bluuebunny/crossref_metadata_2025 huggingface dataset:
Three-Year Point Prevalence Survey of Antimicrobial Use in a Chinese University Hospital
Authors: Jing Fa-Hong , Wang Qiang , He Tian-Jiao , Xin Na , Wang Yao-Wei , Han Yang , Wang Xin , Li Zhuo
Published: February 2024

To evaluate the prevalence and quality of antimicrobial prescriptions using a Global Point Prevalence Survey (PPS) tool and help identify targets for improvement of antimicrobial prescribing and inform the development of antimicrobial stewardship activities. Antimicrobial prescriptions for inpatients staying at a hospital overnight were surveyed on one weekday in October 2018, November 2019, and November 2020. Data including basic patient information, antimicrobial drugs, quality evaluation of antimicrobial drug prescription, and the risk factors of nosocomial infection were collected from doctor network workstation. Patient information was anonymized and entered in the PPS Web application by physicians. A total of 720 patients (median age, 62 years) were surveyed. Of them, 246 (34.2%) were prescribed antimicrobials on the survey days. Hospital-wide antimicrobial use had a significantly decreasing trend (P<0.001). The most commonly prescribed antimicrobial drugs were third-generation cephalosporins (40.5%), followed by quinolones (21.8%) and second-generation cephalosporin (12.5%). In our study, cefoperazone/sulbactam, ceftazidime, and levofloxacin were the most commonly used antimicrobials. The most common indication for antimicrobial use was pneumonia or lower respiratory tract infection (159/321, 49.5%). Antimicrobial for surgical prophylaxis represented 16.2% of the total antibiotic doses. Of those, 67.3% were administered for more than 24 h. The rate of adherence to antibiotic guidelines was 61.4%. The indications for antimicrobials were not documented in 54.5% of the prescriptions. Stop/review date was documented for 36.8% of prescriptions. The PPS tool is useful in identifying targets to enhance the quality of antimicrobial prescriptions to improve the adherence rate in hospitals. This survey can be used as a control to assess the rational application quality of antimicrobial after regular application of antimicrobial intervention.
MiR-205-5p-Mediated MAGI1 Inhibition Attenuates the Injury Induced by Diabetic Nephropathy
Authors: Xiang Yuanbing , Sun Min , Wu Yuxi , Hu Yao
Published: February 2024

Introduction: Membrane-associated guanylate kinase with an inverted domain structure-1 (MAGI1) is dysregulated in diabetes; however, its role in diabetic nephropathy (DN) remains unclear. In this study, we determined the function and associated mechanisms of MAGI1 in DN. Methods: Serum samples from 28 patients with DN and 28 normal volunteers were collected. High-glucose (HG)-treated human renal mesangial cells (HRMCs) and streptozotocin-treated rats were used as cell and animal models of DN, respectively. MAGI1 mRNA expression was measured by quantitative reverse transcription polymerase chain reaction. An 5-Ethynyl-2′-deoxyuridine assay was used to assess cell proliferation, whereas Western blot analysis was performed to quantitate the levels of markers associated with proliferation, the extracellular matrix (ECM), and inflammation. These included collagens I, collagen IV, cyclin D1, AKT, phosphorylated-AKT (p-AKT), PI3K, and phosphorylated-PI3K (p-PI3K). The predicted binding of miR-205-5p with the MAGI1 3′UTR was verified using a luciferase assay. Results: MAGI1 expression was increased in serum samples from DN patients and in HRMCs treated with HG. MAGI1 knockdown attenuated excessive proliferation, ECM accumulation, and inflammation in HG-induced HRMCs as well as injury to DN rats. MiR-205-5p potentially interacted with the 3′UTR of MAGI1 and binding was verified using a dual-luciferase reporter assay. Moreover, miR-205-5p repression offset the inhibitory influence of MAGI1 knockdown on proliferation, collagen deposition, and inflammation in HG-treated HRMCs. Conclusion: MAGI1 contributes to injury caused by DN. Furthermore, miR-205-5p binds to MAGI1 and suppresses MAGI1 function. These findings suggest that miR-205-5p-mediates MAGI1 inhibition, which represents a potential treatment for DN.
Multiplex Proteomics in the Identification of Potential Biomarkers of Very Severe Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease in Allogeneic Hematopoietic Cell Transplant Patients Treated with Defibrotide
Authors: Vasudevan Nampoothiri Ram , Avery Lisa , Pasic Ivan , Prassas Ioannis , Diamandis Eleftherios , Michelis Fotios V.
Published: February 2024

Introduction: Despite well-established clinical criteria for diagnosis of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) following allogeneic hematopoietic cell transplantation (HCT), there is a lack of established diagnostic protein biomarkers. Methods: Prospective samples were collected from patients with very severe SOS/VOD at diagnosis and days +3, +7, +14, and +30 post-initiation of defibrotide. Samples from age-matched controls with no VOD were collected at days +14, +30, +60, +90, and +180 following allogeneic HCT. Serum samples were analyzed for 2,925 protein levels by antibody-based proximity extension assay (PEA). Mean differences in the log-transformed abundance values were compared using t tests in a volcano plot. Results: Five patients with very severe SOS/VOD and 5 control patients were compared. Ten proteins were identified that showed a statistically significant and log-transformed 3-fold increase in concentration. They were CALCA, CCL20, GPR37, IGFBP4, IL1RL1, SLC39A14, SPINK4, FABP3, MYL3, and CHCHD10. Four different proteins, namely, CD83, leukocyte associated immunoglobulin-like receptor 2 (LAIR2), CD7, and HEM6 showed a significant decrease with defibrotide treatment. SOS/VOD resolved in 80% (n = 4) of patients, while 1 patient deceased due to SOS/VOD. Conclusion: PEA technology identified 10 proteins that were significantly elevated in patients with very severe SOS/VOD. Prospective studies in a larger cohort using this technology may be able to conclusively identify diagnostic protein biomarkers for SOS/VOD.
Efficacy of Acupuncture Combined with Traditional Chinese Medicine Fumigation Therapy in Sequelae of Pelvic Inflammatory Disease: A Systematic Review and Meta-Analysis
Authors: Yang Li , Li Yajun , Zhang Shuang , Qian Haiqing , Xu Wenting , Yu Jinfen
Published: February 2024

