bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of immunoglobulin G on cytokine response in necrotising soft‐tissue infection: A post hoc analysis
Authors: Hedetoft Morten , Madsen Martin B. , Perner Anders , Garred Peter , Hyldegaard Ole
Published: June 2021

Background

A marked inflammatory response in necrotising soft‐tissue infection (NSTI) may contribute to the severe clinical course. Intravenous polyspecific immunoglobulin G (IVIG) is used by some as adjuvant treatment for NSTI, but in the randomised INSTINCT trial, no effect of IVIG in NSTI patients was seen on physical quality of life. In experimental studies, IVIG may induce immunosuppressive effects by reducing the pro‐inflammatory response and neutralising circulating superantigens. However, data on the potential immunomodulatory effects are sparse and remain to be investigated in a clinical setting. In this post hoc analysis of the INSTINCT trial, we aimed to assess the effect of IVIG on various inflammatory cytokines up to day 3 after randomisation.

Methods

Tumour necrosis factor (TNF), interleukin‐1β, interleukin‐6, interleukin‐10 and granulocyte colony‐stimulating factor were measured at admission, days 1, 2 and 3.

Results

A total of 100 ICU patients with NSTI were included; 50 were allocated to IVIG (25 g/d for 3 days) and 50 to placebo. No difference in the overall inflammatory response was observed between groups except from TNF, which was higher in the IVIG group as compared to the placebo group (area under curve‐admission to day 3, 93.6 vs 60.2, P = .02). Similarly, no differences were observed in percentage change from baseline to day 3 in any of the studied cytokines between patients allocated to IVIG group and those allocated to placebo group.

Conclusion

In ICU patients with NSTI, IVIG did not reduce the plasma concentration of cytokines in the first 3 days.
Paracetamol, non‐steroidal anti‐inflammatory drugs and glucocorticoids for postoperative pain: A protocol for a systematic review with meta‐analysis and trial sequential analysis
Authors: Ritsmer Stormholt Emma , Steiness Joakim , Bauer Derby Cecilie , Esta Larsen Mia , Maagaard Mathias , Mathiesen Ole
Published: June 2021

Background

Multimodal analgesia is the leading principle for managing postoperative pain. Recent guidelines recommend combinations of paracetamol and a non‐steroidal anti‐inflammatory drug (NSAID) for most surgeries. Glucocorticoids have been used for decades due to their potent anti‐inflammatory and antipyretic properties. Subsequently, glucocorticoids may improve postoperative analgesia. We will perform a systematic review to assess benefits and harms of adding glucocorticoids to paracetamol and NSAIDs. We expect to uncover pros and cons of the addition of glucocorticoid to the basic standard regimen of paracetamol and NSAIDs for postoperative analgesia.

Method

This protocol for a systematic review was written according to the The Preferred Reporting Items for Systematic Review and Meta‐Analysis Protocols guidelines. We will search for trials in the following electronic databases: Medline, CENTRAL, CDSR and Embase. Two authors will independently screen trials for inclusion using Covidence, extract data and assess risk of bias using Cochrane's ROB 2 tool. We will analyse data using Review Manager and Trial Sequential Analysis.

Meta‐analysis will be performed according to the Cochrane guidelines and results will be validated according to the eight‐step procedure suggested by Jakobsen et al We will present our primary findings in a ‘summary of findings’ table. We will evaluate the overall certainty of evidence using the GRADE approach.

Discussion

This review will aim to explore the combination of glucocorticoids together with paracetamol and NSAIDs for postoperative pain. We will attempt to provide reliable evidence regarding the role of glucocorticoids as part of a multimodal analgesic regimen in combination with paracetamol and NSAID.
Antidepressant treatment effects and country income: meta‐regression analysis of individual participant data from duloxetine trials
Authors: Klein Thomas , Weinmann Stefan , Becker Thomas , Koesters Markus
Published: June 2021

Objective

In recent decades, significant numbers of pharmaceutical trials have gradually been relocated to low‐ and middle‐income countries. However, there is little evidence regarding the transferability of trial outcomes across countries. Analysing duloxetine randomised controlled trials (RCTs) conducted in different countries, we investigated whether per capita gross national income (GNI) and healthcare expenditure (HE) are associated with pre‐post mean changes of depression severity and differences in duloxetine‐placebo effect sizes.

Method

Meta‐analyses included RCTs investigating duloxetine efficacy in patients with depression. Individual participant data (IPD) from multi‐centre duloxetine trials were provided by the manufacturer. Data extracted from published reports also entered analyses in case of trials conducted in only one country. A meta‐regression approach was applied to analyse associations of GNI and HE with standardised pre‐post mean change using raw score standardisation (SMCR) and comparative effect size, that is, the mean differences (MD) in pre‐post effect size between duloxetine and placebo treatment.

Results

23 trials with 8417 randomised participants entered analyses. Regression coefficients indicated a negative linear relationship of SMCR with GNI (z‐standardisedβ = −3.61,R2 = 14.8%,p< 0.001) and HE (β = −4.72,R2 = 24.8%,p< 0.001) for participants treated with duloxetine. Similar associations were found for placebo treatment (GNI:β = −3.52,R2 = 23.8%,p< 0.001;β = −3.34,R2 = 21.0%p< 0.001). Neither GNI nor HE was associated with the MD between duloxetine and placebo pre‐post differences.

