Storylines, metaphors, and solutions in the work-readiness literature: A frame analysis.
To investigate how the literature frames the reported poor work-readiness of new graduate nurses and the solutions it recommends. Critical frame analysis of work-readiness literature storylines. Deductive and inductive analysis of work-readiness literature published 2016-2019. The three systematic reviews, literature review, and analysis of transition guidelines reinforced the belief that nursing graduates should be work-ready. In addition, the articles summarized service and academic innovations intended to assist newly qualified nurses transition to practice. The literature attributes perceived graduates' poor work-readiness to divergent faculty and employer expectations, personal deficiencies, defective learning environments, and poor workplace support. Internships, mentorship, academic-service partnerships, and curricular and pedagogical innovation are the dominant recommendations for reform. Workplace clinical education and training are not mechanisms for correcting graduates' work performance but essential activities for sustaining the nursing workforce. The study should encourage more use of frame analysis in nursing education research. Fact-checking storylines must be a priority for future studies. Research that clarifies the fault lines between advocates of work-readiness and dissident academic leaders has the potential to promote dialogue. Work-ready, theory-gap, and other deficit metaphors must be put aside for the debate because universities must not relinquish their responsibility for educating students for the 21st century.


Autoimmune hepatitis: the present status in Japan.
A nationwide survey using questionnaires was carried out concerning lupoid hepatitis and related diseases (518 cases) during the 8-year period from January, 1975 to December, 1982. The following results were obtained. A total of 253 cases of autoimmune hepatitis, consisting of 97 lupoid hepatitis and 156 lupoid type CAH, were reported. Autoimmune hepatitis was overwhelmingly predominant in females, while male cases of B type CAH with a gamma-globulin level of more than 2 g/dl significantly outnumbered female CAH cases of the same type. The liver function tests at the first examination demonstrated that transaminases, total bilirubin, ICG (R15) and gamma-globulin were increased, and ChE was decreased in lupoid hepatitis. Lupoid type CAH showed a close similarity with lupoid hepatitis rather than to the nLnB type or B type with regard to liver function. Of the 289 patients who could be followed up, 280 cases (97%) received steroid hormones, and 247 (85%) received no another drug. Immunosuppressive treatment was also performed in 40% of the HBs antigen-positive cases of B type CAH. The efficacy was about 90% in the lupoid hepatitis group as well as in the lupoid type CAH group. It was no greater than approximately 70% in any other group. Analysis of survival revealed the following: 1) The cumulative survival rates of autoimmune hepatitis was lowest among the different types of CAH. 2) Patients who had a high serum level of total bilirubin tended to die sooner than those who had a low level. There was no correlation between the cumulative survival rate and serum gamma-globulin concentration or antinuclear antibody titer. 3) The duration of steroid hormone therapy and the total dosage of immunosuppressants were thought to be important factors affecting the prognosis of autoimmune hepatitis.


Drug-induced chronic hepatic disease.
A number of chronic hepatic lesions can result from adverse reactions to medicinal agents. Such lesions include a form of chronic active hepatitis; hepatic steatosis, phoepholipidosis and granulomatosis; several vascular lesions; two types of noncirrhotic portal hypertension; several types of cirrhosis and several neoplasms.


Do gender and torus mandibularis affect mandibular cortical index? A cross-sectional study.
The interactions between torus and several factors such as age, gender, and dental status have not been studied comprehensively. The purpose of this study was to determine the effect of gender on the mandibular cortical index (MCI) and to investigate a possible association between torus mandibularis (TM) and MCI. The study consisted of 189 consecutive patients referred to Department of Oral Diagnosis and Radiology of Hacettepe University within 30 workdays. Patients who did not have systemic disorders affecting bone density were included; and the age, gender, dental status and existing TM of the patients were recorded. Morphology of the mandibular inferior cortex was determined according to Klemitti's classification on panoramic radiographs. MCI was affected by age and gender (P < 0.05). No significant relationship was found between TM and MCI (P > 0.05). In the study population, MCI was affected by age and gender. As age increased, semilunar defects could be seen on the cortex of the mandible and MCI values increased. Women appeared to have higher MCI values than men.


Paraplegia after Hypotension with Pneumothorax Episode during Thoracic Spine Tumor Surgery.
Paraplegia after spine surgery is a catastrophic complication. Here, we present a patient who, following laminectomy and fusion for decompression of metastatic tumor, developed paraplegia. We tried to find out the possible reason for the paraplegia. Due to prolonged hypotension during operation and new onset of pneumothorax, we think that intraoperative prolonged hypotension leads to the spinal cord ischemia which may cause neurological deterioration of paraplegia. Maintaining hemodynamic stability during spinal surgery is very important.


[Determining myocardial viability in myocardial infarct. Comparison of single and multisclice MRI techniques with TurboFlash and TrueFISP sequences].
The aim of the study was to compare the diagnostic accuracy in imaging viability of the myocardium with a multislice inversions recovery 2D single shot TrueFISP sequence and an established inversion recovery TurboFlash sequence. Twelve patients with myocardial infarction were examined at a 1.5 tesla MR system (Sonata, Siemens, Medical Systems) 10 min after application of a single dose multihance (0,1 mmol/kg body weight) with a 2D multislice technique (inversion recovery single shot TrueFISP), that allows to image the entire short axis during one breathhold and a 2D single slice technique (inversion recovery TurboFlash), that requires one breathhold per slice. Signal intensity was determined in normal myocardium, in the infarcted myocardium and in the left ventricle. The contrast/noise ratio of normal and infarcted myocardium was determined. The areas of hyperintense infarction were compared for both sequence techniques. The multislice single shot 2D IR-TrueFisp sequence has a lower contrast/noise ratio than the IR-TurboFlash sequence (mean values 6.9 vs. 12.5) for viable and non viable myocardium. The assessment of the volume of the infarction is possible with excellent correlation of both techniques (r=0.97, p <0.036). In addition, an assessment of the transmural extent of the infarction is possible with identical spatial resolution. The inversions recovery 2D single shot TrueFisp technique allows for accurate detection of the infarction, for accurate determination of the area of the infarction and for assessment of the transmural extent of the infarction with high spatial resolution.


Attentional biases for food stimuli in external eaters: possible mechanism for stress-induced eating?
External eaters reportedly increase snack intake when stressed, which could be due to an attentional shift towards food stimuli. Attentional biases for food stimuli were tested in high and low external eaters in stress and control conditions, using a computerised Stroop. A significant interaction was observed between external eating group and condition for snack word bias. This suggested that low external eaters have a greater bias for snack words when unstressed and that stressed, high external eaters have a greater bias for snack words than stressed, low external eaters, which could contribute to stress-induced snack intake in high external eaters.


A novel immunoassay with direct relevance to protection against organophosphate poisoning.
Antiparaoxon immune sera were employed in a new immunoassay based on competition between acetylcholinesterase and antibodies for the binding of paraoxon. Unlike radioimmunoassay, the new assay described herein can be extended to predict the feasibility of antibodies to confer in vivo protection of acetylcholinesterase against organophosphate poisoning. The toxicity of paraoxon was reduced in mice which were preinjected with the immune sera.


Molecular subtype analysis determines the association of advanced breast cancer in Egypt with favorable biology.
Prognostic markers and molecular breast cancer subtypes reflect underlying biological tumor behavior and are important for patient management. Compared to Western countries, women in North Africa are less likely to be prognosticated and treated based on well-characterized markers such as the estrogen receptor (ER), progesterone receptor (PR) and Her2. We conducted this study to determine the prevalence of breast cancer molecular subtypes in the North African country of Egypt as a measure of underlying biological characteristics driving tumor manifestations. To determine molecular subtypes we characterized over 200 tumor specimens obtained from Egypt by performing ER, PR, Her2, CK5/6, EGFR and Ki67 immunohistochemistry. Our study demonstrated that the Luminal A subtype, associated with favorable prognosis, was found in nearly 45% of cases examined. However, the basal-like subtype, associated with poor prognosis, was found in 11% of cases. These findings are in sharp contrast to other parts of Africa in which the basal-like subtype is over-represented. Egyptians appear to have favorable underlying biology, albeit having advanced disease at diagnosis. These data suggest that Egyptians would largely profit from early detection of their disease. Intervention at the public health level, including education on the benefits of early detection is necessary and would likely have tremendous impact on breast cancer outcome in Egypt.


Rapid production of engineered human primary hepatocyte/fibroblast sheets.
This data article contains data related to the research article entitled "Vascularized subcutaneous human liver tissue from engineered hepatocyte/fibroblast sheets in mice," published in Biomaterials[1]. Engineered hepatocyte/fibroblast sheets (EHFSs) are used for construction of vascularized subcutaneous liver tissue without a pre-transplant vascularization procedures. Here, we described a rapid production technique of EHFSs by controlling fibroblast density and coating fetal bovine serum (FBS) onto temperature-responsive culture dishes (TRCDs). The human fibroblast monolayer formed on FBS-coated TRCDs within 1 h when seeded at a high density (at least 1.56×10(5) cells/cm(2)). The most rapid EHFS production was achieved soon after the adhesion of human primary hepatocytes onto the fibroblast layer.


Luteolin alleviates inorganic mercury-induced liver injury in quails by resisting oxidative stress and promoting mercury ion excretion.
BackgroundInorganic mercury is a well-known toxic substance that can cause oxidative stress and liver damage. Luteolin (Lut) is a kind of natural antioxidant, which is widely found in plants. Therefore, we focused on exploring the alleviative effect of Lut on liver injury induced by mercuric chloride (HgCl2), and the potential molecular mechanism of eliminating mercury ions in quails.Methods and resultsTwenty-one-day-old male quails were randomly split into four groups: control group, Lut group, HgCl2 group, and HgCl2 + Lut group. The test period was 12 weeks. The results showed that Lut could significantly ameliorate oxidative stress, the release of inflammatory factors, and liver damage caused by HgCl2, and reduce the accumulation of Hg2+ in quail liver. Furthermore, Lut evidently increased the levels of protein kinase C α (PKCα), nuclear factor-erythroid-2-related factor 2 (Nrf2), and its downstream proteins, and inhibited nuclear factor-kappaB (NF-κB) production in the liver of quails treated by HgCl2.ConclusionsTo sum up, our results suggest that Lut not only reduces the levels of oxidative stress and inflammation, but also promotes the excretion of Hg2+ by promoting the PKCα/Nrf2 signaling pathway to alleviate HgCl2-induced liver injury in quails.


