bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between biomarkers and findings on low-dose computed tomography in hospitalised patients with acute exacerbation of COPD
Authors: Prins Hendrik J. , Duijkers Ruud , Kramer Gerdien , Boerhout Els , Rietema Floris J. , de Jong Pim A. , Schoorl Marianne I. , van der Werf Tjip S. , Boersma Wim G.
Published: May 2022

Background

Acute exacerbations of COPD (AECOPD) and community acquired pneumonia (CAP) often coexist. Although chest radiographs may differentiate between these diagnoses, chest radiography is known to underestimate the incidence of CAP in AECOPD. In this exploratory study, we prospectively investigated the incidence of infiltrative changes using low-dose computed tomography (LDCT). Additionally, we investigated whether clinical biomarkers of CAP differed between patients with and without infiltrative changes.

Methods

Patients with AECOPD in which pneumonia was excluded using chest radiography underwent additional LDCT-thorax. The images were read independently by two radiologists; a third radiologist was consulted as adjudicator. C-reactive protein (CRP), procalcitonin (PCT), and serum amyloid A (SAA) at admission were assessed.

Results

Out of the 100 patients included, 24 had one or more radiographic abnormalities suggestive of pneumonia. The interobserver agreement between two readers (Cohen's κ) was 0.562 (95% CI 0.371–0.752; p<0.001). Biomarkers were elevated in the group with radiological abnormalities compared to the group without abnormalities. Median (interquartile range (IQR)) CRP was 76 (21.5–148.0) mg·L−1compared to 20.5 (8.8–81.5) mg·L−1(p=0.018); median (IQR) PCT was 0.09 (0.06–0.15) µg·L−1compared to 0.06 (0.04–0.08) μg·L−1(p=0.007); median (IQR) SAA was 95 (7–160) µg·mL−1compared to 16 (3–89) µg·mL−1(p=0.019). Sensitivity and specificity for all three biomarkers were moderate for detecting radiographic abnormalities by LDCT in this population. The area under the receiver operating characteristic curve was 0.66 (95% CI 0.52–0.80) for CRP, 0.66 (95% CI 0.53–0.80) for PCT and 0.69 (95% CI 0.57–0.81) for SAA.

Conclusion

LDCT can detect additional radiological abnormalities that may indicate acute-phase lung involvement in patients with AECOPD without infiltrate(s) on the chest radiograph. Despite CRP, PCT and SAA being significantly higher in the group with radiological abnormalities on LDCT, they proved unable to reliably detect or exclude CAP. Further research is warranted.
Characterization of erenumab and rimegepant on calcitonin gene-related peptide induced responses in Xenopus Laevis oocytes expressing the calcitonin gene-related peptide receptor and the amylin-1 receptor
Authors: Hage La Cour Sanne , Juhler Kiki , Kogelman Lisette J. A. , Olesen Jes , Klærke Dan Arne , Kristensen David Møbjerg , Jansen-Olesen Inger
Published: May 2022

Background

The clinical use of calcitonin gene-related peptide receptor (CGRP-R) antagonists and monoclonal antibodies against CGRP and CGRP-R has offered new treatment possibilities for migraine patients. CGRP activates both the CGRP-R and structurally related amylin 1 receptor (AMY1-R). The relative effect of erenumab and the small-molecule CGRP-R antagonist, rimegepant, towards the CGRP-R and AMY-R needs to be further characterized.

Methods

The effect of CGRP and two CGRP-R antagonists were examined in Xenopus laevis oocytes expressing human CGRP-R, human AMY1-R and their subunits.

Results

CGRP administered to receptor expressing oocytes induced a concentration-dependent increase in current with the order of potency CGRP-R> > AMY1-R > calcitonin receptor (CTR). There was no effect on single components of the CGRP-R; calcitonin receptor-like receptor and receptor activity-modifying protein 1. Amylin was only effective on AMY1-R and CTR. Inhibition potencies (pIC50 values) for erenumab on CGRP induced currents were 10.86 and 9.35 for CGRP-R and AMY1-R, respectively. Rimegepant inhibited CGRP induced currents with pIC50 values of 11.30 and 9.91 for CGRP-R and AMY1-R, respectively.

Conclusion

Our results demonstrate that erenumab and rimegepant are potent antagonists of CGRP-R and AMY1-R with 32- and 25-times preference for the CGRP-R over the AMY1-R, respectively. It is discussed if this difference in affinity between the two receptors is the likely reason why constipation is a common and serious adverse effect during CGRP-R antagonism but less so with CGRP binding antibodies.
Effect of berberine on global modulation of lncRNAs and mRNAs expression profiles in patients with stable coronary heart disease
Authors: Han Ye-Chen , Xie Hong-Zhi , Lu Bo , Xiang Ruo-Lan , Li Jing-Yi , Qian Hao , Zhang Shu-Yang
Published: May 2022

Background

Berberine (BBR) is an isoquinoline alkaloid found in the Berberis species. It was found to have protected effects in cardiovascular diseases. Here, we investigated the effect the regulatory function of long noncoding RNAs (lncRNAs) during the treatment of stable coronary heart disease (CHD) using BBR. We performed microarray analyses to identify differentially expressed (DE) lncRNAs and mRNAs between whole blood samples from 5 patients with stable CHD taking BBR and 5 no BBR volunteers. DE lncRNAs and mRNAs were validated by quantitative real-time PCR.

