Intensity of inflammation as the most important predictor of myocardial involvement in JIA. A 3D echocardiographic study.
Myocardial dysfunction is an important complication in the context of juvenile idiopathic arthritis (JIA). Several mechanisms might be involved in the induction of myocardial injury in such a disabling disease. Among several factors involved, myocardial inflammation and cardiotoxic drugs were thought to be the most incriminated factors. The aim of this paper was to determine the most important factors that implicated myocardial injury in JIA and to weigh whether the severity of inflammation varies significantly among the several subtypes or not. Sixty JIA patients as well as sixty, age and surface area, matched controls were subjected to conventional Echocardiography, 3D Speckle tracking and the disease activity was measured as by Juvenile Arthritis Disease Score 27 (JADAS 27). JIA cases showed statistically significant systolic and diastolic dysfunction when compared to controls. Global longitudinal strain (GLS) (index of systolic function) was lower in cases compared to controls (JIA: 16.1±6.7 vs Controls: 23.9±1.4, P < 0.0001), Left Ventricular ratio of early diastolic mitral inflow velocity to average of early diastolic velocities of the mitral annulus and basal septum (LV E/E') (index of diastolic function) was higher in cases compared to controls (JIA: 14.8±7 vs. Controls: 5.9±1.3). There was no statistically significant difference in echocardiographic parameters as well as JADAS 27 between subtypes of JIA patients. Multivariate analysis showed that the best predictor of both systolic and diastolic involvement of the myocardium in JIA patients was the severity of inflammation rather than the duration or the type of medications used. This study points out the potential of inflammation as an important inducer of myocardial injury in JIA. It also underlines the fact that this inflammation does not differ significantly according to the disease subtype.


Immunogenicity and safety of a measles-mumps-rubella-varicella vaccine following a 4-week or a 12-month interval between two doses.
The MMRV combination vaccine, Priorix-Tetra™, is currently licensed in several European countries using a two-dose schedule in infants aged ≥9 months, with a preferred 6-week to 3-month interval between doses. This study was undertaken to generate safety and immunogenicity data for two doses of MMRV vaccine administered according to dose schedules using the shortest permitted interval of 4 weeks versus a longer interval of 12 months, which would allow flexible adaptation to local immunization calendars. Healthy children aged 11-13 months were randomized (1:1:1) to receive 2 doses of either: MMRV vaccine with a 4-week interval between doses (MMRV-4W group, N=188), MMRV vaccine with a 12-month interval between doses (MMRV-12M group, N=184), or MMR vaccine with a 4-week interval between doses (MMR group, N=187). Blood samples were taken prior to, and 4-6 weeks after each vaccination. Post-Dose 2, both MMRV groups exhibited an adequate immunogenic response for all components; however the MMRV-12M group showed significantly greater geometric mean titers for mumps, rubella and varicella. Two varicella breakthrough cases occurred within the 12-month interval between doses in the MMRV-12M group. Local and general reactogenicity results were similar for all groups except for the MMRV-4W group, which had a greater incidence of fever during Days 0-14 post-Dose 1. Two doses of MMRV vaccine administered in the second year of life elicited adequate immunogenicity and were well-tolerated whether administered with a dose interval of 4 weeks or 12 months.


Time-series transcriptome of Brachypodium distachyon during bacterial flagellin-induced pattern-triggered immunity.
Plants protect themselves from microorganisms by inducing pattern-triggered immunity (PTI) via recognizing microbe-associated molecular patterns (MAMPs), conserved across many microbes. Although the MAMP perception mechanism and initial events during PTI have been well-characterized, knowledge of the transcriptomic changes in plants, especially monocots, is limited during the intermediate and terminal stages of PTI. Here, we report a time-series high-resolution RNA-sequencing (RNA-seq) analysis during PTI in the leaf disks of Brachypodium distachyon. We identified 6,039 differentially expressed genes (DEGs) in leaves sampled at 0, 0.5, 1, 3, 6, and 12 hours after treatment (hat) with the bacterial flagellin peptide flg22. The k-means clustering method classified these DEGs into 10 clusters (6 upregulated and 4 downregulated). Based on the results, we selected 10 PTI marker genes in B. distachyon. Gene ontology (GO) analysis suggested a tradeoff between defense responses and photosynthesis during PTI. The data indicated the recovery of photosynthesis started at least at 12 hat. Over-representation analysis of transcription factor genes and cis-regulatory elements in DEG promoters implied the contribution of 12 WRKY transcription factors in plant defense at the early stage of PTI induction.


[Vaccine development: strategies for coping with the antigenic diversity of bacteria].
Bacterial pathogens have evolved a whole range of anti-immune strategies to overcome both the innate and acquired immunity of their hosts. These strategies play a crucial role in the capacity of pathogens to trigger disease and also explain why it is so difficult to develop vaccines and to control these microorganisms. One of the main problems is that bacteria are highly antigenically diverse. The vaccination strategies for coping with this variability, which we are starting to understand more fully as a result of sequencing bacterial genomes, consist of using either several variants of one or more proteins capable of inducing protective antibodies, or else proteins (or protein fragments) or epitopes that have been relatively well preserved notably because they are involved in the pathogen's metabolism. The most sophisticated approach calls upon 'pan genomic' inverse vaccinology which compares the protein profiles of a large number of isolates from various strains of a single species in order to reveal the surface-expressed proteins present in all the isolates. Of these proteins, the ones which are expressed when the host is infected are then evaluated in order to determine their capacity to induce a protective immune response. So far this approach has been successful in controlling bacteria in humans and the way is now open for its application in veterinary medicine, thanks to progress with the genomic sequencing of pathogens of veterinary importance.


[The value of otoneurologic findings for prognosing the outcome of severe cranio-cerebral injury].
The otoneurological symptoms of the acute period of craniocerebral injuries provide clear data for the determination of the severity of the trauma and depth of coma, the distinctness of the general cerebral, hypertensive and brain stem symptoms; they are important for the diagnosis of fissures of the temporal bone pyramids and anterior cranial fossa, and for revealing the penetrating nature of the injury. Otoneurological symptoms are observed during the residual period of the trauma in 94% of the injured; their importance consists in the determination of the residual local disorders due to the trauma in order to define the degree of rehabilitation of the patients.


Stability or improvement in forced vital capacity with nintedanib in patients with idiopathic pulmonary fibrosis.
In the Phase III INPULSIS® trials, nintedanib reduced the annual rate of decline in forced vital capacity (FVC) versus placebo in patients with idiopathic pulmonary fibrosis (IPF).We conducted post hoc analyses of the distribution of changes in FVC in the INPULSIS® trials and FVC changes in the open-label extension trial INPULSIS®-ON in subgroups of patients based on whether patients had shown an improvement or no decline in FVC in INPULSIS®. Analyses were descriptive.Based on the annual rate of change in FVC, 158 of 638 patients (24.8%) treated with nintedanib and 38 of 423 patients (9.0%) treated with placebo had an improvement/no decline in FVC in the INPULSIS® trials. In patients whose FVC improved/did not decline, median (interquartile range) improvements in FVC at week 52 were 76.5 (31-152) mL and 57.5 (31-103) mL in the nintedanib and placebo groups, respectively. Changes in FVC from baseline to week 48 of INPULSIS®-ON were similar in patients whose FVC improved or declined in the preceding INPULSIS® trial.In the INPULSIS® trials, treatment with nintedanib resulted in a greater proportion of patients with IPF showing an improvement/no decline in FVC compared to taking placebo. Mechanisms underlying improvement in FVC in patients with IPF are unknown.


Painful trigeminal neuropathy associated with anti-Plexin D1 antibody.
To determine whether anti-Plexin D1 antibody (Plexin D1-immunoglobulin G [IgG]), which is associated with limb and trunk neuropathic pain (NP) and binds to pain-conducting small unmyelinated dorsal root ganglion (DRG) neurons, exists in patients with idiopathic painful trigeminal neuropathy (IPTN) and whether Plexin D1-IgG binds to trigeminal ganglion (TG) neurons. We enrolled 21 consecutive patients with IPTN and 35 age- and sex-matched controls without NP (25 healthy persons and 10 with neurodegenerative diseases). We measured serum Plexin D1-IgG using a mouse DRG tissue-based indirect immunofluorescence assay (IFA) and by Western blotting (WB) using a recombinant human Plexin D1 (rhPlexin D1) accompanied by immunoadsorption tests with rhPlexin D1. The reactivity of Plexin D1-IgG toward mouse TG, brain, heart, and kidney was assessed by tissue-based IFAs. Serum Plexin D1-IgG was detected more frequently in IPTN than in controls by both IFA and WB (14.3% vs 0%, p = 0.048). Three Plexin D1-IgG-positive patients also had limb or trunk NP and commonly showed tongue pain. In tissue-based IFAs, IgG from 2 Plexin D1-IgG-positive patients immunostained small TG neurons, which was prevented by preincubation with rhPlexin D1. Moreover, Plexin D1-IgG immunostaining mostly colocalized with isolectin B4-positive pain-conducting unmyelinated TG neurons. IFAs of other tissues with the same IgG revealed weak immunoreactivity only in endothelial cells, which was prevented by preincubation with rhPlexin D1. Plexin D1-IgG, which binds to pain-conducting small TG neurons in addition to DRG neurons, can be present in IPTN as well as limb and trunk NP.


Powerlessness, empowerment, and health: implications for health promotion programs.
PURPOSE AND SCOPE. This article reviews the health and social science research relevant to both the role of powerlessness as a risk factor for disease, and the role of empowerment as a health-enhancing strategy. The research literature surveyed includes studies that address these key concepts from the fields of social epidemiology, occupational health, stress research, social psychology, community psychology, social support and networks, community competence and community organizing. Definitions are provided to operationalize these sometimes loosely-applied terms. IMPORTANT FINDINGS. Powerlessness, or lack of control over destiny, emerges as a broad-based risk factor for disease. Empowerment, though more difficult to evaluate, can also be demonstrated as an important promoter of health. MAJOR CONCLUSIONS. Given the importance and currency of these concepts of powerlessness and empowerment, a model of empowerment education is proposed for health-promotion practitioners. Measurement of empowerment raises issues for researchers on how to test the multiple personal and community changes that may result from an empowering education intervention.


