bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between drugs and small‐bowel mucosal bleeding: Multicenter capsule‐endoscopy study
Authors: Niikura Ryota , Yamada Atsuo , Maki Koutarou , Nakamura Masanao , Watabe Hirotsugu , Fujishiro Mitsuhiro , Oka Shiro , Esaki Motohiro , Fujimori Shunji , Nakajima Atsushi , Ohmiya Naoki , Matsumoto Takayuki , Tanaka Shinji , Koike Kazuhiko , Sakamoto Choitsu
Published: July 2017

Background and Aim

Although several drugs may induce small‐bowel mucosal injuries, it is unclear whether these injuries contribute to overt small‐bowel bleeding. This study was designed to evaluate the associations between drug use and small‐bowel mucosal injury and between these mucosal injuries and overt bleeding in a disease‐relevant population.

Methods

We retrospectively studied patients with suspected small‐bowel diseases who underwent capsule endoscopy between 2010 and 2013. Drug exposure, Charlson Comorbidity Index, smoking, and alcohol consumption were assessed before capsule endoscopy. Adjusted odds ratios (AOR) and confidence intervals (CI) were estimated for small‐bowel mucosal injury and small‐bowel overt bleeding.

Results

In total, 850 patients were analyzed during the study period. Median age was 64 years, and 544 patients (64.0%) were men. Among the patients with small‐bowel mucosal injury (n = 60) and without mucosal injury (n = 705), use of non‐steroidal anti‐inflammatory drugs (NSAIDs) (AOR 1.8, 95% CI 1.01–3.31) was significantly associated with an increased risk of small‐bowel mucosal injury compared with non‐use. Patients with small‐bowel mucosal injury with overt bleeding (n = 85) and without overt bleeding (n = 60) were compared, and no significant difference between the groups in the usage rates for NSAIDs, thienopyridine, other antiplatelets, anticoagulants, acetaminophen, tramadol hydrochloride, or steroids was revealed, even after adjusting for confounders.

Conclusion

Although the use of NSAIDs was significantly associated with an increased risk of small‐bowel mucosal injury, no significant associations were observed between the use of such drugs and small‐bowel overt bleeding.
Comparative efficacy and safety of gemigliptin versus linagliptin in type 2 diabetes patients with renal impairment: A 40‐week extension of the GUARD randomized study
Authors: Han Sang Youb , Yoon Sun Ae , Han Byoung Geun , Kim Sung Gyun , Jo Young‐Il , Jeong Kyung Hwan , Oh Kook‐Hwan , Park Hyeong Cheon , Park Sun‐Hee , Kang Shin‐Wook , Na Ki‐Ryang , Kang Sun Woo , Kim Nam‐Ho , Jang Younghwan , Kim Bogyeong , Shin Seonghye , Cha Dae Ryong
Published: July 2017

Aims

The long‐term safety and efficacy of gemigliptin was evaluated in the present extension study after a 12‐week study during a 40‐week follow‐up period.

Methods

The main study was a randomized, placebo‐controlled, double‐blinded, phase IIIb study in which 50 mg of gemigliptin (N = 66) or placebo (N = 66) was administered to patients with type 2 diabetes mellitus (T2DM) and moderate or severe renal impairment over a 12‐week period. Patients with a glycated haemoglobin (HbA1c) level of 7% to 11% and an estimated glomerular filtration rate (eGFR) of 15 to 59 mL/min/1.73 m2 were enrolled in the main study. After 12 weeks, patients in the gemigliptin group continued to receive gemigliptin (N = 50), whereas patients in the placebo group were transitioned from placebo to linagliptin (N = 52). Each group received the indicated treatment over the subsequent 40‐week period. A total of 102 patients consented to participate in the extension study, and 79 patients ultimately completed the study.

Results

The HbA1c levels of both groups were significantly reduced at week 52 compared with baseline. Specifically, the adjusted mean change ± standard error in HbA1c level in the gemigliptin and placebo/linagliptin groups was 1.00% ± 0.21% and 0.65% ± 0.22% lower at week 52 than at baseline (P < .001 and P = .003), respectively. No significant difference in the change in HbA1c level was found between the 2 groups (P = .148). Trends in fasting plasma glucose, fructosamine and glycated albumin levels in the 2 groups were similar to trends in HbA1c levels. The eGFR of both groups was also significantly lower at week 52 than at baseline, and no significant difference in change in eGFR was found between the 2 groups. In contrast, both drugs had little effect on urinary albumin excretion, although both drugs significantly reduced the urinary type IV collagen level. The overall rates of adverse events were similar between the 2 groups.

Conclusions

Gemigliptin and linagliptin did not differ with respect to safety and efficacy in patients with T2DM and renal impairment. The 2 drugs had similar glucose‐lowering effects, and the changes in eGFR and albuminuria were also similar. Additionally, the risk of side effects, including hypoglycaemia, was similar between the 2 groups.
The effect of exercise on sleep in adults with type 1 diabetes
Authors: Reddy Ravi , El Youssef Joseph , Winters‐Stone Kerri , Branigan Deborah , Leitschuh Joseph , Castle Jessica , Jacobs Peter G.
Published: July 2017

