bluuebunny/crossref_metadata_2025 huggingface dataset:
Reproduction of I‐type cosmic spherules and characterization in an Fe‐Ni‐O system
Authors: Shao Huimin , Isobe Hiroshi , Miao Bingkui
Published: September 2020

The chemical composition and texture of cosmic spherules are influenced by atmospheric conditions and the characteristics of their parent interplanetary particles. The objective of this study was to reproduce I‐type cosmic spherules, which consist mainly of Fe oxide and Fe‐Ni metal, and compare their textural characteristics with those of natural I‐type cosmic spherules. Thus, a series of rapid heating and quenching experiments were performed on free falling iron meteorite powders obtained from Canyon Diablo, in the United States. The experiments were conducted using a high‐temperature furnace with controlled gas flow rates at oxygen fugacities of FMQ + 2.4, FMQ, and FMQ − 2.5 log unit. The resulting Fe‐Ni metal and oxide phases showed the nonequilibrium state of the melted spherules formed during quenching. Two types of magnetite crystals in different orientations were found in iron oxide. As temperatures decreased, the molten metal was oxidized to form immiscible molten iron oxide that then covered the former. As the oxide melt increased at the expense of metal, magnetite began to crystallize from the iron oxide melt, as the liquidus phase, either on the surface or within the melt phase. The characteristics of the run products obtained under different oxygen fugacities were similar to those of natural I‐type cosmic spherules, which have textures and compositions that may contain information regarding the oxygen content of the upper atmosphere. Our study suggests that CO2‐bearing molecules in the atmosphere could form iron oxide with a texture similar to natural I‐type cosmic spherules. During this process, rapid crystallization of magnetite plays an important role in texture formation in disequilibrium states.
A revised shock history for the youngest unbrecciated lunar basalt—Northwest Africa 032 and paired meteorites
Authors: Mijajlovic Tatiana , Xue Xi , Walton Erin
Published: September 2020

Northwest Africa (NWA) 032 is an unbrecciated porphyritic basalt found in the Moroccan desert in 1999. Constituent igneous minerals—olivine, pyroxene, and plagioclase—exhibit shock deformation and transformation effects. NWA 032 is among the youngest radiometrically dated sample from the Moon, with concordant Sm‐Nd and Rb‐Sr ages of 2.947 ± 0.016 Ga and 2.931 ± 0.092, respectively, representing the timing of igneous crystallization. We present the first comprehensive study of shock metamorphism in NWA 032, with a focus on the structural state of fine‐grained plagioclase feldspar, shock deformation in olivine and pyroxene, and the microtexture and mineralogy of shock melts. Micro‐Raman spectroscopy, optical properties, and electron imaging confirm that plagioclase in this meteorite has been shock amorphized, which, for calcic plagioclase (An80‐90), requires shock pressures on the order of ~25–27 GPa. Shock pressures in this range are accompanied by a postshock temperature increase <200 °C. Shock deformation in olivine and pyroxene phenocrysts comprises undulose extinction to weak mosaicism, irregular fractures, polysynthetic mechanical twinning in pyroxene, and development of planar fractures in olivine. The shock effects in mafic minerals constrain the upper limit of shock in NWA 032 to have been <30 GPa. Shock melt in NWA 032 has quenched to glass of basaltic composition, representing localized in situ melting of igneous minerals by shearing along lithological boundaries to form shock veins and shock impedance contrasts to form isolated pockets of shock melt. These melts quench‐crystallized olivine and pyroxene during the pressure release (<14 GPa). Using recent experimental data on shock amorphization of feldspars, coupled with constraints on the formation of metastable minerals associated with shock melt, we have revised the shock pressure experienced by paired meteorites NWA 10597, NWA 4734, and LaPaz Icefield 02205/02224/0226/02436/03632/04841. These largely unbrecciated, basaltic meteorites experienced an equilibration shock pressure on the order of ~22–25 GPa, constrained by partial amorphization of precursor igneous bytownite. Our results are consistent with crater pairing and ejection in a single impact cratering event.
Systemic delivery of human GlyR IgG antibody induces GlyR internalization into motor neurons of brainstem and spinal cord with motor dysfunction in mice
Authors: Carvajal‐González A. , Jacobson L. , Clover L. , Wickremaratchi M. , Shields S. , Lang B. , Vincent A.
Published: September 2020

Aims

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a life‐threatening condition often associated with highly raised serum antibodies to glycine receptors (GlyRs); these bind to the surface of large neurons and interneurons in rodent brain and spinal cord sections and, in vitro, inhibit function and reduce surface expression of the GlyRs. The effects in vivo have not been reported.

Methods

Purified plasma IgG from a GlyR antibody‐positive patient with PERM, and a healthy control (HC), was injected daily into the peritoneal cavity of mice for 12 days; lipopolysaccharide (LPS) to open the blood–brain barrier, was injected on days 3 and 8. Based on preliminary data, behavioural tests were only performed 48 h post‐LPS on days 5–7 and 10–12.

Results

The GlyR IgG injected mice showed impaired ability on the rotarod from days 5 to 10 but this normalized by day 12. There were no other behavioural differences but, at termination (d13), the GlyR IgG‐injected mice had IgG deposits on the neurons that express GlyRs in the brainstem and spinal cord. The IgG was not only on the surface but also inside these large GlyR expressing neurons, which continued to express surface GlyR.

