-18 K) of temperature could be observed in most of the materials; soon afterwards the primary situation was reached again. The measured high temperatures should be considered to might be one of the factors, which lead to an affection of the pulp tissue.


Enzymatic catalysis in nonaqueous solvents.
Subtilisin and alpha-chymotrypsin vigorously act as catalysts in a variety of dry organic solvents. Enzymatic transesterifications in organic solvents follow Michaelis-Menten kinetics, and the values of V/Km roughly correlate with solvent's hydrophobicity. The amount of water required by chymotrypsin and subtilisin for catalysis in organic solvents is much less than needed to form a monolayer on its surface. The vastly different catalytic activities of chymotrypsin in various organic solvents are partly due to stripping of the essential water from the enzyme by more hydrophilic solvents and partly due to the solvent directly affecting the enzymatic process. The rate enhancements afforded by chymotrypsin and subtilisin in the transesterification reaction in octane are of the order of 100 billion-fold; covalent modification of the active center of the enzymes by a site-specific reagent renders them catalytically inactive in organic solvents. Upon replacement of water with octane as the reaction medium, the specificity of chymotrypsin toward competitive inhibitors reverses. Both thermal and storage stabilities of chymotrypsin are greatly enhanced in nonaqueous solvents compared to water. The phenomenon of enzymatic catalysis in organic solvents appears to be due to the structural rigidity of proteins in organic solvents resulting in high kinetic barriers that prevent the native-like conformation from unfolding.


Severity of coronary artery disease in postmenopausal diabetic women.
Coronary artery disease (CAD) risk increases in women after the menopause. The aim of this study was to determine the effect of diabetes on the severity of CAD in postmenopausal women undergoing coronary angiography. 180 postmenopausal women underwent coronary angiography for suspected CAD. CAD severity was assessed by the number of arteries (0-3) with >50% stenosis in the angiography. Forty-four women had type 2 diabetes mellitus (T2DM). Predisposing risk factors and biochemical and hormonal parameters were recorded. The diabetic women were older (p=0.014), had higher BMI and waist circumference (p<0.001), higher prevalence of hypertension (p=0.002), higher levels of triglycerides, uric acid and higher HOMA-Insulin Resistance Index (p=0.009). The women with diabetes had a higher prevalence of severe stenosis in the angiography: T2DM: 0-vessels 25%, 1-vessel disease 18.2%, 2-vessels disease 22.7%, 3-vessels disease 34.1%, vs. 49.2%, 23.5%, 22.1%, 5.1% in the non-diabetic women, respectively (p<0.001). Binary logistic regression analysis showed that T2DM was a significant predictor of severe CAD (>or=3 vessel disease) independently of age, family history of T2DM, BMI, time since menopause, hypertension and hypercholesterolemia. Women with T2DM also had lower sex hormone binding globulin (SHBG, p=0.010) levels compared to non-diabetic women. Diabetic postmenopausal women develop more severe CAD compared to non-diabetic women. This association is independent of other predisposing factors and suggests an independent effect of T2DM on the atherosclerotic process, at least in women after menopause.


Surgical management of hip prosthetic failure in metallosis: A case series and literature review.
Local and remote complications can be observed in hip prosthesis failures associated with metallosis. Structural changes in the periprosthetic bone and soft tissues may not always be precisely assessed preoperatively due to metal artifacts. The unpredictability of the damage extension, potentially leading to complex and insidious surgeries, requires the availability of alternative surgical plan(s) for the reconstruction of the joint. The aim of the study is to present and analyze, with the literature data support, practical tips for the revision of the prosthetic components, the management of ARMD and of intraoperative complications in the unusual scenario of metallosis.


Graphene-Modified Interface Controls Transition from VCM to ECM Switching Modes in Ta/TaOx Based Memristive Devices.
By modification of the electrode-solid-electrolyte interface with graphene, transit from valence change memories (VCM) to electrochemical metallization memories (ECM) in the cell Ta(C)/Ta2 O5 /Pt is demonstrated, thus, bridging both mechanisms. The ECM operation is discussed in the light of Ta-cation mobility in TaOx . The crucial role of electrochemical processes and moisture in the resistive switching process is also highlighted.


Behavioural responses to photographs by pictorially naïve baboons (Papio anubis), gorillas (Gorilla gorilla) and chimpanzees (Pan troglodytes).
This study assessed how pictorially naïve nonhuman primates understand pictures. Fifty-five baboons with no prior exposure to pictures were trained to grasp a slice of banana presented against a pebble in a two alternative forced choice task. Post-training testing involved three stimulus pairs: (1) real banana slice vs. its picture, (2) the banana picture vs. a real pebble and (3) banana picture vs. a pebble picture which were presented twice. Preliminary data were also collected on naïve gorillas (n=4) and chimpanzees (n=7) using the same procedure. Baboons revealed a preference for the food picture in (2) and (3) and often ate this stimulus, but the food item and its picture were accurately discriminated in (1). These results suggest that baboons mistook the pictorial stimulus and its referent, but processed the banana pictures as poor exemplars of the real banana category. Among apes, only gorillas ate the banana pictures, suggesting that picture-object confusion may also occur in this species. Findings are discussed as pertaining to the general issue of representational abilities in nonhuman primates, and its evolution.


