bluuebunny/crossref_metadata_2025 huggingface dataset:
Determination of nasal carriage and skin colonization, antimicrobial susceptibility and genetic relatedness of Staphylococcus aureus isolated from patients with atopic dermatitis in Szczecin, Poland
Authors: Masiuk Helena , Wcisłek Aleksandra , Jursa-Kulesza Joanna
Published: July 2021

Background

Atopic dermatitis (AD) is one of the most frequent chronic and inflammatory skin condition. AD is characterized by damaged epidermal barrier, xerosis and pruritus of eczematous skin lesions which tend to flare. The duration and frequency of exacerbation of AD symptoms markedly affects the quality of patient life. AD results from the interplay between host genetics, immunity, and environmental factors, however the detailed pathogenesis of this disease is still not entirely cleared. Furthermore, disturbances of the skin microbiota and skin functional impairment predispose to secondary skin infections. Staphylococcus aureus colonizes skin and mucous membranes of 20 to 80% of healthy individuals and of 90% of patients with AD in whom this bacterium is accounted as an important AD exacerbating factor. It is also proven, that S. aureus nasal carriage significantly increases the risk for self-transmission and endogenous infection. In the current study the presence of S. aureus either in nasal vestibule and on lesioned skin of 64 patients with AD enrolled in 10-year autovaccination program was determined. The genetic relatedness of 86 S. aureus isolated from patients nose and skin using Pulsed Field Gel Electrophoresis (PFGE) and antimicrobial susceptibility of all strains to methicillin, erythromycin, clindamycin, mupirocin, gentamicin, amikacin, tetracycline, chloramphenicol and cotrimoxazole was also evaluated.

Results

In total 23 PFGE genotypes and 24 unique patterns were distinguished. 34 patients were S. aureus nasal carriers. Simultaneous presence of S. aureus in nose and on affected skin was found in 16 carriers colonized by indistinguishable or potentially related S. aureus vs 2 carriers colonized with non-related S. aureus in nasal vestibule and on skin.

4 isolates were methicillin resistant (MRSA) among which 3 showed constitutive MLSB resistance phenotype and remaining one was resistant to tetracycline and chloramphenicol.

In 4 isolates inducible MLSB resistance phenotype was found, one of them was additionally resistant to tetracycline. 7 S. aureus were mupirocin resistant among them 3 - isolated from one patient, were resistant simultaneously to tetracyclines and chloramphenicol. 7 strains demonstrated resistance to chloramphenicol and susceptibility to all tested antimicrobial agents. The susceptibility to gentamicin, amikacin and cotrimoxazole among all examined S. aureus was confirmed.

Conclusion

The obtained results indicated non-clonal structure of S. aureus circulating in AD patients. PFGE results showed the clonal-structure of vast majority of S. aureus isolated from nose and skin from nasal carriers what may prove the autoinfection in these patients. All examined patients the moderate or strong severity of AD was reported. Susceptibility to most antibiotics among isolated strains was also observed.
A prospective observational study of community acquired pneumonia in Kenya: the role of viral pathogens
Authors: Nambafu Jamila , Achakolong Mary , Mwendwa Fridah , Bwika Jumaa , Riunga Felix , Gitau Samuel , Patel Hanika , Adam Rodney D.
Published: July 2021

Background

Lower respiratory tract infections continue to contribute significantly to morbidity and mortality across all age groups globally. In sub-Saharan Africa, many studies of community acquired pneumonia in adults have focused on HIV-infected patients and little attention has been given to risk factors and etiologic agents in an urban area with a more moderate HIV prevalence.

Methods

We prospectively enrolled 77 patients admitted to a 280 bed teaching hospital in Kenya with radiographically confirmed community acquired pneumonia from May 2019 to March 2020. The patients were followed for etiology and clinical outcomes. Viral PCR testing was performed using the FTD respiratory pathogen-21 multiplex kit on nasopharyngeal or lower respiratory samples. Additional microbiologic workup was performed as determined by the treating physicians.

Results

A potential etiologic agent(s) was identified in 57% including 43% viral, 5% combined viral and bacterial, 5% bacterial and 4% Pneumocystis. The most common etiologic agent was Influenza A which was associated with severe clinical disease. The most common underlying conditions were cardiovascular disease, diabetes and lung disease, while HIV infection was identified in only 13% of patients. Critical care admission was required for 24, and 31% had acute kidney injury, sometimes in combination with acute respiratory distress or sepsis.

Conclusion

Viruses, especially influenza, were commonly found in patients with CAP. In contrast to other studies from sub-Saharan Africa, the underlying conditions were similar to those reported in high resource areas and point to the growing concern of the double burden of infectious and noncommunicable diseases.
Preliminary study on the application of renal ultrasonography radiomics in the classification of glomerulopathy
Authors: Zhang Lijie , Chen Zhengguang , Feng Lei , Guo Liwei , Liu Dong , Hai Jinjin , Qiao Kai , Chen Jian , Yan Bin , Cheng Genyang
Published: July 2021

Background

The aim of this study was to investigate the potential use of renal ultrasonography radiomics features in the histologic classification of glomerulopathy.

