Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015.
Yellow fat disease or steatitis is characterised by a local or general inflammation of fat tissue and is occasionally found in horses. Diagnosis is challenging because of the wide range of nonspecific clinical signs. To describe clinical signs, treatment, outcome and ultrasonographic findings in horses with steatitis. Retrospective study (January 2008 to January 2015). History, clinical signs, ultrasonographic findings, diagnosis, treatment and outcome were recorded. Twenty cases (18 horses, 2 donkeys; 9 mares, 9 stallions, 2 geldings) were retrieved from 13,707 patient records. Mean age was 1.6 (± 0.8) years (range 1 month-3.5 years). All cases appeared between October and February except for one (August). History included dullness, recumbency, decreased appetite and weight loss. Fever, ventral oedema, stiff/painful gait and painful neck were found. Low haematocrit, low vitamin E and selenium and increased levels of creatinine kinase and particularly lactate dehydrogenase were almost consistent findings. On ultrasound, ventral oedema was found. Subperitoneal, perirenal, mesenteric, coronary and caudal mediastinal fat showed homogenously increased echogenicity. Especially the subperitoneal fat was surrounded by oedema or free fluid. Increased amounts of abdominal, thoracic and pericardial fluid were often found. Fat biopsies were taken in the neck or from the retroperitoneal fat in the ventral flank. In all horses where fat biopsy was taken (n = 13), steatitis was confirmed. Treatment consisted of selenium and vitamin E (intra-muscular injection followed by oral treatment) supplementation and anti-inflammatory treatment (dexamethasone or prednisolone parenteral or oral) for at least 1-4 weeks. Fourteen animals (70%) survived. Full recovery took about 2-6 months. Yellow fat disease may be underdiagnosed because of the nonspecific clinical signs. Ultrasound was extremely helpful for making a diagnosis. Recovery was rather slow but was achieved in 70% of the animals. Ethical animal research: Research ethics committee oversight not currently required by this conference: retrospective study of clinical records. Explicit owner informed consent for inclusion of animals in this study was not stated. Ghent University (institutional). Competing interests: None declared.


Extraction protocol for nontargeted NMR and LC-MS metabolomics-based analysis of hard coral and their algal symbionts.
Metabolomics and in particular, nontargeted metabolomics, has become a popular technique for the study of biological samples as it provides considerable amounts of information on extractable metabolites and is ideal for studying the metabolic response of an organism to stressors in its environment. One such organism, the symbiotic hard coral, presents its own complexity when considering a metabolomics approach in that it forms intricate associations with an array of symbiotic macro- and microbiota. While not discounting the importance of these many associations to the function of the coral holobiont, the coral-Symbiodinium relationship has been the most studied to date and as such, is the primary focus of this extraction protocol. This protocol provides details for the sample collection, extraction, and measurement of hard coral holobiont metabolites using both (1)H nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography coupled with mass spectrometry (LC-MS). Using this nontargeted metabolomics approach, the holobiont metabolism can be investigated for perturbations resulting from either (1) natural or anthropogenic environmental challenges, (2) the controlled application of stressors, and (3) differences between phenotypes or species. Consequently, this protocol will benefit both environmental and natural products based research of hard coral and their algal symbionts. Every effort has been made to provide the reader with all the details required to perform this protocol, including many of the costly and time consuming "pitfalls" or "traps" that were discovered during its development. As a result, this protocol can be confidently accomplished by those with less experience in the extraction and analysis of symbiotic hard coral, requiring minimal user input whilst ensuring reproducible and reliable results using readily available lab ware and reagents.


Effects of supplementing with Humulus scandens on the growth performance and gut microbiota in piglets.
This study was conducted to evaluate the effects of feeding Humulus scandens (Hu) on growth performance and gut microbiota in piglets. A total of 120 piglets were allocated to four dietary treatments (1) CON, basal diet; (2) T1, basal diet + 2.0% Hu; (3) T2, basal diet + 2.8% Hu and (4) T3, basal diet + 3.6% Hu. The results showed that dietary H. scandens supplementation increased the final body weight and average daily gain. Furthermore, H. scandens supplementation in T1 groups increased the content of total protein, globulin and IgG in serum and the apparent digestibility of crude protein. Gut microbiota analysis showed that H. scandens treatment in T1 groups increased the abundances of Lactobacillus, Ruminococcaceae, Enterococcus and Pseudomonas in cecum content. These findings suggested that dietary H. scandens supplementation improved the growth performance, immunological function and nutrient apparent digestibility as well as modulating the gut microbiota in piglets. This study contributed to developing new feed resources and might provide an alternative strategy for growth promotion in piglets.


Aging, esophageal motility, and gastroesophageal reflux.
To compare esophageal motility and gastroesophageal reflux characteristics in young, middle-aged, and older healthy volunteers. Comparison of conventional esophageal manometry and scintigraphic study of gastroesophageal reflux in volunteers aged 20 to 30 years, 50 to 60 years, and 70 to 80 years. Gastroenterology and nuclear medicine laboratories of a tertiary care university hospital. Forty healthy adult volunteers recruited from the community, 20 aged 20 to 30 years, 10 aged 50 to 60 years, and 10 aged from 70 to 80 years. Each volunteer underwent conventional esophageal manometry and scintigraphic study of gastroesophageal reflux. Contractile wave amplitude, duration, velocity, and lower esophageal sphincter relaxation duration, as well as the presence of abnormal peristalsis, were correlated with the proportion of volunteers with gastroesophageal reflux and the number and duration of gastroesophageal reflux episodes. Quantitative manometric parameters showed no correlation with gastroesophageal reflux patterns. Abnormal peristalsis was found more frequently in the older volunteers. The number of gastroesophageal reflux episodes per volunteer was similar in the three age groups, but the duration of gastroesophageal reflux episodes was longer in the older volunteers. Healthy older persons have impaired clearance of refluxed materials associated with a high incidence of defective esophageal peristalsis. This may explain the higher severity of reflux esophagitis in older people.


Unequal development of thresholds for various phenomena induced by cortical stimulation in rats.
Electrical stimulation of sensorimotor cortical area was performed in 9-, 12-, 18-, 25-, 35- and 90-day-old rats with implanted electrodes to establish threshold intensities of currents necessary to elicit four different motor or EEG phenomena. Two different stimulation frequencies (8 and 50 Hz) were used. Development of thresholds for stimulation-bound movements, spike-and-wave afterdischarges and clonic seizures accompanying these afterdischarges was similar: the lowest threshold was found in 18-, respectively, in 18- and 25-day-old rats with the 8 and 50 Hz frequencies. Younger as well as older animals exhibited higher threshold intensities. The fourth phenomenon, transition into another, 'limbic' type of afterdischarges appeared only exceptionally in the youngest rats and its incidence increased whereas the threshold decreased with age. Higher frequency was more efficient in elicitation of limbic afterdischarges than the 8 Hz stimulation in rats aged 18 and more days. Our data represent a background for pharmacological studies and indicate the development of cortical excitability and of connections between the thalamocortical system and limbic structures.


Explore the dominant factor in prime editing via a view of DNA processing.
Prime editing is a revolutionary gene-editing method that is capable of introducing insertions, deletions and base substitutions into the genome. However, the editing efficiency of Prime Editor (PE) is limited by the DNA repair process. Here, we show that overexpression of the flap structure-specific endonuclease 1 (FEN1) and the DNA ligase 1 (LIG1) increases the efficiency of prime editing, which is similar to the dominant negative mutL homolog 1 (MLH1dn). In addition, MLH1 is still the dominant factor over FEN1 and LIG1 in prime editing. Our results help to further understand the relationship of proteins involved in prime editing and envisage future directions for the development of PE.


Morphology and Intramolecular Interactions in P(VDF-TrFE) Electrospun Nanofibers Doped with Disperse Orange 3 Dye: A Joint Infrared Spectroscopy and Electron Microscopy Study.
In this study, we describe a host-guest system consisting of a push-pull dye, the 4-amino-4'-nitroazobenzene (Disperse Orange 3, DO3), mixed with the copolymer poly(vinylidene fluoride-co-trifluoroethylene) [P(VDF-TrFE)] as a potential candidate for nonlinear optics (NLO) applications. We developed electrospun nanofibers of the polymer/dye blend, showing a highly anisotropic molecular structure, where DO3 molecules are mostly oriented parallel to the polymer chain, running in the fiber axis direction. The technique opens a way for obtaining non-centrosymmetric ordering of the NLO chromophore without requiring further poling. The supramolecular architecture is deeply investigated through infrared vibrational spectroscopy, which allows detecting a new phase involving DO3 molecules linked together by strong directional H-bonds. Electron microscopies highlight peculiar nanofiber morphologies with a preferred localization of DO3 at the surface layers.


Willingness to participate in organ donation among black Seventh-Day Adventist college students.
The authors studied a group of black and white Seventh-Day Adventist (SDA) college students (N = 334) to compare the power of religious socialization with racial socialization. The authors compared the levels of willingness to donate organs between black and nonblack students in an availability sample. Black SDA college students were significantly more likely than white SDA students or SDA students of other races to perceive racism in the healthcare system and to believe that doctors would not make heroic efforts to save their lives if they knew they were organ donors; they were 66.9% less likely to donate organs than were white SDA students or SDA students of other races. Despite a common religion with a purposive indoctrination, the racial socialization of black SDA students exerted a stronger influence on willingness to participate in organ donation than did that of white students and students of other races within this religion.


Skin Infiltrate Composition as a Telling Measure of Responses to Checkpoint Inhibitors.
Checkpoint inhibitors treat a variety of tumor types with significant benefits. Unfortunately, these therapies come with diverse adverse events. Skin rash is observed early into treatment and might serve as an indicator of downstream responses to therapy. We studied the cellular composition of cutaneous eruptions and whether their contribution varies with the treatment applied. Skin samples from 18 patients with cancer and 11 controls were evaluated by mono- and multiplex imaging, quantification, and statistical analysis. T cells were the prime contributors to skin rash, with T cells and macrophages interacting and proliferating on site. Among T cell subsets examined, type 1 and 17 T cells were relatively increased among inflammatory skin infiltrates. A combination of increased cytotoxic T cell content and decreased macrophage abundance was associated with dual checkpoint inhibition over PD1 inhibition alone. Importantly, responders significantly separated from nonresponders by greater CD68+ macrophage and either CD11c+ antigen-presenting cell or CD4+ T cell abundance in skin rash. The microenvironment promoted epidermal proliferation and thickening as well. The combination of checkpoint inhibitors used affects the development and composition of skin infiltrates, whereas the combined abundance of two cell types in cutaneous eruptions aligns with responses to checkpoint inhibitor therapy.