The aim of this pilot study was to investigate the effect of exercise on sleep and nocturnal hypoglycaemia in adults with type 1 diabetes (T1D). In a 3‐week crossover trial, 10 adults with T1D were randomized to perform aerobic, resistance or no exercise. During each exercise week, participants completed 2 separate 45‐minutes exercise sessions at an academic medical center. Participants returned home and wore a continuous glucose monitor and a wrist‐based activity monitor to estimate sleep duration. Participants on average lost 70 (±49) minutes of sleep (P = .0015) on nights following aerobic exercise and 27 (±78) minutes (P = .3) following resistance exercise relative to control nights. The odds ratio with confidence intervals of nocturnal hypoglycaemia occurring on nights following aerobic and resistance exercise was 5.4 (1.3, 27.2) and 7.0 (1.7, 37.3), respectively. Aerobic exercise can cause sleep loss in T1D possibly from increased hypoglycaemia.
Policy development: An analysis of disability inclusion in a selection of African Union policies
Authors: Lang Raymond , Schneider Marguerite , Kett Maria , Cole Ellie , Groce Nora
Published: July 2017

Contemporary debates in international development discourse are concerned with the non‐tokenistic inclusion and participation of marginalized groups in the policy‐making process in developing countries. This is directly relevant to disabled people in Africa, which is the focus of this article. The United Nations Convention on the Rights of Persons with Disabilities delineates the principles of inclusion in society. Furthermore, the African Union (AU) plays a key role in advising its Member States about disability issues, and this advice should be reflected in disability‐inclusive policies. This article analyses nine policy or strategy documents produced by the AU, covering the policy domains of education, health, employment and social protection that are crucial to the inclusion of disabled people in international development. These were analysed according to seven discrete elements (rights, accessibility, inclusivity, implementation plans, budgetary allocations, enforcement mechanisms or disaggregated management information systems) using a rating scale of one to four, with four being the highest level of inclusion. The process (for example, level of consultation), the context (for example, the Sustainable Development Goals) and actors involved in the policy development were reviewed as far as was possible from the documents. None of the policies reached even 50% of the total possible score, indicating poor levels of genuine inclusion. Rights scored a highest rating, but still at a low level. This suggests that there is recognition of the rights of disabled people to inclusion, but this is not generally integrated within inclusive implementation plans, budgetary allocations, enforcement mechanisms or disaggregated management information systems for monitoring. The limited socio‐economic inclusion of disability within AU policies is a lost opportunity that should be reviewed and rectified. The findings have broader ramifications for the non‐tokenistic and genuine involvement of poor and marginalized groups in the international policy‐making arena.
Bone marrow harvest from unrelated donors—up‐to‐date methodology
Authors: Pruszczyk Katarzyna , Skwierawska Kamila , Król Małgorzata , Moskowicz Albert , Jabłoński Dariusz , Torosian Tigran , Piotrowska Iwona , Urbanowska Elżbieta , Wiktor‐Jędrzejczak Wiesław , Snarski Emilian
Published: July 2017

Objectives

Bone marrow harvesting is one of the essential sources of stem cells for hematopoietic stem cell transplantation. We describe here the current “up‐to‐date” standard of the bone marrow harvest in unrelated stem cell donors.

Methods

We analyzed medical data of 187 unrelated hematopoietic stem cell donors who underwent bone marrow harvest without previous peripheral blood stem collection at the center between 2011 and 2015.

The methodology of marrow collection includes multiple cells aimed at safety of the procedure, for example, educational movie, modified skin disinfection protocol, cell enumeration during the procedure, reduction of the contamination surfaces, and ongoing monitoring of the quality of work of the doctors.

Results

The total nucleated cell count over 2×108 per kg of recipient has been reached in 93.6% of harvests. All of the donors harvested more than 1×108 per kg of the recipient. There were no donors who required transfusions or had serious adverse events during and after the harvest.

Conclusion

We describe here the current up‐to‐date standard of bone marrow harvest, which leads to excellent results in majority of donors without causing significant complications during the donation.
Proliferation of elastic fibres in idiopathic pulmonary fibrosis: a whole‐slide image analysis and comparison with pleuroparenchymal fibroelastosis
Authors: Kinoshita Yoshiaki , Watanabe Kentaro , Ishii Hiroshi , Kushima Hisako , Fujita Masaki , Nabeshima Kazuki
Published: July 2017

Aims

We occasionally encounter patients with idiopathic pulmonary fibrosis (IPF) who have similar imaging patterns to those of pleuroparenchymal fibroelastosis (PPFE) in the upper lung fields but are not diagnosed as having PPFE clinically. The aim of this study is to identify the clinicopathological features and intrapulmonary distribution of elastic fibres and collagen fibres in these patients.

Methods and results

We retrospectively reviewed the medical records of patients with a clinical diagnosis of IPF, and selected consecutive patients who underwent autopsy or pneumonectomy for lung transplantation. Patients with histologically confirmed PPFE were also reviewed for comparison. We quantified the collagen fibres and elastic fibres in each lobe as a percentage of the non‐aerated lung area (collagen fibre score and elastic fibre score, respectively) in histological specimens by using whole‐slide image analysis, and compared these scores between IPF and PPFE patients. In a total of 55 patients (IPF, 48; PPFE, 7), there were no significant differences in the collagen fibre scores between IPF and PPFE patients. The elastic fibre scores in the upper lobe in PPFE patients were significantly higher than those in IPF patients (23.5 versus 10.3, P = 0.005). However, it is of note that, in 12 of 48 IPF patients, the elastic fibre scores of the upper lobes were above the first quartile of those in PPFE patients.

