HELMINTH FAUNA OF THECADACTYLUS RAPICAUDA (HOUTTUYN, 1782) (SQUAMATA, PHYLLODACTYLIDAE) IN THE CAXIUANÃ NATIONAL FOREST, FROM THE BRAZILIAN EASTERN AMAZON.
The Amazon region is an important region for biodiversity, and many new species are described for this region each year. However, the diversity of parasites infecting Amazonian reptiles is still poorly known, and there are few studies about how parasite communities of these hosts are structured. Our study was designed to elucidate the parasite community structure of Thecadactylus rapicauda, one of the largest species of gekkonid lizards in the world, and to discover the relative utility of size, sex, and body mass of Thecadactylus rapicauda as predictive factors of the abundance of helminth parasites. We analyzed 40 individuals of T. rapicauda, of which 34 had parasites (85% of prevalence), with 269 specimens allocated to 10 species. Body size of the host showed a positive influence on the abundance of helminths. Host sex is another important factor related to the abundance of nematodes: females were usually heavily infected. We conclude that T. rapicauda has a high richness of the helminth species and that most of the species found infecting this host were nematodes with a direct life cycle. Additionally, we found new helminth species, which should be described formally in the future.


Chromosomal mosaicism detected during preimplantation genetic screening: results of a worldwide Web-based survey.
Embryonic mosaicism, the presence of more than one distinct cell line within an embryo, has recently become the focus of growing attention and controversy in the context of preimplantation genetic screening (PGS). To evaluate the extent of mosaic aneuploidy in clinical practice and to gain insight on the practices and views regarding this issue, we conducted a survey using a prospective, 20-item Web-based questionnaire with questions related to practices and views regarding mosaicism in PGS. A total of 102 in vitro fertilization (IVF) units from 32 countries that performed 108,900 IVF cycles annually responded to the survey. More than half responded that embryonic mosaic aneuploidy is reported by the laboratory, but 31.9% stated that samples are reported as euploid or aneuploid only. If mosaic aneuploidy is reported, 46% stated that it was present in ≤10% of the embryos. More than two-thirds were of the opinion that next-generation sequencing is required to reliably detect mosaicism. Among centers performing PGS, 47.9% consider embryonic mosaicism when detected in >20% of the cells, and nearly two-thirds believe that mosaic aneuploid embryos should be stored for potential therapeutic use after extensive and appropriate counseling. In summary, mosaicism has always existed in preimplantation embryos, and new technologies can now detect its presence with higher resolution. More studies are needed before definite conclusions can be drawn.


Soy consumption during menopause.
In developed countries, the life expectancy of women is currently extending more than 30 years beyond the age of menopause. The menopausal transition is often associated with complaints. The conflicting results on the effectivity of phytoestrogens to alleviate menopausal symptoms. This discrepancy in treatment effect may be due to the large interindividual variation in isoflavone bioavailability in general and equol production in particular. Equol, a microbial metabolite of daidzein, has been hypothesized as a clue to the effectiveness of soy and its isoflavones, but only about 30-50% of the population harbor an intestinal microbial ecosystem supporting the conversion of daidzein into equol. There is much concern on breast cancer, since this incidence of this disease increases with age. There is indication that soy phytoestrogens may decrease this breast cancer incidence. In order to evaluate the estrogenic potential of these exposure levels, we studied the isoflavone-derived E2α- and E2β-equivalents (i.e. 17β-estradiol (E2)-equivalents towards ERα and ERβ, respectively) in human breast tissue. Total isoflavones showed a breast adipose/glandular tissue distribution of 40/60 and their derived E2β-equivalents exceeded on average 21 ± 4 and 40 ± 10 times the endogenous E2 concentrations in corresponding adipose and glandular biopsies, respectively, whereas the E2α/E2 ratios were 0.4 ± 0.1 and 0.8 ± 0.2 in adipose and glandular breast tissue, respectively. These calculations suggest that, at least in this case, soy consumption could elicit partial ERβ agonistic effects in human breast tissue. We are currently characterizing the differential activation of estrogen-responsive genes between dietary isoflavones, the chemopreventive selective ER modulators tamoxifen and raloxifene and exogenous estrogens in a controlled dietary intervention trial that integrates data on the exposure to estrogenically active compounds, expression of isoflavone and estrogen target genes, and epigenetic events. During the menopause, there is a close relation between the drop in serum estrogen and negative metabolic changes such as the increase in bone resorption and negative change in the serum lipid profile. Randomized controlled trials measuring bone turnover markers in menopausal women revealed that soy isoflavone supplements significantly but moderately decrease the bone resorption marker urinary deoxypyridinoline without significant effects on the bone formation markers serum bone alkaline phosphatase and osteocalcin.


Discovering Students' Personalised Uses of a Paediatrics Acute Care E-book - a Qualitative study.
This article was migrated. The article was marked as recommended. Background: Medical educators are increasingly developing and recommending e-books to supplement students' learning. Despite this, there is a gap in the literature surrounding E-book developers' understanding of how students can personalize an e-book for multiple different purposes. This qualitative research project aimed to explore students' experiences of using a pediatric acute care E-book (pRRAPID) within a spiral, multi-method teaching package. The researchers aimed to get an insight into the ways that learners used E-books outside of the classroom. Methods: Three focus groups were conducted with 12 fourth-year medical students who had completed a pediatric acute care course. Students were invited to discuss their use of the E-book during the course. Thematic analysis was conducted on the transcripts to identify codes in the data; these were grouped to determine the overarching themes. Results: Students outlined five different ways that they personalized the use of the E-book. Three of these were related to uses of the E-book within the context of the pediatric acute care course; students using the E-book to prepare for a formal teaching session ("Flipped classroom"),students using the E-book as a workbook (going from start to end) and students using the E-book to prepare for an exam. The other two themes related to the use of the E-book outside of the acute care course; students using the E-book as a resource "on the go" and students using the E-book within clinical practice. Conclusions This qualitative study outlines how an educational resource can be utilized in numerous different ways in order to satisfy the needs of the student. Focus-group participants outlined how important it was to engage with the students, as the primary stakeholder, when developing an E-book.


A non-aqueous synthesis of TiO₂/SiO₂ composites in supercritical CO₂ for the photodegradation of pollutants.
Titania/silica composites with different Ti/Si ratios are synthesized via a nonconventional synthesis route. The synthesis involves non-aqueous reaction of metal alkoxides and formic acid at 75 °C in supercritical carbon dioxide. The as-prepared composite materials contain nanometer-sized anatase crystallites and amorphous silica. Large specific surface areas are obtained. The composites are evaluated in the photocatalytic degradation of phenol in aqueous medium, and in the elimination of acetaldehyde from air. The highest photocatalytic activity in both processes is achieved with a composite containing 40 wt % TiO₂.


Salicylic Acid Acts Antagonistically to Plastid Retrograde Signaling by Promoting the Accumulation of Photosynthesis-associated Proteins in Arabidopsis.
Plastids are involved in phytohormone metabolism as well as photosynthesis. However, the mechanism by which plastid retrograde signals and phytohormones cooperatively regulate plastid biogenesis remains elusive. Here, we investigated the effects of an inhibitor and a mutation that generate biogenic plastid signals on phytohormones and vice versa. Inhibition of plastid biogenesis by norflurazon (NF) treatment and the plastid protein import2 (ppi2) mutation caused a decrease in salicylic acid (SA) and jasmonic acid (JA). This effect can be attributed in part to the altered expression of genes involved in the biosynthesis and the metabolism of SA and JA. However, SA-dependent induction of the PATHOGENESIS-RELATED1 gene was virtually unaffected in NF-treated plants and the ppi2 mutant. Instead, the level of chlorophyll in these plants was partially restored by the exogenous application of SA. Consistent with this observation, the levels of some photosynthesis-associated proteins increased in the ppi2 and NF-treated plants in response to SA treatment. This regulation in true leaves seems to occur at the posttranscriptional level since SA treatment did not induce the expression of photosynthesis-associated genes. In salicylic acid induction deficient 2 and lesions simulating disease resistance 1 mutants, endogenous SA regulates the accumulation of photosynthesis-associated proteins through transcriptional and posttranscriptional mechanisms. These data indicate that SA acts antagonistically to the inhibition of plastid biogenesis by promoting the accumulation of photosynthesis-associated proteins in Arabidopsis, suggesting a possible link between SA and biogenic plastid signaling.


Leprosy Scenario at a Tertiary Level Hospital in Delhi: A 5-year Retrospective Study.
Leprosy has been officially eliminated from India since December, 2005; still, there are districts and blocks reporting high prevalence indicating ongoing transmission. The present study aimed at determining the current clinical profile of leprosy from a tertiary level hospital in Delhi. A retrospective, record-based study was carried out on patients diagnosed and registered in the leprosy clinic of a tertiary level teaching hospital in East district of Delhi (April 2007 to March 2012). Data regarding demographic details, clinical features, treatment started and complications was analyzed. A total of 849 patients were registered over a 5-year period, with M: F ratio of 2.3:1. 9.3% were children (≤14 years). 54.3% patients were immigrants from adjoining states. Multibacillary leprosy was the most common clinical type (86.9%). Borderline tuberculoid leprosy was the most frequent morphologic type, seen in 56.3% followed by borderline-borderline (1.5%), borderline lepromatous (24.9%), lepromatous leprosy (8.1%), pure neuritic (8.1%), histoid and indeterminate leprosy (0.5% each). 37.4% patients presented in reaction (Type I in 30.4% cases and Type II in 7% cases). WHO grade II deformities were diagnosed in 37.9% with claw hand being the most common paralytic deformity (23.3% cases). Our study offers insight into the current status of the disease in an area of otherwise low prevalence. It is seen that despite statistical elimination, multibacillary disease, leprosy reactions and deformities are commonly seen as presenting manifestations, in contrast to national projected trends. Delhi's unique demography with a high degree of migrant workers, presenting to our center (near border location) could be a possible contributing factor towards these aberrations. It highlights the need for continuation of targeted leprosy control activities and active case detection.


