bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in intravenous immunoglobulin use in New South Wales, Australia
Authors: Wood James G. , Heywood Anita E. , Dennington Peta M. , Lloyd Andrew R. , Ziegler John B.
Published: July 2023

Background

Intravenous immunoglobulin (IVIg) is a critical replacement therapy for immunodeficiencies and immunomodulatory treatment for autoimmune and inflammatory diseases. Adequate supply of IVIg is a global issue, necessitating supply restrictions. In Australia, despite strict criteria for use, demand for IVIg has increased over time and exceeds domestic supply.

Objective

Factors associated with the upward trend in overall IVIg use were examined, including in the number of unique patients, IVIg dosing and treatment frequency and variations by prescribing discipline and disease group.

Methods

De‐identified data of IVIg dispensed in the largest Australian state (New South Wales) from 2007 to 2013 were provided by Australian Red Cross Lifeblood. Trends and projections were calculated using log‐linear regression of unique patients, treatment episodes and grams of IVIg for overall use and use stratified by discipline and disease group.

Results

During the study period, 169 453 treatment episodes were recorded for 12 547 unique patients accounting for 5 827 787 g of IVIg use. Overall, IVIg use increased by 12.0% (11.5–12.6%) per year representing a 97.7% increase (91.6–104%) over the study period. The highest growth was among neurological conditions (16.0% (14.9–17.1%) per year). An increase in the number of unique patients was the primary driver of this growth, augmented by increases in the frequency and average dose per treatment.

Conclusions

Clinically acceptable measures to improve management of IVIg supply are needed including optimising dose, frequency and duration of treatment. Formal evaluation of IVIg versus alternatives, including cost‐effectiveness and comparative efficacy, is warranted.
Costs and consequences of over‐investigation of minor transfusion reactions
Authors: Joel Cliford T. , Burgess Maria , Crispin Philip
Published: July 2023

Background

Adverse transfusion events create a direct cost burden on the healthcare system through increased morbidity, mortality, extra investigations for diagnosis, patient treatment and increased use of hospital resources. Understanding the costs and impact minor transfusion reactions have on the healthcare system presents an opportunity for potential cost savings and improved clinical practice.

Aims

To determine the cost associated with investigating minor transfusion reactions, to identify opportunities to improve the management of blood transfusion reactions and potential cost savings through the application of current national guidelines.

Methods

A retrospective review of all suspected transfusion reactions reported to the laboratory over a 6‐year period was performed. Reports were assessed for appropriateness of clinical management and associated investigations. Cost of inappropriate investigations and associated blood product discard was calculated using current national tariffs.

Results

Of the 274 reports, febrile non‐haemolytic transfusion reactions were the most common reactions, with 96 (35%) cases. One hundred forty‐eight patients were unnecessarily investigated for suspected transfusion reactions totalling AU$ 32 427.00. The initial total value of partially discarded blood products was AU$ 55 656.00.

Conclusion

The study demonstrated that unnecessary investigation of minor transfusion reactions adds a significant financial burden to the healthcare system.
Intravenous iron: an update
Authors: Lucas Sarah , Garg Mayur
Published: July 2023

Iron deficiency is the most common nutritional deficiency worldwide, with significant adverse health consequences in the presence or absence of anaemia. Total dose intravenous iron replacement is recommended for replacement of iron in patients with severe iron deficiency, especially in the presence of anaemia, intolerance or inefficacy following oral iron, or states of inflammation where upregulation of hepcidin may impair gastrointestinal absorption of iron. Currently, available intravenous iron formulations have been demonstrated to have an excellent overall safety profile, but potential adverse effects, including skin staining, infusion‐related reactions and hypophosphataemia, have been described. Knowledge of differences in administration and safety profiles of currently available iron formulations will allow appropriate prescription, counselling, as well as recognition and management of adverse events in patients requiring intravenous iron.
Essence of culture and nature: Governance as the emerging correlates of quality‐of‐life experiences in the communities of Himachal, India
Authors: Chand Puran , Thakur B. R.
Published: July 2023

The aim of this work is to uncover factors influencing the quality of life in the study area. The idea is operationalized by collecting data at the household level on subjective and objective aspects of quality of life. For this study, data were collected from 18 sample villages using a stratified random sampling method. The villages were chosen to represent two distinct communities, namely the scheduled castes (SC) and the general population, spread across three altitudinal zones. In all, 436 households (about 20% of the total) were surveyed with respect to 10 domains of quality of life, namely environment and cleanliness, housing, education, health, personal well‐being, democratic and social participation, information and communication, employment, income and wealth and governance. To identify the key domains of quality of life, the principal components analysis (PCA) technique was applied. The findings support the idea that Asian predictors of satisfaction with life are similar to those of the Western world, but social and cultural backgrounds determine some culture‐oriented predictors. The PCA results show that governance is the key determinant of life satisfaction. This study reveals that due to higher levels of educational attainment, good income conditions, and greater participation in community affairs, the general community has reported higher quality of life satisfaction compared to the SC community population.
Factors that affect GP referral of a child with intellectual disability for a mild illness: A discrete choice experiment
Authors: Nicholson Emma , McDonnell Thérèse , Conlon Ciara , De Brún Aoife , Doherty Edel , Collins Claire , Bury Gerard , McAuliffe Eilish
Published: July 2023

Background

General practitioners (GP) report multiple challenges when treating individuals with intellectual disabilities which may influence referral rates. The study aimed to establish factors that influence GP's decision‐making when referring a child with intellectual disabilities to the emergency department.

