bluuebunny/crossref_metadata_2025 huggingface dataset:
GPVI expression is linked to platelet size, age, and reactivity
Authors: Veninga Alicia , Handtke Stefan , Aurich Konstanze , Tullemans Bibian M. E. , Brouns Sanne L. N. , Schwarz Silas L. , Heubel-Moenen Floor C. J. I. , Greinacher Andreas , Heemskerk Johan W. M. , van der Meijden Paola E. J. , Thiele Thomas
Published: May 2022

Platelets within one individual display heterogeneity in reactivity, size, age, and expression of surface receptors. To investigate the combined intraindividual contribution of platelet size, platelet age, and receptor expression levels on the reactivity of platelets, we studied fractions of large and small platelets from healthy donors separated by using differential centrifugation. Size-separated platelet fractions were perfused over a collagen-coated surface to assess thrombus formation. Multicolor flow cytometry was used to characterize resting and stimulated platelet subpopulations, and platelet age was determined based on RNA and HLA-I labeling. Signal transduction was analyzed by measuring consecutive phosphorylation of serine/threonine-protein kinase Akt. Compared with small platelets, large platelets adhered faster to collagen under flow and formed larger thrombi. Among the large platelets, a highly reactive juvenile platelet subpopulation was identified with high glycoprotein VI (GPVI) expression. Elevated GPVI expression correlated with high HLA-I expression, RNA content, and increased platelet reactivity. There was a stronger difference in Akt phosphorylation and activation upon collagen stimulation between juvenile and older platelets than between large and small platelets. GPVI expression and platelet reactivity decreased throughout platelet storage at 22°C and was better maintained throughout cold storage at 4°C. We further detected higher GPVI expression in platelets of patients with immune thrombocytopenia. Our findings show that high GPVI expression is a feature of highly reactive juvenile platelets, which are predominantly found among the large platelet population, explaining the better performance of large platelets during thrombus formation. These data are important for studies of thrombus formation, platelet storage, and immune thrombocytopenia.
Fibrin protofibril packing and clot stability are enhanced by extended knob-hole interactions and catch-slip bonds
Authors: Asquith Nathan L. , Duval Cédric , Zhmurov Artem , Baker Stephen R. , McPherson Helen R. , Domingues Marco M. , Connell Simon D. A. , Barsegov Valeri , Ariëns Robert A. S.
Published: May 2022

Fibrin polymerization involves thrombin-mediated exposure of knobs on one monomer that bind to holes available on another, leading to the formation of fibers. In silico evidence has suggested that the classical A:a knob-hole interaction is enhanced by surrounding residues not directly involved in the binding pocket of hole a, via noncovalent interactions with knob A. We assessed the importance of extended knob-hole interactions by performing biochemical, biophysical, and in silico modeling studies on recombinant human fibrinogen variants with mutations at residues responsible for the extended interactions. Three single fibrinogen variants, γD297N, γE323Q, and γK356Q, and a triple variant γDEK (γD297N/γE323Q/γK356Q) were produced in a CHO (Chinese Hamster Ovary) cell expression system. Longitudinal protofibril growth probed by atomic force microscopy was disrupted for γD297N and enhanced for the γK356Q mutation. Initial polymerization rates were reduced for all variants in turbidimetric studies. Laser scanning confocal microscopy showed that γDEK and γE323Q produced denser clots, whereas γD297N and γK356Q were similar to wild type. Scanning electron microscopy and light scattering studies showed that fiber thickness and protofibril packing of the fibers were reduced for all variants. Clot viscoelastic analysis showed that only γDEK was more readily deformable. In silico modeling suggested that most variants displayed only slip-bond dissociation kinetics compared with biphasic catch-slip kinetics characteristics of wild type. These data provide new evidence for the role of extended interactions in supporting the classical knob-hole bonds involving catch-slip behavior in fibrin formation, clot structure, and clot mechanics.
Application of Bayesian genomic prediction methods to genome-wide association analyses
Authors: Wolc Anna , Dekkers Jack C. M.
Published: May 2022

Background

Bayesian genomic prediction methods were developed to simultaneously fit all genotyped markers to a set of available phenotypes for prediction of breeding values for quantitative traits, allowing for differences in the genetic architecture (distribution of marker effects) of traits. These methods also provide a flexible and reliable framework for genome-wide association (GWA) studies. The objective here was to review developments in Bayesian hierarchical and variable selection models for GWA analyses.

Results

By fitting all genotyped markers simultaneously, Bayesian GWA methods implicitly account for population structure and the multiple-testing problem of classical single-marker GWA. Implemented using Markov chain Monte Carlo methods, Bayesian GWA methods allow for control of error rates using probabilities obtained from posterior distributions. Power of GWA studies using Bayesian methods can be enhanced by using informative priors based on previous association studies, gene expression analyses, or functional annotation information. Applied to multiple traits, Bayesian GWA analyses can give insight into pleiotropic effects by multi-trait, structural equation, or graphical models. Bayesian methods can also be used to combine genomic, transcriptomic, proteomic, and other -omics data to infer causal genotype to phenotype relationships and to suggest external interventions that can improve performance.

