bluuebunny/crossref_metadata_2025 huggingface dataset:
Allosteric modulation of integral protein activity by differential stress in asymmetric membranes
Authors: Piller Paulina , Semeraro Enrico F , Rechberger Gerald N , Keller Sandro , Pabst Georg
Published: April 2023

The activity of integral membrane proteins is tightly coupled to the properties of the surrounding lipid matrix. In particular, transbilayer asymmetry, a hallmark of all plasma membranes, might be exploited to control membrane-protein activity. Here, we hypothesized that the membrane-embedded enzyme outer membrane phospholipase A (OmpLA) is susceptible to the lateral pressure differences that build up between such asymmetric membrane leaflets. Upon reconstituting OmpLA into synthetic, chemically well-defined phospholipid bilayers exhibiting different lateral pressure profiles, we indeed observed a substantial decrease in the enzyme’s hydrolytic activity with increasing membrane asymmetry. No such effects were observed in symmetric mixtures of the same lipids. To quantitatively rationalize how the differential stress in asymmetric lipid bilayers inhibits OmpLA, we developed a simple allosteric model within the lateral pressure framework. Thus, we find that membrane asymmetry can serve as the dominant factor in controlling membrane-protein activity, even in the absence of specific, chemical cues or other physical membrane determinants such as hydrophobic mismatch.
Liquidity Constraints, Consumption, and Debt Repayment: Evidence from Macroprudential Policy in Turkey
Authors: Agarwal Sumit , Hadzic Muris , Song Changcheng , Yildirim Yildiray
Published: April 2023

Using account-level credit card data from a large Turkish bank, we study the impact of a unique credit card policy that increases minimum payment on consumption and debt repayment. We show that the policy reduces credit card spending and debt, boosts existing debt repayment, and reduces credit card delinquency. The credit card debt of affected consumers falls on average by 50$\%$ two years into the policy’s implementation. An increase in minimum payment has a stronger effect than does a decrease of a similar magnitude. We build a benchmark life cycle model with soft liquidity constraint to explain the reduction in credit card spending.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Prevalence of and factors associated with childhood anaemia in remote villages of the Peruvian Amazon: a cross-sectional study and geospatial analysis
Authors: Morocho-Alburqueque Noelia , Quincho-Lopez Alvaro , Nesemann John M , Cañari-Casaño Jorge L , Elorreaga Oliver A , Muñoz Marleny , Talero Sandra , Harding-Esch Emma M , Saboyá-Díaz Martha Idalí , Honorio-Morales Harvy A , Durand Salomón , Carey-Angeles Cristiam A , Klausner Jeffrey D , Keenan Jeremy D , Lescano Andres G
Published: April 2023

Background

Anaemia is a public health problem in Peru. In the Loreto region of the Amazon, ≥50% of children may be anaemic, although insufficient information exists for rural villages.

Methods

To generate more data about childhood anaemia in the Peruvian Amazon, haemoglobin was measured as part of a trachoma survey in 21 randomly selected villages. All children 1–9 y of age from 30 randomly selected households per village were recruited. Anaemia was classified according to the World Health Organization guidelines and a socio-economic status (SES) index was created for each household using principal component analysis. Spatial autocorrelation was determined using Moran's I and Ripley's K function.

Results

Of 678 children with complete haemoglobin data, 25.4% (95% confidence interval [CI] 21.2 to 30.1) had mild-or-worse anaemia and 22.1% (95% CI 15.6 to 30.3) had moderate-or-worse anaemia. Mild-or-worse anaemia was more common among children whose primary source of drinking water was surface water (prevalence ratio [PR] 1.26 [95% CI 1.14 to 1.40], p<0.001) and who were in the lowest SES tercile (PR 1.16 [95% CI 1.02 to 1.32], p=0.021). Moderate-or-worse anaemia was more common among boys (PR 1.32 [95% CI 1.09 to 1.60], p=0.005). No evidence of geospatial clustering was found.

Conclusions

Remote villages of the Amazon would benefit from interventions for childhood anaemia and the poorest households would have the most to gain. Integrating anaemia screening into neglected tropical diseases surveys is an opportunity to use public health resources more efficiently.
The best is yet to come: six new species within a large-bodied earthworm genus (Scherotheca, Lumbricidae) in a densely sampled region (south-western France)
Authors: Marchán Daniel Fernández , Novo Marta , Domínguez Jorge , Da Silva Alberto , Martínez Alejandro , Gerard Sylvain , Hedde Mickaël , Decaëns Thibaud
Published: April 2023

Since the 18th century, several taxonomists have contributed to knowledge of the French earthworm fauna, one of the best-known earthworm communities in Europe, with 164 species currently described. Surprisingly, new species keep being added constantly, even large ones, which are usually the first to be described. The recent discovery of six undescribed morphospecies of Scherotheca during a sampling survey in southern France suggests that other large Lumbricidae remain to be discovered. We provide here an integrative description of these six species, Scherotheca albina Marchán & Decaëns sp. nov., Scherotheca betharramensis Marchán & Decaëns sp. nov., Scherotheca microthomasi Marchán & Decaëns sp. nov., Scherotheca shaihulud Marchán & Decaëns sp. nov., Scherotheca etcheberryensis Marchán & Decaëns sp. nov. and Scherotheca trezencensis Marchán & Decaëns sp. nov., formally name them and place them in a molecular phylogenetic framework together with their Scherotheca relatives from south-western France. This increases the diversity of Scherotheca to 51 species, including Scherotheca haymozi comb. nov. as a small-sized representative of the genus. The validity of the elevation of several subspecies to specific status was corroborated by molecular phylogenetic evidence, and previously unknown cryptic speciation within Scherotheca was detected. Two geographically coherent clades (roughly matching Nouvelle-Aquitaine and Occitanie) correspond to two existing subgenera. The unusually high taxonomic and morphological diversity of Scherotheca within the Pyrénées-Atlantiques may be related to biotic interactions, climatic factors and historical causes. These features highlight the importance of the conservation of these unique earthworm species.
Effect of Different Rates, Application Timing, and Combination of Nonfumigant Nematicides in Control of Meloidogyne incognita in Watermelon
Authors: Nnamdi Chinaza , Hajihassani Abolfazl
Published: April 2023