Background and Objective: Acupuncture combined with traditional Chinese medicine fumigation is increasingly being used in treating sequelae of pelvic inflammatory disease (SPID). However, there is a lack of meta-analysis on the effectiveness of acupuncture combined with traditional Chinese medicine fumigation in treating SPID. The aim of this study was to assess the feasibility of combining acupuncture with traditional Chinese medicine fumigation in the treatment of SPID. Methods: We searched eight databases for studies on acupuncture combined with traditional Chinese medicine fumigation for the treatment of SPID from the date of establishment to October 29, 2022. We assessed the quality of included studies by using the Cochrane bias risk tool. Pooled results were expressed as risk ratios (RRs), with a 95% confidence interval (CI). In addition, we identified sources of heterogeneity by sensitivity analysis, assessed publication bias by Egger’s test, and assessed the quality of the evidence by Grades of Recommendation, Assessment, Development, and Evaluation (GRADE). All statistical analyses were performed by Review Manager 5.3 and Stata 14. Results: Finally, seven studies with a total of 663 participants were included. We found a significant difference in the total effective rate in the acupuncture combined with the fumigation group compared with the acupuncture group in the treatment of SPID (RR = 1.17, 95% CI [1.09, 1.25], p = 0.0001 < 0.05; I2 = 0%; 6 trials), and a significant difference in the total effective rate in the acupuncture combined with fumigation group compared with the fumigation group in the treatment of SPID (RR = 1.42, 95% CI [1.21, 1.66], p = 0.0001 < 0.05; 5 trials). Conclusion: The clinical efficacy of acupuncture combined with herbal fumigation in the treatment of SPID is relatively good. Larger scale studies are needed in the future.
A Rare Case of High-Grade Spindle Cell Sarcoma of the Breast: A Case Report
Authors: Tharwani Zoaib Habib , Habib Zehra , Ahmed Yumna , Ishrat Samreena , Nashwan Abdulqadir J.
Published: February 2024

Introduction: Spindle cell sarcomas are rare breast lesions which are difficult to diagnose due to resemblance with other breast lesions. Histopathological examination and immunohistochemical staining are essential for diagnosis. Case Presentation: We present a rare case of a 15-year-old female presenting with high-grade rapidly progressive spindle cell sarcoma of the breast, differentiated as phyllodes tumor, with axillary lymph node involvement. Her lesion, on the left breast, measured 16.9 × 10.1 × 13.7 cm. Histology revealed malignant neoplasm arranged in sheets and individual neoplastic cells with an epithelioid to spindled morphology with scant cytoplasm and irregular nuclear membranes. Immunohistochemistry showed weakly positive focal CD-99, and negative WT-1, Myogenin, Desmin, p63, Cytokeratin, Synaptophysin, and CD-34 markers. She was successfully managed with modified radical mastectomy and discharged with regular follow-up advised. Conclusion: Spindle cell sarcomas have a very aggressive course and prompt diagnosis, and management is mandatory for better patient outcomes. Modified radical mastectomy is the mainstay of treatment.
p53 Acetylation Exerts Critical Roles in Pressure Overload–Induced Coronary Microvascular Dysfunction and Heart Failure in Mice
Authors: He Xiaochen , Cantrell Aubrey C. , Williams Quinesha A. , Gu Wei , Chen Yingjie , Chen Jian-Xiong , Zeng Heng
Published: February 2024

BACKGROUND:

Coronary microvascular dysfunction (CMD) has been shown to contribute to cardiac hypertrophy and heart failure (HF) with preserved ejection fraction. At this point, there are no proven treatments for CMD.

METHODS:

We have shown that histone acetylation may play a critical role in the regulation of CMD. By using a mouse model that replaces lysine with arginine at residues K98, K117, K161, and K162R of p53 (p53
4KR
), preventing acetylation at these sites, we test the hypothesis that acetylation-deficient p53
4KR
could improve CMD and prevent the progression of hypertensive cardiac hypertrophy and HF. Wild-type and p53
4KR
mice were subjected to pressure overload by transverse aortic constriction to induce cardiac hypertrophy and HF.

RESULTS:

Echocardiography measurements revealed improved cardiac function together with a reduction of apoptosis and fibrosis in p53
4KR
mice. Importantly, myocardial capillary density and coronary flow reserve were significantly improved in p53
4KR
mice. Moreover, p53
4KR
upregulated the expression of cardiac glycolytic enzymes and Gluts (glucose transporters), as well as the level of fructose-2,6-biphosphate; increased PFK-1 (phosphofructokinase 1) activity; and attenuated cardiac hypertrophy. These changes were accompanied by increased expression of HIF-1α (hypoxia-inducible factor-1α) and proangiogenic growth factors. Additionally, the levels of SERCA-2 were significantly upregulated in sham p53
4KR
mice, as well as in p53
4KR
mice after transverse aortic constriction. In vitro, p53
4KR
significantly improved endothelial cell glycolytic function and mitochondrial respiration and enhanced endothelial cell proliferation and angiogenesis. Similarly, acetylation-deficient p53
4KR
significantly improved coronary flow reserve and rescued cardiac dysfunction in SIRT3 (sirtuin 3) knockout mice.

