bluuebunny/crossref_metadata_2025 huggingface dataset:
MicroRNA‐204‐5p: A novel candidate urinary biomarker of Xp11.2 translocation renal cell carcinoma
Authors: Kurahashi Ryoma , Kadomatsu Tsuyoshi , Baba Masaya , Hara Chiaki , Itoh Hitoshi , Miyata Keishi , Endo Motoyoshi , Morinaga Jun , Terada Kazutoyo , Araki Kimi , Eto Masatoshi , Schmidt Laura S. , Kamba Tomomi , Linehan W. Marston , Oike Yuichi
Published: April 2019

Xp11.2 translocation renal cell carcinoma (Xp11 tRCC) is a rare sporadic pediatric kidney cancer caused by constitutively active TFE3 fusion proteins. Tumors in patients with Xp11 tRCC tend to recur and undergo frequent metastasis, in part due to lack of methods available to detect early‐stage disease. Here we generated transgenic (Tg) mice overexpressing the human PRCC‐TFE3 fusion gene in renal tubular epithelial cells, as an Xp11 tRCC mouse model. At 20 weeks of age, mice showed no histological abnormalities in kidney but by 40 weeks showed Xp11 tRCC development and related morphological and histological changes. MicroRNA (miR)‐204‐5p levels in urinary exosomes of 40‐week‐old Tg mice showing tRCC were significantly elevated compared with levels in control mice. MicroRNA‐204‐5p expression also significantly increased in primary renal cell carcinoma cell lines established both from Tg mouse tumors and from tumor tissue from 2 Xp11 tRCC patients. All of these lines secreted miR‐204‐5p‐containing exosomes. Notably, we also observed increased miR‐204‐5p levels in urinary exosomes in 20‐week‐old renal PRCC‐TFE3 Tg mice prior to tRCC development, and those levels were equivalent to those in 40‐week‐old Tg mice, suggesting that miR‐204‐5p increases follow expression of constitutively active TFE3 fusion proteins in renal tubular epithelial cells prior to overt tRCC development. Finally, we confirmed that miR‐204‐5p expression significantly increases in noncancerous human kidney cells after overexpression of a PRCC‐TFE3 fusion gene. These findings suggest that miR‐204‐5p in urinary exosomes could be a useful biomarker for early diagnosis of patients with Xp11 tRCC.
Improving glucocorticoid replacement profiles in adrenal insufficiency
Authors: Choudhury Sirazum , Lightman Stafford , Meeran Karim
Published: April 2019

There is an increased mortality associated with adrenal insufficiency despite glucocorticoid replacement therapy with a standardized mortality ratio greater than two. The cause of the increased mortality is yet to be definitively elucidated, but may be due to excess steroid exposure, or replacement regimens that are uncoupled from the normal physiological cortisol profile. Cortisol secretion follows an ultradian pattern which is not possible to reproduce using oral replacement. With the advent of new pumps, it is now possible to mimic the pulsatility of the adrenal glands. While the cognitive and emotional benefits of reproducing the ultradian rhythm are known, the presence of long‐term benefits is not yet clear. There is a dearth of evidence and high‐quality studies to underline our current understanding of the pathophysiology of adrenal insufficiency and replacement therapy. There is a particular lack of research comparing objective outcomes between patients receiving hydrocortisone replacement (either standard therapy or new sustained release preparations), prednisolone replacement and ultradian pumps. Direct comparative studies are now warranted to understand the optimal approach.
Influence of implant neck and abutment characteristics on peri‐implant tissue health and stability. Oral reconstruction foundation consensus report
Authors: Schwarz Frank , Messias Ana , Sanz‐Sánchez Ignacio , Carrillo de Albornoz Ana , Nicolau Pedro , Taylor Tom , Beuer Florian , Schär Alex , Sader Robert , Guerra Fernando , Sanz Mariano
Published: April 2019

Objective

The aim of this consensus meeting was to assess the influence of implant neck and abutment characteristics on peri‐implant tissue health and stability.

Material and Methods

Group and plenary discussions were based on two systematic reviews focusing on the effect of titanium implants with different collar designs/surface modifications and the abutment material on the stability of marginal bone levels (MBLs), peri‐implant health, and survival rates.

Results

The changes in MBLs were not influenced by the abutment material and were also similar at one‐ and two‐piece implants after one year of loading. Rough collar implants improved MBLs in comparison to machined collar implants. Additional modifications of the collar had no beneficial clinical effect on MBLs. Titanium abutments were associated with significantly higher increases in bleeding on probing when compared with zirconia abutments.

Conclusion

MBLs are mainly influenced by the microstructure (i.e., rough surfaced) of the implant neck. Consensus statements and specific recommendations for future research were elaborated during the consensus meeting.
Effect of enamel matrix derivative liquid in combination with a natural bone mineral on new bone formation in a rabbit GBR model
Authors: Kobayashi Eizaburo , Fujioka‐Kobayashi Masako , Saulacic Nikola , Schaller Benoit , Sculean Anton , Miron Richard J.
Published: April 2019

Objectives

Recently, a new liquid carrier system for enamel matrix derivate (EMD‐liquid) was developed with better physico‐chemical properties for improved adsorption of EMD to biomaterial surfaces. The aim of the present study was to investigate the bone regenerative potential of EMD‐liquid in combination with a natural bone mineral (NBM) in vivo.