Conclusions

Bayesian hierarchical and variable selection methods provide a unified and powerful framework for genomic prediction, GWA, integration of prior information, and integration of information from other -omics platforms to identify causal mutations for complex quantitative traits.
High-resolution detection of quantitative trait loci for seven important yield-related traits in wheat (Triticum aestivum L.) using a high-density SLAF-seq genetic map
Authors: Li Tao , Li Qiao , Wang Jinhui , Yang Zhao , Tang Yanyan , Su Yan , Zhang Juanyu , Qiu Xvebing , Pu Xi , Pan Zhifen , Zhang Haili , Liang Junjun , Liu Zehou , Li Jun , Yan Wuyun , Yu Maoqun , Long Hai , Wei Yuming , Deng Guangbing
Published: May 2022

Background

Yield-related traits including thousand grain weight (TGW), grain number per spike (GNS), grain width (GW), grain length (GL), plant height (PH), spike length (SL), and spikelet number per spike (SNS) are greatly associated with grain yield of wheat (Triticum aestivum L.). To detect quantitative trait loci (QTL) associated with them, 193 recombinant inbred lines derived from two elite winter wheat varieties Chuanmai42 and Chuanmai39 were employed to perform QTL mapping in six/eight environments.

Results

A total of 30 QTLs on chromosomes 1A, 1B, 1D, 2A, 2B, 2D, 3A, 4A, 5A, 5B, 6A, 6D, 7A, 7B and 7D were identified. Among them, six major QTLs QTgw.cib-6A.1, QTgw.cib-6A.2, QGw.cib-6A, QGl.cib-3A, QGl.cib-6A, and QSl.cib-2D explaining 5.96-23.75% of the phenotypic variance were detected in multi-environments and showed strong and stable effects on corresponding traits. Three QTL clusters on chromosomes 2D and 6A containing 10 QTLs were also detected, which showed significant pleiotropic effects on multiple traits. Additionally, three Kompetitive Allele Specific PCR (KASP) markers linked with five of these major QTLs were developed. Candidate genes of QTgw.cib-6A.1/QGl.cib-6A and QGl.cib-3A were analyzed based on the spatiotemporal expression patterns, gene annotation, and orthologous search.

Conclusions

Six major QTLs for TGW, GL, GW and SL were detected. Three KASP markers linked with five of these major QTLs were developed. These QTLs and KASP markers will be useful for elucidating the genetic architecture of grain yield and developing new wheat varieties with high and stable yield in wheat.
Distribution of FIB-4 index in the general population: analysis of 75,666 residents who underwent health checkups
Authors: Sugiyama Aya , Kurisu Akemi , E Bunthen , Ouoba Serge , Ko Ko , Rakhimov Anvarjon , Akita Tomoyuki , Harakawa Takayuki , Sako Toru , Koshiyama Makoto , Kumada Takashi , Tanaka Junko
Published: May 2022

Background

Fatty liver is frequently found in a general population, and it is critical to detect advanced fibrosis. FIB-4 index is considered a useful marker for evaluating liver fibrosis but the distribution of FIB-4 index in the general population remains unknown.

Methods

This cross-sectional study included residents who underwent ultrasonography at health checkups in Hiroshima or Iwate prefectures. The distribution of FIB-4 index in the total study population (N = 75,666) as well as in non-alcoholic fatty liver disease (NAFLD) populations (N = 17,968) and non-drinkers without fatty liver populations (N = 47,222) was evaluated. The distribution of aspartate aminotransferase (AST) levels, alanine aminotransferase (ALT) levels was also evaluated.

Results

The mean FIB-4 index in the total study population was 1.20 ± 0.63. FIB-4 index ≥ 2.67, which indicates a high risk of liver fibrosis, was found in 16.4% of those aged ≥ 70 years. In the NAFLD population, 58.1% of those in their 60 s and 88.1% of those ≥ 70 years met the criteria for referral to hepatologists by using the recommended FIB-4 index cutoff value (≥ 1.3). The mean FIB-4 index in the NAFLD population (1.12 ± 0.58) was significantly lower than in the non-drinkers without fatty liver (1.23 ± 0.63, p < 0.0001). The non-drinkers without fatty liver tended to have higher AST relative to ALT levels (60.0% with AST/ALT > 1.0), whereas the results in the NAFLD population were opposite (14.8% with AST/ALT > 1.0). AST > ALT resulted in a higher FIB-4 index in non-drinkers without fatty liver due to the nature of FIB-4 index formula.

Conclusions

The cutoff value of FIB-4 index (≥ 1.3) for triaging the elderly people with fatty liver for referral to hepatologists should be reconsidered to avoid over-referral. Due to the impact of age and characteristics of AST/ALT ratios, there is no prospect of using FIB-4 index for primary screening for liver fibrosis in a general population of unknown presence or absence of liver disease, even though it can be easily calculated using routine clinical indices. It is desired to develop a non-invasive method for picking up cases with advanced fibrosis latent in the general population.
Oropharyngeal dysphagia and associated factors among individuals living in nursing homes in northern Sweden in 2007 and 2013
Authors: Hägglund Patricia , Gustafsson Maria , Lövheim Hugo
Published: May 2022

Background

Swallowing difficulties in the oral cavity or pharynx (i.e., oropharyngeal dysphagia) are a common problem in the aging population, which may result in severe consequences, such as malnutrition, aspiration pneumonia, and mortality. Identifying oropharyngeal dysphagia and its associated factors is essential for establishing better healthcare policies in nursing homes. In this study, we aimed to describe the oropharyngeal dysphagia prevalence among nursing home residents, and to investigate the association between dysphagia and potentially related factors in a large survey of nursing home residents in Sweden, including individuals with various degrees of cognitive impairment. A secondary aim was to compare findings between years on oropharyngeal dysphagia and its associated factors.

