Long-term outcomes of thoracic endovascular aortic repair: A single institution's 11-year experience.
Thoracic endovascular aortic repair (TEVAR) has largely replaced traditional open aortic repair for anatomically suitable lesions, however, long-term outcomes are unknown. All patients who underwent TEVAR from December 2004 to October 2015 at a single tertiary care institution were included. Demographics, injury pattern, operative details, outcomes, and surveillance were reviewed. Follow-up ranged from 2 to 132 months and was obtained from clinic notes and imaging reports. A total of 88 patients underwent TEVAR; all suffered from blunt mechanisms, 72.7% were men. Median age, Injury Severity Score, and Trauma and Injury Severity Score was 47 (19.7), 38 (13.5), 0. 8 (0.34). Injuries included 2% grade II, 90% grade III, and 8% grade IV. Overall mortality was 6.8%, TEVAR-related mortality was 0%. Overall in-hospital complication rate was 57%, whereas TEVAR-related complication rate was 9.1%: four typ 1a endoleaks, two typ 2, and two typ 3. Of the typ 1 endoleaks, all required reoperation, whereas all types 2 and 3 endoleaks resolved on subsequent imaging. The left subclavian artery (LSCA) was intentionally covered at index operation in 19 patients (21.6%), and 7 patients (8%) had partial LSCA coverage. The rate of postoperative left upper extremity ischemia was 0%. Left carotid-subclavian bypasses were performed prophylactically in two patients before LSCA coverage at index operation. Eighty-seven percent of endograft access was by performed by open femoral artery exposure and one via retroperitoneal conduit. Percutaneous TEVAR (pTEVAR) was performed more recently in 11.4% of patients with no complications. Heparin was administered intraoperatively in 23 patients with TBI, and 12 patients were not heparinized; no adverse events or outcomes resulted from its use or lack thereof. First, second, and third surveillance imagings occurred at mean intervals of 14 days, 4 months, and 1 year, respectively. Percent of patients followed at 1, 3, and 5 years from operation was 62.1%, 25%, 13.6%, respectively. TEVAR continues to be a feasible treatment modality for blunt traumatic aortic injury with minimal and early device and procedure-specific complications. Follow-up continues to be a significant challenge, and protocols for surveillance imaging are needed. This is the first study to describe access specific outcomes of pTEVAR in trauma patients. Long-term outcomes of TEVAR are still largely unknown; however, these data suggest that it may be at least comparable to open repair. Prognostic/epidemiologic study, level IV; therapeutic study, level V.


The SalGI restriction endonuclease. Purification and properties.
The type II restriction endonuclease SalGI has been purified to near homogeneity. At least 80% of the protein remaining after the final stage of the preparation is SalGI restriction endonuclease; no contaminating nucleases remain detectable. The principal form of the protein under both native and denaturing conditions is a monomer of M(r) about 29000. The optimal conditions for both enzyme stability and enzyme activity have been determined.


Cryptic diversity of African tigerfish (genus Hydrocynus) reveals palaeogeographic signatures of linked neogene geotectonic events.
The geobiotic history of landscapes can exhibit controls by tectonics over biotic evolution. This causal relationship positions ecologically specialized species as biotic indicators to decipher details of landscape evolution. Phylogeographic statistics that reconstruct spatio-temporal details of evolutionary histories of aquatic species, including fishes, can reveal key events of drainage evolution, notably where geochronological resolution is insufficient. Where geochronological resolution is insufficient, phylogeographic statistics that reconstruct spatio-temporal details of evolutionary histories of aquatic species, notably fishes, can reveal key events of drainage evolution. This study evaluates paleo-environmental causes of mitochondrial DNA (mtDNA) based phylogeographic records of tigerfishes, genus Hydrocynus, in order to reconstruct their evolutionary history in relation to landscape evolution across Africa. Strong geographical structuring in a cytochrome b (cyt-b) gene phylogeny confirms the established morphological diversity of Hydrocynus and reveals the existence of five previously unknown lineages, with Hydrocynus tanzaniae sister to a clade comprising three previously unknown lineages (Groups B, C and D) and H. vittatus. The dated phylogeny constrains the principal cladogenic events that have structured Hydrocynus diversity from the late Miocene to the Plio-Pleistocene (ca. 0-16 Ma). Phylogeographic tests reveal that the diversity and distribution of Hydrocynus reflects a complex history of vicariance and dispersals, whereby range expansions in particular species testify to changes to drainage basins. Principal divergence events in Hydrocynus have interfaced closely with evolving drainage systems across tropical Africa. Tigerfish evolution is attributed to dominant control by pulses of geotectonism across the African plate. Phylogenetic relationships and divergence estimates among the ten mtDNA lineages illustrates where and when local tectonic events modified Africa's Neogene drainage. Haplotypes shared amongst extant Hydrocynus populations across northern Africa testify to recent dispersals that were facilitated by late Neogene connections across the Nilo-Sahelian drainage. These events in tigerfish evolution concur broadly with available geological evidence and reveal prominent control by the African Rift System, evident in the formative events archived in phylogeographic records of tigerfish.


STRA6 is critical for cellular vitamin A uptake and homeostasis.
Vitamin A must be adequately distributed within the body to maintain the functions of retinoids in the periphery and chromophore production in the eyes. Blood transport of the lipophilic vitamin is mediated by the retinol-binding protein, RBP4. Biochemical evidence suggests that cellular uptake of vitamin A from RBP4 is facilitated by a membrane receptor. This receptor, identified as the Stimulated by retinoic acid gene 6 (Stra6) gene product, is highly expressed in epithelia that constitute blood-tissue barriers. Here we established a Stra6 knockout mouse model to analyze the metabolic basis of vitamin A homeostasis in peripheral tissues. These mice were viable when bred on diets replete in vitamin A, but evidenced markedly reduced levels of ocular retinoids. Ophthalmic imaging and histology revealed malformations in the choroid and retinal pigmented epithelium, early cone photoreceptor cell death, and reduced lengths of rod outer segments. Similar to the blood-retina barrier in the RPE, vitamin A transport through the blood-cerebrospinal fluid barrier in the brain's choroid plexus was impaired. Notably, treatment with pharmacological doses of vitamin A restored vitamin A transport across these barriers and rescued the vision of Stra6(-/-) mice. Furthermore, under conditions mimicking vitamin A excess and deficiency, our analyses revealed that STRA6-mediated vitamin A uptake is a regulated process mandatory for ocular vitamin A uptake when RBP4 constitutes the only transport mode in vitamin A deficiency. These findings identifying STRA6 as a bona fide vitamin A transporter have important implications for disease states associated with impaired blood vitamin A homeostasis.


Growth of the young heart: influence of nutrition and stress.
Newborn rat pups reared in litters of 4 and 16 inhaled up to 500 ppm carbon monoxide for 14 days, while others in litters of equal size remained in room air. Body weight, combined ventricle weight, hemoglobin concentration, hematocrit, and myocardial DNA content were measured. Differences in hemoglobin concentration and hematocrit between the four groups of pups were small. Cardiomegaly resulting from CO-stress was intensified in pups from small, as opposed to large litters. Relative combined ventricle weight was unaltered by change in litter size in the absence of CO-stress, although combined ventricle weight and body weight were increased with small litter size. Ventricular DNA content, indicative of cellularity, was increased in small litters and with CO-stress. Exacerbated postnatal anemia is not responsible for the differential effects of litter size and stress on the heart.


Sternomental distance as the sole predictor of difficult laryngoscopy in obstetric anaesthesia.
Sternomental distance and view at laryngoscopy were documented in 523 parturients undergoing elective or emergency Caesarean section under general anaesthesia. Eighteen (3.5%) had a grade III or IV laryngoscopic view (Cormack and Lehane's classification) and were classified as potentially difficult tracheal intubations. There was a significant difference between sternomental distance in those patients with a grade III or IV laryngoscopic view compared with those with a grade I or II (13.17 (SD 1.54) cm vs 14.3 (1.49) cm; P = 0.0013). A sternomental distance of 13.5 cm or less with the head fully extended on the neck and the mouth closed provided, using discriminant analysis, the best cut-off point for predicting subsequent difficult laryngoscopy. A sternomental distance of 13.5 cm or less had a sensitivity, specificity, positive and negative predictive values of 66.7%, 71.1%, 7.6% and 98.4%, respectively. While there was no association between sternomental distance and age, weight, height or body mass index (BMI), there was a significant association between grade of laryngoscopy (III and IV) and older (P = 0.049) and heavier (P = 0.0495) mothers. The results suggest that while sternomental distance on its own may not be an adequate sole predictor of subsequent difficult laryngoscopy the measurement should be incorporated into a series of quick and simple preoperative tests.


Circular RNA HIPK3: A Key Circular RNA in a Variety of Human Cancers.
Circular RNAs (circRNAs), which act as initiators and promoters of various diseases, were thought to be mostly noncoding RNAs (ncRNAs) in eukaryotes, until recent studies confirmed that some circRNAs have the function of encoding proteins. Accumulating research findings have proved that dysregulation of circRNAs is associated with the developmental process of multiple cancers. circHIPK3, an example of circRNA, is frequently expressed in many diseases, such as diabetes, age-related cataract, idiopathic pulmonary fibrosis, preeclampsia, osteoblasts, and retinal vascular dysfunction, leading to disease development and progression. In addition, circHIPK3 may also serve as a potential biomarker, to help us know more about the rules of occurrence and development of cancers. In recent studies, many circHIPK3-related cancers have been identified, including nasopharyngeal carcinoma, gallbladder cancer, lung cancer, hepatocellular carcinoma, osteosarcoma, glioma, colorectal cancer, ovarian cancer, bladder cancer, prostate cancer, gastric cancer, oral squamous cell carcinoma, and chronic myeloid leukemia. This review summarizes recent studies on the biological mechanisms of circHIPK3 and expounds the molecular mechanisms of circHIPK3 in these malignant tumors.