Population genetic testing and SERPINA1 sequencing identifies unidentified alpha-1 antitrypsin deficiency alleles and gene-environment interaction with hepatitis C infection.
Alpha-1 antitrypsin deficiency (AATD), a relatively common autosomal recessive genetic disorder, is underdiagnosed in symptomatic individuals. We sought to compare the risk of liver transplantation associated with hepatitis C infection with AATD heterozygotes and homozygotes and determine if SERPINA1 sequencing would identify undiagnosed AATD. We performed a retrospective cohort study in a deidentified Electronic Health Record (EHR)-linked DNA biobank with 72,027 individuals genotyped for the M, Z, and S alleles in SERPINA1. We investigated liver transplantation frequency by genotype group and compared with hepatitis C infection. We performed SERPINA1 sequencing in carriers of pathogenic AATD alleles who underwent liver transplantation. Liver transplantation was associated with the Z allele (ZZ: odds ratio [OR] = 1.31, p<2e-16; MZ: OR = 1.02, p = 1.2e-13) and with hepatitis C (OR = 1.20, p<2e-16). For liver transplantation, there was a significant interaction between genotype and hepatitis C (ZZ: interaction OR = 1.23, p = 4.7e-4; MZ: interaction OR = 1.11, p = 6.9e-13). Sequencing uncovered a second, rare, pathogenic SERPINA1 variant in six of 133 individuals with liver transplants and without hepatitis C. Liver transplantation was more common in individuals with AATD risk alleles (including heterozygotes), and AATD and hepatitis C demonstrated evidence of a gene-environment interaction in relation to liver transplantation. The current AATD screening strategy may miss diagnoses whereas SERPINA1 sequencing may increase diagnostic yield for AATD, stratify risk for liver disease, and inform clinical management for individuals with AATD risk alleles and liver disease risk factors.


[Botallo's duct calcification in children: radiologic findings].
Calcification of the ductus and ligamentum Botalli with no cardio-respiratory symptoms is normally a sign of their closure. However, as the calcification can be associated with a patent duct or a ductal aneurysm, its presence must not be misinterpreted. The frequency and the different patterns of this calcification must be known, as well as is diagnostic relevance. It is also important to differentiate it from other types of upper mediastinal calcification. Thirty-two cases of ducts Botalli calcification were collected over 16 years, during which time period 38,476 children (24,095 males, 14,381 females) were submitted to chest radiography. Patient populations were divided into the following age-groups: preterms-newborns; 2-3 months; 4-6 months; 7-12 months; 2-3 years; 4-6 years; 7-10 years; 11 years on. We studied the ductus Botalli according to the following parameters; conspicuity, location, size and shape of the calcification; prevalence of the radiographic finding in 1,000 patients by gender and age; persistence of the finding in follow-up examinations. The calcification was found in left mediastinal site at the posterior aspect of the 4-6th ribs, ranging 1-6 mm in length, and 1-4 mm in width. It had a round, comma-like or elongated shape. In all, 32 cases of ductal calcification (.83/1000) were found: 14 (44%) were in males (age range 7 months-12 years), 18 (56%) in females (age range 11 months-10 years). Age range analysis shows that the calcification is distributed more evenly in the male population with the highest number of calcified ducts (5 = 94/1000) found in the 4-6 year age group and a relative prevalence in the age group 7-12 months (2 cases = 1.05/1000). A marked prevalence is found in females 4-6 years old (11 cases = 3.8/1000). The duct calcification was an occasional finding during chest radiography for other, more severe conditions in 9 of 14 males and in 6 of 18 females. No data can be found in the literature on the frequency of ductus Botalli calcification at chest radiography: our results indicate it to be less than 1/1000 (.83/1000). We have found a prevalence of ductus calcification (1.25/1000) in females even though females are less numerous in our population. The ductal calcification is often associated with severe, mostly hematologic, diseases. We believe that the conspicuity of the calcification is due to its density more than to its shape and size. Literature data indicate that ductus calcification may still be visible 6 months to 8 years after its discovery: our results, although on a small series, confirm this observation. The clinical significance of the calcification is still unclear.


Effect of sodium-potassium-dependent ATPase inhibition on noradrenaline-activated calcium sensitivity of mesenteric resistance vessels in adult spontaneously hypertensive rats.
1. We have investigated the noradrenaline-activated calcium sensitivity of 150 micrometer mesenteric resistance blood vessels from spontaneously hypertensive and control Wistar-Kyoto rats. 2. Under control conditions the spontaneously hypertensive rat blood vessels had a greater calcium sensitivity than the Wistar-Kyoto rat vessels. 3. In the presence of 1 mmol of ouabain/l, a treatment known to inhibit the sodium-potassium-dependent ATPase, the responses of the spontaneously hypertensive rat blood vessels were reduced more than those of the Wistar-Kyoto rat blood vessels, so that the responses of spontaneously hypertensive rat and Wistar-Kyoto rat blood vessels were then similar. 4. Similar results were obtained by removing external potassium, a procedure which should also inhibit the sodium-potassium-ATPase. 5. The results suggest that the greater noradrenaline-activated calcium sensitivity of spontaneously hypertensive rat blood vessels may be associated with an increased sodium-potassium-ATPase activity.


Dynamic interactions between a membrane binding protein and lipids induce fluctuating diffusivity.
Pleckstrin homology (PH) domains are membrane-binding lipid recognition proteins that interact with phosphatidylinositol phosphate (PIP) molecules in eukaryotic cell membranes. Diffusion of PH domains plays a critical role in biological reactions on membrane surfaces. Although diffusivity can be estimated by long-time measurements, it lacks information on the short-time diffusive nature. We reveal two diffusive properties of a PH domain bound to the surface of a PIP-containing membrane using molecular dynamics simulations. One is fractional Brownian motion, attributed to the motion of the lipids with which the PH domain interacts. The other is temporally fluctuating diffusivity; that is, the short-time diffusivity of the bound protein changes substantially with time. Moreover, the diffusivity for short-time measurements is intrinsically different from that for long-time measurements. This fluctuating diffusivity results from dynamic changes in interactions between the PH domain and PIP molecules. Our results provide evidence that the complexity of protein-lipid interactions plays a crucial role in the diffusion of proteins on biological membrane surfaces. Changes in the diffusivity of PH domains and related membrane-bound proteins may in turn contribute to the formation/dissolution of protein complexes in membranes.


An Open Source, Iterative Dual-Tree Wavelet Background Subtraction Method Extended from Automated Diffraction Pattern Analysis to Optical Spectroscopy.
Background subtraction is a general problem in spectroscopy often addressed with application-specific techniques, or methods that introduce a variety of implementation barriers such as having to specify peak-free regions of the spectrum. An iterative dual-tree complex wavelet transform-based background subtraction method (DTCWT-IA) was recently developed for the analysis of ultrafast electron diffraction patterns. The method was designed to require minimal user intervention, to support streamlined analysis of many diffraction patterns with complex overlapping peaks and time-varying backgrounds, and is implemented in an open-source computer program. We examined the performance of DTCWT-IA for the analysis of spectra acquired by a range of optical spectroscopies including ultraviolet-visible spectroscopy (UV-Vis), X-ray photoelectron spectroscopy (XPS), and surface-enhanced Raman spectroscopy (SERS). A key benefit of the method is that the user need not specify regions of the spectrum where no peaks are expected to occur. SER spectra were used to investigate the robustness of DTCWT-IA to signal-to-noise levels in the spectrum and to user operation, specifically to two of the algorithm parameter settings: decomposition level and iteration number. The single, general DTCWT-IA implementation performs well in comparison to the different conventional approaches to background subtraction for UV-Vis, XPS, and SERS, while requiring minimal input. The method thus holds the same potential for optical spectroscopy as for ultrafast electron diffraction, namely streamlined analysis of spectra with complex distributions of peaks and varying signal levels, thus supporting real-time spectral analysis or the analysis of data acquired from different sources.


Interactive Visualization of 3D Histopathology in Native Resolution.
We present a visualization application that enables effective interactive visual analysis of large-scale 3D histopathology, that is, high-resolution 3D microscopy data of human tissue. Clinical work flows and research based on pathology have, until now, largely been dominated by 2D imaging. As we will show in the paper, studying volumetric histology data will open up novel and useful opportunities for both research and clinical practice. Our starting point is the current lack of appropriate visualization tools in histopathology, which has been a limiting factor in the uptake of digital pathology. Visualization of 3D histology data does pose difficult challenges in several aspects. The full-color datasets are dense and large in scale, on the order of 100,000 × 100,000× 100 voxels. This entails serious demands on both rendering performance and user experience design. Despite this, our developed application supports interactive study of 3D histology datasets at native resolution. Our application is based on tailoring and tuning of existing methods, system integration work, as well as a careful study of domain specific demands emanating from a close participatory design process with domain experts as team members. Results from a user evaluation employing the tool demonstrate a strong agreement among the 14 participating pathologists that 3D histopathology will be a valuable and enabling tool for their work.


Comparison of standards in training and non-training practices.
The in-practice component of vocational training should take place in practices working to high clinical and teaching standards. By means of a survey of its members, the Severn Faculty of the Royal College of General Practitioners was able to compare training practices with the criteria of the Joint Committee on Postgraduate Training for General Practice, and with non-training practices. The training practices fell short of the criteria in a few areas, but the differences between the training and non-training practices were extensive. Progress towards achieving the standards set by the criteria should be monitored, and the criteria themselves should be made more precise.


Master World Records show minor gender differences of performance decline with aging.
Aging behaviours are significantly different in females and males, e.g., the former have a longer life expectancy, but consistently a weaker muscle force. Our purpose is to analyse possible gender-differential declines of skeletal muscle performance. The method to find out the decline of performances with aging is based on a parametric analysis of the World Records of Master athletes in different Track and Field events. The analysis is a transformation (normalization) of sports results into dimensionless parameters ranging from the maximum value of 1 (for the absolute world record) to decreasing values with decreasing performances. Master athletes compete in age groups of 5 years till the age of 100 years, thus their World Records are lists of up to 16 data. Results of the normalization procedure are trend-lines indicating that the decline starts not later than the age of thirty years for both women and women. The decline with aging of the muscle performances indicates only minor gender differences in the aging process and all trend-lines tend to zero at about the age of 110 years. The approach, making use of a homogeneous cohort of testers, gets rid of the main confounding factors biasing other kind of studies of the muscle performance decline with aging, in particular clinical studies. Comparing normalized female and male World Records of Master athletes, a surprise emerged: aging decline is very similar, if not identical, the unique exception to the general rule of gender differences in sports activities. The substantial identity of decline trends among females and males suggests that neuro-hormonal differences among genders poorly influence the aging decline, being conceivably related to fundamental cell bioregulators, such as those of cellular energy metabolism and/or their epigenetic regulatory mechanisms.