Methods

A total of 623 renal ultrasound images from 46 membranous nephropathy (MN) and 22 IgA nephropathy patients were collected. The cases and images were divided into a training group (51 cases with 470 images) and a test group (17 cases with 153 images). A total of 180 dimensional features were designed and extracted from the renal parenchyma in the ultrasound images. Least absolute shrinkage and selection operator (LASSO) logistic regression was then applied to these normalized radiomics features to select the features with the highest correlations. Four machine learning classifiers, including logistic regression, a support vector machine (SVM), a random forest, and a K-nearest neighbour classifier, were deployed for the classification of MN and IgA nephropathy. Subsequently, the results were assessed according to accuracy and receiver operating characteristic (ROC) curves.

Results

Patients with MN were older than patients with IgA nephropathy. MN primarily manifested in patients as nephrotic syndrome, whereas IgA nephropathy presented mainly as nephritic syndrome. Analysis of the classification performance of the four classifiers for IgA nephropathy and MN revealed that the random forest achieved the highest area under the ROC curve (AUC) (0.7639) and the highest specificity (0.8750). However, logistic regression attained the highest accuracy (0.7647) and the highest sensitivity (0.8889).

Conclusions

Quantitative radiomics imaging features extracted from digital renal ultrasound are fully capable of distinguishing IgA nephropathy from MN. Radiomics analysis, a non-invasive method, is helpful for histological classification of glomerulopathy.
Associations between insulin resistance and adverse pregnancy outcomes in women with gestational diabetes mellitus: a retrospective study
Authors: Lin Jing , Jin Hua , Chen Lei
Published: July 2021

Background

This study aimed to explore the relationship between insulin resistance (IR) and adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM), and to determine the risk factors for IR in women with GDM.

Methods

This study employed a retrospective survey of 710 women diagnosed with GDM. Serum lipids, fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), and serum protein were measured in the first trimester (6–12 weeks), and OGTT and fasting insulin tests were performed in the second trimester (24–28 weeks). These results were then used to evaluate IR by homeostasis model assessment (HOMA). When HOMA-IR ≥ 2.0, IR was diagnosed. The relationship between HOMA-IR and adverse pregnancy outcomes was analyzed by a logistic regression model, and multiple stepwise regression was used to analyze the risk factors of IR.

Results

IR significantly increasd the risk of the hypertensive disorders of pregnancy and large for gestational age (LGA) (OR = 5.31,95%CI:1.87,15.10;OR = 1.65,95%CI:1.10, 2.48, respectively) in women with GDM, but not for cesarean section, premature delivery, premature rupture of membranes, postpartum hemorrhage, macrosomia and SGA. Compared to normal groups, greater body mass index (BMI) before pregnancy category (overweight or obesity group) were associated with higher risk of IR in the second trimester, theOR (95% CI)were 4.09 (2.65, 6.30) and 6.52 (2.99, 14.20). And higher level of FPG (OR = 1.63,95%CI:1.11, 2.40), TG (OR = 1.32,95%CI:1.08, 1.63) and weight gain before diagnosis of GDM (OR = 1.08,95%CI:1.02, 1.15) were also associated with higher risk of IR in the second trimester in women with GDM, while age (OR = 0.94,95%CI: 0.90, 0.98)was the weak protective factor for IR.

Conclusion

GDM with IR in the second trimester increased adverse pregnancy outcomes, especially the risk of hypertensive disorders of pregnancy and LGA. In addition, FPG, HbA1c, and TG in early pregnancy, pre-pregnant BMI and weight gain before diagnosis of GDM were all independent risk factors for IR.
Seven key hub genes identified by gene co-expression network in cutaneous squamous cell carcinoma
Authors: Chen Huizhen , Yang Jiankang , Wu Wenjuan
Published: July 2021

Background

Cutaneous squamous cell carcinoma (cSCC) often follows actinic keratosis (AK) and is the second most common skin cancer worldwide. To reduce metastasis risk, it is important to diagnose and treat cSCC early. This study aimed to identify hub genes associated with cSCC and AK.

Methods

This study used three datasets GSE45216, GSE98774, and GSE108008. We combined samples from the GSE45216 and GSE98774 datasets into the new dataset GSE45216–98774. We applied a weighted gene co-expression network analysis (WGCNA) to investigate key modules and hub genes associated with cSCC and AK. We considered the hub genes found in both the GSE45216–98774 and GSE108008 datasets as validated hub genes. We tested whether the expression of hub genes could predict patient survival outcomes in other cancers using TCGA pan-cancer data.

Results

We identified modules most relevant to cSCC and AK. Additionally, we identified and validated seven hub genes of cSCC: GATM, ARHGEF26, PTHLH, MMP1, POU2F3, MMP10 and GATA3. We did not find validated hub genes for AK. Each hub gene was significantly associated with the survival of various cancer types. Only GATA3 was significantly associated with melanoma survival.

