bluuebunny/crossref_metadata_2025 huggingface dataset:
Respiratory complications after adenotonsillectomy in high‐risk children with obstructive sleep apnea: A retrospective cohort study
Authors: Ekstein Margaret , Zac Lilach , Schvartz Reut , Goren Or , Weiniger Carolyn F. , DeRowe Ari , Fishman Gad
Published: October 2019

Background

Obstructive sleep apnea (OSA) occurs in 1%‐4% of children; adenotonsillectomy is an effective treatment. Mortality/severe brain injury occurs among 0.6/10 000 adenotonsillectomies; in children, 60% are secondary to airway/respiratory events. Earlier studies identified that children aged <2 years, extremes of weight, with co‐morbidities of craniofacial, neuromuscular, cardiac/respiratory disease, or severe OSA are at high risk for adverse post‐operative respiratory events (AE).

We aimed to: Firstly, investigate which risk factors were associated with AEs either in the post‐anesthesia care unit (PACU), pediatric intensive care unit (PICU), or both in this population. Secondly, we investigated factors associated with post‐operative PICU AE despite no event in the PACU in order to predict need of post‐operative PICU after their PACU stay.

Methods

Retrospective study of children admitted to the PICU after adenotonsillectomy between 08/2006‐09/2015. Demographics, risk factors, and occurrence of AE (oxygen saturation <92, stridor, bronchospasm, pneumonia, pulmonary edema, re‐intubation) were recorded.

Results

During the studied time period 4029 tonsil/adenoid procedures were performed in 3997 children. 179, admitted to the PICU post‐operatively, met criteria for analysis. PICU AEs occurred in 59%: 44%‐83% in any particular risk category. PACU AEs occurred in 42%. Of those with PACU events: 92% suffered AEs in the PICU; however, 35% of those without a PACU AE still suffered a PICU AE.

Conclusions

Among high‐risk children undergoing TA, absence of adverse events in PACU during a 2‐hour observation period does not predict absence of subsequent AEs in the PICU.
Environmental, social, and governance practices and perceived tail risk
Authors: Shafer Michael , Szado Edward
Published: October 2019

Using the implied volatility smirk on individual equity securities to measure perceived tail risk, we find that better environmental, social and governance (ESG) practices significantly reduce ex‐ante expectations of a left‐tail event. Our findings are robust to using multiple model specifications and to adjusting for potential endogeneity concerns. We also show that, while practices in each ESG pillar are important in reducing perceived tail risk, the environmental pillar plays the most important role. Our results indicate that investors consider strong ESG practices to be insurance against left‐tail events rather than wasteful investment borne out of managers’ own values or self‐interest.
Induction of IgG2 and IgG4 B‐cell memory following sublingual immunotherapy for ryegrass pollen allergy
Authors: Heeringa Jorn J. , McKenzie Craig I. , Varese Nirupama , Hew Mark , Bakx Amy T. C. M. , Aui Pei M. , Rolland Jennifer M. , O’Hehir Robyn E. , van Zelm Menno C.
Published: October 2019

Background

While treatment for atopic rhinitis is aimed mostly to relieve symptoms, only allergen‐specific immunotherapy (AIT) is targeted to modify the natural history of allergic diseases. This results in sustained clinical tolerance, even when treatment has stopped. The immunomodulatory effects of AIT are attributed mainly to increased regulatory T‐cell function and increased allergen‐specific IgG4, yet little is known about the effect on the memory B‐cell compartment.

Objective

We aimed to examine the effects of AIT on the IgE‐ and IgG subclass‐expressing memory B cells.

Methods

We recruited 29 patients with atopic seasonal rhinoconjunctivitis and performed a longitudinal analysis of the peripheral immune compartment before, during, and after sublingual immunotherapy (SLIT) for allergy to temperate grass pollen, predominantly to ryegrass pollen (RGP; Lolium perenne). Using flow cytometry on peripheral blood mononuclear cells and serum immunoassays, we analyzed the effects of a 4 months preseasonal treatment regimen comprising two or three courses in consecutive years on circulating IgE+ and IgG+ memory B cells and allergen‐specific Ig levels.

Results

SLIT increased RGP‐specific serum IgG2 and IgG4, as well as the frequencies of IgG2+ and IgG4+ memory B cells, whereas no effect was observed on the IgE+ memory B‐cell compartment. Furthermore, SLIT enhanced proportions of regulatory T cells specific to RGP. These changes were associated with clinical improvement.

Conclusion

Our data provide evidence for immunological effects of SLIT on B‐cell memory. Skewing responses toward IgG2 and IgG4 subclasses might be a mechanism to suppress IgE‐mediated allergic responses.
Fragmented QRS as a candidate marker for left ventricular nonrecovery in patients with peripartum cardiomyopathy
Authors: Tekin Tak Bahar , Cay Serkan , Ekizler Firdevs Aysenur , Ozcan Cetin Elif Hande , Pamukcu Hilal Erken , Kafes Habibe , Ulvan Nedret , Ozeke Ozcan , Ozcan Firat , Topaloglu Serkan , Aras Dursun
Published: October 2019

Background

Fragmented QRS (fQRS) complex, with various morphology, has been recently described as a diagnostic criterion of several cardiac diseases. However, there are little data regarding the prognostic role of fQRS in peripartum cardiomyopathy (PPCM) patients. We aimed to investigate the effect of fQRS on predicting left ventricular (LV) nonrecovery in patients with peripartum cardiomyopathy (PPCM).

