bluuebunny/crossref_metadata_2025 huggingface dataset:
Validity of the Malnutrition Universal Screening Tool for Evaluation of Frailty Status in Older Hospitalised Patients
Authors: Sharma Yogesh , Avina Peter , Ross Emelie , Horwood Chris , Hakendorf Paul , Thompson Campbell
Published: July 2022

The malnutrition-universal-screening-tool (MUST) is commonly used for screening malnutrition in hospitalised patients but its utility in the detection of frailty is unknown. This study determined the utility of MUST in detection of frailty in older hospitalised patients. This prospective-study enrolled 243 patients ⩾65 years in a tertiary-teaching hospital in Australia. Patients with a MUST score of ⩾1 were classified as at-risk of malnutrition. Frailty status was determined by the Edmonton-Frail-Scale (EFS) and patients with an EFS score of >8 were classified as frail. We validated the MUST against the EFS by plotting a receiver-operating-characteristic-curve (ROC) curve and area-under-the-curve (AUC) was determined. The mean (SD) age was 83.9 (6.5) years and 126 (51.8%) were females. The EFS determined 149 (61.3%) patients as frail, while 107 (44.1%) patients were at-risk of malnutrition according to the MUST. There was a positive linear but weak association between the MUST and the EFS scores (Pearson’s correlation coefficient= .22, 95% CI .12– .36, p < .001). The sensitivity, specificity, positive and negative predictive value of MUST in the detection of frailty was 51%, 67%, 78.5% and 37%, respectively and the AUC was .59 (95% CI .53–.65, p < .001). The MUST is moderately sensitive in detection of frailty in older-hospitalised patients.
The temporality of on-street parking – exploring the role of land-use mix and change on parking dynamics
Authors: Kimpton Anthony , Stead Dominic , Corcoran Jonathan
Published: July 2022

Parking is often overlooked by urban researchers even though parking consumes large proportions of a city’s physical footprint and imposes a significant impediment to more sustainable travel. Underpinning this lack of attention is suitable data and methods capable of capturing the complex dynamics of parking. Here we redress this gap by drawing on an emergent source of parking data and deploying empirical techniques to unpack this complexity. Data from 3542 on-street parking sensors observed over a 9-year period are used to delineate the first typology of parking routines before using a fixed-effects logistic regression model to explain how nearby land-use types and land-use mix shapes tempo and timing of parking utilisation. The benefit of our approach lies in its capacity to discriminate broad types of temporal rhythms associated with parking dynamics at particular places, how these change over time and how these rhythms are associated with different types and mixes of nearby land use. This knowledge is important to inform policies seeking to optimise the use of on-street parking and invoke more sustainable patterns of mobility.
Specific Design of a Press Fit Humeral Stem Provides low Stress Shielding in Reverse Shoulder Arthroplasty at minimum 5 Years FU
Authors: Nourissat Geoffroy , Corsia Simon , Harris Howard W , Bouché Pierre-Alban
Published: July 2022

Press fit fixation is becoming more popular in RSA to preserve, in theory, bone capital. Several studies report that bone resorption can be very high around humeral stems depending on their size, shape and mode of fixation. The aim of the current study is to mid-term follow-up clinical and radiological result of a press fit ovoid regular stem RSA in non acute trauma cases.

Materials and Methods

We performed a retrospective monocentric study of patients continuously implanted with the Humeris® stem RSA for degenerative change of the shoulder. Nineteen shoulders, in eighteen patients (74.6 y.o (from 69 to 81)), were available at minimum five years follow-up.

Results

The mean final adjusted Constant score was 111.9 (65 to 130), and the mean ASES score was 49.82 (10 to 60). Humeral resorption was observed in 21% of cases. We found a statistically significant ( p = .014) lower adjusted Constant score in patients presenting with resorption on post-operative X-rays compared to those without resorption (115.6 vs. 98.25). Half cases of patients presenting a resorption underwent L’Episcopo procedure during surgery. Humeral resorption occurs the first year after surgery and do not increase even 8 years after surgery. Analysis demonstrated no correlation between the value of filling ratios and bone resorption.

Conclusion

The current study confirms a low rate of stress shielding around the studied stem, with rare bony resorption and no osteopenia around the humeral stem. This study highlights the importance of choosing the appropriate proximal shape and length of the humeral stem for press fit fixation in RSA.
GRK2 regulates ADP signaling in platelets via P2Y1 and P2Y12
Authors: Zhao Xuefei , Cooper Matthew , Michael James V. , Yarman Yanki , Baltz Aiden , Chuprun J. Kurt , Koch Walter J. , McKenzie Steven E. , Tomaiuolo Maurizio , Stalker Timothy J. , Zhu Li , Ma Peisong
Published: July 2022