Neurodevelopmental profile of HIVEP2-related disorder.
To characterize the neurodevelopmental profile and systemic features of HIVEP2-related disorder. This study used retrospective medical history and standardized assessment data from Simons Searchlight to describe the clinical characteristics of 12 individuals (eight males, four females; age range 3y 3mo-12y 8mo; mean age [SD] 7y 7mo [2y 11mo]) with pathogenic HIVEP2 variants, focusing on their levels of adaptive functioning, autism symptomology, and emotional and behavioral characteristics. Common features included neonatal complications, hypotonia, developmental delay, intellectual disability, language impairment, gastroesophageal reflux, and strabismus. A minority of individuals had epilepsy, microcephaly, or a movement disorder. Based on the Vineland Adaptive Behavior Scales, Second Edition, affected individuals showed impairments in adaptive behavior (mean composite standard score [SD] 56.4 [10.2]; n=8). The cohort also had significant impairments in social problems, as measured by the Social Responsiveness Scale, Second Edition (mean total score [SD] 76.4 [11.3]; n=10) and clinically significant emotional and behavioral difficulties, as measured by the Child Behavior Checklist for ages 6-18 (mean total T score [SD] 66.9 [8.2]; n=8). These results show that individuals with HIVEP2-related disorder have impairments in adaptive and social-related behaviors as well as difficulties in emotional and behavioral symptoms.


Prediction of the beta Bp crystallin dimer structure by the complementary surfaces (CS) method.
The method of searching for complementary surfaces of proteins was used to evaluate the modes of beta Bp crystallin autoassociation. The dimer structure of beta Bp is predicted and characterized.


Investigation of Pseudomonas aeruginosa quorum-sensing signaling system for identifying multiple inhibitors using molecular docking and structural analysis methodology.
Pseudomonas aeruginosa is an opportunistic human pathogen and a common Gram-negative bacterium in hospital-acquired infections. It causes death in many burn victims, cystic-fibrosis and neutropenic-cancer patients. It is known that P. aeruginosa biofilm maturation and production of cell-associated and extracellular virulence factors such as pyocyanin, elastase and rhamnolipids are under the control of a quorum-sensing (QS) system. Among several proteins involved in the Pseudomonas QS mechanism, LasR and PqsE play an important role in its cascade signaling system. They can cause increases in QS factors, biofilm maturation, and the production of virulence factors. Therefore, inhibition of these proteins can reduce the pathogenicity of P. aeruginosa. According to the structure of corresponding auto-inducers bound to these proteins, in silico calculations were performed with some non-steroidal anti-inflammatory drugs (NSAIDs) to estimate possible interactions and find the co-inhibitors of LasR and PqsE. The results showed that oxicams (Piroxicam and Meloxicam) can interact well with active sites of both proteins with the Ki of 119.43 nM and 4.0 μM for Meloxicam and 201.39 nM and 4.88 μM against LasR and PqsE, respectively. These findings suggested that Piroxicam and Meloxicam can be used as potential inhibitors for control of the P. aeruginosa QS signaling system and biofilm formation, and may be used in the design of multiple inhibitors.


Hypokalaemic thyrotoxic periodic paralysis: case report and review of an Oriental syndrome.
Presentations of acute systemic weakness are rare and appear dramatic and frightening to both patients and physicians. Aetiologies are multifactorial and diverse. Morbidity and mortality are associated with the unrecognized disease. One of the underlying disorders is hypokalaemic thyrotoxic periodic paralysis (HTPP), an uncommon disorder. HTPP is characterized by periodic occurrences of muscle weakness during attacks of hyperthyroidism and appears predominantly in Orientals. This article describes a patient of Chinese origin with hyperthyroidism and attacks of paralysis and considers several problems: a lack of familiarity with the syndrome, increasing numbers of patients with this disease in European hospitals as a result of migration of populations, and the importance of patient compliance in therapeutic management. Finally, a review of the literature concerning presentation, differential diagnosis, pathophysiology, and therapeutic management is provided.


Gene expression profiling of blood to predict the onset of leukemia.
No studies have tested the hypothesis that the onset of a disease can be predicted by gene expression profiling. The AKR/J mouse strain, which spontaneously develops acute T cell lymphatic leukemia, was used to implement a novel strategy to generate global gene expression profiles of WBCs at different time points. The experimental approach was bias free because it was unknown as to which individuals in the mouse population would eventually develop the disease. Our results suggest that profiling WBC gene expression may be an effective means for the very early diagnosis of disease in humans.


Glucosaminylmuramyl dipeptide potentiates the effects of tumor necrosis factor-alpha and cisplatin on transformed cells in vitro.
We studied the effect of combined treatment with cisplatin, glucosaminylmuramyl dipeptide, and TNF-alpha on viability of MCF-7, U-937, B16, and L-929 tumor cells, Ehrlich ascites carcinoma cells, and normal cells (human peripheral blood lymphocytes, peritoneal macrophages, and mouse bone marrow cells). Glucosaminylmuramyl dipeptide was nontoxic for normal and tumor cells, but promoted death of tumor cells after administration in combination with cisplatin and/or TNF-alpha. At the same time, glucosaminylmuramyl dipeptide did not modulate the cytotoxic effect of individual or combined treatment with cisplatin and TNF-alpha on normal cells. Administration of glucosaminylmuramyl dipeptide to cultured MCF-7 cells 20 h before the study increased the potentiating effect of muramyl peptide.


The human oxytocin gene promoter is regulated by estrogens.
Gonadal steroids affect brain function primarily by altering the expression of specific genes, yet the specific mechanisms by which neuronal target genes undergo such regulation are unknown. Recent evidence suggests that the expression of the neuropeptide gene for oxytocin (OT) is modulated by estrogens. We therefore examined the possibility that this regulation occurred via a direct interaction of the estrogen-receptor complex with cis-acting elements flanking the OT gene. DNA-mediated gene transfer experiments were performed using Neuro-2a neuroblastoma cells and chimeric plasmids containing portions of the human OT gene 5'-glanking region linked to the chloramphenicol acetyltransferase gene. We identified a 19-base pair region located at -164 to -146 upstream of the transcription start site which is capable of conferring estrogen responsiveness to the homologous as well as to a heterologous promoter. The hormonal response is strictly dependent on the presence of intracellular estrogen receptors, since estrogen induced stimulation occurred only in Neuro-2a cells co-transfected with an expression vector for the human estrogen receptor. The identified region contains a novel imperfect palindrome (GGTGACCTTGACC) with sequence similarity to other estrogen response elements (EREs). To define cis-acting elements that function in synergism with the ERE, sequences 3' to the ERE were deleted, including the CCAAT box, two additional motifs corresponding to the right half of the ERE palindrome (TGACC), as well as a CTGCTAA heptamer similar to the "elegans box" found in Caenorhabditis elegans. Interestingly, optimal function of the identified ERE was fully independent of these elements and only required a short promoter region (-49 to +36). Our studies define a molecular mechanism by which estrogens can directly modulate OT gene expression. However, only a subset of OT neurons are capable of binding estrogens, therefore, direct action of estrogens on the OT gene may be restricted to a subpopulation of OT neurons.


A projection from nucleus reticularis tegmenti pontis of Bechterew to the medial vestibular nucleus in rabbits.
This study documents a bilateral projection from nucleus reticularis tegmenti pontis (NRTP) to the rostral aspect of the medial vestibular nucleus (MVN) in rabbits. Horseradish peroxidase injections in rostral MVN produced retrogradely labeled neurons in the caudal half of NRTP; caudal MVN injections produced negative results. This supports the hypothesis that NRTP relays visual input to the vestibular nuclei via an extracerebellar pathway (Precht and Strata 1980), and indicates the importance of examining the contributions of both direct and cerebellar-mediated visual pathways to oculomotor physiology.


Gallbladder patterns in acute pancreatitis: an MRI study.
The aim of this study was to assess the gallbladder patterns on magnetic resonance imaging (MRI) associated with acute pancreatitis (AP). There were 197 patients with AP, all of whom had undergone abdominal MRI. AP was categorized as either edematous or necrotizing according to its findings on MRI and graded as mild (0-3 points), moderate (4-6 points), or severe (7-10 points) according to the magnetic resonance severity index. The changes to the walls and dimensions of the gallbladder and common bile duct, in addition to the presence of biliary stones and pericholecystic fluid, were noted and compared with the severity of AP on the basis of the magnetic resonance severity index. Of the 197 patients with AP, 81% were classified as edematous and 19% as necrotizing on MRI. There were 35%, 59%, and 6% of patients with mild, moderate, and severe AP according to the magnetic resonance severity index, respectively. Seventy-six percent of patients had at least one gallbladder abnormality on MRI, including a thickened gallbladder wall (42%), pericholecystic fluid (38%), gallbladder stones (35%), an enlarged gallbladder (24%), dilatation of the common bile duct (16%), and subserosal edema (15%). Eighty-nine percent of patients (34 of 38) with necrotizing AP had gallbladder abnormalities, which was significantly higher than the 72% of patients (115 of 159) with edematous AP (P < .05). The prevalence of gallbladder abnormalities was 64% in patients with mild AP, 81% in those with moderate AP, and 91% in those with severe AP (P < .05 among the three groups). Most patients with AP have gallbladder abnormalities on MRI, including a thickened gallbladder wall and pericholecystic fluid. The prevalence of gallbladder abnormalities has a positive correlation with the severity of AP on MRI.


[Discrepancies in medical textbooks and their impact on medical school students].
Textbooks endorsed by national medical specialty societies and colleges are used as official references for faculty and national examinations. Oncology is transdisciplinary, practiced and taught by oncologists but also by other specialists. We aimed at identifying discrepancies between chapters on cancers in different official specialty textbooks and evaluating their impact on students. Volunteer 6th-year medical students of the Sorbonne University faculty were paired and asked to list the discrepancies between all official specialty textbooks addressing a given cancer and then individually asked to evaluate the impact of discrepancies on their learning experience. In March 2018, the 17 cancers listed in the French medical school education program were addressed in 14 official specialty textbooks (2 to 4 textbooks/cancer). Out of a class of 390 students, 78 volunteered and were paired; each cancer was analyzed by 3 pairs of students (1 or 2 cancers/pair); 154 discrepancies were reported (range: 4-18 per cancer). Discrepancies induced doubt and anxiety in students; 85% considered that harmonization should be achieved for all topics of the national medical school program. Discrepancies between official textbook are frequent, generate anxiety in students and impact learning experience.