Methods

Four 6‐mm defects were created in the calvaria of six New Zealand white rabbits. Defects were filled with either (1) control (empty), (2) 20 mg of NBM, or (3) 20 mg of NBM + 20 µl of EMD‐liquid (n = 8). All defects were covered with collagen barrier membranes. The bone regenerative potential was investigated by micro‐CT and histomorphological analyses at 8 weeks postsurgery.

Results

The mineralized tissue volume was significantly higher in the NBM + EMD‐liquid group when compared to control, whereas no difference was observed between the NBM alone and control groups. While no significant difference was observed for horizontal bone defect closure between the NBM + EMD‐liquid and the NBM alone groups, NBM + EMD‐liquid significantly increased the total mineralized area and reduced the percentage of soft/connective tissue infiltration. No statistically significant difference was observed between the NBM + EMD‐liquid group and NBM alone group for amount of mineralized bone.

Conclusion

The addition of EMD‐liquid did not lead to statistically significant bone formation when compared to NBM alone. The combination of NBM + EMD‐liquid but not NBM alone did however induce superior mineralized tissues when compared to control (empty). Further research investigating the adsorption potential of EMD‐liquid to bone‐grafting particles with/without collagen may provide valuable insights into future regenerative strategies with enamel matrix proteins.
Changes in ventilation and perfusion following lower lobe endoscopic lung volume reduction (ELVR) with endobronchial valves in severe COPD
Authors: Yang Li , Hsu Kelvin , Williamson Jonathan P. , Peters Matthew J. , Ho‐Shon Kevin , Ing Alvin J.
Published: April 2019

Background

We have previously reported significant improvements in ventilation and perfusion (VQ) and V/Q matching in the contralateral lung, especially the non‐targeted lower zone in patients with severe COPD following upper lobe ELVR with endobronchial valves. However, V/Q changes after lower lobe ELVR have not been described.

Methods

Seven patients with lower lobe heterogeneous emphysema underwent unilateral lower lobe ELVR at Macquarie University Hospital. Lung function tests, 6‐minute walk tests (6MWT), St George’s Respiratory Questionnaire (SGRQ) and planar differential VQ scans were performed at baseline and at 1, 3 and 12 months post‐ELVR.

Results

Compared to baseline, patients showed significant improvements in FEV1 (0.83 ± 0.09L‐0.97 ± 0.12L, p < 0.05), 6MWD (200.33 ± 56.54 m‐274.24 ± 48.03 m, p < 0.05) and SGRQ (61.13 ± 5.33‐42.86 ± 6.99, p < 0.05) at 3 months after ELVR. This improvement was maintained at 12 months. There was a corresponding significant improvement in the differential ventilation (30.21 ± 3.04%‐37.82 ± 3.76%, p < 0.05) and perfusion (31.77 ± 2.53%‐35.60 ± 2.58%, p < 0.05) of the contralateral non‐targeted upper zone.

Conclusions

Within the limitations of a small sample size, we have found that in heterogeneous severe COPD patients undergoing ELVR targeting the lower lobes, there are clinical and PFT improvements similar to that reported in ELVR targeting upper lobes. Contralateral improvement in V/Q matching also occurs following lower lobe ELVR with the greatest improvement in the contralateral upper zone, suggesting the contralateral upper lobe should be the least affected lobe if the lower lobe is targeted in ELVR. These findings need to be confirmed in a study with a larger number of patients.
Corticosteroids and methotrexate as adjuvants to costimulation blockade in non‐human primate renal transplantation
Authors: Anderson Douglas J. , Lo Denise J. , Leopardi Francis , Song Mingqing , Strobert Elizabeth A. , Jenkins Joe B. , Larsen Christian P. , Kirk Allan D.
Published: April 2019

Belatacept, the CD28‐B7 costimulation pathway inhibitor, has been approved as a calcineurin inhibitor (CNI) alternative in kidney transplantation. Although costimulation blockade (CoB) allows for CNI avoidance, it is associated with increased rates of early rejection, prompting a search for agents to pair with belatacept. Methotrexate (MTX) is an antimetabolite that has been found to be complimentary with abatacept, a lower affinity CD28‐B7‐specific analogue of belatacept, in the treatment of rheumatoid arthritis (RA). We examined whether this synergy would extend to prevention of kidney allograft rejection. Rhesus macaques underwent kidney transplantation treated with abatacept maintenance therapy with either a steroid taper, MTX, or both. The combination of abatacept maintenance with steroids prolonged graft survival compared to untreated historical controls and previous reports of abatacept monotherapy. The addition of MTX did not provide additional benefit. These data demonstrate that abatacept with adjuvant therapy may delay the onset of acute rejection, but fail to show synergy between abatacept and MTX beyond that of steroids. These findings indicate that MTX is unlikely to be a suitable adjuvant to CoB in kidney transplantation, but also suggest that with further modification, a CoB regimen used for advanced RA may suffice for RA patients requiring kidney transplantation.
Factors predicting kidney delayed graft function among recipients of simultaneous liver‐kidney transplantation: A single‐center experience
Authors: Korayem Islam M. , Agopian Vatche G. , Lunsford Keri E. , Gritsch Hans A. , Veale Jeffrey L. , Lipshutz Gerald S. , Yersiz Hasan , Serrone Coney L. , Kaldas Fady M. , Farmer Douglas G. , Bunnapradist Suphamai , Danovitch Gabriel M. , Busuttil Ronald W. , Zarrinpar Ali
Published: April 2019

Background

Kidney delayed graft function (kDGF) remains a challenging problem following simultaneous liver and kidney transplantation (SLKT) with a reported incidence up to 40%. Given the scarcity of renal allografts, it is crucial to minimize the development of kDGF among SLKT recipients to improve patient and graft outcomes. We sought to assess the role of preoperative recipient and donor/graft factors on developing kDGF among recipients of SLKT.