Conclusions

Findings challenge the idea of the universal transferability of antidepressant trial outcomes across countries. Understanding the results of antidepressant RCTs demands more sophisticated clarification of context factors involved in determining effectiveness of antidepressant medication and should be discussed with a view to socio‐economic context in their countries of origin.
Use of register‐ and survey‐based measures of anxiety in a population‐based Danish cohort
Authors: Osler Merete , Rozing Maarten Pieter , Wium‐Andersen Ida Kim , Wium‐Andersen Marie Kim , Dantoft Thomas Meinertz , Fink Per , Jørgensen Martin Balslev , Jørgensen Terese Sara Høj
Published: June 2021

Objective

We explored the comparability of anxiety measures from register‐ and survey‐based data including analyses of prevalence and associations with selected psychiatric and somatic diseases.

Methods

We measured anxiety using Danish registers (hospital diagnosis and anxiolytic drug prescriptions), self‐reports, symptom checklist (SCL) scores, and a clinical interview in 7493 adults with mean age 52 (SD 13.3) years who participated in a health survey between 2012 and 2015. We estimated the prevalence of anxiety, agreement between different measures and performed quantitative bias analysis.

Results

The lifetime prevalence of hospital diagnosed anxiety, anxiolytic drug prescriptions, and self‐reported anxiety were 4.4%, 6.2%, and 5.1%, respectively, after adjusting for selective participation. The agreement between the different anxiety measures was low. Thus, 25% with an anxiety diagnosis and 20% with anxiolytic drug prescriptions also had a high SCL score. Anxiolytic drugs were the only measure significantly associated with higher odds of heart disease. Hospital diagnosis and self‐reported anxiety were associated with depression with odds ratio (OR) above 15, whereas anxiolytic drug prescriptions were less strongly associated (OR = 2.2(95% confidence interval: 1.26–3.91)). The risk estimates attenuated considerably when correcting for measurement error, whereas the ORs became slightly higher when the selective participation in the survey was accounted for.

Conclusion

Anxiety diagnosed in hospitals and self‐reported anxiety showed low level of agreement but provide comparable results regarding frequency measures and associations with disease outcomes.
Distance disintegration characterizes node‐level topological dysfunctions in cocaine addiction
Authors: Costumero Víctor , Rosell Negre Patricia , Bustamante Juan Carlos , Fuentes‐Claramonte Paola , Adrián‐Ventura Jesús , Palomar‐García María‐Ángeles , Miró‐Padilla Anna , Llopis Juan José , Sepulcre Jorge , Barrós‐Loscertales Alfonso
Published: June 2021

Previous investigations have used global graph theory measures in order to disentangle the complexity of the neural reorganizations occurring in cocaine use disorder (CUD). However, how these global topological alterations map into individual brain network areas remains unknown. In this study, we used resting state functional magnetic resonance imaging (fMRI) data to investigate node‐level topological dysfunctions in CUD. The sample was composed of 32 individuals with CUD and 32 healthy controls, matched in age, years of education and intellectual functioning. Graph theory measures of optimal connectivity distance, node strength, nodal efficiency and clustering coefficient were estimated in each participant using voxel‐wise functional connectivity connectomes. CUD individuals as compared with healthy controls showed higher optimal connectivity distances in ventral striatum, insula, cerebellum, temporal cortex, lateral orbitofrontal cortex, middle frontal cortex and left hippocampus. Furthermore, clinical measures quantifying severity of dependence were positively related with optimal connectivity distances in the right rolandic operculum and the right lateral orbitofrontal cortex, whereas length of abstinence was negatively associated with optimal connectivity distances in the right temporal pole and the left insula. Our results reveal a topological distancing of cognitive and affective related areas in addiction, suggesting an overall reduction in the communication capacity of these regions.
Delayed release improves site fidelity but has little effect on survival or breeding success of reintroduced western quolls (Dasyurus geoffroii)
Authors: Jensen Melissa A. , Paton David C. , Moseby Katherine E.
Published: June 2021

Reintroductions of threatened species can fail due to a lack of site fidelity and dispersal of individuals away from the release site. Delayed‐release techniques are commonly used in reintroduction programmes to acclimatise animals to novel sites to improve site fidelity and survival following release. However, some studies have found negative or little effect of initial containment on post‐release outcomes, suggesting that the benefits of a delayed release may be species‐specific or dependent on the methods used. The western quoll (Dasyurus geoffroii) is a 900–1300 g carnivorous marsupial that has previously been found to travel long distances after release, potentially contributing to reintroduction failure. We investigated the effect of immediate versus delayed release on the survival, site fidelity and breeding success of western quolls reintroduced to the Ikara‐Flinders Ranges National Park in South Australia. Delayed‐release animals were confined to individual 10 × 10 m outdoor release pens and provided with supplementary food and water for ten days prior to release. Immediate‐release animals were released without any additional assistance provided. Monitoring of 39 radio‐collared quolls for three months after release failed to detect a difference in survival probability between release treatments. There was also no evidence to suggest that the success or timing of breeding differed between immediate‐ and delayed‐released quolls. However, a delayed release did significantly improve site fidelity. On average, delayed‐release quolls remained within a linear distance of 1.6 km (SE = 0.348, 95% CI = 0.98–2.39) of their release site over three months, compared to 3.26 km (SE = 0.36, 95% CI = 2.57–4.03) for immediate‐released animals. In unbounded release sites, delayed releases may assist with keeping western quolls within predator‐controlled release areas. Results from this study may be used to guide future reintroductions of this threatened species.
Morphometry of cervical spinal cord in cat using design‐based stereology
Authors: Sadeghinezhad Javad , Nyengaard Jens Randel
Published: June 2021