The use of plasticulture systems, which consist of raised beds, plastic mulch, and drip irrigation, for watermelon production has increased in the Southern United States in recent decades. The root-knot nematode (RKN), Meloidogyne incognita, is a significant pathogen of watermelon production in plasticulture systems and can cause varying levels of yield loss depending on the nematode population density if not properly controlled. A few new nonfumigant nematicides (fluensulfone, fluazaindolizine, and fluopyram) have emerged in the last decade to help manage RKNs. A 2-year field study was conducted to examine the impact of different rates, application timing (i.e., days before transplanting, at transplanting, and days after transplanting), and combinations of these new nematicides and an older one (oxamyl) in control of RKN in watermelon cultivar Fascination. The nematicide treatments, except for a single-time application of oxamyl in 2019 and 2020, significantly reduced root galling compared with the untreated check. Similarly, all treatments, except a single application of oxamyl in 2020, resulted in a lower soil population level of M. incognita than the untreated check. All nematicide treatments, except a single application of fluensulfone and a two-time application of fluopyram at a half-recommended rate, increased fruit yields when compared with the untreated check. Overall, the drip application of new chemistries, known as 3-F nematicides, has been shown to be a useful option for RKN management in watermelon. At-planting application of fluazaindolizine or fluopyram and two-time applications of oxamyl based on the manufacturer's recommended rate show potential to prevent crop loss.
Binding of USP4 to cortactin enhances cell migration in HCT116 human colon cancer cells
Authors: Yun Sun‐Il , Kwak Chulhwan , Lee Song‐Yi , Shin Sanghee , Oh Changsuk , Kim Jong‐Seo , Rhee Hyun‐Woo , Kim Kyeong Kyu
Published: April 2023

Ubiquitin‐specific protease 4 (USP4) is highly overexpressed in colon cancer and acts as a potent protooncogenic protein by deubiquitinating β‐catenin. However, its prominent roles in tumor formation and migration in cancer cells are not fully understood by its deubiquitinating enzyme (DUB) activity on β‐catenin. Thus, we investigated an additional role of USP4 in cancer. In this study, we identified cortactin (CTTN), an actin‐binding protein involved in the regulation of cytoskeleton dynamics and a potential prognostic marker for cancers, as a new cellular interacting partner of USP4 from proximal labeling of HCT116 cells. Additionally, the role of USP4 in CTTN activation and promotion of cell dynamics and migration was investigated in HCT116 cells. We confirmed that interacting of USP4 with CTTN increased cell movement. This finding was supported by the fact that USP4 overexpression in HCT116 cells with reduced expression of CTTN was insufficient to promote cell migration. Additionally, we observed that USP4 overexpression led to a significant increase in CTTN phosphorylation, which is a requisite mechanism for cell migration, by regulating Src/focal adhesion kinase (FAK) binding to CTTN and its activation. Our results suggest that USP4 plays a dual role in cancer progression, including stabilization of β‐catenin as a DUB and interaction with CTTN to promote cell dynamics by inducing CTTN phosphorylation. Therefore, this study demonstrates that USP4 is important for cancer progression and is a good target for treating or preventing cancer.
Disrupted intercellular bridges and spermatogenesis in fatty acyl‐CoA reductase 1 knockout mice: A new model of ether lipid deficiency
Authors: Pan Bo , Yuan Shuo , Mayernik Linda , Yap Yi Tian , Moin Kamiar , Chung Charles S. , Maddipati Krishnarao , Krawetz Stephen A. , Zhang Zhibing , Hess Rex A. , Chen Xuequn
Published: April 2023

Peroxisomal fatty acyl‐CoA reductase 1 (FAR1) is a rate‐limiting enzyme for ether lipid (EL) synthesis. Gene mutations in FAR1 cause a rare human disease. Furthermore, altered EL homeostasis has also been associated with various prevalent human diseases. Despite their importance in human health, the exact cellular functions of FAR1 and EL are not well‐understood. Here, we report the generation and initial characterization of the first Far1 knockout (KO) mouse model. Far1 KO mice were subviable and displayed growth retardation. The adult KO male mice had smaller testes and were infertile. H&E and immunofluorescent staining showed fewer germ cells in seminiferous tubules. Round spermatids were present but no elongated spermatids or spermatozoa were observed, suggesting a spermatogenesis arrest at this stage. Large multi‐nucleated giant cells (MGC) were found lining the lumen of seminiferous tubules with many of them undergoing apoptosis. The immunofluorescent signal of TEX14, an essential component of intercellular bridges (ICB) between developing germ cells, was greatly reduced and mislocalized in KO testis, suggesting the disrupted ICBs as an underlying cause of MGC formation. Integrative analysis of our total testis RNA‐sequencing results and published single‐cell RNA‐sequencing data unveiled cell type‐specific molecular alterations underlying the spermatogenesis arrest. Many genes essential for late germ cell development showed dramatic downregulation, whereas genes essential for extracellular matrix dynamics and cell–cell interactions were among the most upregulated genes. Together, this work identified the cell type‐specific requirement of ELs in spermatogenesis and suggested a critical role of Far1/ELs in the formation/maintenance of ICB during meiosis.
Cholinergic drugs reduce metabolic inflammation and diabetic myocardial injury by regulating the gut bacterial component lipopolysaccharide‐induced ERK/Egr‐1 pathway
Authors: Wu Qing , Zhao Ming , Li Dongling , He Xi , Zang Weijin
Published: April 2023