Conclusions

Despite the partial clinical phenotype, not uncommon in passive transfer studies, the results suggest that the antibodies had accessed the GlyRs in relevant brain regions, led to antibody‐mediated internalization and increased GlyR synthesis, compatible with the temporary loss of function.
Diagnostic accuracy of fibroblast growth factor 23 for predicting acute kidney injury in patients with acute decompensated heart failure
Authors: Pramong Nattha , Gojaseni Pongsathorn , Suttipongkeat Sarunyoo , Kiattisunthorn Kraiwiporn , Chittinandana Anutra
Published: September 2020

Background

Elevated plasma levels of fibroblast growth factor 23 (FGF23) have emerged as a predictor for the development of acute kidney injury (AKI) in patients undergoing cardiac surgery and those with critical illnesses. However, accurate data in cases involving acute decompensated heart failure (ADHF) remains limited.

Methods

Single centre cohort study was performed in patients admitted for ADHF. Plasma c‐terminal FGF23 (c‐FGF23) was measured at baseline and 24 hours after being diagnosed with ADHF. AKI was defined by KDIGO 2012 criteria.

Results

The study enrolled 62 patients diagnosed with ADHF. The incidence of AKI was 45% and significantly increased the risk of death. Patients developing AKI had significantly higher levels of plasma c‐FGF23 at baseline in comparison with those not developing AKI [median value 1258.5 (57.2, 15 850) vs 230.2 (68.515 850) RU/mL, P = .005]. During the first 24 hours, plasma c‐FGF23 levels decreased in both groups, and the levels of c‐FGF23 at 24 hours were consistent with the baseline [861.8 (75.7, 15 850) vs 226.3 (56, 5450.8) RU/mL, P = .006]. Receiver operating characteristic analysis of both first time and second time for plasma c‐FGF23 collection yielded an area under curve of 0.71 for the prediction of AKI incidence. With the cut‐off point at 450 RU/mL, the sensitivity and specificity of plasma c‐FGF23 at the baseline for predicting AKI were 71.4% and 61.8% respectively.

Conclusion

Plasma c‐FGF23 may serve as a novel biomarker for development of AKI in patients with ADHF. These results should be revalidated in larger‐scale, cohort studies.
An adult case of diffuse midline glioma with H3 K27M mutation
Authors: Tu Jin‐hua , Piao Yue‐shan , Lu De‐hong , Wang Lei‐ming , Liu Li , Bai Dong‐yu , Han Hai‐Wei , Lin Yi‐kai , Zhong Shan
Published: September 2020

Cartilaginous metaplasia is rare in primary central nervous system (CNS) neoplasms and has not been described in the histone 3 (H3) gene (H3) with a substitution of lysine to methionine (H3 K27M mutant) diffuse midline glioma before. Here, we report a case of H3 K27M mutant diffuse midline glioma with cartilaginous metaplasia in a 56‐year‐old woman. Magnetic resonance imaging (MRI) revealed a ring‐enhanced lesion located in the medulla oblongata and extended superiorly into the fourth ventricle. The tumor was macroscopically completely resected. Histologically, the tumor was composed of a gliomatous component and a well‐differentiated cartilaginous component. Microvascular proliferation and necrosis were noted. According to immunohistochemical staining, glial cells were diffusely and strongly positive for glial fibrillary acidic protein (GFAP), oligodendrocyte lineage transcription factor 2 (Olig2), H3 K27M, and S‐100 protein but negative for H3K27me3. The chondrocytes also were positive for GFAP and S‐100 protein. The H3 K27M mutation was confirmed by sequencing in both the gliomatous and cartilaginous components, suggesting a common origin from the same progenitor cells. Based on these findings, the tumor was diagnosed as a diffuse midline glioma with H3 K27M mutation with widespread cartilaginous metaplasia, corresponding to WHO grade IV. This is an extremely rare H3 K27M mutant diffuse midline glioma with cartilaginous metaplasia, and reporting this unusual case adds to the understanding of this tumor type.
A political economy model of the Ganges pollution cleanup problem
Authors: Batabyal Amitrajeet A. , Beladi Hamid
Published: September 2020

We study pollution cleanup in the Ganges in Varanasi, India. Voters elect politicians and elected politicians decide how much pollution to clean up. Between the two time periods, there is an election. Politicians are sincere or insincere. The marginal cost of public funds measures how efficiently elected politicians transform tax receipts into pollution cleanup. Voters have identical per period utility functions. We ascertain the equilibrium outcome and per period voter welfare. Second, we show that an increase in reduces the equilibrium pollution cleanup and voter welfare. Third, an insincere politician can delay the revelation of his insincerity. We show that a critical value of exists such that the insincere incumbent separates and loses the election if and only if and that he pools and is re‐elected otherwise. Finally, we note that an increase in can raise voter welfare when politicians are more likely to be insincere.

Recommendations for Resource Managers

Successful cleanup policies depend on whether elected politicians are sincere or insincere about pollution cleanup.

When cleanup is publically financed, the marginal cost of public funds greatly influences how much pollution is cleaned up.

In some circumstances, an insincere politician can get elected and do very little to clean up pollution.
Functional retinal outcomes in patients with prediabetes and type 2 diabetes
Authors: Karson Nicole , Smith Jennyffer , Jones Morgan , Datta Ananya , Richdale Kathryn , Harrison Wendy W.
Published: September 2020

Purpose

Type 2 diabetes (T2DM) is a leading cause of visual impairment. Its precursor, prediabetes (preDM), is growing in numbers every year. While it is well known that T2DM causes changes in retinal function early in the disease process, it is likely that some of these changes emerge during the preDM stage. This study evaluates retinal function measures in patients with preDM to determine if there are differences in colour vision, contrast sensitivity (CS), and multifocal electroretinogram (mfERG) measures present before T2DM is diagnosed.