The critical role of G protein–coupled receptor kinase 2 (GRK2) in regulating cardiac function has been well documented for >3 decades. Targeting GRK2 has therefore been extensively studied as a novel approach to treating cardiovascular disease. However, little is known about its role in hemostasis and thrombosis. We provide here the first evidence that GRK2 limits platelet activation and regulates the hemostatic response to injury. Deletion of GRK2 in mouse platelets causes increased platelet accumulation after laser-induced injury in the cremaster muscle arterioles, shortens tail bleeding time, and enhances thrombosis in adenosine 5′-diphosphate (ADP)-induced pulmonary thromboembolism and in FeCl3-induced carotid injury. GRK2−/− platelets have increased integrin activation, P-selectin exposure, and platelet aggregation in response to ADP stimulation. Furthermore, GRK2−/− platelets retain the ability to aggregate in response to ADP restimulation, indicating that GRK2 contributes to ADP receptor desensitization. Underlying these changes in GRK2−/− platelets is an increase in Ca2+ mobilization, RAS-related protein 1 activation, and Akt phosphorylation stimulated by ADP, as well as an attenuated rise of cyclic adenosine monophosphate levels in response to ADP in the presence of prostaglandin I2. P2Y12 antagonist treatment eliminates the phenotypic difference in platelet accumulation between wild-type and GRK2−/− mice at the site of injury. Pharmacologic inhibition of GRK2 activity in human platelets increases platelet activation in response to ADP. Finally, we show that GRK2 binds to endogenous Gβγ subunits during platelet activation. Collectively, these results show that GRK2 regulates ADP signaling via P2Y1 and P2Y12, interacts with Gβγ, and functions as a signaling hub in platelets for modulating the hemostatic response to injury.
Burden of tension-type headache in the Middle East and North Africa region, 1990-2019
Authors: Safiri Saeid , Kolahi Ali-Asghar , Noori Maryam , Nejadghaderi Seyed Aria , Aslani Armin , Sullman Mark J. M. , Farhoudi Mehdi , Araj-Khodaei Mostafa , Collins Gary S. , Kaufman Jay S. , Gharagozli Kurosh
Published: July 2022

Introduction

Tension-type headache (TTH) is the most prevalent neurological disorder. As there is a gap in the literature regarding the disease burden attributable to TTH in the Middle East and North Africa (MENA) region, the aim of the present study was to report the epidemiological indicators of TTH in MENA, from 1990 to 2019, by sex, age and socio-demographic index (SDI).

Methods

Publicly available data on the point prevalence, annual incidence and years lived with disability (YLDs) were retrieved from the global burden of disease (GBD) 2019 study for the 21 countries and territories in MENA, between 1990 and 2019. The results were presented with numbers and age-standardised rates per 100000 population, along with their corresponding 95% uncertainty intervals (UIs).

Results

In 2019, the age-standardised point prevalence and annual incidence rates for TTH in the MENA region were 24504.5 and 8680.1 per 100000, respectively, which represents a 2.0% and a 0.9% increase over 1990-2019, respectively. The age-standardised YLD rate of TTH in this region in 2019 was estimated to be 68.1 per 100000 population, which has increased 1.0% since 1990. Iran [29640.4] had the highest age-standardised point prevalence rate for TTH, while Turkey [21726.3] had the lowest. In 2019, the regional point prevalence of TTH was highest in the 35-39 and 70-74 age groups, for males and females, respectively. Furthermore, the number of prevalent cases was estimated to be highest in those aged 35-39 and 25-29 years, in both males and females, respectively. Moreover, the burden of TTH was not observed to have a clear association with SDI.

Conclusions

While the prevalence of TTH in the MENA region increased from 1990 to 2019, the incidence rate did not change. In addition, the burden of TTH in MENA was higher than at the global level for both sexes and all age groups. Therefore, prevention of TTH would help alleviate the attributable burden imposed on the hundreds of millions of people suffering from TTH around the region.
CAD systems for COVID-19 diagnosis and disease stage classification by segmentation of infected regions from CT images
Authors: Alshayeji Mohammad H. , ChandraBhasi Sindhu Silpa , Abed Sa’ed
Published: July 2022

Background

Here propose a computer-aided diagnosis (CAD) system to differentiate COVID-19 (the coronavirus disease of 2019) patients from normal cases, as well as to perform infection region segmentation along with infection severity estimation using computed tomography (CT) images. The developed system facilitates timely administration of appropriate treatment by identifying the disease stage without reliance on medical professionals. So far, this developed model gives the most accurate, fully automatic COVID-19 real-time CAD framework.

Results

The CT image dataset of COVID-19 and non-COVID-19 individuals were subjected to conventional ML stages to perform binary classification. In the feature extraction stage, SIFT, SURF, ORB image descriptors and bag of features technique were implemented for the appropriate differentiation of chest CT regions affected with COVID-19 from normal cases. This is the first work introducing this concept for COVID-19 diagnosis application. The preferred diverse database and selected features that are invariant to scale, rotation, distortion, noise etc. make this framework real-time applicable. Also, this fully automatic approach which is faster compared to existing models helps to incorporate it into CAD systems. The severity score was measured based on the infected regions along the lung field. Infected regions were segmented through a three-class semantic segmentation of the lung CT image. Using severity score, the disease stages were classified as mild if the lesion area covers less than 25% of the lung area; moderate if 25–50% and severe if greater than 50%. Our proposed model resulted in classification accuracy of 99.7% with a PNN classifier, along with area under the curve (AUC) of 0.9988, 99.6% sensitivity, 99.9% specificity and a misclassification rate of 0.0027. The developed infected region segmentation model gave 99.47% global accuracy, 94.04% mean accuracy, 0.8968 mean IoU (intersection over union), 0.9899 weighted IoU, and a mean Boundary F1 (BF) contour matching score of 0.9453, using Deepabv3+ with its weights initialized using ResNet-50.

