A toxic interaction between mitomycin C and tamoxifen causing the haemolytic uraemic syndrome.
A comparison of patients receiving combination chemotherapy with mitomycin C, mitozantrone and methotrexate (3M) with and without tamoxifen for treatment of primary breast cancer indicates an increased risk of anaemia (P < 0.0001) and thrombocytopenia (P < 0.001), but not leucopenia for patients receiving tamoxifen with their chemotherapy compared to those receiving the chemotherapy alone. Furthermore, 9 out of 94 patients receiving tamoxifen with 3M developed progressive anaemia, thrombocytopenia and abnormal renal function as early features of microangiopathic haemolytic anaemia, progressing on to various degrees of the haemolytic uraemic syndrome (HUS). This is only rarely seen with patients receiving mitomycin C alone at higher doses than used in the 3M combination and in the presence of active metastatic disease. This syndrome can be fatal and 1 of our 9 patients died. These observations indicate that there may be an interaction between tamoxifen and mitomycin C, causing an increased incidence of anaemia, thrombocytopenia and an increased risk of HUS. The combination of these two drugs should be avoided or carefully monitored.


Characteristics and tachyphylaxis of gastrin-stimulated gastric acid secretion in the cat.
1. The characteristics of gastrin-stimulated gastric acid secretion were investigated in conscious cats fitted with chronic cannulated gastric fistulae, with particular reference to tachyphylaxis. 2. There is a significant postive correlation between the peak acid secretion in response to pentagastrin 8 microgram kg-1 hr-1 and body weight. Male cats secret significantly greater amounts of acid in response to pentagastrin than females. The difference is lessened, but not eliminated, by expressing the acid out put in terms of body weight. 3. Pentagastrin stimulates a dose-dependent increase in acid secretion in the range 0.5-32 microgram kg-1 hr-1 when the response to each dose is assayed on separate occasions. Pentagastrin 64 microgram kg-1 hr-1 does not produce a further increase in acid secretion. The acid response to pentagastrin 1-16 microgram kg-1 hr-1 assayed on a single occasion by a continuous infusion method shows a dose-response relationship up to 8 microgram kg-1 hr-1 when it reaches a plateau of secretion. There is no difference between the two methods of assaying the gastric acid stimulating activity using doses of pentagastrin up to 8 microgram kg-1 hr-1. 4 The acid secretion in response to pentagastrin 8 microgram kg-1 hr-1 reaches a maximum after 45 min of stimulation and thereafter shows tachyphylaxis. Over a period of 5 hr there are at least two phases of tachyphylaxis distinguishable. During the period 0.75--2.5 hr of stimulation there is a fast phase of tachyphylaxis (-32.0 muequivH+kg-1 15 min-1). This is followed by a slow phase of tachyphylaxis (-9.4 muequivH+kg-1 15 min-1) up to 5 hr of stimulation. 5. The absolute rate of the fast phase of tachyphylaxis of acid secretion (muequivH+kg-1 15 min-1) increases with increasing doses of pentagastrin, but rates of tachyphylaxis are similar when expressed as a percentage of the peak acid response to the particular dose of pentagastrin (5.1--7.8% 15 min-1). Synthetic human gastrin-17, the synthetic C-terminal decapeptide of human gastrin and the C-terminal tetrapeptide of gastrin have comparable rates of tachyphylaxis. The possible receptor models for the tachyphylaxis of gastrin-stimulated acid secretion are discussed.


Mesenchymal stem cells and their microenvironment.
Mesenchymal stem cells (MSCs), coming from a wide range of sources, have multi-directional differentiation ability. MSCs play vital roles in immunomodulation, hematopoiesis and tissue repair. The microenvironment of cells often refers to the intercellular matrix, other cells, cytokines and humoral components. It is also the place for cells' interaction. The stability of the microenvironment is pivotal for maintaining cell proliferation, differentiation, metabolism and functional activities. Abnormal changes in microenvironment components can interfere cell functions. In some diseases, MSCs can interact with the microenvironment and accelerate disease progression. This review will discuss the characteristics of MSCs and their microenvironment, as well as the interaction between MSCs and microenvironment in disease.


Atherosclerosis: a classic inflammatory disease.
Atherosclerosis is an inflammatory disease due to a diet high in saturated fat, hypercholesterolemia, obesity, hypoglycemia, etc. mainly mediated by the infiltration of macrophage and T cells into the vascular wall. Once the endothelial is damaged monocytes penetrate the tissue and are transformed in scavenger cells. Upon stimulation of Th1 cells, a group of cytokines is released and contributes to the inflammatory response of atherosclerotic tissue. When macrophages proliferate they amplify inflammatory response through the secretion of growth factors and cytokines such as TNF and IL-1. In addition, chemokines such as RANTES and other C-C chemokines are generated, and matrix metalloprotinease 9 (MMP-9) are produced by activated monocytes. However, the immune system in atherosclerosis still remains unclear. Here, in this study we revisited the inter-relationship between atherosclerosis and inflammation.


Automated classification of primary progressive aphasia subtypes from narrative speech transcripts.
In the early stages of neurodegenerative disorders, individuals may exhibit a decline in language abilities that is difficult to quantify with standardized tests. Careful analysis of connected speech can provide valuable information about a patient's language capacities. To date, this type of analysis has been limited by its time-consuming nature. In this study, we present a method for evaluating and classifying connected speech in primary progressive aphasia using computational techniques. Syntactic and semantic features were automatically extracted from transcriptions of narrative speech for three groups: semantic dementia (SD), progressive nonfluent aphasia (PNFA), and healthy controls. Features that varied significantly between the groups were used to train machine learning classifiers, which were then tested on held-out data. We achieved accuracies well above baseline on the three binary classification tasks. An analysis of the influential features showed that in contrast with controls, both patient groups tended to use words which were higher in frequency (especially nouns for SD, and verbs for PNFA). The SD patients also tended to use words (especially nouns) that were higher in familiarity, and they produced fewer nouns, but more demonstratives and adverbs, than controls. The speech of the PNFA group tended to be slower and incorporate shorter words than controls. The patient groups were distinguished from each other by the SD patients' relatively increased use of words which are high in frequency and/or familiarity.


Screening of phage displayed human liver cDNA library against dexamethasone.
This paper described an attempt to establish a new method to screen the target biomolecule from phage displayed cDNA library against small molecule drug insoluble in water. Dexamethasone was selected as the model drug, and the screening was carried out in an Eppendorf tube packed with the drug. The whole procedure was monitored by PCR with the enriched specific phage clone as the template. After four rounds screening, the PCR products of selected phages with the lengths of 400 and 600 bp were sequenced, and revealed identical sequences with cytochrome c oxidase subunit III and albumin respectively by GenBank searching. Furthermore, frontal analysis-capillary electrophoresis (FA-CE) was performed to study the interaction between dexamethasone and albumin, and the binding constant was calculated to be 1.153 x 10(3), validating the weak specific interaction between the drug and the target protein. All these results demonstrated that with insoluble drug as the solid phase directly, the screening of target large molecule expressed in phage display cDNA library was feasible, which might pave an easy way to screen the candidate drug targets.


Post-colectomy assessment of gastrointestinal function: a prospective study on colorectal cancer patients.
Anatomical changes after intestinal resection and the effects of adjuvant treatment for colorectal cancer may lead to gastrointestinal disturbances. The aim of our study was to assess gastrointestinal function using validated health-related quality of life (HRQoL) questionnaires that are able to reliably quantify patients' symptoms. Two hundred and eighty-nine colorectal cancer patients underwent HRQoL assessment preoperatively and at 3,6 and 12 months postoperatively. They were evaluated with the Gastrointestinal Quality of Life Index (GIQLI) ["global" and "symptoms" scales and questions 3 ("bloating"), 4 ("excessive gas"), 6 ("gurgling noises"), 7 ("frequent bowel movements (BMs)"), 30 ("urgent BMs"), 31 ("diarrhea"), 32 ("constipation"), 36 ("uncontrolled stools")] and the European Organization for Research and Treatment of Cancer (EORTC) modules QLQ-C30 (symptom scales: "constipation" and "diarrhea") and QLQ-CR29 (symptom scales: "defecation problems," "incontinence," and "bloating"). GIQLI "global" and "symptom" indices and the majority of single-item scores and the EORTC QLQ-C30 "constipation" and "diarrhea" subscales showed significant postoperative improvement (p < 0.05). Females and younger age (<70 years) patients appeared to have worse postoperative gastrointestinal function. Rectal cancer patients had more "urgent BMs," "uncontrolled stools" and worse "global" and "symptom" scores at 3 months and more "diarrhea" at 3 and 6 months than colon cancer patients (p < 0.03). Right colectomy patients had less "excessive passage of gas," "constipation," and "uncontrolled stools" than left colectomy patients (3 months, p < 0.01). Anterior resection patients faced more gastrointestinal difficulties, especially in the first 6 months after surgery. Adverse effects related to stage and adjuvant treatment were predominant only at baseline (p < 0.05). GIQLI "diarrhea" and "constipation" scores were correlated with the respective EORTC QLQ-C30 domains (p = 0.0001). Overall, gastrointestinal function is improved after colorectal cancer surgery. However, women and younger patients are at higher risk of postoperative gastrointestinal dysfunction.


DNA polymerase β mutations and survival of patients with esophageal squamous cell carcinoma in Linzhou City, China.
Linzhou City in northern China has a high incidence of esophageal squamous cell carcinoma (ESCC). This study retrospectively analyzed the data of 231 cases with ESCC collected from 1998 to 2012. Mutations of DNA polymerase β (polβ) gene in the ESCC samples from patients in Linzhou City were examined by amplifying polβ cDNA by RT-PCR followed by cloning and sequencing. Mutations in polβ were found in 105 cases (45.9%). Nine types of mutations were identified in the polβ cDNA; the most common were 177–234 nt deletion (11.3%), 462 nt G → T (9.1%), and 648 nt G → C (6.9%). Mutations in polβ appeared to be associated with TNM status (P = 0.048). Follow-up data was used for survival analysis. The overall 5-year survival rate of the 231 patients was 37.4%; the rate for patients with wild-type (WT) polβ was 41.8%. Compared with the WT polβ group, the median survival for patients with specific mutations (177–234 nt deletion, 462 nt G → T, or 613 nt A → T) was significantly shorter (all P = 0.000), and the 5-year survival rate decreased to 0%. Patients with the 648 nt G → C mutation had improved survival (P = 0.000) with a 5-year survival rate of 100%. Our results identified nine types of mutations within polβ cDNA in ESCC patients with four mutations related to patient survival.


