bluuebunny/crossref_metadata_2025 huggingface dataset:
Compound fire‐drought regimes promote ecosystem transitions in Mediterranean ecosystems
Authors: Batllori Enric , De Cáceres Miquel , Brotons Lluís , Ackerly David D. , Moritz Max A. , Lloret Francisco
Published: November 2018

Understanding ecosystem responses to compound disturbance regimes and the influence of specific sequences of events in determining ecosystem shifts remains a challenge.

We use a modelling framework for Mediterranean‐type ecosystems to assess the effects of fire–drought interactions on long‐term vegetation dynamics and to identify disturbance‐driven changes in trait composition (tree seeder vs. tree resprouter prevalence) and ecosystem state (forest vs. non‐forest).

Changes in tree seeder and the tree resprouter dominance show nonlinear, threshold‐type trends over gradients of increasing compound disturbance frequency. Vegetation composition thresholds mostly occur in a narrow range of the compound fire–drought disturbance space. Additionally, trait compositional switches and the likelihood of sudden changes in ecosystem state are promoted by fire‐drought interactions.

Distinct sequences of disturbance events cause vegetation transitions, disrupting ecosystem resilience, even under moderate recurrence of individual disturbances. An extreme drought year followed by one or two large fire events promotes shifts from resprouter‐ to seeder dominance. Contrastingly, a large crown fire followed by an extreme drought promotes changes from seeder to resprouter dominance. This disturbance sequence is also a mechanism strong enough to trigger sudden shifts in ecosystem state (from forest to non‐forest).

Synthesis. Thresholds of change in vegetation composition occur over a narrow range of the modelled gradients of compound fire‐drought recurrence, and the loss of ecosystem resilience is contingent on particular sequences of disturbance events. Overall, our findings highlight that disturbance interactions define the relative location of tipping points in ecosystem state, and that effects and feedbacks of compound disturbance regimes increase the long‐term likelihood of sudden ecosystem shifts and, therefore, uncertainty in predicting vegetation state.
Trimebutine maleate relaxes the isolated rat thoracic aorta: The role of nitric oxide and L‐type calcium channels
Authors: Kadioglu Mine , Kaya Yasar Yesim , Barut Elif Nur , Engin Seckin
Published: November 2018

Trimebutine maleate (TMB), a widely prescribed drug for functional gastrointestinal disorders, has been reported to regulate smooth muscle contractility by modulating multiple ion channel activities in the gastrointestinal tract. However, its action on isolated aorta has not yet been reported. The aim of the present study was to evaluate in vitro vasorelaxant properties and the underlying pharmacological mechanisms of TMB in isolated rat thoracic aortic rings. Vascular activity experiments were performed on thoracic aorta isolated from Sprague‐Dawley rats in vitro, including endothelium‐intact and endothelium‐denuded aortic rings. TMB (10−10‐10−5 mol/L) induced relaxation in endothelium‐intact aortic rings precontracted by phenylephrine with a potency similar to that of carbachol. TMB‐induced relaxation was not altered by glibenclamide and atropine in endothelium‐intact aortic rings. However, L‐NAME and endothelium denudation significantly reduced but not completely reversed the vasorelaxant effect of TMB. Also, TMB‐induced relaxation wasn't affected by diclofenac in endothelium‐intact aortic rings. TMB at 10−5 mol/L significantly reduced the CaCl2‐induced contractions in endothelium‐intact aortic rings stimulated with KCl, but not stimulated with phenylephrine under Ca2+free conditions. Moreover, TMB at 10−5 mol/L effectively attenuated Bay‐K8644‐induced contractions in aortic rings. These results suggest that TMB‐induced relaxation was mediated by both endothelium‐dependent and endothelium‐independent manner in isolated rat thoracic aorta. The mechanism of TMB‐induced relaxation at low concentrations is partially related to NO‐ and endothelium‐dependent but unrelated to prostanoids formation. However, inhibition of Ca2+ influx through voltage‐operated calcium channels and L‐type Ca2+channel blocking effect appears to be involved in the mechanism of vasorelaxant effect of TMB at high concentrations.
First‐dose effect of the SGLT2 inhibitor ipragliflozin on cardiovascular activity in spontaneously diabetic Torii fatty rats
Authors: Takakura Shoji , Takasu Toshiyuki
Published: November 2018

The first dose of a sodium‐dependent glucose cotransporter 2 (SGLT2) inhibitor induces osmotic diuresis and can thereby affect cardiovascular activity in hyperglycemic patients. We aimed to determine whether the first dose of the selective SGLT2 inhibitor ipragliflozin affects cardiovascular activity in non‐diabetic Sprague‐Dawley (SD) rats and Spontaneously Diabetic Torii (SDT) fatty rats in two studies, a urine collection study and a telemetry study. In the former study, urine was collected for 24 hours after a single oral dose of ipragliflozin. In the latter study, systolic blood pressure (SBP) and heart rate (HR) were continuously monitored for 24 hours under conscious and unrestrained conditions from immediately before the administration of ipragliflozin. The telemetry study was conducted in a crossover design at successive 1 week intervals. Cardiovascular autonomic nerve activity was calculated from the SBP and HR. SDT fatty rats exhibited polyuria, glucosuria and hyperglycemia. In addition, the mean and standard deviation of SBP were higher, while the coefficient of variance of HR was lower than the respective parameters in SD rats. Ipragliflozin increased both urine output and urinary glucose excretion, and the increases were more pronounced in SDT fatty rats than in SD rats. In contrast, ipragliflozin had no effect on SBP, the standard deviation of SBP, HR, and the coefficient of variance of HR, or on autonomic nerve activity in either rat strain. These results suggest that the first dose of the SGLT2 inhibitor ipragliflozin has little impact on cardiovascular activity despite causing glucosuria with osmotic diuresis.
Chemically mediated interactions between Microcystis and Planktothrix: impact on their growth, morphology and metabolic profiles
Authors: Briand Enora , Reubrecht Sébastien , Mondeguer Florence , Sibat Manoëlla , Hess Philipp , Amzil Zouher , Bormans Myriam
Published: November 2018