Conclusions

The developed CAD system model is able to perform fully automatic and accurate diagnosis of COVID-19 along with infected region extraction and disease stage identification. The ORB image descriptor with bag of features technique and PNN classifier achieved the superior classification performance.
Change point detection for clustered expression data
Authors: Sieg Miriam , Sciesielski Lina Katrin , Kirschner Karin Michaela , Kruppa Jochen
Published: July 2022

Background

To detect changes in biological processes, samples are often studied at several time points. We examined expression data measured at different developmental stages, or more broadly, historical data. Hence, the main assumption of our proposed methodology was the independence between the examined samples over time. In addition, however, the examinations were clustered at each time point by measuring littermates from relatively few mother mice at each developmental stage. As each examination was lethal, we had an independent data structure over the entire history, but a dependent data structure at a particular time point. Over the course of these historical data, we wanted to identify abrupt changes in the parameter of interest - change points.

Results

In this study, we demonstrated the application of generalized hypothesis testing using a linear mixed effects model as a possible method to detect change points. The coefficients from the linear mixed model were used in multiple contrast tests and the effect estimates were visualized with their respective simultaneous confidence intervals. The latter were used to determine the change point(s). In small simulation studies, we modelled different courses with abrupt changes and compared the influence of different contrast matrices. We found two contrasts, both capable of answering different research questions in change point detection: The Sequen contrast to detect individual change points and the McDermott contrast to find change points due to overall progression. We provide the R code for direct use with provided examples. The applicability of those tests for real experimental data was shown with in-vivo data from a preclinical study.

Conclusion

Simultaneous confidence intervals estimated by multiple contrast tests using the model fit from a linear mixed model were capable to determine change points in clustered expression data. The confidence intervals directly delivered interpretable effect estimates representing the strength of the potential change point. Hence, scientists can define biologically relevant threshold of effect strength depending on their research question. We found two rarely used contrasts best fitted for detection of a possible change point: the Sequen and McDermott contrasts.
Research on the frailty status and adverse outcomes of elderly patients with multimorbidity
Authors: Lv Jing , Li Rao , Yuan Li , Yang Xiao-ling , Wang Yi , Ye Zi-Wei , Huang Feng-Mei
Published: July 2022

Background

As patients age, the frailty of those with multimorbidity increases, often resulting in adverse health outcomes. The current study investigated the frailty status and the factors which influence it in elderly patients with multimorbidity in Chinese hospitals. The relationship between the frailty of patients with multimorbidity and adverse outcomes was explored.

Methods

The current prospective cohort study investigated inpatients in the internal medicine department of 5 tertiary hospitals in Sichuan Province, China. A total of 3836 elderly patients with multimorbidity were enrolled. Frailty was assessed using the FRAIL scale and adverse outcome events occurring during hospitalization were tracked. Descriptive statistics and logistic regressions were used for data analysis.

Results

The prevalence of frailty was 27.2% and of pre-frailty, 58.9%. Logistic regression analysis showed that increasing age, low BMI, low education level, lack of exercise, multiple types of medications and multiple numbers of chronic diseases were the main risk factors for frailty in elderly patients with multimorbidity (OR values: 1.020, 1.469, 2.350, 2.836, 1.156 and 1.308, respectively). The incidence of adverse outcomes was 13.9% among the cohort with the most common being deep vein thrombosis (42.4%), followed by pressure injury (38.8%). Regression analysis showed a significant correlation of frailty with adverse outcome (OR: 1.496; p < 0.01).

Conclusions

The prevalence of frailty and pre-frailty in hospitalized elderly patients with multimorbidity was high. Increasing age, low BMI, low education level, lack of exercise, multiple types of medications and multiple numbers of chronic diseases were factors which influenced frailty and frailty was an important factor in the occurrence of adverse outcomes. The most common adverse outcome of elderly multimorbidity patients during hospitalization was deep vein thrombosis.
Staff-to-resident abuse in nursing homes: a scoping review
Authors: Hirt Julian , Adlbrecht Laura , Heinrich Steffen , Zeller Adelheid
Published: July 2022

Background

Elder abuse in long-term care is an important public health concern with social,

health-related, and economic implications. Staff-to-resident abuse is of particular interest since institutions should protect residents’ rights and prevent harm. To provide an up-to date comprehensive overview of staff-to-resident abuse in nursing homes, we performed a scoping review considering types of abuse, their prevalence and associated factors, descriptions, experiences, and preventive interventions.

Methods

We performed a scoping review following the framework provided by Arksey and O’Malley. We searched MEDLINE (via PubMed), CINAHL, PsycINFO via Ovid, and Cochrane Library.

Additionally, we performed free web searching using Google Scholar and checked relevant reviews. Two reviewers independently selected studies. We narratively synthesised the results.

Results

Out of 3876 references retrieved by our search, we included 46 studies in 47 reports. The prevalence rates of abuse varied widely, ranging from 0 to 93% depending on the type of abuse. Associated factors of abuse at the staff, resident, and nursing home level were evaluated inconsistently. Abuse was perceived ambiguous: even though it was considered unacceptable, it was underreported. We found only four studies addressing preventive interventions. Of these, four made recommendations for intervention development. Only one study with an experimental design examined a multi-component intervention including education and mutual support.