Conclusions

We applied WGCNA to find seven hub genes that play important roles in cSCC tumorigenesis. These results provide new insights that help explain the pathogenesis of cSCC. These hub genes may become biomarkers or therapeutic targets for accurate diagnosis and treatment of cSCC in the future.
TGF-β regulates nerve growth factor expression in a mouse intervertebral disc injury model
Authors: Yokozeki Yuji , Uchida Kentaro , Kawakubo Ayumu , Nakawaki Mitsufumi , Okubo Tadashi , Miyagi Masayuki , Inoue Gen , Itakura Makoto , Sekiguchi Hiroyuki , Takaso Masashi
Published: July 2021

Background

Intervertebral disc (IVD) degeneration is a major cause of low back pain (LBP). Following disc injury, nerve growth factor (NGF) concentrations rise in IVDs, and anti-NGF therapy has been shown to attenuate LBP in humans. Increased levels of tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β) in degenerative IVDs and in in vitro studies suggest that these factors promote NGF production. However, whether these factors regulate NGF in vivo remains unclear. Thus, we studied NGF regulation in a mouse model of IVD injury.

Methods

After inducing IVD injury, we examined mRNA levels of Tnfa, Tgfb, and Ngf in IVDs from control and IVD-injured mice across 7 days. To do this, we used magnetic cell separation to isolate CD11b ( +) (macrophage-rich) and CD11b (-) (IVD cell-rich) cell fractions from injured IVDs. To study the effect of TNF-α on Ngf expression, we examined Ngf expression in injured IVDs from C57BL/6 J and Tnfa-knockout (KO) mice (C57BL/6 J background). To study the effect of TGF-β on Ngf expression, C57/BL6J mice were given an intraperitoneal injection of either the TGF-β inhibitor SB431542 or DMSO solution (vehicle) one and two days before harvesting IVDs.

Results

mRNA expression of Tnfa, Tgfb, and Ngf was significantly increased in injured IVDs. Tnfa was predominantly expressed in the CD11b ( +) fraction, and Tgfb in the CD11b (-) fraction. Ngf expression was comparable between CD11b ( +) and CD11b (-) fractions, and between wild-type and Tnfa-KO mice at post-injury day (PID) 1, 3, and 7. SB431542 suppressed TGF-β-mediated Ngf expression and NGF production in vitro. Further, administration of SB431542 significantly reduced Ngf expression in IVDs such that levels were below those observed in vehicle-treated animals at PID3 and PID7.

Conclusion

A TGF-β inhibitor reduced Ngf expression in a mouse model of IVD injury, suggesting that TGF-β may regulate NGF expression in vivo.
Predicting dental caries increment using salivary biomarkers in a remote Indigenous Australian child population
Authors: Fernando Surani , Tadakamadla Santosh , Kroon Jeroen , Lalloo Ratilal , Johnson Newell W.
Published: July 2021

Background

The burden of childhood dental caries amongst Indigenous Australians is higher than in other Australians. Because of differences in lifestyle and the evolutionary history of the oral microbiota, associated risk indicators may differ. Here, we evaluate associations between caries increment, salivary biomarkers and baseline caries among children aged 5–17 years residing in a remote rural Indigenous community.

Methods

This study was part of a trial assessing cost-effectiveness of an intervention to prevent dental caries among children. Baseline epidemiology and application of topical caries-preventive measures was conducted in 2015, followed-up in 2016 and 2017. Children who did not consent or failed to attend the prevention visits but did attend for follow-up epidemiology constituted a natural comparison group for evaluating the intervention. Saliva flow, pH, buffering and bacterial loads were measured at all visits. Caries was scored by the International Caries Detection and Assessment system. Outcome was caries increment. Explanatory variables were sex, being in experimental or comparison group, baseline caries, saliva flowrate and buffering, pH, and salivary loads of mutans streptococci (MS), Lactobacilli (LB), and yeast. Chi Square tests compared caries incidence in relation to explanatory variables and Generalised Linear Models explored associations between explanatory and outcome variables.

Results

Of 408 participants at baseline, only 208 presented at 2-year follow-up. Of caries-free children at baseline, significantly fewer had incipient (p = 0.01) and advanced (p = 0.04) caries after two years. Children in the experimental group experienced fewer tooth surfaces with advanced caries (p = 0.02) than comparison children. Having caries at baseline (p = 0.02) and low salivary flow-rates (p < 0.001) saw a significant increase in advanced caries after two years. Children with high salivary loads of MS (p = 0.03) and LB (p = 0.004) experienced more advanced carious surfaces. Multivariable analysis revealed 58% reduction (p = 0.001) in advanced caries among children with high salivary flow rates. Caries increment was 61% (p = 0.03) more for incipient and 121% (p = 0.007) more for advanced caries among children who harboured higher loads of MS.

Conclusion

As with other ethnicities, children with low salivary flow and those with high MS had higher incipient and advanced caries increments after two years. Such risk assessments facilitate targeted preventive interventions for such communities.

Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR), No: ACTRN12615000693527: 3 July 2015.
Teaching Minimally Invasive Interventions in Paediatric Dentistry: A Cross-Sectional Survey of Dental Schools in Iran
Authors: Moradi S. , Sabbagh S. , Timms L. , Ravaghi V.
Published: July 2021

Background

Dental caries is a significant public health problem in Iran. Teaching  minimally invasive interventions in paediatric dentistry may facilitate the provision of treatment for untreated dental caries in children. We evaluated the teaching of such interventions in both undergraduate dental curriculum and Paediatric Dentistry Specialty Training Programme (PDSTP) in Iran.