Freshwater cyanobacteria are known for their ability to produce bioactive compounds, some of which have been described as allelochemicals. Using a combined approach of co‐cultures and analyses of metabolic profiles, we investigated chemically mediated interactions between two cyanobacterial strains, Microcystis aeruginosa PCC 7806 and Planktothrix agardhii PCC 7805. More precisely, we evaluated changes in growth, morphology and metabolite production and release by both interacting species. Co‐culture of Microcystis with Planktothrix resulted in a reduction of the growth of Planktothrix together with a decrease of its trichome size and alterations in the morphology of its cells. The production of intracellular compounds by Planktothrix showed a slight decrease between monoculture and co‐culture conditions. Concerning Microcystis, the number of intracellular compounds was higher under co‐culture condition than under monoculture. Overall, Microcystis produced a lower number of intracellular compounds under monoculture than Planktothrix, and a higher number of intracellular compounds than Planktothrix under co‐culture condition. Our investigation did not allow us to identify specifically the compounds causing the observed physiological and morphological changes of Planktothrix cells. However, altogether, these results suggest that co‐culture induces specific compounds as a response by Microcystis to the presence of Planktothrix. Further studies should be undertaken for identification of such potential allelochemicals.
Improved protein production and codon optimization analyses in Escherichia coli by bicistronic design
Authors: Nieuwkoop Thijs , Claassens Nico J. , van der Oost John
Published: November 2018

Different codon optimization algorithms are available that aim at improving protein production by optimizing translation elongation. In these algorithms, it is generally not considered how the altered protein coding sequence will affect the secondary structure of the corresponding RNA transcript, particularly not the effect on the 5′‐UTR structure and related ribosome binding site availability. This is a serious drawback, because the influence of codon usage on mRNA secondary structures, especially near the start of a gene, may strongly influence translation initiation. In this study, we aim to reduce the effect of codon usage on translation initiation by applying a bicistronic design (BCD) element. Protein production of several codon‐optimized gene variants is tested in parallel for a BCD and a standard monocistronic design (MCD). We demonstrate that these distinct architectures can drastically change the relative performance of different codon optimization algorithms. We conclude that a BCD is indispensable in future studies that aim to reveal the impact of codon optimization and codon usage correlations. Furthermore, irrespective of the algorithm used, using a BCD does improve protein production compared with an MCD. The overall highest expression from BCDs for both GFP and RFP is at least twofold higher than the highest levels found for the MCDs, while for codon variants having very low expression from the MCD, even 10‐fold to 100‐fold increases in expression were achieved by the BCD. This shows the great potential of the BCD element for recombinant protein production.
Characteristics of gout patients according to the laterality of nephrolithiasis: A cross‐sectional study using helical computed tomography
Authors: Shimizu Toru , Hori Hiroshi , Umeyama Masanori , Shimizu Kentaro
Published: November 2018

Objective

To clarify the clinical and laboratory characteristics of nephrolithiasis in gout by computed tomography (CT).

Methods

In 350 gout patients, unenhanced CT was performed at the 1st visit to hospital. Calculus density spots exceeding 1 mm in diameter with a CT value >120 Hounsfield units in the kidneys were defined as kidney stones. The association between laterality and the number of stones was investigated in each stone carrier. The 350 patients were classified into three groups (bilateral, unilateral and non‐stone carriers). Then serum urate (Sua), renal function, uric acid metabolism, and the prevalence of metabolic syndrome (Mets) were compared among these groups by the Tukey‐Kramer test or Fisher's exact test.

Results

Kidney stone(s) were detected in 108 (31%) of the 350 patients (bilateral in 58 and unilateral in 50). In 64 of the 108 patients (59%), there was no history of urolithiasis. Sua, serum creatinine and uric acid clearance were significantly higher (P = 0.001, P < 0.001, P = 0.043, respectively), while the estimated glomerular filtration rate was significantly lower (P = 0.039) in bilateral stone carriers than in non‐stone carriers. No significant differences of uric acid metabolism or the prevalence of Mets were noted among the three groups.

Conclusions

Approximately one‐third of gout patients had kidney stones and more than half of the patients with stones were bilateral and multiple stone carriers. Elevation of Sua might increase the stone burden in gout, leading to more severe renal dysfunction. An association between nephrolithiasis and Mets was not demonstrated in gout patients.
Changes in the incidence and uptake of reproductive surgery versus in vitro fertilisation in Australia between 2001 and 2015: A population‐based study
Authors: Foster Leon , Robson Stephen J. , Yazdani Anusch , O'Shaughnessy Pauline Y.
Published: November 2018

Objective

Improvements in success rates of assisted reproduction led to predictions that infertility surgery in both women and men would become extinct in developed countries. We sought to identify the changes in reproductive surgery that occurred between 2001 and 2015 to determine whether these predictions have been accurate.

Design

The Australian Institute of Health and Welfare (AIHW) national procedural dataset and the Australian Medicare Benefits Scheme (MBS) claims database were searched for procedure data for male and female reproductive surgery and assisted reproduction from January 2001 to December 2015. The denominators were based on annual point estimates of the total population aged 25–44 years (female) and 25–55 years (male) from the Australian Bureau of Statistics (ABS). This dataset provides procedures undertaken but not their indications.