Autonomic imbalance and metabolic inflammation are important pathological processes in diabetic cardiomyopathy. Gut microbiota dysbiosis and increased levels of bacterial component lipopolysaccharide (LPS) are associated with diabetic myocardial injury, but the mechanism by which gut microbes affect metabolic inflammation and cardiac injury remains unclear. We determined whether pyridostigmine (PYR), which inhibits cholinesterase to improve vagal activity, could regulate the disordered gut microbiota and attenuate gut barrier dysfunction, metabolic endotoxemia, and inflammation in diabetes. Db/db mice exhibited high blood glucose levels, insulin resistance, low vagal activity, and diabetic myocardial injury. Db/db mice also exhibited gut microbiota perturbations and subsequent disruption of gut barrier function, resulting in an influx of LPS, metabolic endotoxemia, and inflammation. PYR ameliorated the dysregulated glucose and lipid metabolism, modulated the overall structure of the gut microbiota, selectively enhanced the abundance of anti‐inflammatory bacteria, and reduced the abundance of proinflammatory and potentially pathogenic bacteria in db/db mice. Importantly, PYR enhanced vagal activity, restored gut microbiota homeostasis, and alleviated gut barrier dysfunction. Therefore, the LPS‐induced extracellular signal‐regulated kinase (ERK)/early growth response‐1 (Egr‐1) pathway and consequent metabolic inflammation were inhibited, and eventually, cardiac hypertrophy, fibrosis, oxidative stress, and dysfunction were ameliorated in db/db mice. In vitro cardiomyocyte injury was induced by exposing primary neonatal rat ventricular cardiomyocytes to high glucose (HG) and LPS. In vitro analyses showed that HG + LPS induced ERK1/2 phosphorylation, Egr‐1 expression, inflammation, and cell apoptosis, which were inhibited by acetylcholine (ACh). Alpha 7 nicotinic ACh receptor but not muscarinic 2 ACh receptor plays an important role in ACh‐mediated anti‐inflammatory effects and inhibiting the ERK/Egr‐1 pathway in HG + LPS‐administered neonatal rat ventricular cardiomyocytes. PYR and ACh ameliorated diabetic myocardial injury by inhibiting the LPS‐induced ERK/Egr‐1 pathway and metabolic inflammation. The vagus–gut–heart axis has provided new insights into the complex mechanisms of diabetes and offers novel therapeutic targets.
Association of Preoperative Growth Differentiation Factor-15 Concentrations and Postoperative Cardiovascular Events after Major Noncardiac Surgery
Authors: Duceppe Emmanuelle , Borges Flavia K. , Conen David , Tiboni Maria , Chan Matthew T. V. , Patel Ameen , Sessler Daniel I. , Kavsak Peter A. , Ofori Sandra , Srinathan Sadeesh , Pearse Rupert , Jaffe Allan S. , Heels-Ansdell Diane , Garg Amit X. , Pettit Shirley , Sapsford Robert , Devereaux P. J.
Published: April 2023

Background

The association between growth differentiation factor-15 concentrations and cardiovascular disease has been well described. The study hypothesis was that growth differentiation factor-15 may help cardiac risk stratification in noncardiac surgical patients, in addition to clinical evaluation.

Methods

The objective of the study was to determine whether preoperative serum growth differentiation factor-15 is associated with the composite primary outcome of myocardial injury after noncardiac surgery and vascular death at 30 days and can improve cardiac risk prediction in noncardiac surgery. This is a prospective cohort study of patients 45 yr or older having major noncardiac surgery. The association between preoperative growth differentiation factor-15 and the primary outcome was determined after adjusting for the Revised Cardiac Risk Index. Preoperative N-terminal-pro hormone brain natriuretic peptide was also added to compare predictive performance with growth differentiation factor-15.

Results

Between October 27, 2008, and October 30, 2013, a total of 5,238 patients were included who had preoperative growth differentiation factor-15 measured (median, 1,325; interquartile range, 880 to 2,132 pg/ml). The risk of myocardial injury after noncardiac surgery and vascular death was 99 of 1,705 (5.8%) for growth differentiation factor-15 less than 1,000 pg/ml, 161 of 1,332 (12.1%) for growth differentiation factor-15 1,000 to less than 1,500 pg/ml, 302 of 1476 (20.5%) for growth differentiation factor-15 1,500 to less than 3,000 pg/ml, and 247 of 725 (34.1%) for growth differentiation factor-15 concentrations 3,000 pg/ml or greater. Compared to patients who had growth differentiation factor-15 concentrations less than 1,000 pg/ml, the corresponding adjusted hazard ratio for each growth differentiation factor-15 category was 1.93 (95% CI, 1.50 to 2.48), 3.04 (95% CI, 2.41 to 3.84), and 4.8 (95% CI, 3.76 to 6.14), respectively. The addition of growth differentiation factor-15 improved cardiac risk classification by 30.1% (301 per 1,000 patients) compared to Revised Cardiac Risk Index alone. It also provided additional risk classification beyond the combination of preoperative N-terminal-pro hormone brain natriuretic peptide and Revised Cardiac Risk Index (16.1%; 161 per 1,000 patients).