The biopsychosocial model of illness: a model whose time has come.
The biopsychosocial model outlined in Engel's classic Science paper four decades ago emerged from dissatisfaction with the biomedical model of illness, which remains the dominant healthcare model. Engel's call to arms for a biopsychosocial model has been taken up in several healthcare fields, but it has not been accepted in the more economically dominant and politically powerful acute medical and surgical domains. It is widely used in research into complex healthcare interventions, it is the basis of the World Health Organisation's International Classification of Functioning (WHO ICF), it is used clinically, and it is used to structure clinical guidelines. Critically, it is now generally accepted that illness and health are the result of an interaction between biological, psychological, and social factors. Despite the evidence supporting its validity and utility, the biopsychosocial model has had little influence on the larger scale organization and funding of healthcare provision. With chronic diseases now accounting for most morbidity and many deaths in Western countries, healthcare systems designed around acute biomedical care models are struggling to improve patient-reported outcomes and reduce healthcare costs. Consequently, there is now a greater need to apply the biopsychological model to healthcare management. The increasing proportion of healthcare resource devoted to chronic disorders and the accompanying need to improve patient outcomes requires action; better understanding and employment of the biopsychosocial model by those charged with healthcare funding could help improve healthcare outcome while also controlling costs.


An algorithm to discover gene signatures with predictive potential.
The advent of global gene expression profiling has generated unprecedented insight into our molecular understanding of cancer, including breast cancer. For example, human breast cancer patients display significant diversity in terms of their survival, recurrence, metastasis as well as response to treatment. These patient outcomes can be predicted by the transcriptional programs of their individual breast tumors. Predictive gene signatures allow us to correctly classify human breast tumors into various risk groups as well as to more accurately target therapy to ensure more durable cancer treatment. Here we present a novel algorithm to generate gene signatures with predictive potential. The method first classifies the expression intensity for each gene as determined by global gene expression profiling as low, average or high. The matrix containing the classified data for each gene is then used to score the expression of each gene based its individual ability to predict the patient characteristic of interest. Finally, all examined genes are ranked based on their predictive ability and the most highly ranked genes are included in the master gene signature, which is then ready for use as a predictor. This method was used to accurately predict the survival outcomes in a cohort of human breast cancer patients. We confirmed the capacity of our algorithm to generate gene signatures with bona fide predictive ability. The simplicity of our algorithm will enable biological researchers to quickly generate valuable gene signatures without specialized software or extensive bioinformatics training.


Does physical activity increase life expectancy? A review of the literature.
Physical activity reduces many major mortality risk factors including arterial hypertension, diabetes mellitus type 2, dyslipidemia, coronary heart disease, stroke, and cancer. All-cause mortality is decreased by about 30% to 35% in physically active as compared to inactive subjects. The purpose of this paper was to synthesize the literature on life expectancy in relation to physical activity. A systematic PubMed search on life expectancy in physically active and inactive individuals was performed. In addition, articles comparing life expectancy of athletes compared to that of nonathletes were reviewed. Results of 13 studies describing eight different cohorts suggest that regular physical activity is associated with an increase of life expectancy by 0.4 to 6.9 years. Eleven studies included confounding risk factors for mortality and revealed an increase in life expectancy by 0.4 to 4.2 years with regular physical activity. Eleven case control studies on life expectancy in former athletes revealed consistently greater life expectancy in aerobic endurance athletes but inconsistent results for other athletes. None of these studies considered confounding risk factors for mortality. In conclusion, while regular physical activity increases life expectancy, it remains unclear if high-intensity sports activities further increase life expectancy.


Evaluation of MDP and NaF in Two-step Self-etch Adhesives on Enamel Microshear Bond Strength and Morphology of the Adhesive-Enamel Interface.
To evaluate the roles of MDP and NaF in the bonding resin of a two-step self-etch adhesive (2-SEA) on enamel bonding performance. The experimental 2-SEAs were composed of an MDP-containing self-etching primer and four different bonding resins which were MDP- and NaF-free (00), MDP-containing and NaF-free (M0), MDP-free and NaF-containing (0F), and MDP- and NaF-containing (MF) adhesives. Microshear bond strength (µSBS) to enamel and ultimate tensile strength (UTS) of the adhesive resin were determined. The morphological characteristics of the adhesive-enamel interface after acid-base challenge were observed using SEM to evaluate the acid-base resistant zone (ABRZ). No decrease in μSBS was observed even after thermocycling (TC) in 00, 0F and MF. However, the μSBS of M0 significantly decreased after TC. The UTS of M0 significantly decreased after 1- and 180-day storage in water. SEM observations indicated that ABRZ was present in all groups. However, formation of erosion beneath the ABRZ was observed in M0 and 00, whereas formation of a slope without erosion was observed at the bottom of the ABRZ in MF. In the experimental 2-SEAs, the addition of MDP alone to the adhesive resin did not contribute to an improvement in enamel bonding durability and interfacial morphology, whereas the addition of NaF in the adhesive resin demonstrated an enhancement of the bonding durability and improvement of acid resistance at the bonded interface.


Activation of epithelial-mesenchymal transition process during breast cancer progression - the impact of molecular subtype and stromal composition.
Breast cancer (BC) is a heterogeneous disease with different molecular subtypes, which can be defined by oestrogen (ER), progesterone (PR) and human epidermal growth factor (HER2) receptors' status as luminal, HER2+ and triple negative (TNBC). Molecular subtypes also differ in their epithelial-mesenchymal phenotype, which might be related to their aggressiveness, as activation of the epithelial-mesenchymal transition (EMT) is linked with increased ability of cancer cells to survive and metastasize. Nevertheless, the reverse process of mesenchymal-epithelial transition was shown to be required to sustain metastatic colonization. In this study we aimed to analyse activation of the EMT process in primary tumours (PT), which have (N+) or have not (N-) colonized the lymph nodes, as well as the lymph nodes metastases (LNM) themselves in 88 BC patients. We showed that luminal N- PT have the lowest activation of the EMT process (27%), in comparison to N+ PT (48%, p=0.06). On the other hand, TNBC do not show statistically significant EMT activation at the stage before lymph colonization (N-, 83%) and after colonization of the lymph nodes (N+, 63%, p=0.58). TNBC are also the least plastic (unable to change the EMT phenotype) in terms of turning EMT on or off between matched PT and LNM (0% EMT plasticity in TNBC vs 36% plasticity in luminal tumours). Moreover, in TNBC activation of EMT was correlated with increased cell division rate of the PT- in mesenchymal TNBC PT median Ki-67 was 45% in comparison to 10% in epithelial TNBC PT (p=0.002), whereas in PT of luminal subtypes Ki-67 did not differ between epithelial and mesenchymal phenotypes. Profiling of immunotranscriptome of epithelial and mesenchymal luminal BC with Nanostring technology revealed that N- PT with epithelial phenotype were enriched in inflammatory response signatures, whereas N+ mesenchymal cancers showed elevated MHC class II antigen presentation. Overall, activation of EMT changes during cancer progression and metastatic colonization of the lymph nodes depending on the PT molecular subtype and is related to differences in stromal signatures. Activation of EMT is associated with colonizing phenotype in luminal PT and proliferative phenotype of TNBC.


Immunofluorescent cell-counting assay for lymphocytic choriomeningitis virus.
A quantitative assay for lymphocytic choriomeningitis virus was developed and standardized. The assay is based on direct immunofluorescent staining of infected L-929 cell monolayers and enumeration of cells containing fluorescent viral antigens. Maximal adsorption of virus to cells occurred within 1 h. Observations on the sequential development of viral antigens within cells showed that specific cytoplasmic fluorescence appeared within 10 h. The optimal time for enumerating fluorescent cells was from 18 to 20 h after addition of virus. A linear relationship was demonstrated between the number of infected cells and the relative virus concentration. Fluorescent cells were distributed randomly in infected cover slip cell monolayers. The immunofluorescent cell-counting assay for lymphocytic choriomeningitis virus was highly precise and reproducible.


Personality, Humor Styles and Happiness: Happy People Have Positive Humor Styles.
The present study examined the relationships between four personality traits, humor styles, and happiness. Replicating previous research, happiness was positively correlated with four personality traits: extraversion, locus of control, self-esteem, and optimism. Further, happiness positively related to self-enhancing and affiliative humor styles; it related negatively to self-defeating and aggressive humor styles. Thus, happy people habitually engage in positive uses of humor and avoid engaging in negative uses of humor in daily life. We also found support for our hypothesis. People high in extraversion, locus of control, self-esteem, and optimism are happier because they engage in positive humor in daily life.


Spherical indentation of free-standing acellular extracellular matrix membranes.
Numerous scaffold materials have been developed for tissue engineering and regenerative medicine applications to replace or repair damaged tissues and organs. Naturally occurring scaffold materials derived from acellular xenogeneic and autologous extracellular matrix (ECM) are currently in clinical use. These biological scaffold materials possess inherent variations in mechanical properties. Spherical indentation or ball burst testing has commonly been used to evaluate ECM and harvested tissue due to its ease of use and simulation of physiological biaxial loading, but has been limited by complex material deformation profiles. An analytical methodology has been developed and applied to experimental load-deflection data of a model hyperelastic material and lyophilized ECM scaffolds. An optimum rehydration protocol was developed based on water absorption, hydration relaxation and dynamic mechanical analysis. The analytical methodology was compared with finite element simulations of the tests and excellent correlation was seen between the computed biaxial stress resultants and geometry deformations. A minimum rehydration period of 5 min at 37°C was sufficient for the evaluated multilaminated ECM materials. The proposed approach may be implemented for convenient comparative analysis of ECM materials and source tissues, process optimization or during lot release testing.


Permian polar forests: deciduousness and environmental variation.
Forests are expected to expand into northern polar latitudes in the next century. However, the impact of forests at high latitudes on climate and terrestrial biogeochemical cycling is poorly understood because such forests cannot be studied in the modern. This study presents forestry and geochemical analyses of three in situ fossil forests from Late Permian strata of Antarctica, which grew at polar latitudes. Stem size measurements and stump spacing measurements indicate significant differences in forest density and canopy structure that are related to the local depositional setting. For forests closest to fluvial systems, tree density appears to decrease as the forests mature, which is the opposite trend of self-thinning observed in modern forests. We speculate that a combination of tree mortality and high disturbance created low-density mature forests without understory vegetation near Late Permian river systems. Stable carbon isotopes measured from permineralized wood in these forests demonstrate two important points: (i) recently developed techniques of high-resolution carbon isotope studies of wood and mummified wood can be applied to permineralized wood, for which much of the original organic matter has been lost and (ii) that the fossil trees maintained a deciduous habit at polar latitudes during the Late Permian. The combination of paleobotanical, sedimentologic, and paleoforestry techniques provides an unrivaled examination of the function of polar forests in deep time; and the carbon isotope geochemistry supplements this work with subannual records of carbon fixation that allows for the quantitative analysis of deciduous versus evergreen habits and environmental parameters, for example, relative humidity.