Connect: Cultivating Academic-Community Partnerships to Address Our Communities' Complex Needs During Public Health Crises.
Black and Latino communities have been disproportionately impacted by coronavirus disease 2019 and we sought to understand perceptions and attitudes in four heavily impacted New Jersey counties to develop and evaluate engagement strategies to enhance access to testing. To establish a successful academic/community partnership team during a public health emergency by building upon longstanding relationships and using principles from community engaged research. We present a case study illustrating multiple levels of engagement, showing how we successfully aligned expectations, developed a commitment of cooperation, and implemented a research study, with community-based and health care organizations at the center of community engagement and recruitment. This paper describes successful approaches to relationship building including information sharing and feedback to foster reciprocity, diverse dissemination strategies to enhance engagement, and intergenerational interaction to ensure sustainability. This model demonstrates how academic/community partnerships can work together during public health emergencies to develop sustainable relationships.


Hyponatremia Promotes Cancer Growth in a Murine Xenograft Model of Neuroblastoma.
In cancer patients, hyponatremia is detected in about 40% of cases at hospital admission and has been associated to a worse outcome. We have previously observed that cancer cells from different tissues show a significantly increased proliferation rate and invasion potential, when cultured in low extracellular [Na+]. We have recently developed an animal model of hyponatremia using Foxn1nu/nu mice. The aim of the present study was to compare tumor growth and invasivity of the neuroblastoma cell line SK-N-AS in hyponatremic vs. normonatremic mice. Animals were subcutaneously implanted with luciferase-expressing SK-N-AS cells. When masses reached about 100 mm3, hyponatremia was induced in a subgroup of animals via desmopressin infusion. Tumor masses were significantly greater in hyponatremic mice, starting from day 14 and until the day of sacrifice (day 28). Immunohistochemical analysis showed a more intense vascularization and higher levels of expression of the proliferating cell nuclear antigen, chromogranin A and heme oxigenase-1 gene in hyponatremic mice. Finally, metalloproteases were also more abundantly expressed in hyponatremic animals compared to control ones. To our knowledge, this is the first demonstration in an experimental animal model that hyponatremia is associated to increased cancer growth by activating molecular mechanisms that promote proliferation, angiogenesis and invasivity.


Nut consumption for vascular health and cognitive function.
Nuts are rich in many nutrients that can benefit multiple cardiometabolic functions, including arterial compliance, blood pressure, inflammation, glucoregulation and endothelial vasodilatation. Impaired vasodilatation may contribute to impaired cognitive performance due to poor cerebral perfusion. The present narrative review examines associations between nut consumption, vascular health and cognitive function. It includes a systematic search which identified seventy-one epidemiological or intervention studies in which effects of chronic nut consumption on blood pressure, glucoregulation, endothelial vasodilator function, arterial compliance, inflammatory biomarkers and cognitive performance were evaluated. Weighted mean changes were estimated where data were available; they indicate that nut consumption reduces blood pressure and improves glucoregulation, endothelial vasodilator function and inflammation, whilst a limited number of studies suggest that nut consumption may also improve cognitive performance. Further clinical trials are warranted to explore relationships between nut consumption, endothelial function and cognitive function.


Gall bladder and extrahepatic bile duct lymphomas: clinicopathological observations and biological implications.
Lymphomas of the gall bladder and extrahepatic bile ducts are exceedingly rare. We present the clinicopathological features of 19 cases from our files; 14 patients had primary lymphoma (13 involving gall bladder and 1 involving common hepatic duct), while 5 had systemic lymphoma on further work-up. Most patients presented with symptoms mimicking cholecystitis. The most common primary lymphoma types were diffuse large B-cell lymphoma, extranodal marginal zone lymphoma, B-lymphoblastic lymphoma, and follicular lymphoma. Two cases had features of lymphomatous polyposis, one a case of follicular lymphoma and the second a case of mantle cell lymphoma, with disease limited to the mantle zones, so-called in situ mantle cell lymphoma. Other rare lymphoma subtypes not described earlier in this site included the extracavitary variant of primary effusion lymphoma and plasmablastic lymphoma. Patients with diffuse large B-cell lymphoma and extranodal marginal zone lymphoma were older (mean age 75.8 y) than those with other subtypes (mean age 47 y) and more likely to have gallstones (60% vs. 12.5%). A comprehensive literature review revealed 36 primary gall bladder and 16 primary extrahepatic bile duct lymphomas. When compared with primary gall bladder lymphomas, those involving the extrahepatic bile ducts present at a younger age (47 y vs. 63 y) usually with obstructive jaundice, and are less often associated with gallstones (17% vs. 50%) or regional lymph node involvement (6% vs. 31%). In conclusion, primary lymphomas of the gall bladder and extrahepatic bile ducts show a broad spectrum of disease types, but in many respects mirror the spectrum of primary lymphomas of the gastrointestinal tract.


Cytostatic, cytotoxic and protein tyrosine kinase inhibitory activity of ursolic acid in A431 human tumor cells.
The effect of the tritepene, ursolic acid, on the proliferation of A431 human epidermoid carcinoma cells was studied. According to our investigations, ursolic acid is a potent inhibitor of A431 cell growth. Ursolic acid markedly reduced A431 cell growth in a time- and dose-dependent manner. We found a good correlation between the results of direct cell counting and the MTT test. During long periods of drug exposure, ursolic acid exhibited both cytotoxic and cytostatic activity. The effect was partially reversible on drug removal. The greatest cytotoxicity was observed both in the trypan blue test and in the MTT test at 50 mM. Investigations on tyrosine kinase inhibition were performed by biochemical and cellular assays on A431 cells. Ursolic acid inhibited tyrosine kinase activity of A431 cells in biochemical assay in a dose-dependent manner with an IC50 of 24 mM. In cellular assay, when A431 cells were pretreated with ursolic acid for 24, 48 and 168 hours at various concentrations (5, 10, 20, 30 and 50 mM), lower values of IC50 were measured: 6.8 microM for 24 hours, 5.2 mM for 48 hours and 1.4 mM for 168 hours. The results suggest that ursolic acid exerts an antiproliferative effect through the inhibition of tyrosine kinase enzymes.


[Seasonal evolution of the biogeochemical cycle in the southwest lagoon of New Caledonia. Application of a compartmental model].
A biogeochemical box model describing the south-west lagoon of New-Caledonia was developed in order to simulate the seasonal cycle of carbon and nitrogen. We used fluxes generated by a 3D hydrodynamic model to simulate horizontal exchanges between boxes and added freshwater influxes as nitrogen sources from the land. Average residence time proved to be less than 11 days for the lagoon as a whole. Standard simulations showed baseline values of chlorophyll a between 0.2 and 0.4 microgram.L-1. Influences of freshwater influxes proved to be significant (increases up to 1 microgram.L-1) only in shallow areas protected from wind exposure and during short periods of heavy rainfall (tropical depressions). Tropical climatic events have reduced impact in space and time and long-term simulations over decades with increased nutrient inputs did not show any significant process of eutrophication. Hydrodynamics seemed to be one of the major control factors with respect to organic matter cycling in the lagoon.


Statins: potentially useful in therapy of systemic sclerosis-related Raynaud's phenomenon and digital ulcers.
Systemic sclerosis (SSc) is characterized by fibrosis and widespread vascular pathology. Raynaud's phenomenon (RP) and digital ulceration are prominent manifestations of vascular involvement in SSc. Digital ulcers (DU) remain a serious complication, and effective therapy remains elusive. Statins display pleiotropic effects on endothelial function that may potentially retard vascular injury. We evaluated the potential efficacy of statin therapy in endothelial dysfunction and in management of RP and DU. Eighty-four SSc patients who fulfilled the American College of Rheumatology criteria for classification of SSc with secondary RP despite ongoing vasodilator therapy were randomized into 2 groups; the first group (n = 56) received 40 mg/day atorvastatin for 4 months; the second group (n = 28) received placebo. Seventy-five healthy volunteers served as controls. Assessment of RP and DU was performed monthly. The primary outcome measure was the number of DU. Secondary endpoints included the modified Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI), safety, and tolerability. Measurement of functional status in relation to RP included the SHAQ-DI, visual analog scale (VAS) for RP, DU and pain scales, and VAS for physician's global assessment for health. Endothelial damage markers were also assessed. Endothelium-dependent flow-mediated dilatation was measured by high-resolution echo-Doppler ultrasonography. The overall number of DU was significantly reduced in the statin group. Among patients in the statin group a mean of 1.6 new ulcers developed per patient compared to 2.5 new ulcers per patient in the placebo group. There was a statistically significant improvement in SHAQ-DI score in patients receiving statin versus those on placebo. VAS for RP, DU severity, and pain scales and the VAS for physician global assessment improved significantly in the statin group compared to the placebo group. Endothelial markers of activation showed statistically significant improvement from baseline values in the statin versus the placebo group. Our results showed that statins retarded vascular injury and improved patient function. The findings suggest that statins may aid in treating RP and DU in SSc patients. Given the safety and relative low cost of statins and good patient tolerability to this class of drugs, statins may be of clinical benefit in SSc patients.


What use is generic prescribing?
The dispensing of generic preparations at four dispensing chemist shops was investigated by means of a questionnaire. Certain generic prescriptions result in the dispensing of proprietary products despite the existence of generic preparations, and the pharmacist may be reimbursed for the cost of the proprietary drug which has been dispensed. Not all generic prescriptions result in the dispensing of cheaper drugs because of the methods of payment to chemists. If doctors write more generic prescriptions there will ultimately be more dispensing of generic products. Even in the case of drugs still under patent, prescribing by generic name should be encouraged. The savings achieved by generic prescribing are to some extent at the cost of the dispensing chemists. The method and scale of payments for dispensing requires urgent review.


What are the patterns of prophylactic postoperative oral antibiotic use after foot and ankle surgery?
The CDC estimates 23% of healthcare-associated infections to be surgical site infections, with alarming prevalence of antibiotic-resistant organisms. While there is consensus regarding preoperative prophylaxis, orthopaedic surgeons' use of prophylactic postoperative oral antibiotics is less defined. We investigated surgeons' use of prophylactic postoperative oral antibiotics after elective outpatient foot or ankle procedures, identifying (1) frequency of use, (2) regimen preferences, (3) personal indications, and (4) associated experience and demographics. Using a cross-sectional survey design, a questionnaire was emailed to all active and candidate members of the American Orthopaedic Foot and Ankle Society. Supplementary questions captured demographic information. We invited 1136 members to participate; 22 addresses produced delivery failure messages, leaving 1114 members as potential participants. After nonresponses and exclusions, 312 (28%) responses were analyzed. Statistical analysis used Pearson's chi-square test, Fisher's exact test, and multivariate regression. The majority (75%) of respondents reported use of prophylactic postoperative oral antibiotics. Most users (69%) prescribed to fewer than 25% of patients, although 16% prescribed for all elective cases. The most frequent regimen was cephalexin 500 mg four times a day (63%) and the most common duration was 5 to 7 days (50%). Surgeons' most common indications were previous infection (71%), medical comorbidities (65%), and previous wound-healing difficulties (56%). Those who do and do not prescribe prophylactic postoperative oral antibiotics showed no difference in surgical site infection rate or any demographic category. Surgeons' reported use of prophylactic postoperative oral antibiotics after elective foot or ankle surgery was common, without demographic association. Commonalities were identified in antibiotic regimen and personal indications for this practice. Comparative clinical studies are warranted to elucidate the efficacy of prophylactic postoperative oral antibiotics and establish evidence-based guidelines for their use.