Methods

The L’Anthony desaturated D‐15 test, Mars Chart CS test, and mfERG were administered on the right eye of 43 participants; 15 controls (HbA1c 5.6%), 17 with preDM (HbA1c 5.7%–6.4%), and 11 with T2DM (either physician diagnosed or with untreated HbA1c ≥ 6.5%). HbA1c values were measured at the time of the other tests. Colour vision confusion scores (CVCS) were calculated from the D‐15 using the method developed by Torok. Multivariate regression (which controlled for age differences) was used to evaluate the relationship of HbA1c and functional measures. Kruskal‐Wallis tests were also used to evaluate differences between groups with post‐hoc analysis.

Results

CVCSs were significantly different between the three groups (p = 0.009). There was an association between higher CVCS and higher HbA1c values across all groups as well as specifically within the preDM group when controlling for age (R2 = 0.29, p = 0.01 and R2 = 0.39, p = 0.02 respectively). Multivariate regression of all of the functional tests together and HbA1c found only colour vision remained significant, indicating that the functional examination metrics may provide redundant data, with similar changes in prediabetes where colour vision may be the strongest indicator early in the process.

Conclusions

Patients with prediabetes have functional changes that can be measured in the retina before the diagnosis of diabetes, with the L’Anthony D‐15 colour vision test providing the strongest association with glucose dysregulation in this population. This has important implications for follow up and screening for diabetes within optometric practices. Further studies are needed to follow these patients over time to see how and when these metrics change.
Transvenous revision of leads with cardiac perforation following device implantation—Safety, outcome, and complications
Authors: Döring Michael , Müssigbrodt Andreas , Ebert Micaela , Bode Kerstin , Lucas Johannes , Dagres Nikolaos , Hindricks Gerhard , Richter Sergio
Published: September 2020

Introduction

Cardiac perforation is a rare complication of cardiac implantable electronic device (CIED) implantation. Transvenous revision of perforated leads is associated with the risk of cardiac tamponade and death. Little is known about periprocedural complications and outcome of these patients.

Methods and results

All patients referred to our department with evidence or suspicion of cardiac perforation following CIED implantation underwent chest X‐ray, transthoracic echocardiography, device interrogation, and, if necessary, a cardiac computed tomography (CT)‐scan to diagnose lead perforation and associated complications. Transvenous lead revision (TLR) was performed in all patients with evidence of lead perforation. Patient characteristics, procedural complications, and outcome were recorded and analyzed.

Fifty‐six patients (75 ± 10 years, 43% male) were diagnosed with cardiac perforation, 34 patients (61%) early within 30 days post‐implantation, and 22 patients (39%) thereafter. The most frequent perforation site was the right ventricular (RV) apex (75%), followed by the RV free wall (16%) and the right atrial appendage (9%). A total of 16 patients (29%) presented with severe complications; 12 patients (21%) with pericardial effusion treated by pericardiocentesis before lead revision and four patients (7%) with hematothorax requiring drainage. Late perforations showed significantly more frequent cardiac tamponades (P = .041). TLR was performed without further complications in 54 patients (96%). None of the patients required surgical treatment or experienced in‐hospital death.

Conclusions

Cardiac perforation following CIED implantation is associated with severe complications in nearly one‐third of the cases. Transvenous revision of the perforated lead can safely be performed with a very low complication rate.
What is new in beta‐lactam allergy in children?
Authors: Atanaskovic‐Markovic Marina
Published: September 2020

This review highlights the novelties in understanding the underlying immunologic mechanisms of drug hypersensitivity reactions (DHRs) with special reference to beta‐lactams (BLs) in the pediatric population, as well as tiny changes in clinical classification and diagnosis of DHRs, in the last couple of years. BLs are still the most commonly prescribed and used antibiotics in children. Viral infections are very often in children, and they can provoke skin rashes which are difficult to differentiate from DHRs. The majority of children are incorrectly labeled as “allergic.” Therefore, allergy to BLs in children is overdiagnosed. These children often receive suboptimal treatment with second‐line broad‐spectrum antibiotics, which are less effective, more costly, and associated with an increased risk of antibiotic‐resistant infections. This prolongs hospitalization and thus more uses health care. The correct diagnosis of BL allergy in children is still an important and hot topic. This review has outlined the need for correct diagnosis of BL allergy in children and all the controversies encountered by pediatricians and pediatric allergists. It is also necessary to change the paradigm.
Melanin‐concentrating hormone like and somatolactin. A teleost‐specific hypothalamic‐hypophyseal axis system linking physiological and morphological pigmentation
Authors: Bertolesi Gabriel E. , McFarlane Sarah
Published: September 2020