Conclusions

IPF occasionally shows intense elastosis in the upper lobes, and such cases are histologically indistinguishable from PPFE. There seem to be histologically borderline cases between PPFE and IPF.
Identification of odorant‐binding and chemosensory protein genes and the ligand affinity of two of the encoded proteins suggest a complex olfactory perception system in Periplaneta americana
Authors: He P. , Li Z.‐Q. , Zhang Y.‐F. , Chen L. , Wang J. , Xu L. , Zhang Y.‐N. , He M.
Published: July 2017

The American cockroach (Periplaneta americana) is an urban pest with a precise chemosensory system that helps it achieve complex physiological behaviours, including locating food and mating. However, its chemosensory mechanisms have not been well studied. Here, we identified 71 putative odorant carrier protein genes in P. americana, including 57 new odorant‐binding proteins (OBPs) and 11 chemosensory proteins (CSPs). To identify their physiological functions, we investigated their tissue expression patterns in antennae, mouthparts, legs, and the remainder of the body of both sexes, and determined that most of these genes were expressed in chemosensory organs. A phylogenetic tree showed that the putative pheromone‐binding proteins of P. americana were in different clades from those of moths. Two genes, PameOBP24 and PameCSP7, were expressed equally in antennae of both sexes and highly expressed amongst the OBPs and CSPs. These genes were expressed in Escherichia coli and the resultant proteins were purified. The binding affinities of 74 common odorant compounds were tested with recombinant PameOBP24 and PameCSP7. Both proteins bound a variety of ligands. Our findings provide a foundation for future research into the chemosensory mechanisms of P. americana and help in identifying potential target genes for managing this pest.
Immunogenomic approaches to understand the function of immune disease variants
Authors: Glinos Dafni A. , Soskic Blagoje , Trynka Gosia
Published: July 2017

Mapping hundreds of genetic variants through genome wide association studies provided an opportunity to gain insights into the pathobiology of immune‐mediated diseases. However, as most of the disease variants fall outside the gene coding sequences the functional interpretation of the exact role of the associated variants remains to be determined. The integration of disease‐associated variants with large scale genomic maps of cell‐type‐specific gene regulation at both chromatin and transcript levels deliver examples of functionally prioritized causal variants and genes. In particular, the enrichment of disease variants with histone marks can point towards the cell types most relevant to disease development. Furthermore, chromatin contact maps that link enhancers to promoter regions in a direct way allow the identification of genes that can be regulated by the disease variants. Candidate genes implicated with such approaches can be further examined through the correlation of gene expression with genotypes. Additionally, in the context of immune‐mediated diseases it is important to combine genomics with immunology approaches. Genotype correlations with the immune system as a whole, as well as with cellular responses to different stimuli, provide a valuable platform for understanding the functional impact of disease‐associated variants. The intersection of immunogenomic resources with disease‐associated variants paints a detailed picture of disease causal mechanisms. Here, we provide an overview of recent studies that combine these approaches to identify disease vulnerable pathways.
Neurofilament light as an immune target for pathogenic antibodies
Authors: Puentes Fabiola , van der Star Baukje J. , Boomkamp Stephanie D. , Kipp Markus , Boon Louis , Bosca Isabel , Raffel Joel , Gnanapavan Sharmilee , van der Valk Paul , Stephenson Jodie , Barnett Susan C. , Baker David , Amor Sandra
Published: July 2017

Antibodies to neuronal antigens are associated with many neurological diseases including paraneoplastic neurological disorders, epilepsy, amyotrophic lateral sclerosis and multiple sclerosis. Immunization with neuronal antigens such as neurofilament light (NF‐L), a neuronal intermediate filament in axons, has been shown to induce neurological disease and spasticity in mice. Also, although antibodies to NF‐L are widely used as surrogate biomarkers of axonal injury in amyotrophic lateral sclerosis and multiple sclerosis, it remains to be elucidated if antibodies to NF‐L contribute to neurodegeneration and neurological disease. To address this, we examined the pathogenic role of antibodies directed to NF‐L in vitro using spinal cord co‐cultures and in vivo in experimental autoimmune encephalomyelitis (EAE) and optic neuritis animal models of multiple sclerosis. Here we show that peripheral injections of antibodies to NF‐L augmented clinical signs of neurological disease in acute EAE, increased retinal ganglion cell loss in experimental optic neuritis and induced neurological signs following intracerebral injection into control mice. The pathogenicity of antibodies to NF‐L was also observed in spinal cord co‐cultures where axonal loss was induced. Taken together, our results reveal that as well as acting as reliable biomarkers of neuronal damage, antibodies to NF‐L exacerbate neurological disease, suggesting that antibodies to NF‐L generated during disease may also be pathogenic and play a role in the progression of neurodegeneration.
Infants Extract Frequency Distributions from Variable Approximate Numerical Information
Authors: Libertus Melissa E. , Feigenson Lisa , Halberda Justin
Published: July 2017

Previous research shows that infants represent approximate number: After habituation to a constant numerosity (e.g., eight dots), 6‐month‐old infants dishabituate to a novel numerosity (e.g., 16 dots). However, numerical information in the real world is far more variable and rarely offers repeated presentations of a single quantity. Instead, we often encounter quantities in the form of distributions around a central tendency. It remains unknown whether infants can represent frequency distributions from this type of distributed numerical input. Here, we asked whether 6‐month‐old infants can represent distributions of large approximate numerosities. In two experiments, we first familiarized infants to sequences of dot collections with varying numerosities. For half the infants, the sequence contained a unimodal frequency distribution, with numerosities centered around a single mean, and for the other half, it contained a bimodal frequency distribution of numerosities with two numerical peaks. We then tested infants with alternating or constant numerosities. Infants who had been familiarized to a unimodal distribution looked longer at alternating numerosities than constant numerosities (experiments 1 and 2), whereas infants who had been familiarized to a bimodal distribution looked longer at constant numerosities (Exp. 2). These findings suggest that infants can spontaneously extract frequency distributions from distributed numerical input.
Drought stress‐induced changes in starch yield and physiological traits in potato
Authors: Rudack K. , Seddig S. , Sprenger H. , Köhl K. , Uptmoor R. , Ordon F.
Published: July 2017