Conclusions

The review yielded heterogenous evidence not allowing a concrete conclusion on prevalence and associated factors. However, the results show the significance of the problem and indicate that there are associate factors of abuse that can be influenced by appropriate interventions. These are amongst other staff education, organisational culture, and conditions. Further research should investigate the composition and content of preventive interventions and their potential to reduce abusive behaviours.
Development of an online patient decision aid for kidney failure treatment modality decisions
Authors: Engels Noel , van der Nat Paul B. , Ankersmid Jet W. , Prick Janine C. M. , Parent Ellen , The Regina , Takahashi Asako , Bart Hans A. J. , van Uden-Kraan Cornelia F. , Stiggelbout Anne M. , Bos Willem J. W. , van den Dorpel Marinus A.
Published: July 2022

Background

Patient decision aids (PtDAs) support patients and clinicians in shared decision-making (SDM). Real-world outcome information may improve patients’ risk perception, and help patients make decisions congruent with their expectations and values. Our aim was to develop an online PtDA to support kidney failure treatment modality decision-making, that: 1) provides patients with real-world outcome information, and 2) facilitates SDM in clinical practice.

Methods

The International Patient Decision Aids Standards (IPDAS) development process model was complemented with a user-centred and convergent mixed-methods approach. Rapid prototyping was used to develop the PtDA with a multidisciplinary steering group in an iterative process of co-creation. The results of an exploratory evidence review and a needs-assessment among patients, caregivers, and clinicians were used to develop the PtDA. Seven Dutch teaching hospitals and two national Dutch outcome registries provided real-world data on selected outcomes for all kidney failure treatment modalities. Alpha and beta testing were performed to assess the prototype and finalise development. An implementation strategy was developed to guide implementation of the PtDA in clinical practice.

Results

The ‘Kidney Failure Decision Aid’ consists of three components designed to help patients and clinicians engage in SDM: 1) a paper hand-out sheet, 2) an interactive website, and 3) a personal summary sheet. A ‘patients-like-me’ infographic was developed to visualise survival probabilities for each treatment modality on the website. Other treatment outcomes were incorporated as event rates (e.g. hospitalisation rates) or explained in text (e.g. the flexibility of each treatment modality). No major revisions were needed after alpha and beta testing. During beta testing, some patients ignored the survival probabilities because they considered these too confronting. Nonetheless, patients agreed that every patient has the right to choose whether they want to view this information. Patients and clinicians believed that the PtDA would help patients make informed decisions, and that it would support values- and preferences-based decision-making. Implementation of the PtDA has started in October 2020.

Conclusions

The ‘Kidney Failure Decision Aid’ was designed to facilitate SDM in clinical practice and contains real-world outcome information on all kidney failure treatment modalities. It is currently being investigated for its effects on SDM in a clinical trial.
Sleep patterns and psychosocial health of parents of preterm and full-born infants: a prospective, comparative, longitudinal feasibility study
Authors: Marthinsen Gunhild Nordbø , Helseth Sølvi , Småstuen Milada , Bjorvatn Bjørn , Bandlien Signe Marie , Fegran Liv
Published: July 2022

Background

The early birth and hospitalization of a preterm infant in neonatal intensive care unit can produce several emotional and behavioural responses including sleep problems for parents. Few studies have explored sleep and its associations with health and HRQoL over time in this vulnerable parent population. This purpose of this study was to evaluate the feasibility of a prospective, comparative, longitudinal study of the sleep patterns and psychosocial health of preterm and full-born infants’ parents during the first postpartum year.

Methods

A prospective, comparative, longitudinal feasibility study was conducted. Parents of preterm infants were compared to parents of full-born infants to identify if there were differences in outcomes between the groups. The parents were instructed to wear actigraphs and complete sleep diaries for two consecutive weeks, and responded to a digital questionnaire covering stress, insomnia, fatigue, depression, social support, self-efficacy, and health-related quality of life. Survey data were collected at infant ages of 2, 6, and 12 months, actigraphy and sleep diary data were collected at infant age of 2 months only. Descriptive analysis was used to describe recruitment and attrition rates. Differences between completers and dropouts were analysed with a chi-square test (categorical data) and Mann–Whitney–Wilcoxon test for two independent samples (continuous variables).

Results

Between June 2019 and March 2020, 25 parents of a preterm infant and 78 parents of a full-born infant were recruited from four neonatal intensive care units and two maternity wards, respectively, in four Norwegian hospitals. Feasibility was predefined as recruiting ≥ 75 parents each of preterm and full-born infants. The target for the full-born group was reached. However, the preterm group recruitment was challenging. Actigraphs, sleep diaries, and questionnaires were evaluated as feasible for use in a future study. Attrition rates were high in both groups at 6 and 12 months. No parent-related characteristics were associated with participation at 6 months. At 12 months, dropouts had a statistically significantly lower age in the full-born group (both parents) and higher age and body mass index in the preterm group (fathers).