Plastic adaptation to match the skin colour to the surrounding is key to survival. Two biological responses in skin colour are associated with background adaptation. A fast “physiological response” that aggregates/disperses the pigment organelles of skin chromatophores, and a slow “morphological response” that alters the type and/or density of pigment cells in the skin. Both responses are linked by unknown mechanisms. In this review, we discuss the role in skin colour regulation of two molecules that form part of a hypothalamic‐hypophyseal pathway unique to teleosts, melanin‐concentrating hormone “like” (MCHL) (previously known as MCH), and somatolactin. MCHL neurons project to the neurohypophysis and to the pars intermedia pituitary, where they interact with somatolactin‐expressing cells. With a white background MCHL is released into the circulation to induce rapid melanosome aggregation and skin lightening. Somatolactin is also a fish‐specific peptide whose expression and secretion are altered in organisms adapted chronically to white/black backgrounds, and that regulates morphological pigmentation. We discuss the evidence for a model whereby in teleosts, MCHL and somatolactin provide the previously unknown link between physiological and morphological pigmentation.
The effect of circadian preferences on insomnia severity and depressive symptoms via sleep hygiene in older adults with depression and healthy controls
Authors: Üzer Ahmet , Yücens Bengü
Published: September 2020

Background

The elderly population is increasing globally. Thus, researches focus on the causes and treatment of insomnia, a noteworthy ageing problem. This study aims to investigate the relationship between chronotype and insomnia and whether sleep hygiene mediates this relationship in older adults with depression (OAD).

Methods

We assessed subjective insomnia severity, sleep hygiene, chronotype, depressive symptoms, and anxiety symptoms of 82 OAD and 70 healthy controls using the Sleep Hygiene Index (SHI), Insomnia Severity Index (ISI), Morningness‐Eveningness Questionnaire (MEQ), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI).

Results

The mediation effect of SHI and ISI scores were evaluated in the relationship between MEQ and BDI total scores in OAD. The results showed that MEQ performed its effect on BDI through ISI with full mediation (effect = −0.16, SE: 0.07, 95% CI: −0.3230 to −0.0336). The mediation effect of SHI and BDI scores were evaluated in the relationship between MEQ and ISI total scores in OAD. In this model, it was found that MEQ significantly performed its effect on ISI through SHI and BDI. BDI and SHI predicted the ISI variable as partial mediators (respectively, effect = −0.05, SE: 0.03, 95% CI: −0.1073 to −0.0100; effect = −0.06, SE: 0.02, 95% CI: −0.1051 to −0.0129).

Conclusions

Sleep hygiene practices could be essential for the natural functioning of the biological clock and the interrelation of depression and insomnia. Longitudinal follow‐up studies of structured sleep hygiene approaches are needed in terms of cost‐effectiveness, in OAD.
Reply
Authors: Savinelli Stefano , McCarthy Cormac , Mallon Patrick W. ,   All Ireland Infectious Diseases (AIID) Cohort Collaborators
Published: September 2020

See related letter
The efficacy of two different oral hygiene regimens on the incidence and severity of oral mucositis in pediatric patients receiving hematopoietic stem cell transplantation: A prospective interventional study
Authors: Mubaraki Sarah , Pani Sharat Chandra , Alseraihy Amal , Abed Hassan , Alkhayal Zikra
Published: September 2020

Aims

This prospective interventional study aimed to assess the efficacy of supersaturated calcium phosphate rinse and the use of an extra‐soft toothbrush twice a day when added to the existing oral hygiene protocol regimen (0.12% chlorhexidine gluconate + 3% sodium bicarbonate + nystatin 5000 U/mL) in reducing the severity of oral mucositis among pediatric patients receiving chemotherapy for the hematopoietic stem cell transplant.

Methods

Forty‐five patients that received chemotherapy for the hematopoietic stem cell transplant were randomly allocated to three groups of 15 patients each. Group A was advised to follow the existing oral hygiene protocol regimen (Control), group B was advised to brush their teeth twice daily using an extra‐soft toothbrush and to follow the control regimen, and lastly group C was advised to use supersaturated calcium phosphate rinse and to follow the control regimen. Oral mucositis was recorded according to World Health Organization criteria from the day of admission (day 1) to the day of discharge (day 28). The incidence of oral mucositis between the three groups was compared using the Kruskall‐Wallis test while the severity of oral mucositis between the three groups was compared using a one‐way ANOVA test.

Results

The results of the study showed no significant difference in the incidence of oral mucositis between the three groups; however, there was a lower severity of oral mucositis in the supersaturated calcium phosphate rinse group when compared to the control group or the group who used an extra‐soft toothbrush with the control regimen.

Conclusion

Although marginally fewer cases and lower severity of oral mucositis was observed in the group using supersaturated calcium phosphate rinse, the lack of statistical significance suggests that the evidence for their use is not conclusive. The results of this study also showed that the introduction of an extra‐soft toothbrush into the oral hygiene regimen did not significantly reduce the incidence of oral mucositis and may actually be responsible for an increase in the severity of oral mucositis.
Exploring predictors of Australian community members' blood donation intentions and blood donation–related behavior during the COVID‐19 pandemic
Authors: Masser Barbara M , Hyde Melissa K , Ferguson Eamonn
Published: September 2020

Background

With the coronavirus disease 2019 (COVID‐19) pandemic continuing to accelerate and blood collection agencies (BCAs) warning of shortages, it is critical to identify the current determinants of donor behavior for donors and nondonors.

Study Design and Methods

In May and June 2020, Australian residents who believed themselves eligible to donate blood responded to measures assessing constructs from an integrated protection motivation theory, organizational trust, and theory of planned behavior framework, with donor status also assessed.