Lopinavir plasma concentrations and changes in lipid levels during salvage therapy with lopinavir/ritonavir-containing regimens.
To determine whether an association existed between lopinavir (LPV) plasma concentrations and changes in lipid levels. A prospective, nonrandomized study. HIV-infected subjects with virologic failure on protease inhibitor-containing regimens. Twenty-two consecutive patients were enrolled, 19 completed 24 weeks of treatment, and 16 completed the full 48-week study period. INTERVENTION Patients were treated with LPV/ritonavir (LPV/r) in combination with other antiretroviral agents. Subjects were evaluated at baseline and weeks 4, 8, 12, 24, 36, and 48. LPV trough plasma concentrations and lipid levels were measured. LPV trough concentrations were higher in patients experiencing grade 3 or higher lipid elevations (mean [SD]: 9.71 microg/mL (5.62) vs. 6.09 microg/mL (3.83); P = 0.002) and in those developing grade 2 or higher hypercholesterolemia (mean [SD]: 8.48 microg/mL [4.64] vs. 5.71 microg/mL [3.94]; P = 0.003). All patients developing grade 2 or higher cholesterol elevation had an LPV trough concentration at week 4 greater than 8 microg/mL. Significant positive correlations were found between LPV trough concentrations and changes in triglyceride and cholesterol levels. In patients receiving salvage therapy with LPV/r, there is an association between LPV plasma concentrations and lipid changes. Patients achieving higher LPV trough concentrations may be at greater risk of experiencing dyslipidemia. Further investigations are warranted to support a direct cause and effect relationship.


Extremely thermophilic energy metabolisms: biotechnological prospects.
New strategies for metabolic engineering of extremely thermophilic microorganisms to produce bio-based fuels and chemicals could leverage pathways and physiological features resident in extreme thermophiles for improved outcomes. Furthermore, very recent advances in genetic tools for these microorganisms make it possible for them to serve as metabolic engineering hosts. Beyond providing a higher temperature alternative to mesophilic platforms, exploitation of strategic metabolic characteristics of high temperature microorganisms grants new opportunities for biotechnological products. This review considers recent developments in extreme thermophile biology as they relate to new horizons for energy biotechnology.


Proline and proline derivatives as anticonvulsants.
1. The anticonvulsant properties of L-proline, of proline derivatives (trans-4-hydroxy-L-proline, cis-4-hydroxy-D-proline, 3,4-dehydro-D,L-proline) and of D- and L-pipecolic acid were studied alone and in combination with vigabatrin (R/S-4-aminohex-5-enoic acid). 3-Mercaptopropionic acid and pentylenetetrazol-induced convulsions in mice were used as animal models of epilepsy. 2. Proline and proline derivatives are weak anticonvulsants if given alone in doses up to 10 mmol/kg, however, they are capable of potentiating the anticonvulsant effects of vigabatrin, in a manner similar to that reported previously for glycine, and some glycine derivatives. Among the compounds tested, trans-4-hydroxy-L-proline was the most potent anticonvulsant in combination with the indirect GABA agonist vigabatrin. 3. A potential explanation for the synergistic anticonvulsant effect of the combination of the GABA agonist and proline is the presumed role of proline as inhibitory neurotransmitter, and/or its glutamate antagonistic effects. 4. The current study points out the lack of basic knowledge on the neurochemistry and pharmacology of proline and hydroxyproline.


A meta-analysis of methotrexate polyglutamates in relation to efficacy and toxicity of methotrexate in inflammatory arthritis, colitis and dermatitis.
In immune-mediated inflammatory diseases (IMIDs), early symptom control is a key therapeutic goal. Methotrexate (MTX) is the first-line treatment across IMIDs. However, MTX is underutilized and suboptimally dosed, partly due to the inability of making individualized treatment decisions through therapeutic drug monitoring (TDM). To implement TDM in clinical practice, establishing a relationship between drug concentration and disease activity is paramount. In this meta-analysis, we investigated the relationship between concentrations of MTX polyglutamates (MTX-PG) in erythrocytes and efficacy as well as toxicity across IMIDs. Studies analysing MTX-PG in relation to disease activity and/or toxicity were included for inflammatory arthritis (rheumatoid [RA] and juvenile idiopathic arthritis [JIA]), inflammatory bowel disease (Crohn's and ulcerative colitis) and dermatitis (psoriasis and atopic dermatitis). Meta-analyses were performed resulting in several summary effect measures: regression coefficient (β), correlation coefficient and mean difference (of MTX-PG in responders vs. nonresponders) for IMIDs separately and collectively. Twenty-five studies were included. In RA and JIA, higher MTX-PG was significantly associated with lower disease activity at 3 months (β: -0.002; 95% confidence interval [CI]: -0.004 to -0.001) and after 4 months of MTX use (β: -0.003; 95% CI: -0.005 to -0.002). Similarly, higher MTX-PG correlated with lower disease activity in psoriasis (R: -0.82; 95% CI: -0.976 to -0.102). Higher MTX-PG was observed in RA, JIA and psoriasis responders (mean difference: 5.2 nmol/L MTX-PGtotal ; P < .01). We showed that higher concentrations of erythrocyte MTX-PG were associated with lower disease activity in RA, JIA and psoriasis. These findings are an important step towards implementation of TDM for MTX treatment across IMIDs.


Clear cell ("mesonephroid") adenocarcinoma of the vulva arising in endometriosis: a case report.
A very unusual case of an apparent primary clear cell adenocarcinoma of the vulva in a 57-year-old female is presented. The carcinoma arose in an area of endometriosis within the canal of Nuck in the superior aspect of the right labium majus. Smooth muscle fibers presumably representing remnants of the extrapelvic round ligament were found associated with the endometriosis. Of interest is the fact that the patient underwent right herniorrhaphy 9 years earlier. Although several cases of primary adenocarcinoma arising within the vulva have been reported, none has arisen in areas of endometriosis within the canal of Nuck. No case in the literature of a primary clear cell adenocarcinoma arising from endometriosis in the canal of Nuck and in association with the extrapelvic portion of the round ligament could be found.


Mechanisms in cardiovascular regulation following chronic exposure of male rats to inorganic mercury.
In this study we verified the possibility that chronic exposure to inorganic mercury may induce hemodynamic changes in the rat by affecting some neurogenic and/or humoral mechanisms regulating cardiovascular function. For this reason, aortic blood pressure, maximum rate of rise of the left ventricular pressure, heart rate, and electrocardiogram were monitored under pentothal anesthesia in rats which received 50 micrograms/ml of mercury (as HgCL2) in drinking water for 320 days and in control rats. No pressor or electrocardiographic changes were found in mercury-treated animals, which showed increase of cardiac inotropism and decrease of the pressor and inotropic responses to bilateral carotid occlusion. Cardiovascular responses to bilateral vagotomy and iv hexamethonium under vagotomy were unchanged in the mercury-exposed rats. In these animals both pressor and inotropic responses to iv norepinephrine and to higher doses of epinephrine were reduced, while the vascular beta-adrenergic response to 0.125 micrograms/kg of iv epinephrine was potentiated. Cardiovascular responses to acetylcholine, angiotensin I, angiotensin II, bradykinin, histamine, and serotonin did not differ in the two groups of rats. These results indicated that chronic mercury exposure affects cardiovascular function by interfering with the baroreflex mechanisms and/or the reactivity to catecholamines. Higher amounts of mercury were found in kidney, but the metal was significantly accumulated also in urine, blood, and brain. Mercury exposure greatly increased the levels of copper and zinc, but not that of iron, in brain and kidney. The increased accumulation of copper and zinc in tissues may be related in part to the mercury-induced synthesis of metallothionein, a protein able to bind these essential metals. It may be suggested that zinc and copper interact with mercury in inducing cardiovascular changes.


[INFORMATION, A FUNDAMENTAL PATIENT RIGHT?].
Although expressed before the "Lambert" case, which has led us to think about refusal and assent in the context of internal rights, conventional rights--and in the context of the patient's bed!--these simple remarks present the patient's right to medical information as a so-called fundamental right. But it can only be understood with a view to a treatment or other medical act; otherwise it has no reason to be and is only an academic exercise, however exciting, but not much use by itself. What if we reversed the terms of the problem: the right of the doctor to information? (The beautiful thesis of Ph. Gaston, Paris 8, 2 December 2014).


CD20-negative diffuse large B cell lymphoma: a comprehensive analysis of 695 cases.
CD20 expression is absent in a variety of diffuse large B cell lymphomas (DLBCLs), including plasmablastic lymphoma, primary effusion lymphoma, anaplastic lymphoma, kinase-positive DLBCL, and large B cell lymphoma arising in human herpesvirus 8-associated multicentric Castleman disease. These rare and heterogeneous tumors are characterized by the presence of proliferating immunoblasts with similar transcriptional profiles as those of plasma cells and are typically associated with highly aggressive pathologies, with high levels of chemotherapy resistance and low survival rates; thus, they pose significant diagnostic and treatment challenges. We conducted a systematic literature review of the limited existing clinical data to summarize the current knowledge regarding the biological basis, diagnostic limits, and potential therapeutic targets of distinct variants of CD20-negative DLBCL. This review will hopefully increase the awareness of these rare disorders among clinicians and pathologists and prompt basic and clinical research.


A pilot study of endothelial dysfunction and aortic stiffness after interleukin-6 receptor inhibition in rheumatoid arthritis.
Interleukin (IL)-6 is a pleiotropic proinflammatory cytokine involved in the pathogenesis of both atherosclerosis and rheumatoid arthritis. The role of the IL-6/IL-6 receptor pathway in the documented acceleration of atherosclerosis in rheumatoid arthritis has not been examined. In a non-randomized prospective pilot study we asked whether endothelial dysfunction, defined as impaired flow mediated dilatation (FMD), and aortic stiffness, assessed by pulse wave velocity (PWV) improve after 3 and 6 monthly therapeutic infusions of the anti-IL-6 receptor antibody tocilizumab for active rheumatoid arthritis. We found that FMD increased from 3.3 ± 0.8 to 4.4 ± 1.2 to 5.2 ± 1.9% (p = 0.003), whereas PWV decreased from 8.2 ± 1.2 to 7.7 ± 1.3 to 7.0 ± 1.0m/s (p < 0.001). Whether these beneficial arterial changes are direct effects of the IL-6/IL-6 receptor pathway inhibition, maintained over time and translate into better clinical outcome warrants further studies.


Effect of treatment zone decentration on axial length growth after orthokeratology.
To study the effect of treatment zone (TZ) decentration on axial length growth (ALG) in adolescents after wearing the orthokeratology lenses (OK lenses). This retrospective clinical study selected 251 adolescents who were fitted OK lenses at the Clinical College of Ophthalmology, Tianjin Medical University (Tianjin, China) from January 2018-December 2018 and wore them continuously for >12 months. The age of the subjects was 8-15 years, spherical equivalent (SE): -1.00 to -5.00 diopter (D), and astigmatism ≤ 1.50 D. The corneal topography were recorded at baseline and 1-, 6-, and 12-month visits, and the axial length (AL) were recorded at baseline and 6-, 12-month visits. The data of the right eye were collected for statistical analysis. The subjects were divided into three groups according to the decentration distance of the TZ after wearing lenses for 1 month: 56 cases in the mild (<0.5 mm), 110 in the moderate (0.5-1.0 mm), and 85 in the severe decentration group (>1.0 mm). A significant difference was detected in the ALG between the three groups after wearing lenses for 6 and 12 months (F = 10.223, P < 0.001; F = 13.380, P < 0.001, respectively). Among these, the 6- and 12-month ALG of the mild decentration group was significantly higher than that of the other two groups. Multivariable linear regression analysis showed that age, baseline SE, and 1-month decentration distance associated with the 12-month ALG (P < 0.001, P < 0.001, and P = 0.001, respectively). The decentration of the TZ of the OK lens affected the growth of the AL in adolescents, i.e., the greater the decentration, the slower the ALG.