Methods

Ninety patients (mean age: 34.7 ± 6.5 years) with the diagnosis of PPCM were analyzed retrospectively. The median follow‐up period of was 67.0 (12.0–192.0) months. Fragmented QRS was defined as the presence of various RSR’ patterns (QRS duration < 120 ms) with or without Q wave, which include an additional R wave (R’ prime) or notching of the R wave or S wave, or the presence of more than one R' (fragmentation) without typical bundle branch block. Recovery of LV function was defined as the presence of LV ejection fraction (EF) >45%.

Results

Of the patients, 54 (60%) did not recover LV function at the last follow‐up visit (nonrecovery group), while 36 of the patients (40%) exhibited LV recovery (recovery group). LV ejection fraction (EF) and fQRS were identified as independent predictors of LV nonrecovery in patients with PPCM (odds ratio OR: 5.546, 95% confidence interval CI: 0.792–0.979, p = .019 and OR: 5.986, 95% CI: 1.313–11.787, p = .014, respectively).

Conclusion

Our data firstly indicated that presence of fQRS was a significant predictor of LV nonrecovery in patients with PPCM. The fQRS might assist in identifying high‐risk patients.
Intravitreal therapy for retinal diseases in Norway 2011–2015
Authors: Kristiansen Ivar Sønbø , Haugli Bråten Ragnhild , Jørstad Øystein Kalsnes , Moe Morten Carstens , Sæther Erik Magnus
Published: October 2019

Purpose

During the past decade, intravitreally administered biologic drugs have advanced the treatment of retinal diseases, such as wet age‐related macular degeneration (AMD), diabetic macular oedema and retinal venous occlusions. The drugs as well as the necessary disease management imply considerable economic burden on healthcare systems. This Norwegian study documents the rates of use of intravitreal therapies and intercounty variation over a 5‐year period.

Methods

We collected data from the Norwegian Patient Register for all episodes of care encompassing intravitreal therapy during the period 2011–2015. For each episode, we received information on patient age, sex, county of residence, diagnosis and name of drug injected.

Results

During the study period, 21 277 patients had in total 236 857 episodes of care. The number of intravitreal injections doubled from 2011 to 2015, reaching 63 601 injections in 2015, of which 77% were for diagnosed wet AMD. In 2015, the age‐adjusted number of episodes varied from 19 to 55 per 1000 population aged 50+ across Norway's 19 counties. The age‐adjusted number of patients treated per 1000 population aged 50+ varied from 5.22 to 8.35.

Conclusion

The use of intravitreal injections increased rapidly with wet AMD as the most frequent diagnosis and with varying utilization across Norway's 19 counties. The causes of the varying use of intravitreal therapies could not be established but may reflect variation in disease prevalence, treatment capacity, travel distance to the nearest ophthalmic service and lack of national treatment guidelines. The geographic variation in utilization may challenge policy goals of equitable care and warrants further studies.
CoPSE: A methodological intervention towards gentle more‐than‐human relations
Authors: Hocknell Suzanne
Published: October 2019

One meaning of “gentle” is consideration for others. However, as Derrida has illustrated, it is impossible for one individual to consider all such others. Here I demonstrate that this impasse arises from the reproduction of self–other binaries. In the case of food, framing eating as consumption co‐produces eater and eaten as different kinds of things. Within this framing, even as the eater endeavours to be considerate to eaten others, there are limits to their hospitality. Yet pertinent to this is a second connotation of gentle, that of being easily controlled. Relating and caring with and for others are always negotiated with and in the trajectories we have become implicated in. Recreating otherwise necessitates shifts in the ways in which others are encountered in the here and now. To this end, in this paper I introduce the methodological intervention of “CoPSE.” CoPSE draws on three principles: Collective doings, Playful practices, and prefigurative Strange Encounters, and on Spinoza's concept of the composite individual. Here, I outline how CoPSE was used to gently disrupt situated norms, momentarily making space for embodied investigations of the world‐making of self–other relations. I demonstrate that such practices are micro‐resistances to social norms that in reproducing self–other binaries co‐create hierarchies of care. I argue that through rehearsal, through repetition and difference, such micro‐resistances have the chance to become generative micro‐refrains that prefigure embodied relations of more‐than‐human subjectivities and outlive the moment in ways that might just take hold.
Developmental changes in executive functions during adolescence: A study of inhibition, shifting, and working memory
Authors: Theodoraki Thalia E. , McGeown Sarah P. , Rhodes Sinead M. , MacPherson Sarah E.
Published: October 2019

The development of executive functions (EFs) has primarily been studied among younger children, despite research suggesting that particular aspects of EFs continue to develop throughout adolescence and into adulthood. This study investigated whether EFs continue to develop during the later stages of adolescence: three related, yet separable EF components – inhibition, shifting, and working memory – were examined in a cross‐sectional sample of 347 adolescents (aged 14–18 years). After adjusting for covariates, age was found to be a significant predictor of pupils’ performance on the inhibition but not the shifting or working memory tasks, suggesting different developmental trajectories for the three EF components. Controlling for non‐executive processes implicated in performing the inhibition and working memory tasks had the most pronounced effect on the relationship between performance on those tasks and age. Finally, socioeconomic status was a significant predictor of performance on all tasks. Implications for research and practice are discussed.

Statement of contribution

What is already known on this subject?

Brain regions associated with EFs continue to mature throughout adolescence, implying ongoing development of EFs.

Behavioural studies demonstrate that certain EFs have not yet reached their adult levels in early adolescence.

What the present study adds

Changes in inhibition, but not shifting or working memory task performance, are evident among older adolescents.

Lower‐order processes tapped by EF tasks act as confounds in the relationship between age and task performance.