Results

A total of 507 residents (47% male, mean age 28.69 years; 272 had donated/attempted to donate) participated. A revised structural equation model was a good fit to these data. In this model, perceived risk, severity, anxiety, and response cost associated with donating during the COVID‐19 pandemic underpinned threat appraisals, while response efficacy, self‐efficacy, and attitude toward donating during COVID‐19 informed coping appraisals. Trust in the BCA predicted lower threat and higher coping appraisals, and higher coping appraisals predicted stronger subjective norms. Intention to donate during the COVID‐19 pandemic was positively predicted by subjective norm and self‐efficacy. Donation‐related behavior was positively predicted by intention, with this relationship stronger for nondonors than donors.

Conclusion

Self‐efficacy and approval from others, underpinned by coping appraisals and organizational trust, play a critical role in intentions to donate. BCAs that focus on maintaining trust with (potential) donors, providing clear messaging stating the minimal threat of contracting COVID‐19 from donating and the protective measures in place, and showing how donating is achievable, may help to ensure a safe and secure blood supply throughout the COVID‐19 pandemic.
Proof‐of‐concept study: Evaluation of plasma and urinary electrolytes as markers of response to L‐asparaginase therapy in dogs with high‐grade lymphoma
Authors: Sayag David , Chamel Gabriel , Bédard Christian , Beauchamp Guy , Couturier Solange , Ponce Frédérique , Rannou Benoit
Published: September 2020

Response to chemotherapy is one of the most important prognostic factors in dogs with lymphoma. The objective of this feasibility study was to evaluate if clinical responses to a specific cytotoxic agent (L‐asparaginase) could be anticipated by measuring analyte concentrations in plasma and urine concentrations of lymphoma‐bearing dogs. We hypothesized that potassium and phosphate concentrations in plasma and urine would be higher in dogs that completely responded to therapy. Plasma and urine samples of dogs with lymphoma were obtained before 12 and 24 hours after intramuscular L‐asparaginase injections. Peripheral lymph node volumes were evaluated according to the Veterinary Cooperative Oncology Group standardized criteria. Plasma and urine electrolyte, calcium, phosphate, creatinine, urea, total protein, and albumin concentrations were measured, and the fractional excretions of each electrolyte were calculated. Statistical analyses compared complete vs partial responders using a linear regression model. Contrast analyses were also performed to differentiate the mean of each group, with adjustments made with the Benjamini‐Hochberg procedure. Fourteen dogs were included, eight with complete responses, and six with partial responses. Plasma phosphate concentrations were significantly higher at 12 hours (P = .0003) and 24 hours (P = .009) after complete responses to therapy. This study demonstrates the potential use of plasma and urine analyte monitoring after chemotherapy induction. Plasma phosphate measurements represent a potential indicator of early responses to L‐asparaginase therapy. Larger population studies are warranted to confirm these preliminary results.
A four stage approach to community archaeology, illustrated with cases studies from Dorset, England
Authors: Roberts Hayley , Gale John , Welham Kate
Published: September 2020

This article presents an approach to guide the planning, development and evaluation of community archaeology. This will assist practitioners of all forms of community archaeology by providing a pathway to ethical practice that will benefit all. The approach focuses attention on four elements that are integral to community archaeology and which should always be considered: Who (the people involved); Why (their motivation); the Archaeology (in the broadest sense, including research questions and research methods); and How (the specific format the community engagement will take). This framework is applied to three case study community archaeology projects in Dorset, England, in order to demonstrate challenging examples of planned and reflexive community archaeology.
Minimal Elements Required for the Formation of Respiratory Syncytial Virus Cytoplasmic Inclusion Bodies
In Vivo
and
In Vitro
Authors: Galloux Marie , Risso-Ballester Jennifer , Richard Charles-Adrien , Fix Jenna , Rameix-Welti Marie-Anne , Eléouët Jean-François
Published: September 2020

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract illness in infants, elderly, and immunocompromised people. No vaccine or efficient antiviral treatment is available against this virus. The replication and transcription steps of the viral genome are appealing mechanisms to target for the development of new antiviral strategies. These activities take place within cytoplasmic inclusion bodies (IBs) that assemble during infection. Although expression of both the viral nucleoprotein (N) and phosphoprotein (P) allows induction of the formation of these IBs, the mechanism sustaining their assembly remains poorly characterized. Here, we identified key elements of N and P required for the scaffolding of IBs and managed for the first time to reconstitute RSV pseudo-IBs
in vitro
by coincubating recombinant N and P proteins. Our results provide strong evidence that the biogenesis of RSV IBs occurs through liquid-liquid phase transition mediated by N-P interactions.
Genotoxic Effect of
Salmonella
Paratyphi A Infection on Human Primary Gallbladder Cells
Authors: Sepe Ludovico P. , Hartl Kimberly , Iftekhar Amina , Berger Hilmar , Kumar Naveen , Goosmann Christian , Chopra Sascha , Schmidt Sven Christian , Gurumurthy Rajendra Kumar , Meyer Thomas F. , Boccellato Francesco
Published: September 2020

Bacterial infections are increasingly being recognized as risk factors for the development of adenocarcinomas. The strong epidemiological evidence linking
Helicobacter pylori
infection to stomach cancer has paved the way to the demonstration that bacterial infections cause DNA damage in the host cells, initiating transformation. In this regard, the role of bacterial genotoxins has become more relevant.
Salmonella enterica
serovars Typhi and Paratyphi A have been clinically associated with gallbladder cancer. By harnessing the stem cell potential of cells from healthy human gallbladder explant, we regenerated and propagated the epithelium of this organ
in vitro
and used these cultures to model
S.
Paratyphi A infection. This study demonstrates the importance of the typhoid toxin, encoded only by these specific serovars, in causing genomic instability in healthy gallbladder cells, posing intoxicated cells at risk of malignant transformation.
Impaired Cytotoxic CD8+T Cell Response in Elderly COVID-19 Patients
Authors: Westmeier Jaana , Paniskaki Krystallenia , Karaköse Zehra , Werner Tanja , Sutter Kathrin , Dolff Sebastian , Overbeck Marvin , Limmer Andreas , Liu Jia , Zheng Xin , Brenner Thorsten , Berger Marc M. , Witzke Oliver , Trilling Mirko , Lu Mengji , Yang Dongliang , Babel Nina , Westhoff Timm , Dittmer Ulf , Zelinskyy Gennadiy
Published: September 2020