A brief history of the rise and fall of the School Medical Service in England.
The paper tracks the history of the School Medical Service over 150 years. The service has changed markedly during this period, with some cyclical recurrence of practice and policy. By 2006, the health of schoolchildren is of major concern, particularly the rise in nutrition-related problems including obesity: the demise of the School Health Service may well be a matter for serious regret to future generations.


Antisense inhibition of expression of cysteine proteinases affects Entamoeba histolytica-induced formation of liver abscess in hamsters.
Trophozoites of virulent Entamoeba histolytica transfected with the antisense gene encoding cysteine proteinase 5 (CP5) have only 10% of the CP activity but retain their cytopathic activity on mammalian monolayers. In the present study we found that the transfected trophozoites with low levels of CP activity were incapable of inducing the formation of liver lesions in hamsters.


Development of a nomogram based on pericoronary adipose tissue histogram parameters to differentially diagnose acute coronary syndrome.
To develop a nomogram based on pericoronary adipose tissue (PCAT) histogram parameters to identify patients with acute coronary syndrome (ACS). This study retrospectively enrolled 114 and 383 eligible patients with ACS and stable coronary artery disease (CAD), respectively, and divided them into training and testing cohorts in a 7:3 ratio. A blinded radiologist obtained PCAT histogram parameters from the right coronary artery's proximal segment using fully automated software and compared clinical characteristics and PCAT histogram parameters between the two patient groups. The binary logistic regression included significant parameters (P < 0.05), and a nomogram was constructed. In both the training and testing cohorts, the mean, 10th percentile, 90th percentile, median, and minimum values of PCAT were higher, and the interquartile range, skewness, and variance values of PCAT were lower in patients with ACS than in those with stable CAD (P ≤ 0.001). The mean (OR = 4.007), median (OR = 0.576), minimum (OR = 0.893), skewness (OR = 85,158.806) and variance (OR = 1.013) values of PCAT were independent risk factors for ACS and stable CAD in the training cohort. The nomogram was constructed using the five variables mentioned above with area under the curve values of 0.903 and 0.897, respectively, while the calibration and decision curves showed the nomogram's good clinical efficacy for the training and testing cohorts. The constructed nomogram had good discrimination and accuracy and can be a noninvasive tool to intuitively and individually distinguish between ACS and stable CAD.


The DNA replication inhibitor microcin B17 is a forty-three-amino-acid protein containing sixty percent glycine.
Microcin B17 is a low-molecular-weight protein that inhibits DNA replication in a number of enteric bacteria. It is produced by bacterial strains which harbor a 70-kilobase plasmid called pMccB17. Four plasmid genes (named mcbABCD) are required for its production. The product of the mcbA gene was identified by labelling minicells. The mcbA gene product was slightly larger when a mutation in any of the other three production genes was present. This indicates that these genes are involved in processing the primary mcbA product to yield the active molecule. The mcbA gene product predicted from the nucleotide sequence has 69 amino acids including 28 glycine residues. Microcin B17 was extracted from the cells by boiling in 100 mM acetic acid, 1 mM EDTA, and purified to homogeneity in a single step by high-performance liquid chromatography through a C18 column. The N-terminal amino acid sequence and amino acid composition demonstrated that mcbA is the structural gene for microcin B17. The active molecule is a processed product lacking the first 26 N-terminal residues. The 43 remaining residues include 26 glycines. While microcin B17 is an exported protein, the cleaved N-terminal peptide does not have the characteristic properties of a "signal sequence", which suggests that it is secreted by a mechanism different from that used by most secreted proteins of E. coli.


A model for the molecular mechanism of interfacial activation of phospholipase A2 supporting the substrate theory.
Changes occurring in the activity of porcine pancreatic phospholipase A2 upon formation of mixed micelles of sodium cholate and the fluorescent phosphocholines 1,2-di[6-(pyren-1-yl)butanoyl]-sn-glycero-3-phosphocholine or 1-[6-(pyren-1-yl)butanoyl]-2-[6-(pyren-1-yl)hexanoyl]- sn-glycero-3- phosphocholine were studied. A 2-fold enhancement was observed in the activity of phospholipase A2 towards both pyrene phospholipids upon exceeding the critical micellar concentration of the system. Changes in the pyrene excimer/monomer fluorescence emission intensity ratio coincide with the enhancement of phospholipase A2 activity at the critical micellar concentration. Due to the different effects of micellization on the alignment of the pyrene in the two fluorescent probes conformational changes could be assessed. A model describing possible conformations of these pyrene phospholipid molecules below and above the critical micellar concentration is presented and correlated with the interfacial activation of phospholipase A2.


Domestic violence among male and female patients seeking emergency medical services.
Gender differences among a cohort of injured patients seeking emergency medical services were examined with respect to their experiences as perpetrators and/or victims of domestic violence. Contextual issues, including violence initiation, emotional and behavioral responses to partner-initiated violence, and injury frequency and severity were analyzed. Women reported male partner-initiated violence more frequently than men reported female partner-initiated violence. Behavioral responses to partner initiated violence varied. Women were more likely to report using force back and to involve law enforcement. Women were more likely to be injured in a domestic assault over their lifetime, within the last year, and at the time of recruitment. Comparison of injury severity revealed that women reported higher rates of injuries than men in all possible severity categories. Women also reported experiencing more fear than men during partner-initiated violence, as well as being subjected to larger numbers of dominating and controlling behaviors, and greater intimidation secondary to their partner's size. Understanding contextual differences in partner violence for women and men has significant implications for policy development, identification, treatment, and referral of patients identified as living in violent relationships.


Hepatic carbohydrate metabolism in rats bred for alcohol preference.
The influence of ethanol on the carbohydrate metabolism was studied in two strains of rats: the AA strain with an inherited preference for alcohol and the ANA strain with an aversion to alcohol. In both strains, a single intraperitoneal dose of ethanol (1.5 g/kg body wt.) slightly increased the blood glucose concentration. In AA rats alcohol increased the rate of gluconeogenesis from alanine and had no effect on the liver glycogen stores, whereas in ANA rats the rate of gluconeogenesis remained unchanged and the glycogen stores decreased. It thus appears that the two rat strains maintain their blood glucose concentration by different mechanisms; the ANA rats utilise both glycogenolysis and gluconeogenesis but the AA rats only gluconeogenesis.


Factors associated with lipid control in outpatients with heart failure.
Dyslipidemia is common among patients with heart failure, and it negatively impacts clinical outcomes. Limited data regarding the factors associated with poor lipid control in patients with HF patients. Therefore, this study aimed to evaluate lipid control and to explore the factors associated with poor lipid control in patients with HF. The current cross-sectional study was conducted at outpatient cardiology clinics at two major hospitals in Jordan. Variables including socio-demographics, biomedical variables, in addition to disease and medication characteristics were collected using medical records and custom-designed questionnaire. Medication adherence was assessed using the validated 4-item Medication Adherence Scale. Binary logistic regression analysis was conducted to explore significant and independent predictors of poor lipid control among the study participants. A total of 428 HF patients participated in the study. Results showed that 78% of the participants had poor lipid control. The predictors that were associated with poor lipid control included uncontrolled BP (OR = 0.552; 95% CI: 0.330-0.923; P < 0.05), higher Hb levels (OR = 1.178; 95% CI: 1.013-1.369; P < 0.05), and higher WBC (OR = 1.133; 95% CI: 1.031-1.246; P < 0.05). This study revealed poor lipid control among patients with HF. Future intervention programs should focus on blood pressure control in order to improve health outcomes among HF patients with dyslipidemia.


First Nearly Complete Genome Sequence of Feline immunodeficiency virus from Brazil.
Feline immunodeficiency virus (FIV) has worldwide distribution; nevertheless, only a few FIV genomes from domestic cats are available. This is the first report of a nearly complete genome of FIV from a Brazilian cat (8,967 nucleotides [nt]), including the entire coding region and the 3' untranslated region.


Patient navigation to promote lung cancer screening in a community health center for people experiencing homelessness: Protocol for a pragmatic randomized controlled trial.
Lung cancer is a major cause of death among people experiencing homelessness, with mortality rates more than double those in the general population. Lung cancer screening (LCS) with low-dose computed tomography (LDCT) could reduce lung cancer deaths in this population, although the circumstances of homelessness present multiple barriers to LCS LDCT completion. Patient navigation is a promising strategy for overcoming these barriers. The Investigating Navigation to Help Advance Lung Equity (INHALE) Study is a pragmatic randomized controlled trial of patient navigation for LCS among individuals receiving primary care at Boston Health Care for the Homeless Program (BHCHP). Three hundred BHCHP patients who meet Medicare/Medicaid criteria for LCS will be randomized 2:1 to usual care with (n = 200) or without (n = 100) LCS navigation. Following a structured, theory-based protocol, the patient navigator assists with each step in the LCS process, providing lung cancer education, facilitating shared decision-making visits with primary care providers (PCPs), assisting in making and attending LCS LDCT appointments, arranging follow-up when needed, and offering tobacco cessation support for smokers. The primary outcome is receipt of LCS LDCT at 6 months. Using a sequential explanatory mixed methods approach, qualitative interviews with participants and PCPs will aid in interpreting and contextualizing the trial results. This trial will produce the first experimental evidence on patient navigation for cancer screening in a homeless health care setting. Results could inform cancer health equity efforts at the 299 Health Care for the Homeless programs that serve over 900,000 patients annually in the US.


Journey to a new era: An innovative academic-practice partnership.
Successful academic-clinical partnerships are mutually beneficial for academic nursing and clinical organizations, supporting the long-term success of nursing programs while simultaneously improving patient outcomes. Advocated by the American Association of Colleges of Nursing in their 2016 report, Advancing Healthcare Transformation: New Era for Academic Nursing, this position paper provides six actions for transforming academic nursing. However, developing sustainable academic-practice models has proven challenging despite this roadmap, as research has not substantiated their benefits. This article describes an innovative academic-practice model that transitioned advanced practice registered nurses practicing at Le Bonheur Children's Hospital to full-time faculty, with a continued primary clinical practice role, in the College of Nursing at the University of Tennessee Health Science Center. We present the origin, development, and implementation of this academic-practice partnership model, offering recommendations for its replication by other universities and clinical agencies on this journey. Creating a sustainable model requires a shared vision, buy-in at all levels, frequent and transparent communication, planning that considers the individual policies of the partnering agencies, and persistence despite leadership changes. Two years into the partnership and remaining intact despite critical leadership changes within the clinical agency, the next phase of the relationship will permit us to document the model's impact on academic and clinical outcomes.