[Treatment of iron deficiency in preschool children with a weekly dose of ferrous sulfate].
Iron deficiency is the most frequent haematological disease during the paediatric age and is a health public problem; the iron deficiency has a special interest during early development of human beings; in recent years the group of research recommend intermittent treatment, with ferrous sulphate every week because is more easily adhesion to treatment. To know iron concentration in plasma after treatment, given oral ferrous sulphate daily and single dose every week. We established two groups A and B, with ten iron deficiency pre-school children each one. Group A: the children received oral ferrous sulphate twice a day during three months; the doses were 3.5 mg of ferric iron per kilogram of weight in children with ages less of three years old, and 2.5 mg/kg/day in children with three to five years old. After the treatment all the patients improved haemoglobin, ferritin an iron concentrations (p = 0.001). Group B: The patient received the some dose per kilogram of weight like that of group A, in a single dose weekly for three months, there was an improvement in haemoglobin not reaching normal levels, half of the patients improved iron and ferritin observing statistical significance; haemoglobin (p = 0.001) iron (p = 0.062) and ferritin (p = 0.01). The administration of ferrous sulphate daily provide an positive balance of iron status for the group A. Group B: that they received iron weekly dose showed changes to positive balance of iron status with a statistical significance, it is probably that the half doses of ferrous sulphate also improve the anaemia by iron deficiency.


Prioritizing land and sea conservation investments to protect coral reefs.
Coral reefs have exceptional biodiversity, support the livelihoods of millions of people, and are threatened by multiple human activities on land (e.g. farming) and in the sea (e.g. overfishing). Most conservation efforts occur at local scales and, when effective, can increase the resilience of coral reefs to global threats such as climate change (e.g. warming water and ocean acidification). Limited resources for conservation require that we efficiently prioritize where and how to best sustain coral reef ecosystems. Here we develop the first prioritization approach that can guide regional-scale conservation investments in land- and sea-based conservation actions that cost-effectively mitigate threats to coral reefs, and apply it to the Coral Triangle, an area of significant global attention and funding. Using information on threats to marine ecosystems, effectiveness of management actions at abating threats, and the management and opportunity costs of actions, we calculate the rate of return on investment in two conservation actions in sixteen ecoregions. We discover that marine conservation almost always trumps terrestrial conservation within any ecoregion, but terrestrial conservation in one ecoregion can be a better investment than marine conservation in another. We show how these results could be used to allocate a limited budget for conservation and compare them to priorities based on individual criteria. Previous prioritization approaches do not consider both land and sea-based threats or the socioeconomic costs of conserving coral reefs. A simple and transparent approach like ours is essential to support effective coral reef conservation decisions in a large and diverse region like the Coral Triangle, but can be applied at any scale and to other marine ecosystems.


Does interpersonal emotion regulation effort pay off?
Interpersonal emotion regulation shapes people's emotional and relational experiences. Yet, researchers know little about the regulation processes that influence these outcomes. Recent works in the intrapersonal emotion regulation space suggest that motivational strength, or effort, people invest in regulation might be the answer. We applied this motivated approach for the first time in the interpersonal space-looking at both intrinsic and extrinsic forms of interpersonal emotion regulation-in order to identify the potential emotional and relational outcomes of putting effort into regulating one's own emotions through others, and regulating others' emotions. In daily diary (N = 171) and experience sampling (N = 239) studies, we examined participants' interpersonal emotion regulation behaviors and socioemotional experiences in everyday social interactions over the course of 1 week. These methods allowed us to examine effort at both momentary and person levels. We found that people who habitually put in more intrinsic effort to feel better through others felt worse overall. People also felt worse on occasions when they put in more effort to extrinsically help others feel better, although at the person level extrinsic effort was associated with higher interaction quality. Together, our findings suggest that interpersonal emotion regulation success is not simply a matter of trying hard. This observation opens new research avenues to investigate the interplay of different factors that determine when, and for whom, investing effort in interpersonal emotion regulation pays off. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


["Children cannot wait": why mothers seek urgency and emergency care services for their children in non-urgent situations].
The scope of this article is to seek to understand the reasons why mothers seek urgency and emergency attention for children in non-urgent situations in a public hospital of the Unified Health System in Belo Horizonte in the state of Minas Gerais. It is a study involving a qualitative approach with semi-structured interviews as the data collection tool. Twenty-seven mothers of children with complaints classified as minor and non-urgent were interviewed. Fever and respiratory problems were found to be the main complaints. Even when the situation is non-urgent, mothers take their children to the emergency service because of the swift resolution, quality and specific pediatric medical care advantages, ease of access, previous experiences and recommendations from others, among other reasons. The statements revealed the mismatch between these mothers' feelings and the rationale of the organization of the service. This work raises questions that can provide input for reflection on the organization of the services centered on the users, who are in the final analysis the subject and scope of the care-giving process.


A polyadenylation factor subunit implicated in regulating oxidative signaling in Arabidopsis thaliana.
Plants respond to many unfavorable environmental conditions via signaling mediated by altered levels of various reactive oxygen species (ROS). To gain additional insight into oxidative signaling responses, Arabidopsis mutants that exhibited tolerance to oxidative stress were isolated. We describe herein the isolation and characterization of one such mutant, oxt6. The oxt6 mutation is due to the disruption of a complex gene (At1g30460) that encodes the Arabidopsis ortholog of the 30-kD subunit of the cleavage and polyadenylation specificity factor (CPSF30) as well as a larger, related 65-kD protein. Expression of mRNAs encoding Arabidopsis CPSF30 alone was able to restore wild-type growth and stress susceptibility to the oxt6 mutant. Transcriptional profiling and single gene expression studies show elevated constitutive expression of a subset of genes that encode proteins containing thioredoxin- and glutaredoxin-related domains in the oxt6 mutant, suggesting that stress can be ameliorated by these gene classes. Bulk poly(A) tail length was not seemingly affected in the oxt6 mutant, but poly(A) site selection was different, indicating a subtle effect on polyadenylation in the mutant. These results implicate the Arabidopsis CPSF30 protein in the posttranscriptional control of the responses of plants to stress, and in particular to the expression of a set of genes that suffices to confer tolerance to oxidative stress.


An improved approach to evacuation of subungual hematoma.
An improved approach to subungual hematoma evacuation has been presented. Hand-held cautery is a cost-effective, precise method of treatment of subungual hematoma. Its use decreases the likelihood of unnecessary delay in the regrowth of the nail plate and secondary dystrophy that might result from pressure on the matrix caused by accumulated blood under the nail. The high temperature and fine tip make the cautery an excellent instrument to precisely and painlessly burn a small hole in the nail plate, allowing for evacuation of subungual hematoma.


Regulation by vitamin E of phosphatidylcholine metabolism in rat heart.
Lysophosphatidylcholine is the major lysophospholipid in mammalian tissues and has been shown to be cytolytic at high concentrations. In the present study we demonstrated that the level of lysophosphatidylcholine was significantly increased in the heart of rats fed with a vitamin E-deficient diet. Moreover, the cardiac lysophosphatidylcholine level was decreased in rats fed with a high vitamin E diet. The alterations in cardiac lysophosphatidylcholine level by dietary vitamin E were attributed to the changes in the activity of cardiac phospholipase A. Dietary vitamin E affected both phospholipase A1 and A2 in the same manner, but had no effect on the other major enzymes which are responsible for the metabolism of lysophosphatidylcholine. Kinetic studies revealed that the inhibition of enzyme activity by vitamin E was essentially non-competitive. The accumulation of lysophosphatidylcholine in the rat heart may be one of the underlying biochemical causes of the observed cardiac dysfunctions produced during vitamin E deficiency.


A trans-activation domain in yeast heat shock transcription factor is essential for cell cycle progression during stress.
Gene expression in response to heat shock is mediated by the heat shock transcription factor (HSF), which in yeast harbors both amino- and carboxyl-terminal transcriptional activation domains. Yeast cells bearing a truncated form of HSF in which the carboxyl-terminal transcriptional activation domain has been deleted [HSF(1-583)] are temperature sensitive for growth at 37 degreesC, demonstrating a requirement for this domain for sustained viability during thermal stress. Here we demonstrate that HSF(1-583) cells undergo reversible cell cycle arrest at 37 degreesC in the G2/M phase of the cell cycle and exhibit marked reduction in levels of the molecular chaperone Hsp90. As in higher eukaryotes, yeast possesses two nearly identical isoforms of Hsp90: one constitutively expressed and one highly heat inducible. When expressed at physiological levels in HSF(1-583) cells, the inducible Hsp90 isoform encoded by HSP82 more efficiently suppressed the temperature sensitivity of this strain than the constitutively expressed gene HSC82, suggesting that different functional roles may exist for these chaperones. Consistent with a defect in Hsp90 production, HSF(1-583) cells also exhibited hypersensitivity to the Hsp90-binding ansamycin antibiotic geldanamycin. Depletion of Hsp90 from yeast cells wild type for HSF results in cell cycle arrest in both G1/S and G2/M phases, suggesting a complex requirement for chaperone function in mitotic division during stress.


Ocular changes in nephropathic cystinosis: The course of the gold-dust.
Cystinosis is an autosomal recessive inherited lysosomal storage disease with an incidence of 1:100.000 up to 1:200.000 caused by a gene mutation of a lysosomal transport protein resulting in deposition of cystine in lysosomes in all cells and tissues. In the cornea, crystalline, gold-dust deposition of cystine leads to visual impairment, recurrent erosions, photophobia, epiphora and blepharospasmus. Standard therapy is topical and systemic application of cysteamine which may resolve the accumulated cystine crystals. This is a case report of a thirty-one-year-old patient who already underwent renal transplantation because of nephropathic cystinosis. Visual impairment by cystine crystal deposition was aggravated by a central avascular pannus formation in his right eye. Penetrating keratoplasty was performed in intention to improve the patient's visual acuity and life quality. After penetrating keratoplasty in the right eye, there was only a slight visual improvement. OCT scans of the macula revealed intraretinal cystine crystals and a cystoid macular edema, which was treated with a bevacizumab injection. Transmission electron microscopy of the excised cornea revealed spiky intracorneal inclusions and confocal in vivo microscopy of the left eye allowed detailed visualization of the cystine crystal deposition. There is a variability of ocular manifestations of nephropathic cystinosis. Ophthalmologists have a central role in the early diagnosis of cystinosis as mostly the first manifestation are cystine crystals in the cornea. Penetrating keratoplasty may be one of the therapeutical options. Nevertheless, the patient has to be informed about the limited prognosis because of the persisting underlying disease.