Alternative end-joining in follicular lymphomas' t(14;18) translocation.
T(14;18) chromosomal translocation is assumed to result from illegitimate rearrangement between the BCL2 proto-oncogene and the IGH locus during the D(H) to J(H) joining phase of V(D)J recombination in early B cells. Analysis of the breakpoint junctions suggests that translocation derives from the fusion between normal V(D)J recombination intermediates at the IGH locus and non-V(D)J-mediated broken-ends at the BCL2 locus. So far, BCL2 broken-ends have only been observed fused to coding-ends, raising questions concerning the molecular constraints of the illegitimate joining process. Using a combination of genome walking and long-range PCR assays, we describe in this report that in 4.5% (2/44) of the t(14;18), one of the BCL2 broken-ends is fused to a signal-end. The formation of these J(H)RSS/BCL2 junctions provides direct evidence that BCL2 broken-ends are capable of joining to both products of V(D)J recombination, suggesting their presence in the RAG-mediated post-cleavage complex. In addition, junctions generated by this alternative end-joining do not involve deletion of the chromosome 14 intervening sequences generally lost in the standard translocation, providing a unique opportunity to investigate the rearrangement status of this region in the translocated IGH allele. In both cases, a DJ(H) rearrangement could be detected 5' of the J(H)-RSS/BCL2 junction. These findings, together with the previously reported bias towards the most external D(H) and J(H) segments in standard breakpoints, strongly suggest that t(14;18) preferentially occurs during an attempted secondary D(H) to J(H) rearrangement. This unusual and restricted window of differentiation opens intriguing questions concerning the etiology of the translocation.


Determination of false negative rate in fine-needle aspiration of prostate. Study of sequential aspirations in 30 untreated carcinoma patients.
Despite several studies comparing the diagnostic accuracy of core needle biopsy and fine-needle aspiration (FNA) in the diagnosis of prostatic adenocarcinoma, no clear picture of the false negative rate for FNA is available. We studied 101 follow-up FNA evaluations in 30 patients with untreated well-differentiated carcinoma. The patients were followed for a median of two years and seven months and had from two to seven FNA follow-up evaluations (median = 2.5 evaluations per patient). If three inadequate evaluations are omitted, the combined rate of positive plus suspicious FNA biopsies was 92.9 percent (88.8% plus 4.1%, respectively). The residual false negative rate was 7.1 percent. The clinical features and follow-up data are described. A semiquantitative definition of "suspicious for malignancy" is suggested. We conclude that in experienced hands. FNA is a highly efficacious method for the diagnosis of prostatic adenocarcinoma.


Episodic-like memory in mice: simultaneous assessment of object, place and temporal order memory.
Episodic memory refers to the conscious recollection of a unique past experience in terms of "what" happened and "where" and "when" it happened. Since deficits in episodic memory are found in a number of neuropsychiatric diseases, such as Alzheimer's disease, for which several pharmacological, lesion and genetic animal models are available, there is a need for animal models of episodic-like memory, which can be used to devise appropriate treatments. However, even when the problem of conscious recollection in animals is factored out, episodic memory has been difficult to demonstrate in nonhuman mammals because it has not yet been possible to demonstrate an integrated memory for "what",-"where"-and-"when". We designed a three-trial "what",-"where"-and-"when" object exploration task in which different versions of the novelty preference paradigm were combined to subsume (a) object recognition memory, (b) the memory for locations in which objects were explored and (c) the temporal order memory for objects presented at distinct time points. Our results suggest that mice are able to (a) recognize previously explored objects, (b) remember the location in which particular objects were previously encountered and (c) discriminate the relative recency in which different objects were presented. We suggest that our protocol providing the simultaneous assessment of object memory for "what",-"where"-and-"when" in mice might be useful in the search for the neural substrates of episodic memory, the screening for promnestic drugs and the behavioral phenotyping of genetic models of neuropsychiatric diseases affecting episodic memory.


Age over 65 years and high levels of C-reactive protein are associated with the risk of preoperative deep vein thrombosis following closed distal femur fractures: a prospective cohort study.
In this study, we investigated the epidemiological characteristics and predictors of preoperative new-onset deep vein thrombosis (DVT) in adult patients with closed distal femur fractures (DFFs). The study was designed as a prospective cohort trial at the Third Hospital of Hebei Medical University. From October 2018 to June 2020, a total of 160 patients with closed DFFs were enrolled to assess the location and prognosis of preoperative DVT. The patients were followed up for 2 months. Duplex ultrasonography (DUS) was used to diagnose patients with DVT. The patients were divided into two groups (DVT group and non-DVT group). The DVT was then classified into proximal, distal, and mixed thromboses. The Mann-Whitney U test or t test, receiver operating characteristic (ROC) analyses, univariate Chi-square analyses, and multiple logistic regression analyses were used to analyze the adjusted predictors of DVT. The overall incidence of preoperative DVTs was 52.5% (n = 84), which was diagnosed at a mean period of 3.1 days after injury. Among patients diagnosed with DVTs, 50.0% (n = 42) had distal thrombosis while 47.6% (n = 40) had mixed thrombosis. The calf muscle veins were the most common sites of DVTs (90.5%, n = 76). Of note, 45.2% (n = 38) of diagnosed DVTs were completely recanalized at a mean period of 12.0 days after the initial (first) diagnosis. Multivariate analysis revealed that age of ≥ 65 years of age (odds ratio [OR], 4.390; 95% confidence interval [CI] 1.727-11.155; p = 0.002), C-reactive protein (CRP) levels exceeding 11 mg/L (OR 4.158; 95% CI 1.808-11.289; p = 0.001), platelet (PLT) levels over 217 × 109/L (OR, 2.55; 95% CI 1.07-6.07; p = 0.035), D-dimer levels over 1.0 mg/L (OR 3.496; 95% CI 1.483-8.237; p = 0.004), and an American Society of Anesthesiologists (ASA) score of III-V (OR 2.753; 95% CI 1.216-6.729; p = 0.026) were the independent risk factors of preoperative DVT. High levels of CRP, PLT, D-dimer, ASA, and ≥ 65 years of age increase the risk of preoperative DVTs in adult patients with closed DFFs. Thus, the prediction of preoperative DVTs can significantly be improved by identifying older patients over the age of 65, and establishing the biochemical cut-off values of CRP, PLT, ASA, and D-dimer. No. 2018-026-1, 24 October 2018, prospectively registered. This trial was registered prospectively on 24 October 2018 before the first participant was enrolled. This study protocol conformed to the Declaration of Helsinki and approved by the Institutional Review Board. The ethics committee approved the study on the factors of prognosis for patients with fractures. Data used in this study were obtained from the patients who underwent orthopedic surgery between October 2018 and June 2020.


Coagulation of the lateral surface of aryepiglottic folds as an alternative to aryepiglottic fold release in management of type 2 laryngomalacia.
Endoscopic supraglottoplasty is the procedure of choice in treatment of laryngomalacia with CO2 laser and cold steel being the most common instruments used with excellent results. However, bleeding, supraglottic stenosis and aspiration may occur leading to serious complications. Using coblation in management of laryngomalacia was found to be beneficial. Therefore, we conducted this study to evaluate the outcome of supraglottoplasty done by coagulation using coblation of the lateral surface of aryepiglottic folds as an alternative technique to aryepiglottic fold release in management of type 2 laryngomalacia. Retrospective study was conducted at Mansoura University Hospitals; Egypt from November 2017 to March 2018 included patients diagnosed with severe type 2 laryngomalacia. Supraglottoplasty was done by using coblator applied to the lateral surface of aryepiglottic folds allowing for lateral scarring thus widening the airway, preventing supraglottic collapse and avoiding re-stenosis. Outcome measures included assessment of presence or absence of the following symptoms preoperatively and postoperatively: inspiratory stridor, failure to thrive, choking and cyanosis. Preoperative and postoperative lowest oxygen saturation levels, weight-by-age percentile, and need for tracheostomy were assessed. Nine patients were included in this study with a mean age of 3.78 ± 1.20 months (range 2-6 months). Overall success rate was 89%. The most significantly improved symptom was stridor (p-value 0.008). Significant improvement in lowest oxygen saturation levels (from 89.11 ± 3.06% pre-operatively to 96.44 ± 3.50% post-operatively) and weight gain (from 4288.9 ± 643.1 gm. preoperatively to 5505.55 ± 1017.4 gm. 1 month postoperatively) was achieved. No detected re-stenosis on follow up and none of our cases needed tracheostomy. Supraglottoplasty by coagulation of the lateral surface of aryepiglottic folds using coblation is an effective and safe technique and can improve airway symptoms and weight gain in patients with type 2 laryngomalacia.


[Combined action on the body of a mixture of the volatile products of lubricating oil thermal oxidative breakdown and of hypoxic hypoxia].
The experiments on white male mice have shown that the combined effect of different concentrations of mixtures of volatile products of thermooxidative decomposition of the lubricating oil 36/IKUA and hypoxia at altitudes 5,000; 7,000 and 8,000 m depends on the intensity of the combined factors. It is indicated that maximally allowable concentrations of the above mixtures in the space cabin atmosphere should be determined, taking into consideration the level of hypoxia.


Retinal receptive fields under different adaptation levels studied with pattern-evoked ERG.
The pattern-evoked electroretinogram (PERG) was studied in three normal subjects under different levels of adaptation using pattern onset-offset stimulation. The occurrence of a response maximum (spatial selectivity) in the onset response at a certain spatial frequency can be interpreted as reflecting the activity of neurons having antagonistic center-surround receptive fields and allows an estimation of receptive-field center sizes. The present data suggest that in the light-adapted state, the majority of receptive fields, dominating the response can be estimated to have center diameters of 6-13 min of arc. With increasing dark adaptation, the spatial selectivity shifts from high to low spatial frequencies over 1.3-2.4 octaves, indicating that large receptive fields are active in the dark and small fields in the light. The physiological mechanisms of these changes are discussed on the basis of findings obtained from single-unit studies.


Intrauterine treatment of a fetal pulmonary cyst by chorioamniotic shunt.
This is a report of a prenatal diagnosis and successful intrauterine drainage of a pulmonary cyst by placement of a thoracoamniotic shunt at 36 weeks gestation. At the time of delivery the newborn had no signs of pulmonary hypoplasia or respiratory insufficiency.