Short-Term Efficacy of an Innovative Mobile Phone Technology-Based Intervention for Weight Management for Overweight and Obese Adolescents: Pilot Study.
In the United States, approximately one-third of adolescents are now overweight or obese, and one in six is obese. This financial cost and the larger nonfinancial costs of obesity make obesity prevention and management for adolescents imperative for the health of the nation. However, primary care visits are typically brief, and primary care providers may lack adequate resources to help overweight or obese adolescents to manage weight issues. To augment the efficacy of primary care visits for adolescent weight management, mobile phone technology can be used as an adjunct treatment that provides additional opportunities for encouraging improvement in lifestyle, attainment, and maintenance of healthy weight. The purposes of this study were to (1) measure effects of an innovative mobile phone technology-based intervention for overweight and obese adolescents and to (2) examine the intervention's feasibility for use in primary care clinics. The mobile phone-based intervention had three components: use of the Fitbit Flex, participation in an online educational program, and receipt of biweekly text messages during the maintenance phase. A randomized controlled study design was utilized. Data regarding anthropometrics (body mass index [BMI] and waist-to-hip ratio), blood pressure, levels of physical and sedentary activity, diet, and self-efficacy regarding physical activity and diet were collected at baseline and at 3 and 6 months after the baseline assessment. A total of 40 adolescents participated in the study. At the 6-month follow-up visit, compared to participants in the control group, the mobile phone-based intervention participants had significant improvement in BMI (z=-4.37, P=.001), diastolic blood pressure (z=-3.23, P=.001), physical activity days per week (z=2.58, P=.01), TV and computer time (z=-3.34, P=.001), servings of fruits and vegetables per day (z=2.74, P=.006), servings of soda and sweetened drinks (z=-3.19, P=.001), physical activity self-efficacy (z=2.75, P=.006), and dietary self-efficacy (z=5.05, P=.001). Medium to large effect sizes were found in these outcome variables. The use of mobile technologies may offer a practical, reliable adjunct to weight management for overweight and obese adolescents in busy primary care clinics serving adolescents. Clinicaltrials.gov NCT 01693250; https://clinicaltrials.gov/ct2/show/NCT01693250? term=Adolescent+ obesity+AND+mhealth&rank=5 (Archived by WebCite at ).


Financial Insecurity and Food Insecurity among U.S. Children with Secondhand and Thirdhand Smoke Exposure.
Objectives: Smokers with financial and food insecurity may find it difficult to quit smoking and reduce their children's tobacco smoke exposure (TSE). The objective was to examine the associations between child TSE and financial and food insecurity among U.S. school-aged children. Methods: We examined the 2018−2019 National Survey of Children's Health data on 17,484 children 6−11 years old. Children were categorized into TSE groups: (1) No TSE: did not live with a smoker; (2) thirdhand smoke (THS) exposure alone: lived with a smoker who did not smoke inside the home; or (3) secondhand smoke (SHS) and THS exposure: lived with a smoker who smoked inside the home. We conducted weighted logistic, ordinal, and linear regression analyses to assess the relationships between child TSE status and financial and food insecurity, adjusting for covariates. Results: Overall, 13.1% and 1.8% of children had THS exposure alone and SHS and THS exposure, respectively. Compared to children with no TSE, children with THS exposure alone were at 2.17 increased odds (95% CI = 1.83, 2.58, p < 0.001) and children with SHS and THS exposure were at 2.24 increased odds (95% CI = 1.57, 3.19, p < 0.001) of having financial insecurity. Children with THS exposure alone were at 1.92 increased odds (95% CI = 1.58, 2.33, p < 0.001) and children with SHS and THS exposure were at 2.14 increased odds (95% CI = 1.45, 3.16, p < 0.001) of having food insecurity. Conclusions: Children with TSE are at increased risk of experiencing financial and food insecurity. When developing tobacco interventions, a holistic approach to tobacco control that addresses ways to decrease financial and food hardships may improve outcomes.


Cortical and subcortical afferents to the nucleus reticularis tegmenti pontis and basal pontine nuclei in the macaque monkey.
Anatomical findings are presented that identify cortical and subcortical sources of afferents to the nucleus reticularis tegmenti pontis (NRTP) and basal pontine nuclei. Projections from the middle temporal visual area (MT), medial superior temporal visual area (MST), lateral intraparietal area (LIP), and areas 7a and 7b to the basal pontine nuclei were studied using 3H-leucine autoradiography. The results complemented a parallel study of retrograde neuronal labeling attributable to injecting WGA-HRP into NRTP and neighboring pontine nuclei. Small 3H-leucine injections confined to MT, MST, LIP, area 7a, or area 7b, produced multiple patches of pontine terminal label distributed as follows: (1) An injection within MT produced terminal label limited to the dorsolateral and lateral pontine nuclei. (2) Injections restricted to MST or LIP showed patches of terminal label in the dorsal, dorsolateral, lateral, and peduncular pontine nuclei. (3) Area 7a targets the dorsal, dorsolateral, lateral, peduncular, and ventral pontine nuclei, whereas area 7b projects, additionally, to the dorsomedial and paramedian pontine nuclei. Notably, no projections were seen to NRTP from any of these cortical areas. In contrast, injections made by other investigators into cortical areas anterior to the central sulcus revealed cerebrocortical afferents to NRTP, in addition to nuclei of the basal pontine gray. With our pontine WGA-HRP injections, retrograde neuronal labeling was observed over a large extent of the frontal cortex continuing onto the medial surface which included the lining of the cingulate sulcus and cingulate gyrus. Significant subcortical sources for afferents to the NRTP and basal pontine nuclei were the zona incerta, ventral mesencephalic tegmentum, dorsomedial hypothalamic area, rostral interstitial nucleus of the medial longitudinal fasciculus, red nucleus, and subthalamic nucleus. The combined anterograde and retrograde labeling data indicated that visuo-motor cortico-pontine pathways arising from parietal cortices target only the basal pontine gray, whereas the NRTP, together with select pontine nuclei, is a recipient of afferents from frontal cortical areas. The present findings implicate the existence of parallel direct and indirect cortico-pontine pathways from frontal motor-related cortices to NRTP and neighboring pontine nuclei.


Development and comparison of a minimally-invasive model of autologous clot pulmonary embolism in Sprague-Dawley and Copenhagen rats.
Experimental models of pulmonary embolism (PE) that produce pulmonary hypertension (PH) employ many different methods of inducing acute pulmonary occlusion. Many of these models induce PE with intravenous injection of exogenous impervious objects that may not completely reproduce the physiological properties of autologous thromboembolism. Current literature lacks a simple, well-described rat model of autlogous PE. Test if moderate-severity autologous PE in Sprague-Dawley (SD) and Copenhagen (Cop) rats can produce persistent PH. blood was withdrawn from the jugular vein, treated with thrombin-Ca++ and re-injected following pretreatment with tranexamic acid. Hemodynamic values, clot weights and biochemical measurements were performed at 1 and 5 days. Infusion of clot significantly increased the right ventricular peak systolic pressure to 45-55 mm Hg, followed by normalization within 24 hours in SD rats, and within 5 days in COP rats. Clot lysis was 95% (24 hours) and 97% (5 days) in SD rats and was significantly lower in COP rats (70%, 24 hours; 87% 5 days). Plasma D-dimer was elevated in surgical sham animals and was further increased 8 hours after pulmonary embolism. Neither strain showed a significant increase in bronchoalveolar chemotactic activity, myeloperoxidase activity, leukocyte infiltration, or chemokine accumulation, indicating that there was no significant pulmonary inflammation. Both SD and COP rats exhibited near complete fibrinolysis of autologous clot PE within 5 days. Neither strain developed persistent PH. Experimental models of PE designed to induce sustained PH and a robust inflammatory response appear to require significant, persistent pulmonary vascular occlusion.


Nuclear factor-kappaB mediates the inhibitory effects of tumor necrosis factor-alpha on growth hormone-inducible gene expression in liver.
TNF inhibits serine protease inhibitor 2.1 (Spi 2.1) and IGF-I gene expression by GH in CWSV-1 hepatocytes. The current study describes construction of a GH-inducible IGF-I promoter construct and investigates mechanisms by which TNF and nuclear factor-kappaB (NFkappaB) inhibit GH-inducible gene expression. CWSV-1 cells were transfected with GH-inducible Spi 2.1 or IGF-I promoter luciferase constructs, incubated with TNF signaling inhibitors (fumonisin B1 for sphingomyelinase and SP600125 for c-Jun N-terminal kinase), treated with or without TNF, and then stimulated with recombinant human GH. The 5- to 6-fold induction of Spi 2.1 and IGF-I promoter activity by GH was inhibited by TNF. Neither fumonisin B1 nor SP600125 prevented the inhibitory effects of TNF on GH-inducible promoter activity. Dominant-negative inhibitor-kappaBalpha (IkappaBalpha) expression vectors (IkappaBalphaS/A or IkappaBalphaTrunc), p65 and p50 expression vectors, and p65 deletion constructs were used to investigate the NFkappaB pathway. IkappaBalphaS/A and IkappaBalphaTrunc ameliorated the inhibitory effects of TNF on GH-inducible Spi 2.1 and IGF-I promoter activity. Cotransfection of CWSV-1 cells with expression vectors for p65 alone or p50 and p65 together inhibited GH-inducible Spi 2.1 and IGF-I promoter activity. Cotransfection with a C-terminal p65 deletion (1-450) enhanced GH-inducible promoter activity, whereas the N-terminal deletion (31-551) was inhibitory for IGF-I but not Spi 2.1. Cycloheximide did not antagonize the inhibitory effects of TNF on GH-inducible IGF-I expression. We conclude the inhibitory effects of TNF on GH-inducible promoter activity are mediated by NFkappaB, especially p65, by a mechanism that does not require protein synthesis.