The spinal cord harbours nerve fibres that facilitate reflex actions and that transmit impulses to and from the brain. The cervical spinal cord is an area of particular interest in medicine and veterinary due to frequent pathologic alterations in this region. This study describes the morphometric features of the cervical spinal cord in cat using design‐unbiased stereological methods. The cervical spinal cords of four male cats were dissected and samples were taken according to systematic uniform random sampling. Each sample was embedded in agar and cut into 60‐µm thick sections and stained with cresyl violet 0.1% for stereological estimations. The total cervical spinal cord volume obtained by the Cavalieri estimator was 2,321.21 ± 285.5 mm3. The relative volume of grey matter and white matter was 23.8 ± 1.3% and 76.1 ± 1.3%. The dorsal horn and ventral horn volume were 12.3 ± 1.2% and 11.4 ± 0.7% of the whole cervical spinal cord. The volume of central canal was estimated to 3.8 ± 1 mm3. The total number of neurons was accounted 3,405,366.2 ± 267,469.4 using the optical disector/fractionator method. The number of motoneurons and interneurons was estimated to be 1,120,433.2 ± 174,796.7 and 2,284,932.9 ± 127,261.5, respectively. The average volume of the motoneurons and interneurons was estimated to 1980 µm3 and 680 µm3, respectively, using the spatial rotator method. This knowledge of cat spinal cord findings may serve as a foundation as a translational model in spinal cord experimental research and provide basic findings for diagnosis and treatment of spinal cord disorders.
Surgical technique for removing vitreous cortex remnants using a diamond‐dusted membrane scraper
Authors: Sartini Francesco , Menchini Martina , Loiudice Pasquale , Nardi Marco , Figus Michele , Casini Giamberto
Published: June 2021

Purpose

The purpose of this paper is to present a new surgical technique to remove vitreous cortex remnants.

Methods

Non‐consecutive retrospective interventional case series.

Results

When the posterior vitreous is split, its outermost layer may remain attached to the retina, developing vitreoschisis‐induced vitreous cortex remnants (VCR). Their role in macular pathology etiopathogenesis has been well documented; however, recently, it has been proposed that VCR also play a crucial role in proliferative vitreoretinopathy and consequent retinal redetachment. The prevalence of VCR is underestimated because triamcinolone acetonide is not routinely used for vitreous staining. Vitreous cortex remnants (VCR) removal is challenging, and several surgical techniques have been proposed. However, they require sclerotomy enlargement, material that may not be readily available, and manual fashioning. Alternatively, a diamond‐dusted membrane scraper (DDMS), already widely used in macular pathology treatment, can follow the contour of the retina, as it is a silicone tube, and remove VCR with its abrasive tip. A DDMS may also be introduced in the vitreous cavity through a standard trocar. Finally, the use of a DDMS provides predictable feedback, making the learning curve short. In this case series, 34 eyes affected by primary rhegmatogenous retinal detachment were enrolled. The retinal redetachment rate was 2.9% at six months of follow‐up, below the average literature value of 21%. No adverse events were reported.

Conclusion

A DDMS can be suitable for use in VCR removal, although further studies are warranted to understand the indications and extent of this surgical technique for improving the management of rhegmatogenous retinal detachment.
Predictive value of non‐ocular findings for retinal haemorrhage in children evaluated for non‐accidental trauma
Authors: Giannakakos Vasiliki P , Dosakayala Neelima , Huang Danning , Yazdanyar Amirfarbod
Published: June 2021

Purpose

To determine non‐ocular examination findings in non‐accidental trauma (NAT) patients that are associated with retinal haemorrhage and warrant urgent examination by an ophthalmologist.

Methods

A hospital‐ and clinic‐based retrospective cross‐sectional and cohort study of children age 0–12 years who underwent workup for NAT over a span of nine years in a level I trauma and tertiary referral centre. Details of ocular and non‐ocular examination and imaging findings at the time of NAT evaluation were collected by chart review. Univariate and logistic regression analysis for association between retinal haemorrhage and non‐ocular examination findings was performed.

Results

A total of 557 patients with ophthalmology evaluation and 425 without were included in this study. All ages combined, none of the cutaneous signs of trauma or non‐skull fractures were associated with retinal haemorrhage on univariate analysis (p > 0.05). By logistic regression, subdural or extra‐axial haemorrhage (OR = 16.2; 95% CI [5.11–51.3]), occipital lobe insult (OR = 6.2; 95% CI [1.77–21.6]) and Glasgow coma score (GCS) <15 (OR = 5.8; 95% CI [1.96–17.4]) were significant predictors of retinal haemorrhage.

Conclusion

Subdural or undistinguished extra‐axial haemorrhage, GCS <15, and occipital lobe insult are risk factors for the presence of retinal haemorrhage in patients with suspected NAT and their presence warrant urgent dilated fundus examination by an ophthalmologist. The presence of cutaneous trauma or non‐skull bone fractures without the aforementioned risk factors does not warrant ophthalmology evaluation.
Incidence and risk factors for macular oedema after primary rhegmatogenous retinal detachment surgery: a prospective single‐centre study
Authors: Gebler Marie , Pfeiffer Sebastian , Callizo Josep , Hoerauf Hans , Feltgen Nicolas , Bemme Sebastian
Published: June 2021

Purpose

To assess the incidence of cystoid macular oedema (CME) diagnosed by spectral domain optical coherence tomography (SD‐OCT) after primary rhegmatogenous retinal detachment (RRD) surgery.