Methods

This was a cross-sectional questionnaire-based survey. Participants in this study were the directors of 40 undergraduate programmes and 15 PDSTPs in all Iranian dental schools (response rate = 100%). Descriptive statistics were reported.

Results

The most commonly taught methods were preventive fissure sealant and preventive resin restoration (PRR), which were taught ‘both didactically and clinically’ in all undergraduate dental programmes. The least commonly taught methods were silver diamine fluoride (SDF), the Hall technique and resin infiltration, which were taught ‘both didactically and clinically’ in less than 5% of dental schools. The same three methods were the least commonly approaches taught in PDSTP, further, they were less often perceived to be ‘essential’.

Conclusions

There was a notable variation in the teaching of the management of dental caries in Iran’s dental education. Some minimally invasive approaches including SDF, the Hall technique and resin infiltration are not being commonly taught in Iranian dental schools despite the evidence base for these techniques.
Gendered experiences of providing informal care for older people: a systematic review and thematic synthesis
Authors: Zygouri Ioanna , Cowdell Fiona , Ploumis Avraam , Gouva Mary , Mantzoukas Stefanos
Published: July 2021

Background and purpose

The caregiving’s impact on informal carers’ quality of life and gender-based stereotypes make older individuals’ informal care a complex process for which our knowledge is still limited. The purpose of this review is to identify how gender relates to informal carers’ experiences of providing care for people aged 60 years and over with mental and physical health needs by synthesising the available empirical data published between 2000 to 2020.

Design and methods

The systematic method for reviewing and synthesising qualitative data was performed using the PRISMA checklist and ENTREQ statement. The CASP tool was used to examine the quality of the included papers. Thematic synthesis was used as the methodological framework.

Results

This review produced two analytical themes, the impact of gender on the caregivers’ labour and negotiating gender identity with self, society, and cultural norms. While informal caregivers share motivators, a linkage between traditional gender stereotypes impacts caregiving burden and coping strategies. Informal carers’ experiences entail a constant pursuit of self-agency after acquiring the caregiver role. Cultural values and their intersection with gender appear to influence caregivers’ healthy adjustment into their new caregiving identities. The flexibility to move beyond gender boundaries could mediate caregivers’ negotiations between self and society on developing their new caregiving identity. Providing intensive informal primary care to older people affects both men’s and women’s mental and physical health. Gender ideals of the feminine nurturing role further disadvantage women as they determine the caregiving arrangements, the strategies and resources to sustain the caring burden, and the adaptability to experience their new caregiving role positively. Men appear more flexible to debate their hegemonic masculinity and defend their existence in the caregiving role.

Conclusion and implications

Transgressing gender lines and expanding gender possibilities can ease the caregiving burden and strengthen caregivers coping potentials. Health professionals can empower informal careers to challenge gender binaries and expand gender possibilities by intentionally injecting the language of diversity in caring information and caring processes. The review findings outline a path for research on gender identity development in older people’s care.
A cost-consequence analysis of normalised advance care planning practices among people with chronic diseases in hospital and community settings
Authors: Jeong Sarah , Ohr Se Ok , Cleasby Peter , Barrett Tomiko , Davey Ryan , Deeming Simon
Published: July 2021

Background

A growing body of international literature concurs that comprehensive and complex Advance Care Planning (ACP) programs involving specially qualified or trained healthcare professionals are effective in increasing documentation of Advance Care Directives (ACDs), improving compliance with patients’ wishes and satisfaction with care, and quality of care for patients and their families. Economic analyses of ACDs and ACP have been more sporadic and inconclusive. This study aimed to contribute to the evidence on resource use associated with implementation of ACP and to inform key decision-makers of the resource implications through the conduct of a cost-consequence analysis of the Normalised Advance Care Planning (NACP) trial.

Methods

The outcomes for the economic evaluation included the number of completed “legally binding” ACDs and the number of completed Conversation Cards (CC). The cost analysis assessed the incremental difference in resource utilisation between Usual Practice and the Intervention. Costs have been categorised into: 1) Contract staff costs; 2) Costs associated with the development of the intervention; 3) Implementation costs; 4) Intervention (delivery) costs; and 5) Research costs.

Results

The cost incurred for each completed ACD was A$13,980 in the hospital setting and A$1248 in the community setting. The cost incurred for each completed Conversation Card was A$7528 in the hospital setting and A$910 in the community setting.

Conclusions

The cost-consequence analysis does not support generalisation of the specified intervention within the hospital setting. The trial realised an estimated incremental cost per completed ACD of $1248, within the community setting. This estimate provides an additional benchmark against which decision-makers can assess the value of either 1) this approach towards the realisation of additional completed ACDs; and/or 2) the value of ACP and ACDs more broadly, when this estimate is positioned within the potential health outcomes and downstream health service implications that may arise for people with or without a completed ACD.

