Theoretical and empirical comparisons of expected and realized relationships for the X-chromosome.
X-chromosomal loci present different inheritance patterns compared to autosomal loci and must be modeled accordingly. Sexual chromosomes are not systematically considered in whole-genome relationship matrices although rules based on genealogical or marker information have been derived. Loci on the X-chromosome could have a significant contribution to the additive genetic variance, in particular for some traits such as those related to reproduction. Thus, accounting for the X-chromosome relationship matrix might be informative to better understand the architecture of complex traits (e.g., by estimating the variance associated to this chromosome) and to improve their genomic prediction. For such applications, previous studies have shown the benefits of combining information from genotyped and ungenotyped individuals. In this paper, we start by presenting rules to compute a genomic relationship matrix (GRM) for the X-chromosome (GX) without making any assumption on dosage compensation, and based on coding of gene content with 0/1 for males and 0/1/2 for females. This coding adjusts naturally to previously derived pedigree-based relationships (S) for the X-chromosome. When needed, we propose to accommodate and estimate dosage compensation and genetic heterogeneity across sexes via multiple trait models. Using a Holstein dairy cattle dataset, including males and females, we then empirically illustrate that realized relationships (GX) matches expectations (S). However, GX presents high deviations from S. GX has also a lower dimensionality compared to the autosomal GRM. In particular, individuals are frequently identical along the entire chromosome. Finally, we confirm that the heritability of gene content for markers on the X-chromosome that are estimated by using S is 1, further demonstrating that S and GX can be combined. For the pseudo-autosomal region, we demonstrate that the expected relationships vary according to position because of the sex-gradient. We end by presenting the rules to construct the 'H matrix' by combining both relationship matrices. This work shows theoretically and empirically that a pedigree-based relationship matrix built with rules specifically developed for the X-chromosome (S) matches the realized GRM for the X-chromosome. Therefore, applications that combine expected relationships and genotypes for markers on the X-chromosome should use S and GX.


Nationwide survey on adult type chronic intestinal pseudo-obstruction in surgical institutions in Japan.
No appropriate management of chronic intestinal pseudo-obstruction (CIP) has been established. The clinicopathological parameters of 103 cases collected by a nationwide questionnaire study were reviewed. The CIP cases were primary in 86 (83%) cases and secondary in 15 (15%) cases. The age of onset of the primary type was significantly younger than that of the secondary type (p = 0.011). The diseased segments of the bowel were the large bowel in 60 (58%), the small bowel in 17 (17%), and both in 23 (22%) cases, respectively. Abdominal distension and pain were common symptoms regardless of the types of the diseased bowel; however, constipation was frequently seen in the large bowel type (p = 0.0258). Vomiting and diarrhea were seen with marginally higher frequency in the small bowel type (p = 0.0569, 0.0642). Surgical treatment was most effective in the large bowel type, less effective in the small bowel type, and least effective in the large and small bowel type. The prognosis of the primary CIP was significantly better than that of the secondary CIP (p = 0.033). The segments of the diseased bowels should be considered in determining the indications for surgical treatments in CIP patients.


Application of Rare-Earth Elements and Comparison to Molecular Markers in Oil-Source Correlation of Tight Oil: A Case Study of Chang 7 of the Upper Triassic Yanchang Formation in Longdong Area, Ordos Basin, China.
The biomarker features of 10 Chang 7 crude oil samples were investigated by gas chromatography-mass spectrometry (GC-MS), and the rare-earth element (REE) compositions of 16 Chang 7 and Chang 8 crude oil samples were determined by inductively coupled plasma-mass spectrometry (ICP-MS) for the first time in Longdong area. Oil-source correlation analysis was improved by biomarkers and REEs. The distribution and relative ratios of a series of biomarker parameters in saturated hydrocarbons and aromatic hydrocarbons of crude oil samples indicate that Chang 7 tight oil has already reached the mature stage. The organic matter mainly comes from lower aquatic organisms of algae, with some contribution of micro-organisms and bacteria, while the forming environment of tight oil is mainly the transitional environment of sub-oxidizing to sub-reducing. The V/(V + Ni) and Ni/Co ratios of crude oil samples suggest that the specific redox conditions of Chang 71 and Chang 72 samples were slightly oxic, while Chang 73 and Chang 8 samples were formed under an anoxic environment. The results of both biomarker-based and REE-based oil-source correlation analysis indicate that Chang 71 and Chang 72 tight oils come from Chang 7 mudstone, while most of the Chang 73 tight oils are from Chang 7 oil shale, with part of mixed from Chang 7 mudstone. This recognition may indicate that Chang 7 mudstone and oil shale are two relatively independent hydrocarbon self-generation and near-storage systems. The analysis results demonstrate that the REE composition in crude oil is an efficient and accurate tool for oil-source correlation in the petroleum system.


Corrigendum to: Genomic epidemiology reveals the reduction of the introduction and spread of SARS-CoV-2 after implementing control strategies in Republic of Korea, 2020.
[This corrects the article DOI: 10.1093/ve/veab077.].


Complexity and simplicity of ligand-macromolecule interactions: the energy landscape perspective.
The energy landscape approach has contributed to recent progress in understanding the complexity and simplicity of ligand-macromolecule interactions. Significant advances in computational structure prediction of ligand-protein complexes have been made using approaches that include the effects of protein flexibility and incorporate a hierarchy of energy functions. The results suggest that the complexity of structure prediction in molecular recognition may be determined by low-resolution properties of the underlying binding energy landscapes and by the nature of the energy funnels near the native structures of the complexes.


Bioisosteric OH- to SH-replacement changes the antioxidant profile of ferulic acid.
We report the synthesis of 4-thioferulic acid (TFA), a new ferulic acid (FA) derivative, and highlight the differences between the two compounds concerning rate and mechanism of radical scavenging activity, redox potential, acidity of the phenol/thiophenol moieties, cytotoxicity in differentiated SH-SY5Y cells, and neuroprotection against hydrogen peroxide (H2O2) and tert-butyl hydroperoxide (t-BHP) in the same cellular model.


Prevalence of bacterial genes in the phage fraction of food viromes.
Antibiotic resistance genes (ARGs) have been identified in viral DNA isolated from different kinds of food, but little is known about their origin. In this study, twenty-one viromes were analyzed from samples of food previously reported to carry ARGs, including meat (poultry, veal, and pork), fish (Mediterranean, Atlantic, frozen, farmed and shellfish) and vegetables (lettuce, cucumber, and spinach). Classification of the contigs by Kraken revealed a large percentage of unclassified contigs (43.7-98.2%) in all the viromes. Only 0.05-7.1% of the contigs were identified as viral and of these, more than 91% belonged to different bacteriophage families, Podophages and Siphophages being the most prevalent. According to VirSorter, the largest number of viral contigs were derived from viromes of shellfish, followed by spinach. Spinach viromes also included the largest number of phage sequences identified by PHASTER. The abundant presence of bacterial genes in the viromes, including 16S rRNA genes, was attributed to the phage packaging of the bacterial genome fragments, as no bacterial DNA was found outside the viral capsids. The detection of 16S rRNA genes in the different viromes allowed diverse phage bacterial hosts to be identified. The three major functional groups of genes determined were related to metabolism, detoxification/resistance, and above all, biosynthesis. Various ARGs were quantified in the viromes by qPCR, the most prevalent being β-lactamases, particularly blaTEM. Analysis of ARG diversity in the viromes by Prokka and CARD revealed various resistance-related genes, whereas a more restrictive search by ResFinder identified blaTEM in all the food viromes, blaOXA in Atlantic fish-1 and spinach-2, oqxB in lettuce-1, and dfr in spinach-2. The presence of ARGs in the food viromes points to bacterial DNA mobilization by transduction mechanisms. Transduction of resistances by phage particles may therefore contribute to the emergence of resistant strains along the food chain and should be monitored.


Pedunculated polypoid melanoma. A case report of a rare spindle-cell variant of melanoma.
We report an 89-year-old man who presented with a slowly growing pigmented pedunculated tumor. The nodule was diagnosed as a spindle cell pedunculated malignant melanoma (PMM), a rare variant of spindle-cell malignant melanoma. The clinical presentation of this tumor and its histological and immunohistological features are discussed.


[Methods for the sampling and tracing of caprolactam monomer dispersed in the air].
The problem of hygiene in the production of epsilon-caprolactam is very important; pollution of work room air is possible when the substance is stored, transported or packed in bags. In this work toxic and irritant properties of epsilon-caprolactam are described. Infrared spectroscopic, gas chromatrographic and spectrophotometric methods used by us, for the determination of epsilon-caprolactam traces, are also described.


A lymphocytotoxic factor(s) in plasma of patients with minimal change nephrotic syndrome: partial characterization.
The incidence, relationship to clinical disease, and physical characteristics of a plasma cytotoxic factor(s) were studied in steroid-responsive minimal change nephrotic syndrome (MCNS) and other renal diseases. Plasma activity was found in 76% of 67 children with MCNS and in 67% of 9 children with focal segmental sclerosis (FSS). Of 31 normal adults and children and 7 adults with membranous glomerulonephritis, only 1 individual had toxic plasma. In MCNS, degree of plasma activity was not related to clinical disease, prednisone dosage, or serum levels of IgG or alpha-2-macroglobulin. The active factor(s) was found more frequently in plasma than in serum, was heat stable and nondialyzable by selected filtration, and was approximately 100,000 to 300,000 molecular weight. By DEAE column chromatography, activity coincided with fractions containing IgA and IgM but not IgG. While the nature of the plasma factor(s) has not been identified, these data indicate that MCNS plasma may adversely affect lymphocyte viability by a slow process of cytotoxicity requiring 24 or more hr, and that such plasma activity occurs frequently in children with MCNS and also with the more severe FSS.


Alcohol decreases serum osteocalcin in a dose-dependent way in normal subjects.
The acute effect of 25 and 50 g of alcohol on the variation in serum osteocalcin, a specific and sensitive marker of bone formation, and on serum cortisol and serum parathyroid hormone (PTH)(1-84) was calculated in 6 normal young adults. They were studied during three periods, each lasting from 4 p.m.-7:30 a.m. Alcohol was ingested between 4:15 and 5 p.m. during period two and three. Blood was taken at 4 p.m. and every 15 minutes from 4:30 til 6 p.m., followed by hourly sampling until 12 p.m. The last blood sample was taken after an overnight fast at 7:30 a.m. Initial and end values before and after alcohol ingestion did not differ significantly from control values. Repeated measures analysis of variance showed that 50 g of ethanol decreased serum osteocalcin significantly (P less than 0.02) and increased serum cortisol (P less than 0.05) during the 4-12 p.m. interval. The interaction of 50 g of ethanol on the variation in serum osteocalcin was already significant during the first 2 hours (P less than 0.02), where no significant effect on serum cortisol could be detected. Although insignificant, the same pattern was observed after 25 g of alcohol. There was no significant change in the variation of serum iPTH(1-84) during the 4-6 p.m. after alcohol intake. We conclude that 3-4 drinks of alcohol taken over 45 minutes decreases serum osteocalcin in a dose-dependent way. The time lag between changes in serum osteocalcin and cortisol indicates that the decrease in serum osteocalcin is not related to the increase in serum cortisol.