Prediction of carrier status in Duchenne dystrophy by creatine kinase measurement.
Serum creatine kinase (CK) was measured in 515 healthy white women and 28 obligate carriers for Duchenne muscular dystrophy. There was substantial overlap between the control and carrier populations. To analyze the impact of the degree of overlap, the predictive value of a CK result was determined by (1) using sensitivity and specificity analysis, which assumes dichotomization into a positive or negative result based on a particular cut-off value; and (2) using likelihood ratio analysis, which evaluates an individual result based on the continuum observed for control and carrier populations. There was no clinically important difference whether an observed 57% or a hypothetical 33% overlap between control and carrier results was used. Because of the substantial overlap, the CK test utility is limited to those suspected carriers whose results fall above the healthy population interval. A low CK result does not provide sufficient assurance of noncarrier status.


Nonpeptide somatostatin receptor agonists specifically target ocular neovascularization via the somatostatin type 2 receptor.
To define the molecular pharmacology underlying the antiangiogenic effects of nonpeptide imidazolidine-2,4-dione somatostatin receptor agonists (NISAs) and evaluate the efficacy of NISA in ocular versus systemic delivery routes in ocular disease models. Functional inhibitory effects of the NISAs and the somatostatin peptide analogue octreotide were evaluated in vitro by chemotaxis, proliferation, and tube-formation assays. The oxygen-induced retinopathy (OIR) model and the laser model of choroidal neovascularization (CNV) were used to test the in vivo efficacy of NISAs. Transscleral permeability of a candidate NISA was also measured. NISAs inhibited growth factor-induced HREC proliferation, migration and tube formation with submicromolar potencies (IC(50), 0.1-1.0 microM) comparable to octreotide. In the OIR model, systemic administration of the NISAs RFE-007 and RFE-011 inhibited retinal neovascularization in a dose-dependent manner, comparable to octreotide. In the CNV model, intravitreal RFE-011 resulted in a 56% reduction (P < 0.01) in CNV lesion area, whereas systemic administration resulted in a 35% reduction (P < 0.05) in lesion area. RFE-011 demonstrated transscleral penetration. Micromolar concentrations of octreotide and NISAs are necessary for antiangiogenic effects, whereas nanomolar concentrations are effective for endocrine inhibition. This suggests that the antiangiogenic activity of NISAs and octreotide is mediated by an overall much less efficient downstream coupling mechanism than is growth hormone release. As a result, the intravitreal or transscleral route of administration should be seriously considered for future clinical studies of SSTR2 agonists used for treatment of ocular neovascularization to ensure efficacious concentrations in the target retinal and choroidal tissue.


Chest Radiographic and CT Findings of the 2019 Novel Coronavirus Disease (COVID-19): Analysis of Nine Patients Treated in Korea.
This study presents a preliminary report on the chest radiographic and computed tomography (CT) findings of the 2019 novel coronavirus disease (COVID-19) pneumonia in Korea. As part of a multi-institutional collaboration coordinated by the Korean Society of Thoracic Radiology, we collected nine patients with COVID-19 infections who had undergone chest radiography and CT scans. We analyzed the radiographic and CT findings of COVID-19 pneumonia at baseline. Fisher's exact test was used to compare CT findings depending on the shape of pulmonary lesions. Three of the nine patients (33.3%) had parenchymal abnormalities detected by chest radiography, and most of the abnormalities were peripheral consolidations. Chest CT images showed bilateral involvement in eight of the nine patients, and a unilobar reversed halo sign in the other patient. In total, 77 pulmonary lesions were found, including patchy lesions (39%), large confluent lesions (13%), and small nodular lesions (48%). The peripheral and posterior lung fields were involved in 78% and 67% of the lesions, respectively. The lesions were typically ill-defined and were composed of mixed ground-glass opacities and consolidation or pure ground-glass opacities. Patchy to confluent lesions were primarily distributed in the lower lobes (p = 0.040) and along the pleura (p < 0.001), whereas nodular lesions were primarily distributed along the bronchovascular bundles (p = 0.006). COVID-19 pneumonia in Korea primarily manifested as pure to mixed ground-glass opacities with a patchy to confluent or nodular shape in the bilateral peripheral posterior lungs. A considerable proportion of patients with COVID-19 pneumonia had normal chest radiographs.


Combination of KRAS and SMAD4 mutations in formalin-fixed paraffin-embedded tissues as a biomarker for pancreatic cancer.
Formalin-fixed paraffin-embedded (FFPE) tissues used for routine pathological diagnosis are valuable for cancer genomic analysis; however, the association between mutation status derived from these specimens and prognosis in pancreatic ductal adenocarcinoma (PDAC) remains unclear. We analyzed 50 cancer-related gene mutations including driver genes in PDAC, using next-generation sequencing (NGS) to clarify the association between gene mutations and prognosis. DNA was extracted from FFPE tissues obtained from 74 patients with untreated resectable PDAC who underwent surgery at our institution between 2013 and 2018. Fifty of the 74 patients with DNA extracts from FFPE samples suitable for NGS were analyzed. The prevalence of driver gene mutations was as follows: 84% for KRAS, 62% for TP53, 32% for SMAD4, and 18% for CDKN2A. There were no cases of single SMAD4 mutations; its rate of coincidence with KRAS or TP53 mutations was 30% and 2%, respectively. The combination of KRAS and SMAD4 mutations resulted in significantly shorter relapse-free survival (RFS; median survival time [MST], 12.3 vs. 28.9 months, P = .014) and overall survival (OS; MST, 22.3 months vs. not reached, P = .048). On multivariate analysis, the combination of KRAS and SMAD4 mutations was an independent prognostic factor for RFS (hazard ratio [HR] 4.218; 95% confidence interval [CI], 1.77-10.08; P = .001) and OS (HR 6.730; 95% CI, 1.93-23.43; P = .003). The combination of KRAS and SMAD4 mutations in DNA obtained from FFPE tissues is an independent poor prognostic factor in PDAC.


New species and geographical records of dactylogyrids (Monogenea) of catfish (Siluriformes) from the Peruvian Amazonia.
Three new species of gill monogeneans (Dactylogyridae: Ancyrocephalinae) are described from siluriform catfish from Iquitos, Peru: Demidospermus mortenthaleri n. sp. from Brachyplatystoma juruense (Boulenger), Demidospermus brevicirrus n. sp. from Pimelodus sp., and Aphanoblastella aurorae n. sp. from Goeldiella eques (Müller & Troschel). Demidospermus mortenthaleri is characterized by a male copulatory organ (MCO) with a small loop at its middle portion; 2 types of hooks, of which pairs 5 and 6 are longer than the remaining hooks; a proximal subunit round and highly depressed thumb; and a sclerotized vagina with a round pad at the vaginal aperture. Demidospermus brevicirrus is distinguished from other congeners by the presence of a short, straight, and robust MCO and boot-shaped accessory piece with a hooked projection directed posteriorly. Aphanoblastella aurorae is the only species of the genus that possesses an arrow-shaped sclerotized vagina and a medial process on the dorsal bar. Another 6 dactylogyrids described previously are recorded for the first time from the Peruvian Amazonia: Cosmetocleithrum bulbocirrus Kritsky, Thatcher and Boeger, 1986 ; Vancleaveus fungulus Kritsky, Thatcher and Boeger, 1986 ; V. janauacaensis Kritsky, Thatcher and Boeger, 1986 ; V. platyrhynchi Kritsky, Thatcher and Boeger, 1986 ; Unilatus unilatus Mizelle and Kritsky, 1967 ; and U. brittani Mizelle, Kritsky and Crane, 1968 . Based on observations of specimens collected in the Peruvian Amazonia, new morphological data for these species are provided. Comparison of new specimens of U. unilatus and U. brittani with those of Unilatus brevispinus Suriano, 1985 and Unilatus longispinus Suriano, 1985 , both originally described from Brazil, has shown that they are conspecific. Therefore, the latter species were synonymized with U. unilatus and U. brittani , respectively. In addition, 56 undescribed monogeneans found in catfish from the Peruvian Amazonia, some of them probably belonging to new genera, are listed.


Measurement of macular fractal dimension using a computer-assisted program.
Macular diseases may be associated with an altered retinal vasculature. We describe and test new software for the measurement of retinal vascular fractal dimension to quantify the complexity of retinal vasculature at the macula (D mac) and to compare this with fractal dimension measured around the optic disc (D disc). A total of 342 macular-centered and optic disc-centered digital retinal photographs from 171 subjects was selected randomly from a population-based study. Retinal vascular fractional dimension (Df) was measured by two trained graders using a computer-assisted program (SIVA-FA, software version 1.0, National University of Singapore) on macula-centered (D mac) and optic disc-centered (D disc) photographs, to assess intergrader reliability. Measurements were repeated after two weeks to determine intragrader reliability. A separate 50 pairs of consecutively repeated images were selected and measured using SIVA-FA to assess intrasession reliability. Reliability analyses were conducted using intraclass correlation coefficients (ICC), and multiple linear regression analyses were performed to compare factors associated with D mac and D disc measurements. The mean (SD) D mac and D disc values were 1.453 (0.060) and 1.484 (0.043), respectively, and were highly correlated (r = 0.70, P < 0.001). Intragrader, intergrader, and intrasession reliability for both Df measures was high (ICCs ranging from 0.88-0.99). In multiple regression analyses, age (both β = -0.03, P < 0.001) and hypertension (β = -0.02, P = 0.011; β = -0.02, P = 0.021, respectively) were independently associated with D mac and D disc. The complexity of the retinal vasculature in the macula can be measured reliably and may be a useful tool to study parafoveal vascular networks in macula diseases, such as diabetic maculopathy.