Results

A total of 1703 DE lncRNAs and 912 DE mRNAs were identified. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated DE mRNAs might be associated with mammalian target of rapamycin and mitogen-activated protein kinase pathway. These pathways may be involved in the healing process after CHD. To study the relationship between mRNAs encoding transcription factors (DNA damage inducible transcript 3, sal-like protein 4 and estrogen receptor alpha gene) and CHD related de mRNAs, we performed protein and protein interaction analysis on their corresponding proteins. AKT and apoptosis pathway were significant enriched in protein and protein interaction network. BBR may affect downstream apoptosis pathways through DNA damage inducible transcript 3, sal-like protein 4 and estrogen receptor alpha gene. Growth arrest-specific transcript 5 might regulate CHD-related mRNAs through competing endogenous RNA mechanism and may be the downstream target gene regulated by BBR. Verified by the quantitative real-time PCR, we identified 8 DE lncRNAs that may relate to CHD. We performed coding and non-coding co-expression and competing endogenous RNA mechanism analysis of these 8 DE lncRNAs and CHD-related DE mRNA, and predicted their subcellular localization and N6-methyladenosine modification sites.

Conclusion

Our research found that BBR may affect mammalian target of rapamycin, mitogen-activated protein kinase, apoptosis pathway and growth arrest-specific transcript 5 in the process of CHD. These pathways may be involved in the healing process after CHD. Our research might provide novel insights for functional research of BBR.
Predicting progression to severe COVID-19 using the PAINT score
Authors: Wang Ming , Wu Dongbo , Liu Chang-Hai , Li Yan , Hu Jianghong , Wang Wei , Jiang Wei , Zhang Qifan , Huang Zhixin , Bai Lang , Tang Hong
Published: May 2022

Objectives

One of the major challenges in treating patients with coronavirus disease 2019 (COVID-19) is predicting the severity of disease. We aimed to develop a new score for predicting progression from mild/moderate to severe COVID-19.

Methods

A total of 239 hospitalized patients with COVID-19 from two medical centers in China between February 6 and April 6, 2020 were retrospectively included. The prognostic abilities of variables, including clinical data and laboratory findings from the electronic medical records of each hospital, were analysed using the Cox proportional hazards model and Kaplan–Meier methods. A prognostic score was developed to predict progression from mild/moderate to severe COVID-19.

Results

Among the 239 patients, 216 (90.38%) patients had mild/moderate disease, and 23 (9.62%) progressed to severe disease. After adjusting for multiple confounding factors, pulmonary disease, age > 75, IgM, CD16+/CD56+ NK cells and aspartate aminotransferase were independent predictors of progression to severe COVID-19. Based on these five factors, a new predictive score (the ‘PAINT score’) was established and showed a high predictive value (C-index = 0.91, 0.902 ± 0.021, p < 0.001). The PAINT score was validated using a nomogram, bootstrap analysis, calibration curves, decision curves and clinical impact curves, all of which confirmed its high predictive value.

Conclusions

The PAINT score for progression from mild/moderate to severe COVID-19 may be helpful in identifying patients at high risk of progression.
Serum leptin level and incidence of CKD: a longitudinal study of adult enrolled in the Korean genome and epidemiology study(KoGES)
Authors: Park Yon Chul , Lee Solam , Kim Young-Sang , Park Jae-Min , Han Kunhee , Lee Hunju , Hong Kyung-Won , Kim Jong-Koo , Cho Eun Suk , Chung Tae-Ha , Kim Bom-Taeck , Koh Sang Baek
Published: May 2022

Background

Chronic kidney disease(CKD) is a major public health issue and is highly prevalent in the general population. Leptin is an adipose tissue-derived endocrine factor that has been associated with several metabolic factors involved in cardiovascular diseases. Several studies have investigated the association between leptin and renal diseases so far. But the results are conflicting between the studies. The objective of our study was to verify the direct association of serum leptin level with CKD development.

Methods

This prospective cohort study included 2646 adult aged 40–70 without CKD in the Korean Genome and Epidemiology Study(KoGES) across South Korea from November 2005 to February 2012. The primary outcome was the development of CKD as defined by National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI). Multivariate stepwise logistic regression analysis was done to assess the independent associations, for with the incident of CKD as the dependent variable, in tertiles of leptin values.

Results

Among 1100 men and 1546 women with 2.8 mean years of follow-up, incidence of CKD was 18(1.63%) for men and 50(3.23%) for women. In the multivariate logistic regression models, individuals in the highest serum leptin tertile showed significant associations with risk of CKD after adjustment compared to the lowest tertiles in the population. The crude odds ratio for trend was 2.95(p = 0.004) for men. After adjusting for age, baseline eGFR variables showed correlation with statistical significance (OR for trend = 2.25, p = 0.037) for men. The same trends were also seen observed in all population and women also, but no statistical significance was found.