Methods

A retrospective review of 194 patients who received SLKT in the period from January 2004 to March 2017 in a single center was performed to assess the effect of preoperative factors on the development of kDGF.

Results

Kidney delayed graft function was observed in 95 patients (49%). Multivariate analysis revealed that donor history of hypertension, cold static preservation of kidney grafts [versus using hypothermic pulsatile machine perfusion (HPMP)], donor final creatinine, physiologic MELD, and duration of delay of kidney transplantation after liver transplantation were significant independent predictors for kDGF. kDGF is associated with worse graft function and patient and graft survival.

Conclusions

Kidney delayed graft function has detrimental effects on graft function and graft survival. Understanding the risks and combining careful perioperative patient management, proper recipient selection and donor matching, and graft preservation using HPMP would decrease kDGF among SLKT recipients.
Long‐term outcome of percutaneous transhepatic biliary drainage for biliary strictures following pediatric liver transplantation
Authors: Sanada Yukihiro , Katano Takumi , Hirata Yuta , Yamada Naoya , Okada Noriki , Onishi Yasuharu , Yasuda Yoshikazu , Mizuta Koichi
Published: April 2019

Background

We present a retrospective analysis of our experience with pediatric liver transplantation (LT), focusing on the long‐term outcome of percutaneous transhepatic biliary drainage (PTBD) for post‐transplant biliary strictures.

Methods

Fifty‐three PTBDs were performed for 41 pediatric recipients with biliary strictures. The median ages at LT and PTBD were 1.4 and 4.4 years, respectively. The median observation period was 10.6 years.

Results

Post‐transplant biliary strictures comprised anastomotic stricture (AS) in 28 cases, nonanastomotic stricture (NAS) in 12, anastomotic obstruction (AO) in 8, and nonanastomotic obstruction (NAO) in 5. The success rate of PTBD was 90.6%, and the 15‐year primary patency rate of PTBD was 52.6%. The recurrence rate of biliary strictures after PTBD was 18.8% (9/48), and among the four NAS cases with recurrence, two underwent re‐LT. The biliary obstruction rate was 27.1% (13/48). Among the eight cases with AO, five underwent the rendezvous method and three underwent surgical re‐anastomosis. Among the five cases with NAO, one underwent re‐LT. The recipient survival rate of PTBD treatment was 100%.

Conclusions

The graft prognosis of AS by PTBD treatment is good and AO is curable by the rendezvous method and surgical re‐anastomosis. However, the graft prognosis of NAS and NAO is poor.
Supply Chain Network Redesign: A Technical Note on Optimising Financial Performance
Authors: Jahani Hamed , Abbasi Babak , Talluri Srinivas
Published: April 2019

Supply chain network (SCN) redesign is a strategic decision that requires the consideration of several important financial aspects. A review of the supply chain network design (SCND) literature shows that most of the provided solutions lack the measurement and incorporation of the company's financial performance. This study extends the SCN redesign model, introduced by Jahani et al. (2018), in order to allow financial performance optimization instead of profit maximization. The model uses essential accounts existing in the basic financial statements of an SCN company to delineate how the strategic financial considerations can influence the network structure and its operational flows. It ascertains the future financial position of the company, as well as the optimal levels of loans and the proportion of available cash required for financing the new design. We examine the applicability of the model by consolidating financial data with the case study used in Jahani et al. (2018). We evaluate the resulting financial ratios of the new model with existing ratios aimed at representing the reliability of the model and introducing future targets. This study offers several managerial insights. For instance, consideration of inventory values as a current asset in designing an SCN leads to a realistic design aligned with financial statements that are also reportable to creditors and investors.
Children lose confidence in their potential to “be scientists,” but not in their capacity to “do science”
Authors: Lei Ryan F. , Green Emily R. , Leslie Sarah‐Jane , Rhodes Marjorie
Published: April 2019

Over the course of middle childhood, children's interest and beliefs about their own capacities for success in science often decline. This pernicious decline is especially evident among underrepresented groups, including girls, members of some racial and ethnic minorities, and children from lower socioeconomic backgrounds. The present research (N = 306, ages 6–11) found that while children lose interest and feelings of efficacy about their potential to “be scientists” across middle childhood, they maintain more robust interest and efficacy about “doing science.” These patterns were confirmed in both longitudinal and cross‐sectional analyses; effects were stable or increased across time and age. Mediation analyses revealed that the positive effect of action framing is partially accounted for by children's views that the group of people who do science is more inclusive than the category of scientists. These findings suggest that using action‐focused language to encourage children in science is more inclusive and may lead to more science engagement across middle childhood than language that emphasizes scientists as an identity category. Implications for educational practices will be discussed.
Testosterone deficiency in men with Type 2 diabetes: pathophysiology and treatment
Authors: Gianatti E. J. , Grossmann M.
Published: April 2019