Cytotoxic T cells are responsible for the elimination of infected cells and are key players in the control of viruses. CD8+T cells with an effector phenotype express cytotoxic molecules and are able to perform target cell killing. COVID-19 patients with a mild disease course were analyzed for the differentiation status and cytotoxic profile of CD8+T cells. SARS-CoV-2 infection induced a vigorous cytotoxic CD8+T cell response. However, this cytotoxic profile of T cells was not detected in COVID-19 patients over the age of 80 years. Thus, the absence of a cytotoxic response in elderly patients might be a possible reason for the more frequent severity of COVID-19 in this age group than in younger patients.
Biophysical and Biochemical Characterization of TP0037, a
d
-Lactate Dehydrogenase, Supports an Acetogenic Energy Conservation Pathway in Treponema pallidum
Authors: Deka Ranjit K. , Liu Wei Z. , Norgard Michael V. , Brautigam Chad A.
Published: September 2020

Because
T. pallidum
lacks a Krebs cycle and the capability for oxidative phosphorylation, historically it has been difficult to reconcile how the syphilis spirochete generates sufficient ATP to fulfill its energy needs, particularly for its robust motility, solely from glycolysis. We have postulated the existence in
T. pallidum
of a flavin-dependent acetogenic energy conservation pathway that would generate additional ATP for
T. pallidum
bioenergetics. In the proposed acetogenic pathway, first
d
-lactate would be converted to pyruvate. Pyruvate would then be metabolized to acetate in three additional steps, with ATP being generated via substrate-level phosphorylation. This study provides structural, biochemical, and biophysical evidence for the first
T. pallidum
enzyme in the pathway (TP0037;
d
-lactate dehydrogenase) requisite for the conversion of
d
-lactate to pyruvate. The findings represent the first experimental evidence to support a role for an acetogenic energy conservation pathway that would contribute to nonglycolytic ATP production in
T. pallidum
.
Eosinophilic colitis: an infrequent disease with difficult diagnose
Authors: Páramo-Zunzunegui Javier , Ortega-Fernandez Ignacio , Benito-Barbero Silvia , Rubio-López Laura
Published: September 2020

Eosinophilic colitis (EC) is a rare entity. It is part of eosinophilic gastroenteritis, a rare inflammatory disorder characterised by eosinophilic infiltration of tissues that can affect any segment of the digestive tract. The diagnosis is established by the presence of an increased eosinophilic infiltrate in the colon wall in symptomatic patients. There is no characteristic clinical picture of EC. It can be associated with abdominal pain, changes in bowel movements, diarrhoea and rectal bleeding. Biopsies are mandatory if EC is suspected and despite visualising a normal mucosa. Although there are no protocol guidelines in this regard, steroid treatment is the first option in controlling the disease. Increasing the knowledge of clinicians and pathologists of this disorder and the recording its real incidence and population impact, could improve the understanding and treatment of the disease.
Role of IgM testing in the diagnosis and post-treatment follow-up of syphilis: a prospective cohort study
Authors: Osbak Kara K , Tsoumanis Achilleas , De Baetselier Irith , Van Esbroek Marjan , Smet Hilde , Kenyon Chris R , Crucitti Tania
Published: September 2020

Objectives

The diagnosis of repeat syphilis and its follow-up remains challenging. We aimed to investigate if IgM testing may assist in the diagnosis of syphilis reinfection/relapse and its treatment follow-up.

Methods

This substudy was conducted in the context of a syphilis biomarker discovery study (ClinicalTrials.gov Nr: NCT02059525). Sera were collected from 120 individuals with a new diagnosis of syphilis (72 with repeat infections) and 30 syphilis negative controls during a cohort study investigating syphilis biomarkers conducted at a sexually transmitted infection/HIV clinic in Antwerp, Belgium. Syphilis was diagnosed based on a simultaneous positive treponemal and non-treponemal assay result and/or positive serum PCR targeting polA. Specimens collected at visit of diagnosis, and 3 and 6 months post-treatment were tested by two enzyme immunoassays (EIAs), recomWell (Mikrogen; MI) and Euroimmun (EU), to detect anti-treponemal IgM. Baseline specimens were also tested for anti-treponemal IgM using a line immunoassay (LIA) recomLine (MI). Quantitative kinetic decay curves were constructed from the longitudinal quantitative EIA results.

Results

An overall sensitivity for the diagnosis of syphilis of 59.8% (95% CI: 50.3%–68.7%), 75.0% (95% CI: 66.1%–82.3%) and 63.3% (95% CI: 54.8%–72.6%) was obtained for the EU, MI EIAs and MI LIA, respectively. When only considering repeat syphilis, the diagnostic sensitivity decreased to 45.7% (95% CI: 33.9%–58.0%), 63.9% (95% CI: 51.7%–74.6%) and 47.2% (95% CI: 35.5%–59.3%), respectively. IgM seroreverted in most cases 6 months after treatment. Post-treatment IgM concentrations decreased almost 30% faster for initial syphilis compared with repeat infection. The IgM EIAs and IgM LIA agreed from fairly to moderately (Cohen’s kappa (κ): 0.36 (EU EIA); κ: 0.53 (MI EIA); κ: 0.40 (MI LIA)) with the diagnosis of syphilis.