Sulphonate functionalized covalent organic framework-based magnetic sorbent for effective solid phase extraction and determination of fluoroquinolones.
Most of the reported covalent organic frameworks (COFs) are hydrophobic, limiting their adsorption application in sample pretreatment field. In this work, sulphonate functionalized magnetic covalent organic frameworks (COFs) composites were first synthesized by loading gold nanoparticles on Fe3O4@COF(TpBD) surface and then functionalized by sodium 3-mercaptopropanesulphonate immobilization via Au-S bonding formation (denoted as Fe3O4@COF(TpBD)@Au-MPS nanocomposites), which were further utilized as adsorbents for magnetic solid-phase extraction (MSPE) of fluoroquinolones. Compared with Fe3O4@COF(TpBD), the composites exhibited higher affinity to fluoroquinolones. Under optimized conditions, the developed MSPE method coupled with HPLC-MS/MS showed good linearity (R2 ≥0.9989) and yielded low limits of detection (0.1-1.0 μg kg-1) for fluoroquinolones. Moreover, the proposed method was successfully applied to extract fluoroquinolones from spiked meats (pork, chicken and bovine). The satisfactory recoveries were in the range of 82-110.2% with the relative standard deviations (RSDs) lower than 7.7%. These results indicated that the Fe3O4@COF(TpBD)@Au-MPS is a promising magnetic adsorbent for trace fluoroquinolones determination in meat samples. This work not only provided a facile strategy for COF functionalization, but also developed an efficient method for detecting fluoroquinolones in foodstuffs.


Effect of external diaphragmatic pacing therapy on patients with chronic cor pulmonale: a randomized, controlled trial.
This study aimed to evaluate the effects of external diaphragmatic pacing (EDP) on patients with chronic cor pulmonale (CCP). Fifty patients with CCP were enrolled in Kashgar Prefecture Second People's Hospital in Xinjiang Uygur Autonomous Region of China from 2016 to 2017. The patients were randomized into a group that received anti-CCP therapy (negative control group) or a group that received additional EDP treatment (EDP group). We recorded and compared maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, and the 6-minute walking test between the two groups on the first and tenth days of treatment. Ten days after treatment began, MIP, FVC, and the 6-minute walking test were significantly improved in both groups. Importantly, MIP and FVC were significantly higher in the EDP group compared with the control group on the tenth day. In addition to treatment for CCP, these patients can obtain extra benefit by using EDP treatment.


OATPB1/B3 and MRP3 expression in hepatocellular adenoma predicts Gd-EOB-DTPA uptake and correlates with risk of malignancy.
Hepatobiliary phase (HBP) Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) has increased the accuracy in differentiating focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA). However, the ability of this technique to distinguish HCA subtypes remains controversial. The aim of this study was to investigate the expression of hepatocyte transporters (OATPB1/B3, MRP2, MRP3) in HCA subtypes, hence to understand their MRI signal intensity on HBP Gd-EOB-DTPA-enhanced MRI. By means of immunohistochemistry (IHC), we scored the expression of OATPB1/B3, MRP2 and MRP3, in resected specimens of FNH (n = 40), subtyped HCA (n = 58) and HCA with focal malignant transformation (HCA-HCC, n = 4). Results were validated on a supplementary set of FNH (n = 6), subtyped HCA (n = 17) and HCA-HCC (n = 1) with Gd-EOB-DTPA MR images. All FNH showed a preserved expression of hepatocytes transporters. Beta-catenin-activated HCA (at highest risk of malignant transformation) and HCA-HCC were characterized by preserved/increased OATPB1/B3 expression (predictor of hyperintensity on HBP), as opposed to other HCA subtypes (P < 0.01) that mostly showed OATPB1/B3 absence (predictor of hypointensity on HBP). HCA-HCC showed an additional MRP3 overexpressed profile (P < 0.01). On HBP Gd-EOB-DTPA-enhanced MRI, FNH and HCA signal intensity reflected the profile predicted by their specific OATPB1/B3 tissue expression. The hyperintense vs hypointense HBP signal criterion was able to distinguish all higher risk HCA and HCA-HCC (100% accuracy). OATPB1/B3 and MRP3 IHC and signal intensity on HBP Gd-EOB-DTPA-enhanced MRI can help to stratify HCA according to their risk of malignant transformation.


Overnight urinary melatonin levels in women with and without HIV: An observational cohort study.
Despite significant improvements in longevity and quality of life associated with antiretroviral therapy, individuals with HIV still suffer from a higher burden of sleep and circadian disruption and inflammatory-based diseases than individuals without HIV. While melatonin is a hormone that has a role in sleep and circadian regulation and has anti-inflammatory properties, the overnight concentration of the urinary melatonin metabolite has not yet been reported in people with HIV. The aim of this study was to compare the overnight urinary melatonin metabolite levels in women aged 35-70 years with HIV (n = 151) to a well-matched comparison group of women without HIV (n = 147). All women wore a wrist actigraphy monitor and completed daily diaries documenting sleep timing and use of medications and drugs or alcohol for 10 days. Participants collected their overnight urine near the end of the monitoring period. Melatonin levels did not differ between women with or without HIV, but more than 40% of women had low levels of melatonin. Higher body mass index predicted lower levels of melatonin, and lower levels of melatonin were associated with lower sleep efficiency as assessed with wrist actigraphy. These data lay the foundation for exploration of the longitudinal consequences of endogenous melatonin levels for inflammatory-based diseases in aging women with and without HIV. Future studies should consider the use of supplemental melatonin to improve sleep in women with lower levels of melatonin.


Acute Care Surgery Billing, Coding and Documentation Series Part 1: Basic Evaluation and Management (E/M), Emergency Department E/M, Prolonged Services, Adult Critical Care Documentation and Coding.
This series of reviews has been produced to assist both the experienced surgeon and coder, as well as those just starting practice that may have little formal training in this area. Understanding this complex system will allow the provider to work 'smarter, not harder' and garner the maximum compensation for their work. We hope we have been successful in achieving that goal and that this series will provide useful information and be worth the time invested in reading it by bringing tangible benefits to the efficiency of practice and its reimbursement.


Investigation on the complex of diperoxovanadate with 2-(2'-pyridyl)-imidazole.
A novel diperoxovanadate complex NH4[OV(O2)2{2-(2'-pyridyl)-imidazole}] x 4H2O was synthesized in aqueous solution under physiological conditions. The solution structure of the complex was characterized by multinuclear (1H, 13C, 14N, and 51V) as well as multi-dimensional (DOSY and C-H COSY) NMR techniques in the interaction system of NH4VO3/H2O2/2-(2'-pyridyl)-imidazole at room temperature. The crystal structure of the complex was determined at 173K by single-crystal X-ray diffraction method. It belongs to the monoclinic space group P21/c with a = 13.048(4), b = 6.984(2), c = 17.814(5) A, beta = 104.695(5), V = 1570.3(8) A3 and Z = 4. The crystal is composed of ammonium ions, {2-(2'-pyridyl)-imidazole}oxodiperoxovanadate(V) ions, and water molecules, which are held together by ionic and hydrogen bond forces. The metal atom in the complex is seven-coordinated with a distorted pentagonal bipyramidal geometry. It is the first mononuclear diperoxovanadate complex with a N, N'-chelating biheteroaromatic ligand and its 51V chemical shift is at the highest field among the known mononuclear diperoxovanadate(V) complexes.


Algorithm for DNA sequence assembly by quantum annealing.
The assembly task is an indispensable step in sequencing genomes of new organisms and studying structural genomic changes. In recent years, the dynamic development of next-generation sequencing (NGS) methods raises hopes for making whole-genome sequencing a fast and reliable tool used, for example, in medical diagnostics. However, this is hampered by the slowness and computational requirements of the current processing algorithms, which raises the need to develop more efficient algorithms. One possible approach, still little explored, is the use of quantum computing. We present a proof of concept of de novo assembly algorithm, using the Genomic Signal Processing approach, detecting overlaps between DNA reads by calculating the Pearson correlation coefficient and formulating the assembly problem as an optimization task (Traveling Salesman Problem). Computations performed on a classic computer were compared with the results achieved by a hybrid method combining CPU and QPU calculations. For this purpose quantum annealer by D-Wave was used. The experiments were performed with artificially generated data and DNA reads coming from a simulator, with actual organism genomes used as input sequences. To our knowledge, this work is one of the few where actual sequences of organisms were used to study the de novo assembly task on quantum annealer. Proof of concept carried out by us showed that the use of quantum annealer (QA) for the de novo assembly task might be a promising alternative to the computations performed in the classical model. The current computing power of the available devices requires a hybrid approach (combining CPU and QPU computations). The next step may be developing a hybrid algorithm strictly dedicated to the de novo assembly task, using its specificity (e.g. the sparsity and bounded degree of the overlap-layout-consensus graph).


Diagnostic Value of Intestinal Fatty-Acid-Binding Protein in Necrotizing Enterocolitis: A Systematic Review and Meta-Analysis.
The present study was undertaken to evaluate the performance of intestinal fatty-acid-binding protein (i-FABP) in the diagnosis of newborn necrotizing enterocolitis (NEC) and prediction of surgical NEC. A comprehensive literature search was performed in PubMed and EMBASE to identify potential relevant studies. QUADAS-2 tool was used to assess the quality of the included studies. The sensitivity, specificity and other measurements of accuracy of i-FABP were pooled. Summary receiver operating characteristic curves (SROC) and area under the curve (AUC) were used to summarize overall diagnostic performance. After screening 150 titles and abstracts, followed by 32 full-text publications, 14 studies were included. The sample size, sensitivity, specificity, diagnostic odds ratio (DOR) and AUC were: plasma i-FABP 217, 0.64(95% CI 0.53 to 0.74), 0.91(95% CI 0.84 to 0.95), 14.22 (95%CI 6.42 to 31.52) and 0.84; urinary i-FABP 211, 0.64(95% CI 0.53 to 0.74), 0.73(95% CI 0.64 to 0.80), 6.35 (95%CI 3.17 to 12.72) and 0.81; urinary i-FABP/Cr 165, 0.78(95% CI 0.65 to 0.88), 0.75(95% CI 0.65 to 0.82), 6.35 (95%CI 3.17 to 12.72) and 0.81; plasma i-FABP for surgical NEC 45, 0.71(95% CI 0.51 to 0.87), 0.76(95% CI 0.50 to 0.93), 7.58 (95%CI 0.87 to 65.82) and 0.80. Plasma i-FABP is a promising biomarker in the diagnosis of NEC with high specificity and DOR; but its usefulness is limited because of medium sensitivity. The urinary i-FABP and urinary i-FABP/Cr add little value in the diagnosis. The findings were somewhat limited by the quality and small size of some of the studies included.