Two year follow-up of astigmatism after phacoemulsification with adjusted and unadjusted sutured versus sutureless 5.2 mm superior scleral incisions.
To evaluate changes in astigmatism 6 months to 2 years after 5.2 mm superior scleral incision phacoemulsification using 3 closures. Department of Ophthalmology, Vejle Hospital, Vejle, Denmark. This long-term follow-up study included 75 consecutive phacoemulsification patients who were randomly allocated to 1 of 3 incision closures: 1 intraoperatively adjusted cross suture, 1 unadjusted cross suture, no suture. Postoperative astigmatism after 1 and 2 years was evaluated by keratometric cylinder, induced astigmatism (Naeser's polar values), induced cylinder (Jaffe's vector analysis), and vector decomposition (Olsen). The data were compared with 1 week values. In the previous study, median astigmatism after 6 months was similar in all 3 groups, but only the sutureless group showed early stability. Significant against-the-rule (ATR) changes were seen in the sutured cases (P < .01). The 1 and 2 year follow-up showed continued stability in the sutureless cases. The adjusted-suture group exhibited stability after 6 months, while the unadjusted-suture group showed a further tendency to change ATR. At 2 years, median ranges of astigmatism were -0.49 to -0.90 diopter (D) (Naeser), 0.77 to 1.02 D (Jaffe), and 96% to 98% ATR (Olsen). The intergroup differences were not statistically significant. Two year follow-up confirmed that sutureless closure led to early astigmatism stability. Using a suture prolonged the postoperative period of astigmatism instability, and if used without intraoperative adjustment, a tendency toward a less predictable outcome persisted after 2 years.


Diacetoxyscirpenol production by Fusarium sambucinum strain KF 735 on solid and liquid media.
The yield of diacetoxyscirpenol (DAS) production by F. sambucinum strain No KF 735, isolated from potato tuber with dry rot symptoms, cultured on solid media and on liquid medium, has been examined.The amount of DAS produced within 28 days at 25°C in the cultures grown on solid media (wheat, rye, rice, oats, corn, barley, triticale and malt) reached 238mg/kg±9 to 789±16mg/kg (mean ± standard error; n=3), on potato cubes -55±3mg/kg and on the potato extract -147±5mg/dcm(3).The best substracts for crystalline compound production were malt and barley grain.


Do commencing nursing and paramedicine students differ in interprofessional learning and practice attitudes: evaluating course, socio-demographic and individual personality effects.
Interprofessional education (IPE) requires health students to learn with, from and about each other in order to develop a modern workforce with client-centred care at its core. Despite the client centred focus of IPE, training programs often utilize standard approaches across student cohorts without consideration of discipline, sociodemographic and personality variability that attract students to different health disciplines. Knowing the students who engage in IPE to tailor training may prove as beneficial as knowing the client to delivered individualized client centred care in interprofessional practice (IPP). This research investigates whether students commencing undergraduate nursing and paramedicine degrees ener training with existing demographic and personality differences and, if these are associated with different attitudes towards health care teams and interprofessional education. This online study recruited 160 nursing and 50 paramedicine students in their first week of their undergraduate course. Students completed questionnaires regarding their background, personality (General Perceived Self Esteem Scale, International Mini Markers) and the attitudes towards health care teams scale (ATHCTS) and interprofessional education perception scale (IEPS). Results show that commencing nursing and paramedicine students are demographically different on education, gender, speaking a language other than English at home (LOTE) and their own experience with healthcare. The results further demonstrate that LOTE, discipline being studied and personality factors play a role in perceptions regarding interprofessional training whilst discipline being studied impacted on attitudes towards health care teams in the workforce. These results highlight a number of existing personal and psychological differences between individuals who choose to train in these selected professions. This suggests a need for tertiary education IPE programs to move towards tailoring their education to value this student diversity in the same client centred manner that students are asked to develop clinically.


Analysis and rearrangement of human karyotypes by computer.
A system useful for the collection and analysis of a large number of abnormal karyotypes and for studies on the relationship between cytogenetic abnormalities and clinical features of diseases is reported. The program is based on the disintegration and rearrangement of abnormal karyotypes recorded according to the 1978 International System for Human Cytogenetic Nomenclature (ISCN).


Biochemical characterization of trinitrotoluene transforming oxygen-insensitive nitroreductases from Clostridium acetobutylicum ATCC 824.
The genes that encode oxygen-insensitive nitroreductases from Clostridium acetobutylicum possessing 2,4,6-Trinitrotoluene (TNT) transformation activity were cloned, sequenced and characterized. The gene products NitA (MW 31 kDa) and NitB (MW 23 kDa) were purified to homogeneity. The NitA and NitB are oxygen-insensitive nitroreductases comprised of a single nitroreductase domain. NitA and NitB enzymes show spectral characteristics similar to flavoproteins. The biochemical characteristics of NitA and NitB are highly similar to those of NfsA, the major nitroreductase from E. coli. NitA exhibited broad specificity similar to that of E. coli NfsA and displayed no flavin reductase activity. NitB showed broad substrate specificity toward nitrocompounds in a pattern similar to NfsA and NfsB of Escherichia coli. NitB has high sequence similarity to NAD(P)H nitroreductase from Archaeoglobus fulgidus. NitA could utilize only NADH as an electron donor, whereas NitB utilized both NADH and NADPH as electron donors with a preference for NADH. The activity of both nitroreductases was high toward 2,4-Dinitrotoluene (2,4-DNT) as a substrate. Both the nitroreductases were inhibited by dicoumarol and salicyl hydroxamate. The nitroreductases showed higher relative expression on induction with TNT, nitrofurazone and nitrofurantoin compared to the uninduced control.


Effect of distamycin a on the structure and template activity of DNA in RNA - polymerase system.
It is shown that native and denatured DNA form complexes with the oligopeptide-antibiotic distamycin A. The pronounced inhibition of the incorporation of AMP into RNA in the DNA directed RNA-polymerase system is due to the interference of the antibiotic with DNA.


The prevalence of nodal upstaging during robotic lung resection in early stage non-small cell lung cancer.
Pathologic nodal upstaging can be considered a surrogate for completeness of nodal evaluation and quality of surgery. We sought to determine the rate of nodal upstaging and disease-free and overall survival with a robotic approach in clinical stage I NSCLC. We retrospectively reviewed patients with clinical stage I NSCLC after robotic lobectomy or segmentectomy at three centers from 2009 to 2012. Data were collected primarily based on Society of Thoracic Surgeons database elements. Robotic anatomic lung resection was performed in 302 patients. The majority were right sided (192; 63.6%) and of the upper lobe (192; 63.6%). Most were clinical stage IA (237; 78.5%). Pathologic nodal upstaging occurred in 33 patients (10.9% [pN1 20, 6.6%; pN2 13, 4.3%]). Hilar (pN1) upstaging occurred in 3.5%, 8.6%, and 10.8%, respectively, for cT1a, cT1b, and cT2a tumors. Comparatively, historic hilar upstage rates of video-assisted thoracoscopic surgery (VATS) versus thoracotomy for cT1a, cT1b, and cT2a were 5.2%, 7.1%, and 5.7%, versus 7.4%, 8.8%, and 11.5%, respectively. Median follow-up was 12.3 months (range, 0 to 49). Forty patients (13.2%) had disease recurrence (local 11, 3.6%; regional 7, 2.3%; distant 22, 7.3%). The 2-year overall survival was 87.6%, and the disease-free survival was 70.2%. The rate of nodal upstaging for robotic resection appears to be superior to VATS and similar to thoracotomy data when analyzed by clinical T stage. Both disease-free and overall survival were comparable to recent VATS and thoracotomy data. A larger series of matched open, VATS and robotic approaches is necessary.


Quality of life of patients with ADPKD-Toranomon PKD QOL study: cross-sectional study.
The quality of life (QOL) of patients with autosomal dominant polycystic kidney disease (ADPKD) has not been investigated well. This study was performed to clarify the QOL of patients with ADPKD and to identify factors that affected their QOL. The present cross-sectional study is part of a prospective observational study on the QOL of ADPKD patients. Patients with ADPKD who were referred to Toranomon Hospital between March 2010 and November 2012 were enrolled. The short form-36 (SF-36) questionnaire and our original 12-item questionnaire were used to evaluate QOL. We analyzed the results of the questionnaire survey and then investigated correlations between QOL and clinical features. A total of 219 patients (93 men and 126 women) were enrolled and their mean age was 55.1 ± 10.8 years. There were 108 patients on dialysis. The SF-36 scores (PCS, MCS, and RCS) of all patients were significantly lower than the mean scores for the Japanese population. Stepwise multiple regression analysis demonstrated that Hb, serum Alb, ascites, and cerebrovascular disease all had a significant influence on the PCS, while mental disease had a significant influence on the MCS and serum Alb significantly influenced the RCS. The total liver and kidney volume (TLKV) and the dialysis status were not significantly associated with any of the SF-36 scores by multiple regression analysis, but TLKV was closely correlated with abdominal distention and distention had an important influence on QOL. Pain, sleep disturbance, heartburn, fever, gross hematuria, and anorexia also affected QOL, but these variables were not correlated with TLKV. Several factors influence QOL, so improving symptoms unrelated to TLKV as well as reducing abdominal distention can improve the QOL of ADPKD patients.


