bluuebunny/crossref_metadata_2025 huggingface dataset:
A276 CANNABINOID RECEPTOR 1 IS LOCALIZED IN ENTERIC NEURONS AND EPITHELIUM IN FETAL AND EARLY POSTNATAL MOUSE INTESTINE
Authors: Sunil M , Adnan M , Farcas S , Pugazhendhi A , Ratcliffe E
Published: March 2023

Background

The endocannabinoid system (ECS) is necessary for gastrointestinal (GI) homeostasis and serves as a target for exogenous medicinal and recreational cannabinoid compounds. While components of the ECS, including receptors, ligands, and biosynthetic/degradative enzymes, have been increasingly characterized in the adult GI tract of both humans and animal models, similar advances in understanding the role of the ECS in GI developmental programming have not yet been made.

Purpose

We tested the hypothesis that the ECS plays a role in the developmental programming of the GI tract.

Method

The developmental timeline of ECS component expression was investigated in the GI tract from fetal and early postnatal mice. Samples from timed-pregnant outbred mice were collected from embryonic days 14 (E14), E16, E18 and postnatal days 1 (P1), P7 and P28, representing a timeline of early colonization of the GI tract by enteric neurons (E14) to 1 week after weaning (P28). Localization of cannabinoid receptor 1 (CB1) expression was examined in fetal and postnatal small intestine by immunohistochemistry. Fetal intestine was processed for RNA extraction and relative expression of ECS components determined by RT-qPCR.

Result(s)

CB1 expression at E14 was observed in the outer wall of the gut and in the developing mucosa. By E18, expression of CB1 became more localized to the enteric plexuses and to mucosal epithelial cells. In postnatal ileum, at least >50% of myenteric ganglia were found to express CB1 from P1 to P28. CB1 expression continued to be present in the mucosal epithelium of ileum from P1 to P28, with a subset of CB1 expression in enterochromaffin cells, as identified by 5-HT immunolabeling. Significant decreases in expression of mRNA encoding CB1 (p<0.0001) and the ECS biosynthetic enzymes NAPE-PLD (p<0.05) and DAGLa (p<0.05) were found between E14 and E18.

Conclusion(s)

Components of the ECS are present in the fetal and early postnatal GI tract. Further research is needed to better characterize the roles and mechanisms of action of the ECS in GI development. The potential impact of exogenous cannabis exposure in early life, either by in utero exposure or via the use of medicinal cannabinoids in childhood, highlights the importance of identifying the contributions of the ECS to normal development.

Disclosure of Interest

None Declared
A293 IS NON AL C OHOLIC FATTY PANCREATIC DISEASESE IS PATHOLOGICAL DISEASESE FOR DEVELOPMENT OF DIABETES :AN EGYPTIAN PILOT STUDY
Authors: Elbadawy R M , Natboli M S , Masoud G M
Published: March 2023

Background

Non Alcoholic Fatty Pancreatic disease(NAFPD), Fatty pancreas emerged as health problem world wide parralel to the epidemic of obesity .NAFPD lead chronic pancreatitis ,exocrine pancreatic insufficiency as per research proved . NAFPD also can lead to Diabeties Mellites (DM ) and lasly pancreatic adenocarcinoma . As per UEG cancer pancreas will be the the 3rd cancer world wide which is so serious and almost most of the patients come late with irriversible stage . Of sure most the patients with cancer pancreas have DM and other pancreatic disorders .

Purpose

The Aim of the research was to explore that NAFPD is the first stage in the development of DM

Method

Eighty -Eight subjects was inculded in the study both male and female ,DM or non DM and obese or not obese with mean age 25-66 years old .The subjects were divided into 4 groups .Group (1)DM subjects withnormal body mass index<25kg/m2. Group (2)Subjects DM with body mass index >25 kg/m2 obese .Group (3)subjects nonDM ,non obese with normal body mass index.Group (4)subjects non DM withbody mass index >25kg/m2 . Each group 22 subjects both male and females.All routine investigations were done inculding lipid profile , liver functions .Nafpd was diagnosed by abdominal ultrasound ,Toshiba using convex probecompared to right kidney , liver and brightness of diaphragm .The echogencity was graded from (0-3 )..statistical analysis by SPSS version 22 was used.

