Mechanistic studies on tyrosinase-catalysed oxidative decarboxylation of 3,4-dihydroxymandelic acid.
Mushroom tyrosinase, which is known to convert a variety of o-diphenols into o-benzoquinones, has been shown to catalyse an unusual oxidative decarboxylation of 3,4-dihydroxymandelic acid to 3,4-dihydroxybenzaldehyde [Sugumaran (1986) Biochemistry 25, 4489-4492]. The mechanism of this reaction was re-investigated. Although visible-region spectral studies of the reaction mixture containing 3,4-dihydroxymandelic acid and tyrosinase failed to generate the spectrum of a quinone product during the steady state of the reaction, both trapping experiments and non-steady-state kinetic experiments provided evidence for the transient formation of unstable 3,4-mandeloquinone in the reaction mixture. The visible-region spectrum of mandeloquinone resembled related quinones and exhibited an absorbance maximum at 394 nm. Since attempts to trap the second intermediate, namely alpha,2-dihydroxy-p-quinone methide, were in vain, mechanistic studies were undertaken to provide evidence for its participation. The decarboxylative quinone methide formation from 3,4-mandeloquinone dictates the retention of a proton on the alpha-carbon atom. Hence, if we replace this proton with deuterium, the resultant 3,4-dihydroxybenzaldehyde should retain the deuterium present in the original substrate. To test this hypothesis, we chemoenzymically synthesized alpha-deuterated 3,4-dihydroxymandelic acid and examined its enzymic oxidation. Our studies reveal that the resultant 3,4-dihydroxybenzaldehyde retained nearly 90% of the deuterium, strongly indicating the transient formation of quinone methide. On the basis of these findings it is concluded that the enzymic oxidation of 3,4-dihydroxymandelic acid generates the conventional quinone product, which, owing to its unstability, is rapidly decarboxylated to generate transient alpha,2-dihydroxy-p-quinone methide. The coupled dienone-phenol re-arrangement and keto-enol tautomerism of this quinone methide produce the observed 3,4-dihydroxybenzaldehyde.


IL-16 induces intestinal inflammation via PepT1 upregulation in a pufferfish model: new insights into the molecular mechanism of inflammatory bowel disease.
Inflammatory bowel disease (IBD) has long been a worldwide health care problem with a persistently increasing incidence. Although its clinical features have been well described, its etiology and pathogenesis remain unclear. IL-16 is a chemoattractant cytokine with various effects on cellular activities and diseases. However, the involvement of IL-16 in IBD remains poorly understood. In this study, to our knowledge we report for the first time the mechanism by which IL-16 induces intestinal inflammation by upregulating the expression of oligopeptide transporter member 1 (PepT1) in a Tetraodon nigroviridis fish model. The dextran sodium sulfate-induced colitis model in this species revealed that IL-16 levels significantly increase accompanied by elevations in PepT1 in the colon. Moreover, the signs of colitis were dramatically attenuated by IL-16 depletion using anti-IL-16 Abs. In vivo IL-16 administration induced remarkable intestinal inflammation with typical ulcerative colitis-like features, including histologic damage, inflammatory cell infiltration, increased myeloperoxidase activity, and proinflammatory cytokines expression, which corresponded with significant PepT1 upregulation in the colon. The IL-16-induced PepT1 expression and its upregulated fMLF transport were also demonstrated in vitro. To our knowledge, our study provides the first evidence of the connection between IL-16 and PepT1, which provides new insights into the molecular mechanism underlying IBD development. Additionally, this study suggests that fish species are an attractive model for studying IBD. By providing a better understanding of IL-16 biology from fish to mammals, this study should aid the development of IL-16-based therapies for IBD.


Workforce Diversity in Eating Disorders: A Multi-Methods Study.
Despite growing recognition of the importance of workforce diversity in health care, limited research has explored diversity among eating disorder (ED) professionals globally. This multi-methods study examined diversity across demographic and professional variables. Participants were recruited from ED and discipline-specific professional organizations. Participants' (n = 512) mean age was 41.1 years (SD = 12.5); 89.6% (n=459) of participants identified as women, 84.1% (n = 419) as heterosexual/straight, and 73.0% (n = 365) as White. Mean years working in EDs was 10.7 years (SD = 9.2). Qualitative analysis revealed three themes resulting in a theoretical framework to address barriers to increasing diversity. Perceived barriers were the following: "stigma, bias, stereotypes, myths"; "field of eating disorders pipeline"; and "homogeneity of the existing field." Findings suggest limited workforce diversity within and across nations. The theoretical model suggests a need for focused attention to the educational pipeline, workforce homogeneity, and false assumptions about EDs, and it should be tested to evaluate its utility within the EDs field.


Artificial Intelligence and Computational Approaches for Epilepsy.
Studies on treatment of epilepsy have been actively conducted in multiple avenues, but there are limitations in improving its efficacy due to between-subject variability in which treatment outcomes vary from patient to patient. Accordingly, there is a growing interest in precision medicine that provides accurate diagnosis for seizure types and optimal treatment for an individual epilepsy patient. Among these approaches, computational studies making this feasible are rapidly progressing in particular and have been widely applied in epilepsy. These computational studies are being conducted in two main streams: 1) artificial intelligence-based studies implementing computational machines with specific functions, such as automatic diagnosis and prognosis prediction for an individual patient, using machine learning techniques based on large amounts of data obtained from multiple patients and 2) patient-specific modeling-based studies implementing biophysical in-silico platforms to understand pathological mechanisms and derive the optimal treatment for each patient by reproducing the brain network dynamics of the particular patient per se based on individual patient's data. These computational approaches are important as it can integrate multiple types of data acquired from patients and analysis results into a single platform. If these kinds of methods are efficiently operated, it would suggest a novel paradigm for precision medicine.


A personalist approach to public-health ethics.
First we give an overview of the historical development of public health. Then we present some public-health deontology codes and some ethical principles. We highlight difficulties in defining ethics for public health, with specific reference to three of them that concern: (i) the adaptability to public health of the classical principles of bioethics; (ii) the duty to respect and safeguard the individual while acting within the community perspective that is typical of public health; and (iii) the application-oriented nature of public health and the general lack of attention towards the ethical implications of collective interventions (compared with research). We then mention some proposals drafted from North American bioethics "principles" and utilitarian, liberal and communitarian views. Drawing from other approaches, personalism is outlined as being the theory that offers a consistent set of values and alternative principles that are relevant for public health.


Resveratrol-induced activation of p53 and apoptosis is mediated by extracellular-signal-regulated protein kinases and p38 kinase.
Resveratrol, a phytoalexin found in grapes, berries, and peanuts, is one of the most promising agents for cancer prevention. Our previous study showed that the antitumor activity of resveratrol occurs through p53-mediated apoptosis. In this study, we have elucidated the potential signaling components underlying resveratrol-induced p53 activation and induction of apoptosis. We found that in a mouse JB6 epidermal cell line, resveratrol activated extracellular-signal-regulated protein kinases (ERKs), c-Jun NH2-terminal kinases (JNKs), and p38 kinase and induced serine 15 phosphorylation of p53. Stable expression of a dominant negative mutant of ERK2 or p38 kinase or their respective inhibitor, PD98059 or SB202190, repressed the phosphorylation of p53 at serine 15. In contrast, overexpression of a dominant negative mutant of JNKI had no effect on the phosphorylation. Most importantly, ERKs and p38 kinase formed a complex with p53 after treatment with resveratrol. Strikingly, resveratrol-activated ERKs and p38 kinase, but not JNKs, phosphorylated p53 at serine 15 in vitro. Furthermore, pretreatment of the cells with PD98059 or SB202190 or stable expression of a dominant negative mutant of ERK2 or p38 kinase impaired resveratrol-induced p53-dependent transcriptional activity and apoptosis, whereas constitutively active MEK1 increased the transcriptional activity of p53. These data strongly suggest that both ERKs and p38 kinase mediate resveratrol-induced activation of p53 and apoptosis through phosphorylation of p53 at serine 15.


Genetic analysis of maize shank length by QTL mapping in three recombinant inbred line populations.
In maize, the shank is a unique tissue linking the stem to the ear. Shank length (SL) mainly affects the transport of photosynthetic products to the ear and the dehydration of kernels via regulated husk morphology. The limited studies on SL revealed it is a highly heritable quantitative trait controlled by significant additive and additive-dominance effects. However, the genetic basis of SL remains unclear. In this study, we analyzed three maize recombinant inbred line (RIL) populations to elucidate the molecular mechanism underlying the SL. The data indicated the SL varied among the three RIL populations and was highly heritable. Additionally, the SL was positively correlated with the husk length (HL), husk number (HN), ear length (EL), and ear weight (EW) in the BY815/K22 (BYK) and CI7/K22 (CIK) RIL populations, but was negatively correlated with the husk width (HW) in the BYK RIL population. Moreover, 10 quantitative trait loci (QTL) for SL were identified in the three RIL populations, five of which were large-effect QTL. The percentage of the total phenotypic variation explained by the QTL for SL was 13.67 %, 20.45 %, and 30.81 % in the BY815/DE3 (BYD), BYK, and CIK RIL populations, respectively. Further analyses uncovered some genetic overlap between SL and EL, SL and ear row number (ERN), SL and cob weight (CW), and SL and HN. Unlike the large-effect QTL qSL BYK-2-2, which spanned the centromere, the other four large-effect QTL were delimited to a single peak bin via bin map. Furthermore, 2, 5, 6, and 12 genes associated with SL were identified for qSL BYK-2-1, qSL CIK-2-1, qSL CIK-9-1, and qSL CIK-9-2, respectively. Five of the candidate genes for SL may contribute to the hormone metabolism and sphingolipid biosynthesis regulating cell elongation, division, differentiation, and expansion. These results may be relevant for future studies on the genetic basis of SL and for the molecular breeding of maize based on marker-assisted selection to develop new varieties with an ideal SL.