Methods

This study is based on two cross-sectional surveys performed in 2007 and 2013, including 4,995 individuals living in nursing homes in the Region of Västerbotten, Sweden. Data were collected from caregivers’ reports regarding swallowing ability, nutritional status, chewing ability, and other baseline characteristics, such as cognitive function and activity of daily living (ADL). Data were analyzed using logistic regression models to calculate the odds of the association between oropharyngeal dysphagia and associated factors.

Results

Oropharyngeal dysphagia was reported in 14.9% (95% CI: 13.9–16.0) of the nursing home residents. An adjusted model revealed that oropharyngeal dysphagia was associated by severe cognitive impairment (OR: 1.56, 95% CI: 1.14–2.12) and ADL independence (OR: 0.81 95% CI: 1.82–2.66) among nursing home residents. We also identified the following as independently associated factors of dysphagia: reduced nutritional status (OR: 1.84, 95% CI: 1.49–2.27), artificial nutrition (OR: 6.33, 95% CI: 2.73–14.71), and clinical signs of aspiration (OR: 10.89, 95% CI: 8.40–14.12).

Conclusions

Oropharyngeal dysphagia was reported among approximately 15% nursing home residents and was associated with cognitive impairment and ADL capability. Furthermore, reduced nutritional status and artificial nutrition were also associated with oropharyngeal dysphagia. Implementing routine protocols in nursing homes may help detect oropharyngeal dysphagia and manage oropharyngeal dysphagia among residents.
Understanding the epidemiology, clinical characteristics, knowledge and barriers to treatment and prevention of malaria among returning international laborers in northern Vietnam: a mixed-methods study
Authors: Edgel Kimberly A. , Canavati Sara , Le Hoi Thi , Tran Tho Huy , Van Nguyen Kinh , Nguyen Trung Vu , Nguyen Nga Thi , Tran Hoa Mai , Ngo Thang Duc , Tran Duong Thanh , Nguyen Binh Thi Huong , Tran Long Khanh , Nguyen Thu Minh , Whedbee Rosalie J. , Milgotina Ekaterina I. , Martin Nicholas J.
Published: May 2022

Background

With the decline in local malaria transmission in Vietnam as a result of the National Malaria Control Program (NMCP) elimination activities, a greater focus on the importation and potential reintroduction of transmission are essential to support malaria elimination objectives.

Methods

We conducted a multi-method assessment of the demographics, epidemiology, and clinical characteristics of imported malaria among international laborers returning from African or Southeast Asian countries to Vietnam. Firstly, we conducted a retrospective review of hospital records of patients from January 2014 to December 2016. Secondly, we conducted a mixed-methods prospective study for malaria patients admitted to the study sites from January 2017 to May 2018 using a structured survey with blood sample collection for PCR analysis and in-depth interviews. Data triangulation of the qualitative and quantitative data was used during analysis.

Results

International laborers were young (median age 33.0 years IQR 28.0–39.5 years), predominantly male (92%) adults returning mostly from the African continent (84%) who stayed abroad for prolonged periods (median time 13.5 months; IQR 6.0–331.5 months) and were involved in occupations that exposed them to a higher risk of malaria infection. Epidemiological trends were also similar amongst study strands and included the importation of Plasmodium falciparum primarily from African countries and P. vivax from Southeast Asian countries. Of 11 P. malariae and P. ovale infections across two study strands, 10 were imported from the African continent. Participants in the qualitative arm demonstrated limited knowledge about malaria prior to travelling abroad, but reported knowledge transformation through personal or co-worker’s experience while abroad. Interestingly, those who had a greater understanding of the severity of malaria presented to the hospital for treatment sooner than those who did not; median of 3 days (IQR 2.0–7.0 days) versus 5 days (IQR 4.0–9.5 days) respectively.

Conclusion

To address the challenges to malaria elimination raised by a growing Vietnamese international labor force, consideration should be given to appropriately targeted interventions and malaria prevention strategies that cover key stages of migration including pre-departure education and awareness, in-country prevention and prophylaxis, and malaria screening upon return.
Venous thromboembolism in COVID-19 patients and prediction model: a multicenter cohort study
Authors: Lee Yi , Jehangir Qasim , Li Pin , Gudimella Deepthi , Mahale Pooja , Lin Chun-Hui , Apala Dinesh R. , Krishnamoorthy Geetha , Halabi Abdul R. , Patel Kiritkumar , Poisson Laila , Balijepally Venugopal , Sule Anupam A. , Nair Girish B.
Published: May 2022

Background

Patients with COVID-19 infection are commonly reported to have an increased risk of venous thrombosis. The choice of anti-thrombotic agents and doses are currently being studied in randomized controlled trials and retrospective studies. There exists a need for individualized risk stratification of venous thromboembolism (VTE) to assist clinicians in decision-making on anticoagulation. We sought to identify the risk factors of VTE in COVID-19 patients, which could help physicians in the prevention, early identification, and management of VTE in hospitalized COVID-19 patients and improve clinical outcomes in these patients.