Result(s)

Mean age was 44.08+_12.4 years old for all subjects. Mean Body Mass Index(BMI) was 29.73_+8.15 kg/m2 .Male was 73% while female 27% of NAFPD diagnosis .NAFPD was present in non obese non DM as follow ,grade 1,2,3(22.7%,27.3% and 22.7% respectively ).While NAFPD was present in DM non obese as follow in grades 1.2,3(22.7%,31.8% and45.4% respectively ) means that there was increas in % of DM development especially grade 2,3 . NAFPD was in obese non DM as follow in grades 2,3(31.8%,68.2% respectively . While in in DM obese NAFPD was present as follow (18.2%,81.2%). .This means that there was increaseincrease in % of DM development.

Conclusion(s)

NAFPD proved to be the first step in development of DM , it is an alert sign for health insitiute to care the issue to prevent DM from the start .

Aknowledgment to Academic Scientific Research & Technology for funding jesor project no 5269 , as this work part from the project

Please acknowledge all funding agencies by checking the applicable boxes below

None

Disclosure of Interest

R. Elbadawy Grant / Research support from: Aknowldgement to Academic Scientific Research & Technology , Egypt (ASRT ) for funding jesor project as this work part of the project, Paid Instructor of: 1000000 egyptian pound, M. Natboli: None Declared, G. Masoud: None Declared
The Disruptive Behavior Disorders Rating Scale: Updated Factor Structure, Measurement Invariance, and National Caregiver Norms
Authors: Fosco Whitney D , Babinski Dara E , Waschbusch Daniel A
Published: March 2023

Objective

To provide the first caregiver-report national norms for the Disruptive Behavior Disorders Rating Scale (DBDRS) and an updated evaluation of its factor structure and measurement invariance across child sex, informant sex, and child age.

Methods

Caregivers of children aged 5–12 years (N = 962) based in the United States completed the four DBDRS subscales. Using both severity scoring and dichotomous scoring procedures, confirmatory factor analyses supported a four-factor model of inattentive and hyperactive/impulsive symptoms, oppositional defiant symptoms, and conduct disorder symptoms.

Results

Measurement invariance was supported, indicating that the DBDRS functions similarly across demographic characteristics. Boys were reported to have more severe symptoms than girls (Cohen’s d = 0.33 [inattention], 0.30 [hyperactivity/impulsivity], 0.18 [oppositional defiant disorder], 0.14 [conduct disorder]), female caregivers rated ADHD symptoms as more severe than male caregivers (ds = 0.15 and 0.19 for inattention and hyperactivity/impulsivity, respectively), and older children were reported to experience more inattention than younger children (d = 0.18). Overall, group differences were modest in magnitude.

Conclusion

This psychometric study supports the continued use of the DBDRS in school-aged youth and will enhance the measure’s clinical and research utility by providing the first caregiver-report norms.
Debiased and thresholded ridge regression for linear models with heteroskedastic and correlated errors
Authors: Zhang Yunyi , Politis Dimitris N
Published: March 2023

High-dimensional linear models with independent errors have been well-studied. However, statistical inference on a high-dimensional linear model with heteroskedastic, dependent (and possibly nonstationary) errors is still a novel topic. Under such complex assumptions, the paper at hand introduces a debiased and thresholded ridge regression estimator that is consistent, and is able to recover the model sparsity. Moreover, we derive a Gaussian approximation theorem for the estimator, and apply a dependent wild bootstrap algorithm to construct simultaneous confidence interval and hypothesis tests for linear combinations of parameters. Numerical experiments with both real and simulated data show that the proposed estimator has good finite sample performance. Of independent interest is the development of a new class of heteroscedastic, (weakly) dependent, and nonstationary random variables that can be used as a general model for regression errors.
Identifying optimally cost-effective dynamic treatment regimes with a Q-learning approach
Authors: Illenberger Nicholas , Spieker Andrew J , Mitra Nandita
Published: March 2023