E-cadherin to P-cadherin switching in lobular breast cancer with tubular elements.
Loss of E-cadherin expression due to mutation of the CDH1 gene is a characteristic feature of invasive lobular breast cancer (ILBC). Beta-catenin, which binds to the cytoplasmic domain of E-cadherin, is simultaneously downregulated, reflecting disassembly of adherens junctions (AJs) and loss of cell adhesion. E-cadherin to P-cadherin expression switching can rescue AJs and cell adhesion. However, P-cadherin has not been implicated in ILBC, so far. We aimed to characterize 13 ILBCs with exceptional histomorphology, which we termed ILBCs with tubular elements. The CDH1 mutational status was determined by next generation sequencing and whole-genome copy number (CN) profiling. Expression of cadherins was assessed by immunohistochemistry. ILBCs with tubular elements were ER-positive (13/13) and HER2-negative (13/13) and harbored deleterious CDH1 mutations (11/13) accompanied by loss of heterozygosity due to deletion of chromosome 16q22.1 (9/11). E-cadherin expression was lost or reduced in noncohesive tumor cells and in admixed tubular elements (13/13). Beta-catenin expression was lost in noncohesive tumor cells, but was retained in tubular elements (11/13), indicating focal rescue of AJ formation. N-cadherin and R-cadherin were always negative (0/13). Strikingly, P-cadherin was commonly positive (12/13) and immunoreactivity was accentuated in tubular elements. Adjacent lobular carcinoma in situ (LCIS) was always P-cadherin-negative (0/7). In a reference cohort of LCIS specimens, P-cadherin was constantly not expressed (0/25). In a reference cohort of invasive mammary carcinomas, P-cadherin-positive cases (36/268, 13%) were associated with triple-negative nonlobular breast cancer (P < 0.001). Compared with ILBCs from the reference cohort, P-cadherin expression was more common in ILBCs with tubular elements (12/13 versus 7/84, P < 0.001). In summary, E-cadherin to P-cadherin switching occurs in a subset of ILBCs. P-cadherin is the molecular determinant of a mixed-appearing histomorphology in ILBCs with tubular elements.


Structural insight into selectivity of amylin and calcitonin receptor agonists.
Amylin receptors (AMYRs), heterodimers of the calcitonin receptor (CTR) and one of three receptor activity-modifying proteins, are promising obesity targets. A hallmark of AMYR activation by Amy is the formation of a 'bypass' secondary structural motif (residues S19-P25). This study explored potential tuning of peptide selectivity through modification to residues 19-22, resulting in a selective AMYR agonist, San385, as well as nonselective dual amylin and calcitonin receptor agonists (DACRAs), with San45 being an exemplar. We determined the structure and dynamics of San385-bound AMY3R, and San45 bound to AMY3R or CTR. San45, via its conjugated lipid at position 21, was anchored at the edge of the receptor bundle, enabling a stable, alternative binding mode when bound to the CTR, in addition to the bypass mode of binding to AMY3R. Targeted lipid modification may provide a single intervention strategy for design of long-acting, nonselective, Amy-based DACRAs with potential anti-obesity effects.


Multilobulated thymoma with an acute angle: a new predictor of lung invasion.
Imaging features of thymomas such as lobulation, infiltration into lung, and adjacent lung abnormality have been associated with lung invasion but are unreliable. The goal of this study was to develop a more objective and reproducible method for predicting lung invasion by thymomas. Fifty-four thymomas resected from 2007 to 2017 were included for analysis. Pre-operative CT scans for these thymomas were reviewed, and multiple features were evaluated, including the interface of each thymoma with the adjacent lung. A multilobulated thymoma with at least one acute angle between lobulations was considered suspicious for lung invasion. Two blinded radiologists then tested this hypothesis by reviewing all 54 CT scans and using this single criterion to predict lung invasion. Twelve thymomas invaded the lung. All lung-invasive thymomas were multilobulated. Twenty-nine thymomas had a multilobulated interface with the lung. Multilobulated thymomas were more likely to invade the lung than thymomas with a single lobulation or no lobulation (p = 0.0008). Using the criterion of multilobulation with at least one acute angle between lobulations to predict lung invasion, the two readers achieved a sensitivity of 67-83%, specificity of 93-98%, positive predictive value of 77-89%, and negative predicted value of 91-95%. Nine lung-invasive thymomas also invaded mediastinal structures or disseminated to the pleura. A multilobulated thymoma with at least one acute angle between lobulations predicts lung invasion with a high degree of accuracy. When lung invasion is suspected, the findings are indicative of a locally aggressive tumor, and the pleura and mediastinal structures should also be closely inspected for invasion. • A multilobulated thymoma with at least one acute angle between lobulations is predictive of lung invasion. • Coronal and sagittal reformations and thin sections are helpful in challenging cases. • Lung invasion indicates a locally aggressive tumor, and the pleura and other mediastinal structures should also be closely inspected for invasion.


Isolation and identification of a snake venom metalloproteinase inhibitor from California ground squirrel (Spermophilus beecheyi) blood sera.
California ground squirrels (Spermophilus beecheyi) show blood-based defenses to a variety of toxins in the venom of the Northern Pacific rattlesnake (Crotalus oreganus oreganus). In this study we demonstrate the presence of an effective snake venom metalloproteinase inhibitor (SVMPI) in S. beecheyi. The blood sera of California ground squirrels were effective at reducing the metalloproteinase activity of Northern Pacific (C. o. oreganus) and prairie rattlesnake (Crotalus viridis viridis) venoms by over 75%, significantly more than its ability to reduce the activity of western diamondback rattlesnake venom. We used anion exchange and affinity chromatography to isolate this protein from the blood sera of S. beecheyi. This SVMPI had a molecular mass of 108.3 kDa and a pI of 5.1. The IC(50) of this inhibitor against whole venom from C. o. oreganus was determined to be 3.14 × 10(-8) M. Subsequent LC MS/MS analysis of a CNBr/tryptic digest of the inhibitor yielded multiple internal peptide sequences. These sequences showed homology to three other known mammalian plasma proteins: inter-α trypsin inhibitor, and two hibernation-associated proteins, HP25 and HP27. The presence of SVMPI in S. beecheyi blood sera is consistent with the resistance of these animals to venom-induced hemorrhage and tissue damage, and consistent with the protective factors conferring venom resistance in other mammals. However, the variety of SVMPI identified to date from mammalian taxa suggests that different species have converged on neutralization of venom metalloproteinase activity as a key step in venom neutralization.


Source apportionment of polycyclic aromatic hydrocarbons (PAHs) in a sediment core from Lake Dagze Co, Tibetan Plateau, China: Comparison of three receptor models.
Receptor models are a useful tool for identifying sources of polycyclic aromatic hydrocarbons (PAHs) in multiple environmental media. In this study, three different receptor models (including the principal component analysis-multiple linear regression (PCA-MLR), positive matrix factorization (PMF), and Unmix models) were used to apportion the sources of 16 priority PAHs in a sediment core of Lake Dagze Co. The ∑PAHs (sum of all 16 measured PAHs) concentrations ranged from 51.89 to 132.82 ng/g with an average of 80.39 ng/g. The ∑PAHs were dominated by 2-3 ring PAHs, accounting for 80.12% on average, thereby indicating that they mainly originated from biomass and coal combustion and/or from long-range atmospheric transportation. The three models produced consistent source apportionment results. The greatest contributor to ∑PAHs was biomass combustion, followed by coal combustion, vehicle emissions, and petrogenic sources. Moreover, the temporal variation of the common sources was well-correlated among models. The multi-method comparison and evaluation results showed that all three models were useful tools for source apportionment of PAHs, with the PMF model providing better results than the PCA-MLR and Unmix models. The temporal trends of factor contributions were verified by PAHs with different ring numbers. Significant correlations were found between the simulated concentrations of each source factor and the PAHs with different ring numbers (P<0.01), except for the petrogenic source identified by the Unmix model (P>0.05). This study can provide useful information for further investigation of source apportionment of PAHs in the sediment cores.


Audiological benefit, quality of life, and factors associated with functional gain in elderly hearing aid users in a developing country between 2017 and 2020: a pre-post-study.
Sensorineural hearing loss (SNHL) is the most common auditory deficit in older adults and may lead to quality-of-life deterioration. However, few studies have been performed in low/middle-income countries, particularly in Latin America. This study aimed to assess the audiological benefit, quality of life, and factors associated with functional gain in elderly hearing aid users in the Fundación Santa Fe de Bogotá and UNIMEQ-ORL, two otology referral centers in Colombia. Pre-post study that included hearing aid users at the otology consult of the Fundación Santa Fe de Bogotá and UNIMEQ-ORL between June 2017 and December 2020. Glasgow Benefit Inventory (GBI) and Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaires were applied. Audiometric (0,5 kHz to 4 kHz) and speech audiometry results were collected. A total of 75 participants (132 ears) were included. The mean age was 70.73 years (SD: 12.66). The median hearing aid use in years was 0.71 (IQR: 0.64-0.90). Mean change in speech audiometry was - 26.53dB (95%CI: -28.09, -24.97; p < 0.001), in functional gain was - 21.75dB (-23.81, -19.68; p < 0.001). The mean changes in the APHAB domains were Ease of Communication: -37.85 (95%CI: -43.01; -32.7), Background Noise: -3.51 (-6.06; -0.95), and Aversiveness of Sounds: -6.9 (-2.04; 11.77). The GBI assessment of quality of life showed improvement in 100% of the population after the use of hearing aids. The number of years of hearing aids use was associated with functional gain. The number of years of hearing aids use may impact on the functional gain in these populations. A significant clinical benefit was found in terms of quality of life, communication, and reverberation related to the use of hearing aids. Access to hearing aids should be granted, and public health strategies are needed to grant the access to hearing rehabilitation in these populations. Fundación Santa Fe de Bogotá (Protocol Number: CCEI-12666-2020).


Campylobacter-Wolinella group organisms are the only oral bacteria that form arylsulfatase-active colonies on a synthetic indicator medium.
Most oral bacteria tested formed colonies on a chemically defined medium with a chromogenic arylsulfatase substrate. Arylsulfatase activity was, however, restricted to Campylobacter-Wolinella group organisms, including Wolinella recta, a possible periodontopathogen. W. recta was the only arylsulfatase-active species against which consistently high levels of antibody were detected in human sera.