CONCLUSIONS:

Our data reveal the importance of p53 acetylation in coronary microvascular function, cardiac function, and remodeling and may provide a promising approach to improve hypertension-induced CMD and to prevent the transition of cardiac hypertrophy to HF.
Secreted Protein Profiling of Human Aortic Smooth Muscle Cells Identifies Vascular Disease Associations
Authors: Aherrahrou Rédouane , Baig Ferheen , Theofilatos Konstantinos , Lue Dillon , Beele Alicia , Örd Tiit , Kaikkonen Minna U. , Aherrahrou Zouhair , Cheng Qi , Ghosh Saikat Kumar B. , Karnewar Santosh , Karnewar Vaishnavi , Finn Aloke V. , Owens Gary K. , Joner Michael , Mayr Manuel , Civelek Mete
Published: February 2024

BACKGROUND:

Smooth muscle cells (SMCs), which make up the medial layer of arteries, are key cell types involved in cardiovascular disease, the leading cause of mortality and morbidity worldwide. In response to microenvironment alterations, SMCs dedifferentiate from a contractile to a synthetic phenotype characterized by an increased proliferation, migration, production of ECM (extracellular matrix) components, and decreased expression of SMC-specific contractile markers. These phenotypic changes result in vascular remodeling and contribute to the pathogenesis of cardiovascular disease, including coronary artery disease, stroke, hypertension, and aortic aneurysms. Here, we aim to identify the genetic variants that regulate ECM secretion in SMCs and predict the causal proteins associated with vascular disease–related loci identified in genome-wide association studies.

METHODS:

Using human aortic SMCs from 123 multiancestry healthy heart transplant donors, we collected the serum-free media in which the cells were cultured for 24 hours and conducted liquid chromatography–tandem mass spectrometry-based proteomic analysis of the conditioned media.

RESULTS:

We measured the abundance of 270 ECM and related proteins. Next, we performed protein quantitative trait locus mapping and identified 20 loci associated with secreted protein abundance in SMCs. We functionally annotated these loci using a colocalization approach. This approach prioritized the genetic variant rs6739323-A at the 2p22.3 locus, which is associated with lower expression of LTBP1 (latent-transforming growth factor beta-binding protein 1) in SMCs and atherosclerosis-prone areas of the aorta, and increased risk for SMC calcification. We found that LTBP1 expression is abundant in SMCs, and its expression at mRNA and protein levels was reduced in unstable and advanced atherosclerotic plaque lesions.

CONCLUSIONS:

Our results unravel the SMC proteome signature associated with vascular disorders, which may help identify potential therapeutic targets to accelerate the pathway to translation.
Sex-Based Disparities in Acute Myocardial Infarction Treatment Patterns and Outcomes in Older Adults Hospitalized Across 6 High-Income Countries: An Analysis From the International Health Systems Research Collaborative
Authors: Lu Hannah , Hatfield Laura A. , Al-Azazi Saeed , Bakx Pieter , Banerjee Amitava , Burrack Nitzan , Chen Yu-Chin , Fu Christina , Gordon Michal , Heine Renaud , Huang Nicole , Ko Dennis T. , Lix Lisa M. , Novack Victor , Pasea Laura , Qiu Feng , Stukel Therese A. , Uyl-de Groot Carin A. , Weinreb Gabe , Landon Bruce E. , Cram Peter
Published: February 2024

BACKGROUND:

Sex differences in acute myocardial infarction treatment and outcomes are well documented, but it is unclear whether differences are consistent across countries. The objective of this study was to investigate the epidemiology, use of interventional procedures, and outcomes for older females and males hospitalized with ST-segment–elevation myocardial infarction (STEMI) and non–ST-segment–elevation myocardial infarction (NSTEMI) in 6 diverse countries.

METHODS:

We conducted a serial cross-sectional cohort study of 1 508 205 adults aged ≥66 years hospitalized with STEMI and NSTEMI between 2011 and 2018 in the United States, Canada, England, the Netherlands, Taiwan, and Israel using administrative data. We compared females and males within each country with respect to age-standardized hospitalization rates, rates of cardiac catheterization, percutaneous coronary intervention, and coronary artery bypass graft surgery within 90 days of hospitalization, and 30-day age- and comorbidity-adjusted mortality.

RESULTS:

Hospitalization rates for STEMI and NSTEMI decreased between 2011 and 2018 in all countries, although the hospitalization rate ratio (rate in males/rate in females) increased in virtually all countries (eg, US STEMI ratio, 1.58:1 in 2011 and 1.73:1 in 2018; Israel NSTEMI ratio, 1.71:1 in 2011 and 2.11:1 in 2018). Rates of cardiac catheterization, percutaneous coronary intervention, and coronary artery bypass graft surgery were lower for females than males for STEMI in all countries and years (eg, US cardiac catheterization in 2018, 88.6% for females versus 91.5% for males; Israel percutaneous coronary intervention in 2018, 76.7% for females versus 84.8% for males) with similar findings for NSTEMI. Adjusted mortality for STEMI in 2018 was higher for females than males in 5 countries (the United States, Canada, the Netherlands, Israel, and Taiwan) but lower for females than males in 5 countries for NSTEMI.