Training physicians in India to interpret pediatric chest radiographs according to World Health Organization research methodology.
Chest radiography is the standard for diagnosing pediatric lower respiratory infections in low-income and middle-income countries. A method for interpreting pediatric chest radiographs for research endpoints was recently updated by the World Health Organization (WHO) Chest Radiography in Epidemiological Studies project. Research in India required training local physicians to interpret chest radiographs following the WHO method. To describe the methodology for training Indian physicians and evaluate the training's effectiveness. Twenty-nine physicians (15 radiologists and 14 pediatricians) from India were trained by two WHO Chest Radiography in Epidemiological Studies members over 3 days in May 2019. Training materials were adapted from WHO Chest Radiography in Epidemiological Studies resources. Participants followed WHO methodology to interpret 60 unique chest radiographs before and after the training. Participants needed to correctly classify ≥80% of radiographs for primary endpoint pneumonia on the post-training test to be certified to interpret research images. We analyzed participant performance on both examinations. Twenty-six of 29 participants (89.7%) completed both examinations. The average score increased by 9.6% (95% confidence interval [CI] 5.0-14.1%) between examinations (P<0.001). Participants correctly classifying ≥80% of images for primary endpoint pneumonia increased from 69.2% (18/26) on the pretraining to 92.3% (24/26) on the post-training examination (P=0.003). The mean scores of radiologists and pediatricians on the post-training examination were not statistically different (P=0.43). Our results demonstrate this training approach using revised WHO definitions and tools was successful, and that non-radiologists can learn to apply these methods as effectively as radiologists. Such capacity strengthening is important for enabling research to support national policy decision-making in these settings. We recommend future research incorporating WHO chest radiograph methodology to consider modelling trainings after this approach.


Effect of prenatal stress on alcohol preference and sensitivity to chronic alcohol exposure in male rats.
In rats, prenatal restraint stress (PRS) induces persistent behavioral and neurobiological alterations leading to a greater consumption of psychostimulants during adulthood. However, little is known about alcohol vulnerability in this animal model. We examined in adolescent and adult male Sprague Dawley rats the long-lasting impact of PRS exposure on alcohol consumption. PRS rats were subjected to a prenatal stress (three daily 45-min sessions of restraint stress to the mothers during the last 10 days of pregnancy). Alcohol preference was assessed in a two-bottle choice paradigm (alcohol 2.5%, 5%, or 10% versus water), in both naïve adolescent rats and adult rats previously exposed to a chronic alcohol treatment. Behavioral indices associated with incentive motivation for alcohol were investigated. Finally, plasma levels of transaminases (marker of hepatic damages) and ΔFosB levels in the nucleus accumbens (a potential molecular switch for addiction) were evaluated following the chronic alcohol exposure. Alcohol preference was not affected by PRS. Contrary to our expectations, stressed and unstressed rats did not display signs of compulsive alcohol consumption. The consequences of the alcohol exposure on locomotor reactivity and on transaminase levels were more prominent in PRS group. Similarly, PRS potentiated alcohol-induced ΔFosB levels in the nucleus accumbens. Our data suggest that negative events occurring in utero do not modulate alcohol preference in male rats but potentiate chronic alcohol-induced molecular neuroadaptation in the brain reward circuitry. Further studies are needed to determine whether the exacerbated ΔFosB upregulation in PRS rats could be extended to other reinforcing stimuli.


Isolation and characterization of a novel temperate bacteriophage infecting Aeromonas hydrophila isolated from a Macrobrachium rosenbergii larvae pond.
Aeromonas hydrophila is an opportunistic pathogen that frequently leads to significant mortality in various commercially cultured aquatic species. Bacteriophages offer an alternative strategy for pathogens elimination. In this study, we isolated, identified, and characterized a novel temperate A. hydrophila phage, designated as P05B. The bacteriophage P05B is a myovirus based on its morphological features, and possesses the capability to lyse A. hydrophila strains isolated from shrimp. The optimal multiplicity of infection (MOI), adsorption rate, latent period, and burst size for phage P05B were determined to be 0.001, 91.7 %, 20 min, and 483 PFU/cell, respectively. Phage P05B displayed stability across a range of temperatures (28-50 °C) and pH values (4.0-10.0). Sequence analysis unveiled that the genome of phage P05B comprises 32,302 base pairs with an average G + C content of 59.4 %. A total of 40 open reading frames (ORF) were encoded within the phage P05B genome. The comparative genomic analyses clearly implied that P05B might represent a novel species of the genus Bielevirus under Peduoviridae family. A phylogenetic tree was reconstructed, demonstrating that P05B shares a close evolutionary relationship with other Aeromonas and Aeromonas phages. In conclusion, this study increased our knowledge about a new temperate phage of A. hydrophila with strong lytic ability.


Incidental Finding of Cryptococcus on Prostate Biopsy for Prostate Adenocarcinoma Following Cardiac Transplant: Case Report and Review of the Literature.
BACKGROUND Cryptococcus is the third most common invasive fungal organism in immunocompromised patients, including transplant patients, and usually involves the central nervous system and lungs, with a median time to infection of 25 months. We report a case of Cryptococcus of the prostate gland, found as an incidental finding on prostate biopsy for prostate adenocarcinoma, four months following cardiac transplantation. CASE REPORT A 62-year-old male African-American who had a cardiac transplant four months previously, underwent a six-core prostate biopsy for a two-year history of increasing prostate-specific antigen (PSA) levels, and a recent history of non-specific urinary tract symptoms. A prostatic adenocarcinoma, Gleason grade 4+4=8, was diagnosed on histopathology, and 'foamy' cells were seen in the biopsies. Histochemical stains, including Grocott methenamine silver (GMS), and periodic acid-Schiff (PAS) showed abundant round and oval 5-7 µm diameter fungal elements; mucicarmine highlighted the fungal polysaccharide capsule, diagnostic for Cryptococcus. Cryptococcal antigen detection was made by the latex agglutination test and cultures. We reviewed the literature and found 70 published cases (from 1946-2008) of Cryptococcus of the prostate gland, with only one previous case presenting five years following cardiac transplantation. CONCLUSIONS Fungal infections of the prostate are rare, and occur mainly in immunocompromised patients. We present a unique case of prostatic Cryptococcus found incidentally at four months following cardiac transplantation. This case report highlights the need to consider atypical fungal infection as a differential diagnosis for prostatitis in immunosuppressed patients, including transplant patients.


Competency is not enough: integrating identity formation into the medical education discourse.
Despite the widespread implementation of competency-based medical education, there are growing concerns that generally focus on the translation of physician roles into "measurable competencies." By breaking medical training into small, discrete, measurable tasks, it is argued, the medical education community may have emphasized too heavily questions of assessment, thereby missing the underlying meaning and interconnectedness of how physician roles shape future physicians. To address these concerns, the authors argue that an expanded approach be taken that includes a focus on professional identity development. The authors provide a conceptual analysis of the issues and language related to a broader focus on understanding the relationship between the development of competency and the formation of identities during medical training. Including identity alongside competency allows a reframing of approaches to medical education away from an exclusive focus on "doing the work of a physician" toward a broader focus that also includes "being a physician." The authors consider the salient literature on identity that can inform this expanded perspective about medical education and training.


The effect of corticosteroid therapy on cyclooxygenase 2, vascular endothelial growth factor, and inducible nitric oxide synthase expression levels in nasal polyposis.
Nasal and oral corticosteroid therapy is the ultimate treatment for sinonasal polyposis. Although there are numerous clinical studies regarding the factors associated with the formation of nasal polyposis, there is not enough literature on how these factors are influenced by steroid treatment. Twenty-one patients that had no prior medical therapy for nasal polyposis or had received medical therapy at least 6 months earlier were included in the study. Patients were treated with oral and nasal corticosteroid therapy. Nasal polyp biopsies were taken before and after medical treatment and immunohistochemical staining for cyclooxygenase 2 (COX-2), vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) were applied to the specimens. In this study, we tried to demonstrate the effects of corticosteroid therapy on nasal polyposis tissue immunohistochemically. There was no change at immunohistochemical expression level of COX-2; however, the decline of immunohistochemical expression levels of VEGF and iNOS was statistically significant. Short-term steroid therapy does not affect COX-2 level of the nasal polyposis tissue, but has an influence on iNOS and VEGF levels. Our findings were harmonious with those of the previous studies of the literature. Further studies are needed to demonstrate the long-term effects with a larger patient group.


Long-term phonological learning begins at the level of word form.
Incidental learning of phonological structures through repeated exposure is an important component of native and foreign-language vocabulary acquisition that is not well understood at the neurophysiological level. It is also not settled when this type of learning occurs at the level of word forms as opposed to phoneme sequences. Here, participants listened to and repeated back foreign phonological forms (Korean words) and new native-language word forms (Finnish pseudowords) on two days. Recognition performance was improved, repetition latency became shorter and repetition accuracy increased when phonological forms were encountered multiple times. Cortical magnetoencephalography responses occurred bilaterally but the experimental effects only in the left hemisphere. Superior temporal activity at 300-600 ms, probably reflecting acoustic-phonetic processing, lasted longer for foreign phonology than for native phonology. Formation of longer-term auditory-motor representations was evidenced by a decrease of a spatiotemporally separate left temporal response and correlated increase of left frontal activity at 600-1200 ms on both days. The results point to item-level learning of novel whole-word representations.


Genomic Landscape of Pleural Mesothelioma and Therapeutic Aftermaths.
In this article, we provide a comprehensive analysis of recent progress in the genetic characterisation of pleural mesothelioma, and the translation of these findings to clinical practice. Advancements in sequencing technology have allowed the identification of driver mutations and improved our understanding of how these mutations may shape the mesothelioma tumour microenvironment. However, the identification of frequently mutated regions including CDKN2A, BAP1 and NF2 have, to date, not yet yielded targeted therapy options that outperform standard chemo- and immunotherapies. Similarly, the association between mutational profile and the immune microenvironment or immunotherapy response is not well characterised. Further research into the link between tumour mutational profile and response to therapy is critical for identifying targetable vulnerabilities and stratifying patients for therapy.


Infrared Brewster-angle polarizing beam splitter using a high-index prism with a small wedge angle.
Specular reflection at the Brewster angle by a planar surface of a high-refractive-index transparent substrate is an effective means of generating linearly polarized light in the infrared. However, in such a reflection linear polarizer, the refracted light beam is usually dumped. In this paper we describe a polarizing beam splitter (PBS) that uses a high-index prism with a small wedge angle to generate two orthogonally p and s linearly polarized beams that travel in orthogonal directions. A single-layer antireflection coating (ARC) at the exit face of the prism can be embedded with aligned Ag nano needles to suppress the transmission of the small, residual, s-polarized refracted component. An example of such PBS that uses a PbTe prism with ZnSe ARC in the mid-infrared is presented.