Conclusions

Growth differentiation factor-15 is strongly associated with 30-day risk of major cardiovascular events and significantly improved cardiac risk prediction in patients undergoing noncardiac surgery.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
External fixator as a safe method in the treatment of distal tibial fractures in children
Authors: Wen Yuwei , Zhu Danjiang , Wang Qiang , Song Baojian , Feng Wei
Published: April 2023

Objective

The objective of this study is to evaluate the functional and radiological results of external fixator application in the treatment of distal tibial metaphyseal diaphyseal junction (MDJ) fractures in children and to analyze differences between stable and unstable fractures.

Methods

Medical records of children with distal tibial MDJ fracture confirmed by imaging from January 2015 to November 2021 were retrospectively analyzed. Patients were divided into stable and unstable groups and parameters, including clinical and imaging data and Tornetta ankle score were compared.

Results

Twenty-five children, comprising 13 with stable and 12 with unstable fractures, were included in our study. The mean age was 7 years (range, 2–13.1 years), and there were 17 males and 8 females. All children had closed reduction, and the basic clinical data of the two groups were comparable. Stable fractures showed shorter intraoperative fluoroscopy, operation, and fracture healing times than unstable fractures. No significant difference in Tornetta ankle score was observed. Twenty-two patients had excellent ankle score, and three had a good ankle score, for a combined incidence of 100%. Two patients in the stable fracture group and one in the unstable fracture group developed a pin site infection, and one patient with unstable fracture showed a length discrepancy (discrepancy<1 cm).

Conclusion

External fixator is safe and effective for the treatment of distal tibial MDJ fractures, whether the fracture is stable or not. It has the advantages of minimally invasive, excellent ankle function score, few major complications, needless auxiliary cast fixation, and early functional exercise and weight bearing.

Level of evidence

Level IV.
Projected Lifetime Cancer Risk Associated with Intraoperative Computed Tomography for Lumbar Spine Surgery
Authors: Crawford Alexander M. , Striano Brendan M. , Giberson-Chen Carew C. , Xiong Grace X. , Lightsey Harry M. , Schoenfeld Andrew J. , Simpson Andrew K.
Published: April 2023

Study Design.

Retrospective cross-sectional study.

Objective.

(1) To determine the incremental increase in intraoperative ionizing radiation conferred by CT as compared to conventional radiography; and (2) To model different lifetime cancer risks contextualized by the intersection between age, sex, and intraoperative imaging modality.

Summary of Background Data.

Emerging technologies in spine surgery like navigation, automation, and augmented reality commonly utilize intraoperative CT. While much has been written about the benefits of such imaging modalities, the inherent risk profile of increasing intraoperative CT has not been well evaluated.

Methods.

Effective doses of intraoperative ionizing radiation were extracted from 610 adult patients who underwent single-level instrumented fusion for lumbar degenerative or isthmic spondylolisthesis from January 2015 through January 2022. Patients were divided into those who received intraoperative CT (n=138) and those who underwent conventional intraoperative radiography (n=472). Generalized linear modeling was utilized with intraoperative CT use as a primary predictor and patient demographics, disease characteristics, and preference-sensitive intraoperative considerations (e.g. surgical approach, surgical invasiveness) as covariates. The adjusted risk difference in radiation dose calculated from our regression analysis was used to prognosticate the associated cancer risk across age and sex strata.

Results.

(1) After adjusting for covariates, intraoperative CT was associated with 7.6 mSv (IQR 6.8–8.4 mSv; P<0.001) more radiation than conventional radiography. (2) For the median patient in our population (a 62-year-old female), intraoperative CT use increased lifetime cancer risk by 2.3 incidents (IQR 2.1–2.6) per 10,000. Similar projections for other age and sex strata were also appreciated.

Conclusion.

Intraoperative CT use significantly increased cancer risk compared to conventional intraoperative radiography for patients undergoing lumbar spinal fusions. As emerging technologies in spine surgery continue to proliferate and leverage intraoperative CT for cross-sectional imaging data, strategies must be developed by surgeons, institutions, and medical technology companies to mitigate long-term cancer risks.
The postoperative analgesic efficacy of liposomal bupivacaine versus long-acting local anaesthetics for peripheral nerve and field blocks
Authors: Nguyen Alexandre , Grape Sina , Gobbetti Mattia , Albrecht Eric
Published: April 2023

BACKGROUND

Liposomal bupivacaine is claimed by the manufacturer to provide analgesia for up to 72 h postoperatively.

OBJECTIVES

To compare the postoperative analgesic efficacy of liposomal bupivacaine versus long-acting local anaesthetics for peripheral nerve or field blocks.

DESIGN

A systematic review and meta-analysis with trial sequential analysis.

DATA SOURCES

MEDLINE, Embase and Web of Science, among others, up to June 2022.

ELIGIBILITY CRITERIA

We retrieved randomised controlled trials comparing liposomal bupivacaine versus bupivacaine, levobupivacaine or ropivacaine for peripheral nerve and field blocks after all types of surgery. Our primary endpoint was rest pain score (analogue scale 0 to 10) at 24 h. Secondary endpoints included rest pain score at 48 and 72 h, and morphine consumption at 24, 48 and 72 h.

RESULTS

Twenty-seven trials including 2122 patients were identified. Rest pain scores at 24 h were significantly reduced by liposomal bupivacaine with a mean difference (95% CI) of -0.9 (-1.4 to -0.4), I
2 = 87%, P < 0.001. This reduction in pain scores persisted at 48 h and 72 h with mean differences (95% CI) of -0.7 (-1.1 to -0.3), I
2 = 82%, P = 0.001 and -0.7 (-1.1 to -0.3), I
2 = 80%, P < 0.001, respectively. There were no differences in interval morphine consumption at 24 h (P = 0.15), 48 h (P = 0.15) and 72 h (P = 0.07). The quality of evidence was moderate.