Health policy decisions regarding patient treatment strategies require consideration of both treatment effectiveness and cost. We propose a two-step approach for identifying an optimally cost-effective and interpretable dynamic treatment regime. First, we develop a combined Q-learning and policy-search approach to estimate optimal list-based regimes under a constraint on expected treatment costs. Second, we propose an iterative procedure to select an optimally cost-effective regime from a set of candidate regimes corresponding to different cost constraints. Our approach can estimate optimal regimes in the presence of time-varying confounding, censoring, and correlated outcomes. Through simulation studies, we examine the operating characteristics of our approach under flexible modelling approaches. We also apply our methodology to identify optimally cost-effective treatment strategies for assigning adjuvant therapies to endometrial cancer patients.
Effect of mindfulness on sexual self-esteem and marital intimacy in postmenopausal women: a quasi-experimental study
Authors: Khazaeian Somayyeh , Rahimi-Nezhad Maryam , Fathnezhad-Kazemi Azita
Published: March 2023

Background

Menopause is a turning point in women’s lives and a major medical challenge, leading to drastic changes in sexual self-esteem and the husband-wife relationship, which can have an undeniable impact on the quality of their life.

Aim

To assess the effect of mindfulness-based education on sexual self-esteem and marital intimacy in postmenopausal women.

Methods

This quasi-experimental study was conducted with 130 women who were assigned to 2 groups, intervention (n = 65) and control (n = 65), out of whom 127 completed the study. The interventional group received 8 training sessions. The mindfulness-based intervention consisted of 8 educational sessions and daily mindfulness exercises. Sexual self-esteem was assessed by the Sexual Self-esteem Index for Woman–Short Form, and marital intimacy was measured with Thompson and Walker’s Intimacy Scale. The collected data were analyzed via analysis of covariance.

Outcomes

Outcomes included changes in sexual self-esteem and marital intimacy scores.

Results

Participants in the intervention group demonstrated higher levels of total self-esteem posttreatment than participants in the control group (125.15 vs 119.46) and higher levels of intimacy (74.22 vs 61.59). The difference was still significant after adjusting for self-esteem (η2 = 0.312, P < .001) and intimacy (η2 = 0.573, P < .001) at baseline.

Clinical Implications

Mindfulness may be used as a strategy to improve sexual self-esteem and marital intimacy.

Strengths and Limitations

Unlike other treatments, mindfulness seems to be low cost and less complex in improving sexual self-esteem and marital intimacy. Limitations of this study include use of available sampling methods, nonrandom allocation of participants, and self-reporting data collection.

Conclusion

As evidenced by the results, 8 weeks of mindfulness training could improve sexual self-esteem and marital intimacy in menopausal women. The mindfulness-based intervention should be incorporated into routine care to help menopausal women.
Rice FERONIA-LIKE RECEPTOR 3 and 14 affect grain quality by regulating redox homeostasis during endosperm development
Authors: He Wei , Li Wanjing , Luo Xiao , Tang Yuqin , Wang Long , Yu Feng , Lin Qinlu
Published: March 2023

Chalky endosperm negatively affects the appearance, milling, and eating qualities of rice (Oryza sativa L.) grains. Here, we report the role of two receptor-like kinases, FERONIA-LIKE RECEPTOR 3 (FLR3) and FERONIA-LIKE RECEPTOR 14 (FLR14), in grain chalkiness and quality. Knockouts of FLR3 and/or FLR14 increased the number of white-core grains caused by aberrant accumulation of storage substances, resulting in poor grain quality. Conversely, the overexpression of FLR3 or FLR14 reduced grain chalkiness and improved grain quality. Transcriptome and metabolome analyses showed that genes and metabolites involved in the oxidative stress response were significantly up-regulated in flr3 and flr14 grains. The content of reactive oxygen species was significantly increased in flr3 and flr14 mutant endosperm but decreased in overexpression lines. This strong oxidative stress response induced the expression of programmed cell death (PCD)-related genes and caspase activity in endosperm, which further accelerated PCD, resulting in grain chalkiness. We also demonstrated that FLR3 and FLR14 reduced grain chalkiness by alleviating heat-induced oxidative stress in rice endosperm. Therefore, we report two positive regulators of grain quality that maintain redox homeostasis in the endosperm, with potential applications in breeding rice for optimal grain quality.
The bar rotation rate as a diagnostic of dark matter content in the centre of disc galaxies
Authors: Buttitta C , Corsini E M , Aguerri J A L , Coccato L , Costantin L , Cuomo V , Debattista V P , Morelli L , Pizzella A
Published: March 2023

