First report of porcine respirovirus 1 in South America.

Porcine respirovirus 1 (PRV1) is an emerging virus in pigs that has been previously described in the USA and China. There are no reports of its presence in the rest of the world. The objective of this study was to determine the occurrence of PRV1 in Chile and to determine its phylogeny. Thus, we collected samples (oral fluids, nasal swabs, and lungs) from a swine influenza A virus (IAV) surveillance program, most of which belonged to pigs with respiratory disease. The samples were analyzed by RT-PCR, and the viral sequencing was obtained using RNA whole-genome sequencing approach. Maximum likelihood phylogeny was constructed with the available references. Thirty-one of 164 samples (18.9 %) were RT-PCR positive for PRV1: 62.5 % oral fluids, 19.0 % nasal swabs, and 8.6 % lungs. All 6 farms in this study had at least one positive sample, with 6-40 % of positive results per farm, which suggests that PRV1 is disseminated in Chilean swine farms. Twenty-one of 31 (677%) PRV1-positive samples were also positive for IAV, so the role of PRV1 as secondary pathogen in respiratory disease needs to be further evaluated. Near to complete genome of two PRV1s were obtained from two farms. The phylogenies, in general, showed low bootstrap support, except the concatenated genome and the L gene trees which showed clustering of the Chilean PRV1 with Asian sequences, suggesting a close genetic relationship. This is the first report of PRV1 in the Southern Hemisphere. Further studies are necessary to determine the genetic diversity of this virus in Chile

Long-term care for patients with coeliac disease in the UK: a review of the literature and future directions.

Coeliac disease is a common digestive disorder that affects 1% of adults. It is characterised by mucosal damage of the small intestine caused by dietary gluten. The main treatment for coeliac disease is a lifelong gluten-free diet, which can reduce morbidity and mortality and also improve quality of life. Despite the benefits, adhering to this diet is often challenging, with patients often struggling to sustain dietary restriction. Structured follow-up for coeliac disease is recommended in international guidelines for improving adherence and for detecting complications;however, uncertainty exists concerning exactly who should be administering this follow-up care. Here, we undertake a review of the current approaches described in the literature to follow-up patients with coeliac disease, and assess the efficacy of these differing models. We also explore future directions for the care of these patients in the context of the UK National Health Service (a publicly funded healthcare system). Although the focus of this review pertains to follow-up within the UK healthcare system, these problems are recognised to be international, and so the findings of our review are likely to be of interest to all healthcare professionals seeing and managing patients with coeliac disease

Associations between age and sleep apnea risk among newborn infants

ObjectiveAmong older children, sleep‐disordered breathing (SDB) is associated with measurable neurocognitive consequences. However, diagnostic SDB thresholds are lacking for infants < 12 months. We sought to evaluate the relationship between SDB indices, gestational age (GA), and postmenstrual age (PMA) for infants who underwent clinically‐indicated polysomnograms at a tertiary care center.MethodsEvery infant < 3‐months chronological age whose first clinically‐indicated polysomnogram was between 2/2012 and 2/2017 was included. Linear regression was used to evaluate associations between apnea‐hypopnea index (AHI), obstructive‐apnea index (OAI), and GA and PMA for infants with and without obvious clinical risk factors for SDB (eg, micrognathia and cleft palate).ResultsFor 53 infants without obvious SDB risk factors (GA 35.6 ± 4.5 weeks; PMA 41.2 ± 4.0 weeks), mean AHI was 27 ± 18 and OAI 2.9 ± 4.5. There was a weak inverse relationship between AHI and PMA (r2 = 0.12, P = 0.01), but AHI was not predicted by GA (r2 = 0.04, P = 0.13). Conversely, OAI was more strongly associated with GA (r2 = 0.33, P < 0.0001) than PMA (r2 = 0.08, P = 0.036). For 28 infants with congenital structural anomalies that predispose to SDB (GA 38.0 ± 3.1 weeks, PMA 43.1 ± 3.3 weeks, AHI 37.7 ± 30, OAI 8.2 ± 11.8), neither AHI nor OAI were related to PMA or GA.ConclusionsAmong infants who received clinically‐indicated polysomnograms but did not have obvious structural risk for SDB, AHI declined with advancing PMA, but obstructive‐apnea was best predicted by prematurity. In contrast, the SDB risk did not improve with increasing GA or PMA for infants with congenital structural risk factors; such infants may not outgrow their risk for SDB.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150552/1/ppul24354_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150552/2/ppul24354.pd