Episodic Ataxia Type 1: Natural History and Effect on Quality of Life.
Episodic ataxia type 1 (EA1) is a rare autosomal potassium channelopathy, due to mutations in KCNA1. Patients have childhood onset of intermittent attacks of ataxia, dizziness or imbalance. In order to quantify the natural history of EA1, its effect on quality of life and in preparation for future clinical trials, we set up an international multi-centre study of EA1. We recruited thirty-three participants with EA1: twenty-three completed 1-year follow-up and eighteen completed 2-year follow-up. There was very little accumulation of disability or impairment over the course of the 2 years of the study. The outcome measures of ataxia (SARA and functional rating of ataxia) and the activities of daily living scale were largely stable over time. Self-reported health-related quality of life (SF-36) scores were lower across all domains than controls, in keeping with a chronic condition. Physical subdomain scores appeared to deteriorate over time, which seems to be driven by the female participants in the study. This is an interesting finding and warrants further study. Attacks of EA1 reported by participants in real time via an interactive voice response system showed that symptoms were not stereotyped; however, attack duration and frequency was stable between individuals. This large prospective study is the first ever completed in subjects with EA1. We document the natural history of the disorder over 2 years. These data will enable the development of outcome measures for clinical trials of treatment.


Interaction of trans-parinaric acid with phosphatidylcholine bilayers: comparison with the effect of other fluorophores.
The effect of the fluorophore trans-parinaric acid on the structure of lipid bilayer was studied and compared with the effect of other 'perturbants'. These include commonly used fluorophores (diphenylhexatriene, heptadecylhydroxycoumarin, cis-parinaric acid and two fatty acids, palmitic and oleic acids). Differential scanning calorimetry (DSC) and proton nuclear magnetic resonance techniques were used to evaluate structural changes in the lipid bilayers. The thermodynamic parameters of dipalmitoylphosphatidylcholine multilamellar vesicles obtained from the DSC thermograms suggest that trans-parinaric acid differs from the other 'perturbants'. trans-Parinaric acid has the most pronounced impact on the Tm, the width (delta T1/2) and the index of asymmetry of the main gel to liquid crystalline phase transition without any effect on its transition, delta H. The presence of trans-parinaric acid in the lipid bilayer of dimyristoylphosphatidylcholine small unilamellar vesicles influences the chemical shift difference between the choline protons of phosphatidylcholine molecules present in the two leaflets of the vesicle bilayer (delta delta H). This suggests that trans-parinaric acid affects the head group packing in the bilayer. Its main effect is abolishing the major alterations in head group packing that occur through the phase transition. The above data indicate that trans-parinaric acid is concentrated in the gel phase domains, whereby it stabilizes the phase separation between the gel and liquid crystalline phases, probably by affecting lipid molecules present in the boundary regions between these two domain types.


Integration of problem-based learning and innovative technology into a self-care course.
To assess the integration of problem-based learning and technology into a self-care course. Problem-based learning (PBL) activities were developed and implemented in place of lectures in a self-care course. Students used technology, such as computer-generated virtual patients and iPads, during the PBL sessions. Students' scores on post-case quizzes were higher than on pre-case quizzes used to assess baseline knowledge. Student satisfaction with problem-based learning and the use of technology in the course remained consistent throughout the semester. Integrating problem-based learning and technology into a self-care course enabled students to become active learners.


Oxidative-induced calcium mobilization is dependent on annexin VI release from lipid rafts.
Oxidative stress results in macrophage reprogramming through the formation of focal adhesion-like complexes on lipid rafts. Although the cellular mechanisms responsible for this reprogramming remain unknown, oxidative stress is known to result in a transient increase in intracellular calcium. This transient flux is thought to occur through the membrane dissociation of the calcium-bound protein annexin VI. The purpose of this study is to clarify the source of the calcium, and determine if it is responsible for the formation of focal adhesion-like complexes during oxidative stress through the activation of calcium/calmodulin dependent protein kinase II (CaMK II). THP-1 cells were stimulated with hydrogen peroxide. Selected cells were pretreated with methyl beta-cyclodextrin (MbetaCD), a cholesterol-depleting agent; 1,2-bis aminophenoxy ethane-N,N,N',N'-tetraacetic acid, an intracellular calcium chelator; or autocamtide 2-related inhibitory peptide, a CaMK II inhibitor. Intracellular calcium flux was determined by a Fluo-3 technique. Lipid raft and cellular protein were extracted and analyzed for active CaMK II, annexin VI, and components of focal adhesion-like complexes. Hydrogen peroxide exposure led to mobilization of annexin VI from lipid rafts to the cytosol, which was followed by an increase in cytosolic calcium, phosphorylation of CaMK II, and formation of focal adhesion-like complexes. Cholesterol depletion from lipid rafts attenuated all of these effects. 1,2-bis Aminophenoxy ethane-N,N,N',N'-tetraacetic acid and autocamtide 2-related inhibitory peptide pretreatment attenuated CaMK II phopshorylation and formation of focal ahdesionlike complexes. Macrophage reprogramming during oxidative stress occurs through the cytosolic mobilization of annexin VI from lipid rafts. As a result, bound calcium dissociates, resulting in the activation of CaMK II and the formation of focal adhesion-like complexes.


Searching the core of emergency medicine.
The purpose of this study was to test whether focus groups involving medical students, house officers, senior doctors, and nurses could identify an undergraduate emergency medicine core curriculum. From May 2001 to January 2002, we interviewed 12 homogeneous focus groups within all 88 participants. Three focus groups were composed of medical students; three of house officers, three of senior doctors, and three focus groups were composed of nurses. Each interview lasted 2 h. Interviews were recorded, transcribed, and analysed using qualitative methods. The focus groups suggested and discussed in all 196 objectives. Students, physicians, and nurses agreed that newly graduated physicians should master history taking, 21 clinical disorders, 15 practical skills, interpretation of two diagnostic tests, two general diagnostic skills, and two leadership skills. Apart from these 43 core objectives, disagreement was substantial. Participants gave very different priorities to communication, knowledge about clinical disorders, practical clinical skills, leadership, and "the art of medicine". In conclusion, focus groups could identify an emergency medicine core curriculum. However, participants had very different perspectives on the curriculum. Focus groups could be one very practicable part of seeking consensus on what is core and securing local roots and ownership to an undergraduate emergency medicine curriculum before and during implementation.


[Non-operative treatment of thoracolumbar spinal fractures. Long-term clinical results over 16 years].
Non-operative treatment of thoracolumbar fractures remains the standard treatment option for stable and slightly unstable spinal injuries at the level of the lower thoracic and lumbar spine. The purpose of the present retrospective study was to determine the outcome and long-term results of patients treated conservatively using either one of the two major non-operative treatment modalities: (1) functional, or (2) closed reduction and immobilisation by cast. The average follow-up time for the 43 patients reviewed was 16.3 years. They showed a radiologic increase in the average kyphosis angle of 5.2 degrees compared to the time of injury. No difference was noted between early functional therapy and treatment with closed reduction and immobilisation by cast. Patients with initial neurologic impairment showed a significant improvement ( P<0.05) in their neurologic status during the follow-up period. Results of validated psychometric questionnaires (SF-36, FSR, VAS-Spinescore) showed the characteristic pattern of a population with chronic back pain. In conclusion, a radiologic increase in the traumatic kyphotic deformity in patients with a non-operative treatment protocol has to be expected. Measurable negative physical and social long-term consequences can be anticipated after sustaining a type-A fracture of thoracolumbar vertebral bodies. Any correlation between radiologic and functional results has not been observed.


The effects of direct versus witnessed threat on emergency department healthcare workers: implications for PTSD criterion A.
We compared post-traumatic stress disorder (PTSD) symptom severity and symptom cluster profiles in hospital emergency department (ED) medical staff (N=100) who experienced an emotionally distressing work event that presented either a direct threat to themselves or a witnessed threat to patients. The two groups displayed similar levels of PTSD symptoms, however, they differed on symptom profiles and work consequences. The direct threat group experienced significantly greater fear during the event, more ongoing arousal symptoms, and more job dissatisfaction than the witnessed threat group. The witnessed threat group was more likely to appraise their PTSD symptoms as reflecting personal weakness. Overall, the results point to the need for further research to identify distinctive features of responses to different types of traumatic stressors.


Giant Centrifugal and Necrotizing Cutaneous Metastases of Melanoma: A Brief Review of the Literature and a Case Report.
Melanoma is a neoplasm derived from melanocytes of the skin and other sites. In the natural history of melanoma, cutaneous metastases occur relatively frequently and can arise in early or late stages of the disease. Melanoma skin metastases have a variable appearance. Several clinical appearances are described in the literature. We describe an unusual clinical pattern of cutaneous melanoma metastasis, defined as giant, centrifugal, and necrotizing, and we provide a brief review of the literature.


Variations in Use of Diabetes Drugs With Cardiovascular Benefits Among Medicaid Patients.
Cardiovascular death remains the leading cause of mortality in patients with type 2 diabetes (T2D). A better understanding of the current use and adoption of glucose-lowering drugs with cardiovascular benefit can inform state policies to ensure their appropriate use in patients with T2D. To characterize the use of glucose-lowering agents with known cardiovascular benefit over time and across states. This cross-sectional pharmacoepidemiological study of Medicaid prescription rates of glucose-lowering agents with known cardiovascular benefit vs those with less well-established cardiovascular benefit was conducted between 2014 and 2019. In 50 states and the District of Columbia, the study focused on nonmetformin, noninsulin glucose-lowering drugs divided into 3 cohorts: (1) sodium-glucose cotransporter 2 (SGLT2) inhibitors, (2) glucagon-like peptide 1 (GLP1) receptor agonists, and (3) all other classes of glucose-lowering drugs. Data were analyzed from January 2014 to December 2019. Number of days supplied of each cohort, use ratios between the aggregated days supplied of glucose-lowering agents with known cardiovascular benefit vs those with less well-established cardiovascular benefit, and the mean change in use ratios per quarter. Across the 50 states and the District of Columbia, the use ratio of glucose-lowering agents with known cardiovascular benefit ranged from 1.58 to 0.14 (mean [SD], 0.48 [0.27]) in 2019. A lower use ratio was seen in states with a higher prevalence of diabetes (β = -0.049; 95% CI, -0.086 to -0.012; P = .01), a larger total population (β = -0.013; 95% CI, -0.023 to -0.003; P = .01), a greater number of Medicaid enrollees (β = -0.054; 95% CI, -0.096 to -0.014; P = .01), a greater proportion of people enrolled in Medicaid (β = -0.018; 95% CI, -0.030 to -0.007; P = .002), and a greater proportion of Medicaid patients enrolled in managed care organizations (β = -0.0032; 95% CI, -0.0051 to -0.0013; P = .002). Higher Medicaid expenditures per enrollee (β = 0.047; 95% CI, 0.007 to 0.089; P = .03) were associated with a higher use ratio of these agents. The relative use of glucose-lowering agents with known cardiovascular benefit by Medicaid enrollees increased 7.4% per year from 2014 to 2019, with wide variations across state Medicaid programs. In this cross-sectional study, glucose-lowering agents with cardiovascular benefit increased in use during the study period, but also demonstrated considerable variation among states in their relative use. Medicaid programs should try to clarify which factors may be contributing to relative underuse of these potentially life-saving drugs.