We investigate the link between the bar rotation rate and dark matter content in barred galaxies by concentrating on the cases of the lenticular galaxies NGC 4264 and NGC 4277. These two gas-poor galaxies have similar morphologies, sizes, and luminosities. But, NGC 4264 hosts a fast bar, which extends to nearly the corotation, while the bar embedded in NGC 4277 is slow and falls short of corotation. We derive the fraction of dark matter fDM, bar within the bar region from Jeans axisymmetric dynamical models by matching the stellar kinematics obtained with the MUSE integral-field spectrograph and using SDSS images to recover the stellar mass distribution. We build mass-follows-light models as well as mass models with a spherical halo of dark matter, which is not tied to the stars. We find that the inner regions of NGC 4277 host a larger fraction of dark matter ($f_{\rm DM, bar}\, =\, 0.53\pm 0.02$) with respect to NGC 4264 ($f_{\rm DM, bar}\, =\, 0.33\pm 0.04$) in agreement with the predictions of theoretical works and the findings of numerical simulations, which have found that fast bars live in baryon-dominated discs, whereas slow bars experienced a strong drag from the dynamical friction due to a dense DM halo. This is the first time that the bar rotation rate is coupled to fDM, bar derived from dynamical modelling.
Multipole expansion for 21 cm intensity mapping power spectrum: Forecasted cosmological parameters estimation for the SKA observatory
Authors: Berti Maria , Spinelli Marta , Viel Matteo
Published: March 2023

The measurement of the large-scale distribution of neutral hydrogen in the late Universe, obtained with radio telescopes through the hydrogen 21 cm line emission, has the potential to become a key cosmological probe in the upcoming years. We explore the constraining power of 21 cm intensity mapping observations on the full set of cosmological parameters that describe the ΛCDM model. We assume a single-dish survey for the SKA Observatory and simulate the 21 cm linear power spectrum monopole and quadrupole within six redshift bins in the range $z$ = 0.25–3. Forecasted constraints are computed numerically through Markov Chain Monte Carlo techniques. We extend the sampler CosmoMC by implementing the likelihood function for the 21 cm power spectrum multipoles. We assess the constraining power of the mock data set alone and combined with Planck 2018 CMB observations. We find that 21 cm multipoles observations alone are enough to obtain constraints on the cosmological parameters comparable with other probes. Combining the 21 cm data set with CMB observations results in significantly reduced errors on all the cosmological parameters. The strongest effect is on Ωch2 and H0, for which the error is reduced by almost a factor four. The percentage errors we estimate are $\sigma _{\Omega _ch^2} = 0.25~{{\ \rm per\ cent}}$ and $\sigma _{H_0} = 0.16~{{\ \rm per\ cent}}$, to be compared with the Planck only results $\sigma _{\Omega _ch^2} = 0.99~{{\ \rm per\ cent}}$ and $\sigma _{H_0} = 0.79~{{\ \rm per\ cent}}$. We conclude that 21 cm SKAO observations will provide a competitive cosmological probe, complementary to CMB and, thus, pivotal for gaining statistical significance on the cosmological parameters constraints, allowing a stress test for the current cosmological model.
INFERNO: Galactic winds in dwarf galaxies with star-by-star simulations including runaway stars
Authors: Andersson Eric P , Agertz Oscar , Renaud Florent , Teyssier Romain
Published: March 2023