Conclusions

Higher plasma leptin levels are associated with the incidence of CKD, independent of traditional factors such as age, baseline eGFR. Our results suggest that leptin may partly explain part of the reported association between obesity and kidney disease.
Maternity care during COVID-19: a qualitative evidence synthesis of women’s and maternity care providers’ views and experiences
Authors: Flaherty Sarah Jane , Delaney Hannah , Matvienko-Sikar Karen , Smith Valerie
Published: May 2022

Background

As COVID-19 continued to impact society and health, maternity care, as with many other healthcare sectors across the globe, experienced tumultuous changes. These changes have the potential to considerably impact on the experience of maternity care. To gain insight and understanding of the experience of maternity care during COVID-19, from the perspectives of women and maternity care providers, we undertook a qualitative evidence synthesis (QES).

Methods

The population of interest for the QES were pregnant and postpartum women, and maternity care providers, who provided qualitative data on their experiences of maternity care during COVID-19. The electronic databases of MEDLINE, CINAHL, EMBASE, PsycINFO and the Cochrane COVID study register were systematically searched from 01 Jan 2020 to 13 June 2021. The methodological quality of the included studies was appraised using a modified version of the quality assessment tool, based on 12-criteria, designed by the Evidence for Policy and Practice Information coordinating Centre (EPPI-Centre). Data were extracted by two reviewers independently and synthesised using the Thomas and Harden framework. Confidence in the findings was assessed using the Grading of Recommendations Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual).

Results

Fifty records relating to 48 studies, involving 9,348 women and 2,538 maternity care providers, were included in the QES. The methodological quality of the studies varied from four studies meeting all 12 quality criteria to two studies meeting one quality criterion only. The synthesis revealed eight prominent themes. Five of these reflected women’s experiences: 1) Altered maternity care (women), 2) COVID-related restrictions, 3) Infection prevention and risk, 4) ‘the lived reality’ – navigating support systems, and 5) Interactions with maternity services. Three themes reflected maternity care providers’ experiences: 6) Altered maternity care (providers), 7) Professional and personal impact, and 8) Broader structural impact. Confidence in the findings was high or moderate.

Conclusion

Although some positive experiences were identified, overall, this QES reveals that maternity care during COVID-19 was negatively experienced by both women and maternity care providers. The pandemic and associated changes evoked an array of emotive states for both populations, many of which have the potential to impact on future health and wellbeing. Resource and care planning to mitigate medium- and longer-term adverse sequelae are required.

PROSPERO registration

CRD42021232684.
Incidence and predictors of paternal anxiety and depression following fetal abnormalities requiring pregnancy termination: a cross-sectional study in China
Authors: Sun Shiwen , Hao Yuping , Qian Jialu , Wang Fang , Sun Yaping , Yu Xiaoyan
Published: May 2022

Background

China is a country with a high prevalence of fetal abnormalities. Termination of pregnancy for fetal abnormalities (TOPFA) is a devastating traumatic event for parents and families, resulting in serious and lasting psychological problems. The impact of TOPFA on mothers has been extensively explored, but little research has been conducted on the resulting paternal psychological problems. This study sought to determine the prevalence and predictors of paternal anxiety and depression following TOPFA.

Methods

We analysed cross-sectional data from 169 Chinese couples (169 mothers and 169 fathers) who experienced TOPFA. Anxiety was assessed with the Self-Rating Anxiety Scale (SAS), and depression was measured with the Self-Rating Depression Scale (SDS) for fathers and the Edinburgh Postnatal Depression Scale (EPDS) for mothers. We used the Social Support Rating Scale (SSRS) to assess levels of social support.

Results

Overall, 19.5% of fathers and 24.3% of mothers had symptoms of anxiety, but there was no significant difference in the incidence of anxiety between fathers and mothers. However, depression was more common in mothers (50.3%) than in fathers (24.9%). Level of income (β = -2.945, 95% CI: -5.448 to -0.442), worry about the pregnancy (β = 3.404, 95% CI: 1.210 to 5.599) and objective support (β = -0.668, 95% CI: -1.163 to -0.173) were predictors of anxiety in fathers. Worry about the pregnancy (β = 4.022, 95% CI: 1.630 to 6.414), objective support (β = -0.652, 95% CI: -1.229 to -0.075) and maternal depression (β = 0.497, 95% CI: 0.159 to 0.836) were predictors of paternal depression.

Conclusion

Anxiety and depression were prevalent among parents following TOPFA in China, and fathers had similar levels of anxiety as mothers. Strategies to support fathers should consider social support and psychological interaction and draw upon father-inclusive intervention recommendations.
Development of multivariable models to predict perinatal depression before and after delivery using patient reported survey responses at weeks 4–10 of pregnancy
Authors: Reps Jenna M. , Wilcox Marsha , McGee Beth Ann , Leonte Marie , LaCross Lauren , Wildenhaus Kevin
Published: May 2022

Background

Perinatal depression is estimated to affect ~ 12% of pregnancies and is linked to numerous negative outcomes. There is currently no model to predict perinatal depression at multiple time-points during and after pregnancy using variables ascertained early into pregnancy.

Methods

A prospective cohort design where 858 participants filled in a baseline self-reported survey at week 4–10 of pregnancy (that included social economics, health history, various psychiatric measures), with follow-up until 3 months after delivery. Our primary outcome was an Edinburgh Postnatal Depression Score (EPDS) score of 12 or more (a proxy for perinatal depression) assessed during each trimester and again at two time periods after delivery. Five gradient boosting machines were trained to predict the risk of having EPDS score >  = 12 at each of the five follow-up periods. The predictors consisted of 21 variables from 3 validated psychometric scales. As a sensitivity analysis, we also investigated different predictor sets that contained: i) 17 of the 21 variables predictors by only including two of the psychometric scales and ii) including 143 additional social economics and health history predictors, resulting in 164 predictors.