Epidemiological studies consistently demonstrate that lowered serum testosterone is not only common in men with established Type 2 diabetes, but also predicts future diabetic risks and increased mortality. Preclinical studies report plausible mechanisms by which low testosterone could mediate dysglycaemia. Exogenous testosterone treatment consistently reduces fat mass, increases muscle mass and improves insulin resistance in some studies, but the majority of currently available randomized controlled trials (RCTs) do not report a consistent glycaemic benefit. In men with diabetes, testosterone treatment effects on androgen deficiency‐like clinical features are inconsistent, and effects on sexual dysfunction may be attenuated compared with men without diabetes. The long‐term risks of testosterone treatment in older men without medical disease of the hypothalamic–pituitary–testicular axis are not known. Current RCTs are not definitive, owing to their small size, short duration and enrolment of men with mostly relatively good baseline glycaemic control not specifically selected for the presence of androgen deficiency symptoms. Although large, well‐designed clinical trials are needed, given the benefit–risk ratio of testosterone treatment is not well understood, routine serum testosterone testing or testosterone treatment of asymptomatic men with Type 2 diabetes is currently not recommended. Carefully selected, symptomatic men with low testosterone who are informed of the lack of high‐level evidence regarding the long‐term benefits and risks of this approach may be offered a trial of testosterone treatment in combination with lifestyle measures, weight loss and optimization of comorbidities.
Differential vascular effects of aspirin in people with Type 2 diabetes without cardiovascular disease and matched controls without diabetes
Authors: Vernstrøm L. , Laugesen E. , Grove E. L. , Baier J. M. , Gullaksen S. , Hvas A.‐M. , Poulsen P. L. , Funck K. L.
Published: April 2019

Aim

We investigated whether the effect of low‐dose aspirin on endothelium‐dependent vasodilation and arterial stiffness in people with Type 2 diabetes is different from a matched control group. We examined acute and chronic effects, and effects over the 24h dosing interval.

Methods

In an open‐label parallel group intervention study, we included 21 participants with Type 2 diabetes and 21 age‐ and sex‐matched controls. Endothelium‐dependent vasodilation was assessed as the reactive hyperaemia index (lnRHI) measured by peripheral arterial tonometry (EndoPAT®). Arterial stiffness was assessed as pulse wave velocity (PWV) measured by applanation tonometry (SphygmoCor®). Measurements were performed prior to aspirin intake and 1h after aspirin administration (75 mg). Participants were then treated for 6 days, and measurements were repeated at 24 h and 1 h after aspirin intake.

Results

Baseline lnRHI did not differ between groups. The controls had an immediate increase in lnRHI after the first aspirin tablet. This was not observed in participants with diabetes (difference between groups; P < 0.05). After 1 week, both groups demonstrated increased lnRHI compared with baseline (P < 0.01). In participants with diabetes, lnRHI was significantly lower 24 h after aspirin administration compared with 1 h after administration (P < 0.05). This difference was not observed in controls (P = 0.84, difference between groups; P = 0.12). The effect on PWV did not differ between groups.

Conclusion

Aspirin had a reduced immediate effect on endothelium‐dependent vasodilation in participants with diabetes. Both groups had improved endothelial function after 1 week of treatment. Further, the effect of aspirin on endothelial function may be declining during a 24 h dosing interval in people with Type 2 diabetes. (Clinical Trial Registry No: 2016‐000515‐32)
LIGHTHOUSE PROVISION IN PREMODERN JAPAN
Authors: Saito Kuniyoshi
Published: April 2019

We investigate how lighthouses were provided in premodern Japan, with a specific focus on the role of the private sector. Using national survey data on lighthouses collected by the government in 1883, we find that lighthouses constructed by the private sector in the Edo period (1603−1868) accounted for nearly 70% of lighthouses existing at the time of the survey and that there was no significant difference in technical features between private and public lighthouses. However, we observe that almost all private lighthouses were located at ports, and additional case studies indicate that the public authorities endorsed the operation of some lighthouses, which might have contributed to their profits and improved their long‐term survival. We also find that various factors, including the formation of merchant coalitions and whether users were identifiable, influenced whether a private organization could circumvent the free rider problem. (JEL H41, L97, N45)
Burden of neurodegenerative diseases in the Eastern Mediterranean Region, 1990–2016: findings from the Global Burden of Disease Study 2016
Authors: Fereshtehnejad S.‐M. , Vosoughi K. , Heydarpour P. , Sepanlou S. G. , Farzadfar F. , Tehrani‐Banihashemi A. , Malekzadeh R. , Sahraian M. A. , Vollset S. E. , Naghavi M. , Vos T. , Feigin V. , Murray C. , Mokdad A. H. , Moradi‐Lakeh M. ,   Global Burden of Disease Study 2016 Eastern Mediterranean Region Collaborators – Neurological Diseases Section
Published: April 2019

Background and purpose

The Eastern Mediterranean Region (EMR) is experiencing a demographic shift towards rapid aging at a time of political unrest. We aimed to estimate the burden of neurodegenerative disorders and its relationship with sociodemographic index in the EMR countries from 1990 to 2016.

Methods

Using data from the Global Burden of Disease Study 2016, we calculated country‐specific trends for prevalence, mortality, disability‐adjusted life‐years (DALY), years of life lost and years lived with disability (YLD) for Alzheimer's disease/other dementias and Parkinson's disease in the EMR during 1990–2016.