Results

Over the study period the incidence of tubal surgery fell by 66%, vasectomy reversal by 33%, and surgical varicocoelectomy by 50%. In contrast, the rate of hysteroscopic myomectomy increased by 48%, hysteroscopic septoplasty by 125%, and laparoscopy for severe endometriosis increased by 84%. In vitro fertilisation oocyte retrievals increased by 90%. The rate of abdominal myomectomy was unchanged.

Conclusion

Fertility surgery is not dead but has evolved.
Complete resection of colorectal cancer with ovarian metastases combined with chemotherapy is associated with improved survival
Authors: Al‐Busaidi Ibrahim S. , Bailey Teresa , Dobbs Bruce , Eglinton Tim W. , Wakeman Christopher J. , Frizelle Frank A.
Published: November 2018

Background

Ovarian metastases (OM) from colorectal cancer (CRC) are uncommon, and data about optimal management are lacking. The aim of this study was to examine the management and outcomes of patients with OM from CRC.

Methods

A retrospective review of records of patients with a histopathological diagnosis of OM from CRC who were treated at Christchurch Hospital between 1 January 2000 and 31 December 2016. Data related to presentation, clinicopathological characteristics, treatment and outcomes were recorded. The primary outcomes were overall survival and disease‐free survival.

Results

Thirty‐one patients were identified (median age 55 years, range 28–77), with a median follow‐up of 23 months (range 3–84 months). Abdominal pain was the most common presenting symptom (22 patients). Synchronous OM occurred in 22 patients, 14 patients had bilateral ovarian involvement. Twenty‐one patients received adjuvant chemotherapy. R0 resection was achieved in 14 patients. For all patients the 5‐year disease‐free and overall survival were 11% and 12%, respectively, while 5‐year overall survival for R0 resections was 30%. Improved median survival was associated with negative colon resection margins (26.7 months versus 7.8 months, P = 0.03), R0 resection (30.5 months versus 23.5 months, P = 0.04), and use of adjuvant chemotherapy (28.8 months versus 8.2 months, P < 0.0001); however, on multivariate analysis adjuvant chemotherapy was the only independent factor associated with improved prognosis (P = 0.01).

Conclusions

OM from CRC are uncommon and carry a poor prognosis. Improved survival was associated with complete surgical resection of the primary tumour and metastatic disease in combination with systemic chemotherapy.
Surveys still teach vital non‐technical lessons in General Surgery
Authors: Hamilton Auerilius E. R. , Young Christopher J.
Published: November 2018

In general surgery, observational studies are disregarded and often seen as non‐noteworthy research. We intend to defend the use of surveys in general surgery and colorectal surgery. This review highlights the historical importance and contemporary utility of surveys internationally and in our region, thus reminding Australasian surgeons and clinicians in numerous disciplines of the usefulness of this research tool. Well‐constructed surveys often successfully capture qualitative data otherwise impossible to collect through randomized controlled trial. The results of these surveys may advise national policies and medical registration agencies thus having a direct influence on individuals and their public health. Samples from contemporary survey‐based research publications from international and Australasian authors are used to illustrate some of the vital non‐technical lessons learned in recent times.
Severe vitamin D deficiency is a prognostic biomarker in autoimmune hepatitis
Authors: Ebadi Maryam , Bhanji Rahima A. , Mazurak Vera C. , Lytvyak Ellina , Mason Andrew , Czaja Albert J. , Montano‐Loza Aldo J.
Published: November 2018

Background

Vitamin D deficiency has been implicated in the outcome of chronic liver disease.

Aim

To determine the frequency of severe vitamin D deficiency in autoimmune hepatitis (AIH), assess its association with treatment non‐response, and evaluate the relationship between vitamin D status and liver‐related mortality and need for transplantation.

Methods

Two hundred and nine patients were evaluated by liver tissue examination at presentation. Serum vitamin D levels were determined, and serum levels <25 nmol/L (10 ng/mL) were considered severely deficient. Treatment non‐response was defined as non‐normalised aspartate aminotransferase/alanine aminotransferase and immunoglobulin G levels during conventional immunosuppressive therapy. Univariate and multivariate analyses were performed using binary logistic regression and Cox proportional hazards model.

Results

The mean vitamin D level was 60 ± 38 nmol/L (range, 3‐263 nmol/L), and 42 patients (20%) had severe vitamin D deficiency. Treatment non‐response was more common in patients with severe vitamin D deficiency than in patients without (59% vs 41%, P = 0.04). Severe vitamin D deficiency was also independently associated with a higher risk of developing cirrhosis (HR 3.40; 95% CI 1.30‐8.87, P = 0.01) and liver‐related mortality or requirement for liver transplantation (LT; HR 5.26, 95% CI, 1.54‐18.0, P = 0.008). Patients with persistent severe deficiency following vitamin D supplementation continued to have poor outcomes.

Conclusions

Severe vitamin D deficiency is associated with treatment non‐response, progression to cirrhosis, and liver‐related death or need for LT. Severe vitamin D deficiency is a prognostic biomarker in AIH.
Review article: emulsifiers in the food supply and implications for gastrointestinal disease
Authors: Halmos Emma P. , Mack Alexandra , Gibson Peter R.
Published: November 2018

Background

Dietary emulsifiers are the latest food additives to be associated with intestinal, cardiovascular and metabolic health. Most recently, there are postulations around certain emulsifiers playing a role in the development of Crohn's disease.

Aim

To review the use of food‐based emulsifiers, their content in the food supply and mechanisms by which they might exert potentially detrimental biological effects.

Methods

Information on emulsifiers and thickeners relevant to human health was critically examined.