Sho-saiko-to, a traditional herbal medicine, regulates gene expression and biological function by way of microRNAs in primary mouse hepatocytes.
Sho-saiko-to (SST) (also known as so-shi-ho-tang or xiao-chai-hu-tang) has been widely prescribed for chronic liver diseases in traditional Oriental medicine. Despite the substantial amount of clinical evidence for SST, its molecular mechanism has not been clearly identified at a genome-wide level. By using a microarray, we analyzed the temporal changes of messenger RNA (mRNA) and microRNA expression in primary mouse hepatocytes after SST treatment. The pattern of genes regulated by SST was identified by using time-series microarray analysis. The biological function of genes was measured by pathway analysis. For the identification of the exact targets of the microRNAs, a permutation-based correlation method was implemented in which the temporal expression of mRNAs and microRNAs were integrated. The similarity of the promoter structure between temporally regulated genes was measured by analyzing the transcription factor binding sites in the promoter region. The SST-regulated gene expression had two major patterns: (1) a temporally up-regulated pattern (463 genes) and (2) a temporally down-regulated pattern (177 genes). The integration of the genes and microRNA demonstrated that 155 genes could be the targets of microRNAs from the temporally up-regulated pattern and 19 genes could be the targets of microRNAs from the temporally down-regulated pattern. The temporally up-regulated pattern by SST was associated with signaling pathways such as the cell cycle pathway, whereas the temporally down-regulated pattern included drug metabolism-related pathways and immune-related pathways. All these pathways could be possibly associated with liver regenerative activity of SST. Genes targeted by microRNA were moreover associated with different biological pathways from the genes not targeted by microRNA. An analysis of promoter similarity indicated that co-expressed genes after SST treatment were clustered into subgroups, depending on the temporal expression patterns. We are the first to identify that SST regulates temporal gene expression by way of microRNA. MicroRNA targets and non-microRNA targets moreover have different biological roles. This functional segregation by microRNA would be critical for the elucidation of the molecular activities of SST.


Role of Bacteria-Derived Flavins in Plant Growth Promotion and Phytochemical Accumulation in Leafy Vegetables.
Sinorhizobium meliloti 1021 bacteria secretes a considerable amount of flavins (FLs) and can form a nitrogen-fixing symbiosis with legumes. This strain is also associated with non-legume plants. However, its role in plant growth promotion (PGP) of non-legumes is not well understood. The present study evaluated the growth and development of lettuce (Lactuca sativa) and kale (Brassica oleracea var. acephala) plants inoculated with S. meliloti 1021 (FL+) and its mutant 1021ΔribBA, with a limited ability to secrete FLs (FL-). The results from this study indicated that inoculation with 1021 significantly (p < 0.05) increased the lengths and surface areas of the roots and hypocotyls of the seedlings compared to 1021ΔribBA. The kale and lettuce seedlings recorded 19% and 14% increases in total root length, respectively, following inoculation with 1021 compared to 1021ΔribBA. A greenhouse study showed that plant growth, photosynthetic rate, and yield were improved by 1021 inoculation. Moreover, chlorophylls a and b, and total carotenoids were more significantly (p < 0.05) increased in kale plants associated with 1021 than non-inoculated plants. In kale, total phenolics and flavonoids were significantly (p < 0.05) increased by 6% and 23%, respectively, and in lettuce, the increments were 102% and 57%, respectively, following 1021 inoculation. Overall, bacterial-derived FLs enhanced kale and lettuce plant growth, physiological indices, and yield. Future investigation will use proteomic approaches combined with plant physiological responses to better understand host-plant responses to bacteria-derived FLs.


Borna disease virus. A possible etiologic factor in human affective disorders?
Borna disease virus is a unique neurotropic agent that appears to have a predilection for the limbic area of the brain. In some animal species, it can produce a behavioral syndrome characterized by aggressive and passive phases. This syndrome has suggested an analogy to certain human affective disorders. In this preliminary study, we examined the possible involvement of Borna disease virus in the etiology of human mood disorders by assaying for virus-specific antibodies in 265 patients with unipolar or bipolar depression and 105 normal, healthy volunteers. Twelve patients (4.5%) and none of the healthy controls demonstrated this antibody in their serum samples. It will be necessary to replicate and extend these intriguing preliminary results to determine if Borna disease virus is possibly involved in the pathogenesis of affective disorders in humans.


Specificity of the FTA-ABS and TPHA tests during pregnancy.
In order to determine whether pregnancy influences the specificity of the fluorescent treponemal antibody absorption (FTA-ABS) and Treponema palidum haemagglutination assay (TPHA) tests, these tests, together with the quantitative fluorescent treponemal antibody (FTA) and Venereal Disease Research Laboratory (VDRL) tests, were carried out simultaneously on 2000 pregnant women who attended for compulsory prenatal screening. In only one patient (0.05% of the total investigated) was a positive result to the TPHA test obtained, the specificity of which it was impossibile to confirm. The FTA-ABS test gave a weakly reactive result of the borderline type but this was found to be non-specific in only four (0.2%) patients. The results of our investigations showed that the specificity of the FTA-ABS and the TPHA tests performed on pregnant women did not differ from the specificity of these tests when carried out on other population groups.


Cutaneous Findings and Systemic Associations in Women With Polycystic Ovary Syndrome.
Understanding of the associations among cutaneous findings, systemic abnormalities, and fulfillment of the diagnostic criteria in women suspected of having polycystic ovary syndrome (PCOS) is incomplete. To identify cutaneous and systemic features of PCOS that help distinguish women who do and do not meet the diagnostic criteria. Retrospective cross-sectional study of a racially diverse referred sample of women seen at the University of California, San Francisco, Polycystic Ovary Syndrome Multidisciplinary Clinic over a 6-year period between May 18, 2006, and October 25, 2012. Participants were 401 women referred for suspected PCOS. In total, 68.8% (276 of 401) met the Rotterdam PCOS diagnostic criteria, while 12.0% (48 of 401) did not. Overall, 11.5% (46 of 401) had insufficient data to render a diagnosis, 1.7% (7 of 401) were excluded from the study, and 6.0% (24 of 401) refused to participate in the study. Comprehensive skin examination and transvaginal ultrasonography. All patients were tested for levels of total testosterone, free testosterone, dehydroepiandrosterone (DHEAS), androstenedione, luteinizing hormone, and follicle-stimulating hormone. Levels of serum cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides were obtained, in addition to 0-hour and 2-hour oral glucose tolerance test (OGTT) results, with measurement of glucose and insulin levels. Findings from comprehensive skin examination, laboratory testing, and transvaginal ultrasonography. In total, 401 women with suspected PCOS were included in the study. The median patient age was 28 years. Compared with women who did not meet the diagnostic criteria for PCOS, women who met the criteria had higher rates of hirsutism (53.3% [144 of 270] vs 31.2% [15 of 48], P = .005) (with higher mean modified Ferriman-Gallwey scores of 8.6 vs 5.6, P = .001), acne (61.2% [164 of 268] vs 40.4% [19 of 47], P = .004), and acanthosis nigricans (AN) (36.9% [89 of 241] vs 20.0% [9 of 45], P = .03). Cutaneous distributions also varied. Women who met the PCOS criteria demonstrated more severe truncal hirsutism and higher rates of axillary AN. Women who met the PCOS criteria had elevated total testosterone levels (40.7% [105 of 258] vs 4.3% [2 of 47], P < .001). Among women with PCOS, the presence of hirsutism (43.9% [54 of 123] vs 30.9% [34 of 110], P = .04) or AN (53.3% [40 of 75] vs 27.0% [40 of 148], P < .001) was associated with higher rates of elevated free testosterone levels as well as several metabolic abnormalities, including insulin resistance, dyslipidemia, and increased body mass index. Although the prevalence of acne was increased among women with PCOS, there were minimal differences in acne types and distribution between the women meeting vs not meeting the PCOS criteria. Hirsutism and AN are the most reliable cutaneous markers of PCOS and require a comprehensive skin examination to diagnose. When present, hirsutism and AN should raise clinical concern that warrants further diagnostic evaluation for metabolic comorbidities that may lead to long-term complications. Acne and androgenic alopecia are prevalent but unreliable markers of biochemical hyperandrogenism among this population.


[Endoscopic treatment of gastric carcinoid. Report of a clinical case].
We report on a case of a gastric carcinoid of the sporadic type successfully treated by endoscopic electroresection. From January 1998 to October 2002, 1523 gastroscopies were performed in the Palermo University General Emergency Surgery and Organ Transplant Unit. In a 59-year-old man with a history of dyspepsia, a sessile polypoid gastric lesion was observed in the gastric corpus. Laboratory data were normal. The lesion was successfully treated by electroresection. Histological evaluation revealed an 8-mm-diameter well-differentiated neuroendocrine polypoid tumour infiltrating the muscularis mucosa. According to Rindi et al.'s classification, the polyp was a carcinoid of the sporadic type. A two-year follow-up consisting in gastroscopy every 6 months and evaluation of tumour markers and CT scans once a year has so far shown no recurrence. Surgical treatment is the therapy of choice for gastric carcinoids, but endoscopic resection may be a successful alternative in cases of carcinoids measuring less than 1 cm and presenting multricentric growth. Moreover, endoscopy can also be used in patents at high surgical risk.


Inosine protects against the development of diabetes in multiple-low-dose streptozotocin and nonobese diabetic mouse models of type 1 diabetes.
Inosine, a naturally occurring purine, was long considered to be an inactive metabolite of adenosine. However, recently inosine has been shown to be an immunomodulator and anti-inflammatory agent. The aim of this study was to determine whether inosine influences anti-inflammatory effects and affects the development of type 1 diabetes in murine models. Type 1 diabetes was induced either chemically by streptozotocin or genetically using the nonobese diabetic mouse (NOD) model. Mice were treated with inosine (100 or 200 mg kg(-1)d(-1)d) and diabetes incidence was monitored. The effect of inosine on pancreas immune cell infiltration, oxidative stress, and cytokine profile also was determined. For the transplantation model islets were placed under the renal capsule of NOD mice and inosine (200 mg kg(-1)d d(-1)d) treatment started the day of islet transplantation. Graft rejection was diagnosed by return of hyperglycemia accompanied by glucosuria and ketonuria. Inosine reduced the incidence of diabetes in both streptozotocin-induced diabetes and spontaneous diabetes in NOD mice. Inosine decreased pancreatic leukocyte infiltration and oxidative stress in addition to switching the cytokine profile from a Th1 to a Th2 profile. Inosine prolonged pancreatic islet graft survival, increased the number of surviving beta cells, and reduced the number of infiltrating leukocytes. Inosine protects against both the development of diabetes and against the rejection of transplanted islets. The purine exerts anti-inflammatory effects in the pancreas, which is its likely mode of action. The use of inosine should be considered as a potential preventative therapy in humans susceptible to developing Type 1 diabetes and as a possible antirejection therapy for islet transplant recipients.