Conclusions

A longitudinal study is feasible; however, procedural changes, including using active methods and contacting participants, are necessary to increase the recruitment of preterm infants’ parents.
Characteristics and in-hospital morbidity trends associated with oral and oropharyngeal cancers in Brazil
Authors: de Miranda Vargas Deborah Gomes , da Cunha Amanda Ramos , Probst Livia Fernandes , Zafalon Edílson José , Pereira Paulo Zárate , da Silva Tagliaferro Elaine Pereira , De-Carli Alessandro Diogo
Published: July 2022

Background

Brazil experienced an expansion of the population's access to oral health policies after the creation of the Unified Health System (SUS, Sistema Único de Saúde). Through public policies, the consolidation of Primary Health Care (PHC) and the incorporation of dental care into primary and hospital care took place. The objective of this study was to identify epidemiological aspects, including the temporal trend, of hospital morbidity from oral and oropharyngeal cancer in Brazil, considering hospitalizations for this neoplasm in a hospital network linked to the public care system.

Methods

Observational study based on information on hospital admissions for oral cancer throughout Brazil. The research used data from the Brazilian Cancer Registry Information System. For the temporal series analysis, generalized linear regression model was used with the Prais-Winsten method.

Results

Of the 121,971 patients hospitalized with oral and oropharyngeal cancers, 76.40% were male and 23.60% were female, resulting in a M:F ratio of 3.24:1. Regarding the anatomical region of involvement among hospitalized patients with oral cavity neoplastic lesions, there was a predominance in non-specific places in the mouth, such as the floor of the mouth, soft and hard palate, among others (32.68%), followed by lesions in the region of tongue (28.89%). In this population, the predominant age group was between the fifth decade (31.09%) and sixth decade of life (24.99%); men presented neoplastic lesions of oral and oropharyngeal cancers at an earlier age than women. In all regions of the country, the staging of cases diagnosed in the tertiary health network accredited to the José Alencar Gomes da Silva National Cancer Institute (INCA) was late, with higher tendency for metastasis. The temporal trend of the adjusted in-hospital morbidity rates showed to be increasing in the Northeast, South and Midwest regions for the male gender. For females, they were increasing in the Northeast and South regions.

Conclusions

It is concluded that the distribution of in-hospital morbidity rates of oral and oropharyngeal cancers in the country is irregular. There is a greater number of cases identified by the study in male patients and in the Southeast and South regions; with an increasing tendency of this coefficient in both genders.
Enhanced production of terrein in marine-derived Aspergillus terreus by refactoring both global and pathway-specific transcription factors
Authors: Yao Guangshan , Bai Xinfeng , Zhang Bingxin , Wang Lu , Chen Songbiao , Wang Zonghua
Published: July 2022

Background

Terrein, a major secondary metabolite from Aspergillus terreus, shows great potentials in biomedical and agricultural applications. However, the low fermentation yield of terrein in wild A. terreus strains limits its industrial applications.

Results

Here, we constructed a cell factory based on the marine-derived A. terreus RA2905, allowing for overproducing terrein by using starch as the sole carbon source. Firstly, the pathway-specific transcription factor TerR was over-expressed under the control of a constitutive gpdA promoter of A. nidulans, resulting in 5 to 16 folds up-regulation in terR transcripts compared to WT. As expected, the titer of terrein was improved in the two tested terR OE mutants when compared to WT. Secondly, the global regulator gene stuA, which was demonstrated to suppress the terrein synthesis in our analysis, was deleted, leading to greatly enhanced production of terrein. In addition, LS-MS/MS analysis showed that deletion of StuA cause decreased synthesis of the major byproduct butyrolactones. To achieve an optimal strain, we further refactored the genetic circuit by combining deletion of stuA and overexpression of terR, a higher terrein yield was achieved with a lower background of byproducts in double mutants. In addition, it was also found that loss of StuA (both ΔstuA and ΔstuA::OEterR) resulted in aconidial morphologies, but a slightly faster growth rate than that of WT.

Conclusion

Our results demonstrated that refactoring both global and pathway-specific transcription factors (StuA and TerR) provides a high-efficient strategy to enhance terrein production, which could be adopted for large-scale production of terrein or other secondary metabolites in marine-derived filamentous fungi.
Birch pollen, air pollution and their interactive effects on airway symptoms and peak expiratory flow in allergic asthma during pollen season – a panel study in Northern and Southern Sweden
Authors: Carlsen Hanne Krage , Haga Susanna Lohman , Olsson David , Behndig Annelie F , Modig Lars , Meister Kadri , Forsberg Bertil , Olin Anna-Carin
Published: July 2022

Background

Evidence of the role of interactions between air pollution and pollen exposure in subjects with allergic asthma is limited and need further exploration to promote adequate preventive measures. The objective of this study was to assess effects of exposure to ambient air pollution and birch pollen on exacerbation of respiratory symptoms in subjects with asthma and allergy to birch.

Methods

Thirty-seven subjects from two Swedish cities (Gothenburg and Umeå) with large variation in exposure to both birch-pollen and air pollutants, participated in the study. All subjects had confirmed allergy to birch and self-reported physician-diagnosed asthma. The subjects recorded respiratory symptoms such as rhinitis or eye irritation, dry cough, dyspnoea, the use of any asthma or allergy medication and peak respiratory flow (PEF), daily for five consecutive weeks during two separate pollen seasons and a control season without pollen. Nitrogen oxides (NOx), ozone (O3), particulate matter (PM2.5), birch pollen counts, and meteorological data were obtained from an urban background monitoring stations in the study city centres. The data were analysed using linear mixed effects models.