Favism: divicine hemotoxicity in the rat.
Favism is an acute hemolytic anemia known to occur in susceptible individuals who ingest fava beans. Susceptibility to favism is conferred by a genetic deficiency in erythrocytic glucose-6-phosphate dehydrogenase (G6PD) activity. Although the fava bean pyrimidine aglycones, divicine and isouramil, have been implicated in the onset of favism in humans, the lack of a well-defined experimental animal model for favism has hampered progress in elucidating the mechanism underlying hemotoxicity. We have examined whether a favic-like response could be provoked in G6PD-normal rats treated with synthetic divicine. Intraperitoneal administration of divicine to rats preloaded with 51Cr-tagged erythrocytes resulted in a severe, dose-dependent decrease in blood radioactivity (TD50 approximately 0.5 mmol/kg) within 24 h. The increased rate of removal of blood radioactivity was accompanied by a rapid decline in reduced glutathione levels in the blood, decreased hematocrits, marked hemoglobinuria, splenic enlargement, and reticulocytosis. In vitro exposure of 51Cr-tagged red cells to divicine before their re-administration to isologous rats also resulted in a sharp, concentration-dependent decrease in erythrocyte survival in vivo (TC50 approximately 1.5 mM), and these divicine-damaged red cells were removed from the circulation by the spleen. These data demonstrate that a favic response can be induced in G6PD-normal rats treated with divicine, and that hemolytic activity can be reproduced in isolated red cells under conditions that will allow a direct examination of the mechanism underlying this hemotoxicity.


Predictors of silent myocardial ischemia in resistant hypertensive patients.
Hypertension is the most prevalent and significant modifiable risk factor for coronary heart disease. A portion of patients with uncontrolled hypertension are considered to have resistant hypertension (RHTN). Myocardial ischemia incidence increases along with blood pressure (BP) levels. However, the prevalence of myocardial ischemia in patients with RHTN, as well as the factors associated with it, is unknown. We enrolled 129 patients with true RHTN regularly followed in our specialty hypertension clinic and evaluated then by resting and dipyridamole pharmacological stress myocardial perfusion scintigraphy. Patients were then divided into 2 groups: those with (I-RHTN; n = 36) and those without (NI-RHTN; n = 93) myocardial ischemia. Echocardiography, 24-hour ambulatory BP monitoring (ABPM), and flow mediated dilation (FMD) were also evaluated. Thirty six (28%) patients had myocardial ischemia. There was no difference between groups regarding age, sex, biochemical parameters, office, and 24-hour ABPM levels. Patients in the I-RHTN group were more likely diabetic (31% vs. 11%; P < 0.05) and obese (75% vs. 40%; P < 0.001). Adjusting for age and body mass index, multiple logistic regression showed that diabetes (odds ratio (OR) = 6.5; 95% confidence interval (CI) = 1.06-40.14; P = 0.04), FMD (OR = 0.18; 95% CI = 0.07-0.41; P < 0.001), heart rate (OR = 1.23; 95% CI = 1.11-1.36; P < 0.001), left ventricular mass index (OR = 1.02; 95% CI = 1.01-1.04; P = 0.04), and microalbuminuria (OR = 1.02; 95% CI = 1.01-1.04; P = 0.002) were independent predictors of ischemia. In conclusion, there is a high prevalence of myocardial ischemia in patients with RHTN. Increased microalbuminuria, heart rate, endothelial dysfunction, and left ventricular mass can be useful to guide the investigation for myocardial ischemia in these high risk patients.


Dietary polyphenols as a safe and novel intervention for modulating pain associated with intervertebral disc degeneration in an in-vivo rat model.
Developing effective therapies for back pain associated with intervertebral disc (IVD) degeneration is a research priority since it is a major socioeconomic burden and current conservative and surgical treatments have limited success. Polyphenols are naturally occurring compounds in plant-derived foods and beverages, and evidence suggests dietary supplementation with select polyphenol preparations can modulate diverse neurological and painful disorders. This study tested whether supplementation with a select standardized Bioactive-Dietary-Polyphenol-Preparation (BDPP) may alleviate pain symptoms associated with IVD degeneration. Painful IVD degeneration was surgically induced in skeletally-mature rats by intradiscal saline injection into three consecutive lumbar IVDs. Injured rats were given normal or BDPP-supplemented drinking water. In-vivo hindpaw mechanical allodynia and IVD height were assessed weekly for 6 weeks following injury. Spinal column, dorsal-root-ganglion (DRG) and serum were collected at 1 and 6 weeks post-operative (post-op) for analyses of IVD-related mechanical and biological pathogenic processes. Dietary BDPP significantly alleviated the typical behavioral sensitivity associated with surgical procedures and IVD degeneration, but did not modulate IVD degeneration nor changes of pro-inflammatory cytokine levels in IVD. Gene expression analyses suggested BDPP might have an immunomodulatory effect in attenuating the expression of pro-inflammatory cytokines in DRGs. This study supports the idea that dietary supplementation with BDPP has potential to alleviate IVD degeneration-related pain, and further investigations are warranted to identify the mechanisms of action of dietary BDPP.


Intracranial Empyema in Children: A Single-center Retrospective Case Series.
We conducted a retrospective, observational study of 42 children with intracranial empyema admitted to a pediatric neurosurgical center over a 9-year period. Intracranial empyema is rare, but causes significant morbidity and mortality. Twenty-eight cases had neurosurgical source control, more commonly for subdural collections. Streptococcus anginosus group bacteria are important pathogens in subdural empyema, whose isolation predicts more complicated postoperative courses.


The effects of temperature on human fertility.
Monthly birth and temperature data for a variety of states and countries are used to estimate the effect of short-run temperature fluctuations on fertility. Regressions of monthly births on a flexible specification of lagged monthly temperature show that temperature has quantitatively important effects on both seasonal and nonseasonal variation in births. Summer temperature extremes reduce conceptions in the southern United States, explaining a substantial part of the observed seasonal birth pattern. Extreme cold shows no evidence of affecting conceptions. The results also show significant seasonality in births even after accounting for temperature. Controls for monthly temperature do not explain the persistent spring peak in births in northern Europe. This finding suggests that other factors play an important role.


Rabdomyosarcoma of the biliary tree.
Rabdomyosarcoma of the biliary tree is one of the rare causes of biliary tract obstruction in childhood. Nevertheless it is the most common cause of obstructive jaundice due to neoplastic biliary obstruction. We present a two-year-old child with obstructive jaundice secondary to an embryonal rhabdomyosarcoma of the biliary tree. She underwent surgery and, after total excision of the mass, a hepaticojejunostomy and Roux-en-Y anastomosis were performed. She was referred to the Pediatric Oncology Group for follow-up. Rhabdomyosarcoma of the bilary tree, although rare, must be considered in the etiology of obstructive jaundice in children.


Israel and the global synthetic biology ecosystem.
The field of synthetic biology emerged a few decades ago, following some key works of researchers in the USA, Europe, and the Far East. It reached Israel through academia and a few years later it finally got the attention of industry, venture capitals, and government authorities, especially the Israeli Innovation Authority, hoping to encourage entrepreneurs to establish startups in this field. Here we provide an overview of the activity of the field of synthetic biology in Israel, including historical notes, current strategy, prospects and developments, and further insight that are relevant to any stakeholders in the synthetic biology field.


Pheromone-sensitive glomeruli in the primary olfactory centre of ants.
Tremendous evolutional success and the ecological dominance of social insects, including ants, termites and social bees, are due to their efficient social organizations and their underlying communication systems. Functional division into reproductive and sterile castes, cooperation in defending the nest, rearing the young and gathering food are all regulated by communication by means of various kinds of pheromones. No brain structures specifically involved in the processing of non-sexual pheromone have been physiologically identified in any social insects. By use of intracellular recording and staining techniques, we studied responses of projection neurons of the antennal lobe (primary olfactory centre) of ants to alarm pheromone, which plays predominant roles in colony defence. Among 23 alarm pheromone-sensitive projection neurons recorded and stained in this study, eight were uniglomerular projection neurons with dendrites in one glomerulus, a structural unit of the antennal lobe, and the remaining 15 were multiglomerular projection neurons with dendrites in multiple glomeruli. Notably, all alarm pheromone-sensitive uniglomerular projection neurons had dendrites in one of five 'alarm pheromone-sensitive (AS)' glomeruli that form a cluster in the dorsalmost part of the antennal lobe. All alarm pheromone-sensitive multiglomerular projection neurons had dendrites in some of the AS glomeruli as well as in glomeruli in the anterodorsal area of the antennal lobe. The results suggest that components of alarm pheromone are processed in a specific cluster of glomeruli in the antennal lobe of ants.


Ginger and Zingerone Ameliorate Lipopolysaccharide-Induced Acute Systemic Inflammation in Mice, Assessed by Nuclear Factor-κB Bioluminescent Imaging.
Ginger is a commonly used spice in cooking. In this study, we comprehensively evaluated the anti-inflammatory activities of ginger and its component zingerone in lipopolysaccharide (LPS)-induced acute systemic inflammation in mice via nuclear factor-κB (NF-κB) bioluminescent imaging. Ginger and zingerone significantly suppressed LPS-induced NF-κB activities in cells in a dose-dependent manner, and the maximal inhibition (84.5% ± 3.5% and 96.2% ± 0.6%) was observed at 100 μg/mL ginger and zingerone, respectively. Moreover, dietary ginger and zingerone significantly reduced LPS-induced proinflammatory cytokine production in sera by 62.9% ± 18.2% and 81.3% ± 6.2%, respectively, and NF-κB bioluminescent signals in whole body by 26.9% ± 14.3% and 38.5% ± 6.2%, respectively. In addition, ginger and zingerone suppressed LPS-induced NF-κB-driven luminescent intensities in most organs, and the maximal inhibition by ginger and zingerone was observed in small intestine. Immunohistochemical staining further showed that ginger and zingerone decreased interleukin-1β (IL-1β)-, CD11b-, and p65-positive areas in jejunum. In conclusion, our findings suggested that ginger and zingerone were likely to be broad-spectrum anti-inflammatory agents in most organs that suppressed the activation of NF-κB, the production of IL-1β, and the infiltration of inflammatory cells in mice.