Method

Discrete choice experiments (DCEs) are increasingly used in health research to further understand complex decision making. A DCE was designed to assess the relative importance of factors that may influence a GP's (N = 157) decision to refer.

Results

A random parameters model indicated that perceived limited parental capacity to manage an illness was the most important factor in the decision to refer a child to the ED, followed by a repeat visit, a referral request from the parent, and a Friday afternoon appointment.

Conclusion

Understanding the factors that influence referral is important for service improvement and to strengthen primary care provision for this population and their families.
Comparison of the efficacy and safety of total laparoscopic hysterectomy without and with uterine manipulator combined with pelvic lymphadenectomy for early cervical cancer
Authors: Zeng Wei‐hong , Liang Ye , Zhou Jing‐qing , Lin Hai‐hong , Huang Li‐shan , He Dan‐feng , Wen Ji‐zhong , Wu Bo‐ming , Liu Hao‐chang , Zhong Yao‐xiang , Lei Nan‐xiang , Yang Hai‐kun
Published: July 2023

Objective

Some studies have reported that the prognosis of total laparoscopic hysterectomy (TLH) for early‐stage cervical cancer (CC) is worse than that of open surgery. And this was associated with the use of uterine manipulator or not. Therefore, this study retrospectively analyzes the efficacy and safety of TLH without uterine manipulator combined with pelvic lymphadenectomy for early‐stage CC.

Methods

Fifty‐eight patients with CC (stage IB1‐IIA1) who received radical hysterectomy from September 2019 to January 2020 were divided into no uterine manipulator (n = 26) and uterine manipulator group (n = 32). Then, clinical characteristics were collected and intraoperative/postoperative related indicators were compared.

Results

Patients in the no uterine manipulator group had significantly higher operation time and blood loss than in the uterine manipulator group. Notably, there was no significant difference in hemoglobin change, blood transfusion rate, number of pelvic nodules, anal exhaust time, complications and recurrence rate between the two groups. Additionally, patients in the uterine manipulator group were prone to urinary retention (15.6%) and lymphocyst (12.5%), while the no uterine manipulator group exhibited high probability of bladder dysfunction (23.1%) and urinary retention (15.4%). Furthermore, the 1‐year disease‐free survival rate and the 1‐year overall survival rate were not significantly different between the two groups.

Conclusion

There was no significant difference in the efficacy and safety of TLH with or without uterine manipulator combined with pelvic lymphadenectomy in the treatment of patients with early‐stage CC. However, the latter requires consideration of the negative effects of high operation time and blood loss.
Exploring intersectoral collaboration in diabetes care: A positioning theoretical perspective
Authors: Andersen Anne Bendix , Frederiksen Kirsten , Laursen Henrik Sehested , Gravesen Janni Dahlgaard
Published: July 2023

Intersectoral collaboration (IC) plays a significant role in the delivery of diabetes care and treatment of patients with type 2 diabetes (DM2), as the treatment and care of these patients take place in both primary care and specialist settings. The collaboration involves a large number of actors from primary and secondary healthcare sectors, who are expected to fulfil various roles when they engage in IC. We explored the actors' roles by applying the framework of positioning theory with the aim of revealing seemingly embedded understandings of such roles. The empirical data consisted of individual and focus group interviews. Our results indicate that naturalised understandings of the roles of actors interact with the way in which health professionals, patients, managers and relatives strive to develop IC that aims to help and guide patients who live with DM2.
Interpreting shoot flammability experiments: from fire behaviour to plant evolution
Authors: Resco de Dios Víctor
Published: July 2023

This article is a Commentary on Cui et al. (2023), 240: 105–113.
Unusual presentation of disseminated cryptococcal infection complicated by myocarditis in a heart transplant recipient
Authors: Barros Kathryn , Tepper John William , Ramchandani Juhi , Kelley Meagan Kristine , Kussin Michelle L. , Israel Emily N. , Tompkins Madeline G. , Alali Muayad
Published: July 2023

Background

Cryptococcus neoformansis the third most common cause of invasive fungal infection in solid organ transplant (SOT) recipients. While cryptococcal infection can involve any organ, cases of myocarditis are exceedingly rare.

Methods

A retrospective chart review was completed for this case report.

Results

We present the case of a 21‐year‐old heart transplant recipient who developed disseminated cryptococcal infection with biopsy‐proven cryptococcal myocarditis.