[Protein kinase C in eosinophil proliferation and infiltration in nasal polyp tissue].
To explore the significance of protein kinase C (PKC) in eosinophil (EOS) proliferation and infiltration in nasal polyp tissues. With the methods of in situ hybridization and immunohistochemistry staining, PKC and apoptosis gene (Bcl-2, Bax) expression were measured between nasal polyps from 26 patients and inferior turbinate mucous membrane tissue (ITMMT) from 20 normal persons. EOS was identified with May-Grünwald-Giemsa (MGG) staining. In EOS, the positive cell expressive rate of Bcl-2 mRNA and its protein were significantly higher in group of nasal polyps than that in group of ITMMT (P < 0.01). Although the positive cell expressive rate of Bax mRNA and its protein were slightly higher in group of nasal polyp tissue than that in group of ITMMT, the difference was not significant (P > 0.05). PKC was expressed in EOS of all 26 cases from nasal polyp tissues, but in 20 cases from ITMMT, only 7 cases showed occasional PKC expression. In both groups, PKC positive cell expression was significantly different, and the expression of PKC and Bcl-2 mRNA as well as their protein in EOS of nasal polyps showed remarkably positive relation (r1 = 0.0875, r2 = 0.0823, P < 0.01). PKC expression increasing in EOS of nasal polyp tissues was closely associated with apoptosis inhibiting. So we presumed that EOS inhibiting in nasal polyp tissues was obtained by activating PKC signal transduction pathway.


Acceptance, Usability and Health Applications of Virtual Worlds by Older Adults: A Feasibility Study.
Virtual worlds allow users to communicate and interact across various environments, scenarios, and platforms. Virtual worlds present opportunities in health care to reduce the burden of illness and disability by supporting education, rehabilitation, self-management, and social networking. The application of virtual worlds to older adults who bear the burden and cost of health conditions associated with age has not been evaluated. The aim of this study is to explore the usability, ease of use, and enjoyment of a virtual world by older adults, the types of virtual world activities that older adults may engage in, and the perceptions of older adults regarding the application of virtual worlds in health care. This quasi-experimental pre-post design research was guided by the Technology Acceptance Model (TAM). Participants were recruited from a Lifelong Learning Institute (LLI) program at Nova Southeastern University. Participants attended four training sessions over a 5-week period in the Second Life (SL) virtual world. Subjects were surveyed before and after the training on perceived ease of use, attitudes towards technology, behavioral intention to use the system, facilitating conditions, effort expectancy, and self-efficacy. Older adults (N=19) completed the informed consent and attended the first training session, and 11 participants (58%, 11/19) completed the full training and the post survey. Completers (82%, 9/11) were more likely than non-completers (37%, 3/8) to consider themselves technologically savvy (P=.048), and to express confidence in being able to use the virtual world (100%, 11/11 vs 37%, 3/8; P=.002). All completers (100%, 11/11) perceived that SL has application in health behaviors and disease and reducing social isolation among people who are homebound. Of the completers, 10 (91%, 10/11) responded that they enjoyed learning how to use SL. Completers suggested that future trainings include more assistants and smaller groups. This pilot study suggests that virtual worlds can be both a feasible and an applicable method to promote health among some seniors. Future research on virtual worlds with older populations should consider using state-of-the art technology including large monitors, providing a minimum of one trainer for every two to three participants, and distributing a comprehensive training manual at the start of the training to support organization and recall.


[Long-term follow-up of tympanoplasty using a ceravital prosthesis for the middle ear].
An 8-year follow-up of Ceravital middle ear prostheses showed an extremely good tolerance in the middle ear space. Incompatibility phenomena were not observed. Inflammatory reactions were neither caused nor supported by the implants. The implantation was always performed without interposition of cartilage. Extrusions were not observed. Long-lasting inflammatory processes destroy implants in the same way as they affect ossicles. Transient inflammatory periods (e.g. in the early postoperative period, POM) do not lead to any remarkable changes of the implant surface. In healthy middle ears, the hearing results are stable.


[Demonstration of hepatitis A virus in the feces].
On the basis of own examinations methodology and results of the demonstration of the virus A in the stools and of the proof of antibodies in the serum are described. The parameters of the virus-A-hepatitis which are important for practice are further the basis for diagnosis, therapy and surrounding prophylaxis in routine work. They were compiled in a table.


Amino-acid and glucose utilization of Leishmania donovani and L. braziliensis.
The availability of a defined medium (STEIGER & STEIGER, 1976) has enabled studies on the nutritional requirements of promastigotes of L. donovani and L. braziliensis (STEIGER & STEIGER, 1977). As outlined elsewhere (STEIGER & MESHNICK, 1977), the present paper describes preliminary experiments dealing with the utilization of amino-acids and glucose by these two Leishmania species. The data are compared to those obtained with Trypanosoma (CROSS et al., 1975a,b; BRUN & JENNI, 1977) and are discussed in relation to the nutrition of Leishmania.


Prevalence of microembolic signals in patients with different types of mono-leaflet and bi-leaflet prosthetic heart valves.
Microembolic signals (MES) have been described in patients with different types of prosthetic valves. The aim of our study was to compare prevalence of MES in patients with mono-leaflet and bi-leaflet valves, and to correlate them with different clinical and echocardiographic parameters. We evaluated 42 patients, 15 with mono-leaflet and 27 with bi-leaflet valves, with 30-minute bilateral simultaneous transcranial Doppler monitoring for the identification of MES. All patients performed blood testing for international normalized ratio (INR), color-coded duplex of supra-aortic vessels, and echocardiography. Eighteen patients (43%) showed MES; 61% of MES were detected bilaterally, 17% only on the left and 22% only on the right middle cerebral artery (MCA), with no interhemispheric difference. MES did not correlate with patient's age, echocardiographic parameters, INR, presence of atrial fibrillation, or site of valve replacement. One (7%) of the 15 patients with mono-leaflet valves had MES, as opposed to 17 (63%) of the 27 with bileaflet valves (p=0.0003). Patients with bileaflet valves and MES had valves of older implantation and, only for aortic valves, larger valve size.


Two-three-year stability and interrelations of bulimotypic indicators and depressive and anxious symptoms in middle-aged women.
There is a paucity of research examining eating disorder symptoms among middle-aged women. This prospective study assessed the stability of bulimic symptoms and 5 associated variables (perfectionism, depressive symptoms, self-esteem, anxiety symptoms, and perceived weight status) in a sample of 150 middle-aged women (mean age = 45.19 years) over a 2.5-year time period. In addition, interrelations among bulimic, anxiety, and depressive symptoms were assessed. Results suggested that all 6 bulimia-related variables remained significantly stable over 2.5 years. In addition, notable relations between Time 1 and Time 2 variables emerged (e.g., anxious symptoms at Time 1 predicted bulimic symptoms at Time 2). Thus, the results indicate that bulimic symptoms exist in middle-aged women, and that they remain relatively stable over a 2.5-year time period. Clinical implications for middle-aged women with eating disorder symptoms are discussed.


The formation and final structure of the oocyst wall of Eimeria acervulina: a transmission and scanning electron microscope study.
The formation and final structure of the oocyst wall of Eimeria acervulina is described, based on a detailed electron microscope study of the maturing oocysts. After fertilization of the macrogametocyte the wall-forming bodies of type I progressively undergo disaggregation into smaller bodies and eventually move into spaces left by the pellicular membranes of the zygote, which simultaneously separate and elevate away from the zygote cytoplasm to form the outer layer of the oocyst wall. A newly formed membrane separates this layer from the cytoplasm. Following the formation of the outer layer, another membrane separates and elevates away from the cytoplasm, and the wall-forming bodies of type II, which by now have migrated to the periphery, move into the spaces and fuse together to form the inner layer of the oocyst wall. A newly formed membrane separates this layer from the cytoplasm. The wall of the young oocyst thus consists of two membrane-bound layers of approximately similar thickness; the outer layer being osmiophilic whilst the inner one is paler. An overlaying membrane covers the oocyst. The surface of the oocyst wall was smooth in appearance when viewed with the scanning electron microscope.


Determination of purine nucleosides and their bases by high-performance liquid chromatography using co-immobilized enzyme reactors.
A selective and sensitive assay of inosine, guanosine, hypoxanthine, guanine and xanthine by high-performance liquid chromatography with immobilized enzyme reactors was developed. The separation was achieved on a Capcell Pak C18 column (15 cm x 0.46 cm I.D.) with a mobile phase of 0.1 M phosphate buffer (pH 8.0) containing 7 mM sodium 1-hexanesulphonate and 0.1 mM p-hydroxyphenylacetic acid. The fluorimetric detection of hydrogen peroxide using immobilized peroxidase and p-hydroxyphenylacetic acid was applied to the assay of these compounds, which were oxidized to yield hydrogen peroxide in the presence of immobilized enzyme (purine nucleoside phosphorylase, guanase and xanthine oxidase). Enzyme reactions occurred sufficiently without post-column addition of reagents. Enzymes that catalysed the conversion of purine compounds were co-immobilized on aminopropyl controlled-pore glass packed in stainless-steel tubing. The detection limits were 30-200 pg per injection.


Piperidine: a microelectrophoretic study in the mammalian brain.
Using unit recording and electrophoretic techniques, the action of piperidine on unit activity of the brain of the rat was studied. Piperidine excited 31%, and inhibited 4% of cortical cells tested. In the hippocampus and caudate nucleus, piperidine excited larger proportions of the cells tested. The actions of piperidine were blocked by tetraethylammonium but not by scopolamine.


Cutaneous horn occurring on the vermilion border of the lower lip.
A case of cutaneous horn of the lower lip is presented. The paper highlights the need for careful management of such lesions due to the high incidence of malignant or premalignant histology.