Closed- and open-class lexical access in agrammatic and fluent aphasics.
Bradley, Garrett, and Zurif (Bradley, Computational distinctions of vocabulary type. Unpublished doctoral dissertation, MIT Press; Cambridge, MA, 1978; Biological studies of mental processes, MIT Press, Cambridge, MA, 1980) have suggested that closed-class word access is normally mediated by a different route than the open-class one, and that the loss of this closed-class route might account for agrammatism. However, in an earlier study (Gordon & Caramazza, Brain and Language, 15, 143-160, 1982) we were not able to confirm a meaningful difference between closed- and open-class word frequency responsiveness of the type Bradley (unpublished dissertation, 1978) had seemed to find in normal subjects. We have now done a direct comparison of closed-class frequency sensitivity in agrammatic and nonagrammatic aphasics, to directly test Bradley and colleagues' hypotheses and to avoid some of the experimental problems with between-class frequency comparisons. We find that closed-class words behave similarly whether or not the subject is agrammatic. Therefore, the differences between agrammatic and nonagrammatic aphasics must arise at a deeper level (or levels) of lexical processing than the one probed by the frequency sensitivity effect.


Comparison of the activity of circular and longitudinal myometrium from pregnant rats: co-ordination between muscle layers.
1. Contractions and electrical activity were recorded from isolated segments of longitudinal (L) and circular (C) myometrium from rats on gestation days 16-17 and 21 before and during parturition. 2. The segments were arranged so that the activity of the two layers could be monitored simultaneously and independently. 3. Out of the 15 preparations from days 16-17, 13 showed no co-ordination of activity between the layers. In the other two preparations a large contraction of C occasionally initiated a contraction of L. Surgical separation of the layers disrupted the co-ordination and L then developed its independent rhythm. 4. On day 21 before delivery, eight of 10 preparations exhibited 1:1 co-ordination of activity between the two layers, but C did not consistently pace L. The pacing shifted from one layer to the other several times during an experiment. 5. During parturition there was a 1:1 co-ordination of activity in all 10 preparations examined. In nine of these L initiated the activity of the C. Surgical separation of the layers disrupted the co-ordination and C developed its independent rhythm. In one the pacing shifted from one layer to the other several times during the experiment. 6. In all cases where co-ordination between the layers was observed it was myogenic and apparently related to the spread of action potentials between the two muscles.


Making features similar: comparison processes affect perception.
In this paper, the constructive nature of comparison processes (both similarity- and difference-oriented judgments) is examined through their effects on visual perception. Previous research has shown that comparison processes enhance the tendency to interpret ambiguous objects in the light of the unambiguous objects with which they are compared (Medin, Goldstone, & Gentner, 1993). In the present paper, it is argued that comparison processes affect not only the interpretation of objects, but also their perception. In addition, it is argued that the perceptual effects of similarity-oriented comparison processes differ from those of difference-oriented comparison processes. Accordingly, it is demonstrated that when estimation of an object's size is preceded by similarity-oriented comparisons, the Ebbinghaus illusion practically disappears, whereas prior difference-oriented comparisons tend to enhance the illusion.


Productive aging: a quality of life agenda.
Although the fact that, in general, the US population is living longer is said to be the public health success story of the 20th century, the boom in the population aged 65 years and older is having and will continue to have major implications for all age groups as well as for the nation's health, social, and economic institutions. The concept of productive aging can provide guidance in addressing these implications. The assumptions of productive aging reflect today's reality that older people are repositories of wisdom and experience and important assets for society; relatively healthy, with the potential for maintaining that condition until late in life; capable of making economic and social contributions that benefit themselves, their families, and their communities; and in need of purposeful and meaningful roles and activities in life. A productive aging activity model emphasizes involvement in paid work, volunteerism, education, fitness and exercise, leisure and travel, advocacy and political action, and consumerism. This article discusses the concept of productive aging, a related activity model, and qualitative focus group research undertaken in conjunction with the 1995 White House Conference on Aging.


Differences between propane in nitrogen versus air matrix analyzed using gas chromatography with flame-ionization detection.
New US Federal low-level automobile emission requirements, such as Zero Level Emission Vehicle (ZLEV), for hydrocarbons and other species have resulted in manufacturers need for new certified reference materials. The new emission requirement for hydrocarbons requires the use, by automobile manufacturing testing facilities, of 100 nmol/mol (ppb) propane in air gas standard. Emission measurement instruments are required, by Federal law, to be calibrated with the US National Institute of Standards and Technology (NIST) traceable reference materials. A NIST Standard Reference Material (SRM) containing 100 nmol/mol propane has been developed. During the development of this SRM a critical question arose as to the matrix of the primary propane standards. The automobile companies make their measurements using total hydrocarbon analyzers with flame-ionization detectors which integrate all hydrocarbons in a sample. NIST uses gas chromatography/flame-ionization detection (GC/FID) with a column to separate all components. Since the SRM mixtures were in air, the question as to the effect of oxygen on the detector arose. To investigate this effect, two suites of propane primary standards were developed: one in air and the other in nitrogen. The two suites of primary standards were analyzed using NIST methods, and the concentration of propane in an air mixture was determined. The results show that there was a difference of 0.63% in the propane concentration determined versus air and nitrogen suites.


Nystagmus responses to water and air caloric stimulation in clinical populations.
The nystagmus responses of two groups of patients referred for electronystagraphy were compared to test for differences between air and water caloric stimulation. Responses from patients with spontaneous or positional nystagmus or who showed greater than 30% directional preponderance or excitability of labyrinth were removed from the data. The 30 degree C and 44 degree C water and the 24 degree C air produced equivalent responses. The 50 degree C air produced responses with slow component velocities greater than expected; however, the distributions of computed directional preponderance and excitability of labyrinth showed no differences between the air and water caloric stimulation.


The Association between Stress Level in Daily Life and Age at Natural Menopause in Korean Women: Outcomes of the Korean National Health and Nutrition Examination Survey in 2010-2012.
Although several risk factors associated with reduced age at natural menopause (ANM) have been investigated, the results are inconsistent. Excessive stress, which leads to elevation of stress hormones, can also negatively affect reproductive ability, including by accelerating menopause. However, a direct association between stress level and ANM has not yet been demonstrated. Therefore, the object of this study was to investigate the association between stress level and ANM in Korean women. Study participants were Korean women between 40 and 70 years old who were in natural menopause during the 5th Korean National Health and Nutrition Examination Survey (n=3,176). The level of stress in daily life was estimated based on data from the mental health topics of the survey. We used the t-test and one-way analysis of variance to analyze the correlation between stress level and ANM. Regression (β) coefficients calculated by multiple regression analysis were used to estimate various factors affecting ANM. Women who experienced a high level of stress in daily life had a lower mean ANM than women with a low stress level (50.17±3.7 and 50.58±3.5 years, respectively), with a statistically significant correlation (P<0.05). This correlation was still observed after adjusting for age, body mass index, menstrual regularity, and personal income (P<0.05 for variables). In Korean women between 40 and 70 years of age who are in natural menopause, there is a statistically significant correlation between stress level and ANM. In particular, women who experience a high level of stress in daily life have reduced ANM.


Ghrelin protects MES23.5 cells against rotenone via inhibiting mitochondrial dysfunction and apoptosis.
Ghrelin is an endogenous ligand for the growth hormone secretagogue (GHS) receptor and has several important physiological functions. Recently, particular attention has been paid to its neuroprotective effect. Rotenone is used to investigate the pathogenesis of Parkinson's disease (PD) for its ability to inhibit mitochondrial complex I. The current study was carried out to investigate the neuroprotective effects of ghrelin against rotenone in MES 23.5 dopaminergic cells and explored the possible mechanisms underlying this protection. Our results showed that rotenone induced significant decrease in cell viability which was counteracted by ghrelin treatment. In addition, rotenone challenge reduced mitochondrial membrane potential, inhibited the activity of mitochondrial complex I and depressed cytochrome C release from mitochondria. This mitochondrial dysfunction was reversed by ghrelin treatment. Furthermore, our results demonstrated that ghrelin protected MES23.5 cells against rotenone-induced apoptosis by inhibiting activation of caspase-3. Overall, our findings showed ghrelin provided protective effects on MES23.5 dopaminergic cells against rotenone via restoring mitochondrial dysfunction and inhibiting mitochondrial dependent apoptosis.


Epigenetic clock analysis of blood samples from Japanese schizophrenia patients.
The accelerated aging hypothesis of schizophrenia (SCZ) has been proposed. DNA methylation profiles were developed for determining "epigenetic age." Here, we assessed intrinsic and extrinsic epigenetic age acceleration (IEAA and EEAA, respectively) in SCZ. We examined two independent cohorts of Japanese ancestry. The first cohort consisted of 80 patients with SCZ under long-term or repeated hospitalization and 40 controls, with the economical DNA pooling technique. The second cohort consisted of 24 medication-free patients with SCZ and 23 controls. Blood of SCZ subjects exhibited decreased EEAA in the first cohort (p = 0.0162), but not in the second cohort. IEAA did not differ in either cohort. We performed replication analyses using publicly available datasets from European ancestry (three blood and one brain datasets). One blood dataset showed increased EEAA in SCZ (p = 0.0228). Overall, our results provide evidence for decreased EEAA in SCZ associated with hospitalization in the Japanese population.


Asteroid and comet impacts: the ultimate environmental catastrophe.
Cosmic impacts represent the most extreme class of natural hazards, combining a very low probability of occurrence with a capability of killing hundreds of millions and destabilizing global civilization. Fortunately, these disasters are amenable to precise prediction and even (in principle) can be avoided entirely by appropriate application of space technology. However, impacts take place so rarely that they have only recently been recognized as a significant natural hazard. Concerted international action to deal with impacts depends on increased public awareness.