Conclusions

Cryptococcal disease in SOT recipients poses diagnostic and therapeutic challenges. There are no current guidelines for the duration of cryptococcal myocarditis treatment. Repeat myocardial biopsy may play a role in guiding length of therapy.
Diversity of Colletotrichum species causing anthracnose on three oak species (Quercus acutissima, Q. mongolica and Q. variabilis) in China
Authors: Wang Cheng‐Bin , Li Yong , Xue Han , Piao Chun‐Gen , Jiang Ning
Published: July 2023

Anthracnose of oak (Quercus) caused by Colletotrichum spp. is one of the most common diseases in oak forests. To investigate the species diversity of Colletotrichum associated with oak anthracnose, symptomatic leaf samples of three oak species (Q. acutissima, Q. mongolica and Q. variabilis) were collected from Anhui, Hainan, Henan, Shaanxi and Shandong Provinces, Inner Mongolia Autonomous Region, and Beijing City in China from 2019 to 2022. A total of 219 Colletotrichum isolates were obtained and identified by morphological and phylogenetic analyses of the rDNA internal transcribed spacer (ITS), glyceraldehyde‐3‐phosphate dehydrogenase (gapdh), chitin synthase 1 (chs‐1), actin (act) and β‐tubulin (tub2) sequences. Nine species were identified: C. fioriniae (two isolates, 0.9%), C. camellia‐japonicae (two isolates, 0.9%), C. karstii (three isolates, 1.4%), C. quercicola (two isolates, 0.9%), C. aenigma (three isolates, 1.4%), C. endophyticum (two isolates, 0.9%), C. fructicola (68 isolates, 31.1%), C. gloeosporioides sensu stricto (74 isolates, 33.8%) and C. siamense (63 isolates, 28.8%). Pathogenicity was confirmed using Koch's postulates, which showed that five species (C. camellia‐japonicae, C. endophyticum, C. fructicola, C. gloeosporioides s. s. and C. siamense) caused Q. acutissima anthracnose, four species (C. karstii, C. fructicola, C. gloeosporioides s. s. and C. siamense) caused Q. mongolica anthracnose and six species (C. fioriniae, C. quercicola, C. aenigma, C. fructicola, C. gloeosporioides s. s. and C. siamense) caused Q. variabilis anthracnose. This study demonstrates the pathogenic species diversity of Colletotrichum on Q. acutissima, Q. mongolica and Q. variabilis.
Complications following alveolar ridge augmentation procedures
Authors: Leblebicioglu Binnaz , Tatakis Dimitris N.
Published: July 2023

Oral rehabilitation through implant supported dental restorations often requires a ridge augmentation procedure (RAP) prior to implant fixture placement since tooth extraction/loss results in alveolar ridge deficiencies. Although RAP‐related surgical techniques and biomaterials have been in practice for several decades, outcomes are not always predictable. Post‐surgical complications experienced during the early or late wound healing phases may jeopardize the targeted ideal ridge dimensions, required for implant fixture placement, and may have other consequences, such as negatively impacting the patient's quality of life. This review describes reported post‐surgical complications following RAP under the following subtitles: complications by tissue type, complications in function and aesthetics, complications by healing time, complications by biomaterial type, and complications by surgical protocol modalities. Specifically, RAP performed by using particulate bone graft substitutes and related complications are explored. Modalities developed to prevent/manage these complications are also discussed.
Role of macrophage scavenger receptor 1 in the progression of dyslipidemia in acne vulgaris patients
Authors: AbdElneam Ahmed Ibrahim , Al‐Dhubaibi Mohammed Saleh , Bahaj Saleh Salem , Mohammed Ghada Farouk
Published: July 2023

Background

Macrophage scavenger receptor 1 gene (MSR1), is responsible for producing macrophage scavenger receptors. MSR1 is primarily located on the surfaces of various macrophage types and is known to exert a range of effects on the human body. These effects include influencing innate and adaptive immunological reactions, as well as contributing to the development of conditions such as atherosclerosis, dyslipidemia, liver and lung disease, and cancer. The unregulated assimilation of lipoproteins by MSR1 leads to the creation of macrophages rich in cholesterol that manifest as foam‐like cells, ultimately contributing to dyslipidemia. This occurrence highlights the significance of MSR1 as a key player in the pathophysiology of dyslipidemia.

Aim

In this study, we aimed to estimate variation in lipid profile in acne vulgaris (AV) patients. Also, we aimed to investigate the role of MSR1 in lipid profile variation.

Subjects and methods

A case‐control study consisting of 100 patients with AV and 104 healthy controls. Lipid profiles were assessed using normalized enzymatic processes and genotype analyses were performed by a polymerase chain reaction and standard Sanger sequencing. Predictions of variant effects were performed using in silico tools.

Result

Our results indicated that the levels of lipid profile were higher in patients with AV than in healthy patients. The two haplotypes that were most prevalent in the patients were TCAC (16.5%) and CAGG (15.47%), whereas the two haplotypes that were more prevalent in the controls were TAAC (16.43%) and CCAC (15.62%). IVS5.59 C > A and rs433235 A > G are in linkage disequilibrium. Additionally, rs433235 A > G has a significant linkage disequilibrium with rs3747531 C > G. In silico analysis, tools indicated that the rs433235 A > G variant was disease‐causing.