Nitrogen uptake and internal recycling in Zostera marina exposed to oyster farming: eelgrass potential as a natural biofilter

Oyster farming in estuaries and coastal lagoons frequently overlaps with the distribution of seagrass meadows, yet there are few studies on how this aquaculture practice affects seagrass physiology. We compared in situ nitrogen uptake and the productivity of Zostera marina shoots growing near off-bottom longlines and at a site not affected by oyster farming in San Quintin Bay, a coastal lagoon in Baja California, Mexico. We used benthic chambers to measure leaf NH4 (+) uptake capacities by pulse labeling with (NH4)-N-15 (+) and plant photosynthesis and respiration. The internal N-15 resorption/recycling was measured in shoots 2 weeks after incubations. The natural isotopic composition of eelgrass tissues and vegetative descriptors were also examined. Plants growing at the oyster farming site showed a higher leaf NH4 (+) uptake rate (33.1 mmol NH4 (+) m(-2) day(-1)) relative to those not exposed to oyster cultures (25.6 mmol NH4 (+) m(-2) day(-1)). We calculated that an eelgrass meadow of 15-16 ha (which represents only about 3-4 % of the subtidal eelgrass meadow cover in the western arm of the lagoon) can potentially incorporate the total amount of NH4 (+) excreted by oysters (similar to 5.2 x 10(6) mmol NH4 (+) day(-1)). This highlights the potential of eelgrass to act as a natural biofilter for the NH4 (+) produced by oyster farming. Shoots exposed to oysters were more efficient in re-utilizing the internal N-15 into the growth of new leaf tissues or to translocate it to belowground tissues. Photosynthetic rates were greater in shoots exposed to oysters, which is consistent with higher NH4 (+) uptake and less negative delta C-13 values. Vegetative production (shoot size, leaf growth) was also higher in these shoots. Aboveground/belowground biomass ratio was lower in eelgrass beds not directly influenced by oyster farms, likely related to the higher investment in belowground biomass to incorporate sedimentary nutrients

A hydraulically driven colonoscope

BACKGROUND: Conventional colonoscopy requires a high degree of operator skill and is often painful for the patient. We present a preliminary feasibility study of an alternative approach where a self-propelled colonoscope is hydraulically driven through the colon. METHODS: A hydraulic colonoscope which could be controlled manually or automatically was developed and assessed in a test bed modelled on the anatomy of the human colon. A conventional colonoscope was used by an experienced colonoscopist in the same test bed for comparison. Pressures and forces on the colon were measured during the test. RESULTS: The hydraulic colonoscope was able to successfully advance through the test bed in a comparable time to the conventional colonoscope. The hydraulic colonoscope reduces measured loads on artificial mesenteries, but increases intraluminal pressure compared to the colonoscope. Both manual and automatically controlled modes were able to successfully advance the hydraulic colonoscope through the colon. However, the automatic controller mode required lower pressures than manual control, but took longer to reach the caecum. CONCLUSIONS: The hydraulic colonoscope appears to be a viable device for further development as forces and pressures observed during use are comparable to those used in current clinical practice

Capsule Endoscopy: A Valuable Tool in the Follow-Up of People With Celiac Disease on a Gluten-Free Diet