Studies on the mucosal hyperaemia of the feline small intestine observed at endoluminal perfusion with substance P.
Substance P-like immunoreactivity (SPLI) was found in the luminal contents of the feline small intestine. A physiological role for endoluminal substance P (SP) was explored in in vivo experiments, where feline jejunal segments were endoluminally perfused with saline or a low concentration of SP. A jejunal segment was initially perfused with saline, followed by SP in saline, and finally perfused with saline alone. The regional blood flow to the small intestine was determined by the microsphere technique. Endoluminal perfusion with SP caused a selective mucosal/submucosal hyperaemia of the experimental jejunum, which was normalized upon subsequent saline perfusion. Since neither acute vagotomy, local neural blockade (TTX, lidocaine), adrenergic blockade (phenoxybenzamine, propranolol), cholinergic blockade (hexamethonium, atropine), histamine - nor prostaglandin blockade - could antagonize the hyperaemic effects of luminally administered SP, it is suggested that this effect is directly paracrine in nature. Substance P may be released from SP nerves on physiological stimulation, that is, augmented vagal tone by a meal, and act at the effector cell, that is, vascular smooth muscle.


An Assessment in SpondyloArthritis International Society (ASAS)-endorsed definition of clinically important worsening in axial spondyloarthritis based on ASDAS.
In a previous phase, 12 draft definitions for clinically important worsening in axial spondyloarthritis (axSpA) were selected, of which 3 were based on absolute changes in Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP (ASDAS). The objective here was to select the best cut-off for ASDAS for clinically important worsening in axSpA for use in clinical trials and observational studies. An international longitudinal prospective study evaluating stable patients with axSpA was conducted. Data necessary to calculate ASDAS were collected at two consecutive visits (spaced 7 days to 6 months). Sensitivity and specificity of the three cut-offs for change in ASDAS were tested against the patient's subjective assessment of worsening as the external standard (ie, the patient reporting that he had worsened and felt a need for treatment intensification). Final selection was made by a consensus and voting procedure among Assessment of SpondyloArthritis International Society (ASAS) members. In total, 1169 patients with axSpA were analysed: 64.8% were male and had a mean age of 41.7 (SD 12.4) years. At the second visit, 127 (10.9%) patients judged their situation as worsened.Sensitivity and specificity for an increase of at least 0.6, 0.9 and 1.1 ASDAS points to detect patient-reported worsening were 0.55 (Se) and 0.91 (Sp), 0.38 (Se) and 0.96 (Sp), and 0.33 (Se) and 0.98 (Sp), respectively. The ASAS consensus was to define clinically important worsening as an increase in ASDAS of at least 0.9 points. This data-driven ASAS consensus process resulted in an ASDAS-based cut-off value defining clinically important worsening in axSpA for use in trials.


[The use of color duplex scanning in the diagnosis of pathology of the venous system of the lower extremities].
During 1993-1996 period of time 175 patients with the lower extremities varication and post-thrombophlebitis syndrome (PTHPHS) were investigated using colour duplex scanning. Definite changes in the veins structure and spectral characteristics of blood flow in them corresponded to every PTHPHS stage. In an acute stage the lumen of the vessel is full of friable thrombotic masses, the blood from is absent. In 2-3 weeks the first recanalization signs appears showing the thrombus consolidation and residual blood flow. The recanalization process completes with the deep veins cusps destruction and retrograde blood escape occurrence, as a rule. The diagnosis criteria of each stage, the permissible limits of venous reflux, the hemodynamics peculiarities in combined affection of the deep veins various segments are substantiated.


Intramedullary epidermoid cyst: preoperative diagnosis and surgical management after MRI introduction. Case report and updating of the literature.
Many patients with spinal tumours of developmental origin do not receive preoperative diagnosis and the surgical management, especially as for capsule resection, is often unplanned. Like other uncommon tumours, the intramedullary epidermoid cyst is often an operative or histological finding. Since magnetic resonance imaging (MRI) introduction, evidence has accumulated that they may be preoperatively suspected. In reporting the case of a young patient with a T3-T4 intramedullary epidermoid cyst, the authors present an overview of the clinical, radiological and surgical aspects of such tumors and review the latest literature in which MRI and microsurgical excision were performed. Despite the introduction of new diagnostic and surgical instrumentation, the preoperative diagnosis and surgical management of such tumours need further discussion.


Direct determination of phenolic secoiridoids in olive oil by ultra-high performance liquid chromatography-triple quadruple mass spectrometry analysis.
In recent years, a large number of biological properties and an important role in the organoleptic characteristics of olive oil have been attributed to phenolic secoiridoids, such as oleacein, oleocanthal, oleuropein aglycone and ligstroside aglycone. Consequently, quantifying them is of great interest for the olive oil sector. Currently, there is no consensus in which analytical method must be use to accurately determine these compounds in olive oil, mainly owing to the lack of reference standards for calibration. In this work, analytical standards of phenolic secoiridoids have been used to develop a quantitative and rapid analytical method by UHPLC-MS/MS, in which sample extraction is not carried out. Simple dilutions of the sample with dry tetrahydrofuran and dry acetonitrile were performed before analysing them. It is worth noting that under these conditions the generation of artefacts such as acetals and hemiacetals of the aldehydic forms is highly reduced. The detection and quantification was performed with a Xevo TQS tandem quadrupole mass spectrometer. The method was validated at four concentration levels and finally applied to six samples of extra virgin olive oil.


Measurement of (1-3)-beta-D-glucan derived from different gauze types.
(1-3)-beta-D-glucan (BDG) is a cell-wall polysaccharide component found in most fungi. The measurement of BDG is a useful diagnostic marker for invasive fungal infections. However, it is well known that interfering substances can result in false positive reactions. We encountered a patient who underwent lung transplantation and presented with highly elevated BDG values, despite having no evidence of invasive fungal infection. We therefore hypothesized that elevated BDG values were originated from the gauze products used during surgery. While it is known that gauze products contain BDG, there have been no previous reports to quantitatively correlate amount of gauze usage and BDG levels. In this study, we extracted BDG from various gauze products and measured BDG to better understand the degree of which gauze contributes to elevated BDG values. Six types of commonly used surgical gauze products were selected for our study. Each of the surgical gauze was immersed in sterile, purified water for up to 120 minutes. At set intervals, BDG values in the water extracts were measured. Purified water samples without gauze were used as negative controls (< 4 pg/ml). After 120-minute extraction, BDG levels varied greatly depending on gauze products, ranging from 11.7 pg/ml to 6612 pg/ml. The gauze made of lyocell, which is a fiber produced from wood pulp cellulose, yielded the lowest levels of BDG, and probably would not cause false positive for fungal infections. There is a need for the development of a gauze product that does not contribute to elevated BDG values.


Spearman's footrule as a measure of cDNA microarray reproducibility.
Replication is a crucial aspect of microarray experiments, due to various sources of errors that persist even after systematic effects are removed. It has been confirmed that replication in microarray studies is not equivalent to duplication, and hence it is not a waste of scientific resources. Replication and reproducibility are the most important issues for microarray application in genomics. However, little attention has been paid to the assessment of reproducibility among replicates. Here we develop, using Spearman's footrule, a new measure of the reproducibility of cDNA microarrays, which is based on how consistently a gene's relative rank is maintained in two replicates. The reproducibility measure, termed index.R, has an R2-type operational interpretation. Index.R assesses reproducibility at the initial stage of the microarray data analysis even before normalization is done. We first define three layers of replicates, biological, technical, and hybridizational, which refer to different biological units, different mRNAs from the same tissue, and separate cDNAs from a cDNA pool. As the replicate layer moves down to a lower level, the experiment has fewer sources of errors and thus is expected to be more reproducible. To validate the method we apply index.R to two sets of controlled cDNA microarray experiments, each of which has two or three layers of replicates. Index.R shows a uniform increase as the layer of the replicates moves into a more homogeneous environment. We also note that index.R has a larger jump size than Pearson's correlation or Spearman's rank correlation for each replicate layer move, and therefore, it has greater expandability as a measure in [0,1] than these two other measures.


Empirical treatment of influenza-associated pneumonia in primary care: a descriptive study of the antimicrobial susceptibility of lower respiratory tract bacteria (England, Wales and Northern Ireland, January 2007-March 2010).
To determine the susceptibility of lower respiratory tract (LRT) isolates of Streptococcus pneumoniae, Staphylococcus aureus and Haemophilus influenzae to antimicrobial agents recommended by UK guidelines for treatment of pneumonia associated with influenza-like illness. Analysis of antimicrobial susceptibility data from sentinel microbiology laboratories in England, Wales and Northern Ireland was carried out. Subjects comprised patients who had an LRT specimen taken in a general practitioner surgery or hospital outpatient setting between January 2007 and March 2010. The main outcome measurements were antimicrobial susceptibility trends of LRT isolates over time, between patient age groups and in different geographical regions. Susceptibility to tetracyclines or co-amoxiclav was high. Of the 70,288 and 45,288 isolates with susceptibility results for tetracyclines or co-amoxiclav, 96% and 92%, respectively, were susceptible. Overall susceptibility to ciprofloxacin, ampicillin/amoxicillin and macrolides was lower than for tetracyclines or co-amoxiclav and varied markedly by organism. There were few clinically relevant variations in susceptibility to doxycycline or co-amoxiclav over time, geographically or between age groups. The data support the use of doxycycline or co-amoxiclav as appropriate empiric treatment for LRT infection caused by the pathogens investigated, for patients in primary care.


Departmental Experience and Lessons Learned With Accelerated Introduction of Telemedicine During the COVID-19 Crisis.
Despite the use of digital technology in healthcare, telemedicine has not been readily adopted. During the COVID-19 pandemic, healthcare systems have begun crisis management planning. To appropriately allocate resources and prevent virus exposure while maintaining effective patient care, our orthopaedic surgery department rapidly introduced a robust telemedicine program during a 5-day period. Implementation requires attention to patient triage, technological resources, credentialing, education of providers and patients, scheduling, and regulatory considerations. This article provides practical instruction based on our experience for physicians who wish to implement telemedicine during the COVID-19 pandemic. Between telemedicine encounters and necessary in-person visits, providers may be able to achieve 50% of their typical clinic volume within 2 weeks. When handling the massive disruption to the routine patient care workflow, it is critical to understand the key factors associated with an accelerated introduction of telemedicine for the safe and effective continuation of orthopaedic care during this pandemic. LEVEL OF EVIDENCE:: V.