Results

The term, “emulsifier,” has been used loosely and has included thickeners as well as agents that truly promote emulsions. These comprise proteins, phospholipids and carbohydrates, alone or in combination, and play roles in optimising food appearance, texture and mouthfeel, delivering or disguising flavours and achieving palatable low‐fat foods. Their presence in the food supply is common, but not “ubiquitous” as frequently stated. Strict regulations limit the amount added to foods, but the lack of established methodologies to measure the actual food content of these diverse compounds limits our knowledge of consumption. Emulsifiers and thickeners have effects on the gut microbiota, mucosal barrier and inflammatory pathways, and can induce disease in experimental models. However, differentiating pharmacological from physiological effects and translating findings in experimental animals to humans raise uncertainties about the relevance of such effects.

Conclusions

There is limited evidence to directly link emulsifiers and thickeners to human disease, but multiple potential pathogenic mechanisms. Knowledge of actual dietary intake and high‐quality interventional studies is needed to enable the risks associated with their intake to be understood.
Hepatitis B virus relapse rates in chronic hepatitis B patients who discontinue either entecavir or tenofovir
Authors: Kuo Ming‐Te , Hu Tsung‐Hui , Hung Chao‐Hung , Wang Jing‐Houng , Lu Sheng‐Nan , Tsai Kai‐Lung , Chen Chien‐Hung
Published: November 2018

Background

Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are first‐line long‐term monotherapy for treatment of chronic hepatitis B (CHB) infection. High virological relapse rates are found after cessation of either ETV or TDF in CHB patients.

Aim

To compare hepatitis B virus (HBV) relapse rates in CHB patients without cirrhosis who discontinued ETV or TDF.

Methods

A retrospective‐prospective study was conducted in 342 CHB patients (108 hepatitis B e antigen (HBeAg)‐positive and 234 HBeAg‐negative) who received ETV and 165 (46 HBeAg‐positive, 119 HBeAg‐negative) who received TDF were recruited. All patients had post‐treatment follow‐up for at least 6 months. All fulfilled the stopping criteria of the Asia‐Pacific Association for the Study of the Liver of 2012.

Results

Patients who discontinued TDF had significantly higher rates and earlier times of virological and clinical relapse than those who discontinued ETV. This was also seen in propensity score (PS)‐matched HBeAg‐positive and HBeAg‐negative patients. Multivariate analysis showed that being in the TDF group was an independent factor for virological and clinical relapse in all patients and PS‐matched HBeAg‐positive and HBeAg‐negative patients. The rate of off‐therapy HBsAg loss was comparable between the ETV and TDF groups after 2‐3 years follow‐up. Clinical relapse tended to be more severe in the TDF group compared with the ETV group.

Conclusion

HBV relapse occurs sooner and is more severe after cessation of TDF than after cessation of ETV.
Vaccination for influenza and pneumococcus in patients with gastrointestinal cancer or inflammatory bowel disease: A prospective cohort study of methods for improving coverage
Authors: Sitte Julien , Frentiu Emilia , Baumann Cédric , Rousseau Hélène , May Thierry , Bronowicki Jean‐Pierre , Peyrin‐Biroulet Laurent , Lopez Anthony
Published: November 2018

Background

Although influenza and pneumococcal vaccinations for high‐risk populations are recommended by current guidelines, vaccination coverage is low in patients with gastrointestinal cancer (GC) or inflammatory bowel disease (IBD).

Aim

To evaluate the impact of a specialised infectious disease consultation on vaccination coverage rates in these patients.

Methods

Between December 2016 and April 2017, all patients with GC or IBD followed in the outpatient clinic of the Gastroenterology department at the Nancy University Hospital enrolled in a 3‐phase vaccination programme. Phase 1: Initial questionnaire (vaccination status, knowledge about vaccines and possible barriers to vaccination); Phase 2: Infectious disease consultation; Phase 3: Subsequent questionnaire (evolution of patients’ knowledge about vaccination).

Results

A total of 366 patients were included (GC = 99, IBD = 267). Vaccination rate was 34.7% for influenza and 14.5% for pneumococcus. About 43% of the patients feared side effects of vaccines. After the initial questionnaire, 49.3% of the interested patients participated in a specialised vaccination consultation (n = 102). 87.3% (n = 89) received new vaccination, 41.2% changed their mind about vaccination, and 92.2% would recommend this programme to other patients. Among vaccinated patients, 97.8% (n = 87) received pneumococcal vaccine, 40.4% received tetanus‐diphtheria‐polio vaccine, and 7.9% received influenza vaccine. In GC patients, anti‐pneumococcal vaccination rate was 87.5% after the specialised consultation compared with 10.1% before. In IBD patients, corresponding rates were 85.7% and 16.1%.

Conclusions

A specialised infectious disease consultation can improve GC and IBD patients’ knowledge about vaccination and vaccination coverage. This approach could be applied to all high‐risk populations.
Differences in cardiovascular safety with non‐steroidal anti‐inflammatory drug therapy—A nationwide study in patients with osteoarthritis
Authors: Barcella Carlo Alberto , Lamberts Morten , McGettigan Patricia , Fosbøl Emil Loldrup , Lindhardsen Jesper , Torp‐Pedersen Christian , Gislason Gunnar Hilmar , Olsen Anne‐Marie Schjerning
Published: November 2018