Methods

From April 2016 to October 2017, 150 eyes of 150 patients presenting with primary RRD were included consecutively in this prospective single‐centre study. Patients with the following characteristics were excluded: previous vitreoretinal surgery, combined cataract surgery, preoperatively presentation with any intraocular or systemic inflammatory condition, visible macular oedema or epiretinal membrane (ERM) on funduscopy. SD‐OCT (Spectralis, Heidelberg Engineering) was conducted 3 and 6 weeks after surgery.

Results

One hundred and twenty‐eight of the 150 patients completed the study, of whom 107 (age: 61.7 ± 11.5 years, mean ± SD) showed successful retinal attachment during follow‐up visits. The most frequent operation method was scleral buckling (54.2%), followed by vitrectomy (25.2%) and the combination of both techniques (20.6%). Postoperative SD‐OCT revealed CME, neurosensory detachment and ERM in 18.7, 31.8 and 32.7% of all cases, respectively. The risk of postoperative CME was significantly elevated in patients with ERM (42.9 versus 6.9%, p < 0.001). In addition, patients with initial detachment of the macula had more postoperative CME (26.5 versus 11.1%, p = 0.044). BCVA improvement was significantly lower in patients with CME compared to patients without 6 weeks after surgery for macula‐on RRD.

Conclusions

This prospective study confirmed that postoperative CME is a frequent complication after RRD surgery; we identified ERM and macula‐off RRD as potential risk factors. As CME potentially delays visual recovery, postoperative follow‐ups should include SD‐OCT.
Accuracy of post‐publication Financial Conflict of Interest corrections in medical research: A secondary analysis of pharmaceutical company payments to the authors of the CREATE‐X trial report in the New England Journal of Medicine
Authors: Ozaki Akihiko , Saito Hiroaki , Sawano Toyoaki , Shimada Yuki , Tanimoto Tetsuya
Published: June 2021

In June 2017, Japanese and Korean authors published the results of the CREATE‐X trial in the New England Journal of Medicine (NEJM). After we identified their inadequate disclosures of Financial Conflict of Interests (FCOIs), the authors made a post‐publication correction of their FCOIs. The purpose of this study is to evaluate the accuracy of the post‐publication corrections by the Japanese authors of the CREATE‐X trial. All the Japanese authors of the CREATE‐X trial were included in the study. We determined the payments received by these authors in 2016 using publicly available data published by 78 pharmaceutical companies based on the stipulated Japanese transparency guidelines. We retrieved the original and revised versions of the FCOI disclosures as published on the NEJM website, and compared the payments reported by the pharmaceutical companies and the original and revised FCOI disclosures of the authors. Of the 12 authors, nine received payments made by the drug manufacturer involved in the CREATE‐X trial. Of these nine, only three (33.3%) originally disclosed their relationships, and another three (33.3%) later disclosed such relationships in the post‐publication corrections. Similarly, of the 11 receiving at least one payment from other manufacturers of breast cancer products, none correctly disclosed the payments in the original or the revised disclosure. In the CREATE‐X trial, FCOIs with pharmaceutical companies were not properly disclosed by 11 of the 12 Japanese authors, even after the post‐publication corrections, which highlights the need to pay more attention to the accuracy of FCOI disclosures in academic publications.
Diverse roles of microbial indole compounds in eukaryotic systems
Authors: Kumar Prasun , Lee Jin‐Hyung , Lee Jintae
Published: June 2021

Indole and its derivatives are widespread across different life forms, functioning as signalling molecules in prokaryotes and with more diverse roles in eukaryotes. A majority of indoles found in the environment are attributed to bacterial enzymes converting tryptophan into indole and its derivatives. The involvement of indoles among lower organisms as an interspecies and intraspecies signal is well known, with many reports showing that inter‐kingdom interactions involving microbial indole compounds are equally important as they influence defence systems and even the behaviour of higher organisms. This review summarizes recent advances in our understanding of the functional properties of indole and indole derivatives in diverse eukaryotes. Furthermore, we discuss current perspectives on the role of microbial indoles in human diseases such as diabetes, obesity, atherosclerosis, and cancers. Deciphering the function of indoles as biomarkers of metabolic state will facilitate the formulation of diet‐based treatments and open unique therapeutic opportunities.
Rapid assessment to facilitate climate‐informed conservation and nature‐based solutions
Authors: Oakes Lauren E. , Cross Molly S. , Zavaleta Erika S.
Published: June 2021

The need to ensure that rising investment in nature‐based climate solutions delivers expected outcomes hinges on incorporating current and future climate into design and implementation. Technical guidelines and formal planning processes serve a purpose in ensuring the quality of climate‐informed strategies for local projects. The inherent complexity, cost, and time required to use these tools, however, can make them inaccessible or daunting. Taking lessons learned from a decade of funding over 100 adaptation initiatives in conservation—some of which also provide mitigation benefits—we describe a simple rapid assessment framework for use by practitioners and funders. This framework, which we refer to as the 5Ws (what, when, where, why, and who) of climate‐informed action, serves as a guide to make projects more robust to future climate.
Diagnostic delay and characterization of the clinical prodrome in AL amyloidosis among 1523 US adults diagnosed between 2001 and 2019
Authors: Hester Laura L. , Gifkins Dina M. , M. Bellew Kevin , Vermeulen Jessica , Schecter Jordan M. , Strony John , Dishy Victor , Weiss Brendan M.
Published: June 2021