APOL1, CDKN2A/CDKN2B, and HDAC9 polymorphisms and small vessel ischemic stroke.
Worldwide, the highest frequencies of APOL1-associated kidney variants are found in indigenous West Africans among whom small vessel disease (SVD) ischemic stroke is the most common stroke phenotype. The objective of this study was to investigate the association and effect sizes of 23 selected SNPs in 14 genes of relevance, including the APOL1 G1 variants, with the occurrence of SVD ischemic stroke among indigenous West African participants in the Stroke Investigative Research and Education Network (SIREN) Study. Cases were consecutively recruited consenting adults (aged 18 years or older) with neuroimaging-confirmed first clinical stroke. Stroke-free controls were ascertained using a locally validated version of the Questionnaire for Verifying Stroke-Free Status (QVSFS). Logistic regression models adjusting for known vascular risk factors were fitted to assess the associations of the 23 SNPs in rigorously phenotyped cases (N = 154) of SVD ischemic stroke and stroke-free (N = 483) controls. Apolipoprotein L1 (APOL1) rs73885319 (OR = 1.52; CI: 1.09-2.13, P-value = .013), rs2383207 in CDKN2A/CDKN2B (OR = 3.08; CI: 1.15-8.26, P -value = .026) and rs2107595 (OR = 1.70; CI: 1.12-2.60, P-value = .014) and rs28688791 (OR = 1.52; CI: 1.03-2.26, P-value = .036) in HDAC9 gene were associated with SVD stroke at 0.05 significance level. Polymorphisms in other genes did not show significant associations. This is the first report of a specific association of APOL1 with a stroke subtype. Further research is needed to confirm these initial findings and deepen understanding of the genetics of stroke in people of African ancestry with possible implications for other ancestries as all humans originated from Africa.


Multiple-locus variable number tandem repeats analysis for genetic fingerprinting of pathogenic bacteria.
DNA fingerprinting has attracted considerable interest as means for identifying, tracing and preventing the dissemination of infectious agents. Various methods have been developed for typing of pathogenic bacteria, which differ in discriminative power, reproducibility and ease of interpretation. During recent years a typing method, which uses the information provided by whole genome sequencing of bacterial species, has gained increased attention. Short sequence repeat (SSR) motifs are known to undergo frequent variation in the number of repeated units through cellular mechanisms most commonly active during chromosome replication. A class of SSRs, named variable number of tandem repeats (VNTRs), has proven to be a suitable target for assessing genetic polymorphisms within bacterial species. This review attempts to give an overview of bacterial agents where VNTR-based typing, or multiple-locus variant-repeat analysis (MLVA) has been developed for typing purposes, together with addressing advantages and drawbacks associated with the use of tandem repeated DNA motifs as targets for bacterial typing and identification.


Can newborns discriminate between their own cry and the cry of another newborn infant?
Two experiments were conducted to test whether newborns could discriminate between their own cry and the cry of another newborn infant. Facial behavior and nonnutritive sucking rate were adopted as dependent measures. In Experiment 1, 20 newborns in an awake state were presented with either their own cry or the cry of another infant. In the latter condition, newborns showed the facial expression of distress more frequently and for a longer duration. In addition, the rate of sucking decreased significantly between the pretest phase and the 1st min of presentation of another infant's cry. Newborns' responses, although delayed and less intense, showed a similar trend in Experiment 2, during which 20 newborns in a sleep state were tested with the same procedure. These results indicate the newborns' capability to discriminate between the 2 cry stimuli and show the effectiveness of a newborn cry in inducing distress signals in another newborn infant.


Irradiation and hypoxia promote homing of haematopoietic progenitor cells towards gliomas by TGF-beta-dependent HIF-1alpha-mediated induction of CXCL12.
Previously we defined a pathway of transforming growth factor beta (TGF-beta) and stromal cell-derived factor-1/CXC chemokine ligand 12 (SDF-1alpha/CXCL12) dependent migration of adult haematopoietic stem and progenitor cells (HPC) towards glioma cells in vitro and their homing to experimental gliomas in vivo. Hypoxia is a critical aspect of the microenvironment of gliomas and irradiation is an essential part of the standard therapy. To evaluate the therapeutic potential of HPC as vectors for a cell-based therapy of gliomas, we investigated the impact of hypoxia and irradiation on the attraction of HPC by glioma cells. Temozolomide (TMZ) treatment and hyperthermia served as controls. Supernatants of irradiated or hypoxic LNT-229 glioma cells promote HPC migration in vitro. Reporter assays reveal that the CXCL12 promoter activity is enhanced in LNT-229 cells at 24 h after irradiation at 8 Gy or after exposure to 1% oxygen for 12 h. The irradiation- and hypoxia-induced release of CXCL12 depends on hypoxia inducible factor-1 alpha (HIF-1alpha), but not on p53. Induction of transcriptional activity of HIF-1alpha by hypoxia or irradiation requires an intact TGF-beta signalling cascade. This delineates a novel stress signalling cascade in glioma cells involving TGF-beta, HIF-1alpha and CXCL12. Stress stimuli can be irradiation, hypoxia or TMZ, but not hyperthermia. Cerebral irradiation of nude mice at 21 days after intracerebral implantation of LNT-229 glioma induces tumour satellite formation and enhances the glioma tropism of HPC to the tumour bulk and even to these satellites in vivo. These data suggest that the use of HPC as cellular vectors in the treatment of glioblastoma may well be combined with irradiation or other anti-angiogenic therapies that induce tumour hypoxia.


[Quality of life of women recovering from breast cancer after being subjected to mastectomies compared with those who had conservative surgery: a review of the literature].
This study reviews the literature on the quality of life (QoL) of women with breast cancer who have been subjected to mastectomy, compared with those who had conservative surgery. Eight random controlled trials were selected. The studies were compared with respect to the moment quality of life was assessed (whether during or after treatment for breast cancer), the measurement tools of quality of life used, and also the methodology and results achieved. The results of four studies suggest a stronger negative impact in the QoL of mastectomized women; the other four studies showed no difference between the groups in terms of QoL. Objective measurements of quality of life may help identify potentially critical situations of daily life and assist in planning actions to promote health among women who have been subjected to breast cancer surgery.


Duplex and quadruplex DNA binding and photocleavage by trioxatriangulenium ion.
The stable trioxatriangulenium ion (TOTA) has previously been shown to bind to and photooxidize duplex DNA, leading to cleavage at G residues, particularly 5'-GG-3' repeats. Telomeric DNA consists of G-rich sequences that may exist in either duplex or G-quadruplex forms. We have employed electrospray ionization mass spectrometry (ESI-MS) to investigate the interactions between TOTA and duplex DNA or G-quadruplex DNA. A variety of duplex decamer oligodeoxynucleotides form complexes with TOTA that can be detected by ESI-MS, and the stoichiometry and fragmentation patterns observed are commensurate with an intercalative binding mode. TOTA also forms complexes with four-stranded and hairpin-dimer G-quadruplex oligodeoxynucleotides that can be detected by ESI-MS. Both the stoichiometry and the fragmentation patterns observed by ESI-MS are different than those observed for G-tetrad end-stacking binding ligands. We have carried out (1)H NMR titrations of a four-stranded G-quadruplex in the presence of TOTA. Addition of up to 1 equiv of TOTA is accompanied by pronounced upfield shifts of the G-tetrad imino proton resonances in the NMR, which is similar to the effect observed for G-tetrad end-stacking ligands. At higher ratios of added TOTA, there is evidence for additional binding modes. Duplex DNA containing either human telomeric repeats (T(2)AG(3))(4) or the Tetrahymena telomeric repeats (T(2)G(4))(4) are readily photooxidized by TOTA, the major sites of oxidation being the central guanine residues in each telomeric repeat. These telomeric repeats were incorporated into duplex/quadruplex chimeras in which the repeats adopt a G-quadruplex structure. Analysis by denaturing polyacrylamide gel electrophoresis reveals significantly less TOTA photocleavage of these quadruplex telomeric repeats when compared to the duplex repeats.


How inhibition relates to impulsivity after moderate to severe traumatic brain injury.
Impulsive behaviors and poor inhibition performances are frequently described in patients with traumatic brain injury(TBI). However, few studies have examined impulsivity and associated inhibition impairments in these patients.Twenty-eight patients with moderate to severe TBI and 27 matched controls performed a stop-signal task designed to assess prepotent response inhibition (the ability to inhibit a dominant or automatic motor response) in a neutral or emotional context and a recent negative task to assess resistance to proactive interference (the ability to resist the intrusion into memory of information that was previously relevant but has since become irrelevant). Informants of each patient completed a short questionnaire designed to assess impulsivity. Patients showed a significant increase in current urgency,lack of premeditation, and lack of perseverance when retrospectively compared with the preinjury condition. Group comparisons revealed poorer prepotent response inhibition and resistance to proactive interference performances inpatients with TBI. Finally, correlation analyses revealed a significant positive correlation between urgency (the tendency to act rashly when distressed) and prepotent response inhibition in patients with TBI. This study sheds new light on the construct of impulsivity after a TBI, its related cognitive mechanisms, and its potential role in problematic behaviors described after a TBI.


Broad neurodevelopmental features and cortical anomalies associated with a novel de novo KMT2A variant in Wiedemann-Steiner syndrome.
Wiedemann-Steiner syndrome (WDSTS) is a rare genetic disorder including developmental delay/intellectual disability (DD/ID), hypertrichosis cubiti, short stature, and distinctive facial features, caused by mutation in KMT2A gene, which encodes a histone methyltransferase (H3K4) that regulates chromatin-mediated transcription. Different neurodevelopmental phenotypes have been described within the WDSTS spectrum, including a peculiar Autism Spectrum Disorder (ASDs) subtype in some affected individuals. Here, we report a 9-year-old Caucasian male found by next-generation panel sequencing to carry a novel heterozygous de novo KMT2A frameshift variant (NM_001197104.2:c.4433delG; p. Arg1478LeufsTer108). This boy presented a WDSTS phenotype associated with broad neurodevelopmental features, including an unusual speech difficulty (i.e., palilalia), and brain imaging studies revealed an array of cortical anomalies (e.g., frontal simplified gyration, focal frontal cortical dysplasia). These clinical and radiological observations expand the known WDSTS-related neurodevelopmental phenotypes and further strengthen the important role of KMT2A in brain function and cortical development.