Method

This is a multicenter, retrospective database of four main health systems in Southeast Michigan, United States. We compiled comprehensive data for adult COVID-19 patients who were admitted between 1st March 2020 and 31st December 2020. Four models, including the random forest, multiple logistic regression, multilinear regression, and decision trees, were built on the primary outcome of in-hospital acute deep vein thrombosis (DVT) and pulmonary embolism (PE) and tested for performance. The study also reported hospital length of stay (LOS) and intensive care unit (ICU) LOS in the VTE and the non-VTE patients. Four models were assessed using the area under the receiver operating characteristic curve and confusion matrix.

Results

The cohort included 3531 admissions, 3526 had discharge diagnoses, and 6.68% of patients developed acute VTE (N = 236). VTE group had a longer hospital and ICU LOS than the non-VTE group (hospital LOS 12.2 days vs. 8.8 days, p < 0.001; ICU LOS 3.8 days vs. 1.9 days, p < 0.001). 9.8% of patients in the VTE group required more advanced oxygen support, compared to 2.7% of patients in the non-VTE group (p < 0.001). Among all four models, the random forest model had the best performance. The model suggested that blood pressure, electrolytes, renal function, hepatic enzymes, and inflammatory markers were predictors for in-hospital VTE in COVID-19 patients.

Conclusions

Patients with COVID-19 have a high risk for VTE, and patients who developed VTE had a prolonged hospital and ICU stay. This random forest prediction model for VTE in COVID-19 patients identifies predictors which could aid physicians in making a clinical judgment on empirical dosages of anticoagulation.
Analyzing inherent biases in SARS-CoV-2 PCR and serological epidemiologic metrics
Authors: Makhoul Monia , Abou-Hijleh Farah , Seedat Shaheen , Mumtaz Ghina R. , Chemaitelly Hiam , Ayoub Houssein , Abu-Raddad Laith J.
Published: May 2022

Background

Prospective observational data show that infected persons with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain polymerase chain reaction (PCR) positive for a prolonged duration, and that detectable antibodies develop slowly with time. We aimed to analyze how these effects can bias key epidemiological metrics used to track and monitor SARS-CoV-2 epidemics.

Methods

An age-structured mathematical model was constructed to simulate progression of SARS-CoV-2 epidemics in populations. PCR testing to diagnose infection and cross-sectional surveys to measure seroprevalence were also simulated. Analyses were conducted on simulated outcomes assuming a natural epidemic time course and an epidemic in presence of interventions.

Results

The prolonged PCR positivity biased the epidemiological measures. There was a lag of 10 days between the true epidemic peak and the actually-observed peak. Prior to epidemic peak, PCR positivity rate was twofold higher than that based only on current active infection, and half of those tested positive by PCR were in the prolonged PCR positivity stage after infection clearance. Post epidemic peak, PCR positivity rate poorly predicted true trend in active infection. Meanwhile, the prolonged PCR positivity did not appreciably bias estimation of the basic reproduction number R0. The time delay in development of detectable antibodies biased measured seroprevalence. The actually-observed seroprevalence substantially underestimated true prevalence of ever infection, with the underestimation being most pronounced around epidemic peak.

Conclusions

Caution is warranted in interpreting PCR and serological testing data, and any drawn inferences need to factor the effects of the investigated biases for an accurate assessment of epidemic dynamics.
Detection of superficial and buried optic disc drusen with swept-source optical coherence tomography
Authors: Guo Xiaohong , Wu Yingjie , Wu Yuhong , Liu Hui , Ming Shuai , Cui Hongpei , Fan Ke , Li Shuyin , Lei Bo
Published: May 2022

Background

To detect the superficial and buried optic disc drusen (ODD) with swept-source optical coherence tomography (SS-OCT).

Methods

Retrospective cross-sectional study. Twenty patients (age 18–74 years) diagnosed with ODD via B-scan ultrasonography were analysed. All patients underwent color fundus photography (CFP), B-scan ultrasonography, fundus autofluorescence (FAF), and SS-OCT. We defined each hyporeflective signal mass of SS-OCT as an ODD, recorded its location and relationship with Bruch’s membrane opening (BMO), and other ophthalmic imaging characteristics.

Results

Twenty (33 eyes) patients had 54 ODDs in all, except one eye did not show abnormal optic disc findings on SS-OCT. We classified ODD into three categories: ODD above BMO, ODD across BMO, and ODD below BMO. The ODDs across BMO were the largest, followed by ODDs below BMO, and those above BMO. The location of the ODDs: One (1.9%) was in the border tissue of Elschnig, 6 (11.1%) might span across the lamina cribrosa, 16 (29.6%) were above BMO located in the neuroepithelial layer, 9 (16.7%) spanned across BMO located near the center of the optic disc, 18 (33.3%) were below BMO located near the center of the optic disc, 4 (7.4%) were below BMO located within the optic disc rim. When the anterior margin was ≥ 100 μm from the BMO, clear autofluorescence could be seen.