Light‐chain (AL) amyloidosis is a multisystem disorder with a high early mortality and diagnostic delays of >1 year from symptom onset. This retrospective observational study sought to characterize the clinical prodrome and diagnostic delay to inform early detection. We identified 1523 adults with newly diagnosed AL amyloidosis in the Optum de‐identified Clinformatics® Datamart US healthcare claims database as those with ≥2 new diagnosis codes for AL or other amyloidosis in 90 days with ≥1 multiple myeloma treatment within 730 days, excluding patients with prior hereditary or secondary amyloidosis and Familial Mediterranean Fever. We considered 34 signs/symptoms using diagnosis codes in all observable time on or before AL amyloidosis diagnosis. Sign/symptom prevalence was compared to that of 1:4 matched population controls. The overlap and sequence of signs/symptoms and the median time from first sign/symptom to AL amyloidosis diagnosis were explored. Healthcare utilization was summarized. The most common individual AL amyloidosis signs/symptoms were malaise/fatigue (61%) and dyspnea (59%). Cardiac signs/symptoms were observed in 77% of patients, followed by renal (62%) and neurologic (59%) signs/symptoms. Multisystem involvement (≥3 systems) was present in 54%. Monoclonal gammopathy was detected in 29% before diagnosis. Median time from symptom onset to AL amyloidosis diagnosis was 2.7 years. Healthcare utilization was high between first AL amyloidosis signs/symptoms and diagnosis, with 50% visiting ≥5 physician types. AL amyloidosis patients have a lengthy and complex clinical prodrome. Novel approaches to early diagnosis are needed to improve outcomes.
Neonatal maternal separation affects metabotropic glutamate receptor 5 expression and anxiety‐related behavior of adult rats
Authors: Tsotsokou Giota , Nikolakopoulou Maria , Kouvelas Elias D. , Mitsacos Ada
Published: June 2021

Exposure to early life stress leads to long‐term neurochemical and behavioral alterations. Stress‐induced psychiatric disorders, such as depression, have recently been linked to dysregulation of glutamate signaling, mainly via its postsynaptic receptors. The role of metabotropic glutamate receptor 5 (mGluR5) in stress‐induced psychopathology has been the target of several studies in humans. In rodents, blockade of mGluR5 produces antidepressant‐like actions, whereas mice lacking mGluR5 exhibit altered anxiety‐like behaviors and learning. In this study, we used well‐known rodent models of early life stress based on mother–infant separation during the first 3 weeks of life in order to examine the effects of neonatal maternal separation on mGluR5 expression and on anxiety‐related behavior in adulthood. We observed that brief (15 min) neonatal maternal separation, but not prolonged (3 h), induced increases in mGluR5 mRNA and protein expression levels in medial prefrontal cortex and mGluR5 protein levels in dorsal, but not ventral, hippocampus of adult rat brain. Behavioral testing using the open‐field and the elevated‐plus maze tasks showed that brief maternal separations resulted in increased exploratory and decreased anxiety‐related behavior, whereas prolonged maternal separations resulted in increased anxiety‐related behavior in adulthood. The data indicate that the long‐lasting effects of neonatal mother–offspring separation on anxiety‐like behavior and mGluR5 expression depend on the duration of maternal separation and suggest that the increased mGluR5 receptors in medial prefrontal cortex and hippocampus of adult rats exposed to brief neonatal maternal separations may underlie their heightened ability to cope with stress.
Human myelin protein P2: from crystallography to time‐lapse membrane imaging and neuropathy‐associated variants
Authors: Uusitalo Maiju , Klenow Martin Berg , Laulumaa Saara , Blakeley Matthew P. , Simonsen Adam Cohen , Ruskamo Salla , Kursula Petri
Published: June 2021

Peripheral myelin protein 2 (P2) is a fatty acid‐binding protein expressed in vertebrate peripheral nervous system myelin, as well as in human astrocytes. Suggested functions of P2 include membrane stacking and lipid transport. Mutations in the PMP2 gene, encoding P2, are associated with Charcot–Marie–Tooth disease (CMT). Recent studies have revealed three novel PMP2 mutations in CMT patients. To shed light on the structure and function of these P2 variants, we used X‐ray and neutron crystallography, small‐angle X‐ray scattering, circular dichroism spectroscopy, computer simulations and lipid binding assays. The crystal and solution structures of the I50del, M114T and V115A variants of P2 showed minor differences to the wild‐type protein, whereas their thermal stability was reduced. Vesicle aggregation assays revealed no change in membrane stacking characteristics, while the variants showed altered fatty acid binding. Time‐lapse imaging of lipid bilayers indicated formation of double‐membrane structures induced by P2, which could be related to its function in stacking of two myelin membrane surfaces in vivo. In order to better understand the links between structure, dynamics and function, the crystal structure of perdeuterated P2 was refined from room temperature data using neutrons and X‐rays, and the results were compared to simulations and cryocooled crystal structures. Our data indicate similar properties for all known human P2 CMT variants; while crystal structures are nearly identical, thermal stability and function of CMT variants are impaired. Our data provide new insights into the structure–function relationships and dynamics of P2 in health and disease.
Diverticulum in buccal mucosa: A rare sac‐like oral pouch
Authors: Kaneko Takahiro , Hino Shunsuke , Yamada Miki , Suzuki Kyoko , Iijima Yosuke , Horie Norio
Published: June 2021

Objective

This article describes a rare case of oral diverticulum.