Melatonin modulates L-arginine metabolism in tumor-associated macrophages by targeting arginase 1 in lymphoma.
L-Arginine metabolism plays a crucial role in determining the M1/M2 polarization of macrophages. The M1 macrophages express inducible nitric oxide synthase (iNOS), while the M2 macrophages express arginase 1 and metabolize arginine into nitric oxide and urea, respectively. The tumor microenvironment promotes M2 macrophage polarization and consequently switches the metabolic fate of arginine from nitric oxide towards urea production. Importantly, infiltration of M2 macrophages or tumor-associated macrophages (TAMs) has been correlated with poor prognosis of various cancer types. Melatonin is well reported to have antitumor and immunomodulatory properties. However, whether and how it impacts the polarization of TAMs has not been elucidated. Considering the crucial role of arginine metabolism in macrophage polarization, we were interested to know the fate of L-arginine in TAMs and whether it can be reinstated by melatonin or not. We used a murine model of Dalton's lymphoma and established an in vitro model of TAMs. For TAMs, we used the ascitic fluid of tumor-bearing hosts to activate the macrophages in the presence and absence of lipopolysaccharide (LPS). In these groups, L-arginine metabolism was evaluated, and then the effect of melatonin was assessed in these groups, wherein the metabolic fate of arginine as well as the expression of iNOS and arginase 1 were checked. Furthermore, in the in vivo system of the tumor-bearing host, the effect of melatonin was assessed. The in vitro model of TAMs showed a Th2 cytokine profile, reduced phagocytic activity, and increased wound healing ability. Upon investigating arginine metabolism, we observed high urea levels with increased activity and expression of arginase 1 in TAMs. Furthermore, we observed reduced levels of LPS-induced nitric oxide in TAMs; however, their iNOS expression was comparable. With melatonin treatment, urea level decreased significantly, while the reduction in nitric oxide level was not as significant as observed in its absence in TAMs. Also, melatonin significantly reduced arginase activity and expression at the transcriptional and translational levels, while iNOS expression was affected only at the translational level. This effect was further investigated in the in vivo system, wherein melatonin treatment reversed the metabolic fate of arginine, from urea towards nitric oxide, within the tumor microenvironment. This effect was further correlated with pro-apoptotic tumor cell death in the in vivo system. Our results reinforced the immunomodulatory role of melatonin and offered a strong prospect for activating the anti-tumor immune response in cancer conditions. L-arginine metabolism in tumor-associated macrophages (TAMs) within tumor microenvironment and its modulation by melatonin.


The neuroimmune guidance cue netrin-1 promotes atherosclerosis by inhibiting the emigration of macrophages from plaques.
Atherosclerotic plaque formation is fueled by the persistence of lipid-laden macrophages in the artery wall. The mechanisms by which these cells become trapped, thereby establishing chronic inflammation, remain unknown. Here we found that netrin-1, a neuroimmune guidance cue, was secreted by macrophages in human and mouse atheroma, where it inactivated the migration of macrophages toward chemokines linked to their egress from plaques. Acting via its receptor, UNC5b, netrin-1 inhibited the migration of macrophages directed by the chemokines CCL2 and CCL19, activation of the actin-remodeling GTPase Rac1 and actin polymerization. Targeted deletion of netrin-1 in macrophages resulted in much less atherosclerosis in mice deficient in the receptor for low-density lipoprotein and promoted the emigration of macrophages from plaques. Thus, netrin-1 promoted atherosclerosis by retaining macrophages in the artery wall. Our results establish a causative role for negative regulators of leukocyte migration in chronic inflammation.


Purification and identification of two structural variants of porcine tissue plasminogen activator by affinity adsorption on fibrin.
Porcine tissue plasminogen activator has been purified from delipidized heart tissue by affinity adsorption to fibrin. A crude fraction is prepared from an acid tissue extract by precipitation with ammonium sulphate. The tissue activator of this fraction is isolated by adsorption on fibrin and elution with KSCN. The procedure also includes chromatography on arginine-Sepharose and two gel-filtration steps. The final product has a specific activity of 250 000 IU/mg (+/- 16 000) as compared to an international urokinase reference preparation. The yield calculated from the active ammonium sulphate precipitate is about 28%. An approx. 7 000-fold increase of specific activity is obtained, most of which is achieved in the fibrin step. The native tissue plasminogen activator consists of a single chain molecule with a molecular weight of 64 000 as measured by SDS-polyacrylamide gel electrophoresis. In a previous report, it was claimed that the activator is composed of two disulphide-connected polypeptide chains. These results were due to a preparation artefact, caused by proteolytic activity present in the tissue extracts. The introduction of the protease inhibitor aprotinin and 6-amino-hexanoic acid in the purification procedure has abolished the effect of the protease contaminant, leading to the production of a one-chain activator. Treatment with plasmin transforms the native, one-chain tissue activator into a variant composed of two chains of about equal size (Mr 32 000) connected by disulphide bonding. This modified activator is indistinguishable from the one obtained at insufficient protection against proteolytic enzymes. The cleavage by plasmin causes about an 8-fold increase of amidolytic activity as measured on H-D-Val-Gly-Arg-p-nitroanilide. The fibrinolytic activity as measured by clot lysis in only slightly increased. The physiological significance of the cleavage is discussed.


Mitochondria, the gut microbiome and ROS.
In this review, we discuss the connections between mitochondria and the gut microbiome provided by reactive oxygen species (ROS). We examine the mitochondrion as an endosymbiotic organelle that is a hub for energy production, signaling, and cell homeostasis. Maintaining a diverse gut microbiome is generally associated with organismal fitness, intestinal health and resistance to environmental stress. In contrast, gut microbiome imbalance, termed dysbiosis, is linked to a reduction in organismal well-being. ROS are essential signaling molecules but can be damaging when present in excess. Increasing ROS levels have been shown to influence human health, homeostasis of gut cells, and the gastrointestinal microbial community's biodiversity. Reciprocally, gut microbes can affect ROS levels, mitochondrial homeostasis, and host health. We propose that mechanistic understanding of the suite of bi-directional interactions between mitochondria and the gut microbiome will facilitate innovative interdisciplinary studies examining evolutionary divergence and provide novel treatments and therapeutics for disease. GLOSS: In this review, we focus on the nexus between mitochondria and the gut microbiome provided by reactive oxygen species (ROS). Mitochondria are a cell organelle that is derived from an ancestral alpha-proteobacteria. They generate around 80% of the adenosine triphosphate that an organism needs to function and release a range of signaling molecules essential for cellular homeostasis. The gut microbiome is a suite of microorganisms that are commensal, symbiotic and pathogenic to their host. ROS are one predominant group of essential signaling molecules that can be harmful in excess. We suggest that the mitochondria- microbiome nexus is a frontier of research that has cross-disciplinary benefits in understanding genetic divergence and human well-being.


Unmodified self antigen triggers human CD8 T cells with stronger tumor reactivity than altered antigen.
Human cancer vaccines are often prepared with altered "analog" or "heteroclitic" antigens that have been optimized for HLA class I binding, resulting in enhanced immunogenicity. Here, we take advantage of CpG oligodeoxynucleotides as powerful vaccine adjuvants and demonstrate the induction of high T cell frequencies in melanoma patients, despite the use of natural (unmodified) tumor antigenic peptide. Compared with vaccination with analog peptide, natural peptide induced T cell frequencies that were approximately twofold lower. However, T cells showed superior tumor reactivity because of (i) increased functional avidity for natural antigen and (ii) enhancement of T cell activation and effector function. Thus, novel vaccine formulations comprising potent immune stimulators may allow to circumvent the need for modified antigens and can induce highly functional T cells with precise antigen specificity.


Sex-Based Differences in Revascularization and 30-Day Readmission After ST-Segment-Elevation Myocardial Infarction in the United States.
Cardiovascular disease is the leading cause of death for women in the United States. Revascularization is considered the standard of care for treatment of ST-segment elevation myocardial infarction (STEMI) and is known to reduce readmission. However there is a paucity of data that examines the sex-dependent impact of revascularization on readmission. We aimed to investigate sex differences in revascularization rates, 30-day readmission rates, and primary cause of readmissions following STEMIs. STEMI hospitalizations were selected in the Nationwide Readmissions Database from 2010 to 2014. Revascularization rates, 30-day readmission rates, and primary cause of readmission were examined. Interaction between sex and revascularization was assessed. Multivariable regression analysis was performed to identify predictors of 30-day readmission and revascularization for both sexes. 219,944 women and 489,605 men were admitted with STEMIs. Women were more likely to be older, and have more comorbidities. Women were less likely to undergo revascularization by percutaneous coronary intervention (adjusted odds ratio [OR]: 0.68; 95% confidence interval [CI]: 0.66-0.70) or coronary artery bypass graft surgery (adjusted OR 0.40; CI 0.39-0.44). Women had higher 30-day readmission rates (15.7% vs. 10.8%, p < 0.001; OR 1.20, CI 1.17-1.23), and revascularization in women was not associated with a decreased likelihood of 30-day readmission. The primary cardiac cause of readmission in women was heart failure. Compared to men, women with STEMIs had lower rates of revascularization and higher rates of 30-day readmission. When revascularized, women were still more likely to be readmitted as compared to non-revascularized women.


Outcomes of preventative care in a diabetic foot specialty clinic.
The purpose of the study was to report the incidence of ulceration, reulceration, and amputation in 341 patients treated in a multidisciplinary clinic over the course of 3 years. Patients enrolled were 57.8% male, with a mean age of 53.2 +/- 11.8 years. All were assessed using the University of Texas Diabetic Foot Classification System. Of these patients, 118 fell into category 0 (protective sensation intact), 98 into category 1 (loss of protective sensation, LOPS), 77 into category 2 (LOPS with deformity), and 48 into category 3 (LOPS, deformity, previous history of ulcer or amputation). Outcomes assessed included any incident ulcerations or amputations. The authors stratified patients based on their compliance to follow up appointments. Non compliance was defined as missing > 50% of scheduled appointments in any calendar year. Thirty of the above subjects were classified as noncompliant. Prior to analysis, the authors initially stratified subjects into compliant and noncompliant groups. If further stratified by foot category, the incidence of ulceration in the compliant group was 0 for diabetic foot categories 0 and 1, 3.5/1,000/year for category 2, and 18/1,000/year for category 3. One category 3 patient required a partial first-ray amputation. The yearly incidence of amputation for the entire cohort was therefore 1.1/1,000/year. For categories 0-2 the incidence was 0, and for category 3, it was 9/1,000/year. Patients stratified into the noncompliant group were approximately 54 times more likely to ulcerate than patients who returned regularly for their scheduled care (81.8% ulcer prevalence vs. 5.4%, p < .0001, OR = 54.0, Cl = 7.5-1,425.0). Additionally, noncompliant category 3 patients were over 20 times more likely to receive an amputation than their compliant counterparts (45.5% amputation prevalence vs. 2.7%, p < .002, OR = 2.5-819.0). The study concluded that multidisciplinary diabetes care team, which includes aggressive foot care and consistent treatment-based risk classification, may be effective in profoundly mitigating the occurrence and recurrence of diabetic foot sequelae, including ulceration and amputation. Furthermore, patient noncompliance to routine preventative care appears to be associated with a significantly higher prevalence of ulceration and amputation.