Trial registration

The study was retrospectively registered with the Australian New Zealand Clinical Trials Registry (Trial ID: ACTRN12618001627246). The URL of the trial registry record.
Health system strengthening in fragile and conflict-affected states: a call to action
Authors: Landry Michel D. , Giebel Clarissa , Cryer Tillie L.
Published: July 2021

Although the speed of global development has been impressive, not all countries have developed at the same pace. The World Bank Group (WBG) report that Fragile and Conflict-Affected States (FCAS) are those countries that have lower health and development outcomes, and risk not being able to achieve Sustainable Development Goals (SDGs) in the next few years. Health systems play an important role in building capacity and infrastructure that can lead towards fulfilling the SDGs. In this editorial, we set the context, and launch a call to action, for a BMC Health Service Research Collection titled “Health services and systems in fragile and conflict-affected regions”.
Single-cell alternative polyadenylation analysis delineates GABAergic neuron types
Authors: Yang Yang , Paul Anirban , Bach Thao Nguyen , Huang Z. Josh , Zhang Michael Q.
Published: July 2021

Background

Alternative polyadenylation (APA) is emerging as an important mechanism in the post-transcriptional regulation of gene expression across eukaryotic species. Recent studies have shown that APA plays key roles in biological processes, such as cell proliferation and differentiation. Single-cell RNA-seq technologies are widely used in gene expression heterogeneity studies; however, systematic studies of APA at the single-cell level are still lacking.

Results

Here, we described a novel computational framework, SAPAS, that utilizes 3′-tag-based scRNA-seq data to identify novel poly(A) sites and quantify APA at the single-cell level. Applying SAPAS to the scRNA-seq data of phenotype characterized GABAergic interneurons, we identified cell type-specific APA events for different GABAergic neuron types. Genes with cell type-specific APA events are enriched for synaptic architecture and communications. In further, we observed a strong enrichment of heritability for several psychiatric disorders and brain traits in altered 3′ UTRs and coding sequences of cell type-specific APA events. Finally, by exploring the modalities of APA, we discovered that the bimodal APA pattern ofPak3could classify chandelier cells into different subpopulations that are from different laminar positions.

Conclusions

We established a method to characterize APA at the single-cell level. When applied to a scRNA-seq dataset of GABAergic interneurons, the single-cell APA analysis not only identified cell type-specific APA events but also revealed that the modality of APA could classify cell subpopulations. Thus, SAPAS will expand our understanding of cellular heterogeneity.
Proteomic analysis revealed the roles of YRR1 deletion in enhancing the vanillin resistance of Saccharomyces cerevisiae
Authors: Cao Wenyan , Zhao Weiquan , Yang Bolun , Wang Xinning , Shen Yu , Wei Tiandi , Qin Wensheng , Li Zailu , Bao Xiaoming
Published: July 2021

Background

Vanillin is one of the important phenolic inhibitors inSaccharomyces cerevisiaefor bioconversion of lignocellulosic materials and has been reported to inhibit the translation process in cells. In our previous studies, it was confirmed that the deletion of the transcription factor geneYRR1enhanced vanillin resistance by promoting some translation-related processes at the transcription level. In this work, we investigated the effects of proteomic changes upon induction of vanillin stress and deletion ofYRR1to provide unique perspectives from a transcriptome analysis for comprehending the mechanisms ofYRR1deletion in the protective response of yeast to vanillin.

Results

In wild-type cells, vanillin reduced two dozens of ribosomal proteins contents while upregulated proteins involved in glycolysis, oxidative phosphorylation, and the pentose phosphate pathway in cells. The ratios of NADPH/NADP+and NADH/NAD+were increased when cells responded to vanillin stress. The differentially expressed proteins perturbed byYRR1deletion were much more abundant than and showed no overlaps with transcriptome changes, indicating that Yrr1 affects the synthesis of certain proteins. Forty-eight of 112 upregulated proteins were involved in the stress response, translational and transcriptional regulation.YRR1deletion increased the expression ofHAA1-encoding transcriptional activator,TMA17-encoding proteasome assembly chaperone andMBF1-encoding coactivator at the protein level, as confirmed by ELISA. Cultivation data showed that the overexpression ofHAA1andTMA17enhanced resistance to vanillin inS. cerevisiae.

Conclusions

Cells conserve energy by decreasing the content of ribosomal proteins, producing more energy and NAD(P)H for survival in response to vanillin stress. Yrr1 improved vanillin resistance by increasing the protein quantities of Haa1, Tma17 and Mbf1. These results showed the response ofS. cerevisiaeto vanillin and howYRR1deletion increases vanillin resistance at the protein level. These findings may advance our knowledge of howYRR1deletion protects yeast from vanillin stress and offer novel targets for genetic engineering of designing inhibitor-resistant ethanologenic yeast strains.
The feasibility, reliability, and incremental value of two-dimensional speckle-tracking for the detection of significant coronary stenosis after treadmill stress echocardiography
Authors: d’Entremont Marc-André , Fortin Gabriel , Huynh Thao , Croteau Étienne , Farand Paul , Lemaire-Paquette Samuel , Brochu Marie-Claude , Do Doan Hoa , Lepage Serge , Mampuya Warner Mbuila , Couture Étienne L. , Nguyen Michel , Essadiqi Btissama
Published: July 2021

Background

Two-dimensional speckle-tracking echocardiography (STE) may help detect coronary artery disease (CAD) when combined with dobutamine stress echocardiography. However, few studies have explored STE with exercise stress echocardiography (ESE). We aimed to evaluate the feasibility, reliability, and incremental value of STE combined with treadmill ESE compared to treadmill ESE alone to detect CAD.