CONCLUSIONS

There is moderate level evidence that liposomal bupivacaine reduces rest pain scores by 0.9 out of 10 units, when compared with long-acting local anaesthetics at 24 hours after surgery, and by 0.7 up to 72 hours after surgery.
Diagnosis, causes, and treatment of dyspareunia in postmenopausal women
Authors: Streicher Lauren F.
Published: April 2023

Importance and Objectives

Evaluation and treatment of dyspareunia remains a significant unmet need despite the availability of safe and effective treatments. The objectives of this review are to consider evaluation techniques, the medical causes, and treatment options for dyspareunia in postmenopausal women.

Methods

This narrative review used PubMed to search for English-language articles related to postmenopausal dyspareunia. Search terms included, but were not limited to, dyspareunia, genitourinary syndrome of menopause, sexual dysfunction, postmenopausal dyspareunia, posthysterectomy dyspareunia, and postcancer dyspareunia.

Findings

Many postmenopausal women with dyspareunia do not discuss their symptoms with their physicians. Healthcare clinicians should broach the topic of dyspareunia with their patients using oral or written questionnaires. In addition to a thorough medical history and physical examination, various tools can be used as further assessments, including vaginal pH, vaginal dilators, imaging, vulvar biopsy, vulvoscopy and photography, the cotton swab test, sexually transmitted infection screening, and vaginitis testing. Although dyspareunia in postmenopausal women is often due to the genitourinary syndrome of menopause, other conditions can also cause dyspareunia, including hypertonic pelvic floor, hysterectomy, cancer treatment, lichen conditions, vulvar cancer, vestibulodynia, and pelvic organ prolapse. Some of the treatments discussed include lubricants, moisturizers, vaginal estrogen, ospemifene, dehydroepiandrosterone, local testosterone therapy, cannabidiol, and fractional CO2 laser treatments. In some cases, dyspareunia may need to be specifically addressed by pelvic floor physical or sex therapists.

Conclusions

Dyspareunia is a common issue in postmenopausal women, which remains largely untreated. Women with dyspareunia require a thorough history, targeted physical examination, and coordination of multiple disciplines including medical clinicians, pelvic floor physical therapists, and sex therapists.
Interactions between genetic variants and environmental risk factors are associated with the severity of pelvic organ prolapse
Authors: Li Lei , Zhao Guangyi , Wu Jie , Pang Haiyu , Zhang Tianli , Chen Juan , Zhang Kunlin , Zhu Lan
Published: April 2023

Objective

Both environmental and genetic risk factors contribute to pelvic organ prolapse (POP). No genome-wide study has investigated the gene-environment (G × E) interactions. In this study, we aim to identify single nucleotide polymorphisms (SNPs) that may interact with the potential environmental factors, maximum birth weight, and age in Chinese women.

Methods

We recruited 576 women for phase 1 and 264 women for phase 2 with stages III and IV prolapse from six geographic regions of China. Genomic DNAs from blood samples were genotyped using Affymetrix Axiom Genome-Wide CHB1 Array of 640,674 SNPs for phase 1 and Illumina Infinium Asian Screening Array of 743,722 SNPs for phase 2. Meta-analysis was used to combine the two results. Interactions of genetic variants with maximum birth weight and age on POP severity were identified.

Results

In phase 1, 502,283 SNPs in 523 women passed quality control and 450 women had complete POP-quantification measurements. In phase 2, 463,351 SNPs in 257 women passed quality control with complete POP-quantification measurements. Three SNPs rs76662748 (WDR59, P
meta = 2.146 × 10−8), rs149541061 (3p26.1, P
meta = 9.273 × 10−9), and rs34503674 (DOCK9, P
meta = 1.778 × 10−9) respectively interacted with maximum birth weight, and two SNPs rs74065743 (LINC01343, P
meta = 4.386 × 10−8) and rs322376 (NEURL1B-DUSP1, P
meta = 2.263 × 10−8), respectively, interacted with age. The magnitude of disease severity associated with maximum birth weight and age differed according to genetic variants.

Conclusions

This study provided preliminary evidence that interactions between genetic variants and environmental risk factors are associated with POP severity, suggesting the potential use of combining epidemiologic exposure data with selected genotyping for risk assessment and patient stratification.
Ocular Manifestations of Peters Plus-Like Syndrome in 8q21.11 Microdeletion Syndrome
Authors: Shigeyasu Chika , Yamada Masakazu , Miyata Yohane , Uchiyama Yuri , Matsumoto Naomichi , Kusumi Yumi , Shiraishi Atsushi
Published: April 2023

Purpose:

The aim of this study was to report a case of Peters plus-like syndrome, which revealed to have an 8q21.11 microdeletion by copy number variation analysis using exome data.

Methods:

A 6-month-old Japanese boy presented with bilateral corneal opacity since birth. The right eye maintained central corneal transparency with slightly inferior nasal and superior peripheral corneal opacities. The entire cornea was opacified in the left eye, particularly in the superior quadrants with vascularization, suggesting Peters anomaly. Identification of intraocular structures in the left eye was difficult; however, hypoplasia of the circumferential anterior iris stroma appeared bilaterally present, and no abnormalities were present in the posterior segment on funduscopic examination of the right eye and ultrasonography in the left eye. He had several facial malformations in addition to corneal opacity, but no other external abnormalities. General examination, including biochemical tests of blood and urine, physiological and imaging tests including abdominal echo, auditory brain stem response, brain computed tomography, and magnetic resonance imaging, showed no abnormalities. However, the patient showed intellectual disability and delayed motor development.