CONCLUSIONS:

We observed a larger decline in acute myocardial infarction hospitalizations for females than males between 2011 and 2018. Females were less likely to receive cardiac interventions and had higher mortality after STEMI. Sex disparities seem to transcend borders, raising questions about the underlying causes and remedies.
Impact of Residential Social Deprivation on Prediction of Heart Failure in Patients With Type 2 Diabetes: External Validation and Recalibration of the WATCH-DM Score Using Real World Data
Authors: Deo Salil V. , Al-Kindi Sadeer , Motairek Issam , McAllister David , Shah Anoop S.V. , Elgudin Yakov E. , Gorodeski Eiran Z. , Virani Salim , Petrie Mark C. , Rajagopalan Sanjay , Sattar Naveed
Published: February 2024

BACKGROUND:

Patients with type 2 diabetes are at risk of heart failure hospitalization. As social determinants of health are rarely included in risk models, we validated and recalibrated the WATCH-DM score in a diverse patient-group using their social deprivation index (SDI).

METHODS:

We identified US Veterans with type 2 diabetes without heart failure that received outpatient care during 2010 at Veterans Affairs medical centers nationwide, linked them to their SDI using residential ZIP codes and grouped them as SDI <20%, 21% to 40%, 41% to 60%, 61% to 80%, and >80% (higher values represent increased deprivation). Accounting for all-cause mortality, we obtained the incidence for heart failure hospitalization at 5 years follow-up; overall and in each SDI group. We evaluated the WATCH-DM score using the C statistic, the Greenwood Nam D’Agostino test χ
2
test and calibration plots and further recalibrated the WATCH-DM score for each SDI group using a statistical correction factor.

RESULTS:

In 1 065 691 studied patients (mean age 67 years, 25% Black and 6% Hispanic patients), the 5-year incidence of heart failure hospitalization was 5.39%. In SDI group 1 (least deprived) and 5 (most deprived), the 5-year heart failure hospitalization was 3.18% and 11%, respectively. The score C statistic was 0.62; WATCH-DM systematically overestimated heart failure risk in SDI groups 1 to 2 (expected/observed ratios, 1.38 and 1.36, respectively) and underestimated the heart failure risk in groups 4 to 5 (expected/observed ratios, 0.95 and 0.80, respectively). Graphical evaluation demonstrated that the recalibration of WATCH-DM using an SDI group-based correction factor improved predictive capabilities as supported by reduction in the χ
2
test results (801–27 in SDI groups I; 623–23 in SDI group V).

CONCLUSIONS:

Including social determinants of health to recalibrate the WATCH-DM score improved risk prediction highlighting the importance of including social determinants in future clinical risk prediction models.
Increased Risk of Recurrent Stroke in Symptomatic Large Vessel Disease With Impaired BOLD Cerebrovascular Reactivity
Authors: van Niftrik Christiaan H.B. , Sebök Martina , Germans Menno R. , Halter Matthias , Pokorny Thomas , Stumpo Vittorio , Bellomo Jacopo , Piccirelli Marco , Pangalu Athina , Katan Mira , Wegener Susanne , Tymianski Michael , Kulcsár Zsolt , Luft Andreas R. , Fisher Joseph A. , Mikulis David J. , Regli Luca , Fierstra Jorn
Published: February 2024

BACKGROUND:

Impaired cerebrovascular reactivity (CVR) has been correlated with recurrent ischemic stroke. However, for clinical purposes, most CVR techniques are rather complex, time-consuming, and lack validation for quantitative measurements. The recent adaptation of a standardized hypercapnic stimulus in combination with a blood-oxygenation-level-dependent (BOLD) magnetic resonance imaging signal as a surrogate for cerebral blood flow offers a potential universally comparable CVR assessment. We investigated the association between impaired BOLD-CVR and risk for recurrent ischemic events.

METHODS:

We conducted a retrospective analysis of patients with symptomatic cerebrovascular large vessel disease who had undergone a prospective hypercapnic-challenged BOLD-CVR protocol at a single tertiary stroke referral center between June 2014 and April 2020. These patients were followed up for recurrent acute ischemic events for up to 3 years. BOLD-CVR (%BOLD signal change per mm Hg CO
2
) was calculated on a voxel-by-voxel basis. Impaired BOLD-CVR of the affected (ipsilateral to the vascular pathology) hemisphere was defined as an average BOLD-CVR, falling 2 SD below the mean BOLD-CVR of the right hemisphere in a healthy age-matched reference cohort (n=20). Using a multivariate Cox proportional hazards model, the association between impaired BOLD-CVR and ischemic stroke recurrence was assessed and Kaplan-Meier survival curves to visualize the acute ischemic stroke event rate.

RESULTS:

Of 130 eligible patients, 28 experienced recurrent strokes (median, 85 days, interquartile range, 5–166 days). Risk factors associated with an increased recurrent stroke rate included impaired BOLD-CVR, a history of atrial fibrillation, and heart insufficiency. After adjusting for sex, age group, and atrial fibrillation, impaired BOLD-CVR exhibited a hazard ratio of 10.73 (95% CI, 4.14–27.81;
P
<0.001) for recurrent ischemic stroke.