Results

We developed five prognostic models: PND-T1 (trimester 1), PND-T2 (trimester 2), PND-T3 (trimester 3), PND-A1 (after delivery 1) and PND-A2 (delayed onset after delivery) that calculate personalised risks while only requiring that women be asked 21 questions from 3 validated psychometric scales at weeks 4–10 of pregnancy. C-statistics (also known as AUC) ranged between 0.69 (95% CI 0.65–0.73) and 0.77 (95% CI 0.74–0.80). At 50% sensitivity the positive predictive value ranged between 30%-50% across the models, generally identifying groups of patients with double the average risk. Models trained using the 17 predictors and 164 predictors did not improve model performance compared to the models trained using 21 predictors.

Conclusions

The five models can predict risk of perinatal depression within each trimester and in two post-natal periods using survey responses as early as week 4 of pregnancy with modest performance. The models need to be externally validated and prospectively tested to ensure generalizability to any pregnant patient.
Social, economic, political, and geographical context that counts: meta-review of implementation determinants for policies promoting healthy diet and physical activity
Authors: Lobczowska Karolina , Banik Anna , Forberger Sarah , Kaczmarek Krzysztof , Kubiak Thomas , Neumann-Podczaska Agnieszka , Romaniuk Piotr , Scheidmeir Marie , Scheller Daniel A. , Steinacker Juergen M. , Wendt Janine , Bekker Marleen P. M. , Zeeb Hajo , Luszczynska Aleksandra ,   on behalf of Policy Evaluation Network (PEN) Consortium
Published: May 2022

Background

This meta-review investigated the context-related implementation determinants from seven domains (geographical, epidemiological, sociocultural, economic, ethics-related, political, and legal) that were systematically indicated as occurring during the implementation of obesity prevention policies targeting a healthy diet and a physically active lifestyle.

Methods

Data from nine databases and documentation of nine major stakeholders were searched for the purpose of this preregistered meta-review (#CRD42019133341). Context-related determinants were considered strongly supported if they were indicated in ≥60% of the reviews/stakeholder documents. The ROBIS tool and the Methodological Quality Checklist-SP were used to assess the quality-related risk of bias.

Results

Published reviews (k = 25) and stakeholder documents that reviewed the evidence of policy implementation (k = 17) were included. Across documents, the following six determinants from three context domains received strong support: economic resources at the macro (66.7% of analyzed documents) and meso/micro levels (71.4%); sociocultural context determinants at the meso/micro level, references to knowledge/beliefs/abilities of target groups (69.0%) and implementers (73.8%); political context determinants (interrelated policies supported in 71.4% of analyzed reviews/documents; policies within organizations, 69.0%).

Conclusions

These findings indicate that sociocultural, economic, and political contexts need to be accounted for when formulating plans for the implementation of a healthy diet and physical activity/sedentary behavior policies.
“The one who doesn’t take ART medication has no wealth at all and no purpose on Earth” – a qualitative assessment of how HIV-positive adults in Uganda understand the health and wealth-related benefits of ART
Authors: Saya Uzaib , MacCarthy Sarah , Mukasa Barbara , Wabukala Peter , Lunkuse Lillian , Wagner Zachary , Linnemayr Sebastian
Published: May 2022

Background

Increases in life expectancy from antiretroviral therapy (ART) may influence future health and wealth among people living with HIV (PLWH). What remains unknown is how PLWH in care perceive the benefits of ART adherence, particularly in terms of improving health and wealth in the short and long-term at the individual, household, and structural levels. Understanding future-oriented attitudes towards ART may help policymakers tailor care and treatment programs with both short and long-term-term health benefits in mind, to improve HIV-related outcomes for PLWH.

Methods

In this qualitative study, we conducted semi-structured interviews among a subsample of 40 PLWH in care at a clinic in Uganda participating in a randomized clinical trial for treatment adherence in Uganda (clinicaltrials.gov: NCT03494777). Interviews were transcribed verbatim and translated from Luganda into English. Two co-authors independently reviewed transcripts, developed a detailed codebook, achieved 93% agreement on double-coded interviews, and analyzed data using inductive and deductive content analysis. Applying the social-ecological framework at the individual, household, and structural levels, we examined how PLWH perceived health and wealth-related benefits to ART.

Results

Our findings revealed several benefits of ART expressed by PLWH, going beyond the short-term health benefits to also include long-term economic benefits. Such benefits largely focused on the ability of PLWH to live longer and be physically and mentally healthy, while also fulfilling responsibilities at the individual level pertaining to themselves (especially in terms of positive long-term habits and motivation to work harder), at the household level pertaining to others (such as improved relations with family and friends), and at the structural level pertaining to society (in terms of reduced stigma, increased comfort in disclosure, and higher levels of civic responsibility).