Results

In the EMR, the age‐standardized prevalence rate of Alzheimer's disease/other dementias and Parkinson's disease was estimated at 759.8/100 000 (95% uncertainty intervals, 642.9–899.9) and 87.1/100 000 (95% uncertainty intervals, 69.8–108.2) people in 2016, demonstrating 0.01% and 42.3% change from 1990, respectively. Neurodegenerative disorders contributed to 5.4% of total DALY and 4.6% of total YLD among the older EMR population (70 years of age or older in 2016). Age‐standardized DALY due to Parkinson's disease were strongly correlated with the sociodemographic index level (r = 0.823, P < 0.001). The YLD:DALY ratio of neurodegenerative diseases declined during this period in the low‐income but not the high‐income EMR countries.

Conclusions

Our findings demonstrated an increasing trend in the burden of dementias and Parkinson's disease in most EMR countries between 1990 and 2016. With aging of the EMR populations, countries should target the modifiable risk factors of neurodegenerative diseases to control their increasing burden.
The cerebrospinal fluid CD4/CD8 ratio and interleukin‐6 and ‐10 levels in neurosarcoidosis: a multicenter, pragmatic, comparative study
Authors: Chazal T. , Costopoulos M. , Maillart E. , Fleury C. , Psimaras D. , Legendre P. , Pineton de Chambrun M. , Haroche J. , Lubetzki C. , Amoura Z. , Legarff‐Tavernier M. , Cohen Aubart F.
Published: April 2019

Background and purpose

Neurosarcoidosis is a rare inflammatory disorder of unknown cause. The aim of this study was to evaluate the value of T/B lymphocyte population counts and the concentrations of the cytokines interleukin (IL) 6 and IL‐10 in the cerebrospinal fluid (CSF) of neurosarcoidosis patients.

Methods

A retrospective study CSF biomarkers was conducted in patients with neurosarcoidosis who underwent CSF analysis between 2012 and 2017 as well as various control populations.

Results

Forty‐three patients with neurosarcoidosis, 14 with multiple sclerosis (MS) and 48 with other inflammatory disorders were analyzed. The CSF IL‐6 levels were higher in sarcoidosis patients than in MS patients (median 8 vs. 3 pg/ml, P = 0.006). The CSF CD4/CD8 ratio was higher in sarcoidosis patients than in MS patients and in patients with other inflammatory disorders (median 3.18 vs. 2.36 and 2.10, respectively, P = 0.008). The CSF IL‐6 level was higher in patients with active neurosarcoidosis than in non‐active neurosarcoidosis patients (median 13 vs. 3 pg/ml, P = 0.0005). In patients with neurosarcoidosis, a CSF IL‐6 concentration >50 pg/ml was associated with a higher risk of relapse or progression‐free survival (hazard ratio 3.60; 95% confidence interval 1.78–23.14). A refractory neurosarcoidosis patient was treated with an anti‐IL‐6 monoclonal antibody that produced a complete neurological response.

Conclusions

The CSF CD4/CD8 ratio and IL‐6 concentration are increased in neurosarcoidosis compared to MS and other inflammatory disorders. A CSF IL‐6 concentration >50 pg/ml is associated with relapse or progression of neurosarcoidosis. IL‐10 levels may be elevated in neurosarcoidosis.
A microbiome analysis of equine peripheral dental caries using next generation sequencing
Authors: Borkent D. , Reardon R. J. M. , McLACHLAN G. , GLENDINNING L. , Dixon P. M.
Published: April 2019

Background

Although, peripheral caries (PC) affects almost half of UK horses, no comprehensive microbiological study has been performed on this disorder. As a high proportion of oral bacteria cannot be conventionally cultured, molecular microbiological techniques such as Next Generation Sequencing are required to examine the complex oral bacteria community.

Objectives

To identify the microbiota involved in equine PC, including comparing microbiota at the more commonly and severely affected three caudal cheek teeth with the less commonly affected three rostral cheek teeth.

Study design and Methods

Equine dental plaque samples were collected from the palatal aspects of cheek teeth of 63 horses. DNA was isolated and amplified using PCR, targeting the V4 region of the 16S rRNA gene and Next Generation Sequencing of these gene amplicons was performed. The acquired data were processed and analysed using Mothur and R.

Results

Streptococcus species was the genus most commonly associated with equine PC, whereas Gemella species was the genus most associated with the control group. In a further analysis where the rostral and caudal cheek teeth were compared with each other and with the control group. Veillonella species was the most commonly associated genus with PC of the rostral cheek teeth, Streptococcus species was the most associated genus with the caudal cheek teeth, and Corynebacterium with the control group.

Main limitations

Some bacteria can have multiple heterogeneous copies of the 16S rRNA gene, which can affect the estimation of their relative abundance.

Conclusions

Similar to caries studies in other species, acidogenic and aciduric microorganisms including Streptococcus species were found to be associated with equine peripheral caries.
Synovial sepsis of unknown origin in the adult Thoroughbred racehorse
Authors: Byrne C. A. , Lumsden J. M. , Lang H. M. , O'Sullivan C. B.
Published: April 2019

Background

Synovial sepsis of unknown origin is a rare cause of lameness in the adult horse, and a haematogenous pathogenesis has been proposed in previous cases.

Objectives

To describe the features and outcome of synovial sepsis of unknown origin in adult Thoroughbred racehorses.

Study design

Retrospective case series.

Methods

Hospital records for admissions between 2005 and 2015 were reviewed to identify adult horses diagnosed with synovial sepsis of unknown origin. Presentation, clinicopathological, microbiological and diagnostic imaging findings were recorded. Treatment methods, surgical findings, complications and long‐term outcome were evaluated.