Is the Walch B3 glenoid significantly worse than the B2?
The Walch B3 glenoid is theorized to be a progression of the B2 biconcave pattern. The present study aimed to compare glenoid indices between B2 and B3 patterns. We hypothesized that the B3 pattern would have significantly worse retroversion, inclination and medialization. Computed tomography scans of 50 patients with B2 erosions [mean (SD) age 68 (9) years; 25 male] and 50 patients with B3 erosions [mean (SD) age 72 (8) years; 22 males] were converted into three-dimensional reconstructions. Retroversion, inclination, medialization and humeral head subluxation were compared. The data demonstrated no statistically significant differences [mean (SD)] between groups when assessing retroversion: B2 = 21 (8)°, B3 = 24 (7)° (p = 0.602); glenoid inclination: B2 = 9 (6)°, B3 = 8 (6)° (p = 0.967); or medialization: B2 = 12 (4) mm, B3 = 14 (4) mm (p = 0.384). In the B2 group, the mean (SD) humeral head subluxation was 80% (10%) according to the scapular plane and 55% (9%) according to the glenoid plane, which was not statistically different from the B3 group with a mean (SD) humeral head subluxation of 81% (7%) according to the scapular plane (p = 0.680) and 54% (7%) according to the glenoid plane (p = 0.292). These results demonstrated no significant differences between the B2 and B3 erosion patterns, with respect to the glenoid indicies measured. The aetiology of the B3 glenoid cannot be completely explained by progression of wear in a B2 glenoid.


Cloning, mapping and molecular analysis of the pyrG (orotidine-5'-phosphate decarboxylase) gene of Aspergillus nidulans.
We have modified the transformation procedures of Ballance et al. [Biochem. Biophys. Res. Commun. 112 (1983) 284-289] to give increased rates of transformation in Aspergillus nidulans. With the modified procedures we have been able to complement pyrG89, a mutation in the orotidine-5'-phosphate decarboxylase gene of A. nidulans, by transformation with a library of wild-type (wt) sequences in pBR329. We have recovered, by marker rescue from one such transformant, a plasmid (pJR15) that carries an A. nidulans sequence that complements pyrG89 efficiently. In three experiments, this plasmid gave an average of 1985 stable transformants/micrograms of transforming DNA. We have analyzed ten of these genetically and by Southern hybridization. In five transformants a single copy of the transforming plasmid had integrated at the pyrG locus, in one transformant several copies of pJR15 had integrated at this locus, in one transformant several copies of the plasmid had integrated into other sites, and in three transformants, the wt allele had apparently replaced the mutant allele with no integration of pBR329 sequences. Sequence and S1 nuclease protection analysis revealed that pJR15 contains a gene that predicts an amino acid sequence with regions of strong homology to the orotidine-5'-phosphate decarboxylases of Neurospora crassa and Saccharomyces cerevisiae. We conclude that this gene is the wt pyrG allele. Finally, we have compared the 5'- and 3'-noncoding sequences and intron splice sequences to other genes of A. nidulans and have mapped the pyrG locus to a region between the fpaB and galD loci on linkage group I.


Efficacy of ω-3 polyunsaturated fatty acids for the treatment of refractory hydroa vacciniforme.
Hydroa vacciniforme (HV) is a rare photodermatosis. Several therapies, with sometimes severe side effects, have been used in isolated cases. We report a case of refractory HV successfully treated with dietary fish oil rich in ω-3 polyunsaturated fatty acids.


Mean platelet volume in very preterm infants: a predictor of morbidities?
Mean platelet volume [MPV] is an important predictor for many diseases and larger platelets are more reactive and associated with shortened bleeding time. Although elevated MPV values are related to respiratory distress syndrome [RDS] in neonates, there are, to our knowledge, no data investigating the relationship between MPV and other diseases of preterm infants. To assess the correlation between MPV and the occurrence of various morbidities of prematurity such as necrotizing enterocolitis [NEC], bronchopulmonary dysplasia [BPD], sepsis, retinopathy of prematurity [ROP], and intraventricular hemorrhage [IVH] in a cohort of very preterm infants. We studied infants with a gestational age of < 34 weeks and a birth weight of < 1500 g admitted to a third level Neonatal Intensive Care Unit. Enrolled infants were divided into NEC and non-NEC, sepsis and non-sepsis, ROP and non-ROP, BPD and non-BPD and IVH and non-IVH groups. MPV was evaluated at birth [cord blood] and repeated at 48-72 hours of life. Two hundred and seventy two infants were studied. MPV measured at birth was similar between sepsis and non-sepsis, and ROP and non-ROP groups. MPV values were higher in infants with BPD [9.08±1.3 fl], IVH [8.4±1.1fl] and NEC [8.6±0.7 f] when compared to the control group [7.6±0.6 fl] in the first day of life. High MPV in the first hours of life may reflect the presence of a risk factor for the development of NEC, BPD and IVH in extremely preterm infants. This might be associated with inflammatory and oxidative process. However, our data indicate that higher MPV values are not associated with the development of sepsis or ROP in this study population.


Dose-reduced [18F]PSMA-1007 PET is feasible for functional imaging of the renal cortex.
In Prostate-specific membrane antigen (PSMA) positron emission tomography with computed tomography (PET-CT), there is significant renal uptake. The standard in renal cortical functional imaging is scintigraphy with technetium-99m labeled dimercaptosuccinic acid (DMSA). Using [68Ga]Ga-PSMA-11 PET for renal imaging has been suggested, but using [18F]PSMA-1007 has not been explored. The aims of this study were to establish the optimal time point for renal imaging after [18F]PSMA-1007 injection, to investigate the reproducibility of split renal uptake measurements, and to determine the margin for reduction in administered activity. Twelve adult male patients with prostate cancer underwent [18F]PSMA-1007 PET-CT at 8 time points up to 5.5 h post-injection (p.i.). List-mode data were binned to durations of 10 to 120 s per bed position (bp). Left renal percentage of total renal uptake (LRU%) was measured, and the difference between highest and lowest measurement per patient ("delta max") was calculated. Images acquired at 1 h, 2 h, and 5.5 h p.i. with durations of 10 to 120 s/bp were rated regarding image quality. Imaging at 2 h p.i. with 60 s/bp yielded acceptable quality in all cases. Increasing acquisition time to 15 min for a single bp would allow reducing administered activity to 0.27 MBq/kg, resulting in an effective dose of 0.4 mSv for a 1-year old child weighing 10 kg. The median delta max of LRU% measurements was 2.7% (range 1.8-7.3%). Renal [18F]PSMA-1007 PET-CT is feasible, with imaging 2 h p.i., acceptable split renal uptake variability, and effective dose and acquisition time comparable to those of [99mTc]Tc-DMSA scintigraphy.


Exposure of human cerebral microvascular endothelial cells hCMEC/D3 to laminar shear stress induces vascular protective responses.
Endothelial cells (ECs) are constantly submitted in vivo to hemodynamical forces derived from the blood circulation, including shear stress (SS). ECs are able to detect SS and consequently adapt their phenotype, thus affecting many endothelial functions. If a plethora of shear stress-regulated molecular networks have been described in peripheral ECs, less is known about the molecular responses of microvascular brain ECs which constitute the blood-brain barrier (BBB). In this work, we investigated the response of human cerebral microvascular ECs to laminar physiological shear stress using the well characterized hCMEC/D3 cell line. Interestingly, we showed that hCMEC/D3 cells responded to shear stress by aligning perpendicularly to the flow direction, contrary to peripheral endothelial cells which aligned in the flow direction. Whole proteomic profiles were compared between hCMEC/D3 cells cultured either in static condition or under 5 or 10 dyn.cm-2 SS for 3 days. 3592 proteins were identified and expression levels were significantly affected for 3% of them upon both SS conditions. Pathway analyses were performed which revealed that most proteins overexpressed by SS refer to the antioxidant defense, probably mediated by activation of the NRF2 transcriptional factor. Regarding down-regulated proteins, most of them participate to the pro-inflammatory response, cell motility and proliferation. These findings confirm the induction of EC quiescence by laminar physiological SS and reveal a strong protective effect of SS on hCMEC/D3 cells, suggesting a similar effect on the BBB. Our results also showed that SS did not significantly increase expression levels nor did it affect the localization of junctional proteins and did not afect either the functional activity of several ABC transporters (P-glycoprotein and MRPs). This work provides new insights on the response of microvascular brain ECs to SS and on the importance of SS for optimizing in vitro BBB models.


Enhanced resistance to an antigenic tumor in immunosuppressed mice by dietary retinyl palmitate plus canthaxanthin.
Retinoids and certain carotenoids, e.g., beta-carotene and canthaxanthin, have been found to prevent photocarcinogenesis in mice and also to act as immunoenhancers. The hypothesis that retinoids and carotenoids inhibit photocarcinogenesis by preventing UV induction of immunosuppression predicts that mice treated with these agents before and during periods of UV radiation treatments should be as resistant as unirradiated mice to an antigenic UV-induced tumor. To test this prediction, mice were fed 120 IU of retinyl palmitate per gram of diet, and/or 1% canthaxanthin, before UV irradiation treatments began, and during the entire experiment. After 4.95 x 10(5) Jm-2, delivered over 12 weeks, resistance of mice to antigenic UV-induced tumor implants (UV20) was studied. Dietary supplementation with retinyl palmitate plus canthaxanthin, but not with either agent alone at these doses, prevented the enhanced growth of UV20 in UV irradiated mice.