Socioeconomic status is a significant predictor of adolescents’ performance on EF tasks.
Mucosal-associated invariant T cells and Vδ2+ γδ T cells in community acquired pneumonia: association of abundance in sputum with clinical severity and outcome
Authors: Hannaway R F , Wang X , Schneider M , Slow S , Cowan J , Brockway B , Schofield M R , Morgan X C , Murdoch D R , Ussher J E
Published: October 2019

Mucosal-associated invariant T (MAIT) cells and Vδ2+ γδ T cells are anti-bacterial innate-like lymphocytes (ILLs) that are enriched in blood and mucosa. ILLs have been implicated in control of infection. However, the role of ILLs in community-acquired pneumonia (CAP) is unknown. Using sputum samples from a well-characterized CAP cohort, MAIT cell and Vδ2+ T cell abundance was determined by quantitative polymerase chain reaction (qPCR). Cytokine and chemokine concentrations in sputum were measured. The capacity of bacteria in sputum to produce activating ligands for MAIT cells and Vδ2+ T cells was inferred by 16S rRNA sequencing. MAIT cell abundance in sputum was higher in patients with less severe pneumonia; duration of hospital admission was inversely correlated with both MAIT and Vδ2+ T cell abundance. The abundance of both ILLs was higher in patients with a confirmed bacterial aetiology; however, there was no correlation with total bacterial load or the predicted capacity of bacteria to produce activating ligands. Sputum MAIT cell abundance was associated with interferon (IFN)-α, IFN-γ, and sputum neutrophil abundance, while Vδ2+ T cell abundance was associated with CXCL11 and IFN-γ. Therefore, MAIT and Vδ2+ T cells can be detected in sputum in CAP, where they may contribute to improved clinical outcome.
Metastatic pancreatic adenosquamous carcinoma to the scalp: A case report and review of the literature
Authors: Salari Behzad , Sheinbein David M. , Rosman Ilana S. , Dehner Louis P.
Published: October 2019

Metastatic carcinoma to the skin occurs in only a minority of patients with a visceral or internal malignancy, with breast, lung, and colorectum accounting for the majority of cases. We present the case of a 66‐year‐old man with a recent violaceous nodule of the left scalp (1.2 × 1.0 × 0.2 cm) that was a metastatic pancreatic adenosquamous carcinoma, representing a seemingly rare event. Two months prior, after complaining of right hip pain, an image revealed a right femoral lesion. A biopsy of that lesion showed moderately differentiated adenocarcinoma. Subsequent imaging showed a mass in the pancreatic tail and also markedly elevated serum tumor markers, CA 19‐9 and carcinoembryonic antigen (5325 and 111.5 U/mL, respectively). Before the appearance of the scalp nodule, the patient received radiotherapy and was started on chemotherapy, which was continued after diagnosis and resection of the nodule. Subsequent metastases developed in the liver, lung and additional cutaneous lesions. He died 11 months after initial presentation with right hip pain. As this case shows, cutaneous metastases confer a poor prognosis, often with less than a year survival following their appearance.
Degenerative mitral valve stenosis: Diagnosis and management
Authors: Al‐Taweel Ahmad , Almahmoud Mohamed Faher , Khairandish Yasmine , Ahmad Masood
Published: October 2019

Mitral stenosis (MS) is a common valvular disease characterized by narrowing of the mitral valve orifice and a reduction in mitral valve area (MVA). While rheumatic MS (RMS) is frequently encountered in young individuals in developing countries, degenerative MS (DMS) is seen in the elderly in developed countries and its prevalence is increasing. DMS is usually a late presentation of mitral annular calcification (MAC). Accurate assessment of MVA in patients with MAC is challenging due to the alterations in the atrial and valvular structures as well as the presence of other comorbidities in this aging population. We will review the epidemiology, etiology, pathophysiology, diagnostic assessment, and management of DMS and compare the findings with RMS. The latest therapeutic approaches, including medical, surgical, and transcatheter valvular interventions, will be discussed.
A near‐infrared fluorescent pH sensing film for wound milieu pH monitoring
Authors: Li Shuxin , Vu Hong , Senkowsky Jon , Hu Wenjing , Tang Liping
Published: October 2019

Studies have shown that wound pH is a potentially influential factor in the healing process. Due to the flaws of traditional pH measurement approaches, wound pH measurement has not become part of current standard of care. A near‐infrared pH‐sensitive ratiometric film was created and characterized for measuring wound pH. This film was fabricated by physically absorbing poly (N‐isopropyl Acrylamide) nanoparticles conjugated with pH‐sensitive (CypHer5E) and pH‐insensitive (Cy7) fluorescent dyes into 2‐hydroxyethyl methacrylate hydrogel film. The pH pattern on wounds can be indirectly measured by pressing freshly discarded wound dressing on top of the pH‐sensitive film and imaging it. In vitro tests show that the film can accurately and rapidly detect a wide range of pH (from pH 4 to 8) in wound milieu. Further, patient studies showed that, by measuring pH on wound contact side of discarded wound gauze, the pH and its non‐homogeneous distribution on wounds can be indirectly determined. By comparing patients with different wound conditions, we find that near‐infrared pH sensing film can be used to measure wound exudate pH with high accuracy and efficiency. In addition, wound pH determination can provide an accurate assessment of wound healing activity in real time.
Snapshots of PLP‐substrate and PLP‐product external aldimines as intermediates in two types of cysteine desulfurase enzymes
Authors: Nakamura Ryosuke , Hikita Masahide , Ogawa Shoko , Takahashi Yasuhiro , Fujishiro Takashi
Published: October 2019