Comparisons of self-ratings on managerial competencies, research capability, time management, executive power, workload and work stress among nurse administrators.
To assess the level of and the differences in managerial competencies, research capability, time management, executive power, workload and work-stress ratings among nurse administrators (NAs), and to determine the best predictors of managerial competencies for NAs. Although NAs require multifaceted managerial competencies, research related to NAs' managerial competencies is limited. A cross-sectional survey was conducted with 330 NAs from 16 acute care hospitals. Managerial competencies were determined through a self-developed questionnaire. Data were collected in 2011. All NAs gave themselves the highest rating on integrity and the lowest on both financial/budgeting and business acumen. All scores for managerial competencies, research capability, time management and executive power showed a statistically significant correlation. The stepwise regression analysis revealed that age; having received NA training; having completed a nursing project independently; and scores for research capability, executive power and workload could explain 63.2% of the total variance in managerial competencies. The present study provides recommendations for future administrative training programmes to increase NAs' managerial competency in fulfilling their management roles and functions. The findings inform leaders of hospitals where NAs need to develop additional competencies concerning the type of training NAs need to function proficiently.


Human health risks from fish consumption following a catastrophic gas oil spill in the Chiquito River, Veracruz, Mexico.
An industrial accident resulted in a gas oil spill of 11,808 barrels in the upper part of the Coatzacoalcos River watershed. After river shore cleanup, concentrations of total petroleum hydrocarbons (TPH) and polycyclic aromatic hydrocarbons (PAH) in muscle (+ skin) were determined in captured fish to evaluate human health risk due to fish consumption post-spill in the most affected communities. Data on fish consumption, body weight, and diet factor were collected by questionnaires and field observations. Using standard formulas for carcinogenic and non-carcinogenic substances, site-specific remediation levels were calculated in fish, comparing them to the real levels observed. Likewise, the levels of PAHs in fish captured pre- and post-spill were compared to determine their origin (pyrolytic vs. petrogenic). The TPH concentrations were between 119,000 and 523,000 ng/g (dry weight) and no significant difference (P > 0.05) was found pre- vs. post-spill. The concentration of total PAHs varied between 2494.83 and 35,412.23 ng/g (dry weight), with the concentrations of naphthalene (520.9 ng/g) and phenanthrene (7532.7 ng/g) being much higher than in control samples, and being from the gas oil spill (petrogenic origin). The site-specific remediation levels calculated for TPH and PAH were much higher than the maximum levels actually detected. No human health risks were found from hydrocarbons from the spill, at least after cleanup efforts and natural attenuation (six months).


Exploration of the potential capacity of fly ash and bottom ash derived from wood pellet-based thermal power plant for heavy metal removal.
This study was conducted to explore the potential capacity for the removal of heavy metals from the fly ash (FA) and bottom ash (BA) emitted by wood pellet thermal power plants. Fly ash consists of inorganic compounds such as CaSiO3, P2O5, and K2O, whereas BA shows properties very similar to the biochar derived from organic biomass. The adsorption properties of both FA and BA for Cd were described well by the Langmuir and pseudo-second-order models, and the maximum adsorption capacity of FA for Cd was 4.2 times higher than that of BA. The results indicate that FA can be applied to the treatment of wastewater that contains heavy metals over pH range from 2-6; however, BA is considered to be most effective for application with wastewater that contains heavy metals at a pH of 5-6. Study of the mechanism concluded that the adsorption of Cd by FA is dominated by the formation of Cd2SiO4 complexes by chemical reactions between CaSiO3 and Cd ions as well as via the precipitation of Cd(OH)2 in the neutral and alkaline solutions that is caused by the dissolution of K. It was found that the adsorption of Cd by BA was influenced by the binding of functional groups (CC and COH), coupled CaCO3 dissolution-CdCO3 precipitation reaction and ion exchange between some minerals with Si and Cd ions in weakly acidic conditions. Results indicate that the FA and BA emitted from wood pellet thermal power plants have high potential for heavy metal removal, and their practical use in the purification and restoration of heavy metals could be an effective way to reduce the waste produced by power plants and clean the environment.