Methods

We conducted a case–control study of all consecutive patients with abnormal ESE in 2018–2020 who subsequently underwent coronary angiography within a six-month interval. We 1:1 propensity score-matched these patients to those with a normal ESE. Two blinded operators generated a 17-segment bull's-eye map of longitudinal strain (LS). We utilized the mean differences between stress and baseline LS values in segments 13–17, segment 17, and segments 15–16 to create receiver operator curves for the overall examination, the left anterior descending artery (LAD), and the non-LAD territories, respectively.

Results

We excluded 61 STEs from 201 (30.3%) eligible ESEs; 47 (23.4%) because of suboptimal image quality and 14 (7.0%) because of excessive heart rate variability precluding the calculation of a bull's-eye map. After matching, a total of 102 patients were included (51 patients in each group). In the group with abnormal ESE patients (mean age 66.4 years, 39.2% female), 64.7% had significant CAD (> 70% stenosis) at coronary angiogram. In the group with normal ESE patients (mean age 65.1 years, 35.3% female), 3.9% were diagnosed with a new significant coronary stenosis within one year. The intra-class correlation for global LS was 0.87 at rest and 0.92 at stress, and 0.84 at rest, and 0.89 at stress for the apical segments. The diagnostic accuracy of combining ESE and STE was superior to visual assessment alone for the overall examination (area under the curve (AUC) = 0.89 vs. 0.84, p = 0.025), the non-LAD territory (AUC = 0.83 vs. 0.70, p = 0.006), but not the LAD territory (AUC = 0.79 vs. 0.73, p = 0.11).

Conclusions

Two-dimensional speckle-tracking combined with treadmill ESE is relatively feasible, reliable, and may provide incremental diagnostic value for the detection and localization of significant CAD.
Variations in regulations to control standards for training and licensing of physicians: a multi-country comparison
Authors: Aftab Wafa , Khan Mishal , Rego Sonia , Chavan Nishant , Rahman-Shepherd Afifah , Sharma Isha , Wu Shishi , Zeinali Zahra , Hasan Rumina , Siddiqi Sameen
Published: July 2021

Background

To strengthen health systems, the shortage of physicians globally needs to be addressed. However, efforts to increase the numbers of physicians must be balanced with controls on medical education imparted and the professionalism of doctors licensed to practise medicine.

Methods

We conducted a multi-country comparison of mandatory regulations and voluntary guidelines to control standards for medical education, clinical training, licensing and re-licensing of doctors. We purposively selected seven case-study countries with differing health systems and income levels: Canada, China, India, Iran, Pakistan, UK and USA. Using an analytical framework to assess regulations at four sequential stages of the medical education to relicensing pathway, we extracted information from: systematically collected scientific and grey literature and online news articles, websites of regulatory bodies in study countries, and standardised input from researchers and medical professionals familiar with rules in the study countries.

Results

The strictest controls we identified to reduce variations in medical training, licensing and re-licensing of doctors between different medical colleges, and across different regions within a country, include: medical education delivery restricted to public sector institutions; uniform, national examinations for medical college admission and licensing; and standardised national requirements for relicensing linked to demonstration of competence. However, countries analysed used different combinations of controls, balancing the strictness of controls across the four stages.

Conclusions

While there is no gold standard model for medical education and practise regulation, examining the combinations of controls used in different countries enables identification of innovations and regulatory approaches to address specific contextual challenges, such as decentralisation of regulations to sub-national bodies or privatisation of medical education. Looking at the full continuum from medical education to licensing is valuable to understand how countries balance the strictness of controls at different stages. Further research is needed to understand how regulating authorities, policy-makers and medical associations can find the right balance of standardisation and context-based flexibility to produce well-rounded physicians.
Using food network analysis to understand meal patterns in pregnant women with high and low diet quality
Authors: Schwedhelm Carolina , Lipsky Leah M. , Shearrer Grace E. , Betts Grace M. , Liu Aiyi , Iqbal Khalid , Faith Myles S. , Nansel Tonja R.
Published: July 2021

Background

Little is known about how meal-specific food intake contributes to overall diet quality during pregnancy, which is related to numerous maternal and child health outcomes. Food networks are probabilistic graphs using partial correlations to identify relationships among food groups in dietary intake data, and can be analyzed at the meal level. This study investigated food networks across meals in pregnant women and explored differences by overall diet quality classification.

Methods

Women were asked to complete three 24-h dietary recalls throughout pregnancy (n = 365) within a prospective cohort study in the US. Pregnancy diet quality was evaluated using the Healthy Eating Index-2015 (HEI, range 0-100), calculated across pregnancy. Networks from 40 food groups were derived for women in the highest and lowest HEI tertiles at each participant-labeled meal (i.e., breakfast, lunch, dinner, snacks) using Gaussian graphical models. Network composition was qualitatively compared across meals and between HEI tertiles.