Results

During pollen seasons all symptoms and medication use were higher, and PEF was reduced in the subjects. In regression analysis, exposure to pollen at lags 0 to 2 days, and lags 0 to 6 days was associated with increased ORs of symptoms and decreased RRs for PEF. Pollen and air pollution interacted in some cases; during low pollen exposure, there were no associations between air pollution and symptoms, but during high pollen exposure, O3concentrations were associated with increased OR of rhinitis or eye irritation, and PM2.5concentrations were associated with increased ORs of rhinitis or eye irritation, dyspnea and increased use of allergy medication.

Conclusions

Pollen and air pollutants interacted to increase the effect of air pollution on respiratory symptoms in allergic asthma. Implementing the results from this study, advisories for individuals with allergic asthma could be improved, minimizing the morbidities associated with the condition.
Rhein attenuates angiotensin II-induced cardiac remodeling by modulating AMPK–FGF23 signaling
Authors: Lu Wei , Zhu Hongqiao , Wu Jiawen , Liao Sheng , Cheng Guobing , Li Xiaoyang
Published: July 2022

Background

Increasing evidence indicates that myocardial oxidative injury plays a crucial role in the pathophysiology of cardiac hypertrophy (CH) and heart failure (HF). The active component of rhubarb, rhein exerts significant actions on oxidative stress and inflammation. Nonetheless, its role in cardiac remodeling remains unclear.

Methods

CH was induced by angiotensin II (Ang II, 1.4 mg/kg/d for 4 weeks) in male C57BL/6 J mice. Then, rhein (50 and 100 mg/kg) was injected intraperitoneally for 28 days. CH, fibrosis, oxidative stress, and cardiac function in the mice were examined. In vitro, neonatal rat cardiomyocytes (CMs) and cardiac fibroblasts (CFs) pre-treated with rhein (5 and 25 μM) were challenged with Ang II. We performed RNA sequencing to determine the mechanistic role of rhein in the heart.

Results

Rhein significantly suppressed Ang II-induced CH, fibrosis, and reactive oxygen species production and improved cardiac systolic dysfunction in vivo. In vitro, rhein significantly attenuated Ang II-induced CM hypertrophy and CF collagen expression. In addition, rhein obviously alleviated the increased production of superoxide induced by Ang II. Mechanistically, rhein inhibited FGF23 expression significantly. Furthermore, FGF23 overexpression abolished the protective effects of rhein on CMs, CFs, and cardiac remodeling. Rhein reduced FGF23 expression, mostly through the activation of AMPK (AMP-activated protein kinase). AMPK activity inhibition suppressed Ang II-induced CM hypertrophy and CF phenotypic transformation.

Conclusion

Rhein inhibited Ang II-induced CH, fibrosis, and oxidative stress during cardiac remodeling through the AMPK–FGF23 axis. These findings suggested that rhein could serve as a potential therapy in cardiac remodeling and HF.
The methyltransferase METTL3 promotes tumorigenesis via mediating HHLA2 mRNA m6A modification in human renal cell carcinoma
Authors: Zhu Dawei , Liu Yingting , Chen Junjun , Wang Qi , Li Yuan , Zhu Yulan , Feng Jun , Jiang Jingting
Published: July 2022

Background

As an important N6-methyladenosine (m6A) regulator, abnormal expression of methyltransferase-like protein 3 (METTL3) has been reported in certain human cancers. Although some data have shown that METTL3 plays an essential role in the progression of clear-cell renal cell carcinoma RCC (ccRCC), the detailed mechanism still remains largely undetermined.

Methods

Immunohistochemistry (IHC) assay was used to examine the expression of METTL3 and its clinical implications in human ccRCC by using tissue-microarray (TMA). The cellular models based on ccRCC cell lines such as 786-O and ACHN, were established by operating METTL3 and HHLA2 via knockdown or overexpression, followed by in vitro cellular function studies and in vivo subcutaneous transplantation tumor model.

Results

We found that METTL3 expression in ccRCC tissues was significantly higher compared with adjacent normal tissues. We also found the overall survival (OS) of the patients with low METTL3 expression was significantly better compared with the patients with high METTL3 expression. Furthermore, HHLA2highMETTL3high could serve as a better prognostic predictor for ccRCC patients. Depletion of METTL3 could significantly inhibit the cell viability, migration, and invasion abilities in ccRCC cell lines. Cellular studies further revealed that METTL3 could regulate HHLA2 expression via m6A modification of HHLA2 mRNA. In vitro studies revealed that HHLA2 overexpression could reverse the inhibition of cellular functions mediated by METTL3 depletion. The subcutaneous transplantation tumor model confirmed that HHLA2 overexpression could reverse the inhibition of tumor growth mediated by METTL3 depletion.