Predictors of mortality, length of stay and discharge destination in blunt trauma.
The present study explored a range of variables to identify predictors of mortality and morbidity and to develop prediction models based on these variables. Tools for predicting mortality, hospital length of stay and a patient's destination post-hospital discharge were developed using logistic regression in one dataset (design) and evaluated for prediction performance in a separate dataset (validation). The performance of the mortality model was compared to the trauma and injury severity score (TRISS) and a severity characterization of trauma (ASCOT). The profile of variables contributing to the final prediction models developed from the design dataset varied across the different outcomes of interest although age, injury severity score, development of complications and triage category were common predictors of all three outcomes. The performance of the new mortality prediction model was superior to both TRISS and ASCOT in the validation dataset. Overall, the new models did not meet the prespecified performance criteria. The present study identified key predictors of mortality and morbidity (length of hospital stay and discharge destination). The newly developed mortality model out-performed published trauma scoring methods. However, further development and trial of the new prediction models is required before implementation as definitive audit and benchmarking tools could be recommended.


Effect of histone deacetylase inhibitor (vorinostat) on new-onset diabetes induced by tacrolimus.
The immunosuppressant tacrolimus is a major cause of new-onset diabetes after transplantation. The aim of this study was to evaluate whether a low dose of the histone-deacetylase inhibitor (vorinostat) might ameliorate tacrolimus-induced new-onset diabetes. Thirty 8-week-old male Wistar rats were randomly divided into five groups: a control group, tacrolimus group (1.5 mg/kg intraperitoneally for 28 days), vorinostat group (15 mg/kg orally for 28 days), a group receiving tacrolimus with vorinostat for 28 days; and a group receiving coadministration of tacrolimus for 28 days and vorinostat for 14 days. Diabetes development was assessed on the basis of serum glucose, insulin, HOMA-IR and C-peptide. To investigate the mechanism of vorinostat, we assessed inflammatory markers (tumor necrosis factor-α and interleukin-1β), an antioxidant marker (glutathione), an oxidant marker (nicotinamide adenine dinucleotide phosphate hydrogen oxidase) and an apoptosis marker (caspase-3). Kidney functions (creatinine and blood urea nitrogen) were also assessed. The administration of tacrolimus for 28 days resulted in significantly increased serum glucose and decreased C-peptide and insulin levels than those in the control group. However, coadministration of vorinostat significantly decreased hyperglycemia and increased C-peptide and insulin levels. Moreover, combined treatment with tacrolimus and vorinostat, compared with tacrolimus treatment alone, resulted in significantly reduced inflammatory and oxidant markers, and increased glutathione. Additionally, vorinostat improved the kidney parameters. Vorinostat at a low dose (15 mg/kg) induces anti-inflammatory and antioxidative effects that protect the pancreas and kidney against the development of new-onset diabetes due to tacrolimus in rats. This experimental study provides insights supporting further clinical trials to improve the post-kidney transplantation protocol through addition of vorinostat to the immunosuppressive regimen.


Increased gulf stream warm core ring formations contributes to an observed increase in salinity maximum intrusions on the Northeast Shelf.
We present observational evidence of a significant increase in Salinity Maximum intrusions in the Northeast US Shelf waters in the years following 2000. This increase is subsequent to and influenced by a previously observed regime-shift in the annual formation rate for Gulf Stream Warm Core Rings, which are relatively more saline than the shelf waters. Specifically, mid-depth salinity maximum intrusions, a cross-shelf exchange process, has shown a quadrupling in frequency on the shelf after the year 2000. This increase in intrusion frequency can be linked to a similar increase in Warm Core Ring occupancy footprint along the offshore edge of the shelf-break which has greatly increased the abundance of warm salty water within the Slope Sea. The increased ring occupancy footprint along the shelf follows from the near doubling in annual Warm Core Ring formation rate from the Gulf Stream. The increased occurrence of intrusions is likely driven by a combination of a larger number of rings in the slope sea and the northward shift in the GS position which may lead to more interactions between rings and the shelf topography. These results have significant implications for interpreting temporal changes in the shelf ecosystem from the standpoint of both larval recruitment as well as habitability for various important commercial species.


Cutaneous drug-induced lupus erythematosus: Clinical and immunological characteristics and update on new associated drugs.
Cutaneous drug-induced lupus erythematosus (CDILE) is a lupus-like syndrome related to drug exposure which typically resolves after drug discontinuation. It can present as a systemic or a sole cutaneous form and different drugs may be associated with each form. CDILE pharmacoepidemiology is constantly changing. Indeed, older drugs primarily associated with systemic CDILE are no longer prescribed and new drugs associated with either cutaneous or systemic CDILE have emerged. The present study discusses the clinical and laboratory aspects of CDILE and the postulated pathogenesis, and it provides an update on implicated drugs. We performed a literature review to single out the new drugs associated with CDILE in the past decade (January 2010-June 2020). Among 109 drugs reported to induce CDILE in 472 patients, we identified anti-TNFα, proton-pump inhibitors, antineoplastic drugs, and, in particular, checkpoint inhibitors, as emerging drugs in CDILE. Most of the published studies are cases reports or small case series, and further larger studies as well as the development of validated classification criteria are needed to better understand and characterize their implication in CDILE.