Conclusions

PLWH consider short and long-term health benefits of ART. Programming designed to shape ART uptake and increase adherence should emphasize the broader benefits of ART at various levels. Having such benefits directly integrated into the design of clinic-based HIV interventions can be useful especially for PLWH who face competing interests to increase medication adherence. These benefits can ultimately help providers and policymakers better understand PLWH’s decision-making as it relates to improving ART-related outcomes.
Femoral rollback at high-flexion during squatting is related to the improvement of sports activities after bicruciate-stabilized total knee arthroplasty: an observational study
Authors: Kono Kenichi , Inui Hiroshi , Kage Tomofumi , Tomita Tetsuya , Yamazaki Takaharu , Taketomi Shuji , Yamagami Ryota , Kawaguchi Kohei , Tanaka Sakae
Published: May 2022

Background

In bicruciate-stabilized total knee arthroplasty (BCS-TKA), the relationship between the postoperative kinematics and sports subscales in patient-reported outcome measures (PROMs) remains unknown. The purpose of this study was to determine the relationship between kinematics and sports subscales using the PROMs after BCS-TKA.

Methods

Sixty-one patients with severe knee osteoarthritis were examined at 13.5 ± 7.8 months after BCS-TKA. The patients performed squats under single fluoroscopic surveillance in the sagittal plane. Range of motion of the knee, axial rotation of the femur relative to the tibial component, and anteroposterior (AP) translation of the medial and lateral femorotibial contact points were measured using a 2D-to-3D registration technique. In addition, the relationship between the kinematics and improvement of the sports subscales in the Knee Injury and Osteoarthritis Outcome Score (KOOS) was evaluated.

Results

In rotation angle, the femoral external rotation was observed from 0 to 50° of flexion. The amount of femoral external rotation did not correlate with PROMs-SP. In medial AP translation, posterior translation was observed from 0 to 20° and 80–110° of flexion. Mild anterior translation was observed from 20 to 80° of flexion. Beyond 80° of flexion, posterior translation was positively correlated with squatting. In lateral AP translation, posterior translation was observed from 0 to 20° and 80–110° of flexion. Beyond 80° of flexion, posterior translation was positively correlated with running, jumping, twisting/pivoting, and kneeling.

Conclusion

Femoral rollback at high flexion during squatting may be important to improve sports performance after BCS-TKA.
Video-assisted subtotal parietal pleurectomy: an effective procedure for recurrent refractory pneumothorax
Authors: Cai Haomin , Mao Rui , Zhou Yiming
Published: May 2022

Background

Refractory pneumothorax combined with diffuse emphysematous changes is an intractable problem requiring surgical treatment. Traditional bullectomy may result in long-term air leakage and has a risk of early recurrence. Pleurectomy is an effective pleurodesis procedure, which appears to be more suitable for these cases. We conducted this study to present our experience with this procedure.

Methods

We collected the clinical data of 14 patients who underwent subtotal pleurectomy via video-assisted thoracic surgery (VATS) in our institution from November 2016 to October 2021. All patients had undergone complete preoperative examinations and met the indications for pleurectomy. Regular follow-up was conducted after surgery.

Results

The study population was composed of 11 males and 3 females, with an average age of 52.4 ± 19.0 years. Subtotal pleurectomy via VATS was successfully performed in all patients, with no conversion to open surgery. The average operation time was 82.5 ± 23.4 min (range 45–120 min), intraoperative blood loss was 92.9 ± 37.1 mL (range 50–200 mL), postoperative hospital stay was 5.0 ± 4.8 days (range 2–19 days), and chest tube duration time was 22.1 ± 13.0 days (range 5–49 days). No major complication occurred except for one case in which reoperation was performed due to massive postoperative hemorrhage. The mean follow-up time was 24.8 ± 17.0 months (range 6–60 months); no recurrence was noted.

Conclusions

Subtotal pleurectomy via VATS is a satisfactorily effective procedure for preventing pneumothorax recurrence.
Role of human organic cation transporter-1 (OCT-1/SLC22A1) in modulating the response to metformin in patients with type 2 diabetes
Authors: Kawoosa Fizalah , Shah Zafar A. , Masoodi Shariq R. , Amin Asif , Rasool Roohi , Fazili Khalid M. , Dar Abid Hamid , Lone Asif , ul Bashir Samir
Published: May 2022

Background

Organic cation transporter 1 primarily governs the action of metformin in the liver. There are considerable inter-individual variations in metformin response. In light of this, it is crucial to obtain a greater understanding of the influence of OCT1 expression or polymorphism in the context of variable responses elicited by metformin treatment.

Results

We observed that the variable response to metformin in the responders and non-responders is independent of isoform variation and mRNA expression of OCT-1. We also observed an insignificant difference in the serum metformin levels of the patient groups. Further, molecular docking provided us with an insight into the hotspot regions of OCT-1 for metformin binding. Genotyping of these regions revealed SNPs 156T>C and 1222A>G in both the groups, while as 181C>T and 1201G>A were found only in non-responders. The 181T>C and 1222A>G changes were further found to alter OCT-1 structure in silico and affect metformin transport in vitro which was illustrated by their effect on the activation of AMPK, the marker for metformin activity.