The effects of a dry heat blood warmer on some components of stored blood.
The plasma potassium, sodium, pH and haemoglobin of stored acid dextrose blood were measured after various periods of storage and after passage through a Fenwall R 4301 dry heat blood warmer. No significant changes were observed except a slight rise in plasma haemoglobin concentration.


[The phlebotomines of Tunisia (Diptera-Phlebotominae). A revision of the systematics, distribution and behaviour (author's transl)].
The authors present a revision of the systematics, distribution and ethology of the phlebotomine sandflies of Tunisia. They present a dichotomous key for 15 taxa. A biogeographical analysis shows the connexion between foci of visceral leishmaniasis and the zones of distribution of the subgenus Larroussius.


Pseudoaneurysm and aorto-bronchial fistula following balloon dilation of recoarctation.
This case report documents the successful surgical repair of an aorto-bronchial fistula and a giant aortic pseudoaneurysm at the proximal anastomosis of a dacron interposition tube graft that was balloon dilated for recurrent coarctation. Balloon dilation for recoarctation of a dacron interposition tube graft may lead to serious complications.


Gastroretentive hydrodynamically balanced systems of ofloxacin: In vitro evaluation.
Hydrodynamically balanced systems (HBSs) of ofloxacin were prepared using lactose, HPMC K4M, PVP K 30, and liquid paraffin, which may increase the mean residence time in the gastrointestinal tract, and may be able to provide maximum drug at the site of absorption to improve oral bioavailability. All these formulated HBS capsules were floated well over 6 h with no floating lag time. They also showed sustained drug release over 6 h. Time for 50% release of ofloxacin was within the range, 2.47 ± 0.02 to 3.07 ± 0.08 h. The in vitro drug release from these HBS capsules was dependent on HPMC K4M, PVP K 30, and liquid paraffin content. The drug release pattern of these HBS capsules containing ofloxacin followed the Higuchi model with the anomalous transport mechanism.


Toripalimab: First Global Approval.
Toripalimab, a recombinant, humanized programmed death receptor-1 (PD-1) monoclonal antibody that binds to PD-1 and prevents binding of PD-1 with programmed death ligands 1 (PD-L1) and 2 (PD-L2), is being developed by Shanghai Junshi Bioscience Co., Ltd in China for the treatment of various cancers. In December 2018, based on positive efficacy results of a phase 2 trial and safety data from several clinical studies, toripalimab received conditional approval in China for the treatment of unresectable or metastatic melanoma that has failed previous systemic therapy. This article summarizes the milestones in the development of toripalimab leading to this first global approval for the treatment of unresectable or metastatic melanoma.


Use of the internal mammary artery in myocardial revascularization.
Internal mammary artery-coronary artery anastomosis is currently considered the newest and best technique for surgical revascularization of ischemic myocardium. The origin and evolution of this technique are reviewed.


Identification and expression of an autosomal paralogue of ribosomal protein S4, X-linked, in mice: potential involvement of testis-specific ribosomal proteins in translation and spermatogenesis.
Recent studies have revealed heterogeneity in the structure of eukaryotic cytoplasmic ribosomes, including a difference in protein composition. It has been proposed that this heterogeneity, or the specialized ribosome, contributes to tissue development and homeostasis through selective mRNA translation, although this remains largely unclear. Our previous proteomic survey of rodent ribosomes found the testis-specific ribosomal proteins L10-like and L39-like, which are paralogues of the X-linked ribosomal proteins L10 and L39, respectively. We have hypothesized that the rodent testis provides a good model for examining the possible functional importance of ribosome heterogeneity. In the present study, a new paralogue of X-linked ribosomal protein S4 has been identified in the mouse testis. The gene encoding this paralogue was autosomal, intronless and expressed predominantly in the testis. It appeared that this paralogue was included in polysomes as a component of the ribosome. Although these properties were similar to those of the ribosomal proteins L10-like and L39-like, this S4 paralogue and L10-like showed partially different expression patterns in spermatogenic cells. These findings are discussed in relation to the unique evolution of genes encoding a paralogue of ribosomal protein S4 in mammals and to the significance of testis-specific paralogues of ribosomal proteins in active ribosomes during spermatogenesis.


A new therapy in Epstein-Barr virus-associated lymphoproliferative disease: a case report and a revision of the literature.
Systemic chronic active Epstein-Barr virus infection is an extremely rare childhood disease. Since chronic active Epstein-Barr virus infection can trigger the onset of Epstein-Barr virus-associated lymphoproliferative disease. The clinical manifestations of the disease vary according to the site of involvement; therefore, management may be challenging. Currently, there are no standardized guidelines for treating Chronic active Epstein-Barr virus infection effectively. We report a case of chronic active Epstein-Barr virus infection in a 5-year-old Chinese boy with intestinal, vascular, and neurological involvement. At age of 2 years and 7 months old, he had hepatomegaly and been diagnosed with Epstein-Barr virus infection. After treatment, he showed some clinical improvement. At age of 3 years and 3 months old, he presented with recurrent fever and diarrhea. Then he received methylprednisolone for 1 year and his symptoms ameliorated. At the age of 5 years, his symptoms recurred and had gastrointestinal hemorrhage and developed polyuria, frequent convulsions and hyponatremia. He was transferred to our hospital for further management. He was unconscious on admission and was diagnosised Epstein-Barr virus-lymphoproliferative disorder, based on the results in situ hybridization of EBV-encoded miRNA in sigmoid colon. Three-dimensional CT angiography demonstrated an aneurysm in the right internal carotid artery. Abdominal CT showed dilatation of vessels in part of the intestinal wall. He was also diagnosised Epstein-Barr virus encephalitis based on the elevated Epstein-Barr virus antibody titers and presence of Epstein-Barr virus DNA in the Cerebrospinal Fluid. A repeated duodenal artery embolization and symptomatic therapy could not control the hemorrhage after admission. He subsequently received treatment with ganciclovir, glucocorticoid, thalidomide, and propranolol. Hemorrhage was controlled in 5 days; his symptoms improved. The fever did not recur and the CSF pressure was also normalized. A follow-up CT at 3 months after admission showed regression of the aneurysm in the right internal carotid artery and the vascular lesion in the duodenum. A new treatment protocol including thalidomide and propranolol resulted in a marked improvement in his clinical symptoms, and shows promise as a novel and effective therapeutic approach for Chronic active Epstein-Barr virus infection-associated lymphoproliferative disorder.


Postexercise nutrient intake enhances leg protein balance in early postmenopausal women.
We investigated the effect of nutrient administration after a session of resistance exercise on muscle protein kinetics in six healthy, early postmenopausal women, in a crossover design of random and double-blinded administration of protein and carbohydrate (PC) or placebo (NON). Fasted participants received a primed-constant infusion of L-[ring-2H5]-phenylalanine. After 90 minutes of rest, the participants performed leg-resistance exercises followed by the oral supplementation. During the following 4 hours, net protein balance (NB) and rate of disappearance and appearance of phenylalanine were calculated from arterial-venous blood samples and blood flow measurements. NB was elevated (p <.001) in the PC group compared to the NON group, and NB was not different from zero in the PC group, whereas it was negative in the NON group. Net balance results were supported by kinetic data from a reduced number of participants, showing that rate of disappearance was responsible for the initial (<1 hour) effect of PC, whereas a reduced rate of appearance enhanced the NB from 1.5 to 3 hours after training in the PC group. In early postmenopausal women, nutrient ingestion following resistance exercise improved anabolism by enhancing NB in skeletal muscle.


Atlanto-axial dislocation in rheumatoid arthritis--diagnostic and therapeutic aspects.
Symptoms, signs and neuroradiological findings of 15 cases with atlanto-axial dislocation (AAD) due to rheumatoid arthritis are presented. CT of the craniocervical region revealed the exact anatomical relationships between the dens, the subarachnoid space and the brain stem, especially after intrathecal contrast medium injection and different positions of the head. From the results of operative procedures to reduce AAD it was concluded that early diagnosis and treatment of AAD leads to prompt relief of painful symptoms within 3 months and protects from neurological deterioration.


Electrochemical detection of cysteine in a flow system based on reductive desorption of thiols from gold.
A simple strategy for cysteine determination using flow-injection analysis with electrochemical detection is described. The approach is based on the chemisorptions reactions of the sulfur moiety of cysteine upon polycrystalline gold electrodes and its subsequent reductive desorption. The electrochemical measurements were accomplished by the application of differential pulse voltammetry (DPV) for the operational optimization and pulsed electrochemical detection (PED) in combination with flow-injection analysis for the electrochemical detection as time function. The electroactive species could be adsorbed in a potential level (0.1 V versus SCE), at other (-0.6 V versus SCE) occurs their reductive desorption from the electrode, while the analytical current is recorded simultaneously, and a third potential step is applied to the complete regeneration of the gold electrode surface (-1.3 V versus SCE). The linear response range was observed between 1.0 x 10(-6) and 6.0 x 10(-6) mol L(-1) with a good reproducibility (R.S.D.<3.2%) and sensitivity (1.1 microA/microM). The repeatability (a series of 27 continuous FIA peaks of 5. 0 micromol L(-1) of cysteine) was 3.8 % and the limit of detection was 5.0 x 10(-7) mol L(-1). The sample throughput was 23 samples per hour with a very high stability in its voltammetric response. The developed methodology was successfully used for the determination of cysteine in commercial supplementary food sample.


Environmental risks of organic fertilizer with increased heavy metals (Cu and Zn) to aquatic ecosystems adjacent to farmland in the northern biosphere of Japan.
In Abashiri, Hokkaido, northern Japan, composted sewage sludge (CSS) containing a large amount of zinc (Zn) and copper (Cu) is used as fertilizer in agriculture. The local environmental risks of Cu and Zn from such organic fertilizers were studied. The study area, especially the brackish lakes located near the farmlands, is important for inland fisheries. The risks posed by heavy metals to the brackish-water bivalve, Corbicula japonica, was therefore investigated as an example. First, the long-term effect of CSS application in agricultural fields was monitored. Second, using pot cultivation, factors influencing Cu and Zn availability in the presence of organic fertilizers were evaluated under different scenarios of SOM content. In addition, the mobility and availability of Cu and Zn in organic fertilizers were evaluated in a field experiment. In the pot cultivation, both organic and chemical fertilizers increased the availability of Cu and Zn with a decrease in pH, possibly caused by nitrification. However, this decrease in pH was inhibited by higher SOM content, i.e. SOM mitigated the heavy metal risk from organic fertilizer. In the field experiment, potato (Solanum tuberosum L.) was cultivated using CSS and pig manure (PM). As observed in the pot cultivation, the applied chemical and organic fertilizers increased the soil-soluble and 0.1 N HCl-extractable Zn with increased nitrate. Considering the habitat and the LC50 values of C. japonica that were lower than the concentration of Cu and Zn in the soil solution phase, there is no significant risk from heavy metals in the organic fertilizers. However, the Kd values for Zn were significantly lower for CSS or the PM-applied plot in the field experiment soil, indicating a higher Zn desorption rate from organically fertilized soil particles. The potential risk of heavy metals from agricultural lands under changing climate conditions must therefore be monitored carefully.