Advanced practice nursing in Texas: the interface of accreditation, regulation, and certification.
The rapidity and degree of development of regulation by boards of nursing of advanced practice nurses (APNs) and programs for their preparation has varied from state to state over the past 20 years. In general, boards have authority only to regulate advanced practice through the recognition of APNs and the setting of standards and scope of their practice. In the early 1990s, lack of consistent APN educational program standards and experiences and criteria for recognition of APNs was problematic at the levels of accreditation, certification, and regulation. The interdependency of these concepts as well as the necessity and difficulty of linking them in a consistent, effective manner has become increasingly evident. The Texas Board of Nurse Examiners has been involved in deriving a model designed to ensure the education and recognition of APNs with emphasis on both professionalism and public safety. Because Texas is unique in size and geography, it mirrors many problems and issues of both large and small states.


GSAE: an autoencoder with embedded gene-set nodes for genomics functional characterization.
Bioinformatics tools have been developed to interpret gene expression data at the gene set level, and these gene set based analyses improve the biologists' capability to discover functional relevance of their experiment design. While elucidating gene set individually, inter-gene sets association is rarely taken into consideration. Deep learning, an emerging machine learning technique in computational biology, can be used to generate an unbiased combination of gene set, and to determine the biological relevance and analysis consistency of these combining gene sets by leveraging large genomic data sets. In this study, we proposed a gene superset autoencoder (GSAE), a multi-layer autoencoder model with the incorporation of a priori defined gene sets that retain the crucial biological features in the latent layer. We introduced the concept of the gene superset, an unbiased combination of gene sets with weights trained by the autoencoder, where each node in the latent layer is a superset. Trained with genomic data from TCGA and evaluated with their accompanying clinical parameters, we showed gene supersets' ability of discriminating tumor subtypes and their prognostic capability. We further demonstrated the biological relevance of the top component gene sets in the significant supersets. Using autoencoder model and gene superset at its latent layer, we demonstrated that gene supersets retain sufficient biological information with respect to tumor subtypes and clinical prognostic significance. Superset also provides high reproducibility on survival analysis and accurate prediction for cancer subtypes.


Electrophilic nitro-fatty acids prevent astrocyte-mediated toxicity to motor neurons in a cell model of familial amyotrophic lateral sclerosis via nuclear factor erythroid 2-related factor activation.
Nitro-fatty acids (NO2-FA) are electrophilic signaling mediators formed in tissues during inflammation, which are able to induce pleiotropic cytoprotective and antioxidant pathways including up regulation of Nuclear factor erythroid 2-related factor 2 (Nrf2) responsive genes. Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motor neurons associated to an inflammatory process that usually aggravates the disease progression. In ALS animal models, the activation of the transcription factor Nrf2 in astrocytes confers protection to neighboring neurons. It is currently unknown whether NO2-FA can exert protective activity in ALS through Nrf2 activation. Herein we demonstrate that nitro-arachidonic acid (NO2-AA) or nitro-oleic acid (NO2-OA) administrated to astrocytes expressing the ALS-linked hSOD1(G93A) induce antioxidant phase II enzyme expression through Nrf2 activation concomitant with increasing intracellular glutathione levels. Furthermore, treatment of hSOD1(G93A)-expressing astrocytes with NO2-FA prevented their toxicity to motor neurons. Transfection of siRNA targeted to Nrf2 mRNA supported the involvement of Nrf2 activation in NO2-FA-mediated protective effects. Our results show for the first time that NO2-FA induce a potent Nrf2-dependent antioxidant response in astrocytes capable of preventing motor neurons death in a culture model of ALS.


Control of petal shape and floral zygomorphy in Lotus japonicus.
Zygomorphic flowers, with bilateral (dorsoventral) symmetry, are considered to have evolved several times independently in flowering plants. In Antirrhinum majus, floral dorsoventral symmetry depends on the activity of two TCP-box genes, CYCLOIDEA (CYC) and DICHOTOMA (DICH). To examine whether the same molecular mechanism of floral asymmetry operates in the distantly related Rosid clade of eudicots, in which asymmetric flowers are thought to have evolved independently, we investigated the function of a CYC homologue LjCYC2 in a papilionoid legume, Lotus japonicus. We showed a role for LjCYC2 in establishing dorsal identity by altering its expression in transgenic plants and analyzing its mutant allele squared standard 1 (squ1). Furthermore, we identified a lateralizing factor, Keeled wings in Lotus 1 (Kew1), which plays a key role in the control of lateral petal identity, and found LjCYC2 interacted with Kew1, resulting in a double mutant that bore all petals with ventralized identity to some extents. Thus, we demonstrate that CYC homologues have been independently recruited as determinants of petal identities along the dorsoventral axis in two distant lineages of flowering plants, suggesting a common molecular origin for the mechanisms controlling floral zygomorphy.


Intrapericardial OK-432 instillation for the management of malignant pericardial effusion.
Ten patients with malignant pericardial effusion were treated with intrapericardial injection of OK-432 (penicillin-treated and heat-treated lyophilized powder of the substrain of Streptococcus pyogenes A3). After intrapericardial insertion of a catheter, a maximal volume of pericardial fluid was withdrawn with cytologic confirmation of malignancy. Five or 10 Klinische Einheit (KE) (KE is a unit used to express the strength of a preparation) of OK-432 diluted in 20 ml of saline was injected into the pericardial space in seven and three patients, respectively. It was repeated in case of reaccumulation. Seven patients were treated only once and the remaining three required a second treatment. Complete control of pericardial effusion was achieved in all patients for an average of 329 days (range, 54 to 790 days). Fever and chest pain were experienced in six and five patients, respectively, but were controlled with antipyretics. Two of three patients who received 10 KE of OK-432 experienced hypotension that was successfully controlled with vasopressor drugs with or without reaspiration of pericardial fluid. Rapid reactive reaccumulation of the pericardial fluid was thought to be a cause of hypotension. A follow-up computed tomography (CT) scan was performed in seven patients and a thickened pericardium was noticed in five; no patients had constrictive pericarditis. These results suggest that intrapericardial administration of 5 KE of OK-432 is an effective and safe treatment for malignant pericardial effusion.


Independent versus coupled inactivation in sodium channels. Role of the domain 2 S4 segment.
The voltage sensor of the sodium channel is mainly comprised of four positively charged S4 segments. Depolarization causes an outward movement of S4 segments, and this movement is coupled with opening of the channel. A mutation that substitutes a cysteine for the outermost arginine in the S4 segment of the second domain (D2:R1C) results in a channel with biophysical properties similar to those of wild-type channels. Chemical modification of this cysteine with methanethiosulfonate-ethyltrimethylammonium (MTSET) causes a hyperpolarizing shift of both the peak current-voltage relationship and the kinetics of activation, whereas the time constant of inactivation is not changed substantially. A conventional steady state inactivation protocol surprisingly produces an increase of the peak current at -20 mV when the 300-ms prepulse is depolarized from -190 to -110 mV. Further depolarization reduces the current, as expected for steady state inactivation. Recovery from inactivation in modified channels is also nonmonotonic at voltages more hyperpolarized than -100 mV. At -180 mV, for example, the amplitude of the recovering current is briefly almost twice as large as it was before the channels inactivated. These data can be explained readily if MTSET modification not only shifts the movement of D2/S4 to more hyperpolarized potentials, but also makes the movement sluggish. This behavior allows inactivation to have faster kinetics than activation, as in the HERG potassium channel. Because of the unique properties of the modified mutant, we were able to estimate the voltage dependence and kinetics of the movement of this single S4 segment. The data suggest that movement of modified D2/S4 is a first-order process and that rate constants for outward and inward movement are each exponential functions of membrane potential. Our results show that D2/S4 is intimately involved with activation but plays little role in either inactivation or recovery from inactivation.


Exact Derivation of a Finite-Size Scaling Law and Corrections to Scaling in the Geometric Galton-Watson Process.
The theory of finite-size scaling explains how the singular behavior of thermodynamic quantities in the critical point of a phase transition emerges when the size of the system becomes infinite. Usually, this theory is presented in a phenomenological way. Here, we exactly demonstrate the existence of a finite-size scaling law for the Galton-Watson branching processes when the number of offsprings of each individual follows either a geometric distribution or a generalized geometric distribution. We also derive the corrections to scaling and the limits of validity of the finite-size scaling law away the critical point. A mapping between branching processes and random walks allows us to establish that these results also hold for the latter case, for which the order parameter turns out to be the probability of hitting a distant boundary.


Functional Characterization of Cucumis metuliferus Proteinase Inhibitor Gene (CmSPI) in Potyviruses Resistance.
Proteinase inhibitors are ubiquitous proteins that block the active center or interact allosterically with proteinases and are involved in plant physiological processes and defense responses to biotic and abiotic stresses. The CmSPI gene identified from Cucumis metuliferus encodes a serine type PI (8 kDa) that belongs to potato I type family. To evaluate the effect of silencing CmSPI gene on Papaya ringspot virus resistance, RNA interference (RNAi) with an inter-space hairpin RNA (ihpRNA) construct was introduced into a PRSV-resistant C. metuliferus line. CmSPI was down-regulated in CmSPI RNAi transgenic lines in which synchronously PRSV symptoms were evident at 21 day post inoculation. Alternatively, heterogeneous expression of CmSPI in Nicotiana benthamiana was also conducted and showed that CmSPI can provide resistance to Potato virus Y, another member of Potyvirus, in transgenic N. benthamiana lines. This study demonstrated that CmSPI plays an important role in resistant function against potyviruses in C. metuliferus and N. benthamiana.


Leading Through Chaos: Perspectives From Nurse Executives.
The COVID-19 crisis created unique and interesting challenges for health care systems and changed how health care professionals delivered care. Evidence suggests that leadership skills remain of utmost importance during crises as it is the leader who often determines the response of the follower. A descriptive qualitative approach was used to ascertain the essence of nurse executive leadership and innovation during the COVID-19 crisis. Nurse executives were recruited via personal invitations to participate in the study. Participants were asked about their current challenges of COVID-19 on health care delivery, their leadership style, and what innovative processes their teams deployed. Using a thematic analysis approach, 3 themes emerged and resonated from the interviews: the importance of communication; the need for leadership presence; and mental toughness. With any health care crisis, leadership is essential to guide followers. As demonstrated by these findings, communication, leadership presence, and mental toughness are 3 key components to promoting and providing quality care in an austere, complex, and changing health care environment. Further understanding of the roles of these key concepts may add insight into nurse leaders and leadership development.