Background

Diverticulum represents a sac‐like protrusion of the gastrointestinal tract, commonly arising in the colon wall of elder individuals. Zenker's diverticulum can also occur in the pharyngeal mucosa. However, oral diverticulum appears rare.

Material and Method

The patient was an 88‐year‐old man with dementia living in a geriatric facility. A dental hygienist incidentally identified a small pouch containing stagnant food residue in the left buccal mucosa during oral hygiene procedures.

Results

The small pouch with stagnant food residue was identified as a diverticulum.

Conclusion

Diverticula may be identified from the stagnation of food residue. Dental specialists who practice oral hygiene should be aware of diverticula as a differential diagnosis.
Experiences of cervical screening participation and non‐participation in women from minority ethnic populations in Scotland
Authors: Nelson Mia , Patton Andrea , Robb Katie , Weller David , Sheikh Aziz , Ragupathy Kalpana , Morrison David , Campbell Christine
Published: June 2021

Background

The introduction of screening in the UK and other high‐income countries led to a significant decrease in the incidence of cervical cancer and increase in survival rates. Minority ethnic groups are often underrepresented in screening participation for reasons that are poorly understood.

Objective

To explore experiences of cervical screening participation and non‐participation of women from minority ethnic populations in Scotland and gain insights to support the development of interventions that could potentially support screening participation and thereby reduce inequalities.

Design

Qualitative comparison group study using in‐depth, semi‐structured individual interviews that were thematically analysed.

Setting and participants

This study took place in Scotland. Fifty women were purposively sampled from four ethnic minority groups: South Asian; East European; Chinese; and Black African or Caribbean. White Scottish women were also interviewed.

Results

Many experiences described were common regardless of ethnicity, such as difficulties managing competing priorities, including work and care responsibilities. However, important differences existed across the groups. These included going abroad for more frequent screening, delayed introduction to screening and not accessing primary care services, language difficulties in health‐care settings despite proficiency in English and not being sexually active at screening commencement. Experiences of racism, ignorance and feeling shamed were also reported.

Conclusions

Key differences exist in the experience of minority ethnic groups in Scotland. These offer potential opportunities to reduce disparity and support screening participation including maximizing co‐incidental interactions and developing outreach work.
Role of pH in skin cleansing
Authors: Hawkins Stacy , Dasgupta Bivash R. , Ananthapadmanabhan Kavssery P.
Published: June 2021

Background

The importance of maintaining the acid‐mantle of human stratum corneum to maintain its healthy barrier and skin’s biological functions such as desquamation and lipid biosynthesis is well recognized in the literature. An outcome of this has been an increase in the number of skincare products formulated at or near the skin pH with an implication that a product formulated at skin pH will be good for skin. Such an assumption often does not take into account the specific interactions of ingredients in the product with the stratum corneum under skin pH conditions.

Objective

The objective of this research was to determine whether a skin cleansing product by virtue of its pH being same as “skin pH” is milder to skin.

Methods

A well established Forearm Controlled Application Test (FCAT) protocol was used in clinical studies to compare “skin pH” cleansing systems with neutral pH cleansing systems. Specifically, certain commercially available “skin pH” cleansing bars were compared with a neutral pH syndet bar in two separate FCAT studies. Since these bars differed in their surfactant composition, in a separate FCAT study, two identical prototype bar formulations differed only in their pH were compared. Additionally, two body wash liquid prototypes, identical in composition but differing only in their pH were also compared in another FCAT study.

Results

The results obtained showed that skin‐cleansing systems formulated solely or predominantly with anionic surfactants under skin pH conditions can result in increased skin dryness and irritation compared to those under neutral pH conditions. The results are explained in terms of the increased electrostatic interaction of anionic surfactants with stratum corneum under low pH conditions compared to neutral pH conditions.

Conclusion

Skin‐cleansing systems formulated solely or predominantly with anionic surfactants under skin pH conditions can result in increased skin dryness and irritation compared to those under neutral pH conditions. Any skin cleansing product by virtue of its pH being same as that of “skin pH” does not guarantee that it will be good for skin. The mildness of a cleanser will be determined by the interactions of its surfactants and other ingredients with stratum corneum under its formulated pH conditions.
Development and tribological studies of a novel metal‐ceramic hybrid brake disc
Authors: Opel Thorsten , Langhof Nico , Krenkel Walter
Published: June 2021