Retroperitoneal liposarcoma: sonographic findings.
This study, based on sonographic (US) results of 10 cases with histologically proven retroperitoneal liposarcoma (eight well-differentiated and two pleomorphic types), shows that the presence of fine echogenic lines within the tumor is a useful sign for diagnosing a well-differentiated liposarcoma. Presence of numerous fine fibrous septa in the lipomatous tumor tissue is thought to be responsible for this interesting phenomenon. Of interest is the fact that the direction of these lines changed according to the probe format used: parallel horizontal lines when using a linear probe and concentric lines converging toward the probe when using a sector or curved linear probe. In contrast, pleomorphic liposarcoma does not show this US sign. Knowledge of these US findings is useful for the diagnosis of retroperitoneal liposarcoma.


Investigating Barriers to Completion of Postpartum Tubal Ligation: A Retrospective Chart Review.
To identify the completion rate for postpartum tubal ligation (PPTL) and predictors of noncompletion of PPTL in a central New Jersey population. We conducted a retrospective chart review at a tertiary care center in New Jersey for patients delivering during an 18-month period. We used the electronic medical record to identify all of the patients who had documented desire for a PPTL at the time of admission. We calculated the rate of PPTL completion and identified predictors of completion and risk factors for noncompletion. We recorded any documented reasons for cancellation and choice of contraception after noncompletion. Of 626 women who requested PPTL on admission, 508 (81.2%) procedures were performed. The most common reasons for noncompletion were patient changing her mind (38.1%) and unknown/not documented (22.9%). Cesarean delivery was the strongest predictor of completion, with 93.4% completion among cesarean deliveries compared with 65.6% among vaginal deliveries (P < 0.01). Lack of insurance also was associated with noncompletion (P < 0.01). There was no difference in body mass index (P = 0.75), gravidity (P = 0.99), parity (P = 0.72), or high-risk status (P = 0.47) between completed and noncompleted PPTL. Cesarean delivery is a strong predictor of PPTL completion, most likely because of easier availability of the operating room, anesthesia, and ancillary staff. Body mass index, gravidity, and parity are not associated with PPTL completion. Future research should focus on exploring whether this association is system, provider, or patient dependent.


Impact of yarn compositions, loop length, and float stitches on the mechanical behavior of knitted fabrics via full factorial design and RSM.
This article presents a study on the tensile properties of knitted fabrics commonly employed in polymeric matrix textile composites. The key mechanical parameters investigated include stress (Pa), strain, Young's modulus (Pa), and work of rupture (J). The knitted fabrics were developed using the Cixing Knitting System software and subsequently manufactured using a double jersey (electronic) flat knitting machine. The primary objective of this research was to explore the impact of various factors on the mechanical behavior of these knitted fabrics. The factors studied were wale and course directions, float stitch density, loop length (cm), and the type of synthetic knitting yarns used (100% polyester and 100% polyamide) along with different combinations of knitting yarns (100% cotton and 67% polyester/33% cotton hybrid). The adopted ASTM D 5034 standard, Response Surface Methodology (RSM), and Analysis of Variance (ANOVA) were employed to evaluate the mechanical performance of these fabric structures. The findings of the study revealed that the statistical adjustment of the data set for stress, strain, Young's modulus, and work of rupture in knitted fabric structures significantly reduced the standard deviations for mechanical responses. This information holds particular significance as it pertains to the frequent use of these knitted fabric structures as reinforcement in textile-reinforced composite materials. Overall, this study sheds light on the mechanical behavior in structures of knitted fabrics used in polymeric matrix composites, providing valuable insights for the design and optimization of advanced textile-based materials.


Arthroscopic anatomy of the shoulder.
Arthroscopic anatomy of the shoulder was evaluated using cadaver dissections. The anatomical areas of clinical importance were documented both photographically and with illustrations. It is hoped this anatomical study will prove to be an aid to arthroscopists during their early experiences with shoulder arthroscopy.


A model for the hapten-induced enhancement of monoclonal antibody binding in ELISA.
The unusual binding properties of three anti-phosphocholine (PC) monoclonal antibodies (MAbs) in ELISA has been reported [Hall T. J. (1987) Molec. Immun. 24, 773-777]. These MAbs gave reproducible 2-4 fold increases in binding to PC-protein coated plates in the presence of PC (approximately 2 mM), nitrophenyl PC (approximately 10 micron) and other PC analogues. A model is proposed here in which the complementary and opposite binding of hapten and PC-protein in the combining sites of these MAbs explains the hapten enhanceable binding in ELISA.