The effects of sex on extinction dynamics of Chlamydomonas reinhardtii depend on the rate of environmental change.
The continued existence of sex, despite many the costs it entails, still lacks an adequate explanation, as previous studies demonstrated that the effects of sex are environment-dependent: sex enhances the rate of adaptation in changing environments, but the benefits level off in benign conditions. To the best of our knowledge, the potential impact of different patterns of environmental change on the magnitude of these benefits received less attention in theoretical studies. In this paper, we begin to explore this issue by examining the effect of the rate of environmental deterioration (negatively correlated with population survival rate), on the benefits of sex. To investigate the interplay of sex and the rate of environmental deterioration, we carried out a long-term selection experiment with a unicellular alga (Chlamydomonas reinhardtii), by manipulating mode of reproduction (asexual, facultative or obligate sexual) and the rate of environmental deterioration (an increase of salt concentration). We monitored both the population size and extinction dynamics. The results revealed that the relative advantage of sex increased at the intermediate rate and plateaued at the highest rate of environmental deterioration. Obligate sexual populations had the slowest extinction rate under the intermediate rate of environmental deterioration, while facultative sexuality was favoured under the high rate-treatment. To the best of our knowledge, our study is the first to demonstrate that the interplay of sex and the rate of environmental deterioration affects the probability of survival, which indicates that mode of reproduction may be an important determinant of survival of the anthropogenic-induced environmental change.


Glycosylation of CD44 is implicated in CD44-mediated cell adhesion to hyaluronan.
CD44-mediated cell adhesion to hyaluronate is controlled by mechanisms which are poorly understood. In the present work we examine the role of N-linked glycosylation and Ser-Gly motifs in regulating CD44-hyaluronate interaction. Our results show that treatment of a panel of human cell lines which constitutively express CD44 with the inhibitor of N-linked glycosylation tunicamycin results in the loss of attachment of these cells to hyaluronate-coated substrate. In contrast, treatment of the same cells with deoxymannojirimycin, which inhibits the conversion of high mannose oligosaccharides to complex N-linked carbohydrates, results in either no change or an increase in CD44-mediated adhesion to hyaluronate, suggesting that complex N-linked oligosaccharides may not be required for and may even inhibit CD44-HA interaction. Using human melanoma cells stably transfected with CD44 N-linked glycosylation site-specific mutants, we show that integrity of five potential N-linked glycosylation sites within the hyaluronate recognition domain of CD44 is critical for hyaluronate binding. Mutation of any one of these potential N-linked glycosylation sites abrogates CD44-mediated melanoma cell attachment to hyaluronate-coated surfaces, suggesting that all five sites are necessary to maintain the HA-recognition domain in the appropriate conformation. We also demonstrate that mutation of serine residues which constitute the four Ser-Gly motifs in the membrane proximal domain, and provide potential sites for glycosaminoglycan side chain attachment, impairs hyaluronate binding. Taken together, these observations indicate that changes in glycosylation of CD44 can have profound effects on its interaction with hyaluronic acid and suggest that glycosylation may provide an important regulatory mechanism of CD44 function.


A taxonomic study of Gardnerella vaginalis (Haemophilus vaginalis) Gardner and Dukes 1955.
Fifty-five strains received as Haemophilus vaginalis or as catalase-negative coryneform bacteria from the vagina together with 61 marker cultures were subjected to numerical phenetic analyses using 149 unit characters. The data were examined using the simple matching (SSM), Jaccard (SJ) and pattern (DP) coefficients and clustering was achieved using the average linkage algorithm. Cluster composition was not markedly affected by the coefficient used or by test error, estimated at 6 . 5%. The H. vaginalis strains formed a tight cluster which was only distantly related to representatives of the genera arthrobacter, Cellulomonas, Corynebacterium sensu stricto, Erysipelothrix, Haemophilus, Kurthia, Lactobacillus, Listeria and Propionibacterium but shared a high overall affinity to unclassified catalase-negative coryneforms which formed a discrete taxon, cluster 9. The H. vaginalis strains could be distinguished from the related strains in cluster 9 by several unrelated phenotypic characters. Using the S1 endonuclease assay, DNA-DNA hybridizations were performed with representative strains from the numerical as well as with reference strains of Bifidobacterium and Actinomyces. Haemophilus vaginalis was found to be a genotypically legitimate group and its DNA showed little homology with DNA from the marker strains tested. The DNA base composition of H. vaginalis was 42 to 44 mol % guanine plus cytosine. A new genus should be created to incorporate strains known as H. vaginalis or Corynebacterium vaginale. The name Gardnerella vaginalis proposed by Greenwood & Pickett (1979) is supported.


Evaluation of Δ(9)-tetrahydrocannabinol metabolites and oxidative stress in type 2 diabetic rats.
The object of the study is to examine the effects of Δ(9)-tetrahydrocannabinol (THC) against oxidative stress in the blood and excretion of THC metabolites in urine of type 2 diabetic rats. The control (n=8), THC control (n=6), diabetes (n=8) and diabetes + THC (n=7) groups were created. Type 2 diabetes was induced by nicotinamide (NA, 85 mg/kg) + streptozotocin (STZ, 65 mg/kg). THC was administered intraperitoneally for seven days. The glutathione (GSH) level in erythrocytes and malondialdehyde (MDA) level, superoxide dismutase (SOD) and catalase (CAT) enzyme activities in plasma were measured. THC metabolites were analyzed in urine. The results showed that the erythrocyte GSH levels were significantly increased (P<0.05), but plasma MDA levels were non-significantly decreased in diabetes group treated with THC when compared with the diabetes group. The CAT activity was non-significantly reduced and SOD was significantly increased (P<0.01) in the plasma of diabetes induced by THC in comparison with the diabetic group. The excretion of THC metabolites was higher in the urine of diabetes + THC rats as compared to the THC control rats. These findings highlight that THC treatment may attenuate slightly the oxidative stress in diabetic rats. The excretion rate of THC may vary in the type 2 diabetes mellitus status.


The influence of nutritional assessment on the outcome of ostomy takedown.
Ostomy takedown is often considered a simple procedure without intention; however, it is associated with significant morbidity. This study is designed to evaluate factors predicting postoperative complications in the ostomy takedown in view of metabolism and nutrition. A retrospective, institutional review-board-approved study was performed to identify all patients undergoing takedown of an ostomy from 2004 to 2010. Of all patients (150), 48 patients (32%; male, 31; female, 17) had complications. Takedown of an end-type ostomy showed a high complication rate; complications occurred in 55.9% of end-type ostomies and 15.7% of loop ostomies (P < 0.001). Severe adhesion was also related to a high rate of overall complication (41.3%) (P = 0.024). In preoperative work-up, ostomy type was not significantly associated with malnutrition status. However, postoperatively severe malnutrition level (albumin <2.8 mg/dL) was statistically significant in increasing the risk of complications (72.7%, P = 0.015). In particular, a significant postoperative decrease in albumin (>1.3 mg/dL) was associated with postoperative complications, particularly surgical site infection (SSI). Marked weight loss such as body mass index downgrading may be associated with the development of complications. A temporary ostomy may not essentially result in severe malnutrition. However, a postoperative significant decrease in the albumin concentration is an independent risk factor for the development of SSI and complications.


Self-Directed Learning During the COVID-19 Pandemic: Perspectives of South African Final-Year Health Professions Students.
Self-directed learning (SDL) has been advocated for effective training of final-year health professions students. COVID-19 challenges conventional teaching, learning, and assessment in the clinical environment. This study aimed to identify and explore enablers and barriers to SDL among final-year health professions students training during the COVID-19 pandemic. Adopting the SWOT (strengths, weaknesses, opportunities and threats) framework, this study explored the clinical learning and training experiences of final-year health professions students during the pandemic. A survey was conducted via online platforms. Data from 155 respondents were thematically analyzed. Personal attributes such as reflection, self-determination, motivation, resilience, and positive learning behaviors and skills were identified as SDL enablers. Collaborative learning networks and online learning platforms facilitate learning needs and goals. Fear and anxiety, untrusted learning sites, uncertainty about graduation, financial issues and challenges in the learning environments were the major themes related to barriers to SDL. The importance of SDL as a skill for uncertain times warrants further investigation in the training of future healthcare professionals. Inclusive planning and engagement with final-year health professions students to address identified stressors, as well as the creation of shared platforms where students are part of the decision-making processes for clinical learning and training are recommended. Responsive curricula that optimize unpredictable disruptions in clinical training are needed to equip students to diagnose their own learning needs and implement appropriate learning strategies.


Metamagnetic transition in UCoAl probed by thermoelectric measurements.
We report field and temperature dependent measurements of the thermoelectric power (TEP) and the Nernst effect in the itinerant metamagnet UCoAl. The magnetic field is applied along the easy magnetization c axis in the hexagonal crystal structure. The metamagnetic transition from the paramagnetic phase at zero field to the field induced ferromagnetic state is of first order at low temperatures and becomes a broad crossover above the critical temperature T(M)(⋆)∼11 K. The field dependence of the TEP reveals that the effective mass of the hole carriers changes significantly at the metamagnetic transition. The TEP experiment reflects the existence of different carrier types in good agreement with band structure calculations and previous Hall effect experiments. According to the temperature dependence of the TEP, no Fermi liquid behavior appears in the paramagnetic state down to 150 mK, but is achieved only in the field induced ferromagnetic state.


Risk of gastric cancer is not increased after partial gastrectomy.
It has been suggested that there is an increased risk of gastric cancer following partial gastrectomy. This question has not been studied in an Australian population. The records of a total of 569 patients who had a partial gastrectomy for peptic ulcer disease at Repatriation General Hospital, Heidelberg, between 1957 and 1976 were reviewed. All were followed to date of death or 31 December 1996. The expected rate of gastric cancer for this population was estimated from published Australian age-and sex-specific gastric cancer mortality rates over this period, and a standardized incidence ratio was calculated. The mean age at surgery was 53.5 years (range 27-83 years). There were 547 male (96.4%) and 22 female (3.6%) patients. Five hundred and seven (83.5%) had a Billroth II procedure. Thirty-eight patients (6.3%) were lost to follow up and were not included in the analysis. From the records of the Department of Veterans' Affairs, it was established that 125 (20.6%) were alive in December 1996, a mean survival after surgery of 18.8 years. The mean documented duration of follow up was 17.3 years (range 1-41 years). Nine patients developed cancer in the gastric remnant. The expected number of cancers in this population was 6.5. Assuming all survivors were free of gastric cancer, the standardized incidence ratio was 1.39 (95% confidence intervals 0.64-2.65, P=0.313). The risk of gastric cancer was not increased after partial gastrectomy in this Australian population.