CONCLUSIONS:

Among patients with symptomatic cerebrovascular large vessel disease, those exhibiting impaired BOLD-CVR in the affected hemisphere had a 10.7-fold higher risk of recurrent ischemic stroke events compared with individuals with nonimpaired BOLD-CVR.
High-Intensity Aphasia Therapy Is Cost-Effective in People With Poststroke Aphasia: Evidence From the COMPARE Trial
Authors: Kim Joosup , Rose Miranda L. , Pierce John E. , Nickels Lyndsey , Copland David A. , Togher Leanne , Godecke Erin , Meinzer Marcus , Rai Tapan , Hurley Melanie , Foster Abby , Carragher Marcella , Wilcox Cassie , Cadilhac Dominique A.
Published: February 2024

BACKGROUND:

Evidence from systematic reviews confirms that speech and language interventions for people with aphasia during the chronic phase after stroke (>6 months) improve word retrieval, functional communication, and communication-related quality of life. However, there is limited evidence of their cost-effectiveness. We aimed to estimate the cost per quality-adjusted life year gained from 2 speech and language therapies compared with usual care in people with aphasia during the chronic phase (median, 2.9 years) after stroke.

METHODS:

A 3-arm, randomized controlled trial compared constraint-induced aphasia therapy plus (CIAT-Plus) and multimodality aphasia therapy (M-MAT) with usual care in 216 people with chronic aphasia. Participants were administered a standardized questionnaire before intervention and at 12 weeks after the 2-week intervention/control period to ascertain health service utilization, employment changes, and informal caregiver burden. Unit prices from Australian sources were used to estimate costs in 2020. Quality-adjusted life years were estimated using responses to the EuroQol-5 Dimension-3 Level questionnaire. To test uncertainty around the differences in costs and outcomes between groups, bootstrapping was used with the cohorts resampled 1000 times.

RESULTS:

Overall 201/216 participants were included (mean age, 63 years, 29% moderate or severe aphasia, 61 usual care, 70 CIAT-Plus, 70 M-MAT). There were no statistically significant differences in mean total costs ($13 797 usual care, $17 478 CIAT-Plus, $11 113 M-MAT) and quality-adjusted life years (0.19 usual care, 0.20 CIAT-Plus, 0.20 M-MAT) between groups. In bootstrapped analysis of CIAT-Plus, 21.5% of iterations were likely to result in better outcomes and be cost saving (dominant) compared with usual care. In contrast, 72.4% of iterations were more favorable for M-MAT than usual care.

CONCLUSIONS:

We observed that both treatments, but especially M-MAT, may result in better outcomes at an acceptable additional cost, or potentially with cost savings. These findings are relevant in advocating for the use of these therapies for chronic aphasia after stroke.
The Three Religious Revivals. Pentecostal, Islamic, and Orthodox Upswings in the Context of Long-Term Secularization
Authors: Stolz Jörg , Novak Maruša
Published: February 2024

Secularization theory is often criticized by pointing to counterexamples where— apparently or really—revivals of religion have coincided with modernization. But secularization theorists have responded to such criticisms by arguing that secularization is compatible with temporary religious upswings. Recently, Stolz and Voas (2023) have proposed a typology, distinguishing 5 mechanisms: “crisis”, “reaction”, “transition”, “state intervention”, and “composition”. This paper puts this typology to the test by examining the three most important religious revivals in the 20th and 21st century: the Pentecostal, the Islamic, and the Orthodox religious revival. We argue that all three revivals have led to strong increases in various indicators of religiosity, each of them built on a different combination of central mechanisms. While the Orthodox revival seems to have come to a standstill, the Pentecostal/Charismatic and Islamic revivals are ongoing.
Relationships Between Nonprofits’ Social Responsibility Structures and Employee Relations: A Multi-Level Approach
Authors: Kim Seok Eun
Published: February 2024

What is the social responsibility (SR) an organization has to its employees? Seasoned experts have observed that existing SR literature predominantly emphasizes external SR to society while largely overlooking internal SR towards organizational employees. This can be misleading when nonprofit organizations (NPOs) provide labor-intensive social services, where the quality of labor inputs directly affects the desired outcomes. This study examines the relationship between the institutionalization of SR structures (SR vision and strategic plans, ethical codes, and SR units) and internal SR as measured by employee relations, using multi-level theoretical approaches. The findings suggest that the presence of SR structures in NPOs leads to improved relationships between employers and employees, manifested through enhanced compensation, working conditions, and employee protection programs. However, structural properties marginally affect NPOs in comparison to for-profit organizations.
Perceptions on Use of Opioids in Palliative Care of Dyspnoea in Patients with Fibrotic interstitial lung disease and Chronic Obstructive Pulmonary Disease: A Qualitative Study
Authors: Hvelplund Camilla Yde , Refsgaard Birgit , Bendstrup Elisabeth
Published: February 2024

Background

Many patients with chronic obstructive pulmonary disease and fibrotic interstitial lung disease suffer from severe dyspnea and reduced quality of life, despite receiving optimal disease-modifying treatment for their illness. Studies have suggested that these patients may benefit from treatment with low-dose opioids. However, many patients decline opioid treatment. This has led to patients not receiving proper palliative treatment of their lung disease.

Aim

To identify potential barriers that prevent patients from receiving adequate palliative care with opioids and enable doctors to address patients’ concerns.

Design

A qualitative study based on semi-structured interviews. Interviews were transcribed and thematic analysis was done using NVivo.