Conclusion

Multimodal imaging provided a deeper understanding of ODD. SS-OCT illustrated more details about the relationship between the posterior surface of ODD, BMO and the lamina cribrosa.
Every child, every day, back to play: the PICUstars protocol - implementation of a nurse-led PICU liberation program
Authors: Waak M. , Harnischfeger J. , Ferguson A. , Gibbons K. , Nguyen K. H. , Long D.
Published: May 2022

Background

As admissions to paediatric intensive care units (PICU) rise and mortality rates decline, the focus is shifting from survival to quality of survivorship. There is paucity of internationally accepted guidelines to manage complications like over-sedation, delirium, and immobility in the paediatric setting. These have a strong adverse impact on PICU recovery including healthcare costs and long-term functional disability. The A2F bundle (ABCDEF), or ICU Liberation, was developed to operationalise the multiple evidence-based guidelines addressing ICU-related complications and has been shown to improve clinical outcomes and health-care related costs in adult studies. However, there is little data on the effect of ICU Liberation bundle implementation in PICU.

Methods

PICU-STARS will be a single centre before-and-after after trial and implementation study. It is designed to evaluate if the multidimensional, nurse-led ICU Liberation model of care can be applied to the PICU and if it is successful in minimising PICU-related problems in a mixed quaternary PICU. In a prospective baseline measurement, the present practises of care in the PICU will be assessed in order to inform the adaptation and implementation of the PICU Liberation bundle. To assess feasibility, implementation outcomes, and intervention effectiveness, the implementation team will use the Consolidated Framework for Implementation Research (CIFR) and process assessment (mixed methods). The implementation process will be evaluated over time, with focus groups, interviews, questionnaires, and observations used to provide formative feedback. Over time, the barriers and enablers for successful implementation will be analysed, with recommendations based on “lessons learned.”

All outcomes will be reported using standard descriptive statistics and analytical techniques, with appropriate allowance for patient differentials in severity and relevant characteristics.

Discussion

The results will inform the fine-tune of the Liberation bundle adaptation and implementation process. The expected primary output is a detailed adaptation and implementation guideline, including clinical resources (and investment) required, to adopt PICU-STARS in other children’s hospitals.

Patient and public involvement statement

The authors thank the PICU education and Liberation Implementation team, and our patients and families for their inspiration and valuable comments on protocol drafts. Results will be made available to critical care survivors, their caregivers, relevant societies, and other researchers.

Trial registration

ACTRN, ACTRN382863. Registered 19/10/2021 - Retrospectively registered.

Study status

recruiting.
Determinants of birth asphyxia among newborn live births in public hospitals of Gamo and Gofa zones, Southern Ethiopia
Authors: Lemma Kebebew , Misker Direslgne , Kassa Mekidim , Abdulkadir Hanan , Otayto Kusse
Published: May 2022

Background

Birth asphyxia is the inability of a newborn to start and conserve breathing immediately after birth. Globally, 2.5 million infants die within their first month of life every year, contributing nearly 47% of all deaths of children. It is the third cause of neonatal deaths next to infections and preterm birth. Ethiopia is one of the countries with the highest neonatal mortality and high burden of birth asphyxia in the world. The state of birth asphyxia is about 22.52% in Ethiopia, with incidence of 18.0% in East Africa Neonatal mortality incidence ratio was 9.6 deaths per 1000 live births among which 13.5% of neonatal mortality cases were due to birth asphyxia in southern Ethiopia. The effect of birth asphyxia is not only limited to common clinical problems and death; it also has a socio-economic impact on the families. Therefore, this study is aimed to identify determinants of birth asphyxia among newborn live births in public hospitals Southern Ethiopia.

Methods

An Institution based unmatched case–control study was conducted among newborn live births in public hospitals of Gamo & Gofa zones, with a total sample size of 356 (89 cases and 267 controls, 1:3 case to control ratio) from March 18 to June 18, 2021, after obtaining ethical clearance from Arba Minch University. Cases were selected consecutively and controls were selected by systematic random sampling method. Data were collected using an adapted pretested semi-structured questionnaire through face-to-face interviews and record reviews using an extraction checklist for intrapartum & neonatal-related information. The collected data were entered into Epi data version 4.4 and exported to STATA version 14 for analysis. Finally, bi-variable and multivariable logistic regression analyses were performed to identify determinants of birth asphyxia. Statistical significance was declared at p-value ≤ 0.05 along with corresponding 95% CI of AOR used to declare statistical significance. Results: Anemia during pregnancy [AOR = 3.87, 95% CI (1.06- 14.09)], breech presentation [AOR = 3.56, 95% CI (1.19–10.65)], meconium stained amniotic fluid [AOR = 6.16, 95% CI (1.95–19.46)], cord prolapse [AOR = 4.69, 95%CI (1.04–21.05)], intrapartum fetal distress [AOR = 9.83, 95% CI (3.82–25.25)] and instrumental delivery [AOR = 5.91, 95% CI (1.51–23.07)] were significantly associated with birth asphyxia.

Conclusion

The study revealed that anemia during pregnancy, breech presentation, meconium-stained amniotic fluid, cord prolapse, intrapartum fetal distress, and instrumental delivery were identified as determinants of birth asphyxia. Therefore, health professional and health institutions should give emphasis on care of mother and the newborn in actively detecting and managing asphyxia.
Changes in healthcare spending attributable to obesity and overweight: payer- and service-specific estimates
Authors: van den Broek-Altenburg Eline , Atherly Adam , Holladay Evon
Published: May 2022

Background

National efforts to control US healthcare spending are potentially undermined by changes in patient characteristics, and in particular increases in rates of obesity and overweight. The objective of this study was to provide current estimates of the effect of obesity and overweight on healthcare spending overall, by service line and by payer using the National Institutes of Health classifications for BMI.