Conclusion

Taken together, our results corroborate the role of OCT-1 in the transport of metformin and also point at OCT1 genetic variations possibly affecting the transport of metformin into the cells and hence its subsequent action in responders and non-responders.
Socio-demographic correlates of diabetes self-reporting validity: a study on the adult Kurdish population
Authors: Moradpour Farhad , Piri Negar , Dehghanbanadaki Hojat , Moradi Ghobad , Fotouk-Kiai Mahdiyeh , Moradi Yousef
Published: May 2022

Background

In this research, data of the DehPCS study were used to assess the validity of self-reported diabetes based on the reference criteria, including the history of taking oral anti-diabetic drugs, insulin injection, or high fasting blood sugar.

Methods

A cross-sectional analytical study was performed on 4400 participants of the DehPCS study, aged 35–70 years. The reference criteria were oral hypoglycemic drug consumption, insulin injection, and/ or fasting blood sugar ≥126 (mg/dl). The self-reporting diabetes was investigated by well-trained interviewers before the diabetes diagnosis based on the reference criteria. The validity of self-reporting diabetes was assessed using sensitivity, specificity, as well as positive and negative predictive values. Socio-demographic correlates of self-reported agreement were examined by multinomial logistic regression.

Results

Three thousand nine hundred ninety-six people participated in this study, and the participation rate was equal to 90.8%. The diabetes prevalence among the study population was 13.1% based on self-reports and 9.7% based on the reference criteria. Five hundred twenty-three participants reported diabetes, 213 (41.28%) of whom did not have it. We found a good agreement of 92.3% with an acceptable kappa value of 65.1% between self-reporting diabetes and the reference criteria. Diabetes self-reporting also guaranteed sensitivity of 78.5%, specificity of 93.9%, as well as the positive and negative predictive values of 58.7% and of 98.0%, respectively. Being female, the higher economic class, the higher body mass index (BMI), and the positive family history of diabetes increased the chance of false positive. Being male, older ages and the moderate economic class increased the chance of false positive.

Conclusion

Self-reporting diabetes is identified as a relatively valid tool which could fairly determine the diabetes prevalence in epidemiological studies. It should be noted that its validity is influenced by some socio-demographic characteristics.
Consultations’ demand for a hospital palliative care unit: how to increase appropriateness? Implementing and evaluating a multicomponent educational intervention aimed at increase palliative care complexity perception skill
Authors: Tanzi Silvia , Martucci Gianfranco , Autelitano Cristina , Alquati Sara , Peruselli Carlo , Artioli Giovanna
Published: May 2022

Background

Planned, multidisciplinary teams’ discussions of cases are common in cancer care, but their impact on patients’ outcome is not always clear. Palliative care (PC) needs might emerge long before the last weeks of life. Many palliative care patients could be managed from the usual care staff, if appropriately trained; specialist palliative care should be provided to patients with more complex needs. Staff needs adequate training, so that only patients presenting a higher complexity are properly referred to the second level (“specialized”) PC services. In the considered hospital setting, “tumour boards” (multidisciplinary discussions) refer often to a low number of patients. Overall complexity of patients’ needs is hardly considered.

Methods

A mixed method pilot study with data triangulation of professionals’ interviews and an independently structured evaluation of complexity of referred patients, before and after the intervention, using the PALCOM instrument. We trained four teams of professionals to deliver first-level palliation and to refer patients with complex needs detected in multidisciplinary discussions. A multicomponent, first level PC educational intervention, including information technology’s adaptation, a training course, and bedside training was offered from the specialized PC Services, to all the HPs involved in multidisciplinary pancreas, lung, ovarian, and liver tumour boards.

Results

While the level of complexity of referred patients did not increase, trainees seemed to develop a better understanding of palliative care and a higher sensitivity to palliative needs. The number of referred patients increased, but patients’ complexity did not. Qualitative data showed that professionals seemed to be more aware of the complexity of PC needs. A “meaning shift” was perceived, specifically on the referral process (e.g., “when” and “for what” referring to specialist PC) and on the teams’ increased focus on patients’ needs. The training, positively received, was adapted to trainees’ needs and observations that led also to organizational modifications.

Conclusions

Our multicomponent intervention positively impacted the number of referrals but not the patients’ complexity (measured with the PALCOM instrument). Hospital staff does not easily recognize that patients may have PC needs significantly earlier than at the end of life.
The risk of outpatient mental health care service use following departure from work: a cohort register study of migrant and non-migrant women
Authors: Straiton Melanie , Hynek Kamila Angelika , Corbett Karina
Published: May 2022

Background

Non-workforce participation is associated with increased risk of mental disorder in the general population. Migrant women face disadvantage in the labour market but use mental health services to a lesser extent. This study investigates the risk of using mental health services following departure from the workforce among women in Norway, and if the strength of the relationship varies for migrant and non-migrant women.

Methods

Using linked registry data, we followed a cohort of 746,635 women who had a stable workforce attachment over a three-year period. We used Cox proportional hazard models to determine the risk of using outpatient mental health services (OPMH) following departure from the workforce. We included an interaction analysis to determine if the relationship differed by migrant group and length of stay and conducted subsequent stratified analyses.

Results

Departure from the workforce was associated with a 40% increased risk of using OPMH services among all women. Interaction analyses and subsequent stratified analyses indicated that departure from the workforce was associated with an increased risk of using OPMH services among non-migrant women and among women from countries outside of the European Economic Area, regardless of length of stay. For women from the European Economic Area with 2–6 years or 7–15 years in Norway, however, there was no increased risk.