Drought stress is an important limitation for potato (Solanum tuberosum L.) production as potato depends on appropriate water availability for high yields of good quality. Therefore, especially in the background of climate change, it is an important goal in potato breeding to improve drought stress tolerance. In this study, 34 European starch potato cultivars were evaluated for drought stress tolerance by growing under well‐watered and long‐term drought stress conditions in rainout shelters in 2 years’ pot trials. Besides yield, six physiological traits, that is free proline content, osmolality, total soluble sugar content, chlorophyll content (SPAD), cell membrane stability and crude protein content, were determined in leaves sampled during vegetative growth and during flowering to investigate their association with drought tolerance. ANOVA revealed significant treatment effects for all physiological traits and increased genotypic effects at flowering. The sensitivity of physiological traits to drought was significantly higher during flowering than during vegetative growth. Drought stress decreased starch yield significantly (p < .001), on average by 55%. Starch yield was significantly influenced by genotype and genotype × treatment interactions. Stress tolerance index (STI) calculated from starch yield ranged from 0.26 (sensitive) to 0.76 (tolerant) with significant genotype effects (p ≤ .001). STI correlated positively with cell membrane stability (r = .59) and crude protein content (r = .38) and negatively with osmolality (r = −.57) and total soluble sugar content (r = −.71). These contrary correlations suggest a dual adaptation strategy in potato under long‐term drought stress conditions including increased membrane stability combined with an increased osmolality due to an increased soluble sugar content.
A historical review of the key bacterial and viral pathogens of Scottish wild fish
Authors: Wallace I S , McKay P , Murray A G
Published: July 2017

Thousands of Scottish wild fish were screened for pathogens by Marine Scotland Science. A systematic review of published and unpublished data on six key pathogens (Renibacterium salmoninarum, Aeromonas salmonicida, IPNV, ISAV, SAV and VHSV) found in Scottish wild and farmed fish was undertaken. Despite many reported cases in farmed fish, there was a limited number of positive samples from Scottish wild fish, however, there was evidence for interactions between wild and farmed fish. A slightly elevated IPNV prevalence was reported in wild marine fish caught close to Atlantic salmon, Salmo salar L., farms that had undergone clinical IPN. Salmonid alphavirus was isolated from wild marine fish caught near Atlantic salmon farms with a SAV infection history. Isolations of VHSV were made from cleaner wrasse (Labridae) used on Scottish Atlantic salmon farms and VHSV was detected in local wild marine fish. However, these pathogens have been detected in wild marine fish caught remotely from aquaculture sites. These data suggest that despite the large number of samples taken, there is limited evidence for clinical disease in wild fish due to these pathogens (although BKD and furunculosis historically occurred) and they are likely to have had a minimal impact on Scottish wild fish.
Is fat tasty for the brain?
Authors: Nałęcz Katarzyna A.
Published: July 2017

Read the commented article ‘Developmental regulation and localization of Carnitine Palmitoyltransferases (CPTs) in rat brain’ on page 407.
Delta‐like protein 1 in the pituitary‐adipose axis in the adult male mouse
Authors: Bello A. R. , Puertas‐Avendaño R. A. , González‐Gómez M. J. , González‐Gómez M. , Laborda J. , Damas C. , Ruiz‐Hidalgo M. , Diaz C.
Published: July 2017

With the aim of studying delta‐like protein 1 (DLK1) with respect to the relationship between adipocyte leptin and adenohypophyseal hormones, we carried out an immunohistochemical study analysing the presence of receptors for these hormones in the pituitary and adipose cells of male wild‐type (WT) mice (Dlk1+/+) compared to knockout (KO) mice (Dlk1−/−). ThemRNAexpression of these molecules was also determined using the reverse transcriptase‐polymerase chain reaction. The results obtained showed that, in WT adipose cells, all of the adenohypophyseal hormone receptors were present, with a highermRNAexpression for growth hormone (GH) receptorand thyroid‐stimulating hormone (TSH) receptor. Of the total cells in the anterior pituitary lobe, 17.09±0.9% were leptin receptor (LEPR) immunoreactive (‐IR), mainly inGH‐IR and prolactin (PRL)‐IR cells (41.5±3.8%; 13.5±1.7%, respectively). InDlk1−/−mice, adipocyte cells showed a significant increase in theTSH receptor mRNAexpression level. Moreover, the percentage ofLEPR‐IRGHcells showed a statistically significant increase compared to controls, from 41.5±3.8% to 53.1±4.0%. By contrast, only 3.0±0.6% ofLEP‐IR anterior pituitary cells were detected in Dlk1 KO mice, as opposed to 6.8±1.1% observed inWTmice. The results suggest that relationships exist between adipocytes and pituitaryGH,PRLandTSHcells, in addition to an influence with respect to the synthesis and release of pituitary leptin, particularly inPRLcells.
Evidence for plical support of the patella
Authors: Geraghty Robert M. , Spear Michelle
Published: July 2017