Osteoarthritis (OA) and the non‐steroidal anti‐inflammatory drugs (NSAIDs) used to relieve OA‐associated pain have been linked independently to increased cardiovascular risk. We examined the risk of cardiovascular events associated with NSAID use in patients with OA. We employed linked nationwide administrative registers to examine NSAID use between 1996 and 2015 by Danish patients with OA aged ≥18 years. Using adjusted Cox proportional hazard analyses, we calculated the risk of the composite outcome of cardiovascular death, non‐fatal myocardial infarction and non‐fatal ischaemic stroke/TIA, and of each outcome separately, up to 5 years after OA diagnosis. Of 533 502 patients included, 64.3% received NSAIDs and 38 226 (7.2%) experienced a cardiovascular event during follow‐up. Compared with non‐use, all NSAIDs were associated with increased risk of the composite outcome: hazard ratio (HR) for rofecoxib, 1.90 (95% confidence interval, 1.74‐2.08); celecoxib, 1.47 (1.34‐1.62); diclofenac, 1.44 (1.36‐1.54); ibuprofen, 1.20 (1.15‐1.25); and naproxen, 1.20 (1.04‐1.39). Similar results were seen for each outcome separately. When celecoxib was used as reference, ibuprofen (HRs: 0.81 [CI: 0.74‐0.90]) and naproxen (HRs: 0.81 [0.68‐0.97]) exhibited a lower cardiovascular risk, even when low doses were compared. Low‐dose naproxen and ibuprofen were associated with the lowest risks of the composite outcome compared to no NSAID use: HRs: 1.12 (1.07‐1.19) and 1.16 (0.92‐1.42), respectively. In patients with OA, we found significant differences in cardiovascular risk among NSAIDs. Naproxen and ibuprofen appeared to be safer compared to celecoxib, also when we examined equivalent low doses. In terms of cardiovascular safety, naproxen and ibuprofen, at the lowest effective doses, may be the preferred first choices among patients with OA needing pain relief.
Thyrotrophin receptor antibody concentration and activity, several years after treatment for Graves’ disease
Authors: Nalla Preethi , Young Stuart , Sanders Jane , Carter Joanne , Adlan Mohamed A. , Kabelis Katarzyna , Chen Shu , Furmaniak Jadwiga , Rees Smith Bernard , Premawardhana Lakdasa D. K. E.
Published: November 2018

Objective

TSH receptor antibodies (TRAb) are responsible for autoimmune hyperthyroid disease (Graves’ disease; GD) with TRAb levels tending to decrease following treatment. Measurement of TRAb activity during follow‐up could prove valuable to better understand treatment effectiveness.

Study design

TRAb concentration and stimulating (TSAb) and blocking (TSBAb) activity of patient serum were assessed following different treatment modalities and follow‐up length.

Methods

Sixty‐six subjects were recruited following treatment with carbimazole (n = 26), radioiodine (n = 27) or surgery (n = 13). TRAb, TPOAb, TgAb and GADAb were measured at a follow‐up visit as well as bioassays of TSAb and TSBAb activity.

Results

Forty‐five per cent of all patients remained TRAb‐positive for more than one year and 23% for more than 5 years after diagnosis, irrespective of treatment method. Overall, TRAb concentration fell from a median (IQR) of 6.25 (3.9‐12.7) to 0.65 (0.38‐3.2) U/L. Surgery conferred the largest fall in TRAb concentration from 11.4 (6.7‐29) to 0.58 (0.4‐1.4) U/L. Seventy per cent of TRAb‐positive patients were positive for TSAb, and one patient (3%) was positive for TSBAb. TRAb and TSAb correlated well (r = 0.83). In addition, 38/66 patients were TgAb‐positive, 47/66 were TPOAb‐positive and 6/66 were GADAb‐positive at follow‐up.

Conclusions

TRAb levels generally decreased after treatment but persisted for over 5 years in some patients. TRAb activity was predominantly stimulatory, with only one patient demonstrating TSBAb. A large proportion of patients were TgAb/TPOAb‐positive at follow‐up. All treatment modalities reduced TRAb concentrations; however, surgery was most effective.
Effects of intravitreal bevacizumab in Gram‐positive and Gram‐negative models of ocular inflammation
Authors: Lafreniere J. Daniel , Toguri James T. , Gupta Rishi R. , Samad Arif , O'Brien Dan M. , Dickinson John , Cruess Alan , Kelly Melanie E. M. , Seamone Mark E.
Published: November 2018

Background

Exogenous endophthalmitis is a potential complication of intraocular surgery and frequently results in visual impairment. Current treatment involves administration of intravitreal (IVT) antibiotics with or without vitrectomy surgery. Evidence for the use of adjunctive anti‐inflammatory agents is conflicting. We set out to determine if bevacizumab, a humanized monoclonal IgG1 antibody targeted against vascular endothelial growth factor (VEGF), has anti‐inflammatory properties in experimental models of Gram‐positive and Gram‐negative inflammation.

Methods

BALB/c mice were subjected to lipopolysaccharide‐ (LPS) or peptidoglycan‐ (PGN) induced ocular inflammation and treated with IVT bevacizumab. Iris microvasculature was imaged 6 hours following irritant/treatment using intravital microscopy (IVM) before the mice were euthanized and the eyes were enucleated immediately post‐mortem. Following enucleation, levels of VEGF and 23 cytokines and chemokines (IL‐1α, IL‐1β, IL‐2, IL‐3, IL‐4, IL‐5, IL‐6, IL‐10, IL‐12 (p40), IL‐12 (p70), IL‐13, IL‐17, TNF, KC, G‐CSF, GM‐CSF, Eotaxin, INF‐γ, MCP‐1, MIP‐1α, MIP‐1β, RANTES) were quantified using a multiplex assay.

Results

Levels of VEGF were significantly increased during the inflammatory response, triggered by either PGN or LPS. Both the adherence of leukocytes to the iris vascular endothelium and the levels of pro‐inflammatory cytokines and chemokines were significantly increased following administration of either irritant. Treatment with bevacizumab decreased levels of leukocyte adherence in LPS‐treated eyes, however, not in PGN‐treated eyes. Conversely, bevacizumab treatment decreased levels of cytokines and chemokines (TNF, IL‐6, MCP‐1, MIP‐1α, MIP‐1β, RANTES, KC) in PGN‐treated eyes, however, not in LPS‐treated eyes.