Mitochondrial diversity and phylogeographic structure of Chinese domestic goats.
China has numerous native domestic goat breeds, but so far there has been no extensive study on genetic diversity, population demographic history, and origin of Chinese goats. Here, we examined the genetic diversity and phylogeographic structure of Chinese domestic goats by determining a 481-bp fragment of the first hypervariable region of mitochondrial DNA (mtDNA) control region from 368 individuals representing 18 indigenous breeds. Phylogenetic analyses revealed that there were four mtDNA lineages (A-D) identified in Chinese goats, in which lineage A was predominant, lineage B was moderate, and lineages C and D were at low frequency. These results further support the multiple maternal origins of domestic goats. The pattern of genetic variation in goat mtDNA sequences indicated that the two larger lineages A and B had undergone population expansion events. In a combined analysis of previously reported sequences and our sequences belonging to lineage B, we detected two subclades, in which one was unique to eastern Asia and another was shared between eastern and southern Asia. A larger genetic variation in eastern Asia than southern Asia and the pattern of phylogeographic variation in lineage B suggest that at least one subclade of lineage B originated from eastern Asia. There was no significant geographical structuring in Chinese goat populations, which suggested that there existed strong gene flow among goat populations caused by extensive transportation of goats in history.


Anaesthetic implications of the trismus pseudocamptodactyly (Dutch-Kentucky or Hecht Beals) syndrome.
The trismus pseudocamptodactyly syndrome is a relatively rare, autosomal dominant condition first described in 1969. Affected patients classically present with two main features: limited excursion of the mandible and flexion deformity of the fingers that occurs with wrist extension (pseudocamptodactyly). Foot deformities and a shorter-than-normal stature may also be present. The underlying abnormality is short muscle tendon units, which prevent normal growth and development. We reviewed the anaesthetic experience in three paediatric patients with the trismus pseudocamptodactyly syndrome and the pertinent clinical findings in three other members of the same family, spanning three generations. Limited mandible excursion was present in all six cases, but was not obvious preoperatively in the patients because of its subtle presentation. All three cases were successfully managed using mask anaesthesia with spontaneous ventilation, avoiding muscle relaxants. Attempts to visualize the larynx under anaesthesia were unsuccessful in two cases. Blind nasotracheal intubation was successful in one patient. Postoperatively, there were no problems with the airway.


MicroRNA-181a-mediated downregulation of AC9 protein decreases intracellular cAMP level and inhibits ATRA-induced APL cell differentiation.
AC9 is one of the adenylate cyclase (AC) isoforms, which catalyze the conversion of ATP to cAMP, an important second messenger. We previously found that the integration of cAMP/PKA pathway with nuclear receptor-mediated signaling was required during all-trans retinoic acid (ATRA)-induced maturation of acute promyelocytic leukemia (APL) cells. Here we showed that AC9 could affect intracellular cAMP level and enhance the trans-activity of retinoic acid receptor. Knockdown of AC9 in APL cell line NB4 could obviously inhibit ATRA-induced differentiation. We also demonstrated that miR-181a could decrease AC9 expression by targeting 3'UTR of AC9 mRNA, finally controlling the production of intracellular cAMP. The expression of miR-181a itself could be inhibited by CEBPα, probably accounting for the differential expression of miR-181a in NB4 and ATRA-resistant NB4-R1 cells. Moreover, we found that AC9 expression was relatively lower in newly diagnosed or relapsed APL patients than in both complete remission and non-leukemia cases, closely correlating with the leukemogenesis of APL. Taken together, our studies revealed for the first time the importance of miR-181a-mediated AC9 downregulation in APL. We also suggested the potential value of AC9 as a biomarker in the clinical diagnosis and treatment of leukemia.


Antithrombotic drugs are risk factors for delayed postoperative bleeding after endoscopic submucosal dissection for gastric neoplasms.
The discontinuation of antithrombotic drugs is recommended during endoscopic submucosal dissection (ESD) for gastric neoplasms; however, controversy remains as to whether antithrombotic drugs are risk factors for postoperative bleeding. To determine the risk factors for post-ESD bleeding. Single-institution, retrospective review. University hospital. From June 2000 to December 2010, we treated 1192 gastric neoplasms in 1032 consecutive patients. The ESD procedures were performed by using the standard techniques. Antithrombotic drug therapy was principally interrupted preoperatively and was restarted when hemostasis was confirmed by second-look endoscopy. Risk factors for postoperative bleeding after ESD (early, delayed, and overall [combined] occurrence of bleeding during the first 5 postoperative days or thereafter) were analyzed by using logistic regression analysis. Among 1166 ESD-induced ulcer lesions, overall postoperative bleeding was evident in 62 lesions (5.3%); early and delayed bleeding occurred in 30 and 32 lesions (2.6% and 2.7%), respectively. Based on a multivariate analysis, a specimen size of >40 mm was the sole independent risk factor for overall bleeding. Moreover, oral antithrombotic drug therapy was selected as independent risk factor for delayed but not early bleeding, according to the multivariate analysis. The delayed bleeding rate in patients who had a specimen size of >40 mm and who used antithrombotic drugs was 11.6%. Retrospective design and single-site data collection. Interruption of antithrombotic drug therapy may be adequate for preventing early post-ESD bleeding; however, reinitiating antithrombotic drug therapy is a significant independent risk factor for delayed post-ESD bleeding.


PYloroplasty versus No Intervention in GAstric REmnant REconstruction after Oesophagectomy: study protocol for the PYNI-GAREREO phase III randomized controlled trial.
After esophagectomy for esophageal and esophagogastric cancer, more than half of patients have lost > 10% of their body weight at 12 months. In most cases, the gastric remnant is used for reconstruction after esophagectomy. One of the most serious nutritional complications of this technique is delayed gastric emptying caused by gastric remnant mobilization and denervation of the vagus nerve. The aim of the PYloroplasty versus No Intervention in GAstric REmnant REconstruction after Oesophagectomy (PYNI-GAREREO) trial is to analyze the clinical outcome of modified Horsley pyloroplasty (mH-P) as a method of preventing delayed gastric emptying. The PYNI-GAREREO trial is designed as an open randomized, single-center superiority trial. Patients will be randomly allocated to undergo gastric remnant reconstruction with mH-P (intervention group) or no intervention (control group) in parallel groups. All patients with esophageal cancer or esophagogastric cancer planning to undergo curative minimally invasive esophagectomy will be considered for inclusion. A total of 140 patients will be included in the study and randomized between the groups in a 1:1 ratio. The primary outcome is the body weight change at 6 months postoperatively, and the secondary outcomes are the nutritional status, postoperative complications, functional outcome, and quality of life until 1 year postoperatively. We hypothesize that mH-P after minimally invasive esophagectomy more effectively maintains patients' nutritional status than no pyloroplasty. UMIN Clinical Trials Registry UMIN000045104. Registered on 25 August 2021. https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000051346 .


Successful Treatment of Near Fatal Cardiogenic Shock Following Toxic Mushroom Ingestion.
Myocardial injury and hemodynamic compromise following toxic mushroom ingestion is rare. Here we present a case of cardiogenic shock after Amanita proxima ingestion, presenting with severe hemodynamic collapse necessitating mechanical circulatory support. Prompt identification, multidisciplinary clinical decision making, and timely treatment resulted in an outstanding complete clinical resolution. (Level of Difficulty: Intermediate.).


A subtype of multiple sclerosis defined by an activated immune defense program.
Given the heterogeneous nature of multiple sclerosis (MS), we applied DNA microarray technology to determine whether variability is reflected in peripheral blood (PB) cells. In this study, we studied whole-blood gene expression profiles of 29 patients with relapsing-remitting MS (RRMS) and 25 age- and sex-matched healthy controls. We used microarrays with a complexity of 43K cDNAs. The data were analyzed using sophisticated pathway-level analysis in order to provide insight into the deregulated peripheral immune response programs in MS. We found a remarkable elevated expression of a spectrum of genes known to be involved in immune defense in the PB of MS patients compared to healthy individuals. Cluster analysis revealed that the increased expression of these genes was characteristic for approximately half of the patients. In addition, the gene signature in this group of patients was comparable with a virus response program. We conclude that the transcriptional signature of the PB cells reflects the heterogeneity of MS and defines a sub-population of RRMS patients, who exhibit an activated immune defense program that resembles a virus response program, which is supportive for a link between viruses and MS.


In situ hybridization study of vascular cell adhesion molecule-1 messenger RNA expression in rheumatoid synovium.
Upregulation of vascular cell adhesion molecule-1 (VCAM-1) has been implicated in various pathological conditions. In this study, we used in situ hybridization to determine the cell types expressing VCAM-1 mRNA in rheumatoid synovium. Synovial tissues from seven rheumatoid arthritis (RA) and four osteoarthritis (OA) patients were examined for VCAM-1 mRNA expression. In situ hybridization as well as immunohistochemical analysis showed that VCAM-1 expression was mainly localized to the hyperplastic synovial lining cells and to a lesser extent endothelial cells and synovial fibroblasts in rheumatoid synovium. VCAM-1 expression in OA is less prominent. Hyperplastic synovial lining cells expressing VCAM-1 were mainly CD13+, CD14+, CD33+ and HLA-DR+. Together with morphological features, this suggests that they are type A macrophage-like synovial cells. Our findings indicate that overexpression of VCAM-1 may contribute to the formation of hyperplastic lining layers in the synovium seen in this disorder.


Coexistence of carriers for dopamine and GABA uptake on a same nerve terminal in the rat brain.
The ability of gamma-aminobutyric acid (GABA) to affect the release of [3H]-dopamine in rat brain synaptosomes prepared from corpus striatum, frontal cortex and hypothalamus and prelabelled with the radioactive catecholamine in the presence of desipramine was examined. GABA (10-300 microM) increased in a concentration-dependent way the basal release of [3H]-dopamine from striatum and cortical synaptosomes; however, its effect was much less pronounced in hypothalamic nerve terminals. 2,4-Diaminobutyric acid (DABA) mimicked GABA although less potently. Neutral amino acids such as leucine, valine or alpha-aminoisobutyric acid (100-300 microM) did not affect or increased minimally the release of [3H]-dopamine. The GABA-induced [3H]-dopamine release was not prevented by the GABAA-receptor antagonists, bicuculline or picrotoxin. The GABAA-receptor agonist, muscimol (10-300 microM), displayed only a very weak, not significant, enhancing effect on [3H]-dopamine release. The GABAB-receptor agonist (-)-baclofen (100 or 300 microM) had no effect. Three novel and selective inhibitors of GABA uptake, N-(4,4-diphenyl-3-butenyl)-nipecotic acid (SK&F 89976A), N-(4,4-diphenyl-3-butenyl)-guvacine (SK&F 100330A) and N-(4,4-diphenyl-3-butenyl)-homo-beta-proline (SK&F 100561) potently counteracted the enhancing effect of GABA on [3H]-dopamine release. Nipecotic acid also reduced the effect of GABA. It is concluded that carriers for the uptake of dopamine and GABA may coexist on the same nerve terminal in the rat brain.