A novel method to construct an air quality index based on air pollution profiles.
Air quality indices based on the maximum of sub-indices of pollutants are easy to produce and help quantify the degree of air pollution. However, they discount the additive effects of multiple pollutants and are only sensitive to changes in highest sub-index. We propose a simple and concise method to construct an air quality index that takes into account additive effects of multiple pollutants and evaluate the extent to which this index predicts health effects. We obtained concentrations of four criteria pollutants: particulate matter with aerodynamic diameter ≤ 10μm (PM10), sulphur dioxide (SO2), nitrogen dioxide (NO2) and ozone (O3) and daily admissions to Hong Kong hospitals for cardiovascular and respiratory diseases for all ages and those 65 years or older for years 2001-2012. We derived sub-indices of the four criteria pollutants, calculated by normalizing pollutant concentrations to their respective short-term WHO Air Quality Guidelines (WHO AQG). We aggregated the sub-indices using the root-mean-power function with an optimal power to form an overall air quality index. The optimal power was determined by minimizing the sum of over- and under-estimated days. We then assessed associations between the pollution bands of the index and cardiovascular and respiratory admissions using a time-stratified case-crossover design adjusted for ambient temperature, relative humidity and influenza epidemics. Further, we conducted case-crossover analyses using the Hong Kong air quality data with the respective standards and classification of pollution bands of the China Air Quality Index (AQI), the United Kingdom Daily AQI (DAQI), and the United States Environmental Protection Agency (USEPA) AQI. The mean concentrations of PM10 and SO2 based on maximum 3-h mean exceeded the WHO AQG by 37% and 50%, respectively. We identified the combined condition of observed high-pollution days as either at least one pollutant > 1.5×WHO AQG or at least two pollutants > 1.0×WHO AQG to characterize the typical pollution profiles over the study period, which resulted in the optimal power=3.0. The distribution of days in different pollution bands of the index was: 5.8% for "Low" (0-50), 37.6% for "Moderate" (51-100), 31.1% for "High" (101-150), 14.7% for "Very High" (151-200), and 10.8% for "Serious" (201+). For cardiovascular and respiratory admissions, there were significant associations with the pollution bands of the index for all ages and those 65 years or older. The trends of increasing pollution bands in relation to increasing excess risks of cardiovascular and respiratory admissions were significant for the proposed index, the China AQI, the UK DAQI and the USEPA AQI (P value for test for linear trend < 0.0001), suggesting a dose-response relation. We have developed a simple and concise method to construct an air quality index that accounts for multiple pollutants to quantify air quality conditions for Hong Kong. Further developments are needed in order to support the extension of the method to other settings.


Population genetic structure of Cheyletus malaccensis (Acari: Cheyletidae) in China based on mitochondrial COI and 12S rRNA genes.
Cheyletus malaccensis is a predatory mite widely distributed in grain storages. It has been regarded as an important biological control agent for pest mites. In this study, we investigated the population genetic structure of C. malaccensis distributed in China based on the partial regions of mitochondrial COI and 12S rRNA genes. We collected 256 individuals of C. malaccensis from stored grain in 34 sites of China. We detected 50 COI gene haplotypes and nine 12S rRNA gene haplotypes. There were three clades in the haplotype network and Bayesian and maximum parsimony phylogenetic trees based on COI sequences, and two based on 12S rRNA sequences. The clustering of haplotypes was not correlated with their geographical distributions. The analysis of molecular variance, AMOVA, indicated that the genetic differentiation between populations was relatively weak. The major genetic differentiation was found within populations. We suggest that the genetic structure of C. malaccensis observed in this study may be the result of long-term climate fluctuations and recent human disturbances.


Diffuse idiopathic skeletal hyperostosis in a patient with right-sided aorta.
Diffuse idiopathic skeletal hyperostosis (DISH) is a non-inflammatory disease with ossifications of paravertebral ligaments. It is normally located on the right side. We here present one patient with left-sided ossifications and a right-sided aorta.


Studies of idiopathic intestinal pseudoobstruction. II. Hereditary hollow visceral myopathy: family studies.
Twelve relatives of a 15-year-old girl with idiopathic intestinal pseudoobstruction were studied with esophageal manometry or cine-esophagography to determine whether the disease was genetically transmitted. Four maternal relatives, including the patient's mother, 13-year-old brother, one aunt, and one of that aunt's children had mild dysphagia and esophageal motor dysfunction. In addition, the patient's mother and 13-year-old brother had a flaccid bladder and bilateral ureteral reflux, respectively. The brother had abnormal bladder smooth muscle by light microscopy. We conclude that idiopathic intestinal pseudoobstruction in this family is secondary to a generalized disease of smooth muscle which is transmitted as a dominant trait of variable expressivity, manifested in some family members as a mild disorder of esophageal smooth muscle dysfunction, at times accompanied by bladder dysfunction. We suggest that this form of idiopathic intestinal pseudoobstruction be called "hereditary hollow visceral myopathy." Esophageal manometry may prove useful as a tool for studying the inheritance of this disorder.


Perceived impact of the Medicare policy to adjust payment for health care-associated infections.
In 2008, the Centers for Medicare and Medicaid Services (CMS) ceased additional payment for hospitalizations resulting in complications deemed preventable, including several health care-associated infections. We sought to understand the impact of the CMS payment policy on infection prevention efforts. A national survey of infection preventionists from a random sample of US hospitals was conducted in December 2010. Eighty-one percent reported increased attention to HAIs targeted by the CMS policy, whereas one-third reported spending less time on nontargeted HAIs. Only 15% reported increased funding for infection control as a result of the CMS policy, whereas most reported stable (77%) funding. Respondents reported faster removal of urinary (71%) and central venous (50%) catheters as a result of the CMS policy, whereas routine urine and blood cultures on admission occurred infrequently (27% and 13%, respectively). Resource shifting (ie, less time spent on nontargeted HAIs) occurred more commonly in large hospitals (odds ratio, 2.3; 95% confidence interval: 1.0-5.1; P = .038) but less often in hospitals where front-line staff were receptive to changes in clinical processes (odds ratio, 0.5; 95% confidence interval: 0.3-0.8; P = .005). Infection preventionists reported greater hospital attention to preventing targeted HAIs as a result of the CMS nonpayment policy. Whether the increased focus and greater engagement in HAI prevention practices has led to better patient outcomes is unclear.


Metabolic syndrome and the likelihood of knee pain and functional disability: evidence from a large middle eastern population-based study.
Metabolic Syndrome (MetS) has been associated with knee osteoarthritis (KOA) in animal studies, but epidemiologic evidence of the association remains controversial. We investigated the association between MetS and knee pain and functional disability, the hallmarks of KOA, in a Middle Eastern population with high reported MetS rates. A population-based study of adult individuals was conducted between 01/2016 and 03/2019. Data collected included age, sex, blood pressure, body mass index (BMI), waist circumference (WC), and comprehensive metabolic panel blood tests. Knee symptoms were assessed using The Western Ontario and McMaster Arthritis index (WOMAC) The Adult Treatment Panel III criteria was applied to determine if participants had MetS. Multivariable regression was used to determine the association of MetS, and its components, with the WOMAC total and subscale scores. Of 6,000 participants enrolled, 15.5% had MetS. The multivariate regression demonstrated that participants with MetS had significantly higher WOMAC total and subscale scores after adjusting for demographic variables; however, these associations were not significant after adjusting for BMI. Multivariate regression examining the association between MetS components and the WOMAC scores showed sex-based significant differences with WOMAC scores; however, the differences were not larger than the minimally clinical important differences. This study demonstrated that after adjustment for BMI, neither MetS nor its individual parameters were associated with worse knee symptoms. As such, the association between MetS and worse knee symptoms requires further study.


Dopamine receptor D2 gene polymorphisms are associated in Taiwanese children with Tourette syndrome.
The pathophysiology of Tourette syndrome may involve the dopamine system. Dysfunction of the dopamine receptor D2 gene leads to many neuropsychiatric disorders. The objective of this study is to test the hypothesis that the dopamine receptor D2 gene may play a role in Tourette syndrome. A total of 151 children with Tourette syndrome and 183 normal control subjects were included in the study. Polymerase chain reaction was used to identify the Taq I DRD2 and DRD2 (H313H) polymorphisms of the dopamine receptor D2 gene. The genotype proportions of Taq I DRD2 and DRD2 (H313H) polymorphisms in the two groups were significantly different (P < 0.01 for both). The odds ratio for developing Tourette syndrome in individuals with the Taq I DRD2 A1 homozygote was 2.253 (95% confidence interval, 1.124-4.517) compared with individuals with the Taq I DRD2 A2 homozygote. The odds ratio for developing Tourette syndrome in individuals with the DRD2 (H313H) C homozygote was 2.96 (95% confidence interval, 1.398-6.269) compared with individuals with DRD2 (H313H) T homozygote. This study has demonstrated an association between the dopamine receptor D2 gene and Tourette syndrome. These data suggest that the dopamine receptor D2 gene or a closely linked gene might be one of the susceptibility factors for Tourette syndrome.


SARC-F at the Emergency Department: Diagnostic Performance for Frailty and Predictive Performance for Reattendances and Acute Hospitalizations.
Sarcopenia is associated with adverse health outcomes including mortality, functional loss, falls, and poorer quality of life. However, the value of screening sarcopenia at the Emergency Department (ED) remains unclear. We aimed to examine the SARC-F questionnaire for its (1) diagnostic ability in identifying frailty, and (2) predictive ability for adverse health outcomes. A secondary analysis of a quasi-experimental study. An ED within a 1700-bed tertiary hospital. ED patients aged ≥85 years (mean age 90.0 years) recruited into the Emergency Department Interventions of Frailty (EDIFY) study. Data of demographics, premorbid function, frailty status [Frailty Index (FI), Clinical Frailty Scale (CFS), FRAIL], comorbidities, medications, and cognitive status were gathered. We also captured outcomes of mortality, acute hospitalization, and ED reattendance at 1-, 3-, and 6-month. We then compared area under the operating characteristic curves (AUCs) for the abovementioned measures against the FI (reference) for diagnosis of frailty. Lastly, we performed univariate analyses and logistic regression to compare SARC-F and other measures against the adverse outcomes of interest. Amongst the various instruments, the SARC-F (AUC 0.92, 95% Confidence Interval (CI) 0.86-0.98, P<0.001; Sensitivity 79.0%, and Specificity 88.9%) performed best for frailty detection as defined by FI. Optimal cutoff was ≥3 (Sensitivity 91.4%, Specificity 83.3%, and Negative Predictive Value 68.2%). Only SARC-F was predictive of acute hospitalization [Adjusted Odds Ratio (OR) 4.00, 95% CI 1.47-10.94, P=0.007] and ED-reattendance [Adjusted OR 3.29, 95% CI 1.26-8.56, P=0.015] at 3-month. The SARC-F demonstrated excellent diagnostic ability for frailty detection and predictive validity for ED reattendance and acute hospitalization at 3 months. Lowering cutoff score to ≥3 may improve case-finding at the ED to facilitate early identification and management of sarcopenia. Further studies are required to validate the diagnostic and predictive performance of SARC-F at ED settings.