Conclusion

Patients diagnosed with TCAC and CAGG exhibited a higher prevalence compared to healthy patients with TAAC and CCAC. The linkage disequilibrium between rs433235 A > G and IVS5.59 C > A has been established. Furthermore, there appears to be significant linkage disequilibrium between rs3747531 C > G and rs433235 A > G. These findings support the notion that genetic variations may play a critical role in the pathogenesis of these conditions.
Geomorphometry and microelectronic metrology: Converged realms
Authors: Dedkova A. A. , Florinsky I. V.
Published: July 2023

This article discusses the application of geomorphometric methods in microelectronic metrology. Six typical microelectronic items were geomorphometrically analyzed using their digital elevation models with nano‐ and micrometer‐range resolution and elevation difference: (1) a silicon–quartz structure; (2) a mechanically polished silicon wafer; (3) a photovoltaic blend sample; (4) an X‐ray optical element (a fused quartz spherical concave substrate); (5) a Bosch process‐formed, 20 aluminum layered membrane; and (6) a silicon–glass assembly with a volumetric defect. Geomorphometric modeling increases significantly the visibility and informativeness of data presentation, allowing to identify effectively the spatial distribution of nano‐ and microforms of the surface of microelectronic items. Geomorphometric methods provide an opportunity to study the size, location, and characteristic features of nano‐ and microtopographic inhomogeneities of microelectronic items using maps of minimum, maximum, mean, and unsphericity curvatures as well as other morphometric variables.
Organ donation following medical assistance in dying, Part II: a scoping review of existing processes and procedures
Authors: Silva e Silva Vanessa , Silva Amina Regina , Rochon Andrea , Lotherington Ken , Hornby Laura , Wind Tineke , Bollen Jan , Wilson Lindsay C. , Sarti Aimee J. , Dhanani Sonny
Published: July 2023

Objective:

The objective of this review was to collate and summarize the current literature on what is known about organ donation following medical assistance in dying (MAiD). For this second part of a 2-part scoping review, the focus is on the existing procedures and processes for organ donation following MAiD.

Introduction:

Organ donation following MAiD is a novel and contentious issue worldwide. To give direction for future research and initiatives, a comprehensive understanding of the available evidence of existing procedures and processes for organ donation following MAiD is needed.

Inclusion criteria:

For this review, the population of interest included all individuals who underwent organ donation following MAiD; the concept was defined as procedures and processes involved in organ donation after MAiD; and the context was reports of organ donation following MAiD at home or in any health care setting worldwide. We considered quantitative and qualitative studies, text and opinion papers, gray literature, and unpublished material provided by stakeholders.

Methods:

This scoping review was conducted in line with JBI methodology. Published studies were retrieved from MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCOhost), PsycINFO (Ovid), Web of Science Core Collection, and Academic Search Complete (EBSCOhost). Gray and unpublished literature included reports from websites and organ donation organizations in Canada, Belgium, and The Netherlands. Two independent reviewers screened all reports (both title and abstract, and full text) against the predetermined inclusion criteria, extracted data, and completed a content analysis. Any disagreements between the 2 reviewers were resolved through discussion or with another reviewer.

Results:

We included 121 documents across parts I and II, and we report on 107 documents in this second part. The majority of the 107 documents were discussion papers, published in English, and in Canada from 2019 to 2021. In the content analysis, we identified 5 major categories regarding existing procedures and processes of organ donation following MAiD: i) clinical pathways for organ donation following MAiD; ii) organ donation following MAiD and the donor; iii) clinical practice tools for organ donation following MAiD; iv) education and support for health care providers involved in organ donation following MAiD; and v) health care providers’ roles and perceptions during organ donation following MAiD.

Conclusions:

Findings from this review can be used to provide support and guidance for improvements in procedures and processes, as well as a rich resource for countries currently planning to establish programs for organ donation after MAiD.
Breaking Mechanism and Performance of Coal Subjected to Water Jets Under High In Situ Stress
Authors: Zhang Di , Cao Shirong , Ge Zhaolong , Zhou Zhe , Liu Xiangjie
Published: July 2023

The effect of in situ stress on the coal-breaking characteristics of water jets remains unclear, prohibiting the deep coalbed methane (CBM) development. Water jet coal-breaking experiments under different mean three-dimensional (3D) stresses and horizontal stress differences were carried out with a self-developed in situ stress simulator. When the mean 3D stress increased, coal changed from shear and tensile failure to shear failure, and the volume of the erosion pit first decreased rapidly and then slowly. Upon increasing the mean 3D stress from 0 to 10 MPa, the volume of the erosion pit decreased by 79.7%, and the specific energy consumption increased nearly five times. With an increase in horizontal stress difference, coal transitioned from shear failure to shear and tensile failure, resulting in a shear crack farther from the erosion pit. At a horizontal stress difference of 15 MPa, the volume of the erosion pit and specific energy consumption had maximum and minimum values, respectively. Consequently, constructing a higher horizontal stress difference helps improve the coal-breaking efficiency of water jets. This study could lay the foundation for applying water jet technology in deep coal seams.
Static Characteristics of High-Speed Water-Lubricated Journal Bearing Considering Turbulence and Cavitation Effects
Authors: Zhang Hao , Lin Xiaohui , Jiang Shuyun
Published: July 2023

The water-lubricated bearings tend to be turbulent and cavitating when running at a high speed. However, the modeling of the water-lubricated bearing considering the turbulence and cavitation effects has not been studied thoroughly. For high-speed water-lubricated journal bearings, a turbulent flow model considering cavitation effect was proposed on the basis of two-phase flow theory. The simulation was conducted to show the influence of turbulence and cavitation effects on the static characteristics of the water-lubricated journal bearing. The proposed model was validated with the test by using a self-developed experimental setup. The result shows that the turbulence effect has a great impact on static characteristics of bearing, and cavitation effect significantly affects the minimum film thickness and leakage flowrate, while the friction torque is hardly affected by the cavitation effect.
Differential benefits of unmasking extended high-frequency content of target or background speech
Authors: Monson Brian B. , Ananthanarayana Rohit M. , Trine Allison , Delaram Vahid , Stecker G. Christopher , Buss Emily
Published: July 2023