[Association between ambient air pollution and hospital emergency room visits for respiratory diseases: a case-crossover study].
Using case-crossover design to explore the association between ambient air pollution and the hospital emergency room visits for respiratory diseases (International Classification of Diseases, tenth vision ICD-10: J00-J99) in Beijing, China. Data regarding the daily hospital emergency room visits of the respiratory diseases (ICD-10: J00-J99) were obtained in 2004.01.01 - 2005.12.31, from the Peking University Third Hospital and data on relevant air pollution and meteorological factors from the local municipal environmental monitoring center and meteorology bureau of Beijing, respectively. Time-stratified case-crossover technique was used to evaluate their relationships. Results from the bi-directional control sampling approach were compared with unidirectional approach. Using a unidirectional control sampling approach, the results obtained from a conditional logistic regression model (multi-pollutant model) after adjusting for meteorological variables, showed that the ORs of the hospital emergency room visits for the respiratory diseases associated with each 10 µg/m(3) increment of PM(10), SO(2), NO(2) were 1.010 (95%CI: 1.005 - 1.014), 1.010 (95%CI: 1.001 - 1.018), 0.996 (95%CI: 0.983 - 1.009) respectively. In the bi-directional control sampling approach, the ORs were 1.002 (95%CI: 0.998 - 1.005), 1.011 (95%CI: 1.003 - 1.018), 1.012 (95%CI: 1.001 - 1.022). Results from this study provided evidence that higher levels of ambient air pollutants increased the risk of hospital emergency room visits for respiratory diseases.


Multilocus molecular systematics of the circumtropical reef-fish genus Abudefduf (Pomacentridae): history, geography and ecology of speciation.
We investigated a pantropical sub-family and genus of damselfishes, the sergeant-majors (Pomacentridae: Abudefdufinae: Abudefduf), to identify the tempo and mechanisms of speciation in the lineage. We examined sequence capture data from 500 loci and 20 species, with multiple individuals sampled from across the geographic ranges of widespread species. Utilizing a maximum likelihood framework, as well as a time-calibrated Bayesian phylogeny, the following key questions are addressed: What is the historical tempo of speciation? What are the relative contributions of vicariant, peripatric and parapatric speciation to sergeant-major diversity? How is speciation related to major variation in trophic ecology? The approximately 20 species of sergeant-majors fall into three main lineages. The ancestral condition appears to be benthivory, which is predominant in two lineages comprising six species. The remaining species of sergeant-majors, of which there are at least 15, fall within a clade composed entirely of planktivores. This clade is sister to a benthivore clade that included one species, Abudefduf notatus, in transition to planktivory. Most speciation of sergeant-majors, which appeared ∼24 million years ago, occurred in the last 10 million years. Present distributional patterns indicate vicariant speciation precipitated by the closure of land barriers between both sides of the Atlantic and the Pacific, and the emergence of land between the Indian and Pacific Oceans. Within this backdrop, frequent oscillations in sea level over the last 10 million years also appear to have generated conditions suitable for both peripatric and vicariant speciation, and most speciation within the genus appears linked to these changes in sea level. Diversification within the genus has been concentrated in planktivorous seargeant-majors rather than benthivores. The root cause is unclear, but does not appear to be related to differences in dispersal potential, which is greater in the planktivorous species, due to the ability of their post-larval juveniles to raft with floating debris. This elevated speciation rate in planktivores and their propensity to form local endemics may reflect relaxation of selective pressures (e.g., on crypticity) that limit speciation in benthivorous sergeant-majors. Finally, our data allow us to clarify relationships of geminate sergeant-major species, indicating that there are subdivisions within the Atlantic for both benthivore and planktivore geminate pairs that may have misled previous studies.


The sentinel node in cervical cancer: scintigraphy and laparoscopic gamma probe-guided biopsy.
The sentinel node (SN) procedure has been proven to be a valuable technique in the staging and treatment of a number of solid tumours. We evaluated the feasibility of SN biopsy with a laparoscopic gamma probe and dye guidance in 34 patients with clinically localised cervical cancer. After peritumoural injection of 140 MBq 99mTc colloidal albumin, dynamic and late static images were obtained. Just before the laparoscopic procedure, blue dye was injected. Blue and radioactive lymph nodes were excised followed by a regular lymphadenectomy. Lymphoscintigraphy revealed 70 SNs in 50 basins during dynamic imaging and 83 SNs in 63 basins at late imaging. SNs were visualised in 97% of the patients, bilaterally in 30 and unilaterally in three. Seventy-four of the 105 radioactive lymph nodes that were excised laparoscopically were considered to be SNs, 53 being blue as well, and were sent for frozen section. Nine foci that had been seen on scintigraphy could not be found either intraoperatively or in the remaining lymphadenectomy specimen. Four blue nodes were excised in three of five basins that had shown no foci during scintigraphy. In 17 basins of 12 patients, tumour-positive lymph nodes were found. In one of them a micrometastasis was found in the hysterectomy specimen while the lymphadenectomy did not contain any metastases (sensitivity 92%). Based on SN histology, the treatment was altered in nine patients (26%). We conclude that laparoscopic SN biopsy is feasible in cervical cancer and may result in custom-designed treatment strategies with a reduction in morbidity.


Awareness of Salt Intake among Community-Dwelling Elderly at Coastal Area: The Role of Public Health Access Program.
A geographical location such as coastal area is known as risk factor hypertension relating to high exposure of salty foods. Public health access had significant effect on reducing salt intake at the community level. This study assesses salt intake in older women resident at urban coastal in Indonesia participating in the public health program. This was a cross-sectional study involving older women (56.98 ± 5.7 years) resident at urban coastal in Kenjeran, Surabaya, Indonesia. Salt intake was calculated and estimated based on 24-h urinary sodium. The mean daily salt intake was 6.16 ± 3.48 g/d; only 11.8% of subjects consumed salt intake <3 g/day. However, majority of subjects (62.8%) consume salt <6 g/d. Awareness and participation were associated significantly with low salt intake. A significant association between participation, awareness, and salt intake may suggest that participating regularly in the public health program might cause our subjects controlled excessive salt intake by limiting their salt consumption. Since daily salt intake is still significant high and hypertension is still prevalence, comprehensive strategies to reduce salt should be considered in development of sodium-reduction initiatives in this region.


Catalytic Graphitization of Biocarbon for Lithium-Ion Anodes: A Minireview.
The demand for electrochemical energy storage is increasing rapidly due to a combination of decreasing costs in renewable electricity, governmental policies promoting electrification, and a desire by the public to decrease CO2 emissions. Lithium-ion batteries are the leading form of electrochemical energy storage for electric vehicles and the electrical grid. Lithium-ion cell anodes are mostly made of graphite, which is derived from geographically constrained, non-renewable resources using energy-intensive and highly polluting processes. Thus, there is a desire to innovate technologies that utilize abundant, affordable, and renewable carbonaceous materials for the sustainable production of graphite anodes under relatively mild process conditions. This review highlights novel attempts to realize the aforementioned benefits through innovative technologies that convert biocarbon resources, including lignocellulose, into high quality graphite for use in lithium-ion anodes.


Promoting peripheral myelin repair.
Compared to the central nervous system (CNS), peripheral nerves have a remarkable ability to regenerate and remyelinate. This regenerative capacity to a large extent is dependent on and supported by Schwann cells, the myelin-forming glial cells of the peripheral nervous system (PNS). In a variety of paradigms, Schwann cells are critical in the removal of the degenerated tissue, which is followed by remyelination of newly-regenerated axons. This unique plasticity of Schwann cells has been the target of myelin repair strategies in acute injuries and chronic diseases, such as hereditary demyelinating neuropathies. In one approach, the endogenous regenerative capacity of Schwann cells is enhanced through interventions such as exercise, electrical stimulation or pharmacological means. Alternatively, Schwann cells derived from healthy nerves, or engineered from different tissue sources have been transplanted into the PNS to support remyelination. These transplant approaches can then be further enhanced by exercise and/or electrical stimulation, as well as by the inclusion of biomaterial engineered to support glial cell viability and neurite extension. Advances in our basic understanding of peripheral nerve biology, as well as biomaterial engineering, will further improve the functional repair of myelinated peripheral nerves.


Engaging with the political imaginaries of science: Near misses and future targets.
The current economic and financial crisis is also a political crisis that requires a rethinking of public engagement with science. In the past, the dominant focus of science, technology and society (STS) has led to a blind spot: political understanding and engagement of policy-makers and politicians with science, which is an integral part of any public engagement. Arguably, it is bound to and emerges from what Ezrahi calls collective political imaginaries. These are necessary fictions, which are causative and performative. In crude form, they manifest themselves in short-term impact measurements of every unit of scientific activity with citizens as the fictitious ultimate beneficiaries. In the future, STS can gain from coming up with a workable definition of the public interest with a focus on the public value of science. It can investigate collective imaginaries as they emerge from interactions with new media. As necessary fictions they may hold answers we never imagined them to hold.


[Multiple endocrine neoplasia of the first type (Wermer's syndrome)].
11 patients with Wermer's syndrome (WS) aged 24-67 years were treated. They had a total of 30 tumors: 4(13.3%) hypophyseal, 11(36.7%) pancreatic, 9(30%) parathyroid, 4(13.3%) adrenal and 2(6.7%) duodenal. Each patient had two tumors minimum and 8 tumors maximum. In 8 cases WS presented clinically as hypoglycemia, in 3 cases as Zollinger-Ellison syndrome. The diagnosis was made using ultrasonography, CT, MRT and angiography. Cytogenetic examination was made in 2 cases. All the patients were operated. Six of them were operated two times, one--four times. The following surgery was made: 4 removals of parathyroid adenomas, 4 adrenalectomies, 1 removal of the hypophysis, 4 enucleations of pancreatic insulinomas, 5 distal hemipancreatectomies, 1 distal subtotal resection of the pancreas, 1 gastropancreatoduodenal resection. Clinically symptomatic tumors should be operated first.