Pretreatment modeling. A technique for reducing children's fear in the dental operatory.
Research on modeling indicates that this technique offers dentists a means of reducing fear in child patients of all ages. As a preventive measure used with children who have had no prior exposure to dental treatment, it can be particularly efficacious. Based on the assumption that much of adult dental avoidance is based on dental fears acquired in childhood treatment, the reduction of children's dental fear would have a positive effect on the individual's tendency to seek out dental health care throughout his or her lifespan. For the dentist, there are also short- and long-term benefits. Dental management of the child is prerequisite to providing good dental care. Pedodontics as a specialty recognizes behavioral management of the child cannot be separated from the quality of the dentist's work. Fear has been identified as an important factor in disruptive behavior of school age children in the dental office. Practicing dentists consider the fearful, disruptive child to be among the most troublesome of problems in their clinical work. The child must cooperate or at least passively comply with the dentist's procedures in order to have the technical work completed. By reducing disruptive patient behavior (crying, screaming children whose peripheral and gross motor movements often make direct contact with the dentist or his equipment) the most unpalatable aspect of pediatric dentistry is minimized. Further, the actual time for treatment becomes shorter rather than longer. Although modeling is not restricted to videotape media, the emergence of current videotape technology provides the practitioner with the means for incorporating patient viewing of prerecorded modeling tapes as part of the usual waiting period. Such a procedure would mean that in the long run, the dentist will spend more time doing dentistry and less in behavioral management tasks.


The Suppressor of fused gene, involved in Hedgehog signal transduction in Drosophila, is conserved in mammals.
The Suppressor of fused [Su(fu)] gene of Drosophila melanogaster encodes a protein containing a PEST sequence [sequence enriched in proline (P), glutamic acid (E), serine (S) and threonine (T)] which acts as an antagonist to the serine-threonine kinase Fused in Hedgehog (Hh) signal transduction during embryogenesis. The Su(fu) gene isolated from a distantly related Drosophila species, D. virilis, shows significantly high homology throughout its protein sequence with its D. melanogaster counterpart. We show that these two Drosophila homologs of Su(fu) are functionally interchangeable in enhancing the fused phenotype. We have also isolated mammalian homologs of Su(fu). The absence of the PEST sequence in the mammalian Su(fu) protein suggests a different regulation for this product between fly and vertebrates. Using the yeast two-hybrid method, we show that the murine Su(fu) protein can interact directly with the Fused and Cubitus interruptus proteins, known partners of Su(fu) in Drosophila. These data are discussed in the light of their evolutionary relationships.


Age-related effects of digoxin on myocardial contractility and Na-K pump in sheep.
The age-dependent effects of an acute nontoxic, positively inotropic dose of digoxin on myocardial monovalent cation active transport were determined in fetal, newborn, and adult sheep. Thirty-five lightly sedated, closed-chest animals were instrumented to record electrocardiogram, left ventricular (LV) pressure, and rate of change of LV pressure (LV dP/dt). Ouabain-inhibitable uptake of Rb+ (86Rb+) was measured in both right ventricular (RV) and LV slices from control animals and in animals infused with [3H]digoxin (0.04 mg/kg) sufficient to cause an increase in LV dP/dt without toxicity. Sixty minutes after digoxin, LV dP/dt increased 123% over base-line values in fetuses, 131% in newborns, and 165% in adult animals. RV and LV myocardial digoxin concentrations were similar in all groups. Rb+ active transport was significantly reduced in both RV and LV tissue from all animals 60 min after digoxin. Control animals showed no significant changes in contractility or Rb+ active transport among the control group of fetal, newborn, or adult sheep. Acute infusions of digoxin increased LV contractility in each age group and was accompanied by digoxin-induced inhibition of myocardial Rb+ active transport. No age-related differences in the extent of Rb+ active transport among control or among digoxin-treated animals were observed under these experimental conditions. These studies suggest that the differential response to the therapeutic and toxic effects of digoxin in sheep of various ages does not reside in an age-dependent response of the myocardial sodium pump to digoxin.


Drug-induced gastropathy in elderly Taiwanese.
Drug-induced gastropathy was common in developing countries in which drug consumption was heavy. The aim of this study is to evaluate the difference in the distribution of clinical features and endoscopic findings between elderly and non-elderly and to determine the risk factors of drug-induced gastrointestinal mucosal damage in elderly. Four hundred and fifty patients with gastrointestinal mucosal damages were recruited from the outpatient clinic or emergency room. All patients were confirmed by endoscopic examination with Olympus Videoscope QX-200 or GIF-p20. Patient's clinical symptoms, endoscopic findings and risk factors were collected. Data was analyzed by chi 2 test and expressed as Odds ratio. The age distribution of gastropathy was predominant at 60-69 years old, and the case number gradually declined as age increased or decreased, respectively. The clinical presentation of asymptomatic bleeding was significantly higher in the elderly than in the non-elderly, while epigastric pain combined with dyspepsia or bleeding was not different between elderly and non-elderly groups. The endoscopic findings of gastric ulcer and erosions were significantly predominant in the elderly group, while no difference was found for duodenal ulcer between these 2 groups. Non-steroidal anti-inflammatory drugs were the popular drug which lead to gastropathy in both elderly and non-elderly groups. Drugs, especially steroids, history of arthritis or peptic ulcer, and alcohol consumption were found to be the risk factors associated with increased risk of gastropathy in the elderly. Stress was also significantly associated with increased risk of gastropathy in the non-elderly. There was no significant difference in smoking habit and use of other drugs between these 2 groups. The clinical features of symptoms, endoscopic findings and risk factors of gastropathy varied significantly between the elderly and the non-elderly. Drug-induced gastropathy, especially steroid treatment for arthritis, was a significant risk factor in the elderly. Program for assessment and management of these elderly patients under treatment is important.


Estimation of internal noise using double passes: does it matter how the second pass is delivered?
Human sensory processing is inherently noisy: if a participant is presented with the same set of stimuli multiple times and is asked to perform a task related to some property of the stimulus by pressing one of two buttons, the set of responses generated by the participant will differ on different presentations even though the set of stimuli remained the same. This response variability can be used to estimate the amount of internal noise (i.e. noise that is not present in the stimulus but in the participant's decision making process). The procedure by which the same set of stimuli is presented twice is referred to as double-pass (DP) methodology. This procedure is well-established, but there is no accepted recipe for how the repeated trials may be delivered (e.g. in the same order as they were originally presented, or in a different order); more importantly, it is not known whether the choice of delivery matters to the resulting estimates. Our results show that this factor (as well as feedback) has no measurable impact. We conclude that, for the purpose of estimating internal noise using the DP method, the system can be assumed to have no inter-trial memory.


Aluminum "pop tops". A hazard to child health.
In a 3 1/2- year period, seven children have been treated for complications of ingestion or aspiration of pull tabs from aluminum beverage cans. One child died from a fistula between the esophagus and a branch of the aortic arch, and two children suffered esophageal perforation with local abscess formation. Since aluminum absorbs x-rays poorly, the pull tabs cannot be seen in frontal projection if they overlie vertebral bodies. Any toddler with unexplained alteration of feeding habits or persistent respiratory symptoms requires evaluation for an aspirated or ingested foreign body.


Management of osteoporosis in children.
Osteoporosis is being increasingly recognised in paediatric practice as a consequence of several factors. These include the increasing complexity of chronic conditions and the associated treatments managed by paediatricians. In addition, the improved care provided to children with chronic illness has led to many of them living long enough to develop osteoporosis. The availability of methods to assess bone density in children as a surrogate marker of bone strength and the possibility of medical treatment to increase bone density have also resulted in an increased awareness of groups of children who may be at risk of osteoporosis. This article reviews the current definition of osteoporosis in children, aetiological factors and the evidence for effective treatment.


A multicenter randomized trial of computer-driven protocolized weaning from mechanical ventilation.
Duration of weaning from mechanical ventilation may be reduced by the use of a systematic approach. We assessed whether a closed-loop knowledge-based algorithm introduced in a ventilator to act as a computer-driven weaning protocol can improve patient outcomes as compared with usual care. We conducted a multicenter randomized controlled study with concealed allocation to compare usual care for weaning with computer-driven weaning. The computerized protocol included an automatic gradual reduction in pressure support, automatic performance of spontaneous breathing trials (SBT), and generation of an incentive message when an SBT was successfully passed. One hundred forty-four patients were enrolled before weaning initiation. They were randomly allocated to computer-driven weaning or to physician-controlled weaning according to local guidelines. Weaning duration until successful extubation and total duration of ventilation were the primary endpoints. Weaning duration was reduced in the computer-driven group from a median of 5 to 3 d (p=0.01) and total duration of mechanical ventilation from 12 to 7.5 d (p=0.003). Reintubation rate did not differ (23 vs. 16%, p=0.40). Computer-driven weaning also decreased median intensive care unit (ICU) stay duration from 15.5 to 12 d (p=0.02) and caused no adverse events. The amount of sedation did not differ between groups. In the usual care group, compliance to recommended modes and to SBT was estimated, respectively, at 96 and 51%. The specific computer-driven system used in this study can reduce mechanical ventilation duration and ICU length of stay, as compared with a physician-controlled weaning process.


Cardiovascular actions of angiotensin in the fowl (Gallus domesticus). II. Angiotensin analog agonists and antagonists.
Like angiotensin II (AII) itself, [SAR1] AII induced a biphasic blood pressure response in the conscious chicken--an initial depressor response followed by a pressor response. Angiotensin III, however, induced only a depressor response in the dose range tested. The response to angiotensin I was similar to that to AII, and appeared to be due to its conversion to AII as it was inhibited by prior infusion of the angiotensin converting enzyme inhibitor SQ 20,881. Two angiotensin analog antagonists [SAR1ALA8] AII and [SAR1ILE8] AII inhibited both components of the response to AII, but the pressor response was inhibited at lower concentrations of antagonist than was the depressor response. These findings give further support to the suggestion that the pressor and depressor component of the response to AII in the conscious chicken are mediated via different AII receptors, and indicate the possibility of selective blockade of these two components.