Current evidence supports the contribution of extended high frequencies (EHFs; >8 kHz) to speech recognition, especially for speech-in-speech scenarios. However, it is unclear whether the benefit of EHFs is due to phonetic information in the EHF band, EHF cues to access phonetic information at lower frequencies, talker segregation cues, or some other mechanism. This study investigated the mechanisms of benefit derived from a mismatch in EHF content between target and masker talkers for speech-in-speech recognition. EHF mismatches were generated using full band (FB) speech and speech low-pass filtered at 8 kHz. Four filtering combinations with independently filtered target and masker speech were used to create two EHF-matched and two EHF-mismatched conditions for one- and two-talker maskers. Performance was best with the FB target and the low-pass masker in both one- and two-talker masker conditions, but the effect was larger for the two-talker masker. No benefit of an EHF mismatch was observed for the low-pass filtered target. A word-by-word analysis indicated higher recognition odds with increasing EHF energy level in the target word. These findings suggest that the audibility of target EHFs provides target phonetic information or target segregation and selective attention cues, but that the audibility of masker EHFs does not confer any segregation benefit.
A comparative study on detection of polymer-shelled microbubbles by different excitation pulses
Authors: Song Xue , Shen Guofeng , Grishenkov Dmitry
Published: July 2023

Contrast agents are widely used in ultrasound imaging. Many imaging techniques have been developed to improve the contrast between tissue and the agents, based on the nonlinear response of microbubbles. In this study, heterodyne excitation was introduced and was compared with traditional sinusoidal signal and chirp excitation for visualizing polymer-shelled microbubbles and degassed water in a tissue-mimicking phantom. Pulse inversion technique was implemented under plane wave (PW) and focused imaging mode. Image enhancement was evaluated by contrast-to-tissue ratio (CTR) at different transmitting peak negative pressures (PNPs). Experimental results showed that heterodyne excitation had a better suppression effect on tissue signals in PW imaging. The CTR reached an approximation of 17 dB at a low peak negative pressure, which was much higher compared to other excitations. In focused wave imaging, a saturation threshold of CTR was observed for the sinusoidal wave burst and chirp excitation at high PNPs. Heterodyne excitation showed considerable contrast-to-noise ratio under both imaging modes. The response of a polymer-shelled microbubble under heterodyne excitation was simulated. Simulations suggest that in future work, specific filters are required to extract the nonlinear components, such as at the two-peak frequencies around fundamental frequency, to achieve a better image enhancement effect.
Extensional rheometry of mobile fluids. Part I: OUBER, an optimized uniaxial and biaxial extensional rheometer
Authors: Haward Simon J. , Pimenta Francisco , Varchanis Stylianos , Carlson Daniel W. , Toda-Peters Kazumi , Alves Manuel A. , Shen Amy Q.
Published: July 2023

Numerical optimization of a “six-arm cross-slot” device yields several three-dimensional shapes of fluidic channels that impose close approximations to an ideal uniaxial (biaxial) stagnation point extensional flow under the constraints of having four inlets and two outlets (two inlets and four outlets) and for Newtonian creeping flow. One of the numerically designed geometries is considered suitable for fabrication at the microscale, and numerical simulations with the Oldroyd-B and Phan-Thien and Tanner models confirm that the optimal flow fields are observed in the geometry for both constant viscosity and shear thinning viscoelastic fluids. The geometry, named the optimized uniaxial and biaxial extensional rheometer (OUBER), is microfabricated with high precision by selective laser-induced etching of a fused-silica substrate. Employing a refractive index-matched viscous Newtonian fluid, microtomographic-particle image velocimetry enables the measurement of the flow field in a substantial volume around the stagnation point. The flow velocimetry, performed at low Reynolds number (<0.1), confirms the accurate imposition of the desired and predicted flows, with a pure extensional flow at an essentially uniform deformation rate being applied over a wide region around the stagnation point. In Part II of this paper [Haward et al., J. Rheol. 67, 1011–1030 (2023)], pressure drop measurements in the OUBER geometry are used to assess the uniaxial and biaxial extensional rheometry of dilute polymeric solutions, in comparison to measurements made in planar extension using an optimized-shape cross-slot extensional rheometer [OSCER, Haward et al., Phys. Rev. Lett. 109, 128301 (2012)].
Decreased nitrosylation of CaMKII causes aging-associated impairments in memory and synaptic plasticity in mice
Authors: Rumian Nicole L. , Freund Ronald K. , Dell’Acqua Mark L. , Coultrap Steven J. , Bayer K. Ulrich
Published: July 2023