Setting/Participants

Patients were recruited when scheduled for out-patient follow-up at Center for Rare Lung Diseases or at the COPD clinic, Aarhus University Hospital. Eligible patients were 18 years of age, did not currently receive opioids or had ever received opioids for dyspnea.

Results

A total of 28 patients participated. One patient was excluded before final analysis of 27 patients. Four themes were identified: Fear of side-effects, Need for more information, Stigma of opioids association with severe illness and dying, and No discernible barriers. Furthermore, three sub-themes to Fear of side-effects were identified: Fear of addiction, concern for sedative effect, and fear for loss of mobility due to inability to drive a car. The most expressed concern was Fear of side-effects, especially addiction.

Conclusions

Pre-conceived notions about opioids prevent some patients with chronic obstructive lung disease or interstitial lung disease from receiving palliative care for breathlessness.
Diabetes Mellitus and Total Ankle Arthroplasty Complications
Authors: Helbing Jordan , Farley Benjamin , Gu Alex , Zhao Amy Y. , Siram Gautam , Stein Benjamin , Chodos Marc D.
Published: February 2024

Background:

Postoperative infection, aseptic loosening, and perioperative medical complications after total ankle arthroplasty (TAA) are all devastating problems. While previous studies have shown diabetes as a risk factor predisposing patients to postoperative complications, not all literature supports this association following TAA. The goal of this study is to determine if diabetes influences midterm outcomes following TAA.

Methods:

An insurance database was utilized to identify patients undergoing TAA for ankle arthritis with a concurrent diagnosis of diabetes based on Current Procedural Terminology ( CPT) and International Classification of Diseases, Ninth Revision ( ICD-9) and Tenth Revision ( ICD-10), diagnosis and procedure codes from 2010 to 2021. The postoperative outcomes of all-cause revision, periprosthetic joint infection (PJI), septic revision, and aseptic revision were compared between patients with and without diabetes with a minimum 2-year follow-up using Kaplan-Meier and multivariate Cox proportional hazards analyses. Patient demographics, comorbidities, and Charlson Comorbidity Index were analyzed via univariate and multivariate analysis.

Results:

The study population included 8317 patients, 345 (4.1%) of whom had a concurrent diabetes diagnosis, who underwent TAA. After multivariate Cox proportional hazards analysis, the 5-year cumulative incidence of being coded as having PJI was 7.3% in patients with known diabetes compared to 3.9% in patients without known diabetes, with a 95% increased risk (hazard ratio [HR] 1.95, 95% CI 1.15-3.30, P = .01). Patients with diabetes also demonstrated a 5-year cumulative incidence of septic revision of 1.4% compared to 0.4% in those without, with a 363% increased risk (HR 4.63, 95% CI 1.22-17.52, P = .02). However, there was no difference in the 5-year cumulative incidence of all-cause revision TAA with 4.6% in patients with diabetes and 4.3% in those without (HR 1.29, 95% CI 0.69-2.44, P = .42)

Conclusion:

In this database, the 5-year risk of PJI and septic revision was higher among patients with diabetes compared to those without, but cumulative incidence of all-cause revision TAA was not different between groups.

Level of Evidence:

Level III, retrospective cohort database study.
“We have to … work for wholeness no matter what”: Family and culture promoting wellness, resilience, and transcendence
Authors: McKinley Catherine E.
Published: February 2024

Sociocultural, mental, behavioral, and physical factors are interrelated associates of chronic health conditions—such as diabetes, obesity, and cardiovascular disease—all of which are disproportionally high and drive much of the mortality and morbidity for Indigenous peoples. Indigenous worldviews conceptualize health holistically, with inseparability across social, spiritual, cultural, familial, mental, behavioral, physical, and social dimensions of wellness. Food, family, and culture are fundamental to Indigenous wellness. The purpose of this article is to use the Framework of Historical Oppression, Resilience, and Transcendence (FHORT) conceptualization of relational wellness to honor urban and rural U.S. Indigenous perspectives that highlight the intersections of family, culture, physical health, spiritual, and mental health to promote resilience and wellness. This research focused on interconnections between wellness, culture, health, and family. Thirty-one critical ethnographic interviews used a life-history approach with methodology following an Indigenous toolkit for ethical and culturally sensitive research strategies, such as building upon cultural strengths, engaging in long-term, relational commitments with communities, incorporating storytelling and oral history traditions, centering Indigenous methodologies and preferences, working with cultural insiders, and prioritizing the perspectives of Indigenous peoples. Emergent themes included: (a) roots of Indigenous wellness: cultural values promoting balance and connection; (b) practicing resilience: family transmission of health information; and (c) wholistic mental wellness and resilience, with the subtheme culture and wellness. Interventions can be developed in collaboration with tribes for optimum efficacy and cultural relevancy and can approach wellness holistically in culturally relevant ways that center foodways, culture, family, and spirituality.
Rare scrotal chylous effusion: A case report
Authors: Ducharme Amy , Côté Benoît
Published: February 2024

Klippel–Trenaunay syndrome is a rare congenital malformation predominantly affecting lower limb. In most cases, it is characterized by a classic triad of cutaneous capillary malformation (port-wine stain), lymphatic and venous abnormalities, in association with variable soft tissue and bone overgrowths. We describe a 48-year-old male presenting on the genitalia several whitish vesicles discharging a milky fluid compatible with chyle. Extensive radiology workup revealed pelvic megalymphatic malformations. Pelvic lymphatic ligations and bleomycin sclerotherapy only allowed a partial improvement. Given the high potential of recurrence, the patient will soon undergo a genetic evaluation for PIK3CA gene mutation and may need further systemic treatment with Sirolimus. As this scrotal chylous effusion in the setting of Klippel–Trenaunay syndrome is rare and highly affects the quality of life, we wanted to raise awareness of this entity and its management.
Syndromic or non-syndromic congenital ichthyosis? A case report of two brothers with ichthyosis but microphthalmia and blindness in only one brother
Authors: Aubry Rachel L , Innes A. Micheil , Haber Richard M
Published: February 2024