Conclusions

IgM detection was not a sensitive method to diagnose syphilis and was even poorer in the diagnosis of syphilis repeat infections.
Depression screening using patient-targeted feedback in general practices: study protocol of the German multicentre GET.FEEDBACK.GP randomised controlled trial
Authors: Kohlmann Sebastian , Lehmann Marco , Eisele Marion , Braunschneider Lea-Elena , Marx Gabriella , Zapf Antonia , Wegscheider Karl , Härter Martin , König Hans-Helmut , Gallinat Jürgen , Joos Stefanie , Resmark Gaby , Schneider Antonius , Allwang Christine , Szecsenyi Joachim , Nikendei Christoph , Schulz Sven , Brenk-Franz Katja , Scherer Martin , Löwe Bernd
Published: September 2020

Introduction

Approximately one out of six patients in primary care suffers from depression, which often remains undetected. Evidence regarding the efficacy of depression screening in primary care, however, is inconsistent. A previous single-centre randomised controlled trial (RCT) in cardiac patients, the DEPSCREEN-INFO trial, provided the first evidence that written feedback to patients following a positive depression screening reduces depression severity and leads to more comprehensive patient engagement in mental healthcare. To amplify these effects, the feedback should be tailored according to patients’ needs and preferences. The GET.FEEDBACK.GP RCT will test the efficacy of this patient-targeted feedback intervention in primary care.

Methods and analysis

The multicentre three-arm GET.FEEDBACK.GP RCT aims to recruit a total of 1074 primary care patients from North, East and South Germany. Patients will be screened for depression using the Patient Health Questionnaire-9 (PHQ-9). In the case of a positive depression screening result (PHQ-9 score ≥10), the participant will be randomised into one of three groups to either receive (a) patient-targeted and general practitioner (GP)-targeted feedback regarding the depression screening results, (b) only GP-targeted feedback or (c) no feedback. Patients will be followed over a period of 12 months. The primary outcome is depression severity (PHQ-9) 6 months after screening. Secondary outcomes include patient engagement in mental healthcare, professional depression care and cost-effectiveness. According to a statistical analysis plan, the primary endpoint of all randomised patients will be analysed regarding the intention-to-treat principle.

Ethics and dissemination

The Ethics Committee of the Hamburg Medical Association approved the study. A clinical trial company will ensure data safety, monitoring and supervision. The multicentre GET.FEEDBACK.GP RCT is the first trial in primary care that tests the efficacy of a patient-targeted feedback intervention as an adjunct to depression screening. Its results have the potential to influence future depression guidelines and will be disseminated in scientific as well as patient-friendly language.

Trial registration number

NCT03988985.
Improving intraoperative administration of surgical antimicrobial prophylaxis: a quality improvement report
Authors: Haney Victoria , Maman Stephan , Prozesky Jansie , Bezinover Dmitri , Karamchandani Kunal
Published: September 2020

Despite widespread adoption of the Surgical Care Improvement Programme, the incidence of surgical site infections (SSIs) remains high. It is possible that lapses in appropriate administration of antimicrobial prophylaxis may play a role. We noted significant discordance with national guidelines with regards to intraoperative antibiotic administration at our institution, leading to implementation of a quality improvement initiative using multidisciplinary education and reminder-based interventions to improve prescribing practices and increase compliance with national guidelines. We observed a significant improvement in adherence to all aspects of antibiotic administration guidelines as a result of such interventions. Targeted multidisciplinary interventions may help improve prescribing practices of surgical antimicrobial prophylaxis and provide an opportunity to potentially decrease the burden of SSI and the related morbidity and mortality.
Short-term efficacy of home-based heart rate variability biofeedback on sleep disturbance in patients with incurable cancer: a randomised open-label study
Authors: Hasuo Hideaki , Kanbara Kenji , Shizuma Hisaharu , Morita Yukihiro , Fukunaga Mikihiko
Published: September 2020

Objectives

Early palliative care reportedly contributes to the quality of life by improving coping skills in patients with cancer. The aims of the study are to (1) Build a self-coping system that makes it possible to perform a session of home-based heart rate variability biofeedback (HRV-BF) with resonant breathing in patients with sleep disturbance and to acquire its techniques early on, and (2) Examine its short-term efficacy and feasibility.

Methods

A randomised, open-label, comparative study was conducted in the presence or absence of home-based HRV-BF with resonant breathing using a portable HRV-BF device prior to bedtime. The participants were 50 patients with incurable cancer with sleep disturbance who underwent a hospital practice of HRV-BF with resonant breathing. The primary end point was the rate of change in sleep efficiency for 10–14 days. The Japanese version of the Pittsburgh Sleep Quality Index (subjective indicator) and actigraphy sleep parameters (objective indicators) were used for sleep assessments.

Results

The completion rate and implementation rate in the home-based HRV-BF group (n=25) were 96.0% and 91.4%, respectively. This group showed a significant improvement in sleep efficiency, sleep duration and the low-frequency component of HRV. Sleep latency worsened in this group, but a significant difference was not observed.