Mechanisms of growth stimulation by suramin in non-small-cell lung cancer cell lines.
Suramin, a polysulfonated naphthylurea, has been shown to be effective in the treatment of several cancers. We have reported that suramin, at dose concentrations higher than 140 microM, exerts growth-stimulatory effects in several non-small-cell lung cancer (NSCLC) cell lines. The purpose of this study was to examine the mechanisms by which suramin exerts this growth-stimulatory effect in NSCLC cells. NCI-H596 cells were treated with agarose-immobilized suramin, directly or by addition on cell culture inserts, after which growth was determined by [3H]thymidine incorporation. PPADS, a specific purinergic receptor antagonist, was used to determine whether suramin acts via purinergic receptors. The effect of suramin on epidermal growth factor receptor (EGFR) was determined by analyzing receptor phosphorylation and dimerization. XAMR 0721, a suramin analogue containing only one of the two polysulfonated arms, was also analyzed for its effects on growth and EGFR activation. Agarose-immobilized suramin stimulated NCI-H596 cell growth, but only when added directly to the cells. When the suramin-conjugated beads were added to the cells on cell culture inserts, which preclude an interaction with the cell surface but allow interaction with the culture medium, there was no effect on proliferation. PPADS had no effect on the growth stimulation by suramin; however suramin treatment resulted in rapid phosphorylation and dimerization of EGFR. Treatment with XAMR 0721 did not affect growth or tyrosine phosphorylation and dimerization of EGFR. Suramin need not enter NCI-H596 cells to exert its growth-stimulatory effect, nor is this effect mediated by an interaction with soluble growth factors. Rather, it appears that suramin acts via an interaction with EGFR, but not with purinergic receptors.


Partial A(1) adenosine receptor agonists from a molecular perspective and their potential use as chronic ventricular rate control agents during atrial fibrillation (AF).
This review provides a molecular perspective of partial agonism at the A(1) adenosine receptor. The structure-activity relationships (SAR) for affinity and intrinsic efficacy of analogues of the full agonist N6-cyclopentyladenosine (CPA) are emphasized. Both general models of activation of G protein-coupled receptors and specific molecular models of the A(1)-adenosine receptor are used to interpret the results of efforts to synthesize and assay effects of partial agonists. The SAR of affinity and intrinsic efficacy of the 2', 3', and especially the 5'-deoxy derivatives of CPA is presented. From this analysis, the nature of the interactions of specific atoms and substituents of the CPA molecule with the A(1)-adenosine receptor are deduced and presented pictorially. As an example of the therapeutic potential of partial agonists, the design and testing of analogues of CPA to provide chronic ventricular rate control during atrial fibrillation is described. The challenges associated with designing a partial A(1)-adenosine receptor agonist for providing chronic ventricular rate control during atrial fibrillation are many. To meet these challenges, further medicinal chemistry efforts in the area of partial A(1)-adenosine receptor agonism are still needed.


Current preferences for breast reduction techniques: a survey of board-certified plastic surgeons 2002.
The purpose of this survey was to assess the current trends in breast reduction techniques and to compare satisfaction rates and complications associated with traditional incision and limited incision techniques. In September of 2002, a breast reduction survey was sent to 1500 members of the American Society for Aesthetic Plastic Surgery; 554 of the members returned the survey. Questions elicited categorical answers, and the data were evaluated using the chi-square test and the comparison of two proportions. The results showed that 56 percent of the respondents use only the inferior pedicle and Wise pattern techniques, whereas 6.9 percent of the respondents use only the limited incision techniques. Physician satisfaction was rated as 4 on a scale of 1 (unsatisfied) to 5 (very satisfied) for both the limited incision and traditional incision groups. Patient satisfaction was rated as 4 for the limited incision group and as 5 for the traditional incision group. This difference in patient satisfaction per surgeon was statistically significant (p < 0.05). The traditional group reported a lower complication rate than did the limited incision group (p < 0.05). The most frequent complications for the traditional incision group were compared with those of the limited incision group. Practice profiles, liposuction, and opinions regarding future changes in breast surgery were also analyzed. The majority of surgeons reported that they did not anticipate changing their practices to accommodate advances in limited incision techniques; however, 89 percent reported that the new limited incision techniques and liposuction are trends that are here to stay.


Papain-like lysosomal cysteine proteases and their inhibitors: drug discovery targets?
Papain-like lysosomal cysteine proteases are processive and digestive enzymes that are expressed in organisms from bacteria to humans. Increasing knowledge about the physiological and pathological roles of cysteine proteases is bringing them into the focus of drug discovery research. These proteases have rather short active-site clefts, comprising three well defined substrate-binding subsites (S2, S1 and S1') and additional broad binding areas (S4, S3, S2' and S3'). The geometry of the active site distinguishes cysteine proteases from other protease classes, such as serine and aspartic proteases, which have six and eight substrate-binding sites respectively. Exopeptidases (cathepsins B, C, H and X), in contrast with endopeptidases (such as cathepsins L, S, V and F), possess structural features that facilitate the binding of N- and C-terminal groups of substrates into the active-site cleft. Other than a clear preference for free chain termini in the case of exopeptidases, the substrate-binding sites exhibit no strict specificities. Instead, their subsite preferences arise more from the specific exclusion of substrate types. This presents a challenge for the design of inhibitors to target a specific cathepsin: only the cumulative effect of an assembly of inhibitor fragments will bring the desired result.


Biological Variation of Iron, Transferrin, Ferritin, Folate, Vitamin B12 and 25-OH Vitamin D in Healthy Individuals.
We aimed to evaluate the use of population-based-reference-intervals by calculating the individuality index and reference change value of iron, transferrin, ferritin, folate, vitamin B12, and 25-OH vitamin D parameters. A total of 5 venous blood samples were taken from 11 female and 10 male individuals on days 0, 7, 14, 21, and 28. All tests were performed on an autoanalyzer and CVI, CVG, II, and RCV values were calculated for both genders and the whole groups. CVA (%)/CVI (%)/CVG (%) for iron, 0.67/27.3/32.3 transferrin, 0.62/3.60/10.27 ferritin, 2.27/6.21/105.6 folate 4.71/10.3/28.56 vitamin B12, 6.1/5.77/34.6, 25-OH Vitamin D 3.4/8.2/54.9 respectively. RCV calculated as a 2-tailed value at level of probability of significant change set at 0.95 - 0.99; 74.9/98.7 - 10.1/13.3 - 18.3/24.1 - 31.4/41.3 - 23.4/30.8 - 24.7/32.5 and II were 0.8-0.4-0.-0.4-0.17-0.1 respectively. CVI and CVG values for iron, transferrin, folate, vitamin B12, and 25-OH vitamin D are in accordance with the literature. Ferritin was calculated differently from the values in the database. This difference might be due to the characteristics of selected individuals for study. Evaluating the suitability and utility of the use of RR with values found for II. For iron, the use of RR was considered appropriate when taken as II < 0.6 and II > 1.4. However, the use of RCV is more appropriate for Transferrin, Folate, Vitamin B12, and 25-OH Vitamin D.


Effect of 2-Hydroxy-4-Methoxy Benzoic Acid from the Roots of Hemidesmus indicus on Streptozotocin-induced Diabetic Rats.
The aim of the present study was to investigate the effect of 2-hydroxy-4-methoxy benzoic acid isolated from the roots of Hemidesmus indicus on plasma glucose, plasma, erythrocyte and erythrocyte membrane lipid peroxidation and membrane-bound Ca(2+) ATPase activity in streptozotocin-induced diabetic rats. In our study, diabetic rats had increased levels of blood glucose and lipid peroxidation in plasma, erythrocytes and erythrocyte membrane and decreased level of plasma insulin and decreased activity of low affinity Ca(2+) ATPase in erythrocytes. Restoration of plasma insulin and glucose in diabetic rats indicates the effect of HMBA on insulin, glucose and lipid peroxidation. HMBA also restored diabetes-induced alterations in the activity of membrane-bound Ca(2+) ATPase. Based on the results of this study it can be concluded that HMBA mediated normalization of membrane-bound ATPase in erythrocytes is due to improved glycemic control and antioxidant activity.


F-RAG: Generating Atomic Coordinates from RNA Graphs by Fragment Assembly.
Coarse-grained models represent attractive approaches to analyze and simulate ribonucleic acid (RNA) molecules, for example, for structure prediction and design, as they simplify the RNA structure to reduce the conformational search space. Our structure prediction protocol RAGTOP (RNA-As-Graphs Topology Prediction) represents RNA structures as tree graphs and samples graph topologies to produce candidate graphs. However, for a more detailed study and analysis, construction of atomic from coarse-grained models is required. Here we present our graph-based fragment assembly algorithm (F-RAG) to convert candidate three-dimensional (3D) tree graph models, produced by RAGTOP into atomic structures. We use our related RAG-3D utilities to partition graphs into subgraphs and search for structurally similar atomic fragments in a data set of RNA 3D structures. The fragments are edited and superimposed using common residues, full atomic models are scored using RAGTOP's knowledge-based potential, and geometries of top scoring models is optimized. To evaluate our models, we assess all-atom RMSDs and Interaction Network Fidelity (a measure of residue interactions) with respect to experimentally solved structures and compare our results to other fragment assembly programs. For a set of 50 RNA structures, we obtain atomic models with reasonable geometries and interactions, particularly good for RNAs containing junctions. Additional improvements to our protocol and databases are outlined. These results provide a good foundation for further work on RNA structure prediction and design applications.


The association between disability and cognitive impairment in an elderly Tanzanian population.
Cognitive impairment is thought to be a major cause of disability worldwide, though data from sub-Saharan Africa (SSA) are sparse. This study aimed to investigate the association between cognitive impairment and disability in a cohort of community-dwelling older adults living in Tanzania. The study cohort of 296 people aged 70years and over was recruited as part of a dementia prevalence study. Subjects were diagnosed as having dementia or mild cognitive impairment according to the DSM-IV criteria. Disability level was assessed according to the WHO Disability Assessment Schedule, version 2.0 (WHODAS). A higher WHODAS score indicates greater disability. The median WHODAS in the background population was 25.0; in those with dementia and in those with mild cognitive impairment, 72 of 78 (92.3%) and 41 of 46 (89.1%), respectively, had a WHODAS score above this level. The presence of dementia, mild cognitive impairment, hearing impairment, being unable to walk without an aid and not having attended school were independent predictors of having a WHODAS score above 25.0, though age and gender were not. In summary, cognitive impairment is a significant predictor of disability in elderly Tanzanians. Screening for early signs of cognitive decline would allow management strategies to be put in place that may reduce the associated disability burden.