Results:

Although his karyotype was normal, copy number variation analysis using exome data and subsequent quantitative polymerase chain reaction identified a de novo 4.6-Mb deletion at 8q21.11q21.13; thus, the patient was diagnosed with 8q21.11 microdeletion syndrome.

Conclusions:

We identified a de novo 4.6-Mb deletion at 8q21.11q21.13 in a patient with ophthalmic anterior segment dysgenesis and systemic complications, clinically diagnosed as Peters plus-like syndrome. Clinically, the 8q21.11 microdeletion syndrome shows a phenotype similar to that of Peters plus syndrome, and a genetic diagnosis is required.
Clinical Pharmacist Transition of Care Model Improves Hospital System Practice by Reducing Readmissions
Authors: Ngo Nha Uyen Tuong , Tangpraphaphorn Soodtida , Kahaku Deborah , Canamar Catherine P. , Young Andrew
Published: April 2023

Purpose:

A primary cause of hospital readmission is medication-related problems (MRPs). Polypharmacy patients taking multiple medications concurrently experience an increased likelihood of MRPs and high occurrence of readmissions to the hospital within 30 days. This study assessed the ability of a pharmacist-led transition of care program to decrease readmissions in polypharmacy patients by evaluating and rectifying MRPs.

Methods:

Over 16 months, patients admitted onto the medicine ward service with ≥10 home medications (n = 536) received medication management interventions from a clinical pharmacist including admission interview, medication reconciliation and consultation, and postdischarge phone follow-up. Admitted patients taking fewer than 10 home medications during the same time served as the control group and received routine standard of care (n = 2317).

Results:

The polypharmacy group who received the pharmacist-led intervention had a statistically significantly lower 30-day readmission rate (8.8%) compared with patients in the control group (12.4%; X2 = 5.63, p = .01). Patients receiving pharmacist intervention were 33% less likely to be readmitted within 30 days of discharge compared with the control group (odds ratio = 0.67, 95% CI = 0.49–0.94). All patients had at least one medication-related discrepancy.

Conclusion:

This pharmacy-led transition of care program can effectively reduce readmission rates through resolution of medication-related problems.
In-hospital waiting time to surgery and functional outcomes in geriatric hip fractures: a directed acyclic graph-based preplanned analysis from a prospective multicenter cohort study
Authors: Cai Qianying , Fu Kai , Jia Weitao , Li Xiaolin , He Haiyan , Yao Zhenjun , Chen Xiaodong , Dong Yuqi , Wang Qiugen , Kang Bin , Qian Biyun , Chen Shengbao , Zhang Changqing
Published: April 2023

Background:

The early recovery of hip function after hip fracture surgery values more attention, especially for patients with delayed surgery of longer than 48 h. We aim to evaluate the associations of in-hospital surgical waiting time with the functional outcomes [Harris Hip Score (HHS), Parker Mobility Score (PMS), and EuroQol 5 dimensions VAS (visual analogue scale) score (EQ-5D VAS)] in elderly patients who sustained hip fractures.

Materials and methods:

Data on sociodemographic and clinical factors were prospectively collected using a multicenter hip fracture registry system. Participants in the cohort underwent a 12-month follow-up investigation. After adjusting potential confounders identified by the directed acyclic graphs, the associations between surgical waiting time longer than 48 h and functional outcomes were estimated by log-binomial regression and multivariable linear regression models with generalized estimating equations.

Results:

Of 863 survival participants with available functional data at 12 months after surgery, an increased risk was obtained from receiving surgery after 48 h and the poor functional outcomes (HHS<80: relative risk (RR)=1.56, 95% CI: 1.00–2.51; PMS<7: RR=1.49, 95% CI: 1.13–2.01; EQ-5D VAS<80: RR=1.97, 95% CI: 1.57–2.47). In-hospital waiting time greater than 48 h were time-invariantly associated with lower PMS during recovery (−0.44 units 95% CI: −0.70 to −0.18). In addition, delayed surgery was time-varying associated with HHS and EQ-5D VAS.

Conclusions:

The associations between in-hospital waiting time and postoperative functional score suggest that delayed surgery can lead to poor functional outcomes, especially in patients waiting longer than 72 h from injury. Delayed surgery mainly impacted hip function and mobility recovery with a slower speed in early recovery of the first 3 months. More attention should be paid to mechanisms behind the associations between delayed surgery on general healthy status.
The role of laparoscopic adrenalectomy in the treatment of large pheochromocytomas (>6 cm): a meta-analysis and systematic review
Authors: Gan Lijian , Peng Lei , Meng Chunyang , Zheng Lei , Zeng Zhiqiang , Ge Si , Wang Zuoping , Li Kangsen , Li Yunxiang
Published: April 2023

Background:

The effectiveness and safety of laparoscopic adrenalectomy (LA) under different routes for the treatment of large pheochromocytomas (PCCs) is unknown.

Materials and methods:

This meta-analysis and systematic review was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (Assessing the methodological quality of systematic reviews) Guidelines. Three databases were systematically searched, including Medline, PubMed, and Web of Science. The time frame of the search was set from the creation of the database to October 2022. Perioperative outcomes were divided into two groups according to tumor size: SMALL group (≤6 cm in diameter), LARGE group (>6 cm in diameter).