Results

Eleven cases were identified over the study period. Diagnosis was established from clinical examination and clinicopathologic findings, which were comparable to other aetiologies of synovial sepsis. Affected structures included synovial joints, tendon sheaths and bursae. Concurrent osteochondritis dissecans or articular cartilage lesions were evident during arthroscopic surgery in three cases. Significant intrasynovial haemorrhage was not identified. Microbial culture of synovial fluid or synovial biopsy was positive in 6/11 of cases, with all isolates being Gram‐positive cocci. Of the 6 positive microbial cultures, all isolates demonstratedin vitrosensitivity to a cephalosporin antimicrobial agent. A concurrent remote wound was present in a single case. No other potential origins of bacteraemia were identified. Treatment methods included endoscopic surgery, standing multineedle lavage, intravenous regional limb perfusion, intrasynovial medication and/or systemic antimicrobial administration. All horses survived to hospital discharge. For the 6/11 cases that raced following synovial sepsis, the median period for return to racing was 221 days.

Main limitations

A small study population, which was retrospectively reviewed.

Conclusions

Synovial sepsis of unknown origin is rare in the adult Thoroughbred racehorse and can affect a range of synovial structures. A concurrent potential source of bacteraemia is rarely identified. With appropriate management, the prognosis to return to racing is fair.
Intra‐articular triamcinolone acetonide improves lung function in horses with severe asthma
Authors: Bessonnat A. , Picotte K. , Lavoie J. P.
Published: April 2019

Background

Locally administered corticosteroids are commonly used to treat joint diseases in sport and racehorses. As they are also the most potent drugs for the treatment of equine asthma, we hypothesised that the intra‐articular corticosteroids used to treat joint diseases also improve the lung function in horses with severe asthma, thus potentially delaying the diagnosis of this common lung condition.

Objectives

To compare the effects of intra‐articular (IA) and intramuscular (IM) triamcinolone acetonide (TA) on lung function in horses with severe asthma.

Study design

Randomised and controlled experiment on asthma‐prone research animals.

Methods

Horses with severe asthma in clinical exacerbation were given either 20 mg of TA in both tarsocrural joints (n = 5; 40 mg/horse) or 40 mg of TA intramuscularly (n = 5). Lung function and TA serum concentrations were measured weekly for 35 days. TA serum concentrations were also evaluated on day 3.

Results

The pulmonary resistance (RL) and elastance (EL) values decreased by day 7 in the IA group (P<0.0001 and P = 0.003, respectively) and by day 14 in the IM group (P = 0.002 and 0.03, respectively). Lung function was improved up to days 21 and 28 in the IA and IM groups, respectively, when compared with baseline. TA serum levels were below the quantification limit (100 pg/ml) for 4 and 3 of the 5 horses in the IA and IM groups, respectively, on day 7. The area under the curve for RL, ELand the serum concentrations of TA were similar in both groups.

Main limitations

The response of horses with severe asthma might differ from that of high‐performance horses with mild/moderate asthma.

Conclusions

Intra‐articular administration of TA improves lung function in horses with severe asthma, an effect that persists when TA serum concentration is below the quantification level that is employed as a threshold by the International Association of Racing Commissioners.
Expression and biological functions of the CCL5‐CCR5 axis in oral lichen planus
Authors: Shan Jing , Li Shan , Wang Chen , Liu Lin , Wang Xuewei , Zhu Dandan , Fan Yuan , Xu Juanyong
Published: April 2019

Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disorder with T cell‐mediated immunological pathogenesis. C‐C motif chemokine ligand 5 (CCL5) and its receptor C‐C motif chemokine receptor 5 (CCR5) play important roles in the activation and recruitment of T cells. This study sought to explore the expression and biological functions of the CCL5‐CCR5 axis in OLP. We examined the expression of the CCL5‐CCR5 axis in the peripheral blood and oral tissue of healthy controls and patients with OLP using quantitative real‐time PCR, Simple Western assays, enzyme‐linked immunosorbent assay (ELISA) and immunohistochemistry. In addition, we investigated the effects of the CCL5‐CCR5 axis on the proliferation, apoptosis and migration of OLP T cells using Cell Counting Kit‐8 (CCK8) assay, flow cytometry and transwell assay. We found that the expression of the CCL5‐CCR5 axis was significantly elevated both in the peripheral blood and oral tissue of patients with OLP compared with healthy controls. CCL5 not only promoted OLP T‐cell proliferation and migration but also inhibited OLP T‐cell apoptosis. Moreover, CCR5 inhibition suppressed OLP T‐cell proliferation and migration, whereas OLP T‐cell apoptosis was promoted. In conclusion, our data suggest that the CCL5‐CCR5 axis may be closely related to the inflammatory infiltration of T cells in OLP.
Managerial effect or firm effect: Evidence from the private debt market
Authors: Francis Bill B. , Hasan Iftekhar , Zhu Yun
Published: April 2019

This paper provides evidence that the managerial effect is a key determinant of firms’ cost of capital, in the context of private debt contracting. Applying the novel empirical method developed by an earlier study to a large sample that tracks the job movement of top managers, we find that the managerial effect is a critical and significant factor that explains a large part of the variation in loan contract terms more accurately than firm fixed effects. Additional evidence shows that banks “follow” managers when they change jobs and offer loan contracts with preferential terms to their new firms.
Why do large shareholders adopt a short‐term versus a long‐term investment horizon in different firms?
Authors: Tosun Onur Kemal
Published: April 2019