Alterations in reward, fear and safety cue discrimination after inactivation of the rat prelimbic and infralimbic cortices.
Accurate discrimination of environmental cues predicting reward, fear, or safety is important for survival. The prelimbic and infralimbic cortices are implicated in regulating reward-seeking and fear behaviors; however, no studies have examined their roles in discriminating among reward, fear, and safety cues. Using a discriminative conditioning task that includes presentations of a reward cue (paired with a reward pellet), fear cue (paired with footshock), and a compound fear+safety cue (no footshock) within the same sessions allowed us to assess the flexibility and precision of fear and reward-seeking behaviors to these cues. We found that fear behavior was appropriately limited to the fear cue in untreated rats, but during infralimbic cortical inactivation, similar levels of fear were seen to the fear and compound fear+safety cues. Reward-seeking behavior was also appropriately limited to the reward cue in untreated rats. Inactivating the prelimbic cortex altered discriminative reward seeking as rats with prelimbic inactivation did not increase their reward seeking behavior during the reward cue to the same degree as saline controls. Our results imply dissociable roles of the two cortical regions: the prelimbic cortex in precise discriminative reward seeking and the infralimbic cortex in discriminating between fear and safety cues. These data suggest that alterations in the balance of activity between areas homologous to the prelimbic and infralimbic cortices may be involved in the processes that go awry in anxiety and addiction disorders.


Evaluating interhemispheric cortical responses to transcranial magnetic stimulation in chronic stroke: A TMS-EEG investigation.
TMS-evoked cortical responses can be measured using simultaneous electroencephalography (TMS-EEG) to directly quantify cortical connectivity in the human brain. The purpose of this study was to evaluate interhemispheric cortical connectivity between the primary motor cortices (M1s) in participants with chronic stroke and controls using TMS-EEG. Ten participants with chronic stroke and four controls were tested. TMS-evoked responses were recorded at rest and during a typical TMS assessment of transcallosal inhibition (TCI). EEG recordings from peri-central gyral electrodes (C3 and C4) were evaluated using imaginary phase coherence (IPC) analyses to quantify levels of effective interhemispheric connectivity. Significantly increased TMS-evoked beta (15-30Hz frequency range) IPC was observed in the stroke group during ipsilesional M1 stimulation compared to controls during TCI assessment but not at rest. TMS-evoked beta IPC values were associated with TMS measures of transcallosal inhibition across groups. These results suggest TMS-evoked EEG responses can index abnormal effective interhemispheric connectivity in chronic stroke.


The distribution of myelin-associated glycoprotein and myelin basic protein in actively demyelinating multiple sclerosis lesions.
Active plaques from 4 patients with multiple sclerosis were examined for myelin-associated glycoprotein (MAG) and myelin basic protein (MBP) using the peroxidase-antiperoxidase (PAP) immunocytochemical procedure applied to paraffin sections. MBP loss was intimately related to the presence of infiltrating macrophages which appeared to remove MBP-positive fragments directly off intact myelin sheaths. Phagocytosis of MAG-positive myelin sheaths was also observed. These findings support previous morphological studies that suggest that phagocytosis by macrophages of myelin attached to axons is an important mechanism of demyelination in multiple sclerosis.


The improvement of maintenance conditions for wild-caught Chrysops silacea and the production of infective larvae of Loa loa.
Previous reports have shown that Chyrsops silacea survive poorly in captivity. Only 5% survive for more than 12 days, which is the time required for Loa loa microfilariae to develop into infective larvae. Improved maintenance conditions for C. silacea for the production of infective larvae were studied. Wild-caught female C. silacea were allowed to feed to repletion on mandrills, (Mandrillus sphinx), which were microfilaremic with human L. loa or on uninfected laboratory rats. Under optimal conditions 30-50% of flies engorged. The survival rates of fed and unfed flies were compared under a variety of conditions. Survival rates varied considerably under the various maintenance conditions. Ingestion of either rat or mandrill blood made no significant difference to fly survival. Optimal conditions were found to be as follows: one to two flies per sterilized jar with damp sand, constant access to sterilized 10% sucrose, a temperature of 23-29 degrees C and 84-98% relative humidity. Under these conditions 42% of the flies survived until day 12, when maximal numbers of infective larvae were present in the head.


Two novel flavi-like viruses shed light on the plant-infecting koshoviruses.
The family Flaviviridae is composed of viruses with a positive-sense single-stranded RNA genome and includes viruses that are important veterinary and human pathogens. Most members of the family are arthropod- and vertebrate-infecting viruses, but more recently, divergent flavi-like viruses have been identified in marine invertebrate and vertebrate hosts. The striking discovery of gentian Kobu-sho-associated virus (GKaV), along with a recent report of a related virus from carrot, has expanded the known host range of flavi-like viruses to plants, suggesting they could be grouped in a proposed genus tentatively named "Koshovirus". Here, we report the identification and characterization of two novel RNA viruses that show a genetic and evolutionary relationship to the previously identified "koshoviruses". Their genome sequences were obtained from transcriptomic datasets of the flowering plants Coptis teeta and Sonchus asper. These two new viruses, which we have named "coptis flavi-like virus 1" (CopFLV1) and "sonchus flavi-like virus 1" (SonFLV1), are members of novel species characterized by the longest monopartite RNA genome observed so far among plant-associated RNA viruses, which is ca. 24 kb in size. Structural and functional annotations of the polyproteins of all koshoviruses resulted in the detection not only of the expected helicase and RNA-dependent RNA polymerase but also of several additional divergent domains, including AlkB oxygenase, trypsin-like serine protease, methyltransferase, and envelope E1 flavi-like domains. Phylogenetic analysis showed that CopFLV1, SonFLV1, GKaV, and the carrot flavi-like virus were grouped together in a monophyletic clade, strongly supporting the recent proposal for creation of the genus "Koshovirus" for the group of related plant-infecting flavi-like viruses.


Changes in T2 relaxation time after stroke reflect clearing processes.
CT and MR imaging techniques are frequently used for the diagnosis and progress monitoring of ischemic stroke in clinical practice and research. After stroke, both methods are characterized by a transient pseudo-normalized imaging signal, the so-called fogging phenomenon. This study evaluates potential pathophysiological changes associated with fogging, as well as its influence on the correct determination of the ischemic lesion in a rat stroke model. Male spontaneously hypertensive rats were subjected to permanent middle cerebral artery occlusion. Ischemic lesion volume, brain edema and gray scale value spread within the ischemic lesion were determined on T2-weighted MR sequences at days 1, 4, 8, 11 and 29 after stroke onset, and compared with immunohistochemistry for astrogliosis, microglia/macrophage infiltration and angiogenesis. All animals showed MR fogging at days 4, 8 and 11 after stroke. The transient normalization of T2 signals occurred independently from the development of infarct volumes, but coincided well with the spatio-temporal occurrence of necrosis, angiogenesis and microglia/macrophage infiltration. Our results suggest that the fogging effect reflects the clearance of necrotic tissue within the ischemic lesion and is thus not relevant for the determination of the lesion volume.


Comparison of tibial plateau angles in dogs with unilateral versus bilateral cranial cruciate ligament rupture: 150 cases (2000-2006).
To compare tibial plateau angle (TPA) in dogs with unilateral versus bilateral cranial cruciate ligament (CCL) rupture, to compare right versus left TPA in dogs with bilateral CCL rupture, and to determine whether TPA can be used to predict whether a dog with unilateral CCL rupture would subsequently rupture the contralateral CCL. Retrospective case series. 150 dogs with unilateral (n=58) or bilateral (92) CCL rupture. Medical records were reviewed and TPA was recorded. Dogs with unilateral CCL rupture that were not known to have ruptured the contralateral ligament were followed up for a minimum of 2 years. Dogs with unilateral CCL rupture were significantly older (median, 7.0 years) than dogs with bilateral CCL rupture (median, 4.5 years). Median TPA for dogs with unilateral CCL rupture (26 degrees) was not significantly different from median TPA for dogs with bilateral rupture (27 degrees in both the right and left limbs), and right and left TPAs were not significantly different in dogs with bilateral CCL rupture. There was no correlation between TPA and the time interval between diagnosis of the initial and subsequent CCL ruptures in dogs with bilateral CCL rupture. Results suggested that TPA in the range studied (mostly<35 degrees) was not a useful predictor of contralateral CCL rupture among dogs with unilateral CCL rupture, although age may be a risk factor for development of bilateral CCL rupture. The incidence of bilateral CCL rupture may be higher than previously reported.


Controlled synthesis of Mn₂O₃ nanowires by hydrothermal method and their bactericidal and cytotoxic impact: a promising future material.
Mn₂O₃ nanowires with diameter ~70 nm were synthesized by a simple hydrothermal method using Mn(II) nitrate as precursor. X-ray diffraction, field emission scanning electron microscopy, transmission electron microscopy (TEM), and energy dispersive X-ray spectroscopy techniques were employed to study structural features and chemical composition of the synthesized nanowires. A biological evaluation of the antimicrobial activity and cytotoxicity of Mn₂O₃ nanowires was carried out using Escherichia coli and mouse myoblast C₂C₁₂ cells as model organism and cell lines, respectively. The antibacterial activity and the acting mechanism of Mn₂O₃ nanowires were investigated by using growth inhibition studies and analyzing the morphology of the bacterial cells following the treatment with nanowires. These results suggest that the pH is critical factor affecting the morphology and production of the Mn₂O₃ nanowires. Method developed in the present study provided optimum production of Mn₂O₃ nanowires at pH ~ 9. The Mn₂O₃ nanowires showed significant antibacterial activity against the E. coli strain, and the lowest concentration of Mn₂O₃ nanowires solution inhibiting the growth of E. coli was found to be 12.5 μg/ml. TEM analysis demonstrated that the exposure of the selected microbial strains to the nanowires led to disruption of the cell membranes and leakage of the internal contents. Furthermore, the cytotoxicity results showed that the inhibition of C₂C₁₂ increases with the increase in concentration of Mn₂O₃ nanowires. Our results for the first time highlight the cytotoxic and bactericidal potential of Mn₂O₃ nanowires which can be utilized for various biomedical applications.