Results

In both HEI tertiles, breakfast food combinations comprised ready-to-eat cereals with milk, quick breads with sweets (e.g., pancakes with syrup), and bread with cheese and meat. Vegetables were consumed at breakfast among women in the high HEI tertile only. Combinations at lunch and dinner were more varied, including vegetables with oils (e.g., salads) in the high tertile and sugary foods with nuts, fruits, and milk in the low tertile at lunch; and cooked grains with fats (e.g., pasta with oil) in the high tertile and potatoes with vegetables and meat in the low tertile at dinner. Fried potatoes, sugar-sweetened beverages, and sandwiches were consumed together at all main meals in the low tertile only. Foods were consumed individually at snacks in both tertiles; the most commonly consumed food were fruits in the high HEI tertile and cakes & cookies in the low tertile.

Conclusions

In this cohort of pregnant women, food network analysis indicated that food combinations differed by meal and between HEI tertiles. Meal-specific patterns that differed between diet quality tertiles suggest potential targets to improve food choices at meals; the impact of meal-based dietary modifications on intake of correlated foods and on overall diet quality should be investigated in simulations and intervention studies.

Trial registration

PEAS was registered with number NCT02217462 in Clinicaltrials.gov on August 13, 2014.
Keep out! SARS-CoV-2 entry inhibitors: their role and utility as COVID-19 therapeutics
Authors: Chitsike Lennox , Duerksen-Hughes Penelope
Published: July 2021

The COVID-19 pandemic has put healthcare infrastructures and our social and economic lives under unprecedented strain. Effective solutions are needed to end the pandemic while significantly lessening its further impact on mortality and social and economic life. Effective and widely-available vaccines have appropriately long been seen as the best way to end the pandemic. Indeed, the current availability of several effective vaccines are already making a significant progress towards achieving that goal. Nevertheless, concerns have risen due to new SARS-CoV-2 variants that harbor mutations against which current vaccines are less effective. Furthermore, some individuals are unwilling or unable to take the vaccine. As health officials across the globe scramble to vaccinate their populations to reach herd immunity, the challenges noted above indicate that COVID-19 therapeutics are still needed to work alongside the vaccines. Here we describe the impact that neutralizing antibodies have had on those with early or mild COVID-19, and what their approval for early management of COVID-19 means for other viral entry inhibitors that have a similar mechanism of action. Importantly, we also highlight studies that show that therapeutic strategies involving various viral entry inhibitors such as multivalent antibodies, recombinant ACE2 and miniproteins can be effective not only for pre-exposure prophylaxis, but also in protecting against SARS-CoV-2 antigenic drift and future zoonotic sarbecoviruses.
Antenatal breastmilk expression for women with diabetes in pregnancy - a feasibility study
Authors: Johnsen Maren , Klingenberg Claus , Brand Meta , Revhaug Arthur , Andreassen Gunnbjørg
Published: July 2021

Background

Mothers with diabetes are less likely to achieve successful breastfeeding. Antenatal breastmilk expression (ABE) may facilitate earlier breastfeeding, but feasibility of introducing ABE and its acceptance among Scandinavian women have previously not been investigated.

Methods

This observational trial was conducted between the 1 January 2019 and the 12 March 2020 in Tromsø, Norway. We aimed to determine the feasibility of ABE in terms of practicality and acceptability among women with medically (metformin or insulin) treated diabetes. Women were invited to participate during antenatal visits from 32 weeks gestation. Participants received instruction and started ABE from gestation week 37 + 0. Participants, and their infants, were followed until 6–8 weeks after birth. We collected data on breastfeeding rates, infant hypoglycemia, transfer to the neonatal unit, and the women’s overall experience and satisfaction with antenatal breastmilk expression.

Results

Twenty-eight of 34 (82%) invited women consented to participate. All started ABE from week 37 + 0, and continued until hospital admission. No women reported any discomfort or side effects. Labor was induced at 38 weeks gestation. Twenty-four women brought harvested colostrum to the maternity ward, which was given to their infants during the first 24 h of life. Breastfeeding rates at discharge were 24/28 (86%) and 21/27 (78%) at 6–8 weeks after delivery. Seven (25%) infants were transferred to the neonatal unit; four because of hypoglycemia. Maternal satisfaction assessed 6–8 weeks after delivery revealed that all participants felt positive about the ABE, but one woman would not recommend it to other pregnant women.

Conclusions

Implementing a structured ABE guideline for women with medically treated diabetes was feasible. The intervention was associated with high level of satisfaction among study participants. No obvious side effects were observed, and breastfeeding rates at discharge and 6–8 weeks after delivery were higher than in comparable studies.

Trial registration

The study was registered at the research study registry at the University Hospital of North Norway (Nr 2018/7181).
Feasibility of Conebeam CT-based online adaptive radiotherapy for neoadjuvant treatment of rectal cancer
Authors: de Jong Rianne , Visser Jorrit , van Wieringen Niek , Wiersma Jan , Geijsen Debby , Bel Arjan
Published: July 2021

Background

Online adaptive radiotherapy has the potential to reduce toxicity for patients treated for rectal cancer because smaller planning target volumes (PTV) margins around the entire clinical target volume (CTV) are required. The aim of this study is to describe the first clinical experience of a Conebeam CT (CBCT)-based online adaptive workflow for rectal cancer, evaluating timing of different steps in the workflow, plan quality, target coverage and patient compliance.