There is a consensus that there is no overt anterior joint capsule in the knee. However, other anterior structures act in lieu of a joint capsule: the quadriceps tendon and patellar retinacular fibres. In the absence of a capsule, the synovium forms the suprapatellar pouch. Other synovial structures, the plicae, are more controversial. They are often described as embryonic remnants with no function, despite surrounding the patella. We aimed to identify plical anatomy and histology on cadaveric dissection and to examine their embryology using the human virtual embryo website. Plicae were identified by two independent observers. Plical histology was examined using a panel of stains: H&E, Ab H&E, EVG and MSB trichrome. Embryonic knees were examined from Carnegie stages 20–23. Each knee had a suprapatellar plica and mediopatellar plica (MPP). The lateropatellar plica (LPP) appeared as a band in 5/10 cadavers, and as a ridge in the remainder. The overall impression, consistent across all specimens, was that the plicae formed a continuous band of synovial tissue around the proximal three‐quarters of the patella. The infrapatellar fat pad (IFP) surrounded the remainder. Histologically, the plicae and IFP consisted of three layers (in order): a synovial layer, an undulated collagenous layer, and an adipose or areoloadipose layer. The subsynovial collagenisation is normally associated with the synovio‐capsular boundary. Embryologically, plicae were not seen in either knee at any level for any given Carnegie stage. We suggest that plicae, along with the dynamic IFP, provide internal support to the patella mirroring the external support of retinacular fibres. Thus, the plicae complete the tissue complex acting in lieu of an anterior joint capsule. Evidence of plical functionality lends credence to the theory that the plicae are anatomical structures not functionless embryonic remnants.
Granulomatous reaction to hyaluronic acid filler material in oral and perioral region: A case report and review of literature
Authors: Alcântara Carlos Eduardo P , Noronha Mariana S , Cunha Joanna F , Flores Isadora L , Mesquita Ricardo A
Published: July 2017

The use of cosmetic fillers agents in orofacial region has become more often used for esthetic concern. Although adverse effects are rare, some patients may develop foreign body reaction to such fillers. Hyaluronic acid (HA) is a biomaterial in the spotlight, because it is normally present in several tissues of human body. The aim of this study was to report a case of a 54‐year‐old white woman with granulomatous reaction to the HA located in the lips. In addition, a review of the English‐language literature of all previously described cases of this condition in oral and perioral region was performed. The location, clinical features, symptoms, time between injection and reaction, type of treatment and treatment outcome of 17 cases were summarized. The clinical and histopathological examination along with a detailed history about this condition is very important to management of patients with nodular lesions in maxillofacial region.
Effectiveness of Helicobacter pylori eradication in pregnant women with idiopathic thrombocytopenic purpura
Authors: Ono Yosuke , Shiozaki Arihiro , Yoneda Noriko , Yoneda Satoshi , Yoshino Osamu , Saito Shigeru
Published: July 2017

Platelet counts increase after eradication of Helicobacter pylori (Hp) infection in non‐pregnant patients with Hp‐associated idiopathic thrombocytopenic purpura (ITP); however, improvement in pregnant patients has not yet been reported. We treated four pregnant women for Hp‐positive ITP after Hp eradication. In three of four cases, platelet counts increased to levels exceeding 10 × 109/L two weeks after eradication, and these levels were maintained until delivery. Vaginal deliveries were uncomplicated, and no excessive blood loss occurred in any of the cases. There were no remarkable side effects of Hp eradication in pregnant women or fetuses. In pregnant women with Hp‐associated ITP, Hp eradication might be worthwhile prior to considering steroid administration.
Safety and dose‐finding trial of tadalafil administered for fetal growth restriction: A phase‐1 clinical study
Authors: Kubo Michiko , Tanaka Hiroaki , Maki Shintaro , Nii Masafumi , Murabayashi Nao , Osato Kazuhiro , Kamimoto Yuki , Umekawa Takashi , Kondo Eiji , Ikeda Tomoaki
Published: July 2017

Aim

We designed a safety and dose‐finding trial of tadalafil administered for fetal growth restriction (FGR).

Methods

Three cases were initially commenced on 10 mg/day and monitored for major adverse events. Should a major adverse event be observed in one or more of the three cases, an examination into its relation with tadalafil would be conducted by a safety evaluation committee. If one or more of these new cases exhibited the same adverse event, the trial would be stopped completely. If there were no harmful side‐effects, the trial would be extended to three cases at 20 mg/day, and the protocol would continue as in the 10‐mg/day dose. The 40‐mg/day dosage was tried in six cases as the dosage was considered to be high.

Results

The study population consisted of pregnant women with FGR. Maternal adverse events in all doses were recorded as least one grade 1 adverse events, as tadalafil was considered acceptable from the viewpoint of the mothers. However, a dose of 40 mg/day increased the number of grade 1 adverse events. The only fetal adverse event was a case of intrauterine fetal death related to the velamentous insertion of the umbilical cord. Neonatal adverse events showed no correlation to tadalafil dose, but were found more frequently in preterm births and, therefore, were correlated to infant prematurity.