CaMKII has molecular memory functions because transient calcium ion stimuli can induce long-lasting increases in its synaptic localization and calcium ion–independent (autonomous) activity, thereby leaving memory traces of calcium ion stimuli beyond their duration. The synaptic effects of two mechanisms that induce CaMKII autonomy are well studied: autophosphorylation at threonine-286 and binding to GluN2B. Here, we examined the neuronal functions of additional autonomy mechanisms: nitrosylation and oxidation of the CaMKII regulatory domain. We generated a knock-in mouse line with mutations that render the CaMKII regulatory domain nitrosylation/oxidation-incompetent, CaMKII
ΔSNO
, and found that it had deficits in memory and synaptic plasticity that were similar to those in aged wild-type mice. In addition, similar to aged wild-type mice, in which CaMKII was hyponitrosylated, but unlike mice with impairments of other CaMKII autonomy mechanisms, CaMKII
ΔSNO
mice showed reduced long-term potentiation (LTP) when induced by theta-burst stimulation but not high-frequency stimulation (HFS). As in aged wild-type mice, the HFS-LTP in the young adult CaMKII
ΔSNO
mice required L-type voltage-gated calcium ion channels. The effects in aged mice were likely caused by the loss of nitrosylation because no decline in CaMKII oxidation was detected. In hippocampal neurons, nitrosylation of CaMKII induced its accumulation at synapses under basal conditions in a manner mediated by GluN2B binding, like after LTP stimuli. However, LTP-induced synaptic CaMKII accumulation did not require nitrosylation. Thus, an aging-associated decrease in CaMKII nitrosylation may cause impairments by chronic synaptic effects, such as the decrease in basal synaptic CaMKII.
Global analysis of putative phospholipases in
Plasmodium falciparum
reveals an essential role of the phosphoinositide-specific phospholipase C in parasite maturation
Authors: Burda Paul-Christian , Ramaprasad Abhinay , Bielfeld Sabrina , Pietsch Emma , Woitalla Anna , Söhnchen Christoph , Singh Mehar Nihal , Strauss Jan , Sait Aaron , Collinson Lucy M. , Schwudke Dominik , Blackman Michael J. , Gilberger Tim-Wolf
Published: July 2023

For its replication within red blood cells, the malaria parasite depends on a highly active and regulated lipid metabolism. Enzymes involved in lipid metabolic processes such as phospholipases are, therefore, potential drug targets. Here, using reverse genetics approaches, we show that only 1 out of the 19 putative phospholipases expressed in asexual blood stages of
Plasmodium falciparum
is essential for proliferation
in vitro
, pointing toward a high level of redundancy among members of this enzyme family. Using conditional mislocalization and gene disruption techniques, we show that this essential phosphoinositide-specific phospholipase C (PI-PLC, PF3D7_1013500) has a previously unrecognized essential role during intracellular parasite maturation, long before its previously perceived role in parasite egress and invasion. Subsequent lipidomic analysis suggests that PI-PLC mediates cleavage of phosphatidylinositol bisphosphate (PIP
2
) in schizont-stage parasites, underlining its critical role in regulating phosphoinositide levels in the parasite.

IMPORTANCE

The clinical symptoms of malaria arise due to repeated rounds of replication of
Plasmodium
parasites within red blood cells (RBCs). Central to this is an intense period of membrane biogenesis. Generation of membranes not only requires
de novo
synthesis and acquisition but also the degradation of phospholipids, a function that is performed by phospholipases. In this study, we investigate the essentiality of the 19 putative phospholipase enzymes that the human malaria parasite
Plasmodium falciparum
expresses during its replication within RBCs. We not only show that a high level of functional redundancy exists among these enzymes but, at the same time, also identify an essential role for the phosphoinositide-specific phospholipase C in parasite development and cleavage of the phospholipid phosphatidylinositol bisphosphate.
Dual pathology: paraneoplastic sarcoidosis emerging at the time of progression from smouldering to symptomatic myeloma
Authors: Aquil Muzna , Giles Hannah , Buka Richard , Bano Fehmida
Published: July 2023

Sarcoidosis is a systemic disease of unknown aetiology, which is diagnosed based on the presence of non-caseating granulomas on histology. The occurrence of sarcoidosis or a sarcoidosis-like reaction with malignancy has been recognised for several years. Although it has been established that there is an increased risk of lymphoproliferative disorder with sarcoidosis, the association between multiple myeloma and sarcoidosis has rarely been reported. Here, we report the case of woman in her mid-50s with an established diagnosis of smouldering myeloma, who presented with gradually worsening shortness of breath and fatigue after 15 months of active observation. A CT scan of her thorax showed mediastinal lymphadenopathy and the nodes were metabolically active on positron emission tomography CT scan. Endobronchial ultrasound with transbronchial needle aspiration confirmed the diagnosis of sarcoidosis. Further evaluation showed preserved lung function on spirometry. Blood analysis showed a simultaneous rise in the serum lambda-free light chain level from 377 mg/L at initial diagnosis up to 807 mg/L with the kappa/lambda ratio falling to 0.012. Repeat bone marrow aspirate and trephine biopsy showed a 15%–20% infiltrate of lambda light chain-restricted plasma cells with aberrant cyclin D1 expression and abundant sarcoid-like non-necrotising giant cell granulomata. Thus, a diagnosis of paraneoplastic sarcoidosis was established.
Proximal tibia triplane fracture with apophyseal avulsion
Authors: Lin Benjamin , Twaij Haider , Monem Mohammed , Sarraf Khaled M
Published: July 2023