OBJECTIVES: Traditional celiac disease guidelines recommend follow-up endoscopy and duodenal biopsies at 6–12 months after commencing a gluten-free diet (GFD). However, histology may remain abnormal even 1–2 years later. We evaluated the role of capsule endoscopy in patients with celiac disease after treatment with a GFD. METHODS: Twelve adult patients with newly diagnosed celiac disease were prospectively enrolled. All patients had baseline symptom assessment, celiac serology (tissue transglutaminase antibody, tTG), and capsule endoscopy. Twelve months after commencing a GFD, patients underwent repeat symptom assessment, celiac serology, upper gastrointestinal endoscopy, and capsule endoscopy. RESULTS: At baseline, capsule endoscopy detected endoscopic markers of villous atrophy in the duodenum and extending to a variable distance along the small intestine. On the basis of small bowel transit time, the mean±s.e.m. percentage of small intestine with villous atrophy was 18.2±3.7%. After 12 months on a GFD, repeat capsule endoscopy demonstrated mucosal healing from a distal to proximal direction, and the percentage of small intestine with villous atrophy was significantly reduced to 3.4±1.2% (P¼0.0014) and this correlated with improvement in the symptom score (correlation 0.69, P¼0.01). There was a significant improvement in symptom score (5.2±1.0 vs. 1.7±0.4, P¼0.0012) and reduction in immunoglobulin A–tTG levels (81.5±10.6 vs. 17.5±8.2, P¼0.0005). However, 42% of subjects demonstrated persistent villous abnormality as assessed by duodenal histology. CONCLUSIONS: After 12 months on a GFD, patients with celiac disease demonstrate an improvement in symptoms, celiac serology, and the extent of disease as measured by capsule endoscopy. Mucosal healing occurs in a distal to proximal direction. The extent of mucosal healing correlates with improvement in symptoms. Duodenal histology does not reflect the healing that has occurred more distally.Ilmars Lidums, Edward Teo, John Field and Adrian G. Cummin

Characterizing low affinity epibatidine binding to α4β2 nicotinic acetylcholine receptors with ligand depletion and nonspecific binding

<p>Abstract</p> <p>Background</p> <p>Along with high affinity binding of epibatidine (<it>K</it>_d1≈10 pM) to α4β2 nicotinic acetylcholine receptor (nAChR), low affinity binding of epibatidine (<it>K</it>_d2≈1-10 nM) to an independent binding site has been reported. Studying this low affinity binding is important because it might contribute understanding about the structure and synthesis of α4β2 nAChR. The binding behavior of epibatidine and α4β2 AChR raises a question about interpreting binding data from two independent sites with ligand depletion and nonspecific binding, both of which can affect equilibrium binding of [³H]epibatidine and α4β2 nAChR. If modeled incorrectly, ligand depletion and nonspecific binding lead to inaccurate estimates of binding constants. Fitting total equilibrium binding as a function of total ligand accurately characterizes a single site with ligand depletion and nonspecific binding. The goal of this study was to determine whether this approach is sufficient with two independent high and low affinity sites.</p> <p>Results</p> <p>Computer simulations of binding revealed complexities beyond fitting total binding for characterizing the second, low affinity site of α4β2 nAChR. First, distinguishing low-affinity specific binding from nonspecific binding was a potential problem with saturation data. Varying the maximum concentration of [³H]epibatidine, simultaneously fitting independently measured nonspecific binding, and varying α4β2 nAChR concentration were effective remedies. Second, ligand depletion helped identify the low affinity site when nonspecific binding was significant in saturation or competition data, contrary to a common belief that ligand depletion always is detrimental. Third, measuring nonspecific binding without α4β2 nAChR distinguished better between nonspecific binding and low-affinity specific binding under some circumstances of competitive binding than did presuming nonspecific binding to be residual [³H]epibatidine binding after adding a large concentration of cold competitor. Fourth, nonspecific binding of a heterologous competitor changed estimates of high and low inhibition constants but did not change the ratio of those estimates.</p> <p>Conclusions</p> <p>Investigating the low affinity site of α4β2 nAChR with equilibrium binding when ligand depletion and nonspecific binding are present likely needs special attention to experimental design and data interpretation beyond fitting total binding data. Manipulation of maximum ligand and receptor concentrations and intentionally increasing ligand depletion are potentially helpful approaches.</p

Emission of Volatile Organic Compounds After Herbivory from Trifolium pratense (L.) Under Laboratory and Field Conditions