Margins and survival in oral cancer.
In the surgical management of oral squamous cell carcinoma (SCC) we aim to resect the tumour with clear margins in all planes. The aim of this study was to identify and compare overall survival in a group of 591 patients who had resections, and to relate this to the clearance of margins at the tumour bed. We used life tables to calculate survival at one, two, three, five, and 10 years after diagnosis by margin (clear=5mm or more; close=2-5mm; and involved=less than 2mm). Kaplan-Meier curves were produced for the margins alone, which were defined as clear in 480 patients (81%), close in 63 (11%), and involved in 48 (8%). Five-year survival was 81%, 75%, and 54% for clear, close, and involved margins, respectively, which highlights the importance of clear margins for survival. There is a significant prognostic implication associated with close, and particularly with involved, margins.


Carotenohematoporphyrins as tumor-imaging dyes. Synthesis and in vitro photophysical characterization.
Multichromophoric dyes for use in tumor imaging have been synthesized and photophysically characterized. Structurally, these dyes are dyads and triads that consist of one or two carotenoid polyenes covalently attached to hematoporphyrin (HP) or hematoporphyrin dimethyl ester (HPDME) moieties via ester linkages. The ground-state absorption of each compound shows that the electronic interaction between the chromophores is small. The fluorescence quantum yield for the dyad monocaroteno-HPDME is 0.033 and the dicaroteno-HPDME triads have yields between 0.016 and 0.007, all of which are reduced with respect to the parent compound HPDME (0.09). Global analysis of the transient fluorescence decays of the dyads and triads requires two exponential components (approximately 5-6 ns and approximately 1-2 ns) to fit the data, while a single exponential component with a lifetime of 9.3 ns describes the decay data of the parent HPDME. Possible mechanisms for the observed porphyrin fluorescence quenching by the nearby carotenoid are discussed. Nanosecond transient absorption reveals a carotene triplet with maximum absorption at 560 nm and a 5.0 microsecond lifetime. No transient was detected at 450 nm, indicating rapid (< or = 10 ns) triplet energy transfer from the hematoporphyrin to the carotenoid moieties in fluid as well as in rigid media. The yield of triplet energy transfer from the porphyrin to the carotenoid moiety is unity. Singlet oxygen (O2(1 delta g), studies support the transient absorption data, as none of these compounds is capable of sensitizing O2(1 delta g). Liposome vesicles were used to study the photophysical characteristics of the dyes in phospholipid membranes. Singlet oxygen was not sensitized by the dyads and triads in liposomes. Transient absorption measurements suggest that the triads are substantially aggregated within the phospholipid bilayer, whereas aggregation in the dyads is less severe.


Architecture of the outbred brown fat proteome defines regulators of metabolic physiology.
Brown adipose tissue (BAT) regulates metabolic physiology. However, nearly all mechanistic studies of BAT protein function occur in a single inbred mouse strain, which has limited the understanding of generalizable mechanisms of BAT regulation over physiology. Here, we perform deep quantitative proteomics of BAT across a cohort of 163 genetically defined diversity outbred mice, a model that parallels the genetic and phenotypic variation found in humans. We leverage this diversity to define the functional architecture of the outbred BAT proteome, comprising 10,479 proteins. We assign co-operative functions to 2,578 proteins, enabling systematic discovery of regulators of BAT. We also identify 638 proteins that correlate with protection from, or sensitivity to, at least one parameter of metabolic disease. We use these findings to uncover SFXN5, LETMD1, and ATP1A2 as modulators of BAT thermogenesis or adiposity, and provide OPABAT as a resource for understanding the conserved mechanisms of BAT regulation over metabolic physiology.


Interactive role of diastolic dysfunction and ventricular remodeling in asymptomatic subjects at increased risk of heart failure.
Diastolic dysfunction (DD) and left ventricular remodeling (LVR) characterize patients at risk for heart failure (HF). To assess the prognostic impact of different diastolic function algorithms and a complex LVR classification (CRC) in asymptomatic subjects with preserved ejection fraction (EF) at risk for HF. We analyzed 1923 asymptomatic patients (male 43%; age 57, 33-76 years) with at least one cardiovascular risk factor and preserved (> 50%) EF. We used three algorithms for LV diastolic function assessment (Paulus et al. in Eur Heart J 28(20):2539-2550, 2007; Nagueh et al. in J Am Soc Echocardiogr 22(2):107-133, 2009, Eur Heart J Cardiovasc Imaging 17(12):1321-1360, 2016), and two algorithms for LVR (classic and CRC). We considered a composite end-point: cardiac death and hospitalization for HF. The highest presence of DD was diagnosed by Nagueh 2009 (211, 11%), while the prevalence according to Nagueh 2016 (63 patients, 3.2%) turned out to be the lowest (p < 0.001 vs the other algorithms). According to CRC, 780 (48.6%) patients had normal or physiologic hypertrophy, 298 (15.5%) concentric remodeling, 85 (4.4%) eccentric remodeling, 294 (15.3%) concentric hypertrophy, 39 (2%) mixed hypertrophy, 80 (4.1%) dilated hypertrophy, 73 (3.7%) eccentric hypertrophy and 294 (15.3%) were unclassifiable. After 39-month follow-up (261 events, 13.6%), Cox-regression (adjusted for age, gender, history of stable ischemic heart disease, classic remodeling classification) identified CRC (p = 0.01) and Nagueh 2016 (p < 0.001) as independent predictors of end-point. The coexistence of an adverse LVR by CRC and DD by Nagueh 2016 was associated with the worst prognosis. A concurrent structural (CRC) and functional (Nagueh Op. Cit) analysis improves prognostic stratification in asymptomatic subjects at risk for HF with preserved EF.


Plasma treatments of dressings for wound healing: a review.
This review covers the use of plasma technology relevant to the preparation of dressings for wound healing. The current state of knowledge of plasma treatments that have potential to provide enhanced functional surfaces for rapid and effective healing is summarized. Dressings that are specialized to the needs of individual cases of chronic wounds such as diabetic ulcers are a special focus. A summary of the biology of wound healing and a discussion of the various types of plasmas that are suitable for the customizing of wound dressings are given. Plasma treatment allows the surface energy and air permeability of the dressing to be controlled, to ensure optimum interaction with the wound. Plasmas also provide control over the surface chemistry and in cases where the plasma creates energetic ion bombardment, activation with long-lived radicals that can bind therapeutic molecules covalently to the surface of the dressing. Therapeutic innovations enabled by plasma treatment include the attachment of microRNA or antimicrobial peptides. Bioactive molecules that promote subsequent cell adhesion and proliferation can also be bound, leading to the recruitment of cells to the dressing that may be stem cells or patient-derived cells. The presence of a communicating cell population expressing factors promotes healing.


Identifying rare variants from exome scans: the GAW17 experience.
Genetic Analysis Workshop 17 (GAW17) provided a platform for evaluating existing statistical genetic methods and for developing novel methods to analyze rare variants that modulate complex traits. In this article, we present an overview of the 1000 Genomes Project exome data and simulated phenotype data that were distributed to GAW17 participants for analyses, the different issues addressed by the participants, and the process of preparation of manuscripts resulting from the discussions during the workshop.


CHIP as a therapeutic target for neurological diseases.
Carboxy-terminus of Hsc70-interacting protein (CHIP) functions both as a molecular co-chaperone and ubiquitin E3 ligase playing a critical role in modulating the degradation of numerous chaperone-bound proteins. To date, it has been implicated in the regulation of numerous biological functions, including misfolded-protein refolding, autophagy, immunity, and necroptosis. Moreover, the ubiquitous expression of CHIP in the central nervous system suggests that it may be implicated in a wide range of functions in neurological diseases. Several recent studies of our laboratory and other groups have highlighted the beneficial role of CHIP in the pathogenesis of several neurological diseases. The objective of this review is to discuss the possible molecular mechanisms that contribute to the pathogenesis of neurological diseases in which CHIP has a pivotal role, such as stroke, intracerebral hemorrhage, Alzheimer's disease, Parkinson's disease, and polyglutamine diseases; furthermore, CHIP mutations could also cause neurodegenerative diseases. Based on the available literature, CHIP overexpression could serve as a promising therapeutic target for several neurological diseases.


Perception of Saudi dentists and lay people to altered smile esthetics.
To evaluate and compare the perceptions of Saudi dentists and lay people to altered smile features. Thirty-six digital smile photographs with altered features were used. Altered features included the following: crown length, width, gingival level of the lateral incisors, gingival display, midline diastema, and upper midline shift. The photographs were presented to a sample of 30 dentists and 30 lay people with equal gender distribution. Each participant rated each picture with a visual analogue scale, which ranged from 0 (very unattractive) to 100 (very attractive). Dentists were more critical than lay people when evaluating symmetrical crown length discrepancies. Compared to lay people, Saudi dentists gave lower ratings to a crown length discrepancy of >2 mm (P < 0.001), crown width discrepancy of ⩾2 mm (P < 0.05), change in gingiva to lip distance of ⩾2 mm (P < 0.01), and midline deviation of >1 mm (P < 0.01). There was no significant difference between dentists and lay people towards alterations in the gingival level of the lateral incisors or towards a space between the central incisors. No significant sex difference was seen across the groups. In this sample, Saudi dentists gave significantly lower attractiveness scores to crown length and crown width discrepancies, midline deviations, and changes in gingiva to lip distance compared to Saudi lay people.


Partitioning behaviour of rat bone marrow cells in aqueous two-phase systems. Dependence of cell partition on the interfacial tension and electrical potential difference between the phases.
The partitioning of heterogeneous cell populations of rat bone marrow, in comparison with that of homogeneous populations of erythrocytes, has been studied in aqueous two-phase systems containing increasing concentrations of dextran-poly-(ethylene glycol) (to increase the interfacial tension) and/or decreasing phosphate concentrations (to decrease both the electrical potential difference between the phases and the interfacial tension). At any polymer and/or phosphate concentration tested the partition is lower for bone marrow cells, reflecting their lower surface charge and hydrophobicity.