We present the cases of two brothers with ichthyosis, born to consanguineous parents, with the eldest having extracutaneous manifestations in the form of microphthalmia and corneal opacities causing complete blindness. Initially, we were faced with the question of whether the phenotype in this family was due to the effects of a single pleiotropic, presumably autosomal recessive gene manifesting as a syndromic form of ichthyosis, or whether there were multiple causal genes, and the ichthyosis was non-syndromic. Ultimately, clinical follow-up of the family, combined with research-based exome sequencing established a diagnosis of NIPAL4 autosomal recessive congenital ichthyosis in both brothers, but the ocular abnormalities causing blindness in the older brother were due to coexisting autosomal recessively inherited loss of function mutations in peroxidasin, the latter finding also seen in a sister unaffected by ichthyosis.
Nonlinear bending examination of nanocomposite cylindrical shell exposed to mechanical loads using dynamic relaxation method
Authors: Rahimi E , Sadeghian M , Golmakani Mohammad E.
Published: February 2024

In the current context, the nonlinear bending examination of a carbon nanotube reinforced composite (CNTRC) shell exposed to mechanical loading using the first-order shear deformation shell model via the dynamic relaxation (DR) procedure, is perused. The composite shell is assumed to be reinforced in the longitudinal axis. The curved morphology distribution of CNTs is considered to be functionally graded (FG) or uniform along the shell thickness. Mechanical properties of the constituents are gathered based on the modified rule of the mixture. For verification, the present numeric outcomes are compared with available references and ABAQUS finite element package. Finally, the roles of effective items including carbon nanotubes (CNTs) distributions, thickness-to-radius and length-to-radius ratios, boundary conditions, and the volume fraction of CNTs are investigated on the maximum non-dimension deflection.
Mitapivat improves ineffective erythropoiesis and iron overload in adult patients with pyruvate kinase deficiency
Authors: van Beers Eduard J. , Al-Samkari Hanny , Grace Rachael F. , Barcellini Wilma , Glenthøj Andreas , DiBacco Melissa , Wind-Rotolo Megan , Xu Rengyi , Beynon Vanessa , Patel Parija , Porter John B. , Kuo Kevin H. M.
Published: February 2024

Pyruvate kinase (PK) deficiency is a rare, hereditary disease characterized by chronic hemolytic anemia. Iron overload is a common complication regardless of age, genotype, or transfusion history. Mitapivat, an oral, allosteric PK activator, improves anemia and hemolysis in adult patients with PK deficiency. Mitapivat’s impact on iron overload and ineffective erythropoiesis was evaluated in adults with PK deficiency who were not regularly transfused in the phase 3 ACTIVATE trial and long-term extension (LTE) (#NCT03548220/#NCT03853798). Patients in the LTE received mitapivat throughout ACTIVATE/LTE (baseline to week 96; mitapivat-to-mitapivat [M/M] arm) or switched from placebo (baseline to week 24) to mitapivat (week 24 to week 96; placebo-to-mitapivat [P/M] arm). Changes from baseline in markers of iron overload and erythropoiesis were assessed to week 96. Improvements in hepcidin (mean, 4770.0 ng/L; 95% confidence interval [CI], −1532.3 to 11 072.3), erythroferrone (mean, −9834.9 ng/L; 95% CI, −14 328.4 to −5341.3), soluble transferrin receptor (mean, −56.0 nmol/L; 95% CI, −84.8 to −27.2), and erythropoietin (mean, −32.85 IU/L; 95% CI, −54.65 to −11.06) were observed in the M/M arm (n = 40) from baseline to week 24, sustained to week 96. No improvements were observed in the P/M arm (n = 40) to week 24; however, upon transitioning to mitapivat, improvements similar to those observed in the M/M arm were seen. Mean changes from baseline in liver iron concentration by magnetic resonance imaging at week 96 in the M/M arm and the P/M arm were −2.0 mg Fe/g dry weight (dw; 95% CI, −4.8 to −0.8) and −1.8 mg Fe/g dw (95% CI, −4.4 to 0.80), respectively. Mitapivat is the first disease-modifying pharmacotherapy shown to have beneficial effects on iron overload and ineffective erythropoiesis in patients with PK deficiency. This trial was registered at www.ClinicalTrials.gov as #NCT03548220 (ACTIVATE) and #NCT03853798 (LTE).
Human Fc gamma receptor IIIA blockade inhibits platelet destruction in a humanized murine model of ITP
Authors: Gil Gonzalez Lazaro , Won Kevin D. , Tawhidi Zoya , Cummins Emma , Cruz-Leal Yoelys , Tundidor Cabado Yaima , Sachs Ulrich J. , Norris Peter A. A. , Shan Yuexin , Bhakta Varsha , Li Janessa , Samudio Ismael , Silva-Moreno Begonia , Cerna-Portillo Liza , Pavon Oro Alequis , Bergqvist Peter , Chan Patrick , Moorehead Amy , Sholzberg Michelle , Sheffield William P. , Lazarus Alan H.
Published: February 2024