Conclusions

Within a 6‐hour window bevacizumab had anti‐inflammatory actions that were distinct in both Gram‐positive (PIU) and Gram‐negative (EIU) models, respectively. Given our findings, this would suggest that bevacizumab may have utility as an adjunctive therapy to IVT antibiotics and vitrectomy in the management of exogenous endophthalmitis.
CSE1L participates in regulating cell mitosis in human seminoma
Authors: Liu Chunyan , Wei Jiajing , Xu Kang , Sun Xiaosong , Zhang Huiping , Xiong Chengliang
Published: November 2018

Objectives

CSE1L has been reported to be highly expressed in various tumours. Testicular germ cell tumours are common among young males, and seminoma is the major type. However, whether CSE1L has functions in the seminoma is unclear.

Materials and methods

The expression of CSE1L was detected by immunohistochemistry in seminoma tissues and non‐tumour normal testis tissues from patients. CSE1L distribution during cell mitosis was determined by immunofluorescent staining with CSE1L, α‐tubulin and γ‐tubulin antibodies. The effects of Cse1L knockdown on cell proliferation and cell cycle progression were determined by Cell Counting Kit‐8 assay, flow cytometry, PH3 staining and bromodeoxyuridine incorporation assay.

Results

CSE1L was significantly enriched in the seminoma tissue compared with the non‐tumour normal testis tissue. CSE1L also co‐localized with α‐tubulin in the cells with a potential to divide. In the seminoma cell line TCam‐2, CSE1L was associated with the spindles and the centrosomes during cell division. The knockdown of CSE1L in TCam‐2 cells attenuated the cells’ proliferative capacity. Cell cycle assay revealed that the CSE1L‐deficient cells were mainly arrested in the G0/G1 phase and moderately delayed in the G2/M phase. The proportion of cells with multipolar spindle and abnormal spindle geometry was obviously increased by CSE1L expression silencing in the TCam‐2 cells.

Conclusions

Overall, these findings showed that CSE1L plays a pivotal role in maintaining cell proliferation and cell division in seminomas.
MiR‐326/Sp1/KLF3: A novel regulatory axis in lung cancer progression
Authors: Wang Rong , Xu Jiali , Xu Jing , Zhu Wei , Qiu Tianzhu , Li Jun , Zhang Meiling , Wang Qianqian , Xu Tongpeng , Guo Renhua , Lu Kaihua , Yin Yongmei , Gu Yanhong , Zhu Lingjun , Huang Puwen , Liu Ping , Liu Lianke , De Wei , Shu Yongqian
Published: November 2018

Objectives

To investigate the function and regulatory mechanism of Krüppel‐like factor 3 (KLF3) in lung cancer.

Materials and Methods

KLF3 expression was analysed by qRT‐PCR and Western blot assays. The proliferation, migration, invasion, cycle and apoptosis were measured by CCK‐8 and EdU, wound‐healing and Transwell, and flow cytometry assays. The tumour growth was detected by nude mouse tumorigenesis assay. In addition, the interaction between KLF3 and Sp1 was accessed by luciferase reporter, EMSA and ChIP assay. JAK2, STAT3, PI3K and p‐AKT levels were evaluated by Western blot and IHC assays.

Results

The results indicated that KLF3 expression was elevated in lung cancer tissues. Knockdown of KLF3 inhibited lung cancer cell proliferation, migration and invasion, and induced cell cycle arrest and apoptosis. In addition, the downregulation of KLF3 suppressed tumour growth in vivo. KLF3 was transcriptionally activated by Sp1. miR‐326 could bind to 3′UTR of Sp1 but not KLF3 and decreased the accumulation of Sp1, which further indirectly reduced KLF3 expression and inactivated JAK2/STAT3 and PI3K/AKT signaling pathways in vitro and in vivo.

Conclusions

Our data demonstrate that miR‐326/Sp1/KLF3 regulatory axis is involved in the development of lung cancer, which hints the potential target for the further therapeutic strategy against lung cancer.
FOXM1c promotes oesophageal cancer metastasis by transcriptionally regulating IRF1 expression
Authors: Zhou Yuzhen , Wang Qi , Chu Li , Dai Weixing , Zhang Xiaozhou , Chen Jianfeng , Zhang Long , Ding Peipei , Zhang Xin , Gu Hongyu , Zhang Pingzhao , Li Ling , Zhang Wei , Li Luying , Lv Xinyue , Zhou Danlei , Cai Guoxiang , Chen Liang , Zhao Kuaile , Hu Weiguo
Published: November 2018

Objectives

We aimed to elucidate the role and molecular mechanisms of FOXM1 in regulating metastasis in oesophageal squamous cell carcinoma (ESCC) as well as its clinical implications.

Materials and methods

The expression levels of four isoforms of FOXM1 were analysed by real‐time PCR. Next, genetically modification using overexpression and RNAi systems and transwell were employed to examine FOXM1c function in invasion and migration. Dual luciferase and ChIP assays were performed to decipher the underlying mechanism for transcriptional regulation. The expression levels of FOXM1 and IRF1 were determined by immunohistochemistry staining in ESCC specimens.

Results

The FOXM1c was predominantly overexpressed in ESCC cell lines compared to the other FOXM1 isoforms. Ectopic expression of FOXM1c promoted invasion and migration of ESCC cells lines, whereas downregulation of FOXM1c inhibited these processes. Moreover, FOXM1c expression was positively correlated with IRF1 expression in ESCC cell lines and tumour specimens. IRF1 is, at least in part, responsible for FOXM1c‐mediated invasion and migration. Mechanistically, we identified IRF1 as a transcriptional target of FOXM1c and found a FOXM1c‐binding site in the IRF1 promoter region. Furthermore, high expression levels of both FOXM1c and IRF1 were positively associated with low survival rate and predicted a poor prognosis of oesophageal cancer patients.