Serum aromatic and branched-chain amino acids associated with NASH demonstrate divergent associations with serum lipids.
Non-alcoholic fatty liver disease (NAFLD) has been associated with multiple metabolic abnormalities. By applying a non-targeted metabolomics approach, we aimed at investigating whether serum metabolite profile that associates with NAFLD would differ in its association with NAFLD-related metabolic risk factors. A total of 233 subjects (mean ± SD: 48.3 ± 9.3 years old; BMI: 43.1 ± 5.4 kg/m2 ; 64 male) undergoing bariatric surgery were studied. Of these participants, 164 with liver histology could be classified as normal liver (n = 79), simple steatosis (SS, n = 40) or non-alcoholic steatohepatitis (NASH, n = 45). Among the identified fasting serum metabolites with higher levels in those with NASH when compared to those with normal phenotype were the aromatic amino acids (AAAs: tryptophan, tyrosine and phenylalanine), the branched-chain amino acids (BCAAs: leucine and isoleucine), a phosphatidylcholine (PC(16:0/16:1)) and uridine (all FDRp < 0.05). Only tryptophan was significantly higher in those with NASH compared to those with SS (FDRp < 0.05). Only the AAAs tryptophan and tyrosine correlated positively with serum total and LDL cholesterol (FDRp < 0.1), and accordingly, with liver LDLR at mRNA expression level. In addition, tryptophan was the single AA associated with liver DNA methylation of CpG sites known to be differentially methylated in those with NASH. We found that serum levels of the NASH-related AAAs and BCAAs demonstrate divergent associations with serum lipids. The specific correlation of tryptophan with LDL-c may result from the molecular events affecting LDLR mRNA expression and NASH-associated methylation of genes in the liver.


[The antibacterial properties of the intestinal microflora of healthy calves].
Antibacterial properties of bacteria of genera Escherichia, Enterococcus, Bacillus, Lactobacillus, Bifidobacterium isolated from different parts of gastro-intestinal tract of the healthy milk-fed and weanling calves were studied against test-bacteria, microorganisms of the Escherichia genus with and without pathogenic factors as well as the genera Klebsiella, Enterobacter, Proteus, Salmonella, Staphylococcus representatives that had been isolated from healthy and sick calves. Certain tolerance was determined between the groups of bacteria under study and only some strains of lactobacteria and bifidobacteria showed selective antibacterial action on pathogenic and conditionally pathogenic microorganisms, thus stabilizing intestinal microbiota in the gastro-enteric tract of calves.


PERC rule to exclude the diagnosis of pulmonary embolism in emergency low-risk patients: study protocol for the PROPER randomized controlled study.
The diagnosis of Pulmonary Embolism (PE) in the emergency department (ED) is crucial. As emergency physicians fear missing this potential life-threatening condition, PE tends to be over-investigated, exposing patients to unnecessary risks and uncertain benefit in terms of outcome. The Pulmonary Embolism Rule-out Criteria (PERC) is an eight-item block of clinical criteria that can identify patients who can safely be discharged from the ED without further investigation for PE. The endorsement of this rule could markedly reduce the number of irradiative imaging studies, ED length of stay, and rate of adverse events resulting from both diagnostic and therapeutic interventions. Several retrospective and prospective studies have shown the safety and benefits of the PERC rule for PE diagnosis in low-risk patients, but the validity of this rule is still controversial. We hypothesize that in European patients with a low gestalt clinical probability and who are PERC-negative, PE can be safely ruled out and the patient discharged without further testing. This is a controlled, cluster randomized trial, in 15 centers in France. Each center will be randomized for the sequence of intervention periods: a 6-month intervention period (PERC-based strategy) followed by a 6-month control period (usual care), or in reverse order, with 2 months of "wash-out" between the 2 periods. Adult patients presenting to the ED with a suspicion of PE and a low pre test probability estimated by clinical gestalt will be eligible. The primary outcome is the percentage of failure resulting from the diagnostic strategy, defined as diagnosed venous thromboembolic events at 3-month follow-up, among patients for whom PE has been initially ruled out. The PERC rule has the potential to decrease the number of irradiative imaging studies in the ED, and is reported to be safe. However, no randomized study has ever validated the safety of PERC. Furthermore, some studies have challenged the safety of a PERC-based strategy to rule-out PE, especially in Europe where the prevalence of PE diagnosed in the ED is high. The PROPER study should provide high-quality evidence to settle this issue. If it confirms the safety of the PERC rule, physicians will be able to reduce the number of investigations, associated subsequent adverse events, costs, and ED length of stay for patients with a low clinical probability of PE. NCT02375919 .


Epidemiology and outcomes of pregnant trauma patients in Japan: a nationwide descriptive study.
Trauma during pregnancy is the leading indirect obstetric cause of death, and its management is challenging owing to its characteristics. We aimed to describe the epidemiology of pregnant trauma patients and explore their characteristics by comparing them with those of non-pregnant patients. Using the Japan Trauma Data Bank data collected between January 2004 and May 2019, we identified pregnant and non-pregnant female trauma patients between the ages of 15-45 years. We described patient characteristics, prehospital information, in-hospital management, and clinical outcomes. We also investigated the differences in the information between pregnant and non-pregnant patients. In total, 165 pregnant trauma patients were identified (0.7%). Motor vehicle collisions were the most frequent mechanism of injury (64.6%) in pregnant patients. The time from call to the arrival of emergency medical services at the hospital was similar for both pregnant and non-pregnant patients. The use of abdominal computed tomography (CT) scans was lower and injury to the abdomen was more frequent in pregnant than non-pregnant patients. In-hospital mortality was 7.2% in pregnant patients and 10.9% in non-pregnant patients. No significant differences in mortality after adjustment for confounding factors were found (adjusted odds ratio: 0.78, 95% confidential interval: 0.35-1.75, p = 0.548). Transport time and mortality were similar between pregnant and non-pregnant trauma patients. Abdominal trauma and surgery were more common in pregnant relative to non-pregnant patients, while the number of CT scans was less. Further research is required to investigate the effects of trauma on the course of pregnancy and the fetus.


Diffusion tensor imaging of superficial prefrontal white matter in healthy aging.
The prefrontal cortex (PFC) is a heterogenous structure that is highly susceptible to the effects of aging. Few studies have investigated age effects on the superficial white matter (WM) contained within the PFC using in-vivo magnetic resonance imaging (MRI). This study used diffusion tensor imaging (DTI) tractography to examine the effects of age, sex, and intracranial volume (ICV) on superficial WM within specific PFC subregions, and to model the relationships with age using higher order polynomial regression modelling. PFC WM of 140 healthy individuals, aged 18-85, was segmented into medial and lateral orbitofrontal, medial prefrontal, and dorsolateral prefrontal subregions. Differences due to age in microstructural parameters such as fractional anisotropy (FA), axial and radial diffusivities, and macrostructural measures of tract volumes, fiber counts, average fiber lengths, and average number of fibers per voxel were examined. We found that most prefrontal subregions demonstrated age effects, with decreases in FA, tract volume, and fiber counts, and increases in all diffusivity measures. Age relationships were mostly non-linear, with higher order regressions chosen in most cases. Declines in PFC FA began at the onset of adulthood while the greatest changes in diffusivity and volume did not occur until middle age. The effects of age were most prominent in medial tracts while the lateral orbitofrontal tracts were less affected. Significant effects of sex and ICV were also observed in certain parameters. The patterns mostly followed myelination order, with late-myelinating prefrontal subregions experiencing earlier and more pronounced age effects, further supporting the frontal theory of aging.


Retention in event-driven PrEP among young Thai men who have sex with men at risk of HIV acquisition.
Background: Daily pre-exposure prophylaxis (PrEP) regimen of tenofovir/emtricitabine (TDF/FTC) tablet is the standard of care for HIV prevention in Thailand. Event-driven PrEP (ED-PrEP), taking two loading pills 2-24 h prior to sex and two doses afterward, is considered an alternative regimen. This pilot study aimed to describe accuracy of and retention in ED-PrEP use among Thai young men who have sex with men (YMSM).Methods: A cohort of YMSM aged 15-19 years at risk of HIV infection, defined as reporting irregular condom use or having an HIV-positive sexual partner, was enrolled. All participants were provided oral TDF/FTC, condoms, and the "Raincoat" mobile application, which reminds users when to administer ED-PrEP. Participants attended clinic visits at Months 1, 3, and 6 and followed up by phone at Months 2, 4, and 5. Proper use of ED-PrEP was reported in person-months.Results: From August 2020 to July 2021, 36 YMSM with a median age of 18.7 (IQR, 17.5-19.4) years were enrolled. Thirty-two participants (88.9%, 95% CI: 73.9-96.9%) were retained at 6 months. No HIV incidence occurred during this study period. Of 197 person-months of follow-up, 69 (35%) involved sexual activity. In this group, 61% used ED-PrEP correctly. "Unplanned sexual activity" was the most commonly cited reason for incorrect use.Conclusions: YMSM who have infrequent sex had very high retention in ED-PrEP. However, about one-third of the sexually active period, ED-PrEP was not used correctly due to not taking the loading dose, suggesting that this regimen may not be suitable for unanticipated sexual activity.


Safety of angiotensin-converting enzyme inhibitors while receiving venom immunotherapy.
Case reports have raised concern about concurrent use of angiotensin-converting enzyme inhibitors (ACE-Is) in patients receiving venom immunotherapy (VIT). No surveys have been performed on the number of venom allergic patients who take ACE-Is and their outcomes. To survey the use of ACE-Is and systemic reaction (SR) characteristics in patients receiving VIT. A retrospective medical record review was performed on all patients evaluated for Hymenoptera venom allergy at a single center from 2000 to 2005. Patient records were evaluated for presenting symptoms, specific IgE testing, VIT treatment course, ACE-I use during VIT, and the presence of any SRs to field stings or VIT. Of 288 patients evaluated from 2000 to 2005 for Hymenoptera venom allergy, 157 were found to have venom specific IgE. Of these 157 patients, 79 (50%) of those with Hymenoptera venom allergy underwent VIT. Seventeen of these 79 patients (21%) were taking an ACE-I during VIT. The mean overlap of a patient taking an ACE-I with the time they were receiving VIT was 30.9 months (range, 3-114 months). Patients taking ACE-Is were older (mean age, 56.2 vs 36.4 years; P < .001) and received VIT for a longer period (mean, 72.3 vs 29.9 months; P < .04). Thirteen of 62 patients not taking an ACE-I (21%) experienced an SR during their VIT. No patients taking an ACE-I experienced an SR to VIT while taking an ACE-I (P = .03). This study suggests that there is not an association between ACE-I use and increased frequency of SRs to venom immunotherapy.


Recessive hyperekplexia due to a new mutation (R100H) in the GLRA1 gene.
Hyperekplexia is commonly familial and with dominant transmission. The gene involved, GLRA1, encodes the alpha1 subunit of the glycine receptor. We describe 3 affected children homozygous for a new mutation, R100H. Both parents were heterozygous carriers; while the father was healthy, the mother has periodic limb movements during sleep. This suggests that Hys-100 could exhibit incomplete penetrance, but was linked to a severe classical form of hyperekplexia in homozygous.