I ask why the same large shareholders have different investment horizons. Using data for 1998–2013, I examine four fundamental firm policies for their potential influence on blockholders’ investments with different time horizons. The panel ordinary least squares, difference‐in‐difference (using the Sarbanes‐Oxley Act), logistic, and dynamic generalized method of moments regression analyses reveal that blockholders adopt a short‐term horizon in smaller firms with a less independent board, high leverage, and high dividends while the same blockholders keep their investments longer in firms with a more independent board and low dividends. Under various economic conditions, different firm characteristics gain importance in blockholders’ decision on short‐term versus long‐term investments.
Carbon dynamics, net primary productivity and human‐appropriated net primary productivity across a forest–cocoa farm landscape in West Africa
Authors: Morel Alexandra C. , Adu Sasu Michael , Adu‐Bredu Stephen , Quaye Marvin , Moore Christine , Ashley Asare Rebecca , Mason John , Hirons Mark , McDermott Constance L. , Robinson Elizabeth J. Z. , Boyd Emily , Norris Ken , Malhi Yadvinder
Published: April 2019

Terrestrial net primary productivity (NPP) is an important metric of ecosystem functioning; however, there are little empirical data on the NPP of human‐modified ecosystems, particularly smallholder, perennial crops like cocoa (Theobroma cacao), which are extensive across the tropics. Human‐appropriated NPP (HANPP) is a measure of the proportion of a natural system's NPP that has either been reduced through land‐use change or harvested directly and, previously, has been calculated to estimate the scale of the human impact on the biosphere. Additionally, human modification can create shifts in NPP allocation and decomposition, with concomitant impacts on the carbon cycle. This study presents the results of 3 years of intensive monitoring of forest and smallholder cocoa farms across disturbance, management intensity, distance from forest and farm age gradients. We measured among the highest reported NPP values in tropical forest, 17.57 ± 2.1 and 17.7 ± 1.6 Mg C ha−1 year−1 for intact and logged forest, respectively; however, the average NPP of cocoa farms was still higher, 18.8 ± 2.5 Mg C ha−1 year−1, which we found was driven by cocoa pod production. We found a dramatic shift in litterfall residence times, where cocoa leaves decomposed more slowly than forest leaves and shade tree litterfall decomposed considerably faster, indicating significant changes in rates of nutrient cycling. The average HANPP value for all cocoa farms was 2.1 ± 1.1 Mg C ha−1 year−1; however, depending on the density of shade trees, it ranged from −4.6 to 5.2 Mg C ha−1 year−1. Therefore, rather than being related to cocoa yield, HANPP was reduced by maintaining higher shade levels. Across our monitored farms, 18.9% of farm NPP was harvested (i.e., whole cocoa pods) and only 1.1% (i.e., cocoa beans) was removed from the system, suggesting that the scale of HANPP in smallholder cocoa agroforestry systems is relatively small.
Trait structure and redundancy determine sensitivity to disturbance in marine fish communities
Authors: McLean Matthew , Auber Arnaud , Graham Nicholas A. J. , Houk Peter , Villéger Sébastien , Violle Cyrille , Thuiller Wilfried , Wilson Shaun K. , Mouillot David
Published: April 2019

Trait diversity is believed to influence ecosystem dynamics through links between organismal traits and ecosystem processes. Theory predicts that key traits and high trait redundancy—large species richness and abundance supporting the same traits—can buffer communities against environmental disturbances. While experiments and data from simple ecological systems lend support, large‐scale evidence from diverse, natural systems under major disturbance is lacking. Here, using long‐term data from both temperate (English Channel) and tropical (Seychelles Islands) fishes, we show that sensitivity to disturbance depends on communities’ initial trait structure and initial trait redundancy. In both ecosystems, we found that increasing dominance by climatically vulnerable traits (e.g., small, fast‐growing pelagics/corallivores) rendered fish communities more sensitive to environmental change, while communities with higher trait redundancy were more resistant. To our knowledge, this is the first study demonstrating the influence of trait structure and redundancy on community sensitivity over large temporal and spatial scales in natural systems. Our results exemplify a consistent link between biological structure and community sensitivity that may be transferable across ecosystems and taxa and could help anticipate future disturbance impacts on biodiversity and ecosystem functioning.
Grain boundary strengthening in nanocrystalline zinc aluminate
Authors: Yang Chenguang , Thron Andrew , Castro Ricardo H. R.
Published: April 2019

Fully dense transparent zinc aluminate ceramics with nanoscaled grain sizes were fabricated by Deformable Punch Spark Plasma Sintering (DP‐SPS). Optical transmission spectra showed high transparency, with up to 70% transmitted light in the visible spectrum. Vickers hardness was measured and grain boundary strengthening observed, showing hardness increase from 18.2 GPa up to 22.5 GPa as the grain sizes decreased from 60.3 to 10.1 nm. The trend followed the Hall‐Petch relationship, with hardness linearly proportional to the inverse of square root of grain size. A low grain size limit reported in previous literature below which hardness decreases, known as inverse Hall‐Petch relationship, was not observed within the studied grain size range. Cross‐sections of the hardness tests' indentations were prepared by focused ion beam and observed by electron microscopy and showed radically different crack patterns underneath the indentation imprint when contrasting samples with dissimilar grain sizes, shedding light on the mechanisms behind the observed grain boundary hardening mechanisms.
HIV status does not worsen oral health outcomes
Authors: Williams‐Wiles Lauren , Vieira Alexandre R.
Published: April 2019