Conclusion

FOXM1c promotes the metastasis by transcriptionally targeting IRF1 and may serve as a potential prognostic predictor for oesophageal cancer.
Touch imprint cytology on endoscopic ultrasound fine‐needle biopsy provides comparable sample quality and diagnostic yield to standard endoscopic ultrasound fine‐needle aspiration specimens in the evaluation of solid pancreatic lesions
Authors: Crinò Stefano Francesco , Larghi Alberto , Bernardoni Laura , Parisi Alice , Frulloni Luca , Gabbrielli Armando , Parcesepe Pietro , Scarpa Aldo , Manfrin Erminia
Published: November 2018

Objectives

Endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) is the gold standard for the diagnosis of solid pancreatic lesions (SPLs). Cytological samples can also be obtained using touch imprint cytology (TIC) on EUS fine‐needle biopsy (FNB) specimens. We aimed to compare sample quality and diagnostic yield of EUS‐FNA‐standard cytology (EUS‐FNA‐SC) to that of EUS‐FNB‐TIC in a series of patients with SPLs.

Methods

Thirty‐two consecutive patients referred for EUS‐tissue acquisition of SPLs who underwent rapid on‐site evaluation of both EUS‐FNA‐SC and paired EUS‐FNB‐TIC during the same endoscopic session were retrospectively identified. Sample quality (evaluated in terms of blood contamination, presence of clots, tissue casts, cellularity, and necrosis) and diagnostic yield were compared between the techniques.

Results

The mean number of passes to reach diagnosis at rapid on‐site evaluation was similar between EUS‐FNA‐SC and EUS‐FNB‐TIC (1.09 ± 0.3 vs 1.13 ± 0.34, P = .711). EUS‐FNA‐SC scores of sample quality were comparable to those of EUS‐FNB‐TIC (blood contamination, 2.47 ± 1.11 vs 2.25 ± 1.14, P = .109; clots, 1.25 ± 0.76 vs 1.19 ± 0.69, P = .624; tissue casts, 3.56 ± 0.88 vs 3.59 ± 1.09, P = .872; cellularity, 2.84 ± 1.11 vs 3.09 ± 1.09, P = .244; necrosis, 2.25 ± 1.08 vs 2.53 ± 1.02 P = .059; total score, 12.38 ± 2.88 vs 17.66 ± 2.38, P = .536). Adequacy, sensitivity and diagnostic accuracy of the two sampling techniques were equal (93.7%, 90.6% and 90.6%, respectively).

Conclusions

EUS‐FNB‐TIC provides comparable samples to those of EUS‐FNA‐SC and combines the benefits of cytology and histology for the evaluation of SPLs by employing a single needle during the same endoscopic procedure.
Factors that hindered care seeking among people with a first diagnosis of psychosis
Authors: Yarborough Bobbi J. , Yarborough Micah T. , Cavese Julie C.
Published: November 2018

Aim

Evidence‐based treatment can improve psychosis outcomes, but service providers need to understand and address the reasons people experiencing first episode psychosis avoid or delay care seeking. The goal of this study was to identify reasons care seeking might be postponed, from the points of view of patients, caregivers and health care professionals in a large health care delivery system, in the United States, without an early psychosis intervention program.

Methods

About 22 patients who had received an initial psychosis diagnosis and 10 of their caregivers were interviewed about their experiences and pathways to care. Additionally, 15 administrator or clinician key informants with responsibility for psychosis services were interviewed and asked to describe ways that they thought early psychosis identification and treatment engagement could be improved. All interviews were transcribed, coded and analysed together using thematic analysis.

Results

Some patients did not perceive their early psychotic experiences as concerning because they were familiar. Among those concerned, the desire to make sense of their experiences and avoid detection or stigma caused some to conceal symptoms or isolate themselves. Caregivers who observed withdrawal often attributed it to typical adolescent behaviour, which led to treatment delays. Legal and privacy protections led to delays among young adults.

Conclusions

To attract individuals to early psychosis services, outreach and engagement programs should help individuals and caregivers recognize their experiences as opportunities for care, and design and market services that promote sense‐making, offer hope and reduce stigma and system‐level privacy‐related barriers to care engagement.
Objective and subjective cognitive functioning in relation to psychopathology among women with early psychosis
Authors: Tong Alan C.Y. , Chang Wing Chung , Chan Angel N.Y. , Lin Jessie J.
Published: November 2018

Background

Subjective cognitive impairment (SCI) among early psychosis is under‐recognized and under‐studied. However, SCI is as important as objective impairment to be understood, since it assesses cognitive difficulties in real‐life situations from a personal perspective and is therefore an essence of individualized medicine. This study aims to explore the associations between the objective and subjective measures of cognitive impairments and to identify factors contributing to SCI among people with early psychosis.

Methods

Participants were 60 females (mean age 24.57 ± 8.28) who had a diagnosis of psychotic‐spectrum disorder within 5 years. They completed a battery of neuropsychological tests assessing a range of cognitive functions including verbal learning, memory, attention, and executive functions. The Subjective Cognitive Impairment Scale (SCIS) was used to assess their perceived cognitive decline. Psychotic symptoms and depression were also assessed.

Results

SCIS was not correlated with any of the objective cognitive tests results. It was positively correlated with depression and positive symptoms. A hierarchical multiple regression model revealed that positive symptoms and depression together explained 31.9% of the total variance in SCIS and only depression significantly predicted SCI. Performances on the memory tests were correlated with, and predicted by negative symptoms.