Conclusions

Departure from the workforce is associated with increased risk of mental health service use, also among migrant women. Migrant women as a group, are more often temporarily employed and therefore at greater risk of falling out of the workforce and developing a mental disorder. However, women with shorter length of stays may experience greater barriers to care and service use may be a poorer indicator of actual mental disorder.
“I have such a hard time hitting myself, I thought it’d be easier”: perspectives of hospitalized patients on injecting drugs into vascular access devices
Authors: Brooks Hannah L. , Salvalaggio Ginetta , Pauly Bernadette , Dong Kathryn , Bubela Tania , Taylor Marliss , Hyshka Elaine
Published: May 2022

Background

Hospital patients who use drugs may require prolonged parenteral antimicrobial therapy administered through a vascular access device (VAD). Clinicians’ concerns that patients may inject drugs into these devices are well documented. However, the perspectives of patients on VAD injecting are not well described, hindering the development of informed clinical guidance. This study was conducted to elicit inpatient perspectives on the practice of injecting drugs into VADs and to propose strategies to reduce associated harms.

Methods

Researchers conducted a focused ethnography and completed semi-structured interviews with 25 inpatients at a large tertiary hospital in Western Canada that experiences a high rate of drug-related presentations annually.

Results

A few participants reported injecting into their VAD at least once, and nearly all had heard of the practice. The primary reason for injecting into a VAD was easier venous access since many participants had experienced significant vein damage from injection drug use. Several participants recognized the risks associated with injecting into VADs, and either refrained from the practice or took steps to maintain their devices while using them to inject drugs. Others were uncertain how the devices functioned and were unaware of potential harms.

Conclusions

VADs are important for facilitating completion of parenteral antimicrobial therapy and for other medically necessary care. Prematurely discharging patients who inject into their VAD from hospital, or discontinuing or modifying therapy, results in inequitable access to health care for a structurally vulnerable patient population. Our findings demonstrate a need for healthcare provider education and non-stigmatizing clinical interventions to reduce potential harms associated with VAD injecting. Those interventions could include providing access to specialized pain and withdrawal management, opioid agonist treatment, and harm reduction services, including safer drug use education to reduce or prevent complications from injecting drugs into VADs.
The granulosa cell response to luteinizing hormone is partly mediated by YAP1-dependent induction of amphiregulin
Authors: Godin Philippe , Tsoi Mayra F. , Morin Martin , Gévry Nicolas , Boerboom Derek
Published: May 2022

Background

The LH surge is a pivotal event that triggers multiple key ovarian processes including oocyte maturation, cumulus expansion, follicular wall rupture and luteinization of mural granulosa and theca cells. Recently, LH-dependent activation of the Hippo signaling pathway has been shown to be required for the differentiation of granulosa cells into luteal cells. Still, the precise interactions between Hippo and LH signaling in murine granulosa cells remain to be elucidated.

Methods

To detect the expression of effectors of the Hippo pathway, western blot, immunohistochemical and RT-qPCR analyses were performed on granulosa cells treated with LH in vitro or isolated from immature mice treated with eCG and hCG. Cultured granulosa cells were pretreated with pharmacologic inhibitors to identify the signaling pathways involved in Hippo regulation by LH. To study the roles of Yap1 and Taz in the regulation of the LH signaling cascade, RT-qPCR and microarray analyses were done on granulosa cells from Yap1f/f;Tazf/f mice treated with an adenovirus to drive cre expression. RT-qPCR was performed to evaluate YAP1 binding to the Areg promoter following chromatin immunoprecipitation of granulosa cells collected from mice prior to or 60 min following hCG treatment.

Results

Granulosa cells showed a transient increase in LATS1, YAP1 and TAZ phosphorylation levels in response to the ovulatory signal. This Hippo activation by LH was mediated by protein kinase A. Furthermore, Yap1 and Taz are required for the induction of several LH target genes such as Areg, Pgr and Ptgs2, and for the activation of the ERK1/2 pathway. Consistent with these results, there was a substantial overlap between genes that are upregulated by LH and those that are downregulated following loss of Yap1/Taz, highlighting a major role for Hippo in mediating LH actions in the ovulation process. Finally, we showed that there is a marked recruitment of YAP1 to the Areg promoter of granulosa cells in response to hCG stimulation.

Conclusions

Overall, these results indicate that Hippo collaborates with the cAMP/PKA and ERK1/2 pathways to participate in the precise regulation of the LH cascade, and that Areg, as a direct transcriptional target of YAP1, is involved in mediating its actions in the ovary.
Associations of ultra-processed food intake with maternal weight change and cardiometabolic health and infant growth
Authors: Cummings Jenna R. , Lipsky Leah M. , Schwedhelm Carolina , Liu Aiyi , Nansel Tonja R.
Published: May 2022

Background

Excessive intake of ultra-processed foods, formulated from substances extracted from foods or derived from food constituents, may be a modifiable behavioral risk factor for adverse maternal and infant health outcomes. Prior work has predominately examined health correlates of maternal ultra-processed food intake in populations with substantially lower ultra-processed food intake compared to the US population. This longitudinal study investigated relations of ultra-processed food intake with maternal weight change and cardiometabolic health and infant growth in a US cohort.