Mapping and characterization of the eukaryotic early pregnancy factor/chaperonin 10 gene family.
Early pregnancy factor and mitochondrial chaperonin 10 have very different functions within mammals but the mature peptides have identical amino acid sequences. In order to understand the mechanisms by which identical proteins can have different functions and sites of activity, we have examined genomic DNA which could encode the protein. In most species studied, there is a large gene family of at least ten members with homology to the DNA sequence for this protein. Using a monochromosomal somatic cell hybrid panel, we have mapped the gene for human chaperonin 10 to chromosome 2. Other members of the human gene family map to several chromosomes. Chromosomes 1, 2 and 9 contain pseudogenes with Alu insertions while chromosome 16 has a pseudogene containing a short direct repeat flanking an insert. Chromosomes 1 and 16 may also carry a functional intronless copy of the EPF/Cpn10 sequence.


[Evaluation of 25 years of antileprosy chemotherapy in French Polynesia. Influence of age on the onset of the disease].
In French Polynesia the cases of leprosy are individually severe, like in Asia, but the endemy always stood under a relatively low level. A strong campaign of chemiotherapy has been conducted for 25 years. Unfortunatly the actions of systematic detection of new cases are not sufficient and the sanitary education is almost non existent. The territory is actualy reached by deep demographic and social upsettings and chemiotherapy used alone is not enough efficient to obtain a definitive decrease of the endemy or even to avoid, for a long time, a new increase. However a significant decrease of the age of advent of the decrease must be credited to the action of chemiotherapy.


Risk factors for unplanned and unwanted teenage pregnancies occurring over two years of follow-up among a cohort of young South African women.
Although teenage pregnancies in South Africa have declined, the short and longer term health and social consequences are a potential public health concern. This longitudinal study aimed to describe the range of risk and protective factors for incident unwanted and unplanned pregnancies occurring over 2 years of follow-up among a cohort of adolescent women in the Eastern Cape, South Africa. It also investigated the relationship between gender inequality and gender-based violence and subsequent unplanned and unwanted pregnancies among the cohort. Teenage girls, aged 15-18 years (n=19), who were volunteer participants in a cluster randomized controlled trial and who had data from at least one follow-up were included in this analysis. To assess risk and protective factors for incident unwanted or unplanned pregnancies, we constructed multivariate polytomous regression models adjusting for sampling clusters as latent variables. Covariates included age, having a pregnancy prior to baseline, education, time between interviews, study intervention arm, contraceptive use, experience of intimate partner violence, belief that the teenage girl and her boyfriend are mutual main partners, and socioeconomic status. Overall, 174 pregnancies occurred over the 2-year follow-up period. Beliefs about relationship control were not associated with unwanted and unplanned pregnancies, nor were experiences of forced first sex or coerced sex under the age of 15. Hormonal contraception was protective against unplanned pregnancies (OR 0.40; 95% CI 0.21-0.79); however, using condoms was not protective. Physical abuse (OR 1.69; 95% CI 1.05-2.72) was a risk factor for, and having a pregnancy prior to baseline was protective against an unwanted pregnancy (OR 0.25; 95% CI 0.07-0.80). Higher socioeconomic status was protective for both unplanned and unwanted pregnancies (OR 0.69; 95% CI 0.58-0.83 and OR 0.78; 95% CI 0.64-0.96). Believing that the teenage girl and her boyfriend were mutual main partners doubled the odds of reporting both an unplanned and unwanted pregnancy (OR 2.58 95% CI 1.07-6.25, and OR 2.21 95% CI 1.13-4.29). Although some of the measures of gender inequity were not associated with unplanned and unwanted pregnancies, there is evidence of the role of both gender power and socioeconomic status. This was evident in teenage girls who experienced physical violence being more likely to have an unwanted pregnancy. Interventions to prevent teenage pregnancies need to be tailored by socioeconomic status because some teenagers may see having a pregnancy as a way to have a more secure future. Interventions that engage with relationship dynamics of teenagers are essential if unwanted and unplanned pregnancies are to be prevented.


Dissociable mechanisms of speed-accuracy tradeoff during visual perceptual learning are revealed by a hierarchical drift-diffusion model.
Two phenomena are commonly observed in decision-making. First, there is a speed-accuracy tradeoff (SAT) such that decisions are slower and more accurate when instructions emphasize accuracy over speed, and vice versa. Second, decision performance improves with practice, as a task is learnt. The SAT and learning effects have been explained under a well-established evidence-accumulation framework for decision-making, which suggests that evidence supporting each choice is accumulated over time, and a decision is committed to when the accumulated evidence reaches a decision boundary. This framework suggests that changing the decision boundary creates the tradeoff between decision speed and accuracy, while increasing the rate of accumulation leads to more accurate and faster decisions after learning. However, recent studies challenged the view that SAT and learning are associated with changes in distinct, single decision parameters. Further, the influence of speed-accuracy instructions over the course of learning remains largely unknown. Here, we used a hierarchical drift-diffusion model to examine the SAT during learning of a coherent motion discrimination task across multiple training sessions, and a transfer test session. The influence of speed-accuracy instructions was robust over training and generalized across untrained stimulus features. Emphasizing decision accuracy rather than speed was associated with increased boundary separation, drift rate and non-decision time at the beginning of training. However, after training, an emphasis on decision accuracy was only associated with increased boundary separation. In addition, faster and more accurate decisions after learning were due to a gradual decrease in boundary separation and an increase in drift rate. The results suggest that speed-accuracy instructions and learning differentially shape decision-making processes at different time scales.


Illness representations in patients with traumatic injury: a longitudinal study.
This study aimed to elucidate the illness representations of patients with traumatic injury and to examine what extent their illness representations change over time. Traumatic injury has attracted global concern because it is the major reason for death and disability in people under 45 years old. One model, the Common Sense Model of Illness Representation (CSMIR), has the potential to help individuals adjust to changes in health status such as traumatic injury. Longitudinal study design. This study was conducted using a and collected data prior to hospital discharge and at three and six months after hospital discharge. One individual question form and the Chinese Illness Perception Questionnaire Revised (IPQ-R) (Trauma) were used to collect demographic data, clinical data and illness representations. A total of 114 participants completed the survey three times. The overall response rate was 79.7%. Six subscales of the Chinese (Trauma): identity, emotional representations, consequences, controllability, illness coherence and causes of the Chinese IPQ-R (Trauma) changed significantly over time. Two subscales, Timeline (acute/chronic) and Timeline Cyclical, did not change significantly. Based on these findings, there may be a window of opportunity to provide appropriate interventions to individuals with traumatic injury at each time point. The results of this study have implications for nursing practice and further nursing research. Understanding illness representation in patients with traumatic injury may help nurses to provide anticipatory guidance and to design nursing interventions before and after hospital discharge, ultimately to improve health outcomes of those patients.


[The simultaneous determination of hippuric acid, o-, m-, p-methylhippuric acids, mandelic acid and phenylglyoxylic acid in urine by HPLC].
A high-performance liquid chromatographic method is described for the simultaneous determination of six metabolites of aromatic hydrocarbons: hippuric acid (HA) from toluene; o-, m-, p-methylhippuric acids (o-, m-, p-MHA) from xylene; mandelic acid (MA) and phenylglyoxylic acid (PGA) from styrene and ethylbenzene. Metabolites were first extracted from urine by solid phase extraction with anion exchange resin, then isocratically separated on a C8 column with 3 microns particle size, 10 cm length and 3 mm internal diameter. Mobile phase was prepared diluting 16 mL of tetrahydrofuran, 14 mL of acetronitrile and 5 mL of methanol to 500 mL with phosphoric acid/potassium dihydrogen phosphate buffer 0.01 M (pH 2.7). The internal standard was 3-hydroxybenzoic acid. Chromatographic runs were completed in about 21 min. The accuracy and reproducibility obtained make this method useful for the biological monitoring of occupational exposure to toluene, xylene, styrene and ethylbenzene.


A Structure-based Data Set of Protein-Peptide Affinities and its Nonredundant Benchmark: Potential Applications in Computational Peptidology.
Peptides play crucial roles in diverse cellular functions and participate in many biological processes by interacting with a variety of proteins, which have also been exploited as a promising class of therapeutic agents to target druggable proteins over the past decades. Understanding the intrinsic association between the structure and affinity ofprotein-peptide interactions (PpIs) should be considerably valuable for the computational peptidology area, such as guiding protein-peptide docking calculations, developing protein-peptide affinity scoring functions, and designing peptide ligands for specific protein receptors. We attempted to create a data source for relating PpI structure to affinity. By exhaustively surveying the whole protein data bank (PDB) database as well as the ontologically enriched literature information, we manually curated a structure-based data set of protein-peptide affinities, PpI[S/A]DS, which assembled over 350 PpI complex samples with both the experimentally measured structure and affinity data. The data set was further reduced to a nonredundant benchmark consisting of 102 culled samples, PpI[S/A]BM, which only selected those of structurally reliable, functionally diverse and evolutionarily nonhomologous. The collected structures were resolved at a high-resolution level with either X-ray crystallography or solution NMR, while the deposited affinities were characterized by dissociation constant, i.e. Kd value, which is a direct biophysical measure of the intermolecular interaction strength between protein and peptide, ranging from subnanomolar to millimolar levels. The PpI samples in the set/benchmark were arbitrarily classified into α-helix, partial α-helix, β-sheet formed through binding, β-strand formed through self-folding, mixed, and other irregular ones, totally resulting in six classes according to the secondary structure of their peptide ligands. In addition, we also categorized these PpIs in terms of their biological function and binding behavior. The PpI[S/A]DS set and PpI[S/A]BM benchmark can be considered a valuable data source in the computational peptidology community, aiming to relate the affinity to structure for PpIs.


Metabolic syndrome in subjects with bipolar disorder and major depressive disorder in a current depressive episode: Population-based study: Metabolic syndrome in current depressive episode.
To assess the differences in the prevalence of the metabolic syndrome (MetS) and their components in young adults with bipolar disorder (BD) and major depressive disorder (MDD) in a current depressive episode. This was a cross-sectional study with young adults aged 24-30 years old. Depressive episode (bipolar or unipolar) was assessed using the Mini International Neuropsychiatric Interview - Plus version (MINI Plus). The MetS was assessed using the National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP III). The sample included 972 subjects with a mean age of 25.81 (±2.17) years. Both BD and MDD patients showed higher prevalence of MetS compared to the population sample (BD = 46.9%, MDD = 35.1%, population = 22.1%, p < 0.001). Higher levels of glucose, total cholesterol and LDL cholesterol, Body Mass Index, low levels of HDL cholesterol, and a higher prevalence of abdominal obesity were observed in both BD and MDD individuals with current depressive episode compared to the general population. Moreover, there was a significant difference on BMI values in the case of BD and MDD subjects (p = 0.016). Metabolic components were significantly associated with the presence of depressive symptoms, independently of the diagnosis.