Effects of distraction forces and frequency of distraction on bony regeneration.
The rate and frequency of distraction have a decisive influence on the regenerative process. We tested a newly developed hydraulic osteodistractor in 12 pigs, which were assigned to have continuous and intermittent osteodistraction of the mandible after osteotomy. The forces necessary to distract the mandible were recorded during intermittent distraction. These data were then used for continuous distraction of the bone. Continuous osteodistraction resulted in intramembranous regeneration of bone, whereas intermittent osteodistraction caused chondroid ossification in the regeneration of the bone. Continuous osteodistraction caused speedier regeneration, and distraction forces were lower than with intermittent distraction.


Intraoperative bile cytology of the dysplasia-carcinoma in situ sequence of gallbladder carcinoma.
The preoperative diagnosis of noninvasive and early carcinoma of the gallbladder is considered to be both difficult and exceptional. In the current study, the authors conducted a cytologic analysis of bile in the intraoperative diagnosis of clinically unsuspected gallbladder carcinoma. Bile samples collected from 40 patients at the time of elective cholecystectomy were centrifuged. Smears prepared from the sediments were stained with May-Grünwald-Giemsa and Papanicolaou stains. Lesions were categorized as hyperplasia with or without metaplasia, dysplasia, carcinoma in situ, and invasive carcinoma. Cytologic diagnoses were compared with histopathology. Two cases of carcinoma in situ and one case of invasive carcinoma diagnosed on bile cytology were confirmed by histopathology. No false-positive diagnoses were made based on cytologic examination of aspirated bile. Cytohistologic concordance in cases of hyperplasia, dysplasia, and chronic cholecystitis varied from 56-60%. Intraoperative bile cytology was found to be a reliable method for the detection of in situ and early invasive carcinoma of the gallbladder.


Modifying beliefs about back pain: A pilot study among healthcare professionals.
This study aimed to explore whether a preventive intervention based on the non-injury model and the biopsychosocial model of back pain succeeded in shifting beliefs toward less negative representations and in decreasing fear-avoidance beliefs related to back pain. One hundred and one healthcare professionals took part in a 10-h educational program held over 2 consecutive days, based on the key messages of the "Back Book." Baseline values were measured 6 weeks before the intervention and when it started. Follow-up was performed at the end of the intervention and six months later. No significant changes were observed between baseline values and values measured at the beginning of the intervention, but participants' beliefs about LBP changed significantly after the program. The benefit remained at 6 months follow-up. A prevention program based on the non-injury and bio-psychosocial models of LBP, introducing empowerment and problem-solving strategies, significantly reduced fear-avoidance and negative beliefs about LBP. The change was clinically relevant and thus could decrease direct and indirect healthcare costs.


Ribonucleic acid antigen from the Reiter treponeme used in an ELISA for antibodies in syphilis.
Purified RNA from Treponema phagedenis biotype Reiter was used as antigen in an enzyme-linked immunosorbent assay (ELISA) for IgG antibodies in syphilis. The RNA ELISA was compared with the fluorescent treponemal antibody absorption test (FTA-ABS), the Treponema pallidum immobilization test (TPI), and with two ELISAs using purified flagellum from the Reiter treponeme as antigen (flagellum ELISA), and sonified Reiter treponeme culture as antigen (sonicate ELISA). A total of 729 sera from patients with and without syphilis were studied. The RNA ELISA had a lower sensitivity (P less than 0.01) in primary syphilis than the flagellum ELISA, the sonicate ELISA, and the FTA-ABS. In treated syphilis the RNA ELISA was also less sensitive than the TPI (P less than 0.01).


Exaggerated epinephrine responses to hypoglycemia in normal and insulin-dependent diabetic children.
To determine whether children with insulin-dependent diabetes mellitus (IDDM) might have exaggerated hormonal responses to hypoglycemia, the euglycemic-hypoglycemic glucose clamp procedure was used to provide a uniform hypoglycemic stimulus (plasma glucose kept at 90 mg/dL for 2 hours, then reduced to 50 to 55 mg/dL for 1 hour) in children and adults with and without IDDM. The chidren with IDDM showed an exaggerated rise in plasma epinephrine levels (625 +/- 112 pg/mL) compared with adults with IDDM (259 +/- 57 pg/mL, P less than 0.02); the same was true for children and adults without IDDM (811 +/- 100 vs 458 +/- 85 pg/mL, P less than 0.05). Among the children, the increase in epinephrine during hypoglycemia was similar in prepubertal and pubertal patients. Children with IDDM showed a greater rise in plasma norepinephrine than did adults with IDDM (P less than 0.001), and both diabetic groups failed to mount a glucagon response. Growth hormone and cortisol responses were unaffected by either childhood or diabetes. Enhanced secretion of epinephrine, induced by mild reductions in plasma glucose, may contribute to the management difficulties characteristically observed in the young patient with diabetes.


Comparison of the therapeutic effects of five antiviral agents on cutaneous herpesvirus infection in guinea pigs.
Cutaneous herpesvirus infection of guinea pigs has been evaluated as a model for testing antiviral compounds. Six infected sites on each animal can be used independently for local treatment. The severity of the infection has been graded in a score system. The cumulative scores during infection and the time to healing can be used to determine antiviral effects. The effects of adenine arabinoside, cytosine arabinoside, iododeoxyuridine, ribavirin and phosphonoacetic acid on the cutaneous infection was compared. Phosphonoacetic acid was the only compound with a good therapeutic activity against herpesvirus infection, causing a reduction of both the cumulative score and the time to healing. Phosphonoacetic acid was skin irritating at 2 per cent, but at 1 per cent, which still had a good therapeutic activity, skin irritation was seen only occasionally.


Fooling your feelings: artificially induced referred sensations are linked to a modulation of the primary somatosensory cortex.
Recent studies demonstrated tactile illusions in healthy subjects by manipulating visual and tactile information. For example, a rubber hand, lying on a table in front of the subject and not connected with the body, can be felt by the subject as belonging to his or her own body by a simple visuotactile manipulation. Aim of the present study was to create an illusion in which the subject feels touch on a body site which is different from the actual touch, hence showing a referral of touch similar to those reported in phantom limb patients. Since it is known from animal studies that tactile illusions can alter early sensory processing, we were interested in the role of the primary somatosensory cortex (SI) during this kind of illusion. Thus, we manipulated the visual and tactile information in eight healthy subjects. The participants were stimulated on their fifth digit (D5) while watching a video, which showed a life-sized hand where the first digit (D1) was stimulated, hence inducing a conflict in feeling and seeing. The visual and tactile stimulation was in-phase in one condition and out-of-phase in a control condition. The video was presented in the peripersonal space of the subject at the distance where the real hand would be expected. Subjects reported a referred sensation of feeling the stimulation on D1 instead of D5 when the stimulation was in-phase with the video. Neuromagnetic source imaging of the topography of the functional organization of SI related to tactile stimulation of D1 and D5 showed that the source extent of the cortical representation of D5 increased during the illusion. The results suggest that a simple manipulation of visual and tactile information can induce referred sensations in healthy subjects in a very fast manner. Since the amount of the referred sensation was significantly correlated with the modulation in SI, we argue that SI is involved in this kind of artificially induced referred sensation.


Rice straw as microalgal biofilm bio-carrier: Effects of indigenous microorganisms on rice straw and microalgal biomass production.
Microalgal biofilm cultivation is a promising method for efficient microalgae production. However, expensive, difficult-to-obtain and non-durable carriers hinder its up-scaling. This study adopted both sterilized and unsterilized rice straw (RS) as a carrier for the development of microalgal biofilm, with polymethyl methacrylate as control. The biomass production and chemical composition of Chlorella sorokiniana, as well as the microbial community composition during cultivation were examined. The physicochemical properties of RS before and after utilized as carrier were investigated. The biomass productivity of unsterilized RS biofilm exceeded that of suspended culture by 4.85 g m-2·d-1. The indigenous microorganisms, mainly fungus, could effectively fixed microalgae to the bio-carrier and enhance its biomass production. They could also degrade RS into dissolved matters for microalgal utilization, leading to the physicochemical properties change of RS in the direction which favored its energy conversion. This study showed that RS can be used effectively as a microalgal biofilm carrier, thus presenting a new possibility for the recycling of rice straw.


Vacuum ultraviolet action spectroscopy of polysaccharides.
We studied the optical properties of gas-phase polysaccharides (maltose, maltotetraose, and maltohexaose) ions by action spectroscopy using the coupling between a quadrupole ion trap and a vacuum ultraviolet (VUV) beamline at the SOLEIL synchrotron radiation facility (France) in the 7 to 18 eV range. The spectra provide unique benchmarks for evaluation of theoretical data on electronic transitions of model carbohydrates in the VUV range. The effects of the nature of the charge held by polysaccharide ions on the relaxation processes were also explored. Finally the effect of isomerization of polysaccharides (with melezitose and raffinose) on their photofragmentation with VUV photons is presented.


Hemodynamic effects of endothelin after systemic and central nervous system administration in the conscious rat.
The effects of endothelin-1 (ET-1) administered i.v. or intracerebroventricularly (i.c.v.) on arterial pressure (MAP), heart rate and cardiac output were studied in the conscious rat. Systemic injection of ET-1 (0.1 to 1 nmol/kg i.v.) increased dose-dependently MAP and decreased heart rate. The doses of 0.3 and 1 nmol/kg produced initially transient hypotension and tachycardia which were accompanied by a decrease in total peripheral resistance index (TPRI). Cardiac output was significantly reduced and TPRI increased during the pressor response to 0.3 and 1 nmol/kg ET-1. ET-1 i.c.v. (30 pmol/kg) produced a profound pressor and vasoconstrictor response which was followed by cardiovascular collapse and death within 20 min after i.c.v. injection. Low doses (1 to 10 pmol/kg) of ET-1 i.c.v. had no effect on the cardiovascular system. The present data are in accordance with the studies demonstrating biphasic blood pressure and heart rate responses to i.v. ET-1 in the rat. Profound cardiac depressor and peripheral vasoconstrictor responses were found to accompany the pressor phase. Our results also showed for the first time direct central pressor and vasoconstrictor effects of ET-1 insinuating that endothelin might be a neuropeptide participating in the central cardiovascular control.


Gastric small cell carcinoma with squamous and neuroendocrine differentiation.
A rare gastric carcinoma containing diverse components, that is, neuroendocrine (small cell carcinoma), squamous and gland-like elements in an 82 yr old woman is described. Radiologic examination revealed a large ulcerated tumor, and a Borrmann type II tumor, 6.5 x 5 cm, was found in the resected stomach. Histologically, the tumor was mainly composed of small cells with hyperchromatic nuclei and scant cytoplasm. Argyrophilic granules were seen in these cells. There were also scattered foci of large cells with features of squamous cells, and many intermediate cells with oncocytic cytoplasm. The small cancer cells were positive for chromogranin A and neuron specific enolase. Squamous cell nests were positive for high molecular cytokeratin (CK), and intermediate cells were positive for low molecular CK. Electron microscopic examination revealed secretory granules in the small cells and tonofilaments in the squamous cells. This tumor might have originated from the pluripotential stem cell in the gastric epithelium.