Combined virtual reality and haptic robotics induce space and movement invariant sensorimotor adaptation.
Prism adaptation is a method for studying visuomotor plasticity in healthy individuals, as well as for rehabilitating patients suffering spatial neglect. We developed a new set-up based on virtual-reality (VR) and haptic-robotics allowing us to induce sensorimotor adaptation and to reproduce the effect of prism adaptation in a more ecologically valid, yet experimentally controlled context. Participants were exposed to an immersive VR environment while controlling a virtual hand via a robotic-haptic device to reach virtual objects. During training, a rotational shift was induced between the position of the participant's real hand and that of the virtual hand in order to trigger sensorimotor recalibration. The use of VR and haptic-robotics allowed us to simulate and test multiple components of sensorimotor adaptation: training either peripersonal or extrapersonal space and testing generalization for the non-trained sector of space, and using active versus robot-guided reaching movements. Results from 60 neurologically intact participants show that participants exposed to the virtual shift were able to quickly adapt their reaching movements to aim correctly at the target objects. When the shift was removed, participants showed a systematic deviation of their movements during open-loop tasks in the direction opposite to that of the shift, which generalized to un-trained portions of space and occurred also when their movements were robotically-guided during the adaptation. Interestingly, follow-up questionnaires revealed that when the adaptation training was robotically-guided, participants were largely unaware of the mismatch between their hand and the virtual hand's position. The stability of the aftereffects, despite the changing experimental parameters, suggests that the induced sensory-motor adaptation does not rely on low-level processing of sensory stimuli during the training, but taps into high-level representations of space. Importantly, the flexibility of the trained space and the option of robotically-guided movements open novel possibilities of fine-tuning the training to patients' level of spatial and motor impairment, thus possibly resulting in a better outcome.


The changing pattern of bronchial carcinoma.
The figures for the incidence of bronchial carcinoma have been monitored in various age groups and in both sexes since 1975 when a previous paper on the subject was published. These figures are available up to 1983. The total incidence of bronchial carcinoma in men started to fall after 1974, while in women it is still rising. The incidence amongst men up to the age of 59 started to fall after 1960; in women, this occurred 20 years later, and it has fallen in the 60-64 age group since 1982. The incidence is still rising in older women, but is falling in all groups of men up to the age of 80. Thus the trend seen amongst the men in 1975 seems to be being repeated amongst the women. The fall in the incidence of bronchial cancer has occurred amongst the group of women who have smoked more than any of their predecessors. Some possible reasons for this surprising finding are discussed.


Improved lung function following dietary antioxidant supplementation in exercise-induced asthmatics.
Oxidative stress is a characteristic of exercise-induced asthma (EIA), however antioxidant supplementation may attenuate EIA. The purpose of this study was to determine if ascorbic (AsA) and α-tocopherol supplementation would improve airway function in subjects with EIA. A single-blind randomized crossover design with eight clinically diagnosed EIA subjects (22.0 ± 0.7 year) and five healthy control subjects (28.2 ± 1.4 year) was used. Subjects consumed vitamins (V) (AsA 500 mg; α-tocopherol 300 IU) or placebo (PLA) daily for three weeks, followed by a three week washout period and then three weeks of the alternative treatment. Ten-minute treadmill tests (90% VO2peak) were performed with pulmonary function testing (forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and between 25 and 75% (FEF25-75%), and peak expiratory flow rates (PEFR)) measured pre-exercise and 1, 5, 15, and 30 min post-exercise. Supplementation led to significant improvements at minute 5 and minute 15 in FVC; FEV1; PERF; FEF25-75% and minute 30 in FEV1 and FEF25-75% post-exercise. AsA and α-tocopherol may aid the recovery of pulmonary function in subjects with EIA.


CryoEM structure of the outer membrane secretin channel pIV from the f1 filamentous bacteriophage.
The Ff family of filamentous bacteriophages infect gram-negative bacteria, but do not cause lysis of their host cell. Instead, new virions are extruded via the phage-encoded pIV protein, which has homology with bacterial secretins. Here, we determine the structure of pIV from the f1 filamentous bacteriophage at 2.7 Å resolution by cryo-electron microscopy, the first near-atomic structure of a phage secretin. Fifteen f1 pIV subunits assemble to form a gated channel in the bacterial outer membrane, with associated soluble domains projecting into the periplasm. We model channel opening and propose a mechanism for phage egress. By single-cell microfluidics experiments, we demonstrate the potential for secretins such as pIV to be used as adjuvants to increase the uptake and efficacy of antibiotics in bacteria. Finally, we compare the f1 pIV structure to its homologues to reveal similarities and differences between phage and bacterial secretins.


Cochlear implants in the forensic identification process.
Decedents who are severely decomposed, skeletonized or incinerated present challenges for identification. Cochlear implants aid hearing and bear unique serial numbers that can be used to assist with identification of bodies that are not visually identifiable. The purpose of this paper was to highlight companies that have or had manufactured cochlear type implants and demonstrate the appearance of the implants to assist crime scene investigators, pathologists, anthropologists and odontologists. Investigation of cochlear implants was conducted on the internet and companies were contacted for information regarding their implants. The functional appearance of a cochlear implant is explained, brands of implants are tabulated and pre and post-incineration images are presented. The prevalence of cochlear implants is predicted to increase, thus they are likely to become relevant to the identification process. Company brand and serial markings can be retrieved from post-incineration implants making them a valuable aid in identification when other identifiers that may be present are not useful because they are heat-sensitive.


Establishing links between health and productivity in the New Zealand workforce.
To provide the first investigation of individual health behaviors and measures of work performance in New Zealand. Health risk assessments were completed by 747 adults aged 18 to 65 years. Associations between measures of productivity and health risk factors were assessed using multiple stepwise regression. Participants with low to moderate psychological distress levels and who were physically active reported a work performance 6.5% (P < 0.001) and 3.5% (P < 0.001) higher, respectively. Furthermore, high psychological distress and smoking accounted for 16.8 (P < 0.001) and 11.6 (P = 0.038) additional absentee hours over the previous 4 weeks. The impact that psychological distress, physical inactivity, and smoking have on productivity suggests that employers may benefit from contributing to health promotion within the workplace.


Anti-cancer therapeutic strategies based on HGF/MET, EpCAM, and tumor-stromal cross talk.
As an intelligent disease, tumors apply several pathways to evade the immune system. It can use alternative routes to bypass intracellular signaling pathways, such as nuclear factor-κB (NF-κB), Wnt, and mitogen-activated protein (MAP)/phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR). Therefore, these mechanisms lead to therapeutic resistance in cancer. Also, these pathways play important roles in the proliferation, survival, migration, and invasion of cells. In most cancers, these signaling pathways are overactivated, caused by mutation, overexpression, etc. Since numerous molecules share these signaling pathways, the identification of key molecules is crucial to achieve favorable consequences in cancer therapy. One of the key molecules is the mesenchymal-epithelial transition factor (MET; c-Met) and its ligand hepatocyte growth factor (HGF). Another molecule is the epithelial cell adhesion molecule (EpCAM), which its binding is hemophilic. Although both of them are involved in many physiologic processes (especially in embryonic stages), in some cancers, they are overexpressed on epithelial cells. Since they share intracellular pathways, targeting them simultaneously may inhibit substitute pathways that tumor uses to evade the immune system and resistant to therapeutic agents.


Design, synthesis, antibacterial activity and docking study of some new trimethoprim derivatives.
In present study, nineteen novel trimethoprim (TMP) derivatives were designed, synthesized and evaluated for their antibacterial potential. Hydroxy trimethoprim 2 (HTMP) was synthesized by following the demethylation of 4-methoxy group at trimethoxy benzyl ring of TMP. Structure-activity relationship (SAR) studies were explored on HTMP by incorporating various substituents leading to the identification of some new compounds with improved antibacterial activities. The results revealed that the introduction of benzyloxy (4a-e) and phenyl ethanone (5a-e) group at 4-position of dimethoxy benzyl ring leads to overall increase in the antibacterial activity. The most potent antibacterial compound discovered is benzyloxy derivative 4b with MIC value of 5.0μM against Staphylococcus aureus and 4.0μM against Escherichia coli strains higher than the standard TMP (22.7μM against S. aureus and 55.1μM against E. coli). Substitution at 4-NH2 group was not tolerated and the resulting Schiff base derivatives 3a-h demonstrated very little or no antibacterial activity in the tested concentration domain. We further performed exploratory docking studies on dihydrofolate reductase (DHFR) to rationalize the in vitro biological data and to demonstrate the mechanism of antibacterial activity. For the ability to cross lipophilic outer membrane, logP was computed. It was found that the compounds possessing high hydrophobicity have high activity against E. coli.


NLRP4 negatively regulates type I interferon signaling by targeting the kinase TBK1 for degradation via the ubiquitin ligase DTX4.
Stringent control of the type I interferon signaling pathway is important for maintaining host immune responses and homeostasis, yet the molecular mechanisms responsible for its tight regulation are still poorly understood. Here we report that the pattern-recognition receptor NLRP4 regulated the activation of type I interferon mediated by double-stranded RNA or DNA by targeting the kinase TBK1 for degradation. NLRP4 recruited the E3 ubiquitin ligase DTX4 to TBK1 for Lys48 (K48)-linked polyubiquitination at Lys670, which led to degradation of TBK1. Knockdown of either DTX4 or NLRP4 abrogated K48-linked ubiquitination and degradation of TBK1 and enhanced the phosphorylation of TBK1 and the transcription factor IRF3. Our results identify a previously unrecognized role for NLRP4 in the regulation of type I interferon signaling and provide molecular insight into the mechanisms by which NLRP4-DTX4 targets TBK1 for degradation.


Associations of the intestinal microbiome with the complement system in neovascular age-related macular degeneration.
Age-related macular degeneration (AMD) is a leading cause of severe vision loss in the aged population. The etiology of AMD is multifactorial including nutritional factors, genetic variants mainly in the complement pathway, environmental risk factors and alterations in the intestinal microbiome. However, it remains unexplored whether there is an interdependency of these factors leading to the development of AMD. To investigate this issue, a shotgun metagenomics analysis of 57 neovascular AMD and 58 healthy controls as well as of 16 complement C3-deficient mice and 16 wildtypes was performed. Whereas the class Negativicutes was more abundant in patients, the genus Oscillibacter and species Bacteroides had a significantly higher prevalence in persons without AMD. Similar taxonomic features were identified that distinguished wildtype mice from C3-deficient mice. Moreover, several purine signaling pathways were associated with both, neovascular AMD and C3 deficiency. While SNPs within the complement factor B gene were more abundant in controls, SNPs within the high temperature requirement A serine peptidase 1 and complement factor H (CFH) genes were associated with neovascular AMD. Using a classification model, Negativicutes was identified as a potential biomarker for AMD and furthermore, it positively correlated with CFH. This study suggests an association between the intestinal microbiome and the complement system in neovascular AMD.