Cysteine desulfurase enzymes catalyze sulfur mobilization from l‐cysteine to sulfur‐containing biomolecules such as iron‐sulfur (Fe‐S) clusters and thio‐tRNAs. The enzymes utilize the cofactor pyridoxal‐5'‐phosphate (PLP), which forms the external substrate‐ and product‐aldimines and ketimines during catalysis and are grouped into two types (I and II) based on their different catalytic loops. To clarify the structure‐based catalytic mechanisms for each group, we determined the structures of the external substrate‐ and product‐aldimines as catalytic intermediates of NifS (type I) and SufS (type II) that are involved in Fe‐S cluster biosynthesis using X‐ray crystallographic snapshot analysis. As a common intermediate structure, the thiol group of the PLP‐l‐cysteine external aldimine is stabilized by the conserved histidine adjacent to PLP through a polar interaction. This interaction makes the thiol group orientated for subsequent nucleophilic attack by a conserved cysteine residue on the catalytic loop in the state of PLP‐l‐cysteine ketimine, which is formed from the PLP‐l‐cysteine aldimine. Unlike the intermediates, structural changes of the loops were different between the type I and II enzymes. In the type I enzyme, conformational and topological change of the loop is necessary for nucleophilic attack by the cysteine. In contrast, the loop in type II cysteine desulfurase enzymes showed no large conformational change; rather, it might possibly orient the thiol group of the catalytic cysteine for nucleophilic attack toward PLP‐l‐cysteine. The present structures allow a revision of the catalytic mechanism and may provide a clue for consideration of enzyme function, structural diversity, and evolution of cysteine desulfurase enzymes.

Database

Structural data are available in PDB database under the accession numbers 5WT2, 5WT4, 5ZSP, 5ZST, 5ZS9, 5ZSK, 5ZSO, 6KFZ, 6KG0, and 6KG1.
Altered ignition catchments threaten a hyperdiverse fire‐dependent ecosystem
Authors: Slingsby Jasper A. , Moncrieff Glenn R. , Rogers Annabelle J. , February Edmund C.
Published: October 2019

Human activities affect fire in many ways, often unintentionally or with considerable time‐lags before they manifest themselves. Anticipating these changes is critical, so that insidious impacts on ecosystems, their biodiversity and associated goods and services can be avoided, mitigated or managed. Here we explore the impact of anthropogenic land cover change on fire and biodiversity in adjacent ecosystems on the hyperdiverse Cape Peninsula, South Africa. We develop a conceptual framework based on the notion of an ignition catchment, or the spatial extent and temporal range where an ignition is likely to result in a site burning. We apply this concept using fire models to estimate spatial changes in burn probability between historical and current land cover. This change layer was used to predict the observed record of fires and forest encroachment into fire‐dependent Fynbos ecosystems in Table Mountain National Park. Urban expansion has created anthropogenic fire shadows that are modifying fire return intervals, facilitating a state shift to low‐diversity, non‐flammable forest at the expense of hyperdiverse, flammable Fynbos ecosystems. Despite occurring in a conservation area, these ecosystems are undergoing a hidden collapse and desperately require management intervention. Anthropogenic fire shadows can be caused by many human activities and are likely to be a universal phenomenon, not only contributing to the observed global decline in fire activity but also causing extreme fires in ecosystems where there is no shift to a less flammable state and flammable fuels accumulate. The ignition catchment framework is highly flexible and allows detection or prediction of changes in the fire regime, the threat this poses for ecosystems or fire risk and areas where management interventions and/or monitoring are required. Identifying anthropogenic impacts on ignition catchments is key for both understanding global impacts of humans on fire and guiding management of human‐altered landscapes for desirable outcomes.
An analysis of the trends of undergraduates' academic achievement based on their admissions type in Korea
Authors: Lee Hyeon Woo , Lee Hye Yeon , Kim Eun Jin
Published: October 2019

This study investigates the establishment and benefits of the comprehensive admissions type recently introduced into Korean universities. We analyse undergraduate students' academic achievement and career readiness across three different admissions types in a medium‐sized university: rolling, comprehensive and regular. First, a series of mixed ANOVAs examined longitudinal changes for academic achievement and a set of ANOVAs found differences for academic achievement, within each semester. Specifically, students admitted via comprehensive admissions were found to have grade point averages (GPAs) similar to students admitted via regular admissions. Second, two‐way MANOVA examined students' career readiness by admissions type and academic standing. Students admitted through comprehensive admissions were found to exhibit a higher level of career readiness across academic years. The implications for admissions types in Higher Education are discussed.
Successful pulp revascularization of an autotransplantated mature premolar with fragile fracture apicoectomy and plasma rich in growth factors: a 3‐year follow‐up
Authors: Gaviño Orduña J. F. , García García M. , Dominguez P. , Caviedes Bucheli J. , Martin Biedma B. , Abella Sans F. , Manzanares Céspedes M. C.
Published: October 2019

Aim

This case report demonstrates a positive outcome of the adjuvant use of fragile fracture (FF), which is a technique used to harvest dental pulp stem cells (DPSCs), and platelet‐rich plasma (PRP) in a mandibular premolar (tooth 44) with a completely formed root that was transplanted into a surgically created socket and which maintained pulp vitality and function.

After virtual surgical planning, a 3D tooth replica of tooth 44 was fabricated. A surgical socket was created in the position of tooth 14; then, tooth 44 was extracted and the root dentine was abraded using a turbine diamond bur 3 mm from the apex until a circular groove was prepared around the outer circumference of the root; and then, an FF was performed without damaging the pulp tissue. PRP was placed in the socket, after which the donor tooth was inserted in the recipient area. At 2 weeks post‐treatment, orthodontic traction was applied. At 3‐year follow‐up, the tooth had adequate alignment and was asymptomatic. Response to pulp testing was positive, and the presence of pulp canal obliteration was observed as a sign of pulpal healing.