Methods

We used a quasi-experimental design and analyzed the data using generalized linear models and two-part models to estimate obesity- and overweight-attributable spending. Data was drawn from the 2006 and 2016 Medical Expenditures Panel Survey. We identified individuals in the different BMI classes based on self-reported height and weight.

Results

Total medical costs attributable to obesity rose to $126 billion per year by 2016, although the marginal cost of obesity declined for all obesity classes. The overall spending increase was due to an increase in obesity prevalence and a population shift to higher obesity classes. Obesity related spending between 2006 and 2016 was relatively constant due to decreases in inpatient spending, which were only partially offset by increases in outpatient spending.

Conclusions

While total obesity related spending between 2006 and 2016 was relatively constant, by examining the effect of different obesity classes and overweight, it provides insight into spend for each level of obesity and overweight across service line and payer mix. Obesity class 2 and 3 were the main factors driving spending increases, suggesting that persons over BMI of 35 should be the focus for policies focused on controlling spending, such as prevention.
Sex-related differences in endothelium-dependent vasodilation of human gingiva
Authors: Vág János , Nagy Tamás László , Mikecs Barbara
Published: May 2022

Background

Sex hormones influence circulation, periodontitis, and wound healing. The aim of the study was to compare the endothelium-dependent and independent vasodilation in human gingiva in men and women.

Methods

Gingival blood flow was evaluated in twelve male and twelve female subjects with healthy gingiva and no systemic conditions after acetylcholine or nitric oxide donor (NitroPOHL). Agonists were administered into the gingival sulcus at the right secondary incisor (test site). Regional gingival blood flow (GBF) was imaged by Laser Speckle Contrast Imager from the marginal gingiva to the mucogingival junction in four consecutive regions (coronal, midway1, midway2 and apical). Blood flow was expressed in Laser Speckle Perfusion Unit (LSPU). The absolute maximal blood flow change (Dmax), the area under the blood flow curve (AUC), and the time to peak (TTP) were calculated.

Results

Males had higher baseline GBF than females (257 ± 18.2 vs. 225 ± 18.8 LSPU, p < 0.001). Acetylcholine and NitroPOHL significantly increased the GBF in all test regions. The Dmax after the acetylcholine was reduced apically compared to the coronal (90 ± 13 LSPU vs. 117 ± 7 LSPU, p < 0.01), but it was similar after NitroPOHL (78 ± 9 LSPU vs. 86 ± 6 LSPU, p = 0.398) in both sexes. The Dmax and AUC were higher, and the TTP was smaller in men in most regions after acetylcholine but not after NitroPOHL.

Conclusion

In the human gingiva, the endothelium-independent vasodilation propagates without attenuation in the line of the vascular supply in both sexes. At the same time, the endothelium-dependent ascending vasodilation attenuates similarly in men and women. However, men had more pronounced endothelium-dependent vasodilation than women. Therefore, it might contribute to the increased severity of periodontal disease in men.

Trial registration

The study was registered with ClinicalTrials.gov on 09.06.2021 (NCT04918563).
Mechanisms of pelvic floor muscle training for managing urinary incontinence in women: a scoping review
Authors: Sheng Ying , Carpenter Janet S. , Ashton-Miller James A. , Miller Janis M.
Published: May 2022

Background

Pelvic floor muscle training is recommended as first line treatment for urinary incontinence in women based on three proposed theorized mechanisms: ‘Enhanced Pelvic Floor Muscle Strength,’ ‘Maximized Awareness of Timing,’ and ‘Strengthened Core Muscles’. The purpose of this scoping review was to systematically map evidence for and against theorized mechanisms through which pelvic floor muscle training interventions work to reduce urinary incontinence in women.

Methods

The scoping review is based upon a comprehensive search of relevant literature published from 1990 to 2020 in PubMed, CINAHL, PsycINFO, ClinialTrials.gov, reference lists from review articles, and hand searches of articles by known researchers in the field. We included English-language, peer-reviewed articles on pelvic floor muscle training as an intervention for adult women if they provided empirical evidence to testing the theorized intervention mechanisms. Two independent reviewers screened articles for inclusion and extracted data to describe details of each study (author, year, country, design, sampling), measures of pelvic floor muscle strength and urinary incontinence, statistical analysis of linkage between changes in the measures, and pelvic floor muscle training regimens. Data were summarized to facilitate the integration of diverse evidence to draw conclusions on supporting or refuting the three proposed theorized mechanisms for managing urinary incontinence in women.

Results

Of the 278 articles identified with the search, 13 (4.7%) met inclusion criteria. There was weak to no evidence for the mechanism of enhanced pelvic floor muscle strength, equivocal support for maximized awareness of timing, and no evidence for strengthened core muscles.

Conclusions

This review revealed extremely limited data supporting the proposed theorized mechanisms underlying pelvic floor muscle training programs to manage urinary incontinence in women. Such evidence is needed to help women and clinicians understand how, why and when a woman benefits from pelvic floor muscle training. Future studies should specifically state and report statistical analysis that relates the theorized mechanisms to the training outcomes observed.
Academic and non-academic predictors of academic performance in medical school: an exploratory cohort study
Authors: Žuljević Marija Franka , Buljan Ivan
Published: May 2022

Background

Medical schools should also evaluate applicants’ non-academic characteristics in the search for successful students and future physicians, but ideal non-academic criteria have not yet been found. We followed two successive generations of medical students at the University of Split School of Medicine (USSM) to assess both academic and non-academic constructs as predictors of academic performance, defined as medical school grade point average (GPA). We also interviewed some of the participants to gain additional insight for future studies.