Repression of glucocorticoid receptor function by the anti-rheumatic gold compound aurothiomalate.
We describe functional interaction between the anti-rheumatic water-soluble gold compound aurothiomalate and glucocorticoid receptors. Aurothiomalate contains gold in the Au(I) state, and Au(I) alone, not thiomalate or malate, reduced the ligand-binding activity of the glucocorticoid receptor. Au(I) also interfered with the productive interaction between the glucocorticoid receptor and the cognate target DNA sequences and repressed the transactivation function of the receptor. Thus, Au(I) variably modulates glucocorticoid receptor-mediated intracellular signals.


N6-cyclohexyladenosine inhibits veratridine-stimulated 22Na uptake by rat brain synaptosomes.
The effect of the stable adenosine analogue, N6-cyclohexyladenosine, on 22Na uptake by rat brain synaptosomes stimulated by veratridine was investigated. In the presence of N6-cyclohexyladenosine, both the initial rate and the maximum sodium uptake were decreased. The inhibitory effect of N6-cyclohexyladenosine on sodium uptake by synaptosomes after 5 s of incubation with 22Na was concentration-dependent, antagonized by 1,3-dipropyl-8-p-sulfophenylxanthine, and attenuated by increasing the concentration of veratridine. The possibility that the adenosine analogue, by activating a xanthine-sensitive adenosine receptor, can operate inhibition of the voltage-dependent sodium channels is discussed.


A unified framework for hybrid breeding and the establishment of heterotic groups in wheat.
Global wheat genetic diversity can be used in a unified framework to support and accelerate hybrid breeding and the development of heterotic groups in wheat. Hybrid wheat breeding has great potential to increase the global wheat grain yield level particularly in view of the increasing abiotic and biotic stress challenges as well as variable climatic conditions. For the long-term success of hybrid wheat breeding and the maximum exploitation of heterosis, high-yielding heterotic patterns must be established. Here, we propose a unified framework for hybrid breeding and the establishment of heterotic groups in autogamous crops and exemplify it for hybrid wheat breeding in Germany. A key component is the establishment of genetic distance between heterotic groups and in this context, we assessed genetic diversity in a global collection of 1110 winter wheat varieties released during the past decades in 35 countries but with a focus on European origin. Our analyses revealed the absence of major population structure but nevertheless suggest genetically distinct subgroups with potential for hybrid wheat breeding. Taking our molecular results and additional phenotypic data together, we propose how global genetic diversity can be used to accelerate and support reciprocal recurrent selection for the development of genetically distinct heterotic groups in hybrid wheat breeding.


Increased solubility of collagen. A biochemical defect in the experimental hydralizine-induced collagen disease-like syndrome.
An increase of soluble fractions of collagen and a decrease of insoluble ones was found in the skin of guinea pigs with collagen disease-like syndrome, produced by prolonged treatment with hydralazine. Chromatography studies showed that the collagen alpha chains content in the skin increased and beta-chains decreased under conditions of the development of lupus-like syndrome. The obtained results suggested the inhibition of collagen maturation as one of biochemical defects of connective tissue in drug-induced collagen disease-like syndrome.


Problems with Early Systematic Reviews: The Case of Coronavirus Disease 2019 (COVID-19) in Pregnancy.
Rapid dissemination of findings regarding the Coronavirus Disease 2019 (COVID-19) and its potential effects on pregnancy is crucial to support understanding and development of recommendations for optimization of obstetrics care. However, much of the current studies published are in the form of case reports or case series which can be prone to biases. Other factors also further complicate attempts to analyze data accurately. Hence, this evaluation hopes to highlight some of these problems and provide suggestions to help clinicians mitigate and make reasonable conclusions when reading the abundant yet limited body of evidence when furthering their research efforts. Studies regarding COVID-19 and pregnancy were searched on databases such as PubMed, EMBASE, Scopus, the Cochrane Library. Manual search of references of select articles were also undertaken. Apart from summarizing study limitations identified by authors, the characteristics of current literature and systematic reviews were also evaluated to identify potential factors affecting accuracy of subsequent analysis. Factors such as innate biasness in study design of current literature, duplicate reporting, differing inclusion criteria of systematic reviews, scarce data, inadequate follow-up period and limitations of systematic reviews have been shown to hinder the ability for accurate data extrapolation. Unless additional studies are conducted in identified areas of data scarcity and a common list of factors affecting accuracy of data analysis are taken into account when developing recommendations, discrepancies will continue to arise and accurate data analysis and valid systematic reviews will be precluded.


Bone marrow stromal cells can be delivered to the site of traumatic brain injury via intrathecal transplantation in rabbits.
Recent studies suggest that bone marrow stromal cells (BMSCs) are promising grafts for treatment of traumatic brain injury (TBI). Neural precursor cells (NPCs) have been detected in the site of cervical cord injury following intrathecal injection by lumbar puncture. So, this study is designed to determine whether BMSCs (after intrathecal administration by lumbar puncture) could also migrate to the TBI site. The cells were cultured in vitro and transfected with adenovirus green fluorescent protein (Ad-GFP), and then transplanted intrathecally or intravenously into an autologous rabbit model of TBI. The labeled, grafted cells were identified in the injured cerebral tissue using fluorescence microscopy. Results showed that the intrathecal protocol was more efficient than the intravenous one. And motor dysfunction was improved after autologous transplantation of BMSCs. This study suggests another attractive minimally invasive option for treating TBI.


Curvilinear prediction of posttraumatic growth on quality of life: a five-wave longitudinal investigation of breast cancer survivors.
Do cancer survivors experience positive changes (i.e., posttraumatic growth; PTG) resulting in better quality of life? The issue has yet to yield consistent notions. This longitudinal study extends the literature on the role of PTG by examining the curvilinear relationship between PTG and Health-Related Quality of Life (HRQoL), and explored whether PTG predicts subsequent HRQoL in a quadratic relationship across 2 years following surgery. Women with breast cancer (N = 359; Mage = 47.5) were assessed at five waves over two years. On every measurement occasion, PTG measured by the posttraumatic growth inventory and HRQoL measured by SF-36 were assessed. The five waves reflect major medical demands and related challenges in the breast cancer trajectory, in which 1-day, 3 months, 6 months, 12 months, and 24 months after surgery were adopted as the survey timing. In a series of hierarchical linear modeling (HLM) analyses, the time-lagged predictions of PTG (i.e., linear, quadratic) on HRQoL were examined, controlling demographic and medical covariates. The results revealed that the quadratic term of PTG consistently significantly predicted physical and mental health quality of life (PCS and MCS), while the linear term of PTG did not significantly predict PCS or MCS. With multi-wave longitudinal data, this study demonstrated that the relationship between PTG and HRQoL is curvilinear, and this finding extends to PTG's prediction of subsequent HRQoL. The quadratic relationship has critical implications for clinical assessment and intervention. Details are discussed.


Comparison of characteristic features and local recurrence in syndromic versus non-syndromic multifocal non-ossifying fibroma.
Multiple non-ossifying fibromas (MNOF) could be presented with other extraskeletal anomalies (syndromic) or not (non-syndromic). In this study, we aimed to compare characteristic features and local recurrence between symptomatic syndromic and non-syndromic MNOFs. Thirty-five patients with symptomatic MNOF were included in this study, comprised of 30 patients without the café-au-lait spot (non-syndromic) and five with café-au-lait spots plus other signs of neurofibromatosis type 1 (syndromic). Characteristic features of the patients and lesions were compared between syndromic and non-syndromic MNOFs. The lesions were treated with curettage and bone graft. The rate of local recurrences was also compared between the two groups of syndromic and non-syndromic MNOF. Study population included 19 (54.3%) males and 16 (45.7%) females with the mean age of 7.63 ± 3.1 years (range 4-11). The mean follow-up of the patients was 65.6 ± 38.2 months (range 24-96). The lesion was bilateral in 13.3% of non-syndromic MNOFs and 80% of syndromic MNOFs. This difference was statistically significant (p = 0.01). After curettage and bone grafting, the lesion recurred in 6.7%of non-syndromic MNOFs and 60% of the syndromic MNOF. This difference was statistically significant, as well (p = 0.01). No other significant difference was found between syndromic and non-syndromic MNOFs. The syndromic form of MNOF is much less prevalent and is associated with a higher rate of recurrence after surgical removal. Therefore, a more rigorous removal of the MNOF lesions might be necessary when presented in a syndromic context.


Ultralight shape-recovering plate mechanical metamaterials.
Unusual mechanical properties of mechanical metamaterials are determined by their carefully designed and tightly controlled geometry at the macro- or nanoscale. We introduce a class of nanoscale mechanical metamaterials created by forming continuous corrugated plates out of ultrathin films. Using a periodic three-dimensional architecture characteristic of mechanical metamaterials, we fabricate free-standing plates up to 2 cm in size out of aluminium oxide films as thin as 25 nm. The plates are formed by atomic layer deposition of ultrathin alumina films on a lithographically patterned silicon wafer, followed by complete removal of the silicon substrate. Unlike unpatterned ultrathin films, which tend to warp or even roll up because of residual stress gradients, our plate metamaterials can be engineered to be extremely flat. They weigh as little as 0.1 g cm(-2) and have the ability to 'pop-back' to their original shape without damage even after undergoing multiple sharp bends of more than 90°.


Dimethyl sulfoxide increases cytoplasmic Ca2+ concentration and inhibits parathyroid hormone release in normal bovine and pathological human parathyroid cells.
The acute effects of dimethyl sulfoxide (DMSO) on parathyroid hormone (PTH) release and the cytoplasmic Ca2+ concentration (Ca2+i) were studied in dispersed bovine cells and cells isolated from human parathyroid adenomas. At extracellular Ca2+ concentrations in the 0.5-3.0 mM range, but not at less than 25 nM, addition of 2% DMSO caused a rapid rise of Ca2+i. This effect corresponded to an inhibition of PTH release and there was a strong negative correlation between Ca2+i and secretion. The actions of DMSO on Ca2+i and PTH release were less pronounced in the pathological human cells. The data are consistent with a DMSO effect on the Ca2+-sensor function of the parathyroid cell, possibly mediated by an altered plasma membrane fluidity.