Conclusions

There was no correlation between SCI and objective cognitive performances in patients with early psychosis. Treatments should not only focus on symptomatic remission and performance of cognitive tests, but also place emphasis on improving moods and subjective cognitive functions of individuals with early psychosis.
Psychiatrists' opinion towards medication discontinuation in remitted first‐episode psychosis: A multi‐site study of the Asian Network for Early Psychosis
Authors: Hui Christy L.‐M. , Wong Andreas K.‐H. , Leung Whitty W.‐T. , Lee Edwin H.‐M. , Chan Sherry K.‐W. , Chang Wing‐Chung , Chen Eric Y.‐H. , Chan Tommy C.‐T. , Swapna Verma , Tagata Hiromi , Tsujino Naohisa , Nemoto Takahiro , Mizuno Masafumi , Kang Nam‐In , Kim Sung‐Wan , Chung Young‐Chul
Published: November 2018

Aim

The study investigated psychiatrists' views towards the issue of medication discontinuation for patients in remission from first‐episode psychosis in four countries (Hong Kong, Korea, Singapore and Japan) that are part of the Asian Network for Early Psychosis, focusing on whether the views of these countries differ with one another.

Methods

A questionnaire was distributed to psychiatrists for completion. The questionnaire contained three sections: direct questions probing at views on medication discontinuation, case vignettes to assess applied decision‐making and a checklist of criteria psychiatrists may view as necessary for the patient to satisfy before discontinuation. Total of 484 psychiatrists (97 from Hong Kong, 88 from Korea, 64 from Singapore and 233 from Japan) completed the questionnaire.

Results

We found that (a) Asian psychiatrists believed that 1% to 19% of remitted patients can discontinue medication, an estimation that was lower than Western psychiatrists; (b) in agreement with clinical guidelines, Asian psychiatrists believed that patients should remain on medication for at least 1 to 2 years following the absence of psychotic symptoms; (c) “Absence of any relapsing episode following first episode” was considered the most important criterion when making a decision; and (d) there were significant differences in clinicians' perceptions across the four countries: for instance, Korean psychiatrists were more conservative with the duration of antipsychotics maintenance, while Singaporean psychiatrists were more open‐minded towards clinical trials.

Conclusions

Culture and social norms appear to determine the relative importance of factors that psychiatrists might consider during the decision‐making process, thereby producing variations in the views held in different countries.
Sedative and antinociceptive effects of different detomidine constant rate infusions, with or without methadone in standing horses
Authors: Gozalo‐Marcilla M. , de Oliveira A. R. , Fonseca M. W. , Possebon F. S. , Pelligand L. , Taylor P. M. , Luna S. P. L.
Published: November 2018

Background

Standing surgery avoids the risks of general anaesthesia in horses.

Objectives

To assess sedation, antinociception and gastrointestinal motility in standing horses after a detomidine loading dose and 2‐h constant rate intravenous (i.v.) infusion, with or without methadone.

Study design

Blinded, randomised, crossover with seven healthy adult cross‐bred horses, three geldings and four females (404 ± 22 kg).

Methods

Five i.v. treatments were administered to all horses with 1‐week washout period: saline (SAL), detomidine low (2.5 μg/kg bwt + 6.25 μg/kg bwt/h) (DL) and high doses (5 μg/kg bwt + 12.5 μg/kg bwt/h) (DH) alone or combined with methadone (0.2 mg/kg bwt + 0.05 mg/kg bwt/h), (DLM) and (DHM), respectively. Height of head above the ground (HHAG), electrical (ET), thermal (TT) and mechanical (MT) nociceptive thresholds and gastrointestinal motility were evaluated at predetermined times between 5 and 240 min. A mixed effect model and Kruskal–Wallis test were used to analyse normally and non‐normally distributed data, respectively.

Results

Sedation (<50% basal HHAG) was achieved for the duration of the infusion, and for an additional 15 min in DH and DHM groups. Nociceptive thresholds were higher than baseline, to the greatest degree and the longest duration, with DHM (ET and TT for 135 min and MT for 150 min). After DH, TT was significantly higher than baseline from 30 to 120 min and MT from 15 to 135 min. After DLM, ET was increased at 90 min, TT at 30 min and MT for 120 min. Gastrointestinal motility was reduced for up to 135 min after DL, 150 min after DLM and 210 min after DH and DHM.

Main limitations

Nociceptive thresholds are not equivalent to surgical stimuli.

Conclusion

Methadone with the highest detomidine dose (DHM) may provide sufficient sedation and analgesia for standing surgical procedures and warrants further investigation.
Proceeding report of the Second Symposium on Hidradenitis Suppurativa Advances (SHSA) 2017
Authors: Shavit Eran , Alavi Afsaneh , Bechara Falk G. , Bennett Richard G. , Bourcier Marc , Cibotti Ricardo , Daveluy Steven , Frew John W. , Garg Amit , Hamzavi Iltefat , Hoffman Lauren K. , Hsaio Jenny , Kirby Joslyn Sciacca , Lev‐Tov Hadar , Martinez Erin , Micheletti Robert , Naik Haley B. , Nassif Aude , Nicholson Cynthia , Parks‐Miller Angie , Patel Zarine , Piguet Vincent , Ramesh Mayur , Resnik Barry , Sayed Christopher , Schultz Gregory , Siddiqui Aamir , Tan Jerry , Wortsman Ximena , Lowes Michelle A.
Published: November 2018

The 2nd Annual Symposium on Hidradenitis Suppurativa Advances (SHSA) took place on 03‐05 November 2017 in Detroit, Michigan, USA. This symposium was a joint meeting of the Hidradenitis Suppurativa Foundation (HSF Inc.) founded in the USA, and the Canadian Hidradenitis Suppurativa Foundation (CHSF). This was the second annual meeting of the SHSA with experts from different disciplines arriving from North America, Europe and Australia, in a joint aim to discuss most recent innovations, practical challenges and potential solutions to issues related in the management and care of Hidradenitis Suppurativa patients. The last session involved clinicians, patients and their families in an effort to educate them more about the disease.