Key learning points

Autotransplantation is a good alternative for replacing missing teeth, with repair of tissues and pulp revascularization.

Revascularization of an autotransplanted mature tooth using the fragile fracture technique and PRP scaffold is a feasible option and might have positive effects on the long‐term outcome of the procedure.

Including completely formed teeth as donors in autotransplantation, maintaining vitality and their functions is an option that warrants further study.
Gaps at the interface between dentine and self‐adhesive resin cement in post‐endodontic restorations quantified in 3D by phase contrast‐enhanced micro‐CT
Authors: Soares A. P. , Bitter K. , Lagrange A. , Rack A. , Shemesh H. , Zaslansky P.
Published: October 2019

Aim

To assess the extent of gaps between root dentine and titanium or fibreglass post restorations following cementation with a self‐adhesive resin cement.

Methodology

Fourteen root filled maxillary central incisors restored with prefabricated posts made of Fibreglass (n = 7) or Titanium (n = 7) and cemented with RelyX Unicem 2 were imaged by rapid, high‐resolution phase contrast‐enhanced micro‐CT (PCE‐CT) in a synchrotron X‐ray imaging facility (ID19, ESRF, 34 KeV, 0.65 µm pixel resolution). Reconstructions were used to measure canal, cement and post perimeters and cross‐sectional areas and interfacial gaps at 0.1 mm increments in the root canal space, along the cervical region of the tooth. Remnants of endodontic sealer (AH Plus), when present, were also quantified. Mann–Whitney and 2‐way ANOVA tests were used to compare findings within slices and between the two post groups. Pearson correlation coefficients (r) were determined between the interfacial gaps and the other measured parameters.

Results

Clearly detectable gaps were found in 45% (±14%) of the interfaces between dentine and cement, along the canal in the cervical area of the tooth beneath the core. The length of interfacial gaps was moderately correlated to the canal cross‐sectional area, to the canal perimeter and to the canal area filled by cement (R = 0.52 ~ 0.55, P < 0.001). There was no significant difference between samples with fibreglass or titanium (P > 0.01). Both post types had defect‐free interfaces with cement. Endodontic sealer remnants were found on ~10% of the canal walls and were moderately correlated to the presence of gaps. Approximately 30% of the sealer‐affected interfaces exhibited no detachment between dentine, sealer and cement.

Conclusions

Self‐adhesive cements had interfacial gaps along substantial regions of the root canal surface, which was not correlated with the amount of cement in the canal. PCE‐CT proved to be an excellent non‐destructive method to study root canal restorations of hydrated samples in 3D.
Analysis of the prevalence of systemic de novo thrombotic microangiopathy after ABO‐incompatible kidney transplantation and the associated risk factors
Authors: Tasaki Masayuki , Saito Kazuhide , Nakagawa Yuki , Imai Naofumi , Ito Yumi , Yoshida Yutaka , Ikeda Masahiro , Ishikawa Shoko , Narita Ichiei , Takahashi Kota , Tomita Yoshihiko
Published: October 2019

Objectives

To analyze the prevalence of systemic de novo thrombotic microangiopathy in ABO‐incompatible kidney transplantation and risk factors associated with this condition.

Methods

A total of 201 patients who received living‐donor kidney transplantation (114 patients with ABO‐identical kidney transplantation and 87 patients with ABO‐incompatible kidney transplantation) were retrospectively analyzed. Systemic de novo thrombotic microangiopathy was diagnosed clinically according to the presence of thrombocytopenia with microangiopathic hemolytic anemia and pathological findings of thrombotic microangiopathy. Anti‐A and anti‐B antibodies were purified from human plasma, and these antibodies’ bindings to human kidney were investigated in vitro.

Results

ABO‐incompatible kidney transplantation was a significant risk factor of systemic de novo thrombotic microangiopathy (odds ratio 55.9, 95% CI 1.8–8.9, P < 0.001) after transplantation. Multivariate logistic regression analysis showed that non‐use of mycophenolate mofetil, pretreatment immunoglobulin G antibody titer ≥64‐fold and pretransplant immunoglobulin M antibody titer ≥16‐fold were significant risk factors for systemic de novo thrombotic microangiopathy in ABO‐incompatible kidney transplantation. Microvascular inflammation of 1‐h post‐transplant biopsy could be observed more frequently in thrombotic microangiopathy patients than in non‐thrombotic microangiopathy patients. Anti‐A and anti‐B antibodies purified from human plasma showed a strong in vitro reaction against human kidney when the antibody titer was ≥16‐fold.