Conclusions

A home practice of HRV-BF with resonant breathing made it possible to acquire its techniques early on and improve sleep and autonomic function; therefore, our study showed high short-term efficacy and feasibility required for a self-coping system.
Ventilator dependence complications in motor neuron disease
Authors: Dewhurst Felicity , Elverson Joanna , Mccleery Amanda , Brown Jolene , McConnell Robert , Lever Owen , Doris Thomas , Messer Ben , Hughes Andrew
Published: September 2020

Long-term dependence on non-invasive ventilation (NIV) without time for advance care planning can result in significant complications that may require innovative management strategies. We present the case of a man who was admitted with respiratory failure and required NIV. Despite effective treatment for community acquired pneumonia, attempts to wean NIV failed. While dependent on NIV, a diagnosis of motor neuron disease was made. Time without ventilation was not tolerated and consequently complications of: facial pressure ulceration, nasal septal prolapse, inspissated secretions and failure to feed occurred. This case illustrates the severity of complications that can result from NIV dependence; however, it also details how these can be effectively managed by the hospice multidisciplinary team, with support from experts both within and external to the hospice enabling the acquisition of appropriate skills and knowledge.
Prescribing in personality disorder: patients’ perspectives on their encounters with GPs and psychiatrists
Authors: Patel Dipen , Konstantinidou Haroula
Published: September 2020

Objective

The purpose of this study was to explore the views of patients with personality disorder on their experiences of prescribing practices by general practitioners (GPs) and psychiatrists, and their expectations of primary and secondary mental health services.

Design

This was a qualitative study involving two focus groups. Discussion in the focus groups was recorded, transcribed verbatim and then analysed by a thematic analysis process to generate the key themes.

Setting

The study took place at a specialist outpatient personality disorder service in the UK.

Participants

A total of seven participants took part in the study. They were purposively sampled from an NHS specialist outpatient personality disorder service. All participants had a primary diagnosis of emotionally unstable personality disorder and their age ranged from 20 to 52 years.

Results

Five key themes emerged. Participants felt that medication has a powerful impact on their mind and body but expressed confusion and uncertainty on how it is affecting them. Participants had a need for a good relationship with their doctors (GPs or psychiatrists). They described a feeling of being dismissed and not believed, expressing a desire to confront the ‘powerful’ position of their doctors by showing anger. The nature of the doctor-patient relationship was seen to moderate positively or negatively the experience of doctors’ prescribing. Finally, there were key expectations of the primary-secondary care interface, including continuity of care, diagnostic clarity and a desire for different healthcare professionals to communicate with one another.

Conclusion

The doctor-patient relationship is an important medium for providing validation and seeking negotiation of therapeutic treatment strategies in patients with personality disorder. Given that personality disorder is associated with high rates of physical and mental health comorbidity, it is therefore vital for clinical guidelines and training packages to take more account of the relational aspects of prescribing in consultations for this patient group with a view to improve outcomes.
Vascular protection and regenerative effects of intranasal DL-3-N-butylphthalide treatment after ischaemic stroke in mice
Authors: Qu Mengyao , Zhao Jingjie , Zhao Yingying , Sun Jinmei , Liu Liping , Wei Ling , Zhang Yongbo
Published: September 2020

Objective

To investigate the effects of DL-3-N-butylphthalide (NBP) via intranasal delivery after ischaemic stroke in mice.

Methods

C57BL/6 mice were divided into three groups: sham, stroke with vehicle and stroke with NBP treatment. Ischaemic stroke was induced by permanent ligation of right middle cerebral artery with 7 min common carotid artery occlusion. NBP (100 mg/kg) or vehicle was intranasally administered at 1 hour after stroke and repeated once a day until sacrifice. Bromodeoxyuridine (BrdU) (50 mg/kg/day) was given from the third day until sacrifice. Sensorimotor function was tested during 1–21 days after stroke. Local cerebral blood flow in the ischaemic and peri-infarct regions was measured using laser Doppler flowmetry before, during and 3 days after ischaemia. Expressions of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase as well as regenerative marker BrdU in the peri-infarct region were analysed by western blotting and immunohistochemical methods.

Results

Compared with the vehicle group, NBP treatment significantly increased the VEGF expression in the poststroke brain. Stroke mice that received NBP showed significantly less vascular damage after stroke and more new neurons and blood vessels in the peri-infarct region at 21 days after stroke. In the adhesive removal test, the sensorimotor function of stroke mice treated with NBP performed significantly better at 1, 3 and 7 days after stroke compared with vehicle controls.

Conclusion

Daily intranasal NBP treatment provides protective and neurogenic/angiogenic effects in the poststroke brain, accompanied with functional improvements after a focal ischaemic stroke in mice.
Traumatic tracheostomy in a dog
Authors: Papageorgiou Virginia , Chatzimisios Kyriakos , Angelou Vasileia , Kazakos George , Papazoglou Lysimachos G
Published: September 2020

A two‐year‐old, mixed breed, female intact dog was referred for further investigation and treatment of a chronic non‐healing wound in the cervical region. The wound was secondary to a circumferential wire collar injury. Clinical examination revealed a cervical tracheal transection resembling a traumatic tracheostomy. The dog underwent closure of the tracheostomy by tracheal resection and anastomosis in a split‐cartilage technique. No serious postsurgical complications were observed apart from short‐term coughing. Eighteen months after surgery, the dog was reported to be free of clinical signs of respiratory disease.