Conclusion

Our study indicated that METTL3 served as an important prognostic predictor for ccRCC patients, and we demonstrated a novel regulatory mechanism of HHLA2 by mRNA epigenetic modification via METTL3. Moreover, we found that the METTL3/HHLA2 axis could promote tumorigenesis of ccRCC. Collectively, our current findings provided new insights into the therapeutic strategy against this malignancy targeting METTL3.
Homoharringtonine is synergistically lethal with BCL-2 inhibitor APG-2575 in acute myeloid leukemia
Authors: Wei Wenwen , Huang Shujuan , Ling Qing , Mao Shihui , Qian Yu , Ye Wenle , Li Fenglin , Pan Jiajia , Lin Xiangjie , Huang Jiansong , Huang Xin , Zhai Yifan , Sun Jie , Jin Jie
Published: July 2022

Background

Despite advances in targeted agent development, effective treatment of acute myeloid leukemia (AML) remains a major clinical challenge. The B-cell lymphoma-2 (BCL-2) inhibitor exhibited promising clinical activity in AML, acute lymphoblastic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL) treatment. APG-2575 is a novel BCL-2 selective inhibitor, which has demonstrated anti-tumor activity in hematologic malignancies. Homoharringtonine (HHT), an alkaloid, exhibited anti-AML activity.

Methods

The synergistic effects of APG-2575 and HHT were studied in AML cell lines and primary samples. MTS was used to measure the cell viability. Annexin V/propidium iodide staining was used to measure the apoptosis rate by flow cytometry. AML cell xenografted mouse models were established to evaluate the anti-leukemic effect of BCL-2 inhibitor, HHT and their combination in vivo. Western blot was used to determine the expression of related proteins.

Results

APG-2575 showed comparable anti-leukemic effect to the FDA-approved BCL-2 inhibitor ABT-199 in vitro and in vivo. Combined treatment of HHT with APG-2575 synergistically inhibited AML cell growth and engraftment. Mechanistically, HHT promoted degradation of myeloid cell leukemia-1 (MCL-1), which was reported to induce BCL-2 inhibitor resistant, through the PI3K/AKT/GSK3β signaling pathway.

Conclusion

Our results provide an effective AML treatment strategy through combination of APG-2575 and HHT, which is worthy of further clinical research.
Extracellular vesicle miR-32 derived from macrophage promotes arterial calcification in mice with type 2 diabetes via inhibiting VSMC autophagy
Authors: Cao Jingsong , Chen Cong , Chen Qian , Gao Yan , Zhao Zhibo , Yuan Qing , Li Anqi , Yang Shiqi , He Yuqi , Zu Xuyu , Liu Jianghua
Published: July 2022

Background

The development of diabetes vascular calcification (VC) is tightly associated with the inhibition of vascular smooth muscle cell (VSMC) autophagy. Previously, our team found that miR-32-5p (miR-32) promotes macrophage activation, and miR-32 is expressed at higher level in the plasma of patients with coronary calcification. However, whether miR-32 mediates the function of macrophages in type 2 diabetes (T2D) VC is still unclear.

Methods

Wild-type (WT) and miR-32−/− mice were used in this study. qRT-PCR and western blotting were used to analyze gene expression. Flow cytometry was used to analyze the influence of glucose concentration on macrophage polarization. Nanoparticle tracking analysis (NTA), transmission electron microscopy, and confocal microscopy were used to identify macrophage extracellular vehicles (EVs). Immunofluorescence, in situ hybridization (ISH), immunohistochemistry, and alizarin red staining were used to analyze the influence of macrophage EVs on autophagy and calcification of the aorta of miR-32−/− mice. A luciferase assay was used to analyze the effect of miR-32 on myocyte enhancer factor 2D (Mef2d) expression. Co-IP combined with mass spectrometry (MS) and transcriptome sequencing was used to analyze the signalling pathway by which Mef2d acts in VSMC autophagy.

Results

We found that high glucose conditions upregulate miR-32 expression in macrophages and their EVs. Importantly, macrophages and their EVs promote VSMC osteogenic differentiation and upregulate miR-32 expression in VSMCs. Moreover, miR-32 mimics transfection promoted osteogenic differentiation and inhibited autophagy in VSMCs. In vitro and in vivo experiments showed that Mef2d is the key target gene of miR-32 that inhibits VSMC autophagy. Furthermore, MS and transcriptome sequencing found that cGMP-PKG is an important signalling pathway by which Mef2d regulates VSMC autophagy. In addition, after T2D miR-32−/− mice were injected with macrophage EVs via the caudal vein, miR-32 was detected in aortic VSMCs of miR-32−/− mice. Moreover, autophagy was significantly inhibited, and calcification was significantly enhanced in aorta cells.

Conclusions

These results reveal that EVs are the key pathway by which macrophages promote T2D VC, and that EVs miR-32 is a key cause of autophagy inhibition in VSMCs.
Missed opportunity for alcohol use disorder screening and management in primary health care facilities in northern rural Tanzania: a cross-sectional survey
Authors: Mushi Dorothy , Moshiro Candida , Hanlon Charlotte , Francis Joel M. , Teferra Solomon
Published: July 2022

Objective

The study aimed to identify the missed opportunity for detection and management of alcohol use disorder by primary health care workers.

Design

A cross-sectional survey

Setting

Outpatient services in the six governmental primary health care facilities in Moshi district council in Tanzania.

Participants

A total of 1604 adults were screened for alcohol use disorder (AUD) using the Alcohol Use Disorder Identification Test (AUDIT). Participants scoring 8 or above then provided details about their help-seeking behavior and barriers to seeking care. Participants’ records were reviewed to assess the screening and management of AUD.