Conclusion

This safety and dose‐finding trial showed that tadalafil had a favorable safety profile for pregnant women and fetuses with FGR.
Drug use and phylogenetic clustering of hepatitis C virus infection among people who use drugs in Vancouver, Canada: A latent class analysis approach
Authors: Jacka B. , Bray B. C. , Applegate T. L. , Marshall B. D. L. , Lima V. D. , Hayashi K. , DeBeck K. , Raghwani J. , Harrigan P. R. , Krajden M. , Montaner J. S. G. , Grebely J.
Published: July 2017

This study estimated latent classes (ie, unobserved subgroups in a population) of people who use drugs in Vancouver, Canada, and examined how these classes relate to phylogenetic clustering of hepatitis C virus (HCV) infection. HCV antibody‐positive people who use drugs from two cohorts in Vancouver, Canada (1996‐2012), with a Core‐E2 sequence were included. Time‐stamped phylogenetic trees were inferred, and phylogenetic clustering was determined by time to most common recent ancestor. Latent classes were estimated, and the association with the phylogenetic clustering outcome was assessed using an inclusive classify/analyse approach. Among 699 HCV RNA‐positive participants (26% female, 24% HIV+), recent drug use included injecting cocaine (80%), injecting heroin (70%), injecting cocaine/heroin (ie, speedball, 38%) and crack cocaine smoking (28%). Latent class analysis identified four distinct subgroups of drug use typologies: (i) cocaine injecting, (ii) opioid and cocaine injecting, (iii) crack cocaine smoking and (iv) heroin injecting and currently receiving opioid substitution therapy. After adjusting for age and HIV infection, compared to the group defined by heroin injecting and currently receiving opioid substitution therapy, the odds of phylogenetic cluster membership was greater in the cocaine injecting group (adjusted OR [aOR]: 3.06; 95% CI: 1.73, 5.42) and lower in the crack cocaine smoking group (aOR: 0.06; 95% CI: 0.01, 0.48). Combining latent class and phylogenetic clustering analyses provides novel insights into the complex dynamics of HCV transmission. Incorporating differing risk profiles associated with drug use may provide opportunities to further optimize and target HCV treatment and prevention strategies.
Directly observed therapy of sofosbuvir/ribavirin +/− peginterferon with minimal monitoring for the treatment of chronic hepatitis C in people with a history of drug use in Chennai, India (C‐DOT)
Authors: Solomon S. S. , Sulkowski M. S. , Amrose P. , Srikrishnan A. K. , McFall A. M. , Ramasamy B. , Kumar M. S. , Anand S. , Thomas D. L. , Mehta S. H.
Published: July 2017

We assessed the feasibility of field‐based directly observed therapy (DOT) with minimal monitoring to deliver HCV treatment to people with a history of drug use in Chennai, India. Fifty participants were randomized 1:1 to sofosbuvir+peginterferon alfa 2a+ribavirin (SOF+PR) for 12 weeks (Arm 1) vs sofosbuvir+ribavirin (SOF+R) for 24 weeks (Arm 2). SOF+R was delivered daily at participant chosen venues and weekly peginterferon injections at the study clinic. HCV RNA testing was performed to confirm active HCV infection and sustained virologic response 12 weeks after treatment completion (SVR12). No baseline genotyping or on‐treatment viral loads were performed. Median age was 46 years. All were male and 20% had significant fibrosis/cirrhosis. All self‐reported history of injection drug use, 18% recent noninjection drug use and 38% alcohol dependence. Six discontinued treatment (88% completed treatment in each arm). Of 22 who completed SOF+PR, all achieved SVR12 (22/25=88%); 15 of 22 who completed SOF+R achieved SVR12 (15/25=60%; P=.05). Among those completing SOF+R, SVR12 was significantly less common in participants reporting ongoing substance use (36% vs 100%) and missed doses. Active substance use and missed doses did not impact SVR with SOF+PR. Field‐based DOT of HCV therapy without real‐time HCV RNA monitoring was feasible; however, achieving 100% adherence was challenging. SOF+PR appeared superior to SOF+R in achieving SVR12, even when doses were missed with no discontinuations due to side effects. Further exploration of short duration treatment with peginterferon plus direct‐acting antivirals is warranted.
A novel framework for analyzing conservation impacts: evaluation, theory, and marine protected areas
Authors: Mascia Michael B. , Fox Helen E. , Glew Louise , Ahmadia Gabby N. , Agrawal Arun , Barnes Megan , Basurto Xavier , Craigie Ian , Darling Emily , Geldmann Jonas , Gill David , Holst Rice Susie , Jensen Olaf P. , Lester Sarah E. , McConney Patrick , Mumby Peter J. , Nenadovic Mateja , Parks John E. , Pomeroy Robert S. , White Alan T.
Published: July 2017

Environmental conservation initiatives, including marine protected areas (MPAs), have proliferated in recent decades. Designed to conserve marine biodiversity, many MPAs also seek to foster sustainable development. As is the case for many other environmental policies and programs, the impacts of MPAs are poorly understood. Social–ecological systems, impact evaluation, and common‐pool resource governance are three complementary scientific frameworks for documenting and explaining the ecological and social impacts of conservation interventions. We review key components of these three frameworks and their implications for the study of conservation policy, program, and project outcomes. Using MPAs as an illustrative example, we then draw upon these three frameworks to describe an integrated approach for rigorous empirical documentation and causal explanation of conservation impacts. This integrated three‐framework approach for impact evaluation of governance in social–ecological systems (3FIGS) accounts for alternative explanations, builds upon and advances social theory, and provides novel policy insights in ways that no single approach affords. Despite the inherent complexity of social–ecological systems and the difficulty of causal inference, the 3FIGS approach can dramatically advance our understanding of, and the evidentiary basis for, effective MPAs and other conservation initiatives.
Development of iFOX‐hunting as a functional genomic tool and demonstration of its use to identify early senescence‐related genes in the polyploid Brassica napus
Authors: Ling Juan , Li Renjie , Nwafor Chinedu Charles , Cheng Junluo , Li Maoteng , Xu Qing , Wu Jian , Gan Lu , Yang Qingyong , Liu Chao , Chen Ming , Zhou Yongming , Cahoon Edgar B. , Zhang Chunyu
Published: July 2017