Neuroprotective effect of selective kappa opioid receptor agonist is gender specific and linked to reduced neuronal nitric oxide.
We have previously shown that treatment with selective kappa-opioid receptor agonist BRL 52537 hydrochloride [(+/-)-1-(3,4-dichlorophenyl) acetyl-2-(1-pyrrolidinyl) methylpiperidine] (1) has a long therapeutic window for providing ischemic neuroprotection and (2) attenuates ischemia-evoked nitric oxide (NO) production in vivo in rats. Neuronally derived NO has been shown to be deleterious in the male, but not in the female, rodent model of focal ischemic stroke. We sought to determine if the agent fails to protect ischemic brain when neuronal NO synthase (nNOS) is genetically deleted in male, but not female, mice. Halothane-anesthetized adult male and female nNOS null mutants (nNOS(-/-)) and the genetically matched wildtype (WT) strain were subjected to transient (2 h) middle cerebral artery occlusion by the intraluminal filament technique. Vehicle or BRL 52537 treatment with continuous intravenous infusion was instituted at the onset of reperfusion and continued for 22 h. In WT male mice, infarct volumes measured at 72 h of reperfusion were robustly decreased with BRL 52537 treatment. In contrast, BRL 52537 did not decrease infarct volume in male nNOS(-/-) mice. BRL 52537 had no effect in the WT or nNOS(-/-) female mice. These data support that BRL 52537's mechanism of neuroprotection in vivo is through attenuation of nNOS activity and ischemia-evoked NO production. Neuroprotective effects of BRL 52537 are lost in the male when nNOS is not present; therefore, BRL 52537 likely acts upstream from NO generation and its subsequent neurotoxicity.


NCX4016 (NO-aspirin) reduces infarct size and suppresses arrhythmias following myocardial ischaemia/reperfusion in pigs.
1. The effect of the nitro-derivative of aspirin, NCX4016, was assessed on ischaemic ventricular arrhythmias and myocardial infarct size in anaesthetized pigs in comparison to native aspirin. 2. Pigs were given aspirin (10 mg kg(-1); n=6), low dose NCX4016 (18.4 mg kg(-1); n=6) or high dose NCX4016 (60 mg kg(-1); n=7) orally for 5 days prior to coronary occlusion and reperfusion. None of the interventions had any effect on baseline haemodynamics prior to coronary occlusion in comparison to control pigs (n=9). Aspirin and high dose NCX4016 both prevented the generation of thromboxane A(2) from platelets activated ex vivo with A23187 (30 microM), whereas all three interventions markedly attenuated platelet aggregation in response to collagen in whole blood in comparison to controls. 3. None of the drug interventions had any effect on the incidence of ventricular fibrillation (VF) during myocardial ischaemia (100% in all groups). However, 60 mg kg(-1) NCX4016 significantly attenuated the total number of premature ventricular beats (PVB's) (62+/-16 vs 273+/-40 in control pigs; P<0.05) during the first 30 min of occlusion. The higher dose of NCX4016 also significantly reduced myocardial infarct size (22.6+/-3.7% of area at risk vs 53.0+/-2.8% of area at risk in control pigs; P<0.05). 4. These results suggest that the nitro-derivative of aspirin, NCX4016, is an effective antiplatelet agent, which unlike aspirin also reduces the extent of myocardial injury following ischaemia and reperfusion.


Associations between the Bovine Myostatin Gene and Milk Fatty Acid Composition in New Zealand Holstein-Friesian × Jersey-Cross Cows.
The myostatin gene (MSTN), which encodes the protein myostatin, is pleiotropic, and its expression has been associated with both increased and decreased adipogenesis and increased skeletal muscle mass in animals. In this study, the polymerase chain reaction, coupled with single strand conformation polymorphism analysis, was utilized to reveal nucleotide sequence variation in bovine MSTN in 410 New Zealand (NZ) Holstein-Friesian × Jersey (HF × J)-cross cows. These cows ranged from 3 to 9 years of age and over the time studied, produced an average 22.53 ± 2.18 L of milk per day, with an average milk fat content of 4.94 ± 0.17% and average milk protein content of 4.03 ± 0.10%. Analysis of a 406-bp amplicon from the intron 1 region, revealed five nucleotide sequence variants (A-E) that contained seven nucleotide substitutions. Using general linear mixed-effect model analyses the AD genotype was associated with reduced C10:0, C12:0, and C12:1 levels when compared to levels in cows with the AA genotype. These associations in NZ HF × J cross cows are novel, and they suggest that this variation in bovine MSTN could be explored for increasing the amount of milk unsaturated fatty acid and decreasing the amount of saturated fatty acid.


A microcomputer-based sleep stage analyzer.
A microcomputer-based sleep stage analysis system for laboratory use is described. Rapid spectral analysis of the electroencephalogram (EEG) is achieved through hardware; subsequent analysis, including determination of the relative power in user-defined EEG frequency bands is provided through software. A decision matrix, based on standard sleep state analysis criteria, enables these spectral data, in conjunction with integrated electromyogram (EMG) power, to determine sleep stages. The system has been configured here to quantify standard sleep stages, but the algorithm can also identify, and provide information about, EEG states which are not easily classified according to earlier criteria used for visual classification of polygraphic records. This low-cost, user-friendly system thus achieves flexible, quantitative analysis of EEG and EMG signals.


PD-L1-negative Non-small-cell Lung Cancer Treated with Nivolumab Plus Ipilimumab During Maintenance Hemodialysis Results in Rapid Initial Progression Followed by a Long-lasting Response.
Nivolumab plus ipilimumab is one of the first-line treatments for advanced non-small-cell lung cancer (NSCLC), but the safety and efficacy in patients on hemodialysis (HD) is unclear. We herein report a patient with NSCLC on HD in whom nivolumab and ipilimumab were initiated. We observed general deterioration and enlarged lesions, followed by a long-term response. The patient developed secondary hypoadrenocorticism, an immune-related adverse event that was easily controlled. Nivolumab plus ipilimumab can be used safely for patients with NSCLC on HD. Long-term effectiveness can be observed after initial progression, so we should carefully assess the response.


Evaluation of ionizing radiation as a risk factor for the incidence of breast cancer: long-term analysis after the cesium-137 accident in Goiânia, Brazil. An ecological study.
The largest radiological accident to occur in any urban area happened in Goiânia, Brazil, in 1987. To evaluate the association between breast cancer incidence and ionizing radiation levels. Ecological study among residents of the city of Goiânia, Brazil. The central region of Goiânia, with seven major sources of contamination from cesium-137, was defined as the study area. The addresses of women diagnosed with breast cancer were identified between 2001 and 2010. The data were geographically referenced and, using census data, the annual averages of crude incidence rates were estimated. The existence of clusters of new cases was ascertained by means of the Moran index. Correlations of radiometric measurements with the incidence were assessed using unconditional linear regression. A total of 4,105 new cases were identified, of which 2,233 were in the study area, and of these, 1,286 (57.59%) were georeferenced. The gross rates of total and referenced cases were 102.91 and 71.86/100,000 women, respectively. These were close to the average for Brazilian state capitals, which is 79.37/100,000 women. The cluster analysis showed slight correlations in three small sets of census tracts, but these were far from the sources of contamination. The scatter plot of points and the R2 value close to zero indicated that there was no association between the variables. This study reinforces the hypothesis that the ionizing radiation levels to which women living in Goiânia are now exposed to are not associated with the onset of new cases of breast cancer.


Successful Treatment of Atopic Dermatitis with a Predominant Nipple Involvement by Abrocitinib During COVID-19 Pandemic: A Case Report.
There is limited literature on AD with a predominant involvement of nipple among the adult male group. SARS-CoV-2 infection might have been an exacerbating factor of AD by initiating the "cytokine storm". Conventional treatment suffers from a dilemma of poor efficacy and a high recurrence. The JAK inhibitors have been clinically applied to treat the AD with a good outcome. We present a case of a 28-year-old male AD patient with a predominant nipple involvement successfully treated with JAK inhibitor abrocitinib, with no adverse affects. The case shows a good clinical efficacy of JAK inhibitor abrocitinib in the treatment of AD with a predominant nipple involvement during the COVID-19 pandemic with a rapid and long-term symptomatic relief. JAK inhibitor abrocitinib might become a promising agent for the treatment with AD with a predominant uncommon region like nipple that might be resistant to conventional therapies during the COVID-19 pandemic.


Modern aqueous shunt implantation: future challenges.
The aqueous shunts that are currently available are based on the principles of the Molteno implant, i.e., a permanent sclerostomy, routing of aqueous to the equatorial subconjunctival space, and an end plate to prevent obstruction, and also to determine the surface area for absorption. While the Ahmed Glaucoma Valve appears to have improved the predictability of early intraocular pressure (IOP) control, the Baerveldt Glaucoma Implant has a tendency towards a lower rate of long-term excessive encapsulation. As a result of improvements in predictability, shunts are used more widely. Because of these positive factors, and ongoing concerns regarding the bleb-related problems associated with mitomycin C trabeculectomy, there is an increasing interest in the use of shunts as primary surgical management for primary glaucoma. At present, the main barrier to wider use of shunts in less-complicated glaucomas will probably be the unknown long-term effect on corneal endothelium, an issue that has not yet been properly addressed.


Splenic vein aneurysm with calcification of splenic and portal veins.
Splenic vein aneurysm is a rare disease, and calcifications in the portal venous system are also rare. Here we present a case of splenic vein aneurysm associated with calcification of the splenic and portal veins, a condition that to our knowledge has not been reported before.


Ontogenic development of brain asymmetry in dopaminergic neurons.
In the present study the right-left brain asymmetry of central dopamine (DA) systems during postnatal brain development is evaluated. DA and dihydroxyphenylacetic acid (DOPAC) levels increased from neonatal to adult life in both the forebrain and mesencephalon. This increase was not similar in the right and left brain sides. From neonatal life to adulthood a fall was observed in (a) DA percentage in the DA high-brain side in the mesencephalon and (b) DOPAC percentage in the DOPAC high-brain side in both the forebrain and mesencephalon. The percentage of lateralized rats (more than 65% of DA or DOPAC levels in either brain side) also decreased during ontogeny. Thus, biochemical lateralization decreases during ontogeny. The right-left brain correlation for DA level and DA turnover was used to evaluate the inter-hemispheric regulation of dopaminergic systems. The correlation coefficient was near to 0 during postnatal life and around -0.8 during adulthood in both forebrain and mesencephalon. Taken together, these data suggest that the ontogenic decrease of in brain asymmetry for DA or DOPAC levels is related to the postnatal development of an inter-hemispheric regulatory system that control dopaminergic neurons activity.