Plants emit a wide range of volatile organic compounds in response to damage by herbivores, and many of the compounds have been shown to attract the natural enemies of insect herbivores or serve for inter- and intra-plant communication. Most studies have focused on volatile emission in the laboratory while little is known about emission patterns in the field. We studied the emission of volatiles by Trifolium pratense (red clover) under both laboratory and field conditions. The emission of 24 compounds was quantified in the laboratory, of which eight showed increased emission rates after herbivory by Spodoptera littoralis caterpillars, including (E)-β-ocimene, the most abundant compound, (Z)-β-ocimene, linalool, (E)-β-caryophyllene, (E,E)-α-farnesene, 4,8-dimethyl-1,3,7-nonatriene (DMNT), 1-octen-3-ol, and methyl salicylate (MeSA). While most of these compounds have been reported as herbivore-induced volatiles from a wide range of plant taxa, 1-octen-3-ol seems to be a characteristic volatile of legumes. In the field, T. pratense plants with varying herbivore damage growing in established grassland communities emitted only 13 detectable compounds, and the correlation between herbivore damage and volatile release was more variable than in the laboratory. For example, the emission of (E)-β-ocimene, (Z)-β-ocimene, and DMNT actually declined with damage, while decanal exhibited increased emission with increasing herbivory. Elevated light and temperature increased the emission of many compounds, but the differences in light and temperature conditions between the laboratory and the field could not account for the differences in emission profiles. Our results indicate that the release of volatiles from T. pratense plants in the field is likely to be influenced by additional biotic and abiotic factors not measured in this study. The elucidation of these factors may be important in understanding the physiological and ecological functions of volatiles in plants

Self-esteem in adolescent patients with attention-deficit/hyperactivity disorder during open-label atomoxetine treatment: psychometric evaluation of the Rosenberg Self-Esteem Scale and clinical findings

To report on (1) psychometric properties of the Rosenberg Self-Esteem Scale (SES) studied in adolescents with ADHD, (2) correlations of SES with ADHD scale scores, and (3) change in patient-reported self-esteem with atomoxetine treatment. ADHD patients (12–17 years), treated in an open-label study for 24 weeks. Secondary analyses on ADHD symptoms (assessed with ADHD-RS, CGI, GIPD scales) and self-esteem (SES) were performed. One hundred and fifty-nine patients were treated. A dichotomous structure of the SES could be confirmed. Reliability and internal consistency were moderate to excellent. Highest coefficients were found for the correlation between SES and GIPD scores. Self-esteem significantly increased over time, accompanied by an improvement of ADHD symptoms and related perceived difficulties. The Rosenberg SES was shown to be internally consistent, reliable, and sensitive to treatment-related changes of self-esteem. According to these findings, self-esteem may be an important individual patient outcome beyond the core symptoms of ADHD

Nuclear envelope protein Lem2 is required for mouse development and regulates MAP and AKT kinases

The nuclear lamina, along with associated nuclear membrane proteins, is a nexus for regulating signaling in the nucleus. Numerous human diseases arise from mutations in lamina proteins, and experimental models for these disorders have revealed aberrant regulation of various signaling pathways. Previously, we reported that the inner nuclear membrane protein Lem2, which is expressed at high levels in muscle, promotes the differentiation of cultured myoblasts by attenuating ERK signaling. Here, we have analyzed mice harboring a disrupted allele for the Lem2 gene (Lemd2). No gross phenotypic defects were seen in heterozygotes, although muscle regeneration induced by cardiotoxin was delayed. By contrast, homozygous Lemd2 knockout mice died by E11.5. Although many normal morphogenetic hallmarks were observed in E10.5 knockout embryos, most tissues were substantially reduced in size. This was accompanied by activation of multiple MAP kinases (ERK1/2, JNK, p38) and AKT. Knockdown of Lem2 expression in C2C12 myoblasts also led to activation of MAP kinases and AKT. These findings indicate that Lemd2 plays an essential role in mouse embryonic development and that it is involved in regulating several signaling pathways. Since increased MAP kinase and AKT/mTORC signaling is found in other animal models for diseases linked to nuclear lamina proteins, LEMD2 should be considered to be another candidate gene for human disease