Ceramic matrix composite (CMC) friction materials show promising tribological properties. Typically, carbon ceramic brake discs consist of a C/SiC rotor which is joined to a brake disc bell. Within this work, a novel metal‐ceramic hybrid brake disc, consisting of C/SiC friction segments which are mounted by screws onto an aluminum carrier body, was designed and investigated. A prototype was built which was tribologically tested with three different brake pad materials, LowMet reference, modified SF C/SiC as well as C/C. A constant starting sliding velocity of 20 m/s and braking pressures of 1, 2, and 3 MPa were investigated. To simulate emergency braking conditions 10 consecutive brake applications were carried out in close succession for each brake pad material and braking pressure. The C/C brake pad material showed the highest average coefficient of friction followed by the LowMet and C/SiC material. However, the wear rates of the C/C and LowMet material were orders of magnitude higher compared to the C/SiC material.
Thermal evaluation of the use of porous ceramic plates on ventilated façades – Part I: Effect of composition and firing temperature on porosity and bending strength
Authors: Pizzatto Sara M. S. , Pizzatto Fernando O. , Angioletto Elidio , Arcaro Sabrina , Junca Eduardo , Montedo Oscar R. K.
Published: June 2021

The effect of composition and firing temperature on porosity and bending strength of porous ceramic plates for using in ventilated façades were investigated. Two byproducts, basalt and lime mud, were used to obtain porous ceramic plates in accordance with the circular economy concept. Basalt, which is a fine powder‐based byproduct generated from the processing of basaltic rock, was used to replace feldspar as the flux mineral in a ceramic composition. Lime mud, a byproduct of the pulp and paper mill process and containing a high content of calcium carbonate (CaCO3), was incorporated in the ceramic composition to generate pores. The specimens were prepared using three different amounts of lime mud (20, 30, and 40 wt%) and three firing temperatures (900°C, 1000°C, and 1100°C), and their porosity and bending strength were determined. The highest performing specimen (5.1 ± 1.3 MPa bending strength and 42.6 ± 0.5% porosity) was obtained by using 40 wt% of lime mud and a firing temperature of 1100°C with potential for further thermal tests in a ventilated façade in comparison with a commercial porcelain ceramic tile as reference material.
Towards collaborative management of non‐alcoholic fatty liver disease: a ‘real‐world’ pathway for fibrosis risk assessment in primary care
Authors: Hayward Kelly L. , McKillen Benjamin J. , Horsfall Leigh U. , McIvor Carolyn , Liew Katerina , Sexton Jo , Johnson Amy L. , Irvine Katharine M. , Valery Patricia C. , McPhail Steven M. , Britton Laurence J. , Rosenberg William , Weate Ingrid , Williams Sue , Powell Elizabeth E.
Published: June 2021

Background

The optimal strategy to support primary care practitioners (PCP) to assess fibrosis severity in non‐alcoholic fatty liver disease (NAFLD) and thereby make appropriate management decisions remains unclear.

Aims

To examine the feasibility of using a two‐step pathway that combined simple scores (NAFLD Fibrosis Score and Fibrosis‐4 Index) with transient elastography (FibroScan) to streamline NAFLD referrals from a ‘routine’ primary care population to specialist hepatology management clinics (HMC).

Methods

The two‐step ‘Towards Collaborative Management of NAFLD’ (TCM‐NAFLD) fibrosis risk assessment pathway was implemented at two outer metropolitan primary healthcare practices in Brisbane. Patients aged ≥18 years with a new or established PCP‐diagnosis of NAFLD were eligible for assessment. The pathway triaged patients at ‘high risk’ of clinically significant fibrosis to HMC for specialist review, and ‘low risk’ patients to receive ongoing management and longitudinal follow up in primary care.

Results

A total of 162 patient assessments between June 2019 and December 2020 were included. Mean age was 58.7 ± 11.7 years, 30.9% were male, 54.3% had type 2 diabetes or impaired fasting glucose, and mean body mass index was 34.2 ± 6.9 kg/m2. A total 122 patients was considered ‘low risk’ for clinically significant fibrosis, two patients had incomplete assessments and 38 (23.5%) were triaged to HMC. Among 31 completed HMC assessments to date, 45.2% were considered to have clinically significant (or more advanced) fibrosis, representing 9.2% of 153 completed assessments.

Conclusion

Implementation of the two‐step TCM‐NAFLD pathway streamlined hepatology referrals for NAFLD and may facilitate a more cost‐effective and targeted use of specialist hepatology resources.
Assessment of subclinical left ventricular systolic dysfunction and structural changes in patients with chronic obstructive pulmonary disease
Authors: Cengiz Elçioğlu Betul , Kamat Sadettin , Yurdakul Selen , Şahin Şükrü Taylan , Sarper Altemur , Yıldız Pınar , Aytekin Saide
Published: June 2021

Background

Patients with chronic obstructive pulmonary disease (COPD) can develop left ventricular (LV) systolic dysfunction and geometric changes due to several reasons.

Aim

To investigate subclinical LV systolic dysfunction and structural features in patients with COPD, and its correlation with the severity of airway obstruction, identified by GOLD classification.

Methods

We studied 52 patients with COPD and 29 age and sex‐matched controls, without any cardiac disease. In addition to conventional echocardiographic evaluation speckle tracking echocardiography (STE)‐based strain imaging were performed to analyse sub‐clinical LV systolic dysfunction. Also LV volumes were measured by using three‐dimensional real time echocardiography (3DRTE). All patients underwent spirometry.