Conclusions

Antibody titer should be decreased to ≤16‐fold until the day of ABO‐incompatible kidney transplantation by desensitization therapy including mycophenolate mofetil. The 1‐h biopsy results might help to diagnose systemic de novo thrombotic microangiopathy.
Lasers for reduction of unwanted hair in skin of colour: a systematic review and meta‐analysis
Authors: Dorgham N.A. , Dorgham D.A.
Published: October 2019

Light‐based therapies are one of the most effective and widely used strategies for removal of undesired hair, with a broadly favourable safety profile. However, subjects with pigmented skin are found to be more prone to laser‐related adverse events. While prolonged pulse‐width and longer treatment duration were proposed to minimize adverse events, the optimal treatment option among available phototherapy modalities – long‐pulsed (Nd:YAG), pulsed diode and alexandrite lasers as well as intense pulsed light (IPL) – remains unclear, particularly for skin of colour. To determine superiority in terms of effectiveness and tolerability, we conducted a systematic review of literature on different types of in‐office laser and IPL for hair removal in subjects with Fitzpatrick skin types III–VI. The meta‐analysis was performed using Review Manager (RevMan) version 5.3 and included 12 eligible comparative trials (nine randomized controlled trials and three quasi‐randomized). In terms of hair count reduction, pooled effect estimates for long‐pulsed ND:YAG laser [OR: 0.26, 95% CI (0.1, 0.78)] and diode laser [standardized mean difference (SMD): −0.11, 95% CI (−0.62, 0.39)] were not statistically significant from those of IPL; in contrast, alexandrite laser was found to be superior to IPL in reducing hair count [SMD: −1.7, 95% CI (−2.6, −0.78)]. In terms of adverse events, the pooled effect estimates favoured long‐pulsed Nd:YAG laser to IPL with respect to postinflammatory hyperpigmentation [OR: 0.26, 95% CI: (0.1, 0.78)]. However, both pulsed diode and alexandrite lasers exhibited a comparable safety profile to IPL, despite higher pain scores with lasers. In conclusion, this systematic review suggests that treatment outcomes for different in‐office laser devices and IPL in subjects with skin type III–VI are broadly similar; nevertheless, we observed a trend towards greater hair reduction following laser therapy compared with IPL.
The more the better? An appraisal of combination therapies for actinic keratosis
Authors: Steeb T. , Wessely A. , Leiter U. , French L.E. , Berking C. , Heppt M.V.
Published: October 2019

Actinic keratoses (AK) are common precancerous lesions of the skin. Numerous interventions exist for the treatment of AK, including lesion‐ and field‐directed approaches. In daily practice, different treatment modalities are often combined to maximize clearance rates. However, whether a combination therapy is preferable to monotherapy in terms of efficacy and safety has been subject of intense debate. In this review, we summarize the current knowledge on the efficacy and safety of local combination therapies for the treatment of patients with AK. Combination approaches of cryosurgery followed by photodynamic therapy (PDT), laser‐assisted PDT, PDT in combination with topical interventions and microneedling‐assisted PDT have shown slightly better efficacy results with similar tolerability compared to the respective monotherapy. However, the individual usage of combination therapies should be checked on a case‐by‐case basis and take into account individual patient‐ and lesion‐specific aspects as more resources are needed and because the individual monotherapies are already highly effective.
Summative Effects of Vascular Risk Factors on the Progression of Alzheimer Disease
Authors: Lee Wei‐Ju , Liao Yi‐Chu , Wang Yen‐Feng , Lin Yung‐Shuan , Wang Shuu‐Jiun , Fuh Jong‐Ling
Published: October 2019

OBJECTIVES

To investigate the summative effects of vascular risk factors (VRFs) on the progression of Alzheimer disease (AD).

DESIGN

Longitudinal follow‐up cohort study.

SETTING

AD patients from two teaching hospitals in Taiwan with 3‐year follow‐ups.

PARTICIPANTS

A total of 330 AD patients with a mean age of 80.7 years, a mean Mini‐Mental State Examination (MMSE) score 18.7, and a mean Clinical Dementia Rating Sum of Boxes (CDRSB) score of 6.9.

MEASUREMENTS

All patients completed a clinically functional assessment and a neuropsychological test battery at baseline and yearly follow‐ups. The VRF burden was combined into a summative VRF index at baseline (ie, having one, two, or more VRFs); VRFs included coronary heart disease, cardiac arrhythmia, hypertension, cerebrovascular disease, diabetes mellitus, obesity, smoking, and physical inactivity. The generalized estimating equation (GEE) method was used to analyze the correlations between the VRFs and longitudinal MMSE and CDRSB changes.

RESULTS

The results of the GEE adjusted for age, years of education, sex, disease duration, baseline MMSE score, time, apolipoprotein E (APOE) ε4 carrier status, use of medications (acetylcholinesterase inhibitors or N‐methyl‐D‐aspartate receptor antagonists), and hospitalization rates and showed that patients with more than three VRFs had more rapid cognitive decline than patients without VRFs (MMSE, P = .02; CDRSB, P = .001) as well as patients with three or fewer VRFs (MMSE, P = .009; CDRSB, P = .02). Subsequent analyses of APOE ε4 carriers with more than three VRFs also showed their more rapid cognitive decline compared with patients without VRFs (MMSE, P = .02; CDRSB, P = .001) and patients with three or fewer VRFs (MMSE, P = .009; CDRSB, P = .02), but no significant difference was found in APOE ε4 noncarriers.

CONCLUSION

Multiple VRFs have summative effects on the progression of AD, especially in APOE ε4 carriers. J Am Geriatr Soc 68:129–136, 2019
Glial pathology in a novel spontaneous mutant mouse of the Eif2b5 gene: a vanishing white matter disease model
Authors: Terumitsu‐Tsujita Mika , Kitaura Hiroki , Miura Ikuo , Kiyama Yuji , Goto Fumiko , Muraki Yoshiko , Ominato Shiho , Hara Norikazu , Simankova Anna , Bizen Norihisa , Kashiwagi Kazuhiro , Ito Takuhiro , Toyoshima Yasuko , Kakita Akiyoshi , Manabe Toshiya , Wakana Shigeharu , Takebayashi Hirohide , Igarashi Hironaka
Published: October 2019