Nosocomial pneumonia during stress ulcer prophylaxis with cimetidine and sucralfate.
Recent studies have questioned the use of histamine (H2) receptor antagonist in stress ulcer prophylaxis because of an increased incidence of nosocomial pneumonia and subsequent death. This prospective randomized study compared prophylaxis with cimetidine vs sucralfate. Medical/surgical intensive care unit in Springfield, Mass. One hundred fourteen patients were enrolled. Cimetidine, administered as a primed continuous infusion using a 300-mg bolus followed by 37.5 mg/h, was compared with sucralfate, administered via nasogastric tube, at a dosage of 1 g every 6 hours suspended in 20 mL of sterile water. End points of the study included nosocomial pneumonia, gastrointestinal hemorrhage, and death. Fifty-six patients were randomized to receive cimetidine and their rate of pneumonia was 12.5%; upper gastrointestinal hemorrhage, 3.6%; and mortality, 33.9%. Fifty-eight patients were given sucralfate, and their rate of pneumonia was 13.8%; upper gastrointestinal hemorrhage, 3.4%; and mortality, 37.9%. There were no significant differences between these study end points. In patients who had pneumonia, 80% of isolates were aerobic gram-negative bacilli. These observations suggest that the rate of nosocomial pneumonia is not increased in patients in the intensive care unit who receive prophylaxis with cimetidine to prevent stress ulcer bleeding.


Cardioprotective Effects of 6-Gingerol against Alcohol-Induced ROS-Mediated Tissue Injury and Apoptosis in Rats.
The present study investigated the cardioprotective properties of 6-gingerol against alcohol-induced ROS-mediated cardiac tissue damage in rats. Experiments were conducted on 4 groups of rats, orally treated with control, 6-gingerol (10 mg/kg body weight), alcohol (6 g/kg body weight) and combination of 6-gingerol plus alcohol for two-month. In the results, we found 6-ginger treatment to alcohol-fed rats substantially suppressed ROS production in cardiac tissue. Alcohol-induced elevated 8-OHDG and protein carbonyls which represent oxidative modification of DNA and proteins were completely reversed by 6-gingerol. This was further endorsed by restored superoxide dismutase and catalase activities with 6-gingerol against alcohol-induced loss. The elevated cardiac biomarkers (CK-MB, cTn-T, cTn-I) and dyslipidemia in alcohol-intoxicated rats was significantly reversed by 6-gingerol. Furthermore, alcohol-induced apoptosis characterized by overexpression of cytochrome C, caspase-8 and caspase-9 was diminished with 6-gingerol treatment. Transmission electron microscope images conferred the cardioprotective properties of 6-gingerol as we have seen less structural derangements in mitochondria and reappearance of myofilaments. Our findings conclude that 6-ginger effectively protect alcohol-induced ROS-mediated cardiac tissue damage, which may be due to its potent antioxidant efficacy. Therefore, 6-gingerol could be a potential therapeutic molecule that can be used in the treatment of alcohol-induced myocardial injury.


Outbreaks of 2009 pandemic influenza A (H1N1) among long-term-care facility residents - three states, 2009.
Hospitalization and death from seasonal influenza are more common among older adults and in long-term--care facilities (LTCFs). Early data from the 2009 pandemic influenza A (H1N1) outbreak indicated that attack rates among persons aged >or=65 years were lower than in other age groups, and anti-influenza A antibodies that cross-react with 2009 H1N1 could be detected in up to one third of healthy adults aged >60 years. Based on these early data and anticipation of limited initial supplies of 2009 H1N1 vaccine, the Advisory Committee on Immunization Practices (ACIP) identified priority groups for vaccination, which did not include persons aged >or=65 years who did not have higher risk for influenza or its complications. During October and November 2009, CDC received reports of 2009 H1N1 outbreaks in LTCFs in Colorado, Maine, and New York. This report summarizes the three outbreaks, which involved facilities primarily housing older patients. These outbreaks illustrate that, despite the lower risk for infection with 2009 H1N1 among persons aged >or=65 years compared with seasonal influenza, 2009 H1N1 outbreaks still can occur in LTCFs. These outbreaks also underscore the importance of respiratory illness surveillance and recommended infection-control procedures in LTCFs. All health-care personnel should be vaccinated against seasonal influenza and 2009 H1N1. LTCF residents should receive seasonal influenza vaccination, and should be vaccinated against 2009 H1N1 after assessment of vaccine availability at the local level indicates that demand for vaccine among younger age groups is being met.


The majority of immunogenic epitopes generate CD4+ T cells that are dependent on MHC class II-bound peptide-flanking residues.
Peptides bind to MHC class II molecules with a defined periodicity such that the peptide-flanking residues (PFRs) P-1 and P11, which lie outside the core binding sequence (P1-P9), are solvent exposed and accessible to the TCR. Using a novel MHC class II:peptide binding assay, we defined the binding register for nine immunogenic epitopes to formally identify the flanking residues. Seven of the nine epitopes, restricted by H-2A(k), H-2A(g7), or H-2E(k), were found to generate T cells that were completely dependent on either P-1 or P11, with dependency on P-1 favored over P11. Such PFR dependency appears to be influenced by the type of amino acid exposed, in that residues that can form salt bridges or hydrogen bonds are favored over small or hydrophobic residues. Peptides containing alanine substitutions at P-1 or P11 in place of PFRs that mediate dependency were considerably less immunogenic and mediated a substantially reduced in vitro recall response to the native protein, inferring that PFR recognition increases immunogenicity. Our data suggest that PFR recognition is a common event characteristic of all MHC class II-restricted T cell responses. This key feature, which is not shared by MHC class I-restricted responses, may underlie the broad functional diversity displayed by MHC class II-restricted T cells.


Model-based registration of ex vivo and in vivo MRI of the prostate using elastography*.
Registration of histopathology to in vivo magnetic resonance imaging (MRI) of the prostate is an important task that can be used to optimize in vivo imaging for cancer detection. Such registration is challenging due to the change in volume and deformation of the prostate during excision and fixation. One approach towards this problem involves the use of an ex vivo MRI of the excised prostate specimen, followed by in vivo to ex vivo MRI registration of the prostate. We propose a novel registration method that uses a patient-specific biomechanical model acquired using magnetic resonance elastography to deform the in vivo volume and match it to the surface of the ex vivo specimen. The forces that drive the deformations are derived from a region-based energy, with the elastic potential used for regularization. The incorporation of elastography data into the registration framework allows inhomogeneous elasticity to be assigned to the in vivo volume. We show that such inhomogeneity improves the registration results by providing a physical regularization of the deformation map. The method is demonstrated and evaluated on six clinical cases.


Assembly of the cysteine synthase complex and the regulatory role of protein-protein interactions.
Macromolecular assemblies play critical roles in regulating cellular functions. The cysteine synthase complex (CSC), which is formed by association of serine O-acetyltransferase (SAT) and O-acetylserine sulfhydrylase (OASS), acts as a sensor and modulator of thiol metabolism by responding to changes in nutrient conditions. Here we examine the oligomerization and energetics of formation of the soybean CSC. Biophysical examination of the CSC by size exclusion chromatography and sedimentation ultracentrifugation indicates that this assembly (complex M(r) approximately 330,000) consists of a single SAT trimer (trimer M(r) approximately 110,000) and three OASS dimers (dimer M(r) approximately 70,000). Analysis of the SAT-OASS interaction by isothermal titration calorimetry reveals negative cooperativity with three distinct binding events during CSC formation with K(d) values of 0.3, 7.5, and 78 nm. The three binding events are also observed using surface plasmon resonance with comparable affinities. The stability of the CSC derives from rapid association and extremely slow dissociation of OASS with SAT and requires the C terminus of SAT for the interaction. Steady-state kinetic analysis shows that CSC formation enhances SAT activity and releases SAT from substrate inhibition and feedback inhibition by cysteine, the final product of the biosynthesis pathway. Cysteine inhibits SAT and the CSC with K(i) values of 2 and 70 microm, respectively. These results suggest a new model for the architecture of this regulatory complex and additional control mechanisms for biochemically controlling plant cysteine biosynthesis. Based on previous work and our results, we suggest that OASS acts as an enzyme chaperone of SAT in the CSC.


A Novel Technique for Transvaginal Retrieval of Enlarged Pelvic Viscera during Minimally Invasive Surgery.
Introduction. With the widespread adoption of laparoscopic and robotic surgery, more and more women are undergoing minimally invasive surgery for complex gynecological procedures. The rate-limiting step is often the delivery of an intact uterus or an unruptured adnexal mass. To avoid conversion to a minilaparotomy for specimen retrieval, we describe a novel technique using an Anchor Tissue Retrieval System bag in conjunction with a pneumo-occluder to easily retrieve large specimens through a colpotomy incision. Surgical Technique. After completion of the robotic-assisted hysterectomy, the uterus, fallopian tubes, and ovaries were too large to be retrieved intact despite multiple attempts of delivery through the colpotomy incision. Prior to resorting to a minilaparotomy or morcellation of the specimen, a 15 mm anchor retrieval bag with a pneumo-occluder was placed through the vagina and the intact specimen was easily placed inside the bag under direct visualization and removed through the colpotomy incision intact. Conclusion. We routinely utilize this technique to retrieve hysterectomy specimens that are not readily delivered through the colpotomy incision and find this technique to be safe, highly efficient, and cost effective when there is a need to remove large intact specimens during minimally invasive surgery.


Quality and safety of broiler meat in various chilling systems.
Chilling is a critical step in poultry processing to attain high-quality meat and to meet the USDA-Food Safety and Inspection Service temperature standards. This study was conducted to determine the effects of commercially available chilling systems on quality and safety of broiler meat. A total of 300 carcasses in 2 replications were randomly selected from a commercial processor and subjected to 3 systems: immersion chill (IC), air chill (AC), and combi in-line air chill (CIAC). Incidence of Salmonella and Campylobacter were determined on pre- and postchilled carcasses. Quality of the meat was evaluated by carcass yield, drip loss, cook loss, texture, moisture content, sensory qualities, and color (L*, a*, and b*) of boneless skinless breast fillets and skin-on drums. Shelf life of whole carcasses, breast fillets, and drums was also determined. The IC resulted in the most reduction of Salmonella (39.7%) and Campylobacter (43%) incidence due to the washing effect and presence of chlorine in the chilled water. There was no significant difference in shelf-life when comparing the chilling methods. The IC had the highest (P < 0.05) carcass yield (6.5%), followed by CIAC (+1.98.0%) and then AC (-1.10%). Drip loss, cook loss, and moisture content of breast fillets were not significantly different for all the chilling systems, but higher L* value was observed for breast fillets at 24 h postmortem treated with IC and CIAC. However, IC exhibited the lightest color and AC was darkest in the drum samples. Shear force of breast meat was significantly more tender for AC and CIAC. There were no differences in the sensory qualities of breast fillets and drums among the 3 chilling systems.