Tibial tuberosity fractures occur in fewer than 1% of all paediatric fractures. We present this unusual case of an early adolescent football player who presented to the emergency department after sustaining an injury during a tackle. CT confirmed a tibial apophyseal fracture concurrent with a proximal tibial triplane fracture. The fracture was subsequently reduced operatively with cancellous cannulated screws. There are only 11 cases published in the literature of triplane fractures of the proximal tibia. Both other cases that involve a concurrent tibial tuberosity fracture with a triplane extension were sustained following a footballing injury. We therefore propose that forced knee flexion alongside a rotational component, common to football, may promote this rare fracture pattern. It is hoped that this case can be used to shed light on a possible mechanism and to guide future management.
Rare vascular complication of ESWL pseudoaneurysm of arc of Buhler
Authors: Ehemann Joanne , Kim Jason Jae Yeun
Published: July 2023

Extracorporeal shock wave lithotripsy (ESWL) is a standard treatment for nephrolithiasis. It is widely employed due to its relative safety profile when compared with other treatment options. Recognised complications include localised pain at site, steinstrasse, perinephric haematoma and ureteric obstruction. This report presents a rare non-documented complication of ESWL, pseudoaneurysm of the arc of Buhler, a branch artery of the superior mesenteric artery.
Safety of BA.4-5 or BA.1 bivalent mRNA booster vaccines: nationwide cohort study
Authors: Andersson Niklas Worm , Thiesson Emilia Myrup , Hansen Jørgen Vinsløv , Hviid Anders
Published: July 2023

Objective

To examine the association between the omicron adapted bivalent mRNA covid-19 booster vaccines received as a fourth dose and risk of adverse events.

Design

Nationwide cohort study.

Setting

Denmark.

Participants

2 225 567 adults aged ≥50 years who received three covid-19 vaccine doses during the study period, 1 January 2021 to 10 December 2022.

Main outcome measures

The main outcome measure was rates of hospital visits for 27 different adverse events in a 28 day main risk period after vaccination with a bivalent omicron adapted mRNA booster vaccine as a fourth dose compared with reference period rates from day 29 after the third or fourth vaccine dose and onward.

Results

1 740 417 adults (mean age 67.8 years, standard deviation 10.7 years) received a bivalent mRNA vaccine as a fourth dose. Fourth dose vaccination with a bivalent mRNA vaccine was not associated with a statistically significant increased rate of any of the 27 adverse outcomes within 28 days (eg, incidence rate ratio of 0.95, 95% confidence interval of 0.87 to 1.04 for ischaemic cardiac events based on 672
v
9992 events during the compared 28 day risk and reference period, respectively), nor when analysed according to age, sex, or vaccine type, or when using alternative analytical approaches. However, post hoc analysis detected signals for myocarditis (statistically significant in female participants), although the outcome was rare and findings were based on few cases. No risk of cerebrovascular infarction was found (incidence rate ratio 0.95, 95% confidence interval 0.87 to 1.05; 644
v
9687 events).

Conclusions

The use of bivalent mRNA vaccines as a fourth vaccine dose against covid-19 was not associated with an increased risk of 27 different adverse events in adults aged ≥50 years.
Refreshing the emergency medicine research priorities
Authors: Cottey Laura , Shanahan Thomas Alexander Gerrard , Gronlund Toto , Whiting Caroline , Sokunbi Moses , Carley Simon David , Smith Jason E
Published: July 2023

Background

The priorities for UK emergency medicine research were defined in 2017 by a priority setting partnership coordinated by the Royal College of Emergency Medicine in collaboration with the James Lind Alliance (JLA). Much has changed in the last 5 years, not least a global infectious disease pandemic and a significant worsening of the crisis in the urgent and emergency care system. Our aim was to review and refresh the emergency medicine research priorities.

Methods

A steering group including patients, carers and healthcare professionals was established to agree to the methodology of the refresh. An independent adviser from the JLA chaired the steering group. The scope was adult patients in the ED. New questions were invited via an open call using multiple communications methods ensuring that patients, carers and healthcare professionals had the opportunity to contribute. Questions underwent minisystematic (BestBETs) review to determine if the question had been answered, and the original 2017 priorities were reviewed. Any questions that remained unanswered were included in an interim prioritisation survey, which was distributed to patients, carers and healthcare professionals. Rankings from this survey were reviewed by the steering group and a shortlist of questions put forward to the final workshop, which was held to discuss and rank the research questions in order of priority.

Results

77 new questions were submitted, of which 58 underwent mini-systematic review. After this process, 49 questions (of which 32 were new, 11 were related to original priorities and 6 unanswered original priorities were carried forward) were reviewed by the steering group and included in an interim prioritisation survey. The interim prioritisation survey attracted 276 individual responses. 26 questions were shortlisted for discussion at the final prioritisation workshop, where the top 10 research priorities were agreed.

Conclusion

We have redefined the priorities for emergency medicine research in the UK using robust and established methodology, which will inform the agenda for the coming years.
Effect of incomplete reperfusion patterns on clinical outcome: insights from the ESCAPE-NA1 trial
Authors: Cimflova Petra , Singh Nishita , Kappelhof Manon , Ospel Johanna M , Sehgal Arshia , Kashani Nima , Almekhlafi Mohammed A , Demchuk Andrew M , Berrouschot Joerg , Dorn Franziska , Kelly Michael E , Buck Brian H , Field Thalia S , Dowlatshahi Dariush , Tymianski Michael , Hill Michael D , Goyal Mayank
Published: July 2023

Background

Incomplete reperfusion (IR) after mechanical thrombectomy (MT) can be a consequence of residual occlusion, no-reflow phenomenon, or collateral counterpressure. Data on the impact of these phenomena on clinical outcome are limited.