Methods

Mothers in the Pregnancy Eating Attributes Study were enrolled at ≤12 weeks gestation and completed multiple 24-Hour Dietary Recalls within six visit windows through one-year postpartum (458 mothers enrolled, 321 retained at one-year postpartum). The NOVA (not an acronym) system categorized food and underlying ingredient codes based on processing level. Maternal anthropometrics were measured throughout pregnancy and postpartum, and infant anthropometrics were measured at birth and ages 2 months, 6 months, and 1 year. Maternal cardiometabolic markers were analyzed from blood samples obtained during the second and third trimesters.

Results

Holding covariates and total energy intake constant, a 1-SD greater percent energy intake from ultra-processed foods during pregnancy was associated with 31% higher odds of excessive gestational weight gain (p= .045, 95% CI [1.01, 1.70]), 0.68±0.29 mg/L higher c-reactive protein during pregnancy (p= .021, 95% CI [0.10, 1.26]), 6.7±3.4% greater gestational weight gain retained (p= .049, 95% CI [0.03, 13.30]), and 1.09±0.36 kg greater postpartum weight retention (p= .003, 95% CI [0.38, 1.80]). No other significant associations emerged.

Conclusions

Ultra-processed food intake during pregnancy may be a modifiable behavioral risk factor for adverse maternal weight outcomes and inflammation. Randomized controlled trials are needed to test whether targeting ultra-processed food intake during pregnancy may support optimal maternal health.

Trial registration

Clinicaltrials.gov. Registration ID –NCT02217462. Date of registration – August 13, 2014.
Free-living gait does not differentiate chronic mTBI patients compared to healthy controls
Authors: Powell Dylan , Godfrey Alan , Parrington Lucy , Campbell Kody R. , King Laurie A. , Stuart Sam
Published: May 2022

Background

Physical function remains a crucial component of mild traumatic brain injury (mTBI) assessment and recovery. Traditional approaches to assess mTBI lack sensitivity to detect subtle deficits post-injury, which can impact a patient’s quality of life, daily function and can lead to chronic issues. Inertial measurement units (IMU) provide an opportunity for objective assessment of physical function and can be used in any environment. A single waist worn IMU has the potential to provide broad/macro quantity characteristics to estimate gait mobility, as well as more high-resolution micro spatial or temporal gait characteristics (herein, we refer to these as measures of quality). Our recent work showed that quantity measures of mobility were less sensitive than measures of turning quality when comparing the free-living physical function of chronic mTBI patients and healthy controls. However, no studies have examined whether measures of gait quality in free-living conditions can differentiate chronic mTBI patients and healthy controls. This study aimed to determine whether measures of free-living gait quality can differentiate chronic mTBI patients from controls.

Methods

Thirty-two patients with chronic self-reported balance symptoms after mTBI (age: 40.88 ± 11.78 years, median days post-injury: 440.68 days) and 23 healthy controls (age: 48.56 ± 22.56 years) were assessed for ~ 7 days using a single IMU at the waist on a belt. Free-living gait quality metrics were evaluated for chronic mTBI patients and controls using multi-variate analysis. Receiver operating characteristics (ROC) and Area Under the Curve (AUC) analysis were used to determine outcome sensitivity to chronic mTBI.

Results

Free-living gait quality metrics were not different between chronic mTBI patients and controls (all p > 0.05) whilst controlling for age and sex. ROC and AUC analysis showed stride length (0.63) was the most sensitive measure for differentiating chronic mTBI patients from controls.

Conclusions

Our results show that gait quality metrics determined through a free-living assessment were not significantly different between chronic mTBI patients and controls. These results suggest that measures of free-living gait quality were not impaired in our chronic mTBI patients, and/or, that the metrics chosen were not sensitive enough to detect subtle impairments in our sample.
COVID-19 infection: an overview on cytokine storm and related interventions
Authors: Montazersaheb Soheila , Hosseiniyan Khatibi Seyed Mahdi , Hejazi Mohammad Saeid , Tarhriz Vahideh , Farjami Afsaneh , Ghasemian Sorbeni Faramarz , Farahzadi Raheleh , Ghasemnejad Tohid
Published: May 2022

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has posed a significant threat to global health. This virus affects the respiratory tract and usually leads to pneumonia in most patients and acute respiratory distress syndrome (ARDS) in 15% of cases. ARDS is one of the leading causes of death in patients with COVID-19 and is mainly triggered by elevated levels of pro-inflammatory cytokines, referred to as cytokine storm. Interleukins, such as interleukin-6 (1L-6), interleukin-1 (IL-1), interleukin-17 (IL-17), and tumor necrosis factor-alpha (TNF-α) play a very significant role in lung damage in ARDS patients through the impairments of the respiratory epithelium. Cytokine storm is defined as acute overproduction and uncontrolled release of pro-inflammatory markers, both locally and systemically. The eradication of COVID-19 is currently practically impossible, and there is no specific treatment for critically ill patients with COVID-19; however, suppressing the inflammatory response may be a possible strategy. In light of this, we review the efficacy of specific inhibitors of IL6, IL1, IL-17, and TNF-α for treating COVID-19-related infections to manage COVID-19 and improve the survival rate for patients suffering from severe conditions.

Graphical Abstract