Quantum optical frequency up-conversion for polarisation entangled qubits: towards interconnected quantum information devices.
Realising a global quantum network requires combining individual strengths of different quantum systems to perform universal tasks, notably using flying and stationary qubits. However, transferring coherently quantum information between different systems is challenging as they usually feature different properties, notably in terms of operation wavelength and wavepacket. To circumvent this problem for quantum photonics systems, we demonstrate a polarisation-preserving quantum frequency conversion device in which telecom wavelength photons are converted to the near infrared, at which a variety of quantum memories operate. Our device is essentially free of noise, which we demonstrate through near perfect single photon state transfer tomography and observation of high-fidelity entanglement after conversion. In addition, our guided-wave setup is robust, compact, and easily adaptable to other wavelengths. This approach therefore represents a major building block towards advantageously connecting quantum information systems based on light and matter.


Recurrent Kikuchi-Fujimoto Disease Successfully Treated by the Concomitant Use of Hydroxychloroquine and Corticosteroids.
Kikuchi-Fujimoto disease (KFD) is a benign disease of unknown etiology characterized by lymphadenopathy and a fever. For the majority of patients with KFD, the course is self-limited; however, the optimum method of managing recurrent cases has not yet been established. We herein report a case of a 42-year-old Japanese woman with KFD (confirmed by a lymph node biopsy). Although high-dose prednisolone (PSL) rapidly induced remission, she experienced four recurrences on treatment tapering. Concomitant use of hydroxychloroquine (HCQ) with low-dose PSL induced continuous remission. This is the first case to suggest the effectiveness of HCQ for recurrent KFD in a Japanese patient.


Surveillance of second-degree relatives from melanoma families with a CDKN2A germline mutation.
Lifetime melanoma risk of mutation carriers from families with a germline mutation in the CDKN2A gene is estimated to be 67%. The necessity to include family members in a melanoma surveillance program is widely endorsed, but there is no consensus on which family members should be invited. In a retrospective follow-up study, we investigated the yield of surveillance of first- and second-degree relatives of melanoma and pancreatic cancer patients from 21 families with the "p16-Leiden" CDKN2A mutation. Melanoma incidence rates were compared with the general population. Three-hundred and fifty-four first-degree relatives and 391 second-degree relatives were included. Forty-five first-degree relatives and 11 second-degree relatives were diagnosed with melanoma. Most (72%) of second-degree relatives diagnosed with melanoma had become a first-degree relative before diagnosis, due to the occurrence of a melanoma in a parent or sibling. Overall, melanoma incidence rate was 2.1 per 1,000 person years [95% confidence interval (CI), 1.2-3.8] in family members still being second-degree relatives at diagnosis, compared with 9.9 per 1,000 person years (95% CI, 7.4-13.3) in first-degree relatives. The standardized morbidity ratio for melanoma of second-degree relatives compared with the general population was 12.9 (95% CI, 7.2-23.4). Second-degree relatives from families with the p16-Leiden mutation in CDKN2A have a considerably increased melanoma risk compared with the general population. This study provides justification for the surveillance of second-degree relatives from families with a CDKN2A germline mutation.


Blood Flow Restriction Training: Implementation into Clinical Practice.
To improve muscular strength and hypertrophy the American College of Sports Medicine recommends moderate to high load resistance training. However, use of moderate to high loads are often not feasible in clinical populations. Therefore, the emergence of low load (LL) blood flow restriction (BFR) training as a rehabilitation tool for clinical populations is becoming popular. Although the majority of research on LL-BFR training has examined healthy populations, clinical applications are emerging. Overall, it appears BFR training is a safe and effective tool for rehabilitation. However, additional research is needed prior to widespread application.


Vascular disrupting agent DMXAA enhances the antitumor effects generated by therapeutic HPV DNA vaccines.
Antigen-specific immunotherapy using DNA vaccines has emerged as an attractive approach for the control of tumors. Another novel cancer therapy involves the employment of the vascular disrupting agent, 5,6-dimethylxanthenone-4-acetic acid (DMXAA). In the current study, we aimed to test the combination of DMXAA treatment with human papillomavirus type 16 (HPV-16) E7 DNA vaccination to enhance the antitumor effects and E7-specific CD8+ T cell immune responses in treated mice. We determined that treatment with DMXAA generates significant therapeutic effects against TC-1 tumors but does not enhance the antigen-specific immune responses in tumor bearing mice. We then found that combination of DMXAA treatment with E7 DNA vaccination generates potent antitumor effects and E7-specific CD8+ T cell immune responses in the splenocytes of tumor bearing mice. Furthermore, the DMXAA-mediated enhancement or suppression of E7-specific CD8+ T cell immune responses generated by CRT/E7 DNA vaccination was found to be dependent on the time of administration of DMXAA and was also applicable to other antigen-specific vaccines. In addition, we determined that inducible nitric oxide synthase (iNOS) plays a role in the immune suppression caused by DMXAA administration before DNA vaccination. Our study has significant implications for future clinical translation.


Considering connections between Hollywood and biodiversity conservation.
Cinema offers a substantial opportunity to share messages with a wide audience. However, there is little research or evidence about the potential benefits and risks of cinema for conservation. Given their global reach, cinematic representations could be important in raising awareness of conservation issues and species of concern, as well as encouraging greater audience engagement due to their heightened emotional impact on viewers. Yet there are also risks associated with increased exposure, including heightened visitor pressure to environmentally sensitive areas or changes to consumer demand for endangered species. Conservationists can better understand and engage with the film industry by studying the impact of movies on audience awareness and behavior, identifying measurable impacts on conservation outcomes, and engaging directly with the movie industry, for example, in an advisory capacity. This improved understanding and engagement can harness the industry's potential to enhance the positive impacts of movies featuring species, sites, and issues of conservation concern and to mitigate any negative effects. A robust evidence base for evaluating and planning these engagements, and for informing related policy and management decisions, needs to be built.


Applications of acellular dermal matrix in revision breast reconstruction surgery.
Acellular dermal matrix has been used for over a decade in primary breast reconstruction. Few articles have specifically examined its use in revision breast reconstruction for fold malposition, capsular contracture, rippling, and symmastia. One hundred thirty-five revision breast reconstructive procedures using acellular dermal matrix (AlloDerm) in 118 patients (154 breasts) over a 5-year period were reviewed. Most procedures were revisions or part of the second stage of previous mastectomy reconstructions; three were revisions after reconstruction of congenital chest wall deformities. Fifty-seven revisions (37 percent) were for inferior fold malposition, followed by 40 (25.9 percent) for inferior pole support, 42 (27.2 percent) for capsular contracture, 10 (6.4 percent) for rippling, and five (3.2 percent) for symmastia. The overall complication rate was 5 percent. Revisions with acellular dermal matrix were successful in 147 of 154 breasts (95.5 percent). The most common complication was capsular contracture, occurring in five breasts (3.2 percent). There was one infection (0.6 percent), failure to lower the inframammary fold in one breast (0.6 percent), and one persistence of rippling (0.6 percent). The mean follow-up was 207 days. Acellular dermal matrix has proven to be a reliable tool for managing some of the most common and challenging problems in implant-based breast reconstruction. Although there are few published data on the success of more conventional solutions to fold malposition, lower pole support, and capsular contracture, the addition of acellular dermal matrix to buttress these repairs has been shown to provide a high likelihood of success with a low risk of complications.


Nursing students' understanding and enactment of resilience: a grounded theory study.
The aim of this study was to explore nursing students' understanding and enactment of resilience. Stress is considered to be a major factor affecting the health, well-being and academic performance of nursing students. Resilience has been extensively researched as a process that allows individuals to successfully adapt to adversity and develop positive outcomes as a result. However, relatively little is known about the resilience of nursing students. A constructivist, grounded theory qualitative design was used for this study. In-depth individual interviews were conducted with 38 nursing students enrolled in a four-year, integrated baccalaureate nursing degree programme at a university in Ontario, Canada. Face-to-face interviews were conducted from January to April 2012 using a semi-structured interview guide. The basic social process of 'pushing through' emerged as nursing students' understanding and enactment of resilience. Participants employed this process to withstand challenges in their academic lives. This process was comprised of three main phases: 'stepping into', 'staying the course' and 'acknowledging'. 'Pushing through' also included a transient 'disengaging' process where students were temporarily unable to push through their adversities. The process of 'pushing through' was based on a progressive trajectory, which implied that nursing students enacted the process to make progress in their academic lives and to attain goals. Study findings provide important evidence for understanding the phenomenon of resilience as a dynamic, contextual process that can be learnt and developed, rather than a static trait or personality characteristic.


Assessing retinal vein occlusion based on color fundus photographs using neural understanding network (NUN).
To develop and validate a novel deep learning architecture to classify retinal vein occlusion (RVO) on color fundus photographs (CFPs) and reveal the image features contributing to the classification. The neural understanding network (NUN) is formed by two components: (1) convolutional neural network (CNN)-based feature extraction and (2) graph neural networks (GNN)-based feature understanding. The CNN-based image features were transformed into a graph representation to encode and visualize long-range feature interactions to identify the image regions that significantly contributed to the classification decision. A total of 7062 CFPs were classified into three categories: (1) no vein occlusion ("normal"), (2) central RVO, and (3) branch RVO. The area under the receiver operative characteristic (ROC) curve (AUC) was used as the metric to assess the performance of the trained classification models. The AUC, accuracy, sensitivity, and specificity for NUN to classify CFPs as normal, central occlusion, or branch occlusion were 0.975 (± 0.003), 0.911 (± 0.007), 0.983 (± 0.010), and 0.803 (± 0.005), respectively, which outperformed available classical CNN models. The NUN architecture can provide a better classification performance and a straightforward visualization of the results compared to CNNs.