The formation and evolution of galaxies have proved sensitive to the inclusion of stellar feedback, which is therefore crucial to any successful galaxy model. We present INFERNO, a new model for hydrodynamic simulations of galaxies, which incorporates resolved stellar objects with star-by-star calculations of when and where the injection of enriched material, momentum, and energy takes place. INFERNO treats early stellar kinematics to include phenomena such as walkaway and runaway stars. We employ this innovative model on simulations of a dwarf galaxy and demonstrate that our physically motivated stellar feedback model can drive vigorous galactic winds. This is quantified by mass and metal loading factors in the range of 10–100, and an energy loading factor close to unity. Outflows are established close to the disc, are highly multiphase, spanning almost 8 orders of magnitude in temperature, and with a clear dichotomy between mass ejected in cold, slow-moving (T ≲ 5 × 104 K, v < 100 km s−1) gas and energy ejected in hot, fast-moving (T > 106 K, v > 100 km s−1) gas. In contrast to massive disc galaxies, we find a surprisingly weak impact of the early stellar kinematics, with runaway stars having little to no effect on our results, despite exploding in diffuse gas outside the dense star-forming gas, as well as outside the galactic disc entirely. We demonstrate that this weak impact in dwarf galaxies stems from a combination of strong feedback and a porous interstellar medium, which obscure any unique signatures that runaway stars provide.
Clinical features of polymyalgia rheumatica patients in Japan: Analysis of real-world data from 2015 to 2020
Authors: Tanaka Yoshiya , Tanaka Shinichi , Takahashi Toshiya , Kato Naoto
Published: March 2023

Objectives

To assess clinical features in patients with polymyalgia rheumatica (PMR) in Japan by the International Classification of Disease (ICD)-10 code assignment.

Methods

Demographics, treatment patterns, and concomitant diseases (identified using ICD-10 code only) in patients who were assigned the PMR ICD-10 code M35.3 at least once between 1 January 2015 and 31 December 2020 were aggregated from a nationwide medical information database owned by the Health, Clinic, and Education Information Evaluation Institute.

Results

The cumulative number of patients with PMR was 6325 (mean [standard deviation] age, 74.3 [11.4] years; male:female, 1:1.3). Most patients were >50 years (96.5%) with >33% between 70 and 79 years. Glucocorticoids were prescribed in ∼54% of patients within 30 days of PMR code assignment. All other drug types were prescribed in <5% of patients. Hypertension, diabetes mellitus, rheumatoid arthritis, and osteoporosis were noted in >25% and giant cell arteritis in 1% of patients. During the study period, 4075 patients were newly assigned the PMR code and 62% were prescribed glucocorticoids within 30 days.

Conclusions

This is the first retrospective real-world data analysis describing the clinical features of PMR in a large patient population from Japan. Further studies of prevalence, incidence, and clinical features are warranted in patients with PMR.
Chemistry, structure and function of approved oligonucleotide therapeutics
Authors: Egli Martin , Manoharan Muthiah
Published: March 2023

Eighteen nucleic acid therapeutics have been approved for treatment of various diseases in the last 25 years. Their modes of action include antisense oligonucleotides (ASOs), splice-switching oligonucleotides (SSOs), RNA interference (RNAi) and an RNA aptamer against a protein. Among the diseases targeted by this new class of drugs are homozygous familial hypercholesterolemia, spinal muscular atrophy, Duchenne muscular dystrophy, hereditary transthyretin-mediated amyloidosis, familial chylomicronemia syndrome, acute hepatic porphyria, and primary hyperoxaluria. Chemical modification of DNA and RNA was central to making drugs out of oligonucleotides. Oligonucleotide therapeutics brought to market thus far contain just a handful of first- and second-generation modifications, among them 2′-fluoro-RNA, 2′-O-methyl RNA and the phosphorothioates that were introduced over 50 years ago. Two other privileged chemistries are 2′-O-(2-methoxyethyl)-RNA (MOE) and the phosphorodiamidate morpholinos (PMO). Given their importance in imparting oligonucleotides with high target affinity, metabolic stability and favorable pharmacokinetic and -dynamic properties, this article provides a review of these chemistries and their use in nucleic acid therapeutics. Breakthroughs in lipid formulation and GalNAc conjugation of modified oligonucleotides have paved the way to efficient delivery and robust, long-lasting silencing of genes. This review provides an account of the state-of-the-art of targeted oligo delivery to hepatocytes.
Effective extraction of polyribosomes exposes gene expression strategies in primary astrocytes
Authors: Mandelboum Shir , Herrero Melisa , Atzmon Andrea , Ehrlich Marcelo , Elroy-Stein Orna
Published: March 2023