Mechanisms of cartilage precursor replacement by bone in the mammalian skeleton.
The initiation of the endochondral process in ontogenesis is preceded by structural and metabolic preparation of the cells of cartilage anlages of the skeleton as well as the satellite cells of the vascular terminations adjoining the cartilage. In the cartilage anlage, due to a progressive specific biosynthesis, the macromolecular chondroitin-protein complexes capable of binding a large amount of water, are accumulated. As a result the volume of a swelling chondrocyte increases twentyfold or more and a high hydrostatic tension is created within it. At the same time the metabolic situation within the cartilage favours a local concentration, near the hypertrophic chondrocytes, of the perivascular cells possessing an increased resorptive function. The resorption of the cartilage partition walls by these cells leads to the opening of swollen chondrocytes. The blood cells and the cells of the blood capillaries themselves are engulfed through the resulting crater into the emptied lacuna. In the lacuna the conditions of stasis are created which promote local redistribution of the supplied cells and reutilization of the cartilage destruction products. The perivascular cells concentrated along the remnants of the cartilaginous matrix are gradually differentiated into preosteoblasts and osteoblasts. The endosteal bony laminae are built on the remnants of the cartilaginous matrix. The perivascular cells of the apical zone of a lacuna retain their clastic function and continue spreading of the endochondral process on the adjacent chondrocytes. In the course of the successive destruction of hypertrophic chondrocytes, the system of vessels is formed in the endochondral centre, according to the sinusoid pattern.


Prognostic factors of non-ampullary duodenal adenocarcinoma.
Non-ampullary duodenal adenocarcinoma, excluding carcinoma in the ampulla of Vater, is a rare disease. Although several prognostic factors have been reported, they remain controversial due to the rarity of non-ampullary duodenal adenocarcinoma. The aims of this study were to investigate prognostic factors in patients with non-ampullary duodenal adenocarcinoma and to assess chemotherapy in patients with recurrence. Records of 25 patients who underwent surgical treatment for non-ampullary duodenal adenocarcinoma from 2004 to 2016 were retrospectively reviewed. The relationship between the clinicopathological factors and outcomes was investigated. Serum level of CA19-9, gross appearance, tumor size, tumor invasion, lymph node metastases, TNM stage and lymphatic and vascular invasion were significant risk factors of recurrence. Patients with recurrence who received chemotherapy according to regimens used to treat colorectal cancer had a better prognosis than those without chemotherapy (P = 0.016). Advanced non-ampullary duodenal adenocarcinoma has a poor prognosis, but chemotherapy possibly improves the prognosis in the patients with recurrent non-ampullary duodenal adenocarcinoma.


Neuraminidase-1: A Sialidase Involved in the Development of Cancers and Metabolic Diseases.
Sialidases or neuraminidases (NEU) are glycosidases which cleave terminal sialic acid residues from glycoproteins, glycolipids and oligosaccharides. Four types of mammalian sialidases, which are encoded by different genes, have been described with distinct substrate specificity and subcellular localization: NEU-1, NEU-2, NEU-3 and NEU-4. Among them, NEU-1 regulates many membrane receptors through desialylation which results in either the activation or inhibition of these receptors. At the plasma membrane, NEU-1 also associates with the elastin-binding protein and the carboxypeptidase protective protein/cathepsin A to form the elastin receptor complex. The activation of NEU-1 is required for elastogenesis and signal transduction through this receptor, and this is responsible for the biological effects that are mediated by the elastin-derived peptides (EDP) on obesity, insulin resistance and non-alcoholic fatty liver diseases. Furthermore, NEU-1 expression is upregulated in hepatocellular cancer at the mRNA and protein levels in patients, and this sialidase regulates the hepatocellular cancer cells' proliferation and migration. The implication of NEU-1 in other cancer types has also been shown notably in the development of pancreatic carcinoma and breast cancer. Altogether, these data indicate that NEU-1 plays a key role not only in metabolic disorders, but also in the development of several cancers which make NEU-1 a pharmacological target of high potential in these physiopathological contexts.


Individual- and organizational-level consequences of organizational citizenship behaviors: A meta-analysis.
Although one of the main reasons for the interest in organizational citizenship behaviors (OCBs) is the potential consequences of these behaviors, no study has been reported that summarizes the research regarding the relationships between OCBs and their outcomes. Therefore, the purpose of this study is to provide a meta-analytic examination of the relationships between OCBs and a variety of individual- and organizational-level outcomes. Results, based on 168 independent samples (N = 51,235 individuals), indicated that OCBs are related to a number of individual-level outcomes, including managerial ratings of employee performance, reward allocation decisions, and a variety of withdrawal-related criteria (e.g., employee turnover intentions, actual turnover, and absenteeism). In addition, OCBs were found to be related (k = 38; N = 3,611 units) to a number of organizational-level outcomes (e.g., productivity, efficiency, reduced costs, customer satisfaction, and unit-level turnover). Of interest, somewhat stronger relationships were observed between OCBs and unit-level performance measures in longitudinal studies than in cross-sectional studies, providing some evidence that OCBs are causally related to these criteria. The implications of these findings for both researchers and practitioners are discussed. (PsycINFO Database Record (c) 2009 APA, all rights reserved).


Genome-Wide Analysis of the Shi-Related Sequence Family and Functional Identification of GmSRS18 Involving in Drought and Salt Stresses in Soybean.
The plant-special SHI-RELATED SEQUENCE (SRS) family plays vital roles in various biological processes. However, the genome-wide analysis and abiotic stress-related functions of this family were less reported in soybean. In this work, 21 members of soybean SRS family were identified, which were divided into three groups (Group I, II, and III). The chromosome location and gene structure were analyzed, which indicated that the members in the same group may have similar functions. The analysis of stress-related cis-elements showed that the SRS family may be involved in abiotic stress signaling pathway. The analysis of expression patterns in various tissues demonstrated that SRS family may play crucial roles in special tissue-dependent regulatory networks. The data based on soybean RNA sequencing (RNA-seq) and quantitative Real-Time PCR (qRT-PCR) proved that SRS genes were induced by drought, NaCl, and exogenous abscisic acid (ABA). GmSRS18 significantly induced by drought and NaCl was selected for further functional verification. GmSRS18, encoding a cell nuclear protein, could negatively regulate drought and salt resistance in transgenic Arabidopsis. It can affect stress-related physiological index, including chlorophyll, proline, and relative electrolyte leakage. Additionally, it inhibited the expression levels of stress-related marker genes. Taken together, these results provide valuable information for understanding the classification of soybean SRS transcription factors and indicates that SRS plays important roles in abiotic stress responses.


Turbulent reconnection and its implications.
Magnetic reconnection is a process of magnetic field topology change, which is one of the most fundamental processes happening in magnetized plasmas. In most astrophysical environments, the Reynolds numbers corresponding to plasma flows are large and therefore the transition to turbulence is inevitable. This turbulence, which can be pre-existing or driven by magnetic reconnection itself, must be taken into account for any theory of magnetic reconnection that attempts to describe the process in the aforementioned environments. This necessity is obvious as three-dimensional high-resolution numerical simulations show the transition to the turbulence state of initially laminar reconnecting magnetic fields. We discuss ideas of how turbulence can modify reconnection with the focus on the Lazarian & Vishniac (Lazarian & Vishniac 1999 Astrophys. J. 517, 700-718 (doi:10.1086/307233)) reconnection model. We present numerical evidence supporting the model and demonstrate that it is closely connected to the experimentally proven concept of Richardson dispersion/diffusion as well as to more recent advances in understanding of the Lagrangian dynamics of magnetized fluids. We point out that the generalized Ohm's law that accounts for turbulent motion predicts the subdominance of the microphysical plasma effects for reconnection for realistically turbulent media. We show that one of the most dramatic consequences of turbulence is the violation of the generally accepted notion of magnetic flux freezing. This notion is a cornerstone of most theories dealing with magnetized plasmas, and therefore its change induces fundamental shifts in accepted paradigms, for instance, turbulent reconnection entails reconnection diffusion process that is essential for understanding star formation. We argue that at sufficiently high Reynolds numbers the process of tearing reconnection should transfer to turbulent reconnection. We discuss flares that are predicted by turbulent reconnection and relate this process to solar flares and γ-ray bursts. With reference to experiments, we analyse solar observations in situ as measurements in the solar wind or heliospheric current sheet and show the correspondence of data with turbulent reconnection predictions. Finally, we discuss first-order Fermi acceleration of particles that is a natural consequence of the turbulent reconnection.


Précis of After Phrenology: Neural Reuse and the Interactive Brain.
Neural reuse is a form of neuroplasticity whereby neural elements originally developed for one purpose are put to multiple uses. A diverse behavioral repertoire is achieved by means of the creation of multiple, nested, and overlapping neural coalitions, in which each neural element is a member of multiple different coalitions and cooperates with a different set of partners at different times. Neural reuse has profound implications for how we think about our continuity with other species, for how we understand the similarities and differences between psychological processes, and for how best to pursue a unified science of the mind. After Phrenology: Neural Reuse and the Interactive Brain (2014; henceforth After Phrenology in this Précis) surveys the terrain and advocates for a series of reforms in psychology and cognitive neuroscience. The book argues that, among other things, we should capture brain function in a multidimensional manner, develop a new, action-oriented vocabulary for psychology, and recognize that higher-order cognitive processes are built from complex configurations of already evolved circuitry.


Effects of DHLA-capped CdSe/ZnS quantum dots on the fibrillation of human serum albumin.
Nanoparticles (NPs) are extremely small in size and possess very large surface areas, which gives them unique properties and applications distinct from those of bulk systems. When exposed to biological fluid, these NPs may become coated with proteins and other biomolecules given their dynamic nature. Hence, there is a significant possibility of an enhanced rate of protein fibrillation by utilizing the NPs as nucleation centers and, thus, promoting fibril formation. Protein fibrillation is closely associated with many fatal human diseases, including neurodegenerative diseases and a variety of systemic amyloidoses. This topic of protein-NP interaction brings about many key issues and concerns, especially with respect to the potential risks to human health and the environment. Herein, we demonstrate the effects of specific NPs, semiconductor quantum dots (QDs), in the process of protein fibril formation from samples of human serum albumin (HSA). The protein-NP systems are analyzed by time-lapse Thioflavin T spectroscopy, Congo red binding assays, circular dichroism (CD), protein fluorescence spectroscopy, and transmission electron microscopy (TEM). Our experimental results illustrate that an increased rate of fibrillation occurs following a thermally activated mechanism in conjunction with the addition of NPs into the protein system. These results give rise to the understanding and possibility of controlling biological self-assembly processes for use in nanobiotechnology and nanomedicine.