Pollen sterols are associated with phylogeny and environment but not with pollinator guilds.
Phytosterols are primary plant metabolites that have fundamental structural and regulatory functions. They are also essential nutrients for phytophagous insects, including pollinators, that cannot synthesize sterols. Despite the well-described composition and diversity in vegetative plant tissues, few studies have examined phytosterol diversity in pollen. We quantified 25 pollen phytosterols in 122 plant species (105 genera, 51 families) to determine their composition and diversity across plant taxa. We searched literature and databases for plant phylogeny, environmental conditions, and pollinator guilds of the species to examine the relationships with pollen sterols. 24-methylenecholesterol, sitosterol and isofucosterol were the most common and abundant pollen sterols. We found phylogenetic clustering of twelve individual sterols, total sterol content and sterol diversity, and of sterol groupings that reflect their underlying biosynthesis pathway (C-24 alkylation, ring B desaturation). Plants originating in tropical-like climates (higher mean annual temperature, lower temperature seasonality, higher precipitation in wettest quarter) were more likely to record higher pollen sterol content. However, pollen sterol composition and content showed no clear relationship with pollinator guilds. Our study is the first to show that pollen sterol diversity is phylogenetically clustered and that pollen sterol content may adapt to environmental conditions.


Gene therapy clinical trials worldwide to 2012 - an update.
To date, over 1800 gene therapy clinical trials have been completed, are ongoing or have been approved worldwide. Our database brings together global information on gene therapy clinical trials from official agency sources, published literature, conference presentations and posters kindly provided to us by individual investigators or trial sponsors. This review presents our analysis of clinical trials that, to the best of our knowledge, have been or are being performed worldwide. As of our June 2012 update, we have entries on 1843 trials undertaken in 31 countries. We have analysed the geographical distribution of trials, the disease indications (or other reasons) for trials, the proportions to which different vector types are used, and which genes have been transferred. Details of the analyses presented, and our searchable database are available on The Journal of Gene Medicine Gene Therapy Clinical Trials Worldwide website at: http://www.wiley.co.uk/genmed/clinical. We also provide an overview of the progress being made in clinical trials of gene therapy approaches around the world and discuss the prospects for the future.


Modulation of Type 1 Diabetes Risk by the Intestinal Microbiome.
The purpose of this review is to summarize potential modulations of the intestinal microbiome aimed at preventing or delaying progression to overt type 1 diabetes in the light of recently identified perturbations of the gut microbiota associated with the development of type 1 diabetes. Accumulated data suggest that the gut microbiota is involved at two different steps in the evolution of type 1 diabetes. At the first step, the intestinal tract is colonized by a microbial community unable to provide an adequate education of the immune system. As a consequence, the infant acquires susceptibility to immune-mediated diseases, type 1 diabetes included. At the other step, the young child seroconverts to positivity for diabetes-associated autoantibodies. This is preceded or accompanied by a decrease in the diversity of the intestinal microbiota and an increased abundance of Bacteroides species. These changes will affect the disease process promoting progression toward overt type 1 diabetes. By providing specific probiotics, one can affect the colonization of the intestinal tract in the newborn infant or strengthen the immune education in early life. Human milk oligosaccharides function as nutrients for "healthy" bacteria. Dietary interventions applying modified starches can influence the numbers and activities of both autoreactive and regulatory T cells and provide protection against autoimmune diabetes in non-obese diabetic mice. Modulation of the intestinal microbiome holds the promise of effective protection against human type 1 diabetes.


Histology of the fertile and infertile testis.
This article has reviewed the diagnostic value of testicular biopsy in the evaluation of male infertility. In order to optimize the interpretation of morphologic findings, it is essential that a full medical and occupational history and careful hormonal evaluation be performed. A karyotype may be indicated in some cases. The pathologist has the opportunity to render a diagnostic opinion based on examination of seminiferous tubules and interstitium and correlated with the results of the history, physical examination, and laboratory studies. A rapid quantitative method is available for determining the likelihood that a significant epididymal obstruction exists that may be relieved surgically.


Deep learning detects genetic alterations in cancer histology generated by adversarial networks.
Deep learning can detect microsatellite instability (MSI) from routine histology images in colorectal cancer (CRC). However, ethical and legal barriers impede sharing of images and genetic data, hampering development of new algorithms for detection of MSI and other biomarkers. We hypothesized that histology images synthesized by conditional generative adversarial networks (CGANs) retain information about genetic alterations. To test this, we developed a 'histology CGAN' which was trained on 256 patients (training cohort 1) and 1457 patients (training cohort 2). The CGAN synthesized 10 000 synthetic MSI and non-MSI images which contained a range of tissue types and were deemed realistic by trained observers in a blinded study. Subsequently, we trained a deep learning detector of MSI on real or synthetic images and evaluated the performance of MSI detection in a held-out set of 142 patients. When trained on real images from training cohort 1, this system achieved an area under the receiver operating curve (AUROC) of 0.742 [0.681, 0.854]. Training on the larger cohort 2 only marginally improved the AUROC to 0.757 [0.707, 0.869]. Training on purely synthetic data resulted in an AUROC of 0.743 [0.658, 0.801]. Training on both real and synthetic data further increased AUROC to 0.777 [0.715, 0.821]. We conclude that synthetic histology images retain information reflecting underlying genetic alterations in colorectal cancer. Using synthetic instead of real images to train deep learning systems yields non-inferior classifiers. This approach can be used to create large shareable data sets or to augment small data sets with rare molecular features. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.


Ternary solvent based homogeneous liquid-liquid microextraction for the preconcentration of organochlorine pesticides from water and apple juice samples.
In the present study, the optimal experimental conditions were determined by optimizing the effect of extraction solvent types and volume, salt types and concentration, centrifugation speed and time using one variable at a time. Under optimal experimental conditions, calibration curves were constructed separately using water and apple juice samples as representative matrices, and good linearities were achieved over a wide concentration range of 0.2-1600 ng L-1 with a coefficient of determination (r2) ≥ 0.998. The limits of detection (LOD) and limits of quantification (LOQ), determined to be 3 and 10 times the signal-to-noise ratios (S/N), were between 0.07-3.9 and 0.2-12.0 ng L-1 for water samples and 2.6-10.0 and 8.0-30.0 ng L-1 for the apple juice sample respectively. The precisions study showed %RSD values of ≤6% for both matrices, indicating satisfactory precisions. The enrichment factors and recoveries of the proposed method ranged from 41.4-74.5 and 86-109% respectively. The proposed method could be used as a simple and environmentally friendly alternative for the analysis of OCPs from environmental and food matrices. This method potentially offers a more sustainable and effective approach to monitoring OCPs in environmental and food products. Its use in the analysis of apple juice samples is particularly novel and can provide valuable insights into pesticide contamination in fruit juices.


360-degree large-scale multiprojection light-field 3D display system.
This paper proposes a 360-deg large-scale multiprojection light-field 3D display system, which can reconstruct the light field of models in real space. The reconstructed contents can be observed by multiple viewers from different angles and positions simultaneously. In this system, 360 projectors project images onto a cylindrical light-field diffusion screen whose height is 1.8 m and diameter is 3 m. When moving around the system, viewers can see 3D scenes with smooth-motion parallax, and the frame rate can reach 30 fps and above. To achieve a large-scale display, we design a wide-field lens with cylindrical lenses to enlarge the projection image. To promote efficiency of data transmission and render 3D contents in real time, we apply computers equipped with multiple graphic cards, and display data are divided by field programmable gate array. Finally, a 360-deg light-field autocalibration method based on CCD and multiview sampling is proposed, whose calibration effect is strongly confirmed by experiment results.


[Investigating occupational risk in visual strain].
The article deals with materials of industrial and laboratory studies on risk of acute and chronic functional overstrain due to visual work in humans. The authors demonstrated value of intensity, structure and duration of visual strain as etiologic risk factors.


Disruptions in surgical flow and their relationship to surgical errors: an exploratory investigation.
Disruptions in surgical flow have the potential to increase the occurrence of surgical errors; however, little is known about the frequency and nature of surgical flow disruptions and their effect on the etiology of errors, which makes the development of evidence-based interventions extremely difficult. The goal of this project was to study surgical errors and their relationship to surgical flow disruptions in cardiovascular surgery prospectively to understand better the effect of these disruptions on surgical errors and ultimately patient safety. A trained observer recorded surgical errors and flow disruptions during 31 cardiac surgery operations over a 3-week period and categorized them by a classification system of human factors. Flow disruptions were then reviewed and analyzed by an interdisciplinary team of experts in operative and human factors. Flow disruptions consisted of teamwork/communication failures, equipment and technology problems, extraneous interruptions, training-related distractions, and issues in resource accessibility. Surgical errors increased significantly with increases in flow disruptions. Teamwork/communication failures were the strongest predictor of surgical errors. These findings provide preliminary data to develop evidence-based error management and patient safety programs within cardiac surgery with implications to other related surgical programs.


Proteomics to display tissue repair opposing injury response to LPS-induced liver injury.
To examine the protein expression alterations in liver injury/repair network regulation as a response to gut-derived lipopolysaccharide (LPS) treatment, in order to anticipate the possible signal molecules or biomarkers in signaling LPS-related liver injury. Male BALB/c mice were treated with intra-peritoneal (i.p.) LPS (4 mg/kg) and sacrificed at 0, 6, 24 and 30 h to obtain livers. The livers were stained with hematoxylin and eosin for histopathologic analyses. Total liver protein was separated by two-dimensional gel electrophoresis (2-DE). The peptide mass of liver injury or repair related proteins were drawn up and the protein database was searched to identify the proteins. Observations were as follows: (1) TRAIL-R2 was down regulated in livers of LPS-treated mice. TNFAIP1 was significantly up regulated at 6 h, then down- regulated at 24, 30 h with silent expression during senescent stage. (2) The amount of metaxin 2 and mitochondria import inner membrane translocase subunit TIM8a (TIMM8A) was increased upon treatment with LPS. (3) P34 cdc2 kinase was significantly up-regulated 30 h after LPS administration with silent expression during senescent, 6, 24 h treated stage. (4) The amount of proteasome activator 28 alpha subunit (PA28), magnesium dependent protein phosphatase (MDPP) and lysophospholipase 2 was decreased 6 h after LPS treatment but recovered or up-regulated 24 and 30 h after LPS treatment. LPS-treated mouse liver displaying a time-dependent liver injury can result in expression change of some liver injury or repair related proteins.