Results

Conventional echocardiographic parameters (LV wall thickness and diameters, LV EF) and LV volume measurements were similar between the groups. LV global longitudinal peak systolic strain (−14.76 ± 2.69% to −20.27 ± 1.41%, P < 0.001) and strain rate (0.75 ± 0.25 1/s to 1.31 ± 0.41 1/s, P < 0.001) were significantly impaired in patients, compared to controls demonstrating sub‐clinical ventricular systolic dysfunction. Significant positive correlation was obtained between LV strain/strain rate and spirometry parameters (FEV1, FEV%, FEV1/FVC, PEF%) (r = 0.78/0.68, P < 0.001; r = 0.83/0.70, P < 0.001); r = 0.74/0.55, P < 0.001; r = 0.72/0.65, P < 0.001 respectively). In addition, there was significant negative correlation between LV strain/strain rate and GOLD classification (r = −0.80/ ‐0.69, P < 0.001 respectively).

Conclusion

Subclinical LV systolic dysfunction can occur in COPD patients despite normal EF. STE is a technique that provides additional information for detailed evaluation of subtle changes in LV myocardial contractility, significantly associated with the severity of the disease in COPD patients.
A Canadian single institution real‐world experience using the CROSS trial regimen in the treatment of oesophageal and gastroesophageal junction carcinoma
Authors: Khalid Sidra , Hopman Wilma M. , Virik Kiran
Published: June 2021

Background

Trimodality therapy using the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) trial protocol is an accepted standard of care for locally advanced oesophageal and gastroesophageal junction cancers. For medically inoperable patients, chemoradiotherapy (CRT) has been a therapeutic option.

Aims

This single institution review aimed to assess the real‐world application of the CROSS trial protocol.

Methods

This is a retrospective review of 83 patients who underwent CRT with carboplatin and paclitaxel with trimodality or definitive intent between June 2012 and June 2018. Sixty‐five patients underwent neoadjuvant CRT (NCRT); 40 had surgery, 18 had definitive CRT (DCRT). Patients' demographics, clinical, pathological, treatment and surgical characteristics were assessed. The data were analysed in exploratory analyses and Kaplan–Meier curves.

Results

For 83 patients, the following median values were seen: radiotherapy dose, 50.4 Gy; chemotherapy doses, 5; and time from CRT to surgery, 62 days. Twenty‐three percent NCRT and 72% DCRT patients were aged ≥75 years, and 49% and 33% of these respectively had no interruptions to CRT. Patients aged ≥75 years were more likely to have DCRT (P = 0.001). Patients who underwent surgery were younger (P = 0.04). For NCRT and surgery, NCRT only and DCRT respectively, median overall survival was 35.5, 12.1 and 17.1 months (log rank P = 0.008); progression‐free survival was 32.2, 10 and 9.6 months (log rank P = 0.001).

Conclusions

Despite broadening of the CROSS trial eligibility criteria in our real‐world data, there appears to be a survival benefit with trimodality therapy. The use of carboplatin and paclitaxel in DCRT may be of value and requires further study.
Impact of subclinical hypothyroidism on health‐related quality of life: a narrative review
Authors: Danicic Joseph M. , Inder Warrick J. , Kotowicz Mark A.
Published: June 2021

A biochemical diagnosis of subclinical hypothyroidism (SCH) is defined by an elevated serum thyroid‐stimulating hormone (TSH) with a normal serum free thyroxine (FT4). This paper discusses SCH in the Australian population, the impact of SCH on health‐related quality of life (HRQoL), and the evidence for thyroid hormone therapy as well as exercise therapy to improve HRQoL in SCH. The prevalence of SCH in Australia is approximately 4–5% and is higher in females and the elderly. Current evidence suggests thyroid hormone therapy is not associated with an improvement in HRQoL. However, there does appear to be a subgroup of those with SCH that experience an impairment in HRQoL who may potentially benefit from treatment. Because the majority of research to date has been done in elderly, largely asymptomatic individuals, this may not be representative of the entire SCH population. In addition, alternative treatments, such as exercise therapy, have not been well explored in the literature, despite exercise therapy's effects on HRQoL in other populations. Further research is required to define clearly which individuals with SCH are likely to experience an impaired HRQoL, as well as explore the effects of thyroid hormone therapy and exercise therapy in these individuals.
Continued root development of immature permanent teeth after regenerative endodontics with or without a collagen membrane: A randomized, controlled clinical trial
Authors: Jiang Xijun , Liu He , Peng Chufang
Published: June 2021

Background

Recent studies evaluated the efficacy of a collagen membrane (Bio‐Gide) to promote root development in regenerative endodontics (REPs). However, the influence of etiology and tooth type on the results was not assessed.

Aims

To evaluate the quantitative and qualitative effect of a collagen membrane (Bio‐Gide), with and without the effect of etiology and tooth type, in promoting root development in immature teeth after REPs.

Design

Eighty nonvital immature teeth were divided randomly into two groups (40 teeth in each group). REPs were performed with (experimental group) and without (control group) a collagen membrane. All teeth were subjected to regular clinical and radiographical follow‐up.

Results

Seventy‐six teeth were included in the final analyses. The average follow‐up periods were 33.1 ± 21.8 months for the control group and 28.1± 18.6 months for the experimental group. Quantitative analysis of root development in the experimental group showed a greater increase in dentin wall thickness in the middle one‐third of the root compared to the control group, with or without the effect of etiology and tooth type. Six types of root development were observed. There was no significant difference in the type of tooth development between the two groups.

Conclusion

The use of a collagen membrane could promote an increase in dentin wall thickness in the middle one‐third of the root, and it had no significant effect in terms of the type of subsequent root development.