Results:

Eight studies including 600 patients were included. In the LA group, complications was comparable in both groups (SMALL group and LARGE group), and the LARGE group had longer operative time [OT weighted mean difference (WMD)=32.55; 95% CI: 11.17, 53.92; P<0.01], length of stay (LOS WMD=0.82; 95% CI: 0.19, 1.44; P<0.05), more estimated blood loss (EBL WMD=85.26; 95% CI: 20.71, 149.82; P<0.05), hypertension [odds ratio (OR)=3.99; 95% CI: 1.84, 8.65; P<0.01], hypotension (OR=1.84; 95% CI: 1.11, 3.05; P<0.05), and conversion (OR=5.60; 95% CI: 1.56, 20.13; P<0.01). In the transabdominal LA group, OT, LOS, EBL, complications, hypertension, and hypotension were the same in both groups. In the retroperitoneal LA group, complications and hypotension were the same in both groups, while the LARGE group had longer OT (WMD=52.07; 95% CI: 26.95, 77.20; P<0.01), LOS (WMD=0.51; 95% CI: 0.00, 1.01; P<0.05), more EBL (WMD=92.99; 95% CI: 27.70, 158.28; P<0.01) and higher rates of hypertension (OR=6.03; 95% CI: 1.95, 18.61; P<0.01).

Conclusions:

LA remains a safe and effective approach for large PCC. Transabdominal LA is superior to retroperitoneal LA.
Preoperative α-blockade versus no blockade for pheochromocytoma–paraganglioma patients undergoing surgery: a systematic review and updated meta-analysis
Authors: Wang Jue , Liu Qingyuan , Jiang Shihao , Zhang Jindong , He Jinke , Li Yunfan , Wang Delin
Published: April 2023

Background:

Surgical resection of pheochromocytomas and paragangliomas (PPGLs) is associated with a significant risk of intraoperative hemodynamic instability and cardiovascular complications. α-blockade remains the routine preoperative medical preparation despite controversies over the lack of evidence. We presented an updated meta-analysis to ulteriorly evaluate the potential efficacy of preoperative α-blockade versus no blockade for PPGL patients undergoing surgery.

Materials and methods:

Randomized and nonrandomized comparative studies assessing preoperative α-blockade for PPGL surgery in adults were identified through a systematic literature search via MEDLINE, Embase, Web of Science, and CENTRAL up to November 2022. Outcome data of intraoperative hemodynamic parameters and major postoperative events were extracted. Mean difference and risk ratio were synthesized as appropriate for each outcome to determine the cumulative effect size.

Results:

Fifteen nonrandomized studies involving 3542 patients were finally eligible. Intraoperatively, none of the analyzed hemodynamic parameters differed between patients with or without α-blockade: maximum and minimum systolic blood pressure, hypertensive and hypotensive hemodynamic instability episodes, and peak heart rate, subgroup analysis of normotensive PPGL patients yielded similar results with the overall effects. Postoperatively, α-blockade was associated with prolonged hypotension and vasopressor usage (risk ratio: 4.21, 95% CI: 1.17–15.18, P=0.03). ICU admission, length of stay, overall cardiovascular morbidity, and mortality were similar between the two groups.

Conclusions:

Preoperative α-blockade ensured neither more stable intraoperative hemodynamics nor better perioperative outcome over no blockade for PPGL surgery. However, large-volume randomized controlled trials are still warranted to ascertain these findings.
From large-for-size to large-for-flow: A paradigm shift in liver transplantation
Authors: Rossignol Guillaume , Muller Xavier , Couillerot Joris , Lebosse Fanny , Delignette Marie-Charlotte , Mohkam Kayvan , Mabrut Jean-Yves
Published: April 2023

Liver graft-recipient matching remains challenging, and both morphologic and hemodynamic characteristics have been shown to be relevant indicators of post-transplant outcomes. However, no combined analysis is available to date. To study the impact of both morphologic and hemodynamic characteristics of liver grafts on transplantation outcomes, we retrospectively evaluated all consecutive 257 liver transplantations with prospective hemodynamic measurements from 2017 to 2020 in a single-center perspective. First, a morphologic analysis compared recipients with or without large-for-size (LFS), defined by a graft/recipient weight ratio >2.5% and excluding extreme LFS. Second, a hemodynamic analysis compared recipients with or without low portal flow (LPF; <80 mL/min per 100 g of liver tissue). Third, an outcome analysis combining LPF and LFS was performed, focusing on liver graft-related morbidity (LGRM), graft and patient survival. LGRM was a composite endpoint, including primary nonfunction, high-risk L-Graft7 category, and portal vein thrombosis. Morphologic analysis showed that LFS (n=33; 12.9%) was not associated with an increased LGRM (12.1% vs 9.4%; p=0.61) or impaired graft and patient survival. However, the hemodynamic analysis showed that LPF (n=43; 16.8%) was associated with a higher LGRM (20.9% vs 7.5%, p = 0.007) and a significantly impaired 90-day graft and patient survival. Multivariable analysis identified LPF but not LFS as an independent risk factor for LGRM (OR: 2.8%; CI:1.088–7.413; and p = 0.03), 90-day (HR: 4%; CI: 1.411–11.551; and p = 0 .01), and 1-year patient survival. LPF is a significant predictor of post-liver transplantation morbi-mortality, independent of LFS when defined as a morphologic metric alone. Consequently, we propose the novel concept of large-for-flow, which may guide graft selection and improve perioperative management of LPF.
Performances of HEART score to predict 6-month prognostic of emergency department patients with chest pain: a retrospective cohort analysis
Authors: Fiore Giorgio , Pinto Giuseppe , Preda Alberto , Rampa Lorenzo , Gaspardone Carlo , Oppizzi Michele , Slavich Massimo , Di Napoli Davide , Bianchi Gianluca , Etteri Massimiliano , Margonato Alberto , Fragasso Gabriele
Published: April 2023

Background and importance

Chest pain is a frequent cause of patient admissions in emergency departments (EDs). Clinical scores can help in the management of chest pain patients with an undefined impact on the appropriateness of hospitalization or discharge when compared to usual care.