Expansion of IgG+ B-cells during mitogen stimulation for memory B-cell ELISpot analysis is influenced by size and composition of the B-cell pool.
The memory B-cell (MBC) ELISpot assay is the main technique used to measure antigen-specific MBCs as a readout of humoral immune memory. This assay relies on the ability of MBCs to differentiate into antibody-secreting cells (ASC) upon polyclonal stimulation. The total number of IgG+ ASCs generated by mitogen-stimulation is often used as a reference point; alternatively antigen-specific MBCs are expressed as a frequency of post-culture peripheral blood mononuclear cells (PBMC) as a surrogate for absolute frequencies. Therefore, it is important to know whether IgG+ B-cells are uniformly expanded during the preceding mitogen-culture as a true reflection of MBC frequencies ex vivo. We systematically compared B-cell phenotype and proportions before and after mitogen stimulation in cultures of 269 peripheral blood mononuclear cell samples from 62 volunteers by flow cytometry and analyzed the number of resulting ASCs. Our data show that the number of total IgG+ ASCs detected by ELISpot after mitogen stimulation correlates with the proportion of IgG+ MBCs ex vivo, highlighting its general robustness for comparisons of study cohorts at group level. The expansion of total and IgG+ B-cells during mitogen-stimulation, however, was not identical in all cultures, but influenced by size and composition of the ex vivo B-cell compartment. The uncorrected readout of antigen-specific MBCs per million post-culture PBMCs therefore only preserves the quality, but not the magnitude of differences in the ex vivo MBC response between groups or time points, particularly when comparing samples where the B-cell compartment substantially differs between cohorts or over time. Therefore, expressing antigen-specific cells per total IgG+ ASCs is currently the best measure to correct for mitogen-culture effects. Additionally, baseline information on the size and composition of the ex vivo B-cell compartment should be supplied to additionally inform about differences or changes in the size and composition of the ex vivo MBC compartment.


Tau in Alzheimer disease and related tauopathies.
Tau is the major microtubule associated protein (MAP) of a mature neuron. The other two neuronal MAPs are MAP1 and MAP2. An established function of MAPs is their interaction with tubulin and promotion of its assembly into microtubules and stabilization of the microtubule network. The microtubule assembly promoting activity of tau, a phosphoprotein, is regulated by its degree of phosphorylation. Normal adult human brain tau contains 2-3 moles phosphate/mole of tau protein. Hyperphosphorylation of tau depresses this biological activity of tau. In Alzheimer disease (AD) brain tau is ~three to four-fold more hyperphosphorylated than the normal adult brain tau and in this hyperphosphorylated state it is polymerized into paired helical filaments ([PHF) admixed with straight filaments (SF) forming neurofibrillary tangles. Tau is transiently hyperphosphorylated during development and during anesthesia and hypothermia but not to the same state as in AD brain. The abnormally hyperphosphorylated tau in AD brain is distinguished from transiently hyperphosphorylated tau by its ability (1) to sequester normal tau, MAP1 and MAP2 and disrupt microtubules, and (2) to self-assemble into PHF/SF. The cytosolic abnormally hyperphosphorylated tau, because of oligomerization, unlike normal tau, is sedimentable and on self-assembly into PHF/SF, loses its ability to sequester normal MAPs. Some of the tau in AD brain is truncated which also promotes its self-assembly. Tau mutations found in frontotemporal dementia apparently promote its abnormal hyperphosphorylation. Thus, the AD abnormally hyperphosphorylated tau (1) is distinguishable from both normal and transiently hyperphosphorylated taus, and (2) is inhibitory when in a cytosolic/oligomeric state but not when it is self-assembled into PHF/SF. Inhibition of abnormal hyperphosphorylation of tau offers a promising therapeutic target for AD and related tauopathies.


Point-counterpoint of sphingosine 1-phosphate metabolism.
Sphingosine 1-phosphate (S1P), an evolutionarily conserved bioactive lipid mediator, is now recognized as a potent modulator of cell regulation. In vertebrates, S1P interacts with cell surface G protein-coupled receptors of the EDG family and induces profound effects in a variety of organ systems. Indeed, an S1P receptor agonist is undergoing clinical trials to combat immune-mediated transplant rejection. Recent information on S1P receptor biology suggests potential utility in the control of cardiovascular processes, including angiogenesis, vascular permeability, arteriogenesis, and vasospasm. However, studies from diverse invertebrates, such as yeast, Dictyostelium, Drosophila, and Caenorhabditis elegans have shown that S1P is involved in important regulatory functions in the apparent absence of EDG S1P receptor homologues. Metabolic pathways of S1P synthesis, degradation, and release have recently been described at the molecular level. Genetic and biochemical studies of these enzymes have illuminated the importance of S1P signaling systems both inside and outside of cells. The revelation of receptor-dependent pathways, as well as novel metabolic/intracellular pathways has provided new biological insights and may ultimately pave the way for the development of novel therapeutic approaches for cardiovascular diseases.


Isolation and identification of bacterial endophytes from pharmaceutical agarwood-producing Aquilaria species.
Resins and gums are used in traditional medicine and do have potential applications in pharmacy and medicine. Agarwood is the fragrant resinous wood, which is an important commodity from Aquilaria species and has been used as a sedative, analgesic, and digestive in traditional medicine. Endophytic bacteria are potentially important in producing pharmaceutical compounds found in the plants. Hence, it was important to understand which types of endophytic bacteria are associated with pharmaceutical agarwood-producing Aquilaria species. This study was undertaken to isolate and identify endophytic bacteria associated with agarwood-producing seven (7) Aquilaria species from Malaysia. Botanical samples of seven Aquilaria species were collected, and endophytic bacteria were isolated from surface-sterilized-tissue samples. The 16S rRNA gene fragments were amplified using PCR method, and endophytic bacterial isolates (EBIs) were identified based on 16S rRNA gene sequence similarity based method. Culturable, 77 EBIs were analyzed, and results of 16S rRNA gene sequences analysis suggest that 18 different types of endophytic bacteria are associated with (seven) Aquilaria species. From 77 EBIs, majority (36.4%) of the isolates were of Bacillus pumilus. These findings indicate that agarwood-producing Aquilaria species are harboring 18 different types of culturable endophytic bacteria.


Integrating nested PCR with high-throughput sequencing to characterize mutations of HBV genome in low viral load samples.
Due to the low viral load of hepatitis B virus (HBV) in plasma samples, conventional techniques have limitations to the detection of antiviral resistance mutations. To solve the problem, we developed a fast, highly sensitive, and accurate method to sequence the HBV whole-genome sequencing in plasma samples which had various viral loads from very low to high.Twenty-one plasma samples were collected from patients who were carriers of HBV from the Hangzhou First People's Hospital. Two pairs of conserved, overlapping, nested primers were used to amplify and sequence the whole HBV genome in 8 plasma samples with different viral loads. High-throughput sequencing was performed on Illumina MiSeq platform. Concomitantly, 3 samples were directly sequenced without PCR amplification. We compared amplicon-sequencing with direct sequencing to develop a method for amplifying and characterizing the whole genome of HBV.HBV genome was amplified from all samples and verified by Sanger sequencing, regardless of the viral loads. Sequencing results revealed that only a few reads were mapped to the HBV genome following direct sequencing, while the amplicon-sequencing reads had a good coverage and depth. We identified 50 intrahost single nucleotide variations (iSNVs), 14 of which were low frequency mutations. Interestingly, iSNVs were more common in low viral load samples than in high viral load samples, and mutations in the reverse transcriptase (RT) region were most prevalent.We conclude that amplicon-sequencing is not only a practical method to detect HBV infection with a high sensitivity and accuracy but also enables to detect mutations in the HBV genome in low viral load samples from HBV-infected patients. Thus, our findings provide a new diagnosis method of HBV infection, which is capable of detection of low frequent mutations in low viral load samples.


Public health research outputs from efficacy to dissemination: a bibliometric analysis.
More intervention research is needed, particularly 'real world' intervention replication and dissemination studies, to optimize improvements in health. This study assessed the proportion and type of published public health intervention research papers over time in physical activity and falls prevention, both important contributors to preventable morbidity and mortality. A keyword search was conducted, using Medline and PsycINFO to locate publications in 1988-1989, 1998-1999, and 2008-2009 for the two topic areas. In stage 1, a random sample of 1200 publications per time period for both topics were categorized as: non-public health, non-data-based public health, or data-based public health. In stage 2 data-based public health articles were further classified as measurement, descriptive, etiological or intervention research. Finally, intervention papers were categorized as: efficacy, intervention replication or dissemination studies. Inter-rater reliability of paper classification was 88%. Descriptive studies were the most common data-based papers across all time periods (1988-89; 1998-1999;2008-2009) for both issues (physical activity: 47%; 54%; 65% and falls 75%; 64%; 63%), increasing significantly over time for physical activity. The proportion of intervention publications did not increase over time for physical activity comprising 23% across all time periods and fluctuated for falls across the time periods (10%; 21%; 17%). The proportion of intervention articles that were replication studies increased over the three time periods for physical activity (0%; 2%; 11%) and for falls (0%; 22%; 35%). Dissemination studies first appeared in the literature in 2008-2009, making up only 3% of physical activity and 7% of falls intervention studies. Intervention research studies remain only a modest proportion of all published studies in physical activity and falls prevention; the majority of the intervention studies, are efficacy studies although there is growing evidence of a move towards replication and dissemination studies, which may have greater potential for improving population health.