Fc gamma receptor (FcγR) IIIA is an important receptor for immunoglobulin G (IgG) and is involved in immune defense mechanisms as well as tissue destruction in some autoimmune diseases including immune thrombocytopenia (ITP). FcγRIIIA on macrophages can trigger phagocytosis of IgG-sensitized platelets, and prior pilot studies observed blockade of FcγRIIIA increased platelet counts in patients with ITP. Unfortunately, although blockade of FcγRIIIA in patients with ITP increased platelet counts, its engagement by the blocking antibody drove serious adverse inflammatory reactions. These adverse events were postulated to originate from the antibody’s Fc and/or bivalent nature. The blockade of human FcγRIIIA in vivo with a monovalent construct lacking an active Fc region has not yet been achieved. To effectively block FcγRIIIA in vivo, we developed a high affinity monovalent single-chain variable fragment (scFv) that can bind and block human FcγRIIIA. This scFv (17C02) was expressed in 3 formats: a monovalent fusion protein with albumin, a 1-armed human IgG1 antibody, and a standard bivalent mouse (IgG2a) antibody. Both monovalent formats were effective in preventing phagocytosis of ITP serum–sensitized human platelets. In vivo studies using FcγR-humanized mice demonstrated that both monovalent therapeutics were also able to increase platelet counts. The monovalent albumin fusion protein did not have adverse event activity as assessed by changes in body temperature, whereas the 1-armed antibody induced some changes in body temperature even though the Fc region function was impaired by the Leu234Ala and Leu235Ala mutations. These data demonstrate that monovalent blockade of human FcγRIIIA in vivo can potentially be a therapeutic strategy for patients with ITP.
Integrated analysis of microRNA and messenger RNA expression profiles reveals functional microRNA in infectious bovine rhinotracheitis virus-induced mitochondrial damage in Madin-Darby bovine kidney cells
Authors: Ma Yingcai , Guo Xueping , He Qin , Liu Lu , Li Zelong , Zhao Xiaomin , Gu Wenxi , Zhong Qi , Li Na , Yao Gang , Ma Xuelian
Published: February 2024

Background

Studies have confirmed that Infectious bovine rhinotracheitis virus (IBRV) infection induces mitochondrial damage. MicroRNAs (miRNAs) are a class of noncoding RNA molecules, which are involved in various biological processes and pathological changes associated with mitochondrial damage. It is currently unclear whether miRNAs participate in IBRV-induced mitochondrial damage in Madin-Darby bovine kidney (MDBK) cells.

Results

In the present study, we used high-throughput sequencing technology, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to screen for mitochondria-related miRNAs and messenger RNAs (mRNAs). In total, 279 differentially expressed miRNAs and 832 differentially expressed mRNAs were identified in 6 hours (IBRV1) versus 24 hours (IBRV2) after IBRV infection in MDBK cells. GO and KEGG enrichment analysis revealed that 42 differentially expressed mRNAs and 348 target genes of differentially expressed miRNAs were correlated with mitochondrial damage, and the miRNA-mitochondria-related target genes regulatory network was constructed to elucidate their potential regulatory relationships. Among the 10 differentially expressed miRNAs, 8 showed expression patterns consistent with the high-throughput sequencing results. Functional validation results showed that overexpression of miR-10a and miR-182 aggravated mitochondrial damage, while inhibition of miR-10a and miR-182 alleviated mitochondrial damage.

Conclusions

This study not only revealed the expression changes of miRNAs and mRNAs in IBRV-infected MDBK cells, but also revealed possible biological regulatory relationship between them. MiR-10a and miR-182 may have the potential to be developed as biomarkers for the diagnosis and treatment of IBRV. Together, Together, these data and analyses provide additional insights into the roles of miRNA and mRNA in IBRV-induced mitochondria damage
Awareness and knowledge of drug decriminalization among people who use drugs in British Columbia: a multi-method pre-implementation study
Authors: Greer Alissa , Xavier Jessica , Loewen Olivia K. , Kinniburgh Brooke , Crabtree Alexis
Published: February 2024

Background

In January 2023, British Columbia implemented a three-year exemption to Controlled Drugs and Substances Act, as granted by the federal government of Canada, to decriminalize the personal possession of small amounts of certain illegal drugs. This decriminalization policy, the first in Canada, was announced in response to the overdose emergency in British Columbia as a public health intervention that could help curb overdose deaths by reducing the impact of criminalization and increasing access to health and social services through stigma reduction.

Methods

The current multi-method study examines people who use drugs’ awareness and knowledge of British Columbia’s decriminalization model through cross-sectional quantitative surveys and qualitative interviews among people who use drugs from September–November 2022, immediately prior to the implementation of decriminalization.

Results

Quantitative findings show that two-thirds (63%) of people who use drugs were aware of the policy, but substantial knowledge gaps existed about the legal protections afforded (threshold amount, substances included, drug trafficking, confiscation). The qualitative findings suggest that people who use drugs misunderstood the details of the provincial decriminalization model and often conflated it with regulation. Results suggest that information sharing about decriminalization were minimal pre-implementation, highlighting areas for knowledge dissemination about people who use drugs' rights under this policy.

Conclusions

Given that decriminalization in British Columbia is a new and landmark reform, and that the success of decriminalization and its benefits may be undermined by poor awareness and knowledge of it, efforts to share information, increase understanding, and empower the community, may be required to promote its implementation and benefits for the community.