Identification of an antigen specific to Trypanosoma congolense by using monoclonal antibodies.
Using indirect immunofluorescence assays on acetone-fixed smears of a series of different parasites, we have shown that two monoclonal antibodies bind specifically to Trypanosoma congolense organisms. The antibodies bind to both bloodstream trypomastigotes and procyclic culture forms of the parasite and are thus not stage specific. Immunoprecipitation and immunoblot analysis showed that both monoclonal reagents bound a protein of approximately 31,000 m.w. This antigen appeared to be located on the plasma membrane of T. congolense, but the epitope was not exposed on the surface of living bloodstream or procyclic organisms. The antigen was detectable on acetone-fixed organisms or in trypanosome lysates in enzyme-linked immunosorbent assays and may therefore by useful as a species-specific marker in field assays for epidemiologic and clinical investigations.


Do gallstones found before sleeve gastrectomy behave the same as those formed after surgery due to weight loss?
Gallstone formation is prevalent in the bariatric population and after weight loss. We believe that gallstones found preoperatively behave differently and may not cause significant complications as those developing after weight loss. Thus, prophylactic cholecystectomy before or during sleeve gastrectomy (SG) may not be necessary. Patients undergoing SG from January 2011 to May 2012 were evaluated for the presence of gallstones and development of symptoms or need for cholecystectomy postoperatively. Group 1 (n = 18) had gallstones preoperatively. Group 2 (n = 29) developed gallstones after weight loss. Both groups' demographics were similar. Symptomatic gallstones occurred in 1 patient (5.6%) in group 1 and in 9 patients (31.0%) in group 2 (P = .19). Percent excess body mass index loss (%EBL) was 58 ± 24% vs 70 ± 22% (P = .11) with a mean follow-up of 8.9 ± 6.2 and 14.7 ± 3.9 months for group 1 and group 2, respectively (P = .005). Asymptomatic gallstones found before SG tend to have less risk of becoming symptomatic than those formed after weight loss. There was no statistical significant difference because of small sample. Prophylactic cholecystectomy, however, may not be warranted in these patients.


Role of cell death in the topogenesis of neuronal distributions in the developing cat retinal ganglion cell layer.
The neurons of the developing and adult ganglion cell layer of the cat retina may be morphologically divided into two major populations. One population, the classic neurons, is mainly composed of ganglion cells, and of a small percentage of displaced amacrines, the bar cells. The remaining neurons are microneurons, which make up the majority of the displaced amacrine population. The loss of ganglion cells during the development has been attributed to cell death. It has alternatively been suggested that some ganglion cells may lose their axon and be transformed into displaced amacrine cells, without degeneration of the cell soma. Reexamination of foetal and postnatal cat retinas confirms the presence of degenerating cells in the ganglion cell layer. Their number appears to be at a maximum on embryonic day (E) 57 but declines rapidly until birth. The peak of cell death thus coincides with the decline in optic nerve fibre counts and classical neuron or ganglion cell numbers. Some cells in early stages of degeneration resemble classical neurons, but the original morphology of those advanced stages of degeneration could not be identified, nor was it possible to identify pyknotic microneurons at any stage. Substantial degeneration of the microneurons is not suggested but if it occurs, it is masked by an overall increase in the population of these cells before birth. Cell death in the microneuron population thus cannot yet be ruled out. It has been argued in the literature that fragments of degenerating cells in developing neural tissue are cleared by microglia within 10-14 hours. In order to test the hypothesis that operation of cell death can alone account for the observed loss of classical neurons in the foetal cat retina, we have modelled the effect of various presumed clearance times on corresponding neuronal population magnitudes. It is found that a constant clearance time of 10-24 hours would be consistent with the observed loss of classical neurons before birth. If this is true, then no ganglion cells would remain for transformation into amacrine cells. The absolute density of degenerating or pyknotic cells is found to be relatively constant across the retina. However their density expressed as a percentage of the local population of classical neurons is markedly higher in peripheral than central retina. In the former region, they compose more than 10% of classical neurons at stage E57. On the same day, the percentage distribution maps define an elongated central area containing only 3-5% pyknotic profiles. This region corresponds to the location of the future visual streak.(ABSTRACT TRUNCATED AT 400 WORDS)


Can microvolt T-wave alternans testing reduce unnecessary defibrillator implantation?
The Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) have established that patients with a reduced ejection fraction gain an overall mortality benefit from prophylactic implantable cardioverter-defibrillator therapy. Only a small proportion of the patients in these studies, however, have received life-saving therapy from the defibrillator. Because defibrillator therapy is invasive and expensive, patients with a low ejection fraction would benefit from effective risk stratification so that defibrillator therapy was used only in those at significant risk. In this review, we analyze prospective clinical trials that have evaluated microvolt T-wave alternans (MTWA) testing as a predictor of ventricular tachyarrhythmic events in populations of patients similar to those studied in MADIT II or SCD-HeFT; that is, patients with a reduced ejection fraction who were not selected on the basis of a history of ventricular tachyarrhythmias. In these studies, the average annual rate of fatal and nonfatal ventricular tachyarrhythmic events among the patients who tested negative for MTWA was around 1%. This rate is so low that it is unlikely that such patients would benefit from implantable cardioverter-defibrillator therapy. The mortality, moreover, was lower among MTWA-negative patients who did not receive implantable defibrillators than that observed in the MADIT II and SCD-HeFT patients who received implantable cardioverter-defibrillators. In response, patients with a low ejection fraction who are being considered for implantable cardioverter-defibrillator therapy should undergo MTWA testing as part of their evaluation.


A comparison of kangaroo mother care and conventional cuddling care.
To compare kangaroo mother care (KMC) and conventional cuddling care (CCC) in premature and small-for-gestational-age infants. Thirty mother-infant dyads in two Australian neonatal nurseries were randomly assigned to the KMC group or the CCC group. Both groups of mothers cuddled their babies for a minimum of two hours a day, five days a week while in the study, with the KMC group having skin-to-skin contact while the CCC group had contact through normal clothing. The main outcome variables were infant weight gain, temperature maintenance during KMC and CCC, and length of hospital stay. The results showed no difference between groups on the Parental Stress Scale (NICU) or the Parental Expectations Survey. Infants in both groups experienced equivalent maintenance of or rise in temperature while out of the incubators, equal weight gain, equal length of stay in the hospital, and equal duration of breastfeeding.


How Does Stigma Affect People Living with HIV? The Mediating Roles of Internalized and Anticipated HIV Stigma in the Effects of Perceived Community Stigma on Health and Psychosocial Outcomes.
Few researchers have attempted to examine the mechanisms through which HIV-related stigma in the community is processed and experienced at an individual level by people living with HIV. We examined how the effects of perceived HIV stigma in the community on health outcomes for people living with HIV are mediated by internalized stigma and anticipated stigma. Participants (N = 203) from an HIV clinic completed self-report measures and their clinical data were obtained from medical records. Results suggested that the association between perceived community stigma and affective, cognitive, and mental health outcomes (self-esteem, depressive symptoms, avoidance coping, self-blame) are mediated by internalized stigma. Furthermore, a serial mediation model suggested that perceived community stigma leads to internalized stigma, which leads to anticipated community stigma, which in turn leads to lower medication adherence. The associations between perceived community stigma and interpersonal outcomes (social support, trust in physicians) were mediated by internalized stigma and anticipated stigma, again in a serial fashion (perceived community stigma leads to internalized stigma, which leads to anticipated stigma, which in turn leads to interpersonal outcomes). These results suggest that perceived HIV-related stigma in the community may cause people living with HIV to internalize stigma and anticipate stigmatizing experiences, resulting in adverse health and psychosocial outcomes-information that can be used to shape interventions.


Paradoxical decrease of brain 5-HT turnover by metergoline, a central 5-HT receptor blocker.
Since metergoline (1-methyl-8-beta-carbobenzyloxy-aminomethyl-10-alpha-ergoline) is a potent 5-HT antagonist in peripheral organs, its possible blocking effects on 5-HT receptors in the rat brain were investigated. In vitro, metergoline inhibited both the specific high affinity binding of 3-H-5-HT onto synaptosomal membranes (IC 50 = 18 nM) and the stimulating effect of 10 micron 5-HT on the adenylate cyclase activity in colliculi homogenates from newborn rats (IC 50 = 12 micron. In vivo, the administration of metergoline (10 mg/kg i.p., 60 min before death) resulted in a significant decrease in the 3-H-5-HT binding capacity of synaptosomal membranes from the forebrain of adult rats. Taken together, these data clearly indicated that metergoline is a potent blocker of some serotoninergic receptors in the rat brain. Surprisingly, the changes in 5-HT turnover occurring in the brainstem and in the forebrain 1 h after metergoline (2-10 mg/kg) treatment were similar to those normally induced by a central 5-HT agonist: both the rate of 5-HT utilisation and that of 5-HT synthesis were significantly decreased. These changes were in contrast to the acceleration of 5-HT turnover induced by the administration of another potent central 5-HT antagonist, methiothepin. These results are discussed in relation to the possible existence of several types of serotoninergic receptors in the rat brain. It is possible that the positive feedback regulation of 5-HT turnover is triggered by the blockade of serotoninergic receptors sensitive to methiothepin, but not to metergoline.


Serologic and hexon phylogenetic analysis of ruminant adenoviruses.
The objectives of this study were to determine the antigenic relationship among ruminant adenoviruses and determine their phylogenetic relationship based on the deduced hexon gene amino acid sequence. Results of reciprocal cross-neutralization tests demonstrated antigenic relationships in either one or both directions among bovine adenovirus type 6 (BAdV-6), BAdV-7, ovine adenovirus type 7 (OAdV-7), caprine adenovirus type 1 (GAdV-1), and deer adenovirus (Odocoileus adenovirus 1, OdAdV-1). No antigenic cross-reactivity was observed among BAdV-1 through -5, and -8 and the other putative ruminant adenoviruses. Two PCR primer sets, one for mastadenovirus and atadenovirus that amplified an approximately 2,700-bp region in the hexon genes were used for comparative studies. Phylogenetic analysis of the deduced hexon amino acid sequences clustered the ruminant adenoviruses on the Mastadenovirus and Atadenovirus genus branches of the Adenoviridae tree. The recent classification of BAdV-6, and -7 as members of the genus Atadenovirus was supported by phylogenetic distance matrix analysis of their deduced hexon amino acid sequences. Further, we propose that BAdV-6 and -7 be recognized as members of new Atadenovirus species, Bovine adenovirus E and Bovine adenovirus F, respectively. Phylogenetic analysis of OdAdV-1 places this virus in the genus Atadenovirus with a proposed new species Odocoileus adenovirus A. OAdV-6 and GAdV-2 are proposed as members of new Mastadenovirus species Ovine adenovirus C and Goat adenovirus A, respectively.