CT evaluation of nasolacrimal relapse of nasopharyngeal carcinoma.
The aim of the current study was to elucidate the anatomy of the nasolacrimal apparatus using computed tomography (CT), and to investigate the CT findings suggestive of recurrent nasopharyngeal carcinoma (NPC) involving the nasolacrimal apparatus. CT images of five patients with clinical or radiological findings suggestive of recurrent NPC who presented with nasolacrimal involvement were reviewed. Involvement of the lacrimal fossa, nasolacrimal canal (NLC), and adjacent anatomic structures including orbit and sinonasal cavities were noted. CT in all patients demonstrated findings of NLC invasion and ostiomeatal complex obliteration. Four of the five patients showed medial canthal mass or pre-septal thickening, ethmoid bulla opacification and inferior nasal meatal involvement. Knowledge of the anatomy of the nasolacrimal apparatus using CT is critical for evaluating images for tumour recurrence at this site. NLC invasion, a medial canthal mass and pre-septal thickening are important primary indicators for potential involvement of the nasolacrimal apparatus by recurrent NPC. Secondary signs suggesting this distinct form of relapse are obliteration of ostiomeatal channel, ethmoid bulla opacification and inferior nasal meatus involvement.


Hepatitis C virus NS3 protease requires its NS4A cofactor peptide for optimal binding of a boronic acid inhibitor as shown by NMR.
NMR spectroscopy was used to characterize the hepatitis C virus (HCV) NS3 protease in a complex with the 24 residue peptide cofactor from NS4A and a boronic acid inhibitor, Ac-Asp-Glu-Val-Val-Pro-boroAlg-OH. Secondary-structure information, NOE constraints between protease and cofactor, and hydrogen-deuterium exchange rates revealed that the cofactor was an integral strand in the N-terminal beta-sheet of the complex as observed in X-ray crystal structures. Based upon chemical-shift perturbations, inhibitor-protein NOEs, and the protonation state of the catalytic histidine, the boronic acid inhibitor was bound in the substrate binding site as a transition state mimic. In the absence of cofactor, the inhibitor had a lower affinity for the protease. Although the inhibitor binds in the same location, differences were observed at the catalytic site of the protease.


Tumour 'budding' as an index to estimate the potential of aggressiveness in rectal cancer.
Although the characteristic of invasive pattern which contributes to Jass's classification is a sensitive prognostic marker in rectal cancer, reproducibility of its assessment has been shown to be problematic. As another histological parameter of invasive margin, we examined the prognostic significance of tumour 'budding' and attempted to establish its appropriate criteria. A total of 638 rectal cancer specimens was examined. We defined tumour 'budding' as an isolated single cancer cell or a cluster composed of fewer than five cancer cells. We divided these into two groups by their intensity, i.e. the number of 'budding' foci within a microscopic field of x 250. Rectal cancer with high-grade 'budding' (>or= 10 foci in a field) was observed in 30.1% of patients, and was associated with lower 5-year survival rates (40.7%) than patients with low-grade 'budding' (84.0%) (P < 0.0001). Based on multivariate analysis, tumour 'budding' was selected as the significant independent variable, together with the number of nodes involved, extramural spread, lymphocytic infiltration, apical nodal involvement and tumour differentiation. Kappa coefficient of two-graded tumour 'budding' in the intraobserver study was 0.84. Because of its value as a prognostic indicator and its reproducibility, tumour 'budding' would be a good index to estimate the aggressiveness of rectal cancer.


Genome-wide association mapping of resistance to the foliar diseases septoria nodorum blotch and tan spot in a global winter wheat collection.
Septoria nodorum blotch (SNB) and tan spot, caused by the necrotrophic fungal pathogens Parastagonospora nodorum and Pyrenophora tritici-repentis, respectively, often occur together as a leaf spotting disease complex on wheat (Triticum aestivum L.). Both pathogens produce necrotrophic effectors (NEs) that contribute to the development of disease. Here, genome-wide association analysis of a diverse panel of 264 winter wheat lines revealed novel loci on chromosomes 5A and 5B associated with sensitivity to the NEs SnTox3 and SnTox5 in addition to the known sensitivity genes for NEs Ptr/SnToxA, SnTox1, SnTox3, and SnTox5. Sensitivity loci for SnTox267 and Ptr ToxB were not detected. Evaluation of the panel with five P. nodorum isolates for SNB development indicated the Snn3-SnTox3 and Tsn1-SnToxA interactions played significant roles in disease development along with additional QTL on chromosomes 2A and 2D, which may correspond to the Snn7-SnTox267 interaction. For tan spot, the Tsc1-Ptr ToxC interaction was associated with disease caused by two isolates, and a novel QTL on chromosome 7D was associated with a third isolate. The Tsn1-ToxA interaction was associated with SNB but not tan spot. Therefore some, but not all, of the previously characterized host gene-NE interactions in these pathosystems play significant roles in disease development in winter wheat. Based on these results, breeders should prioritize the selection of resistance alleles at the Tsc1, Tsn1, Snn3, and Snn7 loci as well as the 2A and 7D QTL to obtain good levels of resistance to SNB and tan spot in winter wheat. The online version contains supplementary material available at 10.1007/s11032-023-01400-5.


Fungation in soft tissue sarcomas is associated with poor survival.
Whilst much is known on the multiple variables associated with a poor prognosis in soft tissue sarcomas, little evidence exists on the impact of fungation at the time of presentation. The aim of this study was to assess the impact of fungation on overall and disease free survival in soft tissue sarcomas. The study comprised a retrospective review of all patients presenting with a soft tissue sarcoma between 1996 and 2014 managed at a single institution. Over the 18-year study period, 2661 patients were diagnosed with a STS. Eighty-six patients (3.2%) presented with a fungating tumour. The five year survival for all patients with a fungating sarcoma was 15.5% (95% confidence interval: 4.6-26.4), which compared to 65.6% (95% confidence interval 63.2-67.8%) (p = 0.0001) for non-fungating tumours. The incidence of metastasis at presentation in the non-fungating tumour group was 11.3% of patients, compared to 20.0% in those with a fungating tumour (p = 0.0113). Factors associated with a poor prognosis in the fungating group included size, grade and tumour-type, patient age, tumour depth, and metastases at presentation. As an independent risk factor, tumour fungation was associated with a poor prognosis when compared to non-fungating tumours. The rate of limb sacrifice as primary treatment was higher in the fungating group (23% versus 73%). In spite of this, the incidence of local recurrence was higher in the fungating group (20% versus 16.5%). Fungation is associated with a poor prognosis with a high incidence of metastases at presentation and a high rate of local recurrence. As an independent variable, fungation confers a poor prognosis when compared to non-fungation in soft tissue sarcomas.


Cone-beam computed tomography is not a mandatory procedure in adrenal venous sampling for primary hyperaldosteronism.
To investigate the necessity of cone-beam computed tomography (CBCT) in adrenal venous sampling (AVS). This retrospective study included 120 consecutive patients with primary hyperaldosteronism who underwent AVS. Based on the learning curve of the interventional radiologists, the patients were divided into the learning (n = 36) and proficiency (n = 84) groups chronologically. Based on the imaging pattern of the right adrenal vein (RAV), the patients were divided into the typical (n = 36) and atypical (n = 84) groups. The success rate, radiation dose, and sampling time were compared among the entire study population and each subgroup. A total of 69 patients underwent CBCT, whereas 51 patients did not. The overall success rate was 85.8%, and no difference was noted between patients with and without CBCT (P = 0.347). However, radiation dose (P = 0.018) and sampling time (P = 0.001) were significantly higher in patients who underwent CBCT than in patients who did not. In learning group, CBCT improved success rate from 62.5 to 96.4% (P = 0.028), whereas it was not found in the proficiency group (P = 0.693). Additionally, success rate in patients with an atypical RAV imaging pattern was significantly higher when CBCT was used than when it was not used (P = 0.041), whereas no difference was noted in patients with typical RAV imaging pattern (P = 0.511). For physicians not very experienced doing AVS, there is a clear significant improvement in success rate when CBCT is used. However, CBCT only has minimal benefit for experienced operators, meanwhile CBCT may take an extra time and increase the radiation dose during AVS.


Protein S4 is near the elongation factor G binding site in the ribosome.
Using a mild iodination method for protein radioactive labeling, it has been shown that elongation factor G, when bound to the ribosome as EFG-GDP-fusidic acid complex, protects protein S4 from labeling. The results indicate that protein S4 is probably near the ribosomal EFG binding site.


Using nursing resource teams to improve quality of care.
The process of setting up and monitoring nursing resource teams for maximum effectiveness involves five key steps: Set the resource team goals and approach. Plan for development and oversight. Gather and analyze the relevant information. Deploy the team. Reevaluate staffing levels and effectiveness.


Repeat treatment of obese mice with BRL 49653, a new potent insulin sensitizer, enhances insulin action in white adipocytes. Association with increased insulin binding and cell-surface GLUT4 as measured by photoaffinity labeling.
(+/-)-5-([4-[2-Methyl-2(pyridylamino)ethoxy]phenyl]methyl) 2,4-thiazolidinedione (BRL 49653) is a new potent antidiabetic agent that improves insulin sensitivity in animal models of NIDDM. In C57BL/6 obese (ob/ob) mice, BRL 49653, included in the diet for 8 days, improved glucose tolerance. The half-maximal effective dose was 3 mumol/kg diet, which is equivalent to approximately 0.1 mg/kg body wt. Improvements in glucose tolerance were accompanied by significant reductions in circulating triacylglycerol, nonesterified fatty acids, and insulin. The insulin receptor number of epididymal white adipocytes prepared from obese mice treated with BRL 49653 (30 mumol/kg diet) for 14 days was increased twofold. The affinity of the receptor for insulin was unchanged. In the absence of added insulin, the rates of glucose transport in adipocytes from untreated and BRL 49653-treated obese mice were similar. Insulin (73 nmol/l) produced only a 1.5-fold increase in glucose transport in adipocytes from control obese mice, whereas after BRL 49653 treatment, insulin stimulated glucose transport 2.8-fold. BRL 49653 did not alter the sensitivity of glucose transport to insulin. The increase in insulin responsiveness was accompanied by a 2.5-fold increase in the total tissue content of the glucose transporter GLUT4. Glucose transport in adipocytes from lean littermates was not altered by BRL 49653. To establish the contribution of changes in glucose transporter trafficking to the BRL 49653-mediated increase in insulin action, the cell-impermeant bis-mannose photolabel 2-N-[4-(1-azi-2,2,2-trifluoroethyl)benzoyl]-1,3-bis-(D-mannos++ +-4-yloxy) -2-[2-3H]-propylamine was used to measure adipocyte cell-surface-associated glucose transporters.(ABSTRACT TRUNCATED AT 250 WORDS)