Methods

We measured study GPA in first and last year, as well as attitudes towards science, motivation, emotional intelligence, self-esteem, and perceived personal incompetence in first year. We also obtained their scores on existing medical school enrollment criteria, the State Graduation Exam (SGE) and high-school GPA. Regression models were constructed for predictors of GPA in the last year of medical school. Four structured pilot interviews were conducted to explore participants’ perceptions of necessary traits for medical school and later practice.

Results

Regression analysis showed that only SGE predicted final academic performance in medical school (β=0.35, 95% confidence interval (CI)=0.06-0.64), while none of the non-academic constructs we assessed predicted this outcome of education. The two generations did not significantly differ in any variable except that intrinsic motivation was higher in the generation that enrolled in 2011 (OR=1.47, 95%CI=1.12-1.93, P=0.005).

Discussion

None of the non-academic constructs predicted academic performance in medical school. Their use as selection criteria may not be warranted as they could impact the academic quality of enrolling medical students.
Pictograms for safer medication handling by health care workers: a validation study in nursing students in Poland
Authors: Merks Piotr , Vaillancourt Regis , Roux Damien , Gierczyński Rafał , Juszczyk Grzegorz , Plagens-Rotman Katarzyna , Religioni Urszula , Cameron Jameason , Zender Mike
Published: May 2022

Background and objective

Medication use often causes errors that are dangerous to the health of patients. Previous studies indicate that the use of pharmaceutical pictograms can effectively reduce medication errors. The purpose of this study was to determine the comprehensibility, representativeness, and recall rate of nine medication safety pictograms in a sample of nursing students in Poland in order to validate these images.

Methods

A pictogram validation study was conducted in two phases among nursing students at the Hipolit Cegielski State University of Applied Sciences, Gniezno, Poland.

All experimental protocols were approved by the Children's Hospital of Eastern Ontario Research Ethics Board (REB Protocol No: 19/122X). All methods were carried out in accordance with relevant guidelines and regulations.

In phase 1, the participants' first exposure to the pictograms, the students were asked to guess the meaning of the pictograms without any additional information in order to assess the pictograms' comprehensibility. To be considered valid, according to ISO standards, the pictograms had to be correctly understood by at least 66.7% of participants. After testing all pictograms, students were given explanations and meanings of the pictograms and asked to rate the representativeness of pictograms. To do so, participants were asked to select a number on a seven-point Likert-style scale to indicate the perceived strength of the relationship between the pictogram and its intended meaning for each pictogram. To be considered valid, a pictogram had to be rated at least five on this scale by at least 66.7% of participants. Phase 2 took place four weeks later, during which recall of the intended meaning and representativeness were assessed following the same procedure.

Results

A total of 66 third-year nursing students participated in both phases. In phase 1, of the nine pictograms, six met ISO requirements for comprehensibility and seven met ISO requirements for representativeness. In phase 2, all nine pictograms were correctly understood and rated at least 5 by at least 66.7% of participants. Therefore, all nine pictograms are considered valid.

Conclusions

The nine medication safety pictograms can be deployed, but must be combined with training and a written hazard statement to improve comprehension.
Emergency services utilization in Jakarta (Indonesia): a cross-sectional study of patients attending hospital emergency departments
Authors: Brice Syaribah Noor , Boutilier Justin J. , Gartner Daniel , Harper Paul , Knight Vincent , Lloyd Jen , Pusponegoro Aryono Djuned , Rini Asti Puspita , Turnbull-Ross Jonathan , Tuson Mark
Published: May 2022

Background

Pre-hospital and emergency services in Indonesia are still developing. Despite recent improvements in the Indonesian healthcare system, issues with the provision of pre-hospital and emergency services persist. The demand for pre-hospital and emergency services has not been the subject of previous research and, therefore, has not been fully understood. Our research explored the utilization of emergency medical services by patients attending hospital emergency departments in Jakarta, Indonesia.

Methods

The study used a cross-sectional survey design involving five general hospitals (four government-funded and one private). Each patient’s demographic profile, medical conditions, time to treatment, and mode of transport to reach the hospital were analysed using descriptive statistics.

Results

A total of 1964 (62%) patients were surveyed. The median age of patients was 44 years with an interquartile range (IQR) of 26 to 58 years. Life-threatening conditions such as trauma and cardiovascular disease were found in 8.6 and 6.6% of patients, respectively. The majority of patients with trauma travelled to the hospital using a motorcycle or car (59.8%). An ambulance was used by only 9.3% of all patients and 38% of patients reported that they were not aware of the availability of ambulances. Ambulance response time was longer as compared to other modes of transportation (median: 24 minutes and IQR: 12 to 54 minutes). The longest time to treatment was experienced by patients with neurological disease, with a median time of 120 minutes (IQR: 78 to 270 minutes). Patients who used ambulances incurred higher costs as compared to those patients who did not use ambulances.