Results

In the last 12 months, 60.7% reported alcohol use, and heavy episodic drinking (HED) was reported by 37.3%. AUD (AUDIT ≥ 8) was present in 23.9%. Males were more likely to have HED (aPR = 1.43;95% CI:1.3 to 1.4) or AUD (aPR = 2.9; 95% CI 1.9 to 4.2). Both HED and AUD increased with age. Only one participant (0.3%) had documented AUD screening and management. Only 5% of participants screening positive for AUD had sought help. Reasons for not seeking care were thinking that the problem would get better by itself (55.0%), wanting to handle the problem alone (42.0%), or not being bothered by the problem (40.0%).

Conclusion

While reported alcohol use, HED, and AUD are common among patients presenting to primary healthcare facilities in northern Tanzania, help-seeking behavior and detection are very low. Not screening for AUD in primary health care is a missed opportunity for early detection and management. There is an urgent need to develop interventions to increase the detection of AUD by health care providers, while also addressing help-seeking behavior and barriers to seeking care.
Efficacy of non-operative treatment of patients with knee arthrofibrosis using high-intensity home mechanical therapy: a retrospective review of 11,000+ patients
Authors: Stinton Shaun K. , Beckley Samantha J. , Branch Thomas P.
Published: July 2022

Background

Recovery from knee surgery or injury can be hindered by knee arthrofibrosis, which can lead to motion limitations, pain and delayed recovery. Surgery or prolonged physical therapy are often treatment options for arthrofibrosis, but they can result in increased costs and decreased quality of life. A treatment option that can regain lost motion without surgery would help minimize risks and costs for the patient. The purpose of this study was to determine treatment efficacy of high-intensity home mechanical stretch therapy in patients with knee arthrofibrosis.

Methods

Records were reviewed for 11,000+ patients who were prescribed a high-intensity stretch device to regain knee flexion. Initial and last recorded knee flexion and days between measurements were available for 9842 patients (Dataset 1). Dataset 2 was a subset of 966 patients from Dataset 1. These 966 patients had separate more rigorous measurements available from physical therapy notes (Dataset 3) in addition to data from the internal database (Dataset 2). Within and between dataset statistics were calculated using t tests for comparison of means and Cohen’s d for determination of effect size.

Results

All dataset showed significant gains in flexion (p < 0.01). Mean initial flexion, last recorded flexion and flexion gain were 79.5°, 108.4°, and 29.9°, respectively in Dataset 1. Differences between Datasets 2 and 3 had small effect sizes (Cohen’s d < 0.17). The were no significant differences when comparing workers’ compensation and non-workers’ compensation patients. The average last recorded flexion for all datasets was above the level required to perform activities of daily living. Motion gains were recorded in under 60 days from device delivery.

Conclusions

High-intensity home mechanical stretch therapy was effective in restoring knee flexion, generally in 2 months or less, and in avoiding additional surgery in severe motion loss patients regardless of sex, age, or workers’ compensation status. We believe high-intensity stretching should be considered in any patient who is at risk for a secondary motion loss surgery, because in over 90% of these patients, the complications and costs associated with surgery can be avoided.
Distal tibial tubercle osteotomy can lessen change in patellar height post medial opening wedge high tibial osteotomy? A systematic review and meta-analysis
Authors: Ren Yi-Ming , Tian Meng-Qiang , Duan Yuan-Hui , Sun Yun-Bo , Yang Tao , Hou Wei-Yu
Published: July 2022

Objective

Medial opening wedge high tibial osteotomy (MOWHTO) is a mainstream surgical method for treating early medial compartment knee osteoarthritis. Undesirable sequelae such as patella infera may happen following tuberosity osteotomy. We conducted this systematic review and meta-analysis to compare the change in patellar position after proximal tibial tubercle osteotomy (PTO) versus distal tibial tubercle osteotomy (DTO) intervention.

Methods

The 11 studies were acquired from PubMed, Medline, Embase and Cochrane Library. The data were extracted by two of the coauthors independently and were analyzed by RevMan5.3. Mean differences, odds ratios and 95% confidence intervals were calculated. Cochrane Collaboration’s Risk of Bias Tool and Newcastle–Ottawa Scale were used to assess risk of bias.

Results

Eleven observational studies were assessed. The methodological quality of the trials ranged from moderate to high. The pooled results of postoperative patellar height (Caton-Deschamps index and Blackburne-Peel index) and postoperative complications showed that the differences were statistically significant between PTO and DTO interventions. Patellar index ratios decreased significantly in the PTO groups, and 12 (9.2%) complications under DTO surgery and 2 (1.6%) complications under PTO surgery were reported. The differences of postoperative posterior tibial slope (angle) was not statistically significant, but postoperative posterior tibial slope of both groups increased. Sensitivity analysis proved the stability of the pooled results and the publication bias was not apparent.

Conclusions

DTO in MOWHTO maintained the postoperative patellar height, and clinically, for patients with serious patellofemoral osteoarthritis, DTO can be preferred. Postoperative complications are easily preventable with caution. In view of the heterogeneity and small sample size, whether these conclusions are applicable should be further determined in future studies.