Impact of overlapping newer generation drug-eluting stents on clinical and angiographic outcomes: pooled analysis of five trials from the international Global RESOLUTE Program.
Overlapping first generation sirolimus- and paclitaxel-eluting stents are associated with persistent inflammation, fibrin deposition and delayed endothelialisation in preclinical models, and adverse angiographic and clinical outcomes--including death and myocardial infarction (MI)--in clinical studies. To establish as to whether there are any safety concerns with newer generation drug-eluting stents (DES). Propensity score adjustment of baseline anatomical and clinical characteristics were used to compare clinical outcomes (Kaplan-Meier estimates) between patients implanted with overlapping DES (Resolute zotarolimus-eluting stent (R-ZES) or R-ZES/other DES) against no overlapping DES. Additionally, angiographic outcomes for overlapping R-ZES and everolimus-eluting stents were evaluated in the randomised RESOLUTE All-Comers Trial. Patient level data from five controlled studies of the RESOLUTE Global Clinical Program evaluating the R-ZES were pooled. Enrollment criteria were generally unrestrictive. 5130 patients. 2-year clinical outcomes and 13-month angiographic outcomes. 644 of 5130 patients (12.6%) in the RESOLUTE Global Clinical Program underwent overlapping DES implantation. Implantation of overlapping DES was associated with an increased frequency of MI and more complex/calcified lesion types at baseline. Adjusted in-hospital, 30-day and 2-year clinical outcomes indicated comparable cardiac death (2-year overlap vs non-overlap: 3.0% vs 2.1%, p=0.36), major adverse cardiac events (13.3% vs 10.7%, p=0.19), target-vessel MI (3.9% vs 3.4%, p=0.40), clinically driven target vessel revascularisation (7.7% vs 6.5%, p=0.32), and definite/probable stent thrombosis (1.4% vs 0.9%, p=0.28). 13-month adjusted angiographic outcomes were comparable between overlapping and non-overlapping DES. Overlapping newer generation DES are safe and effective, with comparable angiographic and clinical outcomes--including repeat revascularisation--to non-overlapping DES.


Optimal and efficient crossover designs under different assumptions about the carryover effects.
In certain studies it is desirable or necessary that a subject, such as a patient in a medical trial, receive a treatment in each period. This facilitates a within-subject comparison of the treatments. Designs for studies of this type are called crossover designs or repeated measurements designs. If there are s subjects in p periods, the design should specify which of the t treatments is assigned to subject j in period i, i = 1,... ,p,j = 1,..., s. Equivalently we may think of a design as assigning each subject to one of the t(p) possible treatment sequences. The choice of a design will clearly depend on the values of p, s, and t, to which we will refer as the design parameters. But for any set of design parameters, we will typically still have many design choices. To distinguish between different designs for the same design parameters, we will compare the designs under criteria that are related to the objective of the study. Often the objective is a comparison of the treatments, and we would choose a design that, in some sense, provides good estimates of the treatment differences. For these criteria, a design that is optimal under one statistical model may not be optimal under another. It is therefore also of interest to identify designs that are efficient (relative to an optimal design) for more than one model. The main difference in the models that we will consider is in how the possible first-order carryover effects are modeled. This is a controversial issue, and it is by no means our intent to resolve this here. But a design that is efficient under a variety of plausible models is preferable to one that performs well under one model but poorly under another. Our main focus will be on two models. One of these models has been considered extensively in the literature, while the other is relatively new. For selected design parameters, we will compare selected designs under these models.


Quality of standardised patient research reports in the medical education literature: review and recommendations.
In order to assess or replicate the research findings of published reports, authors must provide adequate and transparent descriptions of their methods. We conducted 2 consecutive studies, the first to define reporting standards relating to the use of standardised patients (SPs) in research, and the second to evaluate the current literature according to these standards. Standards for reporting SPs in research were established by representatives of the Grants and Research Committee of the Association of Standardized Patient Educators (ASPE). An extensive literature search yielded 177 relevant English-language articles published between 1993 and 2005. Search terms included: 'standardised patient(s)'; 'simulated patient(s)'; 'objective structured clinical examination (OSCE)', and 'clinical skills assessment'. Articles were limited to those reporting the use of SPs as an outcome measure and published in 1 of 5 prominent health sciences education journals. Data regarding the SP encounter, SP characteristics, training and behavioural measure(s) were gathered. A random selection of 121 articles was evaluated according to 29 standards. Reviewers judged that few authors provided sufficient details regarding the encounter (21%, n = 25), SPs (16%, n = 19), training (15%, n = 15), and behavioural measures (38%, n = 44). Authors rarely reported SP gender (27%, n = 33) and age range (22%, n = 26), whether training was provided for the SPs (39%, n = 47) or other raters (24%, n = 29), and psychometric evidence to support the behavioural measure (23%, n = 25). The findings suggest that there is a need for increased rigor in reporting research involving SPs. In order to support the validity of research findings, journal editors, reviewers and authors are encouraged to provide adequate detail when describing SP methodology.


Differential longitudinal associations between domains of cognitive function and physical function: A 20-year follow-up study.
Cognitive and physical functions are both associated with disability and death. Recent studies have addressed the relationship between cognitive declines and physical declines; however, whether various facets of cognition are diversely associated with specific physical functions is yet to be ascertained. The present work examines the longitudinal associations between fluid and crystallized cognitive functions (Gf and Gc) and physical functions. The sample consisted of 863 community-dwelling older adults (baseline age 60-79 years) from the National Institute for Longevity Sciences - Longitudinal Study of Aging (NILS-LSA). The participants were tested on a set of Gf and Gc tests and physical tests (grip strength and gait speed). We ran a series of Multivariate Latent Growth Curve (MLGC) models. Specifically, we tested the relationship between cognitive and physical functions in terms of baseline performance (intercept) and rate of change (slope). The slope-slope correlations between Gf and physical function were large (grip strength r = 0.64 and gait speed r = 0.68, ps < 0.001). By contrast, the slope correlations between Gc and physical functions were weak (rs ≤ 0.31) and barely or marginally significant (ps ≤ 0.06). The results show that distinct domains of cognitive functions have different associations with physical functions. Namely, the aging-associated declines in the tested physical functions are robustly correlated with the declines in Gf, but are only weakly correlated with the declines in Gc. Therefore, Gc measures may be poor proxies for the patient's frailty and should be considered with caution in clinical assessment.


Amyloidogenic Mutation Promotes Fibril Formation of the N-terminal Apolipoprotein A-I on Lipid Membranes.
The N-terminal amino acid 1-83 fragment of apolipoprotein A-I (apoA-I) has a strong propensity to form amyloid fibrils at physiological neutral pH. Because apoA-I has an ability to bind to lipid membranes, we examined the effects of the lipid environment on fibril-forming properties of the N-terminal fragment of apoA-I variants. Thioflavin T fluorescence assay as well as fluorescence and transmission microscopies revealed that upon lipid binding, fibril formation by apoA-I 1-83 is strongly inhibited, whereas the G26R mutant still retains the ability to form fibrils. Such distinct effects of lipid binding on fibril formation were also observed for the amyloidogenic prone region-containing peptides, apoA-I 8-33 and 8-33/G26R. This amyloidogenic region shifts from random coil to α-helical structure upon lipid binding. The G26R mutation appears to prevent this helix transition because lower helical propensity and more solvent-exposed conformation of the G26R variant upon lipid binding were observed in the apoA-I 1-83 fragment and 8-33 peptide. With a partially α-helical conformation induced by the presence of 2,2,2-trifluoroethanol, fibril formation by apoA-I 1-83 was strongly inhibited, whereas the G26R variant can form amyloid fibrils. These findings suggest a new possible pathway for amyloid fibril formation by the N-terminal fragment of apoA-I variants: the amyloidogenic mutations partially destabilize the α-helical structure formed upon association with lipid membranes, resulting in physiologically relevant conformations that allow fibril formation.


Children not receiving adequate immunization in Ibadan, Nigeria: what reasons and beliefs do their mothers have?
Immunization coverage in most areas in Nigeria has remained low with continued high morbidity and mortality from vaccine preventable diseases. To identify the reasons and beliefs about immunization among mothers whose children have not received adequate immunization or not at all. The study was a descriptive cross sectional survey that involved mothers trading in a large market in Ibadan who had children between the ages of 12 and 23 months. Data were collected by means of a semi-structured questionnaire. Mothers who did not immunize or failed to completely immunize their children were selected for analysis. A total of 248 mothers were interviewed, their mean age was 27.3 5.5 years (range 16 42 yrs). The commonest reasons for incomplete immunization included: non availability of vaccines (26.2%), not being aware of need for additional doses (16.5%) and inconvenient time/venue (13.7%). Logistic regression analysis showed that Mothers with no formal education were about six times more likely than those with secondary education and higher to give reasons related to lack of motivation (95% CI OR = 1.88 17.93). Analysis of the mothers' beliefs on immunization were as follows; 186 (75.0%) believed it was beneficial, 161 (64.9%) believed that immunization will save the life of the child and 129 (52.0%) believed that taking the child to the clinic for immunization wasted a lot oftime. Most mothers in this study agreed that immunization is beneficial. It is therefore recommended that routine immunization be strengthened, vaccines made readily available and mothers educated on the immunization schedule.


Real-time Doppler spectrum analysis: predictive value in defining operable carotid artery disease.
A prospective study compared the sensitivity, specificity, and predictive value of indirect periorbital Doppler screening and direct carotid Doppler interrogation using real-time sound spectrum analysis to detect operable extracranial carotid occlusive disease. The results of noninvasive studies were compared with independently assessed contrast arteriograms of carotid arteries of patients studied for symptomatic cerebrovascular disease. Periorbital Doppler ultrasound was insensitive to carotid stenosis of less than 75% and did not distinguish operable stenosis from inoperable occlusion of the internal carotid artery. Carotid Doppler spectrum analysis was sensitive to 98% of hemodynamically significant disease and correctly discriminated 77% of carotid occlusions, 96% of stenoses larger than 50%, and 70% of stenoses of less than 50%. The predictive value for direct carotid interrogation in identifying carotid occlusion or operable stenosis was 94% and 86%, respectively. Real-time spectrum analysis of direct carotid Doppler signals substantially improves the diagnostic accuracy of noninvasive identification of operable carotid artery disease.