Last January 31st, Journal of Clinical Periodontology just made available the report titled “A Retrospective Analysis of Dental Implant Survival in HIV Patients,” which concluded that “implants placed in HIV‐positive patients had similar survival rates as HIV‐negative patients.” These data support our hypothesis that infection by HIV does not lead to worse oral health outcomes, including worse periodontitis. We looked 6,092 individuals and selected all HIV‐positive subjects (N = 73) and matched them by age, sex, ethnicity, and smoking habits with 261 HIV‐negative control subjects. Based on these 334 total individuals, several dental conditions, including the need for root canal treatment, gingivitis, periodontitis, hairy leukoplakia, and dental caries were compared between the two groups. Overall, there was no difference in dental disease between the HIV‐positive and HIV‐negative groups. In our data, it was found that the prevalence of periodontitis in HIV‐positive patients was 16.4% and in HIV‐negative patients 19.2%.
Association of meal and snack patterns with micronutrient intakes among Greek children and adolescents: data from the Hellenic National Nutrition and Health Survey
Authors: Mitsopoulou A.‐V. , Magriplis E. , Dimakopoulos I. , Karageorgou D. , Bakogianni I. , Micha R. , Michas G. , Chourdakis M. , Ntouroupi T. , Tsaniklidou S.‐M. , Argyri K. , Panagiotakos D. B. , Zampelas A. ,   HNNHS Contributors,   HNNHS Advisory Committee
Published: April 2019

Background

The present study aimed to examine how different meal and snack patterns are associated with micronutrient intakes and diet quality among a nationally representative sample of Greek children and adolescents aged 1–19 years from the cross‐sectional Hellenic National Nutrition and Health Survey (n = 598).

Methods

Meal and snack patterns were derived using 24‐h dietary recalls. Mean adequacy ratio (MAR) was used as an overall measure of diet quality. Multiple linear regression adjusted for covariates was conducted to examine associations between eating patterns, nutrient intakes and MAR.

Results

Four most frequently reported eating schemes were identified including breakfast (B), lunch (L), dinner (D) and two snacks (S) (20.9%); B, L, D and 1S (16.2%); B, L, D and 3S (10.8%); and B, L and D (7.9%). Based on these schemes, the daily consumption of all main meals from the majority of the sample was highlighted. In children and adolescents aged 4–19 years, increasing snack frequency was positively associated with intakes of vitamin D, vitamin K, riboflavin, niacin, pantothenic acid, folate, magnesium, copper and selenium. An inverse association was recorded for vitamin E, vitamin B6, calcium and iron. Among children aged 1–3 years, only niacin and copper were significantly associated with number of snacks, with the group of ‘B‐L‐D‐2S’ presenting the highest intake. As for the overall diet quality, among all participants, there was no significant association of MAR with the type of meal and snack pattern, and thus the snack frequency.

Conclusions

Snacking behaviour is a common practice among children and adolescents. Modifying current snack foods with nutrient‐rich choices could lead to an improvement of their diet's nutritional quality.
Two‐stage Variscan metamorphism in the Canigou massif: Evidence for crustal thickening in the Pyrenees
Authors: de Hoÿm de Marien Luc , Le Bayon Benjamin , Pitra Pavel , Van Den Driessche Jean , Poujol Marc , Cagnard Florence
Published: April 2019

The Variscan metamorphism in the Pyrenees is dominantly of the low‐pressure–high‐temperature (LP‐HT) type. The relics of an earlier, Barrovian‐type metamorphism that could be related to orogenic crustal thickening are unclear and insufficiently constrained. A microstructural and petrological study of micaschists underlying an Ordovician augen orthogneiss in the core of the Canigou massif (Eastern Pyrenees, France) reveals the presence of two syntectonic metamorphic stages characterized by the crystallization of staurolite (M1) and andalusite (M2), respectively. Garnet is stable during the two metamorphic stages with a period of resorption between M1 and M2. The metamorphic assemblages M1 and M2 record similar peak temperatures of 580°C at different pressure conditions of 5.5 and 3 kbar, respectively. Using chemical zoning of garnet and calculated P–T pseudosections, a prograde P–T path is constrained with a peak pressure at ~6.5 kbar and 550°C. This P–T path, syntectonic with respect to the first foliation S1, corresponds to a cold gradient (of ~9°C/km), suggestive of crustal thickening. Resorption of garnet between M1 and M2 can be interpreted either in terms of a simple clockwise P–T path or a polymetamorphic two‐stage evolution. We argue in favour of the latter, where the medium‐pressure (Barrovian) metamorphism is followed by a period of significant erosion and crustal thinning leading to decompression and cooling. Subsequent advection of heat, probably from the mantle, leads to a new increase in temperature, coeval with the development of the main regional fabric S2. LA‐ICP‐MS U–Th–Pb dating of monazite yields a well‐defined date at c. 300 Ma. Petrological evidence indicates that monazite crystallization took place close to the M1 peak pressure conditions. However, the similarity between this age and that of the extensive magmatic event well documented in the eastern Pyrenees suggests that it probably corresponds to the age of monazite recrystallization during the M2 LP‐HT event.