Depression and clinical progression in HIV-infected drug users treated with highly active antiretroviral therapy.
To disentangle the impact of adherence from that of injecting drug status and depressive syndrome on HIV clinical progression in a cohort of highly active antiretroviral therapy (HAART)-treated HIV patients infected through drug use. MANIF 2000 is a French cohort of HIV-infected drug users with scheduled medical visits every 6 months. Only patients enrolled in the MANIF 2000 cohort who had a CD4 cell count >200 cells/microl at HAART initiation were selected. The follow-up period included all post-HAART initiation visits. HIV clinical progression was defined as either AIDS-related death or reaching a CD4 level <200 cells/microl. Adherence was assessed using a self-administered questionnaire and a structured face-to-face interview. Depressive symptoms were evaluated by a Center for Epidemiologic Studies Depression Scale (CES-D) score at each visit. Cox proportional hazards model was used to calculate crude and adjusted relative hazards and 95% confidence intervals and thus identify independent predictors of clinical progression. Of the 305 HAART-treated patients in the cohort, 243 had CD4 cell count >200 cells/microl at HAART initiation. At the first visit after HAART initiation, median CD4 cell count was 466 cells/microl and 45% had undetectable viral load. Injecting drug users accounted for 17% of the study group. Over the follow-up period, 32 patients experienced HIV clinical progression. Probable depression was encountered in 46% of patients and non-adherence in 31% of the sample. After adjustment on baseline CD4 cell count, predictors of clinical progression were: having a higher level of cumulative non-adherence over the follow-up period [HR (95% CI)=1.2 (1.1-1.3) per 10% increase] and having a high score of depressive symptoms following HAART initiation [HR (95% CI)=5.3 (2.21-3.0)]. Although depressive syndrome is known to influence non-adherence behaviours that are amongst the major reasons for clinical progression, it is also a predictor of clinical progression in HIV-infected intravenous drug users on HAART, independently of non-adherence behaviours. HIV care providers should be more sensitive to depressive symptoms in order to detect them early and supply HIV patients with specific care. Further research is needed to determine whether treating depressive symptoms may improve adherence and thus delay disease progression and mortality.


Synthesis and characterization of Ag2S and Ag2S/Ag2(S,Se) NIR nanocrystals.
Syntheses of metal sulfide nanocrystals (NCs) by heat-up routes in the presence of thiols yield NC arrangements difficult to further functionalize and transfer to aqueous media. By means of different NMR techniques, and exemplified by Ag2S NCs, a metal-organic polymer formed during the synthesis acting as a ligand has been identified to be responsible for such aggregation. In this work, a new synthetic hot-injection strategy is presented to synthesize Ag2S NCs which are easily ligand exchangeable in water. Furthermore, the hot-injection route allows an extra NC treatment with Se to produce Ag2S/Ag2(S,Se) NCs with improved optical properties with respect to the Ag2S cores, and better resistance to oxidation, as demonstrated by X-ray absorption experiments.


Mitochondrial Membrane Potential and Nuclear and Gene Expression Changes During Human Disc Cell Apoptosis: In Vitro and In Vivo Annulus Findings.
A study using cultured human annulus cells and human annular tissue. To further explore and define mitochondrial mechanisms related to disc cell apoptosis in vitro and in vivo. Mitochondrial-dependent intrinsic signaling pathways are a well-recognized component of apoptosis (programmed cell death). Disc cell apoptosis is important because it is a major mechanism by which cell numbers decrease during disc degeneration. Our objective was to further explore and define mitochondrial mechanisms related to disc cell apoptosis. High-content screening techniques were used to study nuclear morphology and mitochondrial membrane potentials in cultured annulus cells. Gene expression in annulus tissue was studied with microarray analysis. Cultured cells showed significantly increased nuclear size (an indicator of apoptosis) with increasing Thompson grade (P < 0.00001 by analysis of variance). A significant negative correlation for mitochondrial potential (which results from the difference in electrical potential generated by the electrochemical gradient across the inner membrane of the mitochondrion) versus Thompson grade was identified in cultured human annulus cells in control conditions (r = 0.356, P < 0.0001). When exposed to the K ionophore valinomycin at sublethal levels to induce apoptosis, a significant reduction in mitochondrial potential was identified versus nontreated cells. Gene expression patterns in more degenerated Thompson grade III, IV, and V discs versus healthier grade I and II discs showed significant upregulation of a number of genes with well-recognized apoptosis roles in mitochondrial potential decline (ITM2B, beta-2-microglobulin, and cathepsin B, DAP, GAS1, and PDCD5) and TNF-α associations (cathepsin B, RAC1, and PPT1). Data presented here show the in vivo expression of apoptosis-related genes associated with the loss of mitochondrial membrane integrity and decreased mitochondrial membrane potential with increasing Thompson scores. These data, which mimic our novel, direct cell-based in vitro findings, stress the importance of mitochondrial changes related to apoptosis and TNF-α during human disc degeneration. N/A.


[Effects of biochar on soil nitrogen cycle and related mechanisms: a review].
Biochar has its unique physical and chemical properties, playing a significant role in soil amelioration, nutrient retention, fertility improvement, and carbon storage, and being a hotspot in the research areas of soil ecosystem, biogeochemical cycling, and agricultural carbon sequestration. As a kind of anthropogenic materials, biochar has the potential in controlling soil nitrogen (N) cycle directly or indirectly, and thus, has profound effects on soil ecological functions. This paper reviewed the latest literatures regarding the effects of biochar applications on soil N cycle, with the focuses on the nitrogen species adsorption and the biochemical processes (nitrification, denitrification, and nitrogen fixation) , and analyzed the related action mechanisms of biochar. The future research areas for better understanding the interactions between biochar and soil N cycle were proposed.


Interstitial Lung Disease Associated With Crizotinib in Patients With Advanced Non-Small Cell Lung Cancer: Independent Review of Four PROFILE Trials.
Interstitial lung disease (ILD) is a rare, but potentially serious, side effect associated with crizotinib, a tyrosine kinase inhibitor for anaplastic lymphoma kinase-positive (ALK+) advanced non-small cell lung cancer. Our objective was to determine the incidence and nature of ILD associated with crizotinib in 4 PROFILE trials (ClinicalTrials.gov identifiers, NCT00585195, NCT00932451, NCT00932893, and NCT01154140). Grade ≥ 3 respiratory adverse events (AEs) and serious AEs (SAEs) and any grade AEs/SAEs reported as pneumonitis, ILD, or radiation pneumonitis in trials PROFILE 1001, PROFILE 1005, PROFILE 1007, and PROFILE 1014 were evaluated by an expert independent review committee that included a pulmonologist, medical oncologist, and radiologist. Events were designated as disease progression, de novo ILD possibly or probably related to crizotinib, exacerbation or recurrence of pre-existing ILD, concurrent illness, other toxicity not thought to be related to ILD, or inconclusive. The independent review committee evaluated 446 events (in 368 of 1669 patients who had received crizotinib therapy). They classified these events as follows: progressive disease, 77; de novo ILD, 20; pre-existing ILD, 3; concurrent illness, 9; other toxicities, 310; and inconclusive, 27. The incidence of de novo ILD was 1.2% overall, 1.3% in whites, and 1.2% overall in Asians, but greater at 3.7% in Japanese patients. The median onset of ILD from the initiation of crizotinib therapy was 23 days (range, 3-763 days). The mortality rate due to ILD was 50%. Survival was improved if crizotinib was discontinued on presentation of ILD (9 of 14 patients) compared with discontinued later or continued (1 of 6 patients). ILD associated with crizotinib, although rare, can occur at any time and requires close monitoring.


Growth rate and stable carbon and nitrogen isotope trophic discrimination factors of lion and leopard whiskers.
Stable isotope analysis (SIA) of whiskers has been used to identify temporal feeding habits, intra-population diet variation, as well as individual dietary specialisation of marine and terrestrial carnivores. However, the potential of the method to disclose such dietary information for large wild felids is hampered by lack of information on species-specific whisker growth rates, whisker growth patterns and whisker-diet trophic discrimination factors (TDFs). Whisker growth rates and growth patterns were measured for four lions (Panthera leo) and one leopard (Panthera pardus) held at the National Zoological Gardens, Pretoria, South Africa. Actively growing whiskers of the felids were 'marked' four times over 185 days using 13 C-depleted, C3 -based giraffe (Giraffa camelopardalis) meat. The periods with low δ13 C values, identified following serial sectioning of the regrown whiskers at 1 mm intervals and isotopic analysis, were then correlated to specific giraffe meat feeding bouts and hence growth periods. δ13 C and δ15 N whisker-diet TDFs were estimated for five lions whose diet remained consistent over multiple years. The whisker growth rates of three lionesses and the leopard were similar (mean = 0.65 mm day-1 ), despite species, sex and age differences. There was a decrease in whisker growth rate over time, suggesting a non-linear whisker growth pattern. However, linear and non-linear growth simulations showed slight differences between the two growth patterns for the proximal ~50 mm of whiskers. δ13 C and δ15 N lion whisker-diet TDFs were also similar amongst individuals (mean = 2.7 ± 0.12 ‰ for δ13 C values and 2.5 ± 0.08 ‰ for δ15 N values), irrespective of age and sex. The whisker growth rate and δ13 C and δ15 N lion whisker-diet TDFs obtained in this study can be applied in future studies to assign dietary information contained in analysed felid whiskers to the correct time period and improve deductions of prey species consumed by wild felids.


FGF21 Mediates Endocrine Control of Simple Sugar Intake and Sweet Taste Preference by the Liver.
The liver is an important integrator of nutrient metabolism, yet no liver-derived factors regulating nutrient preference or carbohydrate appetite have been identified. Here we show that the liver regulates carbohydrate intake through production of the hepatokine fibroblast growth factor 21 (FGF21), which markedly suppresses consumption of simple sugars, but not complex carbohydrates, proteins, or lipids. Genetic loss of FGF21 in mice increases sucrose consumption, whereas acute administration or overexpression of FGF21 suppresses the intake of both sugar and non-caloric sweeteners. FGF21 does not affect chorda tympani nerve responses to sweet tastants, instead reducing sweet-seeking behavior and meal size via neurons in the hypothalamus. This liver-to-brain hormonal axis likely represents a negative feedback loop as hepatic FGF21 production is elevated by sucrose ingestion. We conclude that the liver functions to regulate macronutrient-specific intake by producing an endocrine satiety signal that acts centrally to suppress the intake of "sweets."