Regulation of mRNA translation in astrocytes gains a growing interest. However, until now, successful ribosome profiling of primary astrocytes has not been reported. Here, we optimized the standard ‘polysome profiling’ method and generated an effective protocol for polyribosome extraction, which enabled genome-wide assessment of mRNA translation dynamics along the process of astrocyte activation. Transcriptome (RNAseq) and translatome (Riboseq) data generated at 0, 24 and 48 h after cytokines treatment, revealed dynamic genome-wide changes in the expression level of ∼12 000 genes. The data clarify whether a change in protein synthesis rate results from a change in mRNA level or translation efficiency per se. It exhibit different expression strategies, based on changes in mRNA abundance and/or translation efficiency, which are specifically assigned to gene subsets depending on their function. Moreover, the study raises an important take-home message related to the possible presence of ‘difficult to extract’ polyribosome sub-groups, in all cell types, thus illuminating the impact of ribosomes extraction methodology on experiments addressing translation regulation.
Functional mesoporous materials in clean energy: an interview with Dongyuan Zhao
Authors: Zhu He
Published: March 2023

National Science Review invited Prof. Dongyuan Zhao of Fudan University for an interview focusing on his team's renowned research on functional mesoporous materials and energy-related applications. Prof. Zhao is a professor of chemistry and materials science, and a member of the Chinese Academy of Sciences. He received his PhD in chemistry from Jilin University in 1990. He has since focused his research on the synthesis and structure of porous materials and molecular sieves. His team received a first-tier national science award in 2021 for their contribution to the research and development of mesoscopic materials. They discovered a method of synthesizing mesoporous organic polymers and carbonaceous materials using organic-organic self-assembly. This work was published in 2005 and since then it has turned into a vibrant new field of more than 40 000 publications so far. His team has named more than 20 of their inventions after Fudan University: the FDU mesoporous series.
Transcription factors MhDREB2A/MhZAT10 play a role in drought and cold stress response crosstalk in apple
Authors: Li Xing-Liang , Meng Dong , Li Min-Ji , Zhou Jia , Yang Yu-Zhang , Zhou Bei-Bei , Wei Qin-Ping , Zhang Jun-Ke
Published: March 2023

Drought and cold stresses seriously affect tree growth and fruit yield during apple (Malus domestica) production, with combined stress causing injury such as shoot shriveling. However, the molecular mechanism underlying crosstalk between responses to drought and cold stress remains to be clarified. In this study, we characterized the zinc finger transcription factor ZINC FINGER OF ARABIDOPSIS THALIANA 10 (ZAT10) through comparative analysis of shoot-shriveling tolerance between tolerant and sensitive apple rootstocks. MhZAT10 responded to both drought and cold stresses. Heterologous expression of MhZAT10 in the sensitive rootstock ‘G935' from domesticated apple (Malus domestica) promoted shoot-shriveling tolerance, while silencing of MhZAT10 expression in the tolerant rootstock ‘SH6' of Malus honanensis reduced stress tolerance. We determined that the apple transcription factor DEHYDRATION RESPONSE ELEMENT-BINDING PROTEIN 2A (DREB2A) is a direct regulator activating the expression of MhZAT10 in response to drought stress. Apple plants overexpressing both MhDREB2A and MhZAT10 genes exhibited enhanced tolerance to drought and cold stress, while plants overexpressing MhDREB2A but with silenced expression of MhZAT10 showed reduced tolerance, suggesting a critical role of MhDREB2A-MhZAT10 in the crosstalk between drought and cold stress responses. We further identified drought-tolerant MhWRKY31 and cold-tolerant MhMYB88 and MhMYB124 as downstream regulatory target genes of MhZAT10. Our findings reveal a MhDREB2A-MhZAT10 module involved in crosstalk between drought and cold stress responses, which may have applications in apple rootstock breeding programs aimed at developing shoot-shriveling tolerance.
Vinyl chloride enhances high-fat diet-induced proteome alterations in the mouse pancreas related to metabolic dysfunction
Authors: Ge Yue , Bruno Maribel , Nash Maliha S , Coates Najwa Haykal , Chorley Brian N , Cave Matthew C , Beier Juliane I
Published: March 2023