Nonadiabatic quantum dynamics based on a hierarchical electron-phonon model: exciton dissociation in semiconducting polymers.
A hierarchical electron-phonon coupling model is applied to describe the ultrafast decay of a photogenerated exciton at a donor-acceptor polymer heterojunction, via a vibronic coupling mechanism by which a charge-localized interfacial state is created. Expanding upon an earlier Communication [H. Tamura et al., J. Chem. Phys. 126, 021103 (2007)], we present a quantum dynamical analysis based on a two-state linear vibronic coupling model, which accounts for a two-band phonon bath including high-frequency C[Double Bond]C stretch modes and low-frequency ring torsional modes. Building upon this model, an analysis in terms of a hierarchical chain of effective modes is carried out, whose construction is detailed in the present paper. Truncation of this chain at the order n (i.e., 3n+3 modes) conserves the Hamiltonian moments (cumulants) up to the (2n+3)rd order. The effective-mode analysis highlights (i) the dominance of the high-frequency modes in the coupling to the electronic subsystem and (ii) the key role of the low-frequency modes in the intramolecular vibrational redistribution process that is essential in mediating the decay to the charge-localized state. Due to this dynamical interplay, the effective-mode hierarchy has to be carried beyond the first order in order to obtain a qualitatively correct picture of the nonadiabatic process. A reduced model of the dynamics, including a Markovian closure of the hierarchy, is presented. Dynamical calculations were carried out using the multiconfiguration time-dependent Hartree method.


Diets containing processed barley grain as a potential rumen bypass starch source enhance productive responses of lactating Holstein dairy cows.
Effect of diets containing untreated or processed barley grain [treated with sugar beet pulp extract (SBPE) or double sulphate of aluminium and potassium (ALUM)] and different levels of rumen undegradable crude protein (RUP) on production, rumen fermentation and blood metabolites of lactating Holstein cows were investigated. Untreated soybean meal (SBM) or xylose protected 'Yasminomax soy® (YAS)' was included to represent a low (LR, 4.2% DM) and high (HR, 5.4% DM) RUP diets, respectively. Experimental diet was as follows: (a) untreated barley grains with high RUP (HRCON); (b) untreated barley grains with low RUP (LRCON); (c) ALUM-treated barley grain with high RUP (HRAL; (d) ALUM-treated barley grain with low RUP (LRAL); (e) SBPE-treated barley grain with high RUP (HRSE); and (f) SBPE-treated barley grain with low RUP (LRSE). The experiment was conducted as a completely randomized design with lactating dairy cows (n = 36) averaging 215 ± 18 days in milk, milk yield 31.7 ± 5.8 kg/day, 620 ± 61 kg body weight. Diets containing processed barley grain increased feed intake, while decreased both rumination and eating (p < 0.001). Feed intake of dairy cows on Low RUP and High RUP were 23 and 24 kg/day, respectively (p < 0.01). Daily production of milk fat, protein, lactose and total solids was improved when the processed barley grain was included in the diets (p < 0.05). Present study pinpointed that the inclusion of the processed barley grain in diets might improve production indices of dairy cows.


Analysis of the association between lactotransferrin (LTF) gene polymorphism and dental caries.
The present study evaluated the association between lactotransferrin (LTF) gene polymorphism (exon 2, A/G, Lys/Arg) and dental caries. A convenience sample of 110 individuals, 12 years old, was divided into: group 1, 48 individuals without caries experience (DMFT=0), and group 2, 62 subjects with caries experience (DMFT>or=1). DNA was obtained from a mouthwash with 3% glucose solution, followed by a scrapping of the oral mucosa. After DNA purification, polymerase chain reaction (PCR), single strand conformation polymorphism (SSCP) was performed to access the study polymorphism. The LTF A/G (Lys/Arg) polymorphism had been previously reported as located in exon 1. Allele 1 of the study polymorphism was associated with low DMFT index and showed a protective effect against caries experience (OR=0.16, IC=0.03-0.76, p=0.01). Lactotransferrin A/G (exon 2, Lys/Arg) polymorphism was associated with susceptibility to dental caries in 12-year-old students.


Estimating the Raman cross sections of single carbon nanotubes.
The order of magnitude of Raman differential cross sections of radial breathing modes (RBMs) of individual carbon nanotubes is measured for 633 and 785 nm laser excitations. This is shown by both a calibration applied to previously published data from other authors at 785 nm and our own measurements of individual nanotubes at 633 nm excitation. We find typical values of differential cross sections of RBMs to be on the order of approximately 10(-22) cm(2)/sr for resonant nanotubes on a silicon substrate. This study therefore provides a rigorous quantification of the accepted view that Raman cross sections of carbon nanotubes are "huge".


Regional variation in human retinal vessel oxygen saturation.
The purpose of this study was to investigate regional differences in oxygen saturation of blood in first degree retinal vessels using a novel non-flash hyperspectral retinal camera (Photon etc Inc). Nine healthy individuals (mean age 24.4 ± 3.6 yrs, 5 males) were imaged at 548, 569, 586, 600, 605 and 610 nm wavelengths. Optical density values were extracted with the aid of Image-J software for blood oxygen saturation (SO2) determination. Arteriolar and venular SO2 were measured at three locations (ranging 1-3 optic nerve head radii) from the disc margin along the vessels in the superior and inferior temporal quadrants. Retinal SO2 was significantly higher in the superior temporal arteriole and venule as compared to the inferior temporal vessels (p = 0.033 and p = 0.032 for arterioles and venules, respectively). SO2 was not significantly different between the three measurement sites for any of the given vessels imaged (p > 0.05). In conclusion, greater SO2 values were found in the superior temporal first degree retinal arterioles and venules in young healthy individuals than in the equivalent inferior vessels. However, there were no detectable differences in retinal SO2 along each of the major vessels, a finding that is consistent with the concept of these vessels not contributing primarily to gas exchange. Moreover, the SO2 was consistently higher in the arterioles than in the equivalent venules (p < 0.0001).


In vitro and in vivo antitumor effects of folate-targeted ursolic acid stealth liposome.
The antitumor efficacy of ursolic acid (UA) was limited by poor hydrophilicity and low bioavailability. To overcome this issue, UA was encapsulated in liposomes modified with folate conjugates for better solubility and bioavailability. This novel agent was prepared by a thin-film dispersion method and characterized by mean diameter, zeta potential, and entrapment efficiency (160.1 nm, -21.2 mV, and 88.9%, respectively). In vitro, cellular uptake efficiency, cytotoxicity, apoptosis, and cell cycle analyses were performed to show that folate-receptor (FR) positive cells endocytose more FR-targeted liposome (FTL-UA) than nontargeted PEGylated liposome (PL-UA) and that FTL-UA induced more cytotoxicity and higher apoptosis than PL-UA. Pharmacokinetic assessments showed advantages of systemic bioavailability of FTL-UA (AUC = 218.32 mg/L·h, t1/2 = 7.61 h) over free UA (AUC = 36.88 mg/L·h, t1/2 = 0.78 h). In vivo, FTL-UA showed significantly higher human epidermoid carcinoma (KB) inhibition in Balb/c nu/nu mice compared to PL-UA or free UA. The results indicate the great potential of FTL-UA against KB tumor.


Four loci explain 83% of size variation in the horse.
Horse body size varies greatly due to intense selection within each breed. American Miniatures are less than one meter tall at the withers while Shires and Percherons can exceed two meters. The genetic basis for this variation is not known. We hypothesize that the breed population structure of the horse should simplify efforts to identify genes controlling size. In support of this, here we show with genome-wide association scans (GWAS) that genetic variation at just four loci can explain the great majority of horse size variation. Unlike humans, which are naturally reproducing and possess many genetic variants with weak effects on size, we show that horses, like other domestic mammals, carry just a small number of size loci with alleles of large effect. Furthermore, three of our horse size loci contain the LCORL, HMGA2 and ZFAT genes that have previously been found to control human height. The LCORL/NCAPG locus is also implicated in cattle growth and HMGA2 is associated with dog size. Extreme size diversification is a hallmark of domestication. Our results in the horse, complemented by the prior work in cattle and dog, serve to pinpoint those very few genes that have played major roles in the rapid evolution of size during domestication.


Knowledge and beliefs of adolescents regarding sexually transmitted infections and HIV/AIDS in a rural district in Pakistan.
To assess the knowledge and beliefs of adolescents (15-19 years girls and boys) regarding sexually transmitted infections (STIs) and HIV/AIDS. A community based cross-sectional survey was conducted in October 2002 in a rural district (Mirpurkhas) of Sindh province, Pakistan. A total of 428 adolescent girls and boys were interviewed. Only 44% correctly named at least one STI, while 55% knew at least two modes of transmission for HIV/AIDS. Adolescents with education greater than or equal to secondary level, those who were able to read the newspaper, possessed electricity in their homes and were allowed to meet their friends once in six months had significantly more HIV/AIDS knowledge. We conclude that rural adolescents of Sindh need more knowledge regarding STIs including HIV/AIDS. There is a need to formulate strategies to raise the levels of awareness and knowledge among adolescents regarding these conditions. Our findings indirectly support the use of mass media and peer education strategies to provide factual information to adolescents.


Measurement of quality of life V. How to use the SEQOL, QOL5, QOL1, and other global and generic questionnaires for research.
A survey can be divided into four phases: (1) planning, (2) distributing and collecting the questionnaires, (3) analysis, and (4) dissemination of the results. This paper provides step-by-step guidance on how the global and generic SEQOL (self-evaluated quality of life) and QOL5 questionnaires can be used in a large- or small-scale survey of quality of life (QOL). It covers what is required to conduct a survey and generate results that should be of interest to local politicians, decision makers, and representatives from the surveyed groups and should be published after it has been processed and edited. If the results are to be published in the scientific literature, it is necessary to seek the assistance of an expert in statistics and/or research and the dissemination of research results.