[Electropulse therapy in the early postoperative rehabilitation period after reconstructive and plastic surgery on fallopian tubes].
The efficiency of sinusoidal modulated currents applied to the vaginosacral region in the early postoperative rehabilitation period after plastic and reconstructive surgery on the fallopian tubes was assessed in 30 women aged from 21 to 38 (mean 29.3+/-0.6) years. All of them had endoscopically diagnosed tubuloperitoneal infertility. Treatment with sinusoidally-modulated current in he early postoperative period had beneficial effect on the luteal phase of the menstrual cycle in 55.6%, on the hypothalamo-pituitary-ovarian axis in 23.3%, on hemodynamics in the small pelvis organs in 46.7%, on uterine tube activity in 36.7%, and on the reproductive function in 30% of the patients. These women suffered tubuloperitoneal infertility for less than 5 years and underwent grade I-II adhesive process in the absence of endoscopic signs of atrophic or hypetrophic changes in uterine tube walls.


Viral modulation of cellular RNA alternative splicing: A new key player in virus-host interactions?
Upon viral infection, a tug of war is triggered between host cells and viruses to maintain/gain control of vital cellular functions, the result of which will ultimately dictate the fate of the host cell. Among these essential cellular functions, alternative splicing (AS) is an important RNA maturation step that allows exons, or parts of exons, and introns to be retained in mature transcripts, thereby expanding proteome diversity and function. AS is widespread in higher eukaryotes, as it is estimated that nearly all genes in humans are alternatively spliced. Recent evidence has shown that upon infection by numerous viruses, the AS landscape of host-cells is affected. In this review, we summarize recent advances in our understanding of how virus infection impacts the AS of cellular transcripts. We also present various molecular mechanisms allowing viruses to modulate cellular AS. Finally, the functional consequences of these changes in the RNA splicing signatures during virus-host interactions are discussed. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Processing > Splicing Regulation/Alternative Splicing.


Fish sedation, analgesia, anesthesia, and euthanasia: considerations, methods, and types of drugs.
Fish display robust neuroendocrine and physiologic stress responses to noxious stimuli. Many anesthetic, sedative, or analgesic drugs used in other vertebrates reduce stress in fish, decrease handling trauma, minimize movement and physiologic changes in response to nociceptive stimuli, and can be used for euthanasia. But extrapolating from limited published anesthetic and sedative data to all fish species is potentially harmful because of marked anatomic, physiologic, and behavioral variations; instead, a stepwise approach to anesthetizing or sedating unfamiliar species or using unproven drugs for familiar species is advisable. Additionally, knowledge of how water quality influences anesthesia or sedation helps limit complications. The most common method of drug administration is through immersion, a technique analogous to gaseous inhalant anesthesia in terrestrial animals, but the use of injectable anesthetic and sedative agents (primarily intramuscularly, but also intravenously) is increasing. Regardless of the route of administration, routine preprocedural preparation is appropriate, to stage both the animals and the supplies for induction, maintenance, and recovery. Anesthetic and sedation monitoring and resuscitation are similar to those for other vertebrates. Euthanasia is most commonly performed using an overdose of an immersion drug but injectable agents are also effective. Analgesia is an area in need of significant research as only a few studies exist and they provide some contrasting results. However, fish have mu and kappa opiate receptors throughout the brain, making it reasonable to expect some effect of at least opioid treatments in fish experiencing noxious stimuli.


The impact of long dry periods on the aboveground biomass in a tropical forests: 20 years of monitoring.
Long-term studies of community and population dynamics indicate that abrupt disturbances often catalyse changes in vegetation and carbon stocks. These disturbances include the opening of clearings, rainfall seasonality, and drought, as well as fire and direct human disturbance. Such events may be super-imposed on longer-term trends in disturbance, such as those associated with climate change (heating, drying), as well as resources. Intact neotropical forests have recently experienced increased drought frequency and fire occurrence, on top of pervasive increases in atmospheric CO2 concentrations, but we lack long-term records of responses to such changes especially in the critical transitional areas at the interface of forest and savanna biomes. Here, we present results from 20 years monitoring a valley forest (moist tropical forest outlier) in central Brazil. The forest has experienced multiple drought events and includes plots which have and which have not experienced fire. We focus on how forest structure (stem density and aboveground biomass carbon) and dynamics (stem and biomass mortality and recruitment) have responded to these disturbance regimes. Overall, the biomass carbon stock increased due to the growth of the trees already present in the forest, without any increase in the overall number of tree stems. Over time, both recruitment and especially mortality of trees tended to increase, and periods of prolonged drought in particular resulted in increased mortality rates of larger trees. This increased mortality was in turn responsible for a decline in aboveground carbon toward the end of the monitoring period. Prolonged droughts influence the mortality of large trees, leading to a decline in aboveground carbon stocks. Here, and in other neotropical forests, recent droughts are capable of shutting down and reversing biomass carbon sinks. These new results add to evidence that anthropogenic climate changes are already adversely impacting tropical forests.


To Peel or Not to Peel: Pars Plana Vitrectomy with Macular Membrane Peel in Eyes with Abnormalities of Vitreomacular Interface and Coexisting Dry Age-Related Macular Degeneration.
To evaluate the outcome of macular surgery with ILM- and epiretinal membrane peel associated with significant dry age-related macular degeneration (AMD) as defined by the Age-Related Eye Disease Study (AREDS). Institutional. Retrospective case-control study. A total of 42 pseudophacic eyes of 39 patients (7 with full thickness macular hole and 35 with epiretinal membrane) with coexisting dry AMD underwent pars plana vitrectomy (PPV) with internal limiting membrane (ILM) and epiretinal membrane peel. Preoperative and postoperative data including best corrected visual acuity (BCVA), AMD grade according to AREDS, central retinal thickness (CRT), development of choroidal neovascularization (CNV), and central retinal atrophy have been evaluated. Twenty-eight fellow eyes with dry AMD of the included 39 patients served as a control group. A significant improvement in the visual acuity could be observed after surgery (initial BCVA 0.47±0.31 logarithm of the minimal angle of resolution (logMAR) vs 0.33±0.29logMAR 9 months postoperatively; p=0.006). CRT decreased significantly after surgery (p<0.001). In the surgery group, there were 4 eyes (9.5%) with CNV and 1 eye (2.5%) with new central retinal atrophy development after surgery. All these eyes had preoperative AREDS 3 (4 eyes) or AREDS 4 (1 eye) AMD category. In the control group, there was 1 eye (4%) with CNV and 4 eyes (14%) with new central retinal atrophy development during the follow-up of 9 months. These eyes had initially AREDS 2 (1 eye), AREDS 3 (3 eyes) or AREDS 4 (1 eye) AMD category. Eyes with dry AMD of AREDS 3 and AREDS 4 with coexisting VMI abnormalities improve significantly after PPV with membrane peel. While there is a higher risk of CNV development after surgery (9.5%) in these eyes, the vitrectomy does not seem to accelerate central retinal atrophy progression compared to the fellow eyes course.


Functional differences between two Tie2 ligands, angiopoietin-1 and -2, in regulation of adult bone marrow hematopoietic stem cells.
Angiopoietin-1 (Ang-1) plays a critical role in the maintenance of hematopoietic stem cells (HSCs) in the bone marrow (BM) through its binding to the Tie2 receptor. Ang-2, another Tie2 ligand, is known to be an antagonist of Tie2/Ang-1 signaling in angiogenesis; however, its function in regulation of HSCs remains unclear. Here, we investigated the functional differences between Ang-1 and Ang-2 in the maintenance of HSCs. We treated mouse BM lineage(-)Sca-1(+)c-Kit(+) side population(+) cells with Ang-1 and/or Ang-2, and evaluated angiopoietin function by gene expression analysis, immunocytochemical staining of phosphorylated Akt, a colony-formation assay, and a long-term BM reconstitution assay. Gene expression analysis and BM transplantation assay revealed that Ang-1 upregulated expression of p57, p18, Itgb1, Alcam, Tie2, Hoxb4, and Bmi1 genes in HSCs, while Ang-2 antagonized the effects of Ang-1. Ang-1 enhanced the phosphorylation of Akt, while Ang-2 again reduced the effect of Ang-1. The colony assay demonstrated that neither Ang-1, nor Ang-2 influenced the colony formation of HSCs. BM transplantation assay, following in vitro cultivation of HSCs with angiopoietins, showed that Ang-1 maintained long-term repopulating activity of HSCs, while the addition of Ang-2 interfered drastically with the effects of Ang-1. Gene expression analysis and BM transplantation assay demonstrated that Ang-1 maintained HSC activity in an in vitro culture. In contrast, Ang-2 reversed the effects of Ang-1/Tie2 signaling in the regulation of long-term HSCs. Our data suggest that Ang-1 is a dominant ligand for the Tie2 receptor in long HSCs in BM.


Subacromial bursography. An anatomical and clinical study.
Impingement of the rotator cuff beneath the coracoacromial arch without associated rupture of the cuff or reactive bone changes on the undersurface of the acromion is a well established clinical diagnosis. The value of subacromial bursography in the assessment of this condition was investigated in an anatomical study of fifteen cadavera and a clinical study of thirty-one patients. The subacromial bursa is situated like a cap over the rotator cuff and can be demonstrated roentgenographically by the injection of contrast material in shoulders from cadavera and living subjects. This bursa is composed of subacromial and subdeltoid portions as well as a subcoracoid extension in some individuals. However, it is the anterior portion of the bursa, under the coracoacromial arch, that is most significant, since this overlies the deep structures involved in the impingement syndrome. The normal subacromial bursa easily accepts five to ten milliliters of contrast medium. However, if the bursal walls are thickened and edematous, the bursa will be difficult to demonstrate roentgenographically or it will accept only a few milliliters of contrast material. The findings in this study suggest that when the findings on the bursogram are normal, a diagnosis of chronic impingement by the coracoacromial arch should be questioned.


III. Uterine fibroid embolization: pain management.
Conscious sedation and analgesia are integral components of successful uterine fibroid embolization (UFE), both in providing comfort to the anxious patient undergoing an elective procedure and for providing relief of the severe pelvic pain, cramps, and nausea that may result from acute uterine ischemia and the postembolization syndrome that may follow. The agents used are typically those with which interventional radiologists already have extensive experience in the performance of a variety of invasive procedures. Immediate postprocedure care benefits greatly from the use of narcotic delivered via PCA (patient-controlled analgesia) pump. Nonsteroidal anti-inflammatory drugs (NSAIDs) are also particularly useful for treating the pain and cramping caused by UFE and help reduce the amount of narcotic necessary for pain relief during the recovery period. Detailed instructions for the first week of convalescence are necessary to insure comfort and avoid complications.