Methods

Twelve consecutive patients eligible for 5 × 5 Gy pre-operative radiotherapy were treated on a ring-based linear accelerator with a multidisciplinary team present at the treatment machine for each fraction. The accelerator is operated using an integrated software platform for both treatment planning and delivery. In all directions for all CTVs a PTV margin of 5 mm was used, except for the cranial/caudal borders of the total CTV where a margin of 8 mm was applied. A reference plan was generated based on a single planning CT. After aligning the patient the online adaptive procedure started with acquisition of a CBCT. The planning CT scan was registered to the CBCT using deformable registration and a synthetic CT scan was generated. With the support of artificial intelligence, structure guided deformation and the synthetic CT scan contours were adapted by the system to match the anatomy on the CBCT. If necessary, these contours were adjusted before a new plan was generated. A second and third CBCT were acquired to validate the new plan with respect to CTV coverage just before and after treatment delivery, respectively. Treatment was delivered using volumetric modulated arc treatment (VMAT). All steps in this process were defined and timed.

Results

On average the timeslot needed at the treatment machine was 34 min. The process of acquiring a CBCT, evaluating and adjusting the contours, creating the new plan and verifying the CTV on the CBCT scan took on average 20 min. Including delivery and post treatment verification this was 26 min. Manual adjustments of the target volumes were necessary in 50% of fractions. Plan quality, target coverage and patient compliance were excellent.

Conclusions

First clinical experience with CBCT-based online adaptive radiotherapy shows it is feasible for rectal cancer.

Trial registration Medical Research Involving Human Subjects Act (WMO) does not apply to this study and was retrospectively approved by the Medical Ethics review Committee of the Academic Medical Center (W21_087 # 21.097; Amsterdam University Medical Centers, Location Academic Medical Center, Amsterdam, The Netherlands).
Transcriptomic profiling of high- and low-spiking regions reveals novel epileptogenic mechanisms in focal cortical dysplasia type II patients
Authors: Srivastava Arpna , Kumar Krishan , Banerjee Jyotirmoy , Tripathi Manjari , Dubey Vivek , Sharma Devina , Yadav Nitin , Sharma M. C. , Lalwani Sanjeev , Doddamani Ramesh , Chandra P. Sarat , Dixit Aparna Banerjee
Published: July 2021

Focal cortical dysplasia (FCD) is a malformation of the cerebral cortex with poorly-defined epileptogenic zones (EZs), and poor surgical outcome in FCD is associated with inaccurate localization of the EZ. Hence, identifying novel epileptogenic markers to aid in the localization of EZ in patients with FCD is very much needed. High-throughput gene expression studies of FCD samples have the potential to uncover molecular changes underlying the epileptogenic process and identify novel markers for delineating the EZ. For this purpose, we, for the first time performed RNA sequencing of surgically resected paired tissue samples obtained from electrocorticographically graded high (MAX) and low spiking (MIN) regions of FCD type II patients and autopsy controls. We identified significant changes in the MAX samples of the FCD type II patients when compared to non-epileptic controls, but not in the case of MIN samples. We found significant enrichment for myelination, oligodendrocyte development and differentiation, neuronal and axon ensheathment, phospholipid metabolism, cell adhesion and cytoskeleton, semaphorins, and ion channels in the MAX region. Through the integration of both MAX vs non-epileptic control and MAX vs MIN RNA sequencing (RNA Seq) data, PLP1, PLLP, UGT8, KLK6, SOX10, MOG, MAG, MOBP, ANLN, ERMN, SPP1, CLDN11, TNC, GPR37, SLC12A2, ABCA2, ABCA8, ASPA, P2RX7, CERS2, MAP4K4, TF, CTGF, Semaphorins, Opalin, FGFs, CALB2, and TNC were identified as potential key regulators of multiple pathways related to FCD type II pathology. We have identified novel epileptogenic marker elements that may contribute to epileptogenicity in patients with FCD and could be possible markers for the localization of EZ.
Challenges in the PREHOSPITAL emergency management of geriatric trauma patients – a scoping review
Authors: Eichinger Michael , Robb Henry Douglas Pow , Scurr Cosmo , Tucker Harriet , Heschl Stefan , Peck George
Published: July 2021

Background

Despite a widely acknowledged increase in older people presenting with traumatic injury in western populations there remains a lack of research into the optimal prehospital management of this vulnerable patient group. Research into this cohort faces many uniqu1e challenges, such as inconsistent definitions, variable physiology, non-linear presentation and multi-morbidity. This scoping review sought to summarise the main challenges in providing prehospital care to older trauma patients to improve the care for this vulnerable group.

Methods and findings

A scoping review was performed searching Google Scholar, PubMed and Medline from 2000 until 2020 for literature in English addressing the management of older trauma patients in both the prehospital arena and Emergency Department. A thematic analysis and narrative synthesis was conducted on the included 131 studies. Age-threshold was confirmed by a descriptive analysis from all included studies. The majority of the studies assessed triage and found that recognition and undertriage presented a significant challenge, with adverse effects on mortality. We identified six key challenges in the prehospital field that were summarised in this review.

Conclusions

Trauma in older people is common and challenges prehospital care providers in numerous ways that are difficult to address. Undertriage and the potential for age bias remain prevalent. In this Scoping Review, we identified and discussed six major challenges that are unique to the prehospital environment. More high-quality evidence is needed to investigate this issue further.