Review of colorectal cancer in patients under age 40 years.
Brooke Army Medical Center Tumor Registry records from 1947 through 1980 were reviewed. One hundred forty of 819 patients with colorectal cancer were aged 40 or less. The 5 year survival rate was 35 percent and the 10 year survival rate 32 percent. The predominant presenting symptoms were bleeding, pain and change of bowel habits. The median duration of symptoms was 3 months. There were no Dukes'A patients. The 5 and 10 year survival rates in 19 Dukes' B patients were 67 percent. Thirty-three Dukes' C patients had 5 and 10 year survival rates of 37 and 30 percent, respectively. In 42 Dukes' D patients, however, there were no 5 year survivors, and the mean length of survival was only 10 months. Our findings support previous surveys which have concluded that stage at the time of diagnosis, rather than symptoms, duration or patient age, is the most accurate prognostic factor.


A realistic approach to locating dental practices: further considerations.
There are considerable demographic data that can be used in an organized manner to give dentists and graduating dental students greater insight relative to locating dental practices. This article further explores the concept and emphasizes the methods that can be used to measure and compare qualitatively the suitability of communities (service areas) and specific sites as practice locations. In addition, a method is reported that enables the user to ascertain the representativeness of a service area in terms of the demographic factors that affect the demand for dental services.


Ideomotor silence: the case of complete paralysis and brain-computer interfaces (BCI).
The paper presents some speculations on the loss of voluntary responses and operant learning in long-term paralysis in human patients and curarized rats. Based on a reformulation of the ideomotor thinking hypothesis already described in the 19th century, we present evidence that instrumentally learned responses and intentional cognitive processes extinguish as a consequence of long-term complete paralysis in patients with amyotrophic lateral sclerosis (ALS). Preliminary data collected with ALS patients during extended and complete paralysis suggest semantic classical conditioning of brain activity as the only remaining communication possibility in those states.


Spatiotemporal expression patterns of sialoglycoconjugates during nephron morphogenesis and their regional and cell type-specific distribution in adult rat kidney.
The expression of alpha2,6- and alpha2,3-linked sialic acids on N-glycans was studied in embryonic, postnatal, and adult rat kidney. Histochemistry and blotting using Polyporus squamosus and Sambucus nigra lectins for alpha2,6-linked sialic acids and the Maackia amurensis lectin for alpha2,3-linked sialic acids were performed and sialyltransferase activity was assayed. N-glycans with alpha2,6- and alpha2,3-linked sialic acid were differently expressed in the two embryonic anlagen and early stages of nephron. Metanephrogenic mesenchyme was positive for alpha2,3-linked sialic acid but not for the alpha2,6-linked one, which became detectable initially in the proximal part of S-shaped bodies. Collecting ducts were positive for alpha2,6-linked sialic acid, whereas alpha2,3-linked sialic acid was restricted to their ampullae. Although positive in embryonic kidney, S1 and S2 of proximal tubules became unreactive for alpha2,3-linked sialic acid in postnatal and adult kidneys. In adult kidney, intercalated but not principal cells of collecting ducts were reactive for alpha2,3-linked sialic acid. In contrast, alpha2,6-linked sialic acids were detected in all cells of adult kidney nephron. Blot analysis revealed a different but steady pattern of bands reactive for alpha2,6- and alpha2,3-linked sialic acid in embryonic, postnatal, and adult kidney. Activity of alpha2,6 and alpha2,3 sialyltransferases was highest in embryonic kidney and decreased over postnatal to adult kidney with the activity of alpha2,6 sialyltransferase always being three to fourfold that of alpha2,3 sialyltransferase. Thus, alpha2,6- and alpha2,3-linked sialic acids are differently expressed in embryonic anlagen and mesenchyme-derived early stages of nephron and show regional and cell type-specific differences in adult kidney.


Conditions of nutrients and dissolved organic matter for the outbreaks of Paralytic Shellfish Poisoning (PSP) in Jinhae Bay, Korea.
We measured the concentrations of nutrients, fluorescent dissolved organic matter (FDOM), and photosynthetic pigments in seawater during the springs of 2018 and 2019 in Jinhae Bay, Korea. The samplings were carried out during the severe and weak outbreaks of paralytic shellfish poisoning (PSP) in April 2018 and March 2019, respectively. The additional sampling campaigns were carried out before and after the PSP outbreak for the comparison. During the severe PSP outbreak, lower salinities, higher organic and total nutrients, and higher humic-like FDOM were observed. Although the environmental condition of April 2018 is favorable for the growth of dinoflagellates, the lowest peridinin (dinoflagellate index) and highest fucoxanthin (diatom index) concentrations were observed amongst all sampling periods. Thus, our results suggest that PSP could be more effectively produced by dinoflagellates in the course of the ecological shift by interspecific competition under the environmental condition favorable for dinoflagellates.


Sensitive D-amino acid biosensor based on oxidase/peroxidase system mediated by pentacyanoferrate-bound polymer.
A sensitive d-amino acid oxidase (DAAO)/peroxidase (POD) bienzyme biosensor is constructed, in which pentacyanoferrate-bound poly(1-vinylimidazole) polymer (PVI[Fe(CN)5]) is selected as a mediator. Reductive current of PVI[Fe(CN)5] related to the H2O2 concentration generated in the DAAO reaction was measured at -0.1V vs. Ag|AgCl with DAAO/POD/PVI[Fe(CN)5]-modified electrode. The result revealed that PVI[Fe(CN)5] is suitable as a mediator for this bienzyme system due to its appropriate formal potential and its extremely low reactivity against DAAO. The stability of DAAO was improved by adding free flavin adenine dinucleotide and the electrode composition was optimized for the detection of d-alanine. Nafion and ascorbate oxidase-immobilized films worked successfully to prevent severe interference from uric acid and ascorbic acid. The low detection limits of d-alanine (2μM) and d-serine (2μM) imply its possibility for the determination of extremely low concentration of d-amino acids in physiological fluids. The proposed bienzyme biosensor is proved to be capable of detecting d-amino acids in urine.


Mammalian cell protein expression for biopharmaceutical production.
Mammalian cell expression has become the dominant recombinant protein production system for clinical applications because of its capacity for post-translational modification and human protein-like molecular structure assembly. While expression and production have been fully developed and Chinese hamster ovary cells are used for the majority of products both on the market and in clinical development, significant progresses in developing and engineering new cell lines, introducing novel genetic mechanisms in expression, gene silencing, and gene targeting, have been reported in the last several years. With the latest analytical methods development, more attention is being devoted towards product quality including glycol profiling, which leads to better understanding the impact of culture condition during production. Additionally, transient gene expression technology platform plays more important role in biopharmaceutical early development stages. This review focused on the latest advancements in the field, especially in active areas such as expression systems, glycosylation impact factors, and transient gene expression.


Comparison of endoscopic ultrasound-guided fine-needle aspiration by capillary action, suction, and no suction methods: a randomized blinded study.
Different types of endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) techniques are used in clinical practice; the best method in terms of outcome has not been determined. The aim of the study was to compare the diagnostic adequacy of aspirated material, and the cytopathological and EUS morphological features between capillary action, suction, and no-suction FNA methods. This was a prospective, single-blinded, randomized study conducted at a tertiary care hospital. Patients were randomized to the three groups: capillary action, suction, and no suction. A total of 300 patients were included, with 100 patients in each arm. A total of 300 patients (195 males) underwent EUS-FNA of 235 lymph nodes and 65 pancreatic masses (distribution not statistically different between the groups). The mean age was 52 ± 14 years. A 22 gauge needle was used in the majority (93 %) of procedures. There was no statistical difference between the three groups regarding lymph node size at the largest axis and ratio, type of needle, echo features, echogenicity, calcification, necrosis, shape, borders (lymph nodes), number of passes, and cellularity. Diagnostic adequacy of the specimen was 91 %, 91 %, and 94 % in the capillary, suction, and no suction groups, respectively ( P = 0.67). Significantly more slides and blood clots were generated by the suction method compared with the other methods. The capillary action, suction, and no suction methods of EUS-FNA are similar in terms of diagnostic adequacy of the specimen. The suction method has the disadvantages of causing more bleeding and generating more slides.


Advances in and applications of imaging and radiomics in head and neck cancer survivorship.
Radiological imaging is an essential component of head/neck cancer (HNC) care. Advances in imaging modalities (including CT, PET, MRI and ultrasound) and analysis have enhanced our understanding of tumour characteristics and prognosis. However, the application of these methods to evaluate treatment-related toxicities and functional burden is still emerging. This review showcases recent literature applying advanced imaging and radiomics to the assessment and management of sequelae following chemoradiotherapy for HNC. Whilst primarily early-stage/exploratory studies, recent investigations have showcased the feasibility of using radiological imaging, particularly advanced/functional MRI (including diffusion-weighted and dynamic contrast-enhanced MRI), to quantify treatment-induced tissue change in the head/neck musculature, and the clinical manifestation of lymphoedema/fibrosis and dysphagia. Advanced feature analysis and radiomic studies have also begun to give specific focus to the prediction of functional endpoints, including dysphagia, trismus and fibrosis. There is demonstrated potential in the use of novel imaging techniques, to help better understand pathophysiology, and improve assessment and treatment of functional deficits following HNC treatment. As larger studies emerge, technologies continue to progress, and pathways to clinical translation are honed, the application of these methods offers an exciting opportunity to transform clinical practices and improve outcomes for HNC survivors.


The Online Cancer Nutrition Misinformation: A framework of behavior change based on exposure to cancer nutrition misinformation.
Patients with cancer and caregivers increasingly use the internet to find health and lifestyle information, yet online recipes, diet, and nutrition content are unregulated and may be confusing or even misleading. We describe cancer-related nutrition and meal planning information from Pinterest. In June 2020, we searched Pinterest using "cancer recipe" and "recipe for cancer" at 3 times daily for 2 weeks. Duplicates were removed for a final sample of n = 103 pins. Each pin was coded for 58 variables including descriptives, cancer claims (eg, treatment, prevention, and cure), and nutrition claims (eg, "turmeric cures cancer"). We summarized each variable to describe the content of cancer nutrition claims on Pinterest and examined associations between claim types and contextual factors, including the use of academic citations, disclaimers, and personal anecdotes. Pinners had on average 116,767 followers (range, 0-1.5 million). Almost half of content sites were for profit (48.5%) and 34% were selling a product. Health claims were common, with content that purported to prevent (41.8%), treat (27.2%), or cure (10.7%) cancer. Vague phrases such as "anti-cancer," "cancer-fighting," or "cancer-busting" were also used. The inclusion of validity indicators including academic citations, disclaimers, and personal anecdotes varied significantly by the types of claims made. Together, these analyses informed the development of a conceptual framework of cancer-related nutrition misinformation. There are clear financial incentives for the promotion of cancer nutrition information online. More research is needed to understand how exposure to nutrition information can influence patient/caregiver behavior and downstream clinical and psychosocial outcomes.