[Treatment of aneurysms in the anterior cerebral circulation].
To analyze the outcome of either surgical or conservative treatment of patients with aneurysms on cerebral arteries. Retrospective study on 114 patients (89 operated and 25 not operated). Clinical state was graded from 0 to V, according to Hunt & Hess (HHG), and the treatment outcome was defined as favorable or poor, according to the modified Glasgow Outcome Score. The outcome was correlated with the type of treatment (operative or conservative), clinical state and aneurysmal localization. Aneurysm was localized mostly on the anterior communicating (33.6%) and middle cerebral arteries (32.8%) and the patients were mostly in HHG II or III (34.4% and 25.2%). HHG after the aneurysmal rupture did not depend on the aneurysmal location (p > 0.05). Favorable treatment outcome was noted: in 74.1% of all operated and in 60% of all conservatively treated patients (p > 0.05); in 81.6% of operated and in 33.3% of not operated patients with HHG = II-III (p < 0.01); in 78.8% of aneurysms of the middle cerebral artery and in 66.7% of those of the anterior communicating artery (p > 0.05); in 73.1% of patients with HHG = III and in 25% of patients with HHG = IV (p < 0.01). Clinical state after the aneurysmal rupture did not depend on its localization. Results were better after the surgical, than after the conservative treatment. Outcome after the surgery depended on the clinical state of the patient, but not on the aneurysmal localization.


[Issues around testicular carcinoma].
Testicular carcinoma is a rare tumour but the most frequently occurring form of cancer in men aged 18-35 years. In metastatic disease, following orchidectomy three or four courses of combination chemotherapy with cisplatin are given. With a general chance of cure of 80-90%, testicular cancer is still regarded as a model for a form of cancer that is curable. Due to this favourable prognosis--and to its rising incidence--the group of people who survive testicular cancer is growing and more attention is being paid to the risk of adverse consequences of treatment: secondary tumours and cardiovascular morbidity. Shared care follow-up for testicular cancer survivors with participation of both primary and secondary care is currently developed.


Trigeminal and occipital peripheral nerve stimulation for craniofacial pain: a single-institution experience and review of the literature.
Treatment of chronic neuropathic pain in the region of the head and face presents a challenge for pain specialists; patients who do not respond to conventional treatment modalities usually continue to suffer from pain due to the lack of reliable medical and surgical approaches. Peripheral nerve stimulation (PNS) has been used to treat neuropathic pain for many decades, but only recently has it been applied systematically to the craniofacial region. To advance the study of this treatment option, the authors present their initial experience with this approach, summarize published data on the use of PNS in treatment of craniofacial pain, and discuss some technical details of the craniofacial PNS procedure. A review of prospectively collected data in 30 patients who underwent PNS surgery for craniofacial pain was performed. The pain location, duration, cause, and previous treatments were analyzed, along with the surgical details, initial and long-term results, complications, and repeated operations. Stimulated nerves in this group included supraorbital (seven patients), infraorbital (six), and occipital (21); in 19 patients more than one nerve was stimulated. Twenty-two patients proceeded with implantation of a permanent system after the trial. Of these, at the time of the latest evaluation (mean follow-up duration 35 months), in two patients the devices had been removed because of pain improvement over time, in three the devices were removed due to loss of effectiveness (two cases) or late infection (one), and the rest are enjoying either complete (15 patients) or partial (two patients) pain relief. Three patients underwent repeated operation due to lead erosion, infection, or migration. Peripheral nerve stimulation appears to be a safe and effective approach in the treatment of craniofacial neuropathic pain. The growing body of literature supports a wider acceptance of this approach in the field of pain surgery.


Role of oleoylethanolamide as a feeding regulator in goldfish.
Oleoylethanolamide (OEA) is a bioactive lipid mediator, produced in the intestine and other tissues, which is involved in energy balance regulation in mammals, modulating feeding and lipid metabolism. The purpose of the present study was to investigate the presence and possible role of OEA in feeding regulation in goldfish (Carassius auratus). We assessed whether goldfish peripheral tissues and brain contain OEA and their regulation by nutritional status. OEA was detected in all studied tissues (liver, intestinal bulb, proximal intestine, muscle, hypothalamus, telencephalon and brainstem). Food deprivation (48 h) reduced intestinal OEA levels and levels increased upon re-feeding, suggesting that this compound may be involved in the short-term regulation of food intake in goldfish, as a satiety factor. Next, the effects of acute intraperitoneal administration of OEA on feeding, swimming and plasma levels of glucose and triglycerides were analysed. Food intake, swimming activity and circulating triglyceride levels were reduced by OEA 2 h post-injection. Finally, the possible interplay among OEA and other feeding regulators (leptin, cholecystokinin, ghrelin, neuropeptide Y, orexin and monoamines) was investigated. OEA actions on energy homeostasis in goldfish could be mediated, at least in part, through interactions with ghrelin and the serotonergic system, as OEA treatment reduced ghrelin expression in the intestinal bulb, and increased serotonergic activity in the telencephalon. In summary, our results indicate for the first time in fish that OEA could be involved in the regulation of feeding, swimming and lipid metabolism, suggesting a high conservation of OEA actions in energy balance throughout vertebrate evolution.


Sequential mitogen stimulation of peripheral blood lymphocytes from chickens inoculated with infectious bursal disease virus.
Chickens were inoculated wih the pathogenic Edgar strain of infectious bursal disease virus at 1 week, 2 weeks, or 1 day of age. In the 3 experiments, phytohemagglutinin stimulation of peripheral blood lymphocytes was significantly decreased on day 3 or 4 after inoculation. Subsequently, on days 7 through 21, stimulations were similar between lymphocytes from inoculated birds and those from control birds. Pokeweed mitogen stimulation was affected minimally in virus-inoculated chickens. In each experiment, on day 7, the spontaneous [3H]thymidine uptake was greater in nonstimulated lymphocyte cultures from inoculated chickens than in such cultures from control chickens. In an additional experiment, chickens 1 week of age were exposed to a pathogenic vaccinal virus given in their water. The vaccinal virus exposure resulted in significant decrease of phytohemagglutinin stimulation of lymphocytes on days 3 and 7 of the experiment. A significant decrease in pokeweed mitogen stimulation was observed on day 10 after inoculation.


Hit or a miss: Concordance between histopathologic-endoscopic findings in gastric mucosal biopsies.
Current literature shows a variable degree of concordance between endoscopic and histopathologic findings in gastric mucosal biopsies. Most prior studies have focused on specific gastric entities such as gastritis in patients with high prevalence of Helicobacter pylori (H. pylori). In this study, we assess concordance between histologic and endoscopic findings in a wide spectrum of targeted as well as non-targeted gastric endoscopic biopsies. We retrospectively reviewed pathology database and slides at Hershey Medical Center to identify 630 gastric mucosal biopsies obtained from 525 consecutive patients. The corresponding clinical and endoscopic findings were retrieved from the electronic medical record. The rate of abnormal endoscopic and histologic findings was 72.9% and 74.4%, respectively, with Cohen's ĸ coefficient of 0.24. There were 444 (70.5%) concordant cases and 186 (29.5%) discordant cases (88 cases with abnormal endoscopy but normal histology, and 98 cases with normal endoscopy but abnormal histology). Some endoscopic findings, in particular, mass, polyp, ulcer, and nodule/papule were highly concordant with abnormal histopathologic findings; while other endoscopic findings such as inflammatory changes, normal and prominent folds were associated with normal and a variety of abnormal histopathology. Multivariate analysis showed no significant association between intestinal metaplasia and H. pylori in this study. Histopathologic-endoscopic correlation in gastric biopsies varies depending on endoscopic mucosal patterns. Intestinal metaplasia may not have a significant association with H. pylori infection in populations with low prevalence of H. pylori.


Biliobiliary fistula. A trap in the surgery of cholelithiasis.
Of 24 cases of abnormal communication between gallbladder and main bile duct occurring in a service specializing in hepatobiliary surgery, jaundice was present in all, but variable in degree and persistence. No particular clinical picture suggested this complication of cholelithiasis, and preoperative diagnosis is rare. At operation, adhesions were strikingly dense, often first suggesting a diagnosis of cancer. The gallbladder, fused to the main bile duct, should not be dissected from it because of the risk of ductal injury. Under these conditions, the gallbladder should be opened peripherally, stones extracted, and a cholangiogram performed to assess the situation. Treatment consists of partial cholecystectomy and closure of a cuff of gallbladder wall over a T tube placed into the main bile duct through the fistula.


Long-term culture of functional liver tissue: three-dimensional coculture of primary hepatocytes and stellate cells.
One of the greatest challenges in the attempt to create functional liver tissue in vitro is the maintenance of hepatocyte-specific functions. The pharmaceutical industry has long awaited the development of engineered liver tissue, which could represent a long-term, inducible, high-fidelity model for high-throughput screening of new drug compounds. It is also anticipated that such engineered models could one day be used in liver transplants, where replacement is limited by chronic donor shortages. As isolated hepatocytes dedifferentiate rapidly in culture the use of hepatocytes in long-term studies has proved to be a difficult challenge. Here we report a system of rat hepatocytes cocultured with primary rat hepatic stellate cells on a biodegradable poly(DL-lactic acid) substratum. These coculture conditions were found to encourage the rapid self-organization of three-dimensional spheroids. The spheroids formed exhibit hepatocyte-specific functionality (CYP-450 activity and albumin secretion) after almost 2 months in static culture.


Spontaneous verbal descriptions of vegans, non-vegan vegetarians, and omnivores and relationships between these descriptions and perceivers' diets.
Participants, 672 US collegians, listed four words/terms that first came to mind when thinking of vegans, non-vegan vegetarians, and omnivores. Participants generated 1264 unique descriptors, which two sets of raters, who were blind to the source of the descriptors, rated on 10 dimensions that included the valence of the descriptors (i.e., positive, negative). A series of multilevel models in which descriptors were nested within persons, found that descriptors referring to environmental issues and health were used more frequently when describing both vegans and vegetarians than when describing omnivores. Descriptors referring to deviance, lifestyle, and politics were used more frequently when describing both vegans and vegetarians than when describing omnivores. Overall, vegans were viewed more negatively than vegetarians who were viewed more negatively than omnivores. These differences were moderated by the extent to which participants restricted meat from their diet. Those who restricted meat from their diets to a greater extent had more negative perceptions and fewer positive perceptions of omnivores, whereas they had more positive perceptions of vegans and vegetarians, and fewer positive perceptions of omnivores. The present study is the first to use spontaneous verbal reports to examine attitudes and perceptions of people based on their eating habits. The results suggest that dietary habits can serve as a basis for social identity, which in turn affects perceptions of others.