Functional genomic studies of many polyploid crops, including rapeseed (Brassica napus), are constrained by limited tool sets. Here we report development of a gain‐of‐function platform, termed ‘iFOX (inducible Full‐length cDNA OvereXpressor gene)‐Hunting’, for inducible expression of B. napus seed cDNAs in Arabidopsis. A Gateway‐compatible plant gene expression vector containing a methoxyfenozide‐inducible constitutive promoter for transgene expression was developed. This vector was used for cloning of random cDNAs from developing B. napus seeds and subsequent Agrobacterium‐mediated transformation of Arabidopsis. The inducible promoter of this vector enabled identification of genes upon induction that are otherwise lethal when constitutively overexpressed and to control developmental timing of transgene expression. Evaluation of a subset of the resulting ~6000 Arabidopsis transformants revealed a high percentage of lines with full‐length B. napus transgene insertions. Upon induction, numerous iFOX lines with visible phenotypes were identified, including one that displayed early leaf senescence. Phenotypic analysis of this line (rsl‐1327) after methoxyfenozide induction indicated high degree of leaf chlorosis. The integrated B. napuscDNA was identified as a homolog of an Arabidopsis acyl‐CoA binding protein (ACBP) gene designated BnACBP1‐like. The early senescence phenotype conferred by BnACBP1‐like was confirmed by constitutive expression of this gene in Arabidopsis and B. napus. Use of the inducible promoter in the iFOX line coupled with RNA‐Seq analyses allowed mechanistic clues and a working model for the phenotype associated with BnACBP1‐like expression. Our results demonstrate the utility of iFOX‐Hunting as a tool for gene discovery and functional characterization of Brassica napus genome.
Virulence determines beneficial trade‐offs in the response of virus‐infected plants to drought via induction of salicylic acid
Authors: Aguilar Emmanuel , Cutrona Carmen , del Toro Francisco J. , Vallarino José G. , Osorio Sonia , Pérez‐Bueno María Luisa , Barón Matilde , Chung Bong‐Nam , Canto Tomás , Tenllado Francisco
Published: July 2017

It has been hypothesized that plants can get beneficial trade‐offs from viral infections when grown under drought conditions. However, experimental support for a positive correlation between virus‐induced drought tolerance and increased host fitness is scarce. We investigated whether increased virulence exhibited by the synergistic interaction involving Potato virus X (PVX) and Plum pox virus (PPV) improves tolerance to drought and host fitness in Nicotiana benthamiana and Arabidopsis thaliana. Infection by the pair PPV/PVX and by PPV expressing the virulence protein P25 of PVX conferred an enhanced drought‐tolerant phenotype compared with single infections with either PPV or PVX. Decreased transpiration rates in virus‐infected plants were correlated with drought tolerance in N. benthamiana but not in Arabidopsis. Metabolite and hormonal profiles of Arabidopsis plants infected with the different viruses showed a range of changes that positively correlated with a greater impact on drought tolerance. Virus infection enhanced drought tolerance in both species by increasing salicylic acid accumulation in an abscisic acid‐independent manner. Viable offspring derived from Arabidopsis plants infected with PPV increased relative to non‐infected plants, when exposed to drought. By contrast, the detrimental effect caused by the more virulent viruses overcame potential benefits associated with increased drought tolerance on host fitness.
Child and family‐related predictors of psychological outcomes in children adopted from abroad; what is the role of caregiver time?
Authors: Rita Niina , Elovainio Marko , Raaska Hanna , Lahti‐Nuuttila Pekka , Matomäki Jaakko , Sinkkonen Jari , Lapinleimu Helena
Published: July 2017

International adoptees need to cope with stressful transitions and to develop secure attachment with their caregivers at the same time. Although most children adopted from abroad adjust fine, they are at increased risk of psychological problems. We investigated whether both child and family‐related factors are associated with later psychological problems and whether the length of time spent at home after adoption before daycare moderates these associations among internationally adopted children in Finland (FinAdo, Finnish Adoption Study). The sample consisted of 1,265 children (708 girls, 557 boys) who arrived in Finland before they started school (mean age 2 years at arrival). Later behavioral problems were measured using the Child Behavior Check List (CBCL). According to our results, male gender, older age, child's early clinical symptoms (problems of sensory processing) and single parenthood were associated with later behavioral problems measured by CBCL scores. Longer stay at home before the start of daycare or school modified these results. Longer stay at home was associated with less later behavioral externalizing problems in girls but not in boys compared to those who spent a shorter time at home.
Evaluating sermons: The function of grades in teaching preaching
Authors: Helsel Carolyn Browning
Published: July 2017

What are grades doing in a homiletics classroom? This article traces the function of grades through the broader history of the educational system in the United States and then makes suggestions for how grades can be used more effectively in teaching preaching. Beginning in the nineteenth century, teachers used grades to rank and motivate students, as well as communicate across institutions. With the more recent assessment movement, educators have conceptualized grading as the larger process of evaluating the success of learning objectives. The commission on accreditation for the Association of Theological Schools does not view grades as part of its assessment, but it evaluates theological schools on whether they achieve intended learning outcomes. Theological educators need to be able to evaluate whether their teaching fulfills their schools' mission and learning objectives. For homiletics, the author measures learning through pre‐ and post‐preaching feedback and incorporates professor‐ and student‐crafted rubrics.
Reducing tillage intensity affects the cumulative emergence dynamics of annual grass weeds in winter cereals
Authors: Scherner A , Melander B , Jensen P K , Kudsk P , Avila LA
Published: July 2017