Vanishing white matter disease (VWM) is an autosomal recessive neurological disorder caused by mutation(s) in any subunit of eukaryotic translation initiation factor 2B (eIF2B), an activator of translation initiation factor eIF2. VWM occurs with mutation of the genes encoding eIF2B subunits (EIF2B1, EIF2B2, EIF2B3, EIF2B4, and EIF2B5). However, little is known regarding the underlying pathogenetic mechanisms or how to treat patients with VWM. Here we describe the identification and detailed analysis of a new spontaneous mutant mouse harboring a point mutation in the Eif2b5 gene (p.Ile98Met). Homozygous Eif2b5I98M mutant mice exhibited a small body, abnormal gait, male and female infertility, epileptic seizures, and a shortened lifespan. Biochemical analyses indicated that the mutant eIF2B protein with the Eif2b5I98M mutation decreased guanine nucleotide exchange activity on eIF2, and the level of the endoplasmic reticulum stress marker activating transcription factor 4 was elevated in the 1‐month‐old Eif2b5I98M brain. Histological analyses indicated up‐regulated glial fibrillary acidic protein immunoreactivity in the astrocytes of the Eif2b5I98M forebrain and translocation of Bergmann glia in the Eif2b5I98M cerebellum, as well as increased mRNA expression of an endoplasmic reticulum stress marker, C/EBP homologous protein. Disruption of myelin and clustering of oligodendrocyte progenitor cells were also indicated in the white matter of the Eif2b5I98M spinal cord at 8 months old. Our data show that Eif2b5I98M mutants are a good model for understanding VWM pathogenesis and therapy development.

image

Cover Image for this issue: doi: 10.1111/jnc.14751.
The impact of in ovo injection of l‐arginine on hatchability, immune system and caecum microflora of broiler chickens
Authors: Omidi Somayeh , Ebrahimi Marziyeh , Janmohammadi Hossein , Moghaddam Gholamali , Rajabi Zolfaghar , Hosseintabar‐Ghasemabad Babak
Published: October 2019

The present article was conducted to evaluate the effect of in ovo injection of arginine on hatchability, immune system and caecum microflora of broiler chickens. For this reason, 300 fertile eggs were used in a completely randomized design with three experimental treatments. The experimental groups included: 1%–0.5% l‐arginine (100 eggs), 2%–1% l‐arginine (100 eggs), 3‐ control [included both sham control (injection of distilled water; 50 eggs) and control (no injection; 50 eggs)], which were injected on d 14 of incubation. After hatching, chicks of each experimental group (0.5% l‐arginine, 1% l‐arginine, and control groups) were randomly divided into four equal groups (as replicates) and reared for 30 days. Weight and feeding of chickens were recorded. Next, blood samples of chickens were collected on day 30 to evaluate antibody titre. Also, chickens were slaughtered on 24 and 30 days of the experiment to evaluate immune system organs and caecum microflora. Based on the results, in ovo injection of l‐arginine had no significant effect on hatchability, body weight, antibody titre, spleen, bursa of Fabricius and thymus weight (p > .05). On the other hand, treatments significantly affected feed intake and feed conversion ratio (p < .05). As a novel finding, in ovo injection of l‐arginine increased caecal Lactobacillus (p < .01), while decreasing Coliform and Escherichia Coli bacteria (p < .01). However, treatments did not influence caecal Enterococcus (p > .05). The overall results indicated that in ovo injection of 0.5% l‐arginine had a better improving effect on caecal microflora and then considered as a recommended level of the present experiment.
Coordinate regulation of virulence and metabolic genes by the transcription factor HbhR in Mycobacterium marinum
Authors: Raze Dominique , Segers Jérôme , Mille Céline , Slupek Stéphanie , Lecher Sophie , Coutte Loïc , Antoine Rudy , Ducrocq Lucie , Rouanet Carine , Appelmelk Ben J. , Locht Camille
Published: October 2019

The heparin‐binding hemagglutinin (HBHA) is a multifunctional protein involved in adherence of Mycobacterium tuberculosis to non‐phagocytic cells and in the formation of intracytosolic lipid inclusions. We demonstrate that the expression of hbhA is regulated by a transcriptional repressor, named HbhR, in Mycobacterium marinum. The hbhR gene, located upstream of hbhA, was identified by screening a transposon insertion library and detailed analysis of a mutant overproducing HBHA. HbhR was found to repress both hbhA and hbhR transcription by binding to the promoter regions of both genes. Complementation restored production of HBHA. RNA‐seq analyses comparing the mutant and parental strains uncovered 27 genes, including hbhA, that were repressed and 20 genes activated by HbhR. Among the former, the entire locus of genes coding for a type‐VII secretion system, including esxA, esxB and pe‐ppe paralogs, as well as the gene coding for PspA, present in intracellular lipid vesicles, was identified, as was katG, a gene involved in the sensitivity to isoniazid. The latter category contains genes that play a role in diverse functions, such as metabolism and resistance to oxidative conditions. Thus, HbhR appears to be a master regulator, linking the transcriptional regulation of virulence, metabolic and antibiotic sensitivity genes in M. marinum.
The effect of ketamine on emergence agitation in children: A systematic review and meta‐analysis
Authors: Ng Ka Ting , Sarode Deep , Lai Yuen Sin , Teoh Wan Yi , Wang Chew Yin
Published: October 2019

Background

Ketamine is believed to reduce the incidence of emergence agitation in children undergoing surgery or procedure. However, recent randomized controlled trials reported conflicting findings.

Aims

To investigate the effect of ketamine on emergence agitation in children.