Objectives

The aim of this study was to assess the performances of the HEART score to predict the 6-month prognostic of patients presenting to the ED of a tertiary referral university hospital with non-traumatic chest pain.

Design, settings, and participants

From 7040 patients presenting with chest pain from 1 January 2015 to 31 December 2017, after applying exclusion criteria (ST-segment elevation >1 mm, shock, absence of telephone number) we selected a sample of 20% chosen randomly. We retrospectively assessed the clinical course, definitive diagnosis, and HEART score according to ED final report. Follow-up was made by telephone interview with discharged patients. In hospitalized patients, clinical records were analyzed to evaluate major adverse cardiac events (MACE) incidence.

Outcome measure and analysis

The primary endpoint was MACE, comprising cardiovascular death, myocardial infarction, or unscheduled revascularization at 6 months. We assessed the diagnostic performance of the HEART score in ruling out MACE at 6 months. We also assessed the performance of ED usual care in the management of chest pain patients.

Results

Of 1119 screened, 1099 were included for analysis after excluding patients lost to follow-up; 788 patients (71.70%) had been discharged and 311 (28.30%) were hospitalized. Incident MACE was 18.3% (n = 205). The HEART score was retrospectively calculated in 1047 patients showing increasing MACE incidence according to risk category (0.98% for low risk, 38.02% for intermediate risk, and 62.21% for high risk). Low-risk category allowed to safely exclude MACE at 6 months with a negative predictive value (NPV) of 99%. Usual care diagnostic performance showed 97.38% sensitivity, 98.24% specificity, 95.5% positive predictive value, and 99% NPV, with an overall accuracy of 98.00%.

Conclusions

In ED patients with chest pain, a low HEART score is associated with a very low risk of MACE at 6 months.
Computer assisted interpretation of Tc-99m mercaptoacetyltriglycine diuretic scintigraphy enhances resident performance
Authors: Taylor Andrew T. , Fazlur Rahman A.K.M. , Folks Russell D. , Moncayo Valeria , Savir-Baruch Bital , Plaxton Nicholas , Polsani Aruna , Halkar Raghuveer K. , Dubovsky Eva V. , Garcia Ernest V. , Manatunga Amita
Published: April 2023

Objective

iRENEX is a software module that incorporates scintigraphic and clinical data to interpret 99mTc- mercaptoacetyltriglycine (MAG3) diuretic studies and provide reasons for their conclusions. Our objectives were to compare iRENEX interpretations with those of expert physicians, use iRENEX to evaluate resident performance and determine if iRENEX could improve the diagnostic accuracy of experienced residents.

Methods

Baseline and furosemide 99mTc-MAG3 acquisitions of 50 patients with suspected obstruction (mean age ± SD, 58.7 ± 15.8 years, 60% female) were randomly selected from an archived database and independently interpreted by iRENEX, three expert readers and four nuclear medicine residents with one full year of residency. All raters had access to scintigraphic data and a text file containing clinical information and scored each kidney on a scale from +1.0 to −1.0. Scores ≥0.20 represented obstruction with higher scores indicating greater confidence. Scores +0.19 to −0.19 were indeterminate; scores ≤−0.20 indicated no obstruction. Several months later, residents reinterpreted the studies with access to iRENEX. Receiver operating characteristic (ROC) analysis and concordance correlation coefficient (CCC) quantified agreement.

Results

The CCC among experts was higher than that among residents, 0.84, versus 0.39, respectively, P < 0.001. When residents reinterpreted the studies with iRENEX, their CCC improved from 0.39 to 0.73, P < 0.001. ROC analysis showed significant improvement in the ability of residents to distinguish between obstructed and non-obstructed kidneys using iRENEX (P = 0.036).

Conclusion

iRENEX interpretations were comparable to those of experts. iRENEX reduced interobserver variability among experienced residents and led to better agreement between resident and expert interpretations.
Cardiac atrial metabolism quantitative assessment with analog and digital time of flight-PET/computed tomography
Authors: Hesse Michel , Marchandise Sébastien , Gerber Bernhard , Roelants Véronique
Published: April 2023

Background

Evaluation of left atrium (LA) remodeling is becoming increasingly relevant in understanding several pathological cardiac conditions. 18F-FDG-PET/computed tomography (CT), the current gold standard for metabolic evaluation of the left ventricle, could be extended to LA using the latest PET technologies. We sought to perform a phantom study to optimize the reconstruction algorithm in this context.

Methods

The liver, heart cavity and walls of an anthropomorphic phantom were filled with typical patient 18F-FDG activity concentrations. Acquisitions were performed on an analog and on a digital TOF-PET/CT, and reconstructed with and without resolution recovery (RR). The Richardson-Lucy RR method was used, either through a third-party software or through the PET/CT manufacturer algorithm. Activity recoveries in the atria and ventricles and signal-to-noise ratios were evaluated to identify the best reconstruction and RR parameters. The same methodology was applied on a patient cardiac study.

Results

Analog PET/CT with the third-party RR cannot improve the activity recovery without markedly degrading the image quality. For the digital PET/CT, the optimal algorithm was the manufacturer RR reconstruction using four iterations and 15 subsets combined with five RR iterations. This reconstruction improved the LA activity recovery from 58% to 70% while preserving images of diagnostic quality. Similar results were obtained for the patient study.

Conclusion

The digital TOF-PET/CT with the identified optimal reconstruction can be used to quantitatively analyze the LA uptake in 18F-FDG cardiac studies while still preserving image reading quality. This may lead to more precise cardiovascular disease status evaluation, especially when atria are concerned.