Conclusion

The low utilization of emergency ambulances in Jakarta could be contributed to patients’ lack of awareness of medical symptoms and the existence of ambulance services, and patients’ disinclination to use ambulances due to high costs and long response times. The emergency ambulance services can be improved by increasing population awareness on symptoms that warrant the use of ambulances and reducing the cost burden related to ambulance use.
Structure modeling hints at a granular organization of the Golgi ribbon
Authors: Page Karen M. , McCormack Jessica J. , Lopes-da-Silva Mafalda , Patella Francesca , Harrison-Lavoie Kimberly , Burden Jemima J. , Quah Ying-Yi Bernadette , Scaglioni Dominic , Ferraro Francesco , Cutler Daniel F.
Published: May 2022

Background

In vertebrate cells, the Golgi functional subunits, mini-stacks, are linked into a tri-dimensional network. How this “ribbon” architecture relates to Golgi functions remains unclear. Are all connections between mini-stacks equal? Is the local structure of the ribbon of functional importance? These are difficult questions to address, without a quantifiable readout of the output of ribbon-embedded mini-stacks. Endothelial cells produce secretory granules, the Weibel-Palade bodies (WPB), whose von Willebrand Factor (VWF) cargo is central to hemostasis. The Golgi apparatus controls WPB size at both mini-stack and ribbon levels. Mini-stack dimensions delimit the size of VWF "boluses” whilst the ribbon architecture allows their linear co-packaging, thereby generating WPBs of different lengths. This Golgi/WPB size relationship suits mathematical analysis.

Results

WPB lengths were quantized as multiples of the bolus size and mathematical modeling simulated the effects of different Golgi ribbon organizations on WPB size, to be compared with the ground truth of experimental data. An initial simple model, with the Golgi as a single long ribbon composed of linearly interlinked mini-stacks, was refined to a collection of mini-ribbons and then to a mixture of mini-stack dimers plus long ribbon segments. Complementing these models with cell culture experiments led to novel findings. Firstly, one-bolus sized WPBs are secreted faster than larger secretory granules. Secondly, microtubule depolymerization unlinks the Golgi into equal proportions of mini-stack monomers and dimers. Kinetics of binding/unbinding of mini-stack monomers underpinning the presence of stable dimers was then simulated. Assuming that stable mini-stack dimers and monomers persist within the ribbon resulted in a final model that predicts a “breathing” arrangement of the Golgi, where monomer and dimer mini-stacks within longer structures undergo continuous linking/unlinking, consistent with experimentally observed WPB size distributions.

Conclusions

Hypothetical Golgi organizations were validated against a quantifiable secretory output. The best-fitting Golgi model, accounting for stable mini-stack dimers, is consistent with a highly dynamic ribbon structure, capable of rapid rearrangement. Our modeling exercise therefore predicts that at the fine-grained level the Golgi ribbon is more complex than generally thought. Future experiments will confirm whether such a ribbon organization is endothelial-specific or a general feature of vertebrate cells.
Comparative whole-genome transcriptome analysis in renal cell populations reveals high tissue specificity of MAPK/ERK targets in embryonic kidney
Authors: Kurtzeborn Kristen , Kwon Hyuk Nam , Iaroshenko Vladislav , Faisal Imrul , Ambrož Martin , Jin Xing , Qureshi Talha , Kupari Jussi , Ihermann-Hella Anneliis , Väänänen Juho , Tyynismaa Henna , Boušová Iva , Park Sunghyouk , Kuure Satu
Published: May 2022

Background

MAPK/ERK signaling is a well-known mediator of extracellular stimuli controlling intracellular responses to growth factors and mechanical cues. The critical requirement of MAPK/ERK signaling for embryonic stem cell maintenance is demonstrated, but specific functions in progenitor regulation during embryonic development, and in particular kidney development remain largely unexplored. We previously demonstrated MAPK/ERK signaling as a key regulator of kidney growth through branching morphogenesis and normal nephrogenesis where it also regulates progenitor expansion. Here, we performed RNA sequencing-based whole-genome expression analysis to identify transcriptional MAPK/ERK targets in two distinct renal populations: the ureteric bud epithelium and the nephron progenitors.

Results

Our analysis revealed a large number (5053) of differentially expressed genes (DEGs) in nephron progenitors and significantly less (1004) in ureteric bud epithelium, reflecting likely heterogenicity of cell types. The data analysis identified high tissue-specificity, as only a fraction (362) of MAPK/ERK targets are shared between the two tissues. Tissue-specific MAPK/ERK targets participate in the regulation of mitochondrial energy metabolism in nephron progenitors, which fail to maintain normal mitochondria numbers in the MAPK/ERK-deficient tissue. In the ureteric bud epithelium, a dramatic decline in progenitor-specific gene expression was detected with a simultaneous increase in differentiation-associated genes, which was not observed in nephron progenitors. Our experiments in the genetic model of MAPK/ERK deficiency provide evidence that MAPK/ERK signaling in the ureteric bud maintains epithelial cells in an undifferentiated state. Interestingly, the transcriptional targets shared between the two tissues studied are over-represented by histone genes, suggesting that MAPK/ERK signaling regulates cell cycle progression and stem cell maintenance through chromosome condensation and nucleosome assembly.

Conclusions

Using tissue-specific MAPK/ERK inactivation and RNA sequencing in combination with experimentation in embryonic kidneys, we demonstrate here that MAPK/ERK signaling maintains ureteric bud tip cells, suggesting a regulatory role in collecting duct progenitors. We additionally deliver new mechanistic information on how MAPK/ERK signaling regulates progenitor maintenance through its effects on chromatin accessibility and energy metabolism.