Annual grass weeds such as Apera spica‐venti and Vulpia myuros are promoted in non‐inversion tillage systems and winter cereal‐based crop rotations. Unsatisfactory weed control in these conditions is often associated with a poor understanding of the emergence pattern of these weed species. The aim of this study was to investigate, understand and model the cumulative emergence patterns of A. spica‐venti, V. myuros and Poa annua in winter cereals grown in three primary tillage regimes: (i) mouldboard ploughing, (ii) pre‐sowing tine cultivation to 8–10 cm soil depth and (iii) direct drilling. Direct drilling delayed the cumulative emergence of A. spica‐venti and V. myuros (counted together) in contrast with ploughing, while the emergence pattern of P. annua was unaffected by the type of tillage system. The total density of emerged weed seedlings varied between the tillage systems and years with a higher total emergence seen under direct drilling, followed by pre‐sowing tine cultivation and ploughing. The emergence patterns of all species were differently influenced by the tillage systems, suggesting that under direct drilling, in which these species occur simultaneously, management interventions should first and foremost consider that A. spica‐venti and V. myuros emerge over a longer period to avoid control failures.
Transient heat conduction in a heat fin
Authors: Brody Jed , Brown Max
Published: July 2017

We immerse the bottom of a rod in ice water and record the time-dependent temperatures at positions along the length of the rod. Though the experiment is simple, a surprisingly difficult problem in heat conduction must be solved to obtain a theoretical fit to the measured data. The required equipment is very inexpensive and could be assigned as a homework exercise or a hands-on component of an online course.
Artificial circumzenithal and circumhorizontal arcs
Authors: Selmke Markus , Selmke Sarah
Published: July 2017

A glass of water, with white light incident upon it, is typically used to demonstrate a rainbow. On a closer look, this system turns out to be a rather close analogy of a different kind of atmospheric optics phenomenon altogether: circumzenithal and the circumhorizontal halos. The work we present here should provide a missing practical demonstration for these beautiful and common natural ice halo displays.
Transmission of Resistant Gram-Negative Bacteria to Health Care Worker Gowns and Gloves during Care of Nursing Home Residents in Veterans Affairs Community Living Centers
Authors: Blanco Natalia , Pineles Lisa , Lydecker Alison D. , Johnson J. Kristie , Sorkin John D. , Morgan Daniel J. ,   the VA Gown and Glove Investigators, Roghmann Mary-Claire
Published: July 2017

The objectives of the study were to estimate the risk of transmission of antibiotic-resistant Gram-negative bacteria (RGNB) to gowns and gloves (G&G) worn by health care workers (HCWs) when providing care to nursing home residents and to identify the types of care and resident characteristics associated with transmission. A multicenter, prospective observational study was conducted with residents and HCWs from Veterans Affairs (VA) nursing homes. Perianal swabs to detect RGNB were collected from residents. HCWs wore G&G during usual care activities, and the G&G were swabbed at the end of the interaction in a standardized manner. Transmission of RGNB from a colonized resident to G&G by type of care was measured. Odds ratios (ORs) associated with type of care or resident characteristics were estimated. Fifty-seven (31%) of 185 enrolled residents were colonized with ≥1 RGNB. RGNB transmission to HCW gloves or gowns occurred during 9% of the interactions (n= 905): 7% to only gloves and 2% to only gowns. Bathing the resident and providing hygiene and toilet assistance were associated with a high risk of transmission. Glucose monitoring and assistance with feeding or medication were associated with a low risk of transmission. In addition, antibiotic use by the resident was strongly associated with greater transmission (OR, 2.51;P< 0.01). RGNB were transferred to HCWs during ∼9% of visits. High-risk types of care were identified for which use of G&G may be prioritized. Antibiotic use was associated with 2.5 times greater risk of transmission, emphasizing the importance of antibiotic stewardship. (This study has been registered at ClinicalTrials.gov under registration no. NCT01350479.)
Phagocytic Receptors Activate Syk and Src Signaling during Borrelia burgdorferi Phagocytosis
Authors: Killpack Tess L. , Ballesteros Maria , Bunnell Stephen C. , Bedugnis Alice , Kobzik Lester , Hu Linden T. , Petnicki-Ocwieja Tanja
Published: July 2017

Phagocytosis of the Lyme disease-causing pathogenBorrelia burgdorferihas been shown to be important for generating an inflammatory response to the pathogen. As a result, understanding the mechanisms of phagocytosis has been an area of great interest in the field of Lyme disease. Several cell surface receptors that participate inB. burgdorferiphagocytosis have been reported, including the scavenger receptor MARCO and integrin α3β1. We sought to define the mechanisms by which these receptors mediate phagocytosis and to identify signaling pathways activated downstream of these receptors upon contact withB. burgdorferi. We identified both Syk and Src signaling pathways as ones that participate inB. burgdorferiphagocytosis and the resulting cytokine activation. In our studies, we found that both MARCO and integrin β1 play a role in the activation of the Src kinase pathway. However, only integrin β1 participates in the activation of Syk. Interestingly, the integrin activates Syk without the help of the signaling adaptor Dap12 or FcRγ. Thus, we report that multiple pathways participate inB. burgdorferiinternalization and that different cell surface receptors act simultaneously in cooperation and independently to mediate phagocytosis.