Amino acid starvation induced by protease inhibition produces differential alterations in redox status and the thiol proteome in organogenesis-stage rat embryos and visceral yolk sacs.
The process of embryonic nutrition in rodent conceptuses during organogenesis has been shown to involve a dominant histiotrophic mechanism where essential developmental substrates and micronutrients are supplied as whole maternal proteins or cargoes associated with proteins. The histiotrophic nutrition pathways (HNP) responsible for uptake and initial processing of proteins across maternal-conceptal interfaces involve uptake via receptor mediated endocytosis and protein degradation via lysosomal proteolysis. Chemical inhibition of either process can lead to growth deficits and malformation in the embryo (EMB), but selective inhibition of either HNP component will elicit a different subset of developmental perturbations. In vitro, whole embryo culture exposure of GD10 or GD11 rat conceptuses to the natural protease inhibitor, leupeptin, leads to significant reductions in all measured embryonic growth parameters as well as a myriad of other effects. Leupeptin doses of 10 μM or 20 μM over a 26-h period (GD10-GD11) and 50 μM over a 3 h pulse period produced significant decreases in the clearance of FITC-albumin from culture media. The near complete loss of acid soluble fluorescence and increased total visceral yolk sac (VYS) protein content confirmed the selective inhibition of proteolysis. Inhibition of lysosomal proteolysis thus deprives the developing EMB of essential nutrient amino acids producing conditions akin to amino acid starvation, but may also cause direct effects on pathways critical for normal growth and differentiation. Following leupeptin exposure for 26 or 6 h, total glutathione (GSH) concentrations dropped significantly in the VYS, but only slightly in yolk sac (YSF) and amniotic (AF) fluids. Cys concentrations increased in VYS and EMB, but dropped in YSF and AF fluids. Redox potentials (Eh) for the glutathione disulfide (GSSG)/glutathione (GSH) redox couple trended significantly toward the positive, confirming the net oxidation of conceptual tissues following leupeptin treatment. Analysis of the thiol proteome showed few alterations to specific pathways mapped to the Kyoto Encyclopedia of Genes and Genomes Pathway database, but did reveal significant increases in concentrations of proteins associated with glycolysis/gluconeogenesis in the VYS and decreased concentrations proteins associated with ribosome biogenesis and function in the EMB. A subset of proteins elevated by >2-23-fold in the VYS were identified as serum (blood) proteins and represent the maternal-side proteins captured by the VYS and which are not degraded in the lysosomes as a result of leupeptin's inhibitory action. The observed constellation of proteins decreased in the EMB by leupeptin represent proteins from several adaptive pathways that are commonly altered in responses to amino acid starvation. These studies show clear differential responses to protease inhibition in VYS and EMB during organogenesis and suggest the possibility for additional roles of redox regulation, cellular adaptations and metabolic insufficiency caused by protease inhibition.


Pathological changes of frozen shoulder in rat model and the therapeutic effect of PPAR-γ agonist.
Frozen shoulder is a common shoulder disorder characterized by a gradual increase of pain and a limited range of motion. However, its pathophysiologic mechanisms remain unclear and there is no consensus as to the most effective treatment. The purpose of the study was to investigate the effect of transforming growth factor-β (TGF-β) on fibrosis and inflammatory response of the shoulder joint of rat models and to explore the therapeutic effect of the peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist. In the study, the effect of PPAR-γ agonist CDDO-IM treatment on cell proliferation, migration, and extracellular matrix proteins synthesis (vimentin, α-smooth muscle actin, collagen I, and collagen III) were tested by cell proliferation test, scratches test, real-time quantitative polymerase chain reaction, and Western blot analysis. The frozen shoulder was also established on the rat model by injecting adenovirus-TGF-β1 into rats' shoulder capsule. Pathological changes of the frozen shoulder tissue of the experimental group and PPAR-γ agonist treatment group were evaluated. The stiffness of joints of the three groups was tested. Inflammatory mediators' expression including cyclooxygenase-1, interleukin-1β, and tumor necrosis factor-α of the shoulder was tested by enzyme-linked immunosorbent assay, and the expression of extracellular matrix proteins was evaluated by hematoxylin and eosin staining and immunohistochemistry. The results showed that pathological changes of the frozen shoulder in the rat model include an abnormal proliferation of fibroblasts, infiltration of inflammatory cells, and disorder of fibrous structure, while rosiglitazone reduced the severity of the frozen shoulder in the treatment group. Clinically, PPAR-γ agonists may be a promising target for the treatment of the frozen shoulder.


Prior infection with Bordetella bronchiseptica enhanced colonization but not disease with Streptococcus suis.
Bordetella bronchiseptica and Streptococcus suis are widely distributed swine pathogens. B. bronchiseptica is a primary pathogen and causes atrophic rhinitis and bronchopneumonia. S. suis is a contributing agent to porcine respiratory disease complex and causes systemic diseases including arthritis, meningitis, polyserositis, and septicemia. Colonization with B. bronchiseptica has been associated with increased colonization by other pathogenic bacteria and increased disease severity with viral and bacterial pathogens. It has also been reported to predispose cesarean derived, colostrum deprived (CDCD) piglets to S. suis systemic disease. Here, we evaluated the role of B. bronchiseptica colonization on S. suis colonization, dissemination, and disease in one study using conventional pigs and another using CDCD pigs. Pigs were challenged with S. suis, B. bronchiseptica, or B. bronchiseptica followed by S. suis. Incidence of S. suis disease was not increased in either study for animals pre-inoculated with B. bronchiseptica. Nasal colonization with S. suis was increased in coinfected animals, while B. bronchiseptica was similar between mono- and co-infected animals. Although increased S. suis disease was not seen in coinfected pigs, there is evidence that B. bronchiseptica can increase colonization with S. suis, which may contribute to enhanced disease when animals are stressed or immunocompromised.


Update on advanced imaging options for thyroid-associated orbitopathy.
Thyroid-associated orbitopathy (TAO) is a diverse spectrum of signs and symptoms that appears to have immunologic and pathologic causative factors as diverse as its clinical presentations. Lymphocytes, hormones, and cytokines affect orbital fibroblasts and other similar cells, which exert their effects on orbital tissues, including the extraocular muscles, orbital fat, and optic nerve. This complicated inflammatory cascade and the myriad of clinical findings that result contributes to the active phase of TAO. The distinction between the active and inactive phases of TAO is an important one, as the proper treatment will depend on the disease phase and degree thereof. Several clinical grading scales and scores have been established to help qualify and quantify the disease severity. Aiding clinical exam and acumen, proper and reproducible imaging of the orbit and ocular adnexa is incredibly important to the management of TAO. Orbital ultrasound, computed tomography, magnetic resonance imaging, and scintigraphy each have unique abilities, including quantifying orbital changes, assessing disease activity, correlating orbital findings with clinical changes, guiding appropriate treatment, and monitoring therapeutic responses. Further, study ease, accessibility, cost, sensitivity, specificity, reproducibility, and risks are all important considerations in picking the right test with which to diagnose and follow TAO. This analysis will provide a review of orbital imaging for TAO, including the mechanism of each imaging technique as well as their rationales, advantages, disadvantages, and utilities.


Genome-wide association study of cocaine dependence and related traits: FAM53B identified as a risk gene.
We report a genome-wide association study (GWAS) for cocaine dependence (CD) in three sets of African- and European-American subjects (AAs and EAs, respectively) to identify pathways, genes and alleles important in CD risk. The discovery GWAS data set (n=5697 subjects) was genotyped using the Illumina OmniQuad microarray (8 90 000 analyzed single-nucleotide polymorphisms (SNPs)). Additional genotypes were imputed based on the 1000 Genomes reference panel. Top-ranked findings were evaluated by incorporating information from publicly available GWAS data from 4063 subjects. Then, the most significant GWAS SNPs were genotyped in 2549 independent subjects. We observed one genome-wide-significant (GWS) result: rs2629540 at the FAM53B ('family with sequence similarity 53, member B') locus. This was supported in both AAs and EAs; P-value (meta-analysis of all samples)=4.28 × 10(-8). The gene maps to the same chromosomal region as the maximum peak we observed in a previous linkage study. NCOR2 (nuclear receptor corepressor 2) SNP rs150954431 was associated with P=1.19 × 10(-9) in the EA discovery sample. SNP rs2456778, which maps to CDK1 ('cyclin-dependent kinase 1'), was associated with cocaine-induced paranoia in AAs in the discovery sample only (P=4.68 × 10(-8)). This is the first study to identify risk variants for CD using GWAS. Our results implicate novel risk loci and provide insights into potential therapeutic and prevention strategies.


Systematic evaluation of surgical strategies for acute malignant left-sided colonic obstruction.
Surgical strategy for acute colorectal obstruction due to colorectal cancer remains controversial. One-, two- and three-stage surgical procedures, and preoperative stenting of the stenosis as a bridge to surgery, are available. A systematic review was conducted, searching MEDLINE, EMBASE and CENTRAL, as well as bibliographies of included studies, to identify randomized and non-randomized controlled trials that compared two or more surgical procedures in acute colonic obstruction. After screening 1748 titles and abstracts, 209 were selected for full text assessment; 29 studies with 2286 patients were finally included. In general, the quality of the studies was limited, with only three randomized trials. Eight non-randomized studies comparing one-stage with two- or three-stage surgery consistently favoured a one-stage procedure in terms of mortality (relative risk difference from - 2 to - 27 per cent), but reported morbidity rates were not different. Trials of different one-stage procedures (segmental and total/subtotal colectomy) showed none to be clearly superior. Stenting procedures were superior to non-stenting treatments. One-stage surgery appears to be superior to two- or three-stage procedures. Stenting is a promising option, allowing the resection to be carried out in an elective setting.