Methods

Databases of MEDLINE, EMBASE, and CENTRAL were systematically searched from their start date until February 2019. Randomized controlled trials comparing intravenous ketamine and placebo in children were sought. The primary outcome was the incidence of emergence agitation. Secondary outcomes included postoperative pain score, duration of discharge time, and the adverse effects associated with the use of ketamine, namely postoperative nausea and vomiting, desaturation, and laryngospasm.

Results

Thirteen studies (1125 patients) were included in the quantitative meta‐analysis. The incidence of emergence agitation was 14.7% in the ketamine group and 33.3% in the placebo group. Children receiving ketamine had a lower incidence of emergence agitation, with an odds ratio being 0.23 (95% confidence interval: 0.11 to 0.46), certainty of evidence: low. In comparison with the placebo, ketamine group achieved a lower postoperative pain score (odds ratio: −2.42, 95% confidence interval: −4.23 to −0.62, certainty of evidence: very low) and lower pediatric anesthesia emergence delirium scale at 5 minutes after operation (odds ratio: −3.99, 95% confidence interval: −5.03 to −2.95; certainty of evidence: moderate). However, no evidence was observed in terms of incidence of postoperative nausea and vomiting, desaturation, and laryngospasm.

Conclusion

In this meta‐analysis of 13 randomized controlled trials, high degree of heterogeneity and low certainty of evidence limit the recommendations of ketamine for the prevention of emergence agitation in children undergoing surgery or imaging procedures. However, the use of ketamine is well‐tolerated without any notable adverse effects across all the included trials.

PROSPERO registration

CRD42019131865.
Building an International Community of Paediatric Anaesthesiologists: An interview with Dr Edward Sumner
Authors: Friesen Robert H.
Published: October 2019

Dr Edward Sumner (1940) enjoyed a remarkably productive career as consultant pediatric anesthetist at the Great Ormond Street Hospital for Children. His leadership in clinical care helped his department rise to eminence. He trained hundreds of registrars in pediatric anesthesia and educated thousands more through invited lectures and by co‐editing leading textbooks of neonatal and pediatric anesthesia. During his long tenure as Editor‐in‐Chief of Pediatric Anesthesia, he led the growth of the young journal to prominence. Based on an interview and a long‐standing professional and personal friendship of forty‐four years, this article reviews Ted Sumner's outstanding contributions to the specialty of pediatric anesthesia and to the development of a strong international community of pediatric anesthesiologists.
Combined ipilimumab and nivolumab first‐line and after BRAF‐targeted therapy in advanced melanoma
Authors: Mason Robert , Dearden Helen C. , Nguyen Bella , Soon Jennifer A. , Smith Jessica Louise , Randhawa Manreet , Mant Andrew , Warburton Lydai , Lo Serigne , Meniawy Tarek , Guminski Alexander , Parente Phillip , Ali Sayed , Haydon Andrew , Long Georgina V. , Carlino Matteo S. , Millward Michael , Atkinson Victoria G. , Menzies Alexander M.
Published: October 2019

The combination of ipilimumab and nivolumab is a highly active systemic therapy for metastatic melanoma but can cause significant toxicity. We explore the safety and efficacy of this treatment in routine clinical practice, particularly in the setting of serine/threonine‐protein kinase B‐Raf (BRAF)‐targeted therapy. Consecutive patients with unresectable stage IIIC/IV melanoma commenced on ipilimumab and nivolumab across 10 tertiary melanoma institutions in Australia were identified retrospectively. Data collected included demographics, response and survival outcomes. A total of 152 patients were included for analysis, 39% were treatment‐naïve and 22% failed first‐line BRAF/MEK inhibitors. Treatment‐related adverse events occurred in 67% of patients, grade 3–5 in 38%. The overall objective response rate was 41%, 57% in treatment‐naïve and 21% in BRAF/MEK failure patients. Median progression‐free survival was 4.0 months (95% CI, 3.0–6.0) in the whole cohort, 11.0 months (95% CI, 6.0‐NR) in treatment‐naïve and 2.0 months (95% CI, 1.4–4.6) in BRAF/MEK failure patients. The combination of ipilimumab and nivolumab can be used safely and effectively in a real‐world population. While first‐line efficacy appears comparable to trial populations, BRAF‐mutant patients failing prior BRAF/MEK inhibitors show less response.
Nitric oxide and hydrogen sulfide crosstalk during heavy metal stress in plants
Authors: Shivaraj Sheelavanta M. , Vats Sanskriti , Bhat Javaid A. , Dhakte Priyanka , Goyal Vinod , Khatri Praveen , Kumawat Surbhi , Singh Akshay , Prasad Manoj , Sonah Humira , Sharma Tilak R. , Deshmukh Rupesh
Published: October 2019

Gases such as ethylene, hydrogen peroxide (H2O2), nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) have been recognized as vital signaling molecules in plants and animals. Of these gasotransmitters, NO and H2S have recently gained momentum mainly because of their involvement in numerous cellular processes. It is therefore important to study their various attributes including their biosynthetic and signaling pathways. The present review provides an insight into various routes for the biosynthesis of NO and H2S as well as their signaling role in plant cells under different conditions, more particularly under heavy metal stress. Their beneficial roles in the plant's protection against abiotic and biotic stresses as well as their adverse effects have been addressed. This review describes how H2S and NO, being very small‐sized molecules, can quickly pass through the cell membranes and trigger a multitude of responses to various factors, notably to various stress conditions such as drought, heat, osmotic, heavy metal and multiple biotic stresses. The versatile interactions between H2S and NO involved in the different molecular pathways have been discussed. In addition to the signaling role of H2S and NO, their direct role in posttranslational modifications is also considered. The information provided here will be helpful to better understand the multifaceted roles of H2S and NO in plants, particularly under stress conditions.