Alterations in physiological processes in pancreas have been associated with various metabolic dysfunctions and can result from environmental exposures, such as chemicals and diet. It was reported that environmental vinyl chloride (VC) exposure, a common industrial organochlorine and environmental pollutant, significantly exacerbated metabolic-related phenotypes in mice fed concurrently with high-fat diet (HFD) but not low-fat diet (LFD). However, little is known about the role of the pancreas in this interplay, especially at a proteomic level. The present study was undertaken to examine the protein responses to VC exposure in pancreas tissues of C57BL/6J mice fed LFD or HFD, with focus on the investigation of protein expression and/or phosphorylation levels of key protein biomarkers of carbohydrate, lipid, and energy metabolism, oxidative stress and detoxification, insulin secretion and regulation, cell growth, development, and communication, immunological responses and inflammation, and biomarkers of pancreatic diseases and cancers. We found that the protein alterations may indicate diet-mediated susceptibility in mouse pancreas induced by HFD to concurrent exposure of low levels of inhaled VC. These proteome biomarkers may lead to a better understanding of pancreas-mediated adaptive or adverse response and susceptibility to metabolic disease.
Chenopodium quinoa, a New Host forAlternariaSectionAlternataandAlternariaSectionInfectoriaeCausing Yellow Leaf Blotch Disease
Authors: Colque-Little Carla , Lund Ole Søgaard , Andreasen Christian , Amby Daniel Buchvaldt
Published: March 2023

Quinoa (Chenopodium quinoa Willd.) is a native American crop mainly grown in the Andes of Bolivia and Peru. During the last decades, the cultivation of quinoa has expanded to more than 125 countries. Since then, several diseases of quinoa have been characterized. A leaf disease was observed on quinoa plants growing in an experimental plot in Eastern Denmark in 2018. The symptoms produced by the associated fungi consisted of small yellow blotches on the upper surface of leaves with a pale chlorotic halo surrounding the lesion. These studies used a combination of morphology, molecular diagnostics, and pathogenicity tests to identify two different Alternaria species belonging to Alternaria sections Infectoriae and Alternata as the causal agent of observed disease symptoms. To the best of our knowledge, this is the first report of Alternaria spp. as foliar pathogens of quinoa. Our findings indicate the need for additional studies to determine potential risks to quinoa production.
Charged multivesicular body protein 4b forms complexes with gap junction proteins during lens fiber cell differentiation
Authors: Zhou Yuefang , Bennett Thomas M. , White Thomas W. , Shiels Alan
Published: March 2023

Charged multivesicular body protein 4b (CHMP4B) is a core sub‐unit of the endosomal sorting complex required for transport III (ESCRT‐III) machinery that serves myriad remodeling and scission processes of biological membranes. Mutation of the human CHMP4B gene underlies rare forms of early‐onset lens opacities or cataracts, and CHMP4B is required for lens growth and differentiation in mice. Here, we determine the sub‐cellular distribution of CHMP4B in the lens and uncover a novel association with gap junction alpha‐3 protein (GJA3) or connexin 46 (Cx46) and GJA8 or Cx50. Immunofluorescence confocal microscopy revealed that CHMP4B localized to cell membranes of elongated fiber cells in the outer cortex of the lens—where large gap junction plaques begin to form—particularly, on the broad faces of these flattened hexagon‐like cells in cross‐section. Dual immunofluorescence imaging showed that CHMP4B co‐localized with gap junction plaques containing Cx46 and/or Cx50. When combined with the in situ proximity ligation assay, immunofluorescence confocal imaging indicated that CHMP4B lay in close physical proximity to Cx46 and Cx50. In Cx46‐knockout (Cx46‐KO) lenses, CHMP4B‐membrane distribution was similar to that of wild‐type, whereas, in Cx50‐KO lenses, CHMP4B localization to fiber cell membranes was lost. Immunoprecipitation and immunoblotting analyses revealed that CHMP4B formed complexes with Cx46 and Cx50 in vitro. Collectively, our data suggest that CHMP4B forms plasma membrane complexes, either directly and/or indirectly, with gap junction proteins Cx46 and Cx50 that are often associated with “ball‐and‐socket” double‐membrane junctions during lens fiber cell differentiation.
Escape the Anxiety: An Interactive Dosage Calculations Escape Room as a Contextualized Math Review
Authors: Murphy Glenn , Slowinski Paulette Dawn , Sweeney Amy B. , Morse Catherine Y.
Published: March 2023