Reproductive performance of three fat-tailed breeds of sheep mated to native, Corriedale and Targhee rams.
Reproduction and lamb production of three fat-tailed, carpet-wool Iranian breeds of sheep; Karakul (130 ewes), Mehraban (103) and Baluchi (119) were studied. The ewes were mated either as purebreds or with Corriedale or Targhee rams. The overall least-squares means for ewes mated (showed oestrus) or ewes exposed, ewes lambed or ewes mated, lambs born of ewes lambing (prolificacy), lambs born alive of total lambs born, lambs weaned of live lambs born, lambs weaned (75 days of age) of ewes mated, kg lamb weaned per ewe mated and kg lamb weaned per 100 kg ewe mated were 98.3%, 93.5%, 103.1%, 94.9%, 97.8%, 90.0%, 18.2 kg and 38.4 kg respectively. The native breeds were not different for any of the traits studied except for prolificacy which was higher in Mehraban than in Karakul. Purebred matings did not differ from the crossbred matings for any of the traits concerning the number of lambs but crossbreeding improved kg lamb weaned per ewe mated (9.2%, P = 0.08) and kg lamb weaned per 100 kg ewe mated (10.0%, P less than 0.05). Among the three native breeds Karakul showed the largest improvement when crossed with the exotic rams for the traits concerning kg lambs weaned. Corriedale and Targhee rams had similar effects on all the traits studied. A lower percentage of virgin ewes showed oestrus, had a lower twinning rate and productivity compared with the mature ones. Sex was not a significant source of variation in lamb livability.


Evaluating the Effectiveness and the Impact of Donated Neurosurgical Equipment on Neurosurgical Units in Low- and Middle-Income Countries: The World Federation of Neurosurgical Societies Experience.
Surgical practice highly depends on the availability of surgical equipment; this is particularly relevant to low- and middle-income countries (LMICs), where resources are limited. A key part of the efforts to improve surgical provision globally include providing affordable equipment to LMICs; however, the effectiveness and the impact of these initiatives have not yet been assessed. We aimed to evaluate the World Federation of Neurosurgical Societies neurosurgical equipment program in this context. Recipients were identified from the World Federation of Neurosurgical Societies records; contact details were gathered. An online survey was used to collect data on equipment, including its current use, any malfunctioning issues, suitability, reliability, serviceability, and the impact it has had on the unit. Responses were received from 16 units, totaling 28 pieces of equipment. A total of 75% of the equipment is still in use; of this, 57% is fully functioning, and 43% is used despite some malfunction. We found that 25% of the equipment is broken and unusable; high-maintenance items, such as high-speed drills, feature in this category (100% broken, n = 3). Units reported an increase in number of operation performed in 74% cases, improved surgery quality in 78%, and breadth of operations in 44%. Satisfaction, equipment suitability, reliability, and serviceability scored highly, with median values of 9 for all fields on a 10-point scale. Equipment donation positively impacts neurosurgical units in LMICs by allowing expansion of neurosurgical practice, improved safety and quality, and affordability. Adequate follow-up, considerations regarding equipment durability and maintenance needs, and improved support for repairs should be prioritized to ensure maximal benefit.


Ablation of the p16(INK4a) tumour suppressor reverses ageing phenotypes of klotho mice.
The p16(INK4a) tumour suppressor has an established role in the implementation of cellular senescence in stem/progenitor cells, which is thought to contribute to organismal ageing. However, since p16(INK4a) knockout mice die prematurely from cancer, whether p16(INK4a) reduces longevity remains unclear. Here we show that, in mutant mice homozygous for a hypomorphic allele of the α-klotho ageing-suppressor gene (kl(kl/kl)), accelerated ageing phenotypes are rescued by p16(INK4a) ablation. Surprisingly, this is due to the restoration of α-klotho expression in kl(kl/kl) mice and does not occur when p16(INK4a) is ablated in α-klotho knockout mice (kl(-/-)), suggesting that p16(INK4a) is an upstream regulator of α-klotho expression. Indeed, p16(INK4a) represses α-klotho promoter activity by blocking the functions of E2Fs. These results, together with the observation that the expression levels of p16(INK4a) are inversely correlated with those of α-klotho throughout ageing, indicate that p16(INK4a) plays a previously unrecognized role in downregulating α-klotho expression during ageing.


Hospitals prepare for medicare cuts: the need to reduce the federal deficit puts seniors and providers on notice.
In view of changing Medicare payment policies, hospitals reassess pharmacy procedures.


Urine and plasma osmolality in patients with autosomal dominant polycystic kidney disease: reliable indicators of vasopressin activity and disease prognosis?
Vasopressin plays an essential role in osmoregulation, but has deleterious effects in patients with ADPKD. Increased water intake to suppress vasopressin activity has been suggested as a potential renoprotective strategy. This study investigated whether urine and plasma osmolality can be used as reflection of vasopressin activity in ADPKD patients. We measured urine and plasma osmolality, plasma copeptin concentration, total kidney volume (TKV, by MRI) and GFR ((125)I-iothalamate). In addition, change in estimated GFR (eGFR) during follow-up was assessed. Ninety-four patients with ADPKD were included (56 males, age 40 ± 10, mGFR 77 ± 32 ml/min/1.73 m(2), TKV 1.55 (0.99-2.40) l. Urine osmolality, plasma osmolality and copeptin concentration were 420 ± 195, 289 ± 7 mOsmol/l and 7.3 (3.2-14.6) pmol/l, respectively. Plasma osmolality was associated with copeptin concentration (R = 0.54, p < 0.001), whereas urine osmolality was not (p = 0.4). In addition, urine osmolality was not associated with TKV (p = 0.3), in contrast to plasma osmolality (R = 0.52, p < 0.001) and copeptin concentration (R = 0.61, p < 0.001). Fifty-five patients were followed for 2.8 ± 0.8 years. Baseline plasma and urine osmolality were not associated with change in eGFR (p = 0.6 and p = 0.3, respectively), whereas baseline copeptin concentration did show an association with change in eGFR, in a crude analysis (St. β = -0.41, p = 0.003) and also after adjustment for age, sex and TKV (St. β = -0.23, p = 0.05). These data suggest that neither urine nor plasma osmolality are valid measures to identify ADPKD patients that may benefit from increasing water intake. Copeptin appears a better alternative for this purpose.


The effects of antipsychotic treatment on quality of life of schizophrenic patients under naturalistic treatment conditions: an application of random effect regression models and propensity scores in an observational prospective trial.
The study examines the effect of different types of antipsychotic treatment on the health related quality of life (HRQL) of people with schizophrenia under naturalistic outpatient treatment conditions. In a prospective study design, 307 schizophrenic patients were followed over a period of 2.5 years. HRQL, clinical characteristics, and type of antipsychotic medication were assessed five times every 6 months. HRQL was assessed by the SF-36. Random effect regression models were computed for the SF-36 mental (MCS) and physical (PCS) component scores. Propensity scores were included in the regression models to reduce a possible sample selection bias. Monotherapeutic treatment with new atypical neuroleptic drugs had a more positive effect on the mental health related quality of life (MCS) in comparison to treatment with polypharmacological treatment but not with oral conventional antipsychotics. Monopharmaceutical treatment with depot-antipsychotic drugs had a more positive effect on the physical health related quality of life (PCS) in comparison to polypharmacological treatment. Study results indicate that atypical antipsychotic drugs are not superior to conventional antipsychotics with regard to the effect on QOL. However, monopharmaceutical treatment can be assumed to be more effective in improving mental and physical related QOL than polypharmaceutical treatment.


Phase II trial of piroxantrone in patients with recurrent and metastatic squamous cell carcinoma of the head and neck. A Southwest Oncology Group trial.
Twenty-two patients with recurrent or metastatic squamous cell carcinoma of the head and neck were treated with piroxantrone 150 mg/m2 intravenously every 21 days. There were no objective responses. The 95% upper confidence bound for response is 15%. Primary toxicity was hematologic.


A pure antiandrogen does not interfere with the LHRH agonist-induced blockade of testicular androgen secretion in the dog.
Daily subcutaneous administration of 50 micrograms of the luteinizing hormone-releasing hormone (LHRH) agonist [D-Trp6]LHRH ethylamide in adult dogs causes a transient increase in the serum testosterone (T) concentration which reaches a maximum at 200% above control on days 2-4 of treatment and progressively decreases to 7% of the pretreatment value on day 21, the last time interval studied. After a transient increase, the concentration of serum bioactive luteinizing hormone (LH) was progressively decreased on days 11 and 19, thus suggesting that in analogy with human findings, the loss of LH bioactivity is responsible for the inhibition of testicular steroidogenesis induced in the dog by LHRH agonists. Of major significance is the finding that the changes in serum T levels observed during the first 3 weeks of treatment, as well as the complete inhibition of the intratesticular concentration of sex steroids observed at the end of this period of treatment with the LHRH agonist were not affected by simultaneous administration of flutamide (125 mg per os every 8 h). Such findings indicate that at the dose used, the LHRH agonist is in full control of gonadotropin secretion, thus completely overcoming feedback influences. Since the administration of the antiandrogen flutamide does not decrease the efficacy of the LHRH agonist as blocker of testicular androgen biosynthesis, the present data support the use of a pure antiandrogen in order to neutralize the effect of the transient rise in testicular androgen secretion which always accompanies the first days of treatment with LHRH agonists in patients with advanced prostate cancer.


Feasibility of stent placement above the sphincter of Oddi ("inside-stent") for patients with malignant biliary obstruction.
Animal studies suggest that placement of endobiliary stents wholly above the papilla (the "inside-stent") prolongs the duration of stent patency. We reviewed the cholangiographic characteristics of patients with malignant obstructive jaundice in order to evaluate the feasibility of this approach and to assist in the design of a new stent. A review was conducted of 270 patients who had undergone endoscopic retrograde cholangiopancreatography (ERCP) for malignant obstructive jaundice at our hospital, to determine the relative frequencies of the types of cancers. The ERCP films of 59 relevant consecutive patients with malignant obstructive jaundice were studied to determine the length of the stricture, the distance between the stricture and the papilla, and the angulation of the common duct. The most frequent primary cancers causing malignant obstructive jaundice were pancreatic cancer (57%), biliary cancer involving the hilum (19%, including metastatic disease), nonhilar biliary cancer (14%), and papillary cancer (10%). The length between the lower end of the stricture and the sphincter was more than 2 cm for all hilar biliary cancer, representing two-thirds of nonhilar biliary cancer cases, while it was less than 1 cm for most pancreatic cancers. There was an average angulation of 30-40 degrees in the axis of the distal common bile duct. For most biliary cancers, the stricture is high enough to allow the placement of a stent fully above the papilla, but this is not possible for most pancreatic cancers (or any papillary cancers). An "inside-stent" approach would be possible in about one-third of patients with malignant obstructive jaundice if a clearance length of over 2 cm between the stricture and the sphincter is required, and in about 45% of patients if a minimum clearance of 1 cm is required. A 30-40 degrees flexion in the distal part of the stent would approximate the average angulation in the axis of the common bile duct and help to prevent dislocation.