Improving access to community-based pulmonary rehabilitation: 3R protocol for real-world settings with cost-benefit analysis.
Pulmonary rehabilitation (PR) has demonstrated patients' physiological and psychosocial improvements, symptoms reduction and health-economic benefits whilst enhances the ability of the whole family to adjust to illness. However, PR remains highly inaccessible due to lack of awareness of its benefits, poor referral and availability mostly in hospitals. Novel models of PR delivery are needed to enhance its implementation while maintaining cost-efficiency. We aim to implement an innovative community-based PR programme and assess its cost-benefit. A 12-week community-based PR will be implemented in primary healthcare centres where programmes are not available. Healthcare professionals will be trained. 73 patients with CRD and their caregivers (dyads patient-caregivers) will compose the experimental group. The control group will include dyads age- and disease-matched willing to collaborate in data collection but not in PR. Patients/family-centred outcomes will be dyspnoea (modified Medical Research Council Questionnaire), fatigue (Checklist of individual strength and Functional assessment of chronic illness therapy - fatigue), cough and sputum (Leicester cough questionnaire and Cough and sputum assessment questionnaire), impact of the disease (COPD Assessment Test), emotional state (The Hospital Anxiety and Depression Scale), number of exacerbations, healthcare utilisation, health-related quality of life and family adaptability/cohesion (Family Adaptation and Cohesion Scale). Other clinical outcomes will be peripheral (biceps and quadriceps-hand held dynamometer, 1 or 10 repetition-maximum) and respiratory (maximal inspiratory and expiratory pressures) muscle strength, muscle thickness and cross sectional area (biceps brachialis, rectus femoris and diaphragm-ultrasound imaging), exercise capacity (six-minute walk test and one-minute sit to stand test), balance (brief-balance evaluation systems test) and physical activity (accelerometer). Data will be collected at baseline, at 12 weeks, at 3- and 6-months post-PR. Changes in the outcome measures will be compared between groups, after multivariate adjustment for possible confounders, and effect sizes will be calculated. A cost-benefit analysis will be conducted. This study will enhance patients access to PR, by training healthcare professionals in the local primary healthcare centres to conduct such programmes and actively involving caregivers. The cost-benefit analysis of this intervention will provide an evidence-based insight into the economic benefit of community-based PR in chronic respiratory diseases. The trial was registered in the ClinicalTrials.gov U.S. National Library of Medicine, on 10th January, 2019 (registration number: NCT03799666 ).


Ecological Location of a Water Source and Spatial Dynamics of Behavior Under Temporally Scheduled Water Deliveries in a Modified Open-Field System: An Integrative Approach.
It has been reported in non-contingent schedules that the variety of patterns of behavior is affected by the temporal variation of water deliveries. While temporal variation is accomplished by delivering water at fixed or variable times, spatial variation is usually accomplished by varying the number of dispensers and distance among them. Such criteria do not consider the possible ecological relevance of the location of water dispensers. Nevertheless, it is plausible to suppose that the intersection of the programed contingencies (e.g., time-based schedules), the ecological differentiated space (e.g., open vs. closed zones), and the relative location of relevant objects and events (e.g., location of the water source-peripherical vs. center zone) could set up an integrated system with the behavioral patterns of the organism. In the present study, we evaluated the eco-functional relevance of two locations of the dispensers upon behavioral dynamics in Wistar rats using fixed and variable time schedules in a modified open-field system. In Experiment 1, three subjects were exposed to a fixed time 30-s water delivery schedule. In the first condition, the water dispenser was located at the center of the experimental chamber. In the second condition, the water dispenser was located at the center of a wall of the experimental chamber. Each location was present for 20 sessions. In Experiment 2, conditions were the same, but a variable time schedule was used. Routes, distance to the dispenser, recurrence patterns, time spent in zones, entropy, and divergence were analyzed. Our findings suggest a robust differential relevance of the location of the dispensers that should be considered in studies evaluating behavioral dynamics. Results are discussed from an integrative, ecological-parametric framework.


Metabolite changes in individual rat muscle fibers during stimulation.
Rat plantaris and soleus muscles were stimulated intensely in vivo for 1 and 15 min, freeze-clamped, and freeze-dried, and individual fibers were dissected free. Fibers, assigned to four groups on the basis of lactate dehydrogenase and malate dehydrogenase, were each separately analyzed for ATP, P-creatine, glycogen, glucose, glucose-6-phosphate (glucose-6-P), lactate, citrate, and malate. Some fibers were also analyzed for fructose 1,6-phosphate, total adenylate and total creatine. Although each group as a whole showed significant and often large differences in control composition and response to stimulation, individual fibers varied enough to create an almost continuous spectrum of metabolite levels from one extreme to the other. The data suggest that the slowest twitch fibers were the most active in the control state. Stimulation for 1 min caused a small increase in ATP in all groups with a large decrease in P-creatine in "fast white" fibers and a modest decrease in the rest. After 15-min stimulation, fast white fibers had lost 60% of initial ATP and 97% of initial P-creatine, whereas in other fiber types these compounds underwent little further change. Metabolite changes with stimulation were also greatest in fast white fibers. Glucose-6-P rose 15-fold in 1 min, then fell to below control by 15 min when glycogen had been exhausted; lactate rose two to six times more than in other types. Glucose rose in all groups to levels at 15 min, compatible with equilibrium with blood plasma.


Doctor-patient communication issues for international medical graduates: research findings from Australia.
Understanding the impact of culture on medical communication is particularly important for international medical graduates (IMGs) who enter health systems from different cultures of origin. This article presents data on IMGs' perception of the impact of cultural factors on IMG doctor-patient communication during their integration into the Australian health system. The methodology used was a descriptive qualitative methodology, using iterative, open-ended, in-depth interviews with a sample of 30 IMGs employed at a hospital in Brisbane, Queensland, Australia. According to subjects' comments, understanding patient-centered communication is a major challenge faced by IMGs during integration in the Australian health system. They perceive that this difficulty is associated with the major shift from the culture of their country of origin (described as paternalistic doctor-dominated communication system; standard practice to talk to the family and not the patient) to the very different health care culture of Australia (perceived to be more educated and informed consumers that demand high levels of information and discussion). The findings detail IMGs' experience with learning about patient-centered communication at the point of arrival, during integration and practice. Subjects' perceived the need to provide education on patient-centered communication for IMGs integrating into the Australian health system. There is a significant need for IMGs to be educated in cultural issues including doctor-patient communication practices in Australia.


Effect of antioxidant extract from cherries on diabetes.
Diabetes is a chronic metabolic disorder in humans constituting a major health concern today whose prevalence has continuously increased worldwide over the past few decades. Production of reactive oxygen species (ROS) and disturbed capacity of antioxidant defense in diabetic subjects have been reported. It has been suggested that enhanced production of free radicals and oxidative stress is the central event for the development of diabetic complications. Antioxidants can play an important role in the improvement of diabetes. There are many reports on the effects of antioxidants in the management of diabetes. This study aimed at evaluating the effect of antioxidant extract and purified sweet and sour Cherries on hyperglycemia, microalbumin and creatinine level in alloxan-induced diabetic rats. Thirty six adult Male Wistar rats were divided equally into six groups. Diabetes was induced in the rats by an intraperitoneal injection with 120 mg/kg body weight of alloxan. Oral administration of cherry extract at a concentration of 200 mg/kg body weight for 30 days significantly reduced the levels of blood glucose, and urinary microalbumin. Also an increase in the creatinine secretion level in urine was observed in the diabetic rats treated with the cherry extract as compared to untreated diabetic rats. In this paper, the most recent patent on the identification and treatment of diabetes is used. In conclusion, cherry antioxidant extract proved to have a beneficial effect on the diabetic rats in this study. In light of these advantageous results, it is advisable to broaden the scale of use of sweet and sour cherries extract in a trial to alleviate the adverse effects of diabetes.


Accuracy of clinical variables in the identification of radiographically proven constipation in children.
To determine whether clinical variables accurately identify children with radiographically proven constipation. Prospective, cross sectional case series of children 2-12 years of age with abdominal pain (AP) requiring radiographic evaluation. Constipation was defined radiographically as the presence of fecal material throughout the colon. The presence of other pathology was noted. The pediatric emergency department (ED) physicians recorded a comprehensive history and physical examination and a provisional diagnosis was made. Radiographs were initially interpreted by the pediatric ED attending physicians; the official interpretation was later provided by a single board certified pediatric radiologist who was blinded to the ED interpretation. A discriminant analysis was performed to identify variables that could best discriminate between patients with, and without, radiographically proven constipation. In total 251 patients were enrolled over a 12 month period. Four variables were noted to be more common in constipated patients: a history of normal or hard stools, absence of rebound tenderness, presence of tenderness in the left lower quadrant and stool in the rectal vault on exam. Stool present on rectal exam was the best discriminator between patients with and without constipation. The discriminant analysis model had a sensitivity of 77%, specificity of 35% and a negative predictive value of 55%. No clinical variable, either as a single variable or in a model, accurately identified patients with abdominal pain and radiographically proven constipation.


Exploring Species-Specificity in TLR4/MD-2 Inhibition with Amphiphilic Lipid A Mimicking Glycolipids.
The Toll-like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD-2) complex is a key receptor of the innate immune system and a major driver of inflammation that is responsible for the multifaceted defense response to Gram-negative infections. However, dysfunction in the tightly regulated mechanisms of TLR4-mediated signaling leads to the uncontrolled upregulation of local and systemic inflammation, often resulting in acute or chronic disease. Therefore, the TLR4/MD-2 receptor complex is an attractive target for the design and development of anti-inflammatory therapies which aim to control the unrestrained activation of TLR4-mediated signaling. Complex structure-activity relationships and species-specificity behind ligand recognition by the TLR4/MD-2 complex complicate the development of MD-2-specific TLR4 antagonists. The restriction of the conformational flexibility of the disaccharide polar head group is one of the key structural features of the newly developed lipid A-mimicking glycophospholipids, which are potential inhibitors of TLR4-mediated inflammation. Since phosphorylation has a crucial influence on MD-2-ligand interaction, glycolipids with variable numbers and positioning of phosphate groups were synthesized and evaluated for their ability to inhibit TLR4-mediated pro-inflammatory signaling in human and murine immune cells. A bis-phosphorylated glycolipid was found to have nanomolar antagonist activity on human TLR4 while acting as a partial agonist on murine TLR4. The glycolipid inhibited mTLR4/MD-2-mediated cytokine release, acting as an antagonist in the presence of lipopolysaccharide (LPS), but at the same time induced low-level cytokine production.