An innovative teaching strategy was designed to prepare undergraduate nursing students for their dosage calculations assessment. An interactive virtual escape room presented students with the opportunity to help discharge their patient from the hospital. Within Google Forms, nurse educators created a branching storyline where the answers selected determined the path the students would take to meet the learning objectives.
Dorsal V-Y Advancement Flap for Lateral Finger Defect Based on Dorsal Skin Branch of Proper Digital Artery
Authors: Siriwittayakorn Wuttipong , Siritattamrong Wichit
Published: March 2023

Managing lateral soft tissue defects, distal to the proximal interphalangeal joint, of the finger can be challenging. The use of antegrade homodigital island flap can be limited due to the length of the defect. Using a heterodigital island flap can be precluded by an injury in the adjacent fingers. Using the locoregional flap from the hand can result in a more extensive soft tissue dissection, which can create additional donor site morbidity. We present our execution technique of the homodigital dorsal skin advancement flap. The pedicle of the flap is based on dorsal branches of the digital artery perforator; hence the proper digital artery and nerve are unharmed. The operation is limited only to the injured digit, which can reduce donor site morbidity.
The Effect of Exercise Modalities on Walking Capacity in Patients With Intermittent Claudication
Authors: Tremblay Renaud , Marcotte-Chénard Alexis , Hamelin-Morrissette Jovane , Poirier Laurence , Perron Pierre-Nicolas , Durivage Andréanne , Mampuya Warner Mbuila , Huard Gabriel , Riesco Eléonor
Published: March 2023

Introduction:

Despite extensive research on the effect of supervised exercise therapy on walking performance in patients with symptomatic peripheral arterial disease (PAD), it remains unclear which training modality provides the greatest improvement in walking capacity. The objective of this study was to compare the effect of different types of supervised exercise therapy on walking capacity in individuals with symptomatic PAD.

Methods:

A random-effect network meta-analysis was performed. The following databases were searched from January 1966 to April 2021: SPORTDiscus, CINAHL, MEDLINE, AMED, Academic Search Complete and, Scopus. Trials had to include at least one type of supervised exercise therapy for patients with symptomatic PAD, with an intervention lasting ≥2 wk with ≥5 training sessions, and an objective measure of walking capacity.

Results:

Eighteen studies were included for a total sample of 1135 participants. Interventions duration ranged from 6-24 wk and included aerobic exercise (treadmill walking, ergometer, and Nordic walking), resistance training (lower and/or upper body), a combination of both, and underwater exercise. Results showed that combined training improved treadmill walking capacity to a comparable extent to aerobic walking (+122.0 [24.2-219.8] m vs +106.8 [34.2-179.4] m), but with a larger effect size (1.20 [0.50-1.90] vs 0.67 [0.22-1.11]). Similar results were observed for the 6-min walk distance, with combined training being the most promising modality (+57.3 [16.2-98.5] m), followed by underwater training (+56.5 [22.4-90.5] m) and aerobic walking (+39.0 [12.8-65.1] m).

Conclusion:

While not statistically superior to aerobic walking, combined exercise seems to be the most promising training modality. Aerobic walking and underwater training also improved walking capacity for patients with symptomatic PAD.
Association between lifetime cannabis use and arterial stiffness in a middle-aged general population
Authors: Vallée Alexandre
Published: March 2023

Background:

No studies have investigated the association between arterial stiffness index (ASI) and cannabis use. The purpose of this study is to examine sex-stratified associations of cannabis use and ASI levels in a middle-aged general population.

Methods:

Cannabis use of 46 219 volunteers of the middle-aged UK Biobank population was assessed by questionnaire and investigates several aspects of cannabis use (lifetime, frequency and current status). Associations between cannabis use and ASI were