Global Trends in Atherosclerosis Research in the Epigenetics Field: Bibliometric and Visualization Studies.
Atherosclerosis is a pathological vascular state caused by the interaction of environmental and hereditary factors. Epigenetic modifications may be the bridge connecting environmental factors and genetic factors. A search for publications on the Web of Science database in the field of atherosclerosis related to epigenetics was conducted from the earliest mention to 31 December 2020. Data on total and annual publications, citations, impact factors, Hirsch (H)-index, citation times, most prolific authors, and frequently published journals were collected for quantitative and qualitative comparison. A total of 1848 publications related to epigenetics and atherosclerosis were found. The major contributing countries were the China (522, 28.23%), United States (485, 26.23%), and Germany (119, 6.44%). The greatest number of retrieved publications were published in the journal, "Arteriosclerosis, Thrombosis, and Vascular Biology" (62, 3.66%). The publication "Oxidative Stress and Diabetic Complications" was cited 2370 times. The most frequent keywords were "DNA methylation" and "LncRNA". Publications on epigenetic research in the atherosclerosis field have increased significantly every year, indicating that the study of epigenetic modifications plays an increasingly important role in understanding the pathology of atherosclerosis.


Arguments for standardizing transposable element annotation in plant genomes.
Whole genome sequence assemblies have been generated for many plants. Annotation of transposable elements (TEs), which constitute the major proportion of genomes and play a significant role in epigenome alterations under stress, has not been given equal importance to that of genes. In this opinion article, we argue that the lack of focus dedicated to the fine-scale characterization of repeat fractions and the absence of consistent methods for their annotation impede our ability to critically understand the influence of TEs on the epigenome with implications in gene expression and non-Mendelian inheritance. Major structural changes occur over an evolutionary time scale. However, epigenetic regulation mediated by TEs can happen in a single generation, thus emphasizing the need for their standardized annotation.


n of 1 trial for an ornithine transcarbamylase deficiency carrier.
Ornithine transcarbamylase deficiency (OTCD) is an X-linked disorder of the urea cycle. It is often fatal in affected males. Treatment for affected individuals includes dietary protein restriction, activation of alternative pathways of nitrogen excretion and L-arginine supplementation. Depending on the amount of X chromosome inactivation skewing, females show variable clinical manifestations, and sometimes the need for treatment, including medications, is unclear. We conducted an n of 1 randomized controlled trial on an obligate OTC carrier. The treating physician and patient were blinded to treatment. Either placebo capsules or L-arginine capsules were given for weekly periods. Weekly efficacy indicators included plasma arginine and glutamine levels and a quality of life/mood assessment questionnaire scale. Clear evidence of benefit with L-arginine compared to placebo was shown. This is the first time an n of 1 randomized controlled trial has been reported for an X-linked metabolic condition. Despite some logistic hurdles, we have demonstrated that this method was an effective tool for determining the value of treatment. We propose that other rare metabolic conditions may be amenable to such trials, if the benefit of treatment is in doubt.


Reactions of vinylidenecyclopropanes with diphenyl diselenide in the presence of AIBN and further transformation to produce new naphthalene derivatives.
The reactions of vinylidencyclopropanes 1 with diphenyl diselenide 2 in the presence of AIBN produced the corresponding products 4 or 5 in moderate to good yields under mild conditions. The transformation of 4 to the corresponding methylenecyclopropanes 6 was achieved by treatment with hydrogen peroxide (H2O2) in toluene, and these were further transformed to the corresponding naphthalene derivatives 7 by treatment with 30 mol % of TfOH in dichloromethane.


Molecular interactions of adenosine triphosphatase with the mitochondrial membrane as revealed by a spin label study.
Mitochondrial ATPase complex has been spin-labeled in the membrane using the inhibitor N-(2,2,6,6-tetramethylpeperidyl-1-OXYL)-N(cyclohexyl)carbodiimide (nccd). the amount of NCCD bound to mitochondrial fragments is 0.5 nmol/mg and cannot be dialyzed or extracted with ether, chloroform, or methanol. The electron paramagnetic resonance spectrum of NCCD bound to fragments is pH-sensitive, a greater label immobilization occurring at pH values lower or higher than 7. Ether extraction removes the ATPase inhibition by NCCD without detaching the label. This effect appears to be the consequence of the dislocation of some components of the ATPase complex. Removal of F1 natural inhibitor or of F1 does not affect the spectrum of NCCD bound to fragments, while the removal of oligomycin sensitivity-conferring protein produces an increase in the extreme splitting. Oligomycin sensitivity-conferring protein may thus interact with the NCCD binding component of the membrane. The isolation of the NCCD-binding proteolipid results in a large increase in the mobility of the label, but addition of dipalmitoyllecithin decreases the mobility of the label to the original level. Phospholipids are thus necessary to keep the NCCD-binding proteolipid in the native conformation.


[Acquired progressive lymphangioma in a 13-year-old boy].
Acquired tumors of lymphatic vessels are rare. Clinically, progressive lymphangioma usually appears as circumscribed plaques of small to medium size. In contrast, our case of a 13-year-old boy demonstrates a case of progressive lymphangioma with a solitary large indurated plaque. No extracutaneous manifestation was found. Systemic therapy with corticosteroids and methotrexate resulted in an improvement of the patient's condition. Dependent on clinical course and appearance of the disease, therapy with mTOR inhibitors may be considered as a therapeutic option.


Towards a pro-resolving concept in systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with prominent chronic inflammatory aspects. SLE most often affects women (9:1) in childbearing age. The multifactorial nature of the etiopathogenesis of SLE involves a deficient clearance of dead and dying cells. This is supported by the occurrence of autoantibodies directed against autoantigens modified in dying and dead cells (dsDNA, high mobility group box 1 protein, apoptosis-associated chromatin modifications, e.g., histones H3-K27-me3; H2A/H4 AcK8,12,16; and H2B-AcK12) that are deposited in various tissues, including skin, kidneys, joints, muscles, and brain. The subsequent hyperinflammatory response often leads to irreparable tissue damage and organ destruction. In healthy individuals, dead and dying cells are rapidly removed by macrophages in an anti-inflammatory manner, referred to as efferocytosis. In SLE, extensive and prolonged cell death (apoptosis, necrosis, neutrophil extracellular trap (NET) formation) leads to autoantigens leaking out of the not cleared cell debris. These neo-epitopes are subsequently presented to B cells by follicular dendritic cells in the germinal centers of secondary lymphoid tissues conditioning the break of self-tolerance. Activation of autoreactive B cells and subsequent production of autoantibodies facilitate the formation of immune complexes (ICs) fueling the inflammatory response and leading to further tissue damage. ICs may also be ingested by phagocytes, which then produce further pro-inflammatory cytokines. These processes establish a vicious circle that leads to sustained inflammation. This review highlights the cell death-related events in SLE, the protagonists involved in SLE pathogenesis, the resolution of inflammation in various tissues affected in SLE, and explores strategies for intervention to restore hemostasis in a hyperinflammatory state.


Primary malignant peripheral nerve sheath tumour of the trachea: a case report and literature review.
Malignant peripheral nerve sheath tumours (MPNSTs) of the trachea are extremely uncommon neoplasms with unknown genetic and clinical profiles. Only individual cases have been reported in the literature to date. Here, we present a rare case of a 61-year-old female patient with a primary MPNST of the trachea who complained of irritating cough and progressively increasing breathlessness for 4 weeks. This patient initially underwent intraluminal resection of the mass and was misdiagnosed with clear cell sarcoma. Less than a year later, the mass relapsed, and the obstructive symptoms reappeared and gradually worsened. Debulking of the endotracheal tumour mass was performed once again, and an MPNST was definitively diagnosed. Open sleeve tracheal resection and tracheoplasty were later performed with curative intent. This patient was alive without recurrence at her six-month postoperative follow-up. We also compared the clinical outcomes of previously reported cases of MPNSTs and our case. This paper emphasizes that thoracic surgeons should be aware that malignant peripheral nerve sheath tumours of the trachea can be misdiagnosed in clinical practice and must be included in the differential diagnosis of tracheal neoplasms.


Breast carcinoma associated with Klinefelter syndrome: a case report.
Klinefelter syndrome increases the risk of developing breast cancer to approximately 1/5 that of women and 20 times that of normal men. A case report and the patient's response to hormone manipulation for metastatic disease is described.


Public health education for emergency medicine residents.
Emergency medicine (EM) has an important role in public health, but the ideal approach for teaching public health to EM residents is unclear. As part of the national Regional Public Health-Medicine Education Centers-Graduate Medical Education initiative from the CDC and the American Association of Medical Colleges, three EM programs received funding to create public health curricula for EM residents. Curricula approaches varied by residency. One program used a modular, integrative approach to combine public health and EM clinical topics during usual residency didactics, one partnered with local public health organizations to provide real-world experiences for residents, and one drew on existing national as well as departmental resources to seamlessly integrate more public health-oriented educational activities within the existing residency curriculum. The modular and integrative approaches appeared to have a positive impact on resident attitudes toward public health, and a majority of EM residents at that program believed public health training is important. Reliance on pre-existing community partnerships facilitated development of public health rotations for residents. External funding for these efforts was critical to their success, given the time and financial restraints on residency programs. The optimal approach for public health education for EM residents has not been defined.


A novel anti-inflammatory role of NCAM-derived mimetic peptide, FGL.
Age-related cognitive deficits in hippocampus are correlated with neuroinflammatory changes, typified by increased pro-inflammatory cytokine production and microglial activation. We provide evidence that the neural cell adhesion molecule (NCAM)-derived mimetic peptide, FG loop (FGL), acts as a novel anti-inflammatory agent. Administration of FGL to aged rats attenuated the increased expression of markers of activated microglia, the increase in pro-inflammatory interleukin-1beta (IL-1beta) and the impairment in long-term potentiation (LTP). We report that the age-related increase in microglial activation was accompanied by decreased expression of neuronal CD200, and suggest that the proclivity of FGL to suppress microglial activation is due to its stimulatory effect on neuronal CD200. We demonstrate that FGL enhanced interleukin-4 (IL-4) release from glial cells and IL-4 in turn enhanced neuronal CD200 in vitro. We provide evidence that the increase in CD200 is reliant on IL-4-induced extracellular signal-regulated kinase (ERK) signal transduction. These findings provide the first evidence of a role for FGL as an anti-inflammatory agent and identify a mechanism by which FGL controls microglial activation.