Methods

Patients from the ESCAPE-NA1 trial with IR (expanded Thrombolysis In Cerebral Infarction (eTICI) 2b) were compared with those with complete or near-complete reperfusion (eTICI 2c-3) on the final angiography run. Final runs were assessed for (a) an MT-accessible occlusion, or (b) a non-MT-accessible occlusion pattern. The primary clinical outcome was modified Rankin Scale (mRS) 0–2 at 90 days. Our imaging outcome was infarction in IR territory on follow-up imaging. Unadjusted and adjusted incidence rate ratios (aIRR) with 95% confidence intervals (95% CI) were obtained.

Results

Of 1105 patients, 443 (40.1%) with IR and 506 (46.1%) with complete or near-complete reperfusion were included. An MT-accessible occlusion was identified in 147/443 patients (33.2%) and a non-MT-accessible occlusion in 296/443 (66.8%). As compared with patients with near-complete/complete reperfusion, patients with IR had significantly lower chances of achieving mRS 0–2 at 90 days (aIRR 0.82, 95% CI 0.74 to 0.91). Rates of mRS 0–2 were lower in the MT-accessible occlusion group as compared with the non-MT-accessible occlusion pattern group (aIRR 0.71, 95% CI 0.60 to 0.83, and aIRR 0.89, 95% CI 0.81 to 0.98, respectively). More patients with MT-accessible occlusion patterns developed infarcts in the non-reperfused territory as compared with patients with non-MT occlusion patterns (68.7% vs 46.3%).

Conclusion

IR was associated with worse clinical outcomes than near-complete/complete reperfusion. Two-thirds of our patients with IR had non-MT-accessible occlusion patterns which were associated with better clinical and imaging outcomes compared with those with MT-accessible occlusion patterns.
Endovascular therapy in patients with internal carotid artery occlusion and patent circle of Willis
Authors: Riegler Christoph , von Rennenberg Regina , Bollweg Kerstin , Nguyen Thanh N , Kleine Justus F , Tiedt Steffen , Audebert Heinrich J , Siebert Eberhard , Nolte Christian H
Published: July 2023

Background

Occlusion of the internal carotid artery (ICA) may extend into the middle or anterior cerebral artery (ICA-T) or be confined to the intracranial (ICA-I) or extracranial segment (ICA-E). While there is excellent evidence for endovascular therapy (EVT) in ICA-T occlusions, studies on EVT in non-tandem ICA-I or ICA-E occlusions are scarce.

Objective

To characterize EVT-treated patients with ICA-I- and ICA-E occlusion by comparing them with ICA-T occlusions.

Methods

The German Stroke Registry (GSR), a national, multicenter, prospective registry was searched for EVT-treated patients with isolated ICA occlusion between June 2015 and December 2021. We stratified patients by ICA occlusion site: (a) ICA-T, (b) ICA-I, (c) ICA-E. Baseline factors, procedural variables, technical (modified Thrombolysis in Cerebral Infarction (mTICI)), and functional outcomes (modified Rankin scale score at 3 months) were analyzed.

Results

Of 13 082 GSR patients, 2588 (19.8%) presented with an isolated ICA occlusion, thereof 1946 (75.2%) ICA-T, 366 (14.1%) ICA-I, and 276 (10.7%) ICA-E patients. The groups differed in age (77 vs 76 vs 74 years, Ptrend=0.02), sex (53.4 vs 48.9 vs 43.1% female, Ptrend<0.01), and stroke severity (median National Institutes of Health Stroke Scale score at admission 17 vs 14 vs 13 points, Ptrend<0.001). In comparison with ICA-T occlusions, both ICA-I and ICA-E occlusions had lower rates of successful recanalization (mTICI 2b/3: 85.4% vs 80.4% vs 76.3%; aOR (95% CI for ICA-I vs ICA-T 0.71 (0.53 to 0.95); aOR (95% CI) for ICA-E vs ICA-T 0.57 (0.42 to 0.78)). In adjusted analyses, ICA-E occlusion was associated with worse outcome when compared with ICA-T occlusion (mRS ordinal shift, cOR (95% CI) 0.70 (0.52 to 0.93)).

Conclusion

Patient characteristics and outcomes differ substantially between ICA-T, ICA-I, and ICA-E occlusions. These results warrant further studies on EVT in ICA-I and ICA-E patients.
Evidence behind the exhortation? A rapid review of servant leadership’s influence and claims in healthcare over the last decade
Authors: Wong Lee Yung , Sendjaya Sen , Wilson Samuel , Rixon Andrew
Published: July 2023

Servant leadership is an other-oriented approach to leadership with multiple positive outcomes. However, its influence in the context of medicine, particularly on healthcare leaders, is less clear. We conducted a rapid review to examine the impact of servant leadership in healthcare over the last decade. We included a total of 28 articles, 26 of which described beneficial organisational, relational and personal outcomes of servant leadership. However, most of these were either conceptual or opinion-based articles. Moreover, most quantitative studies were cross-sectional, precluding causal inferences. Our review demonstrates that the purported positive association between servant leadership and healthcare outcomes lacks a strong evidence base. We conclude by calling for more rigorous empirical research to examine the effects and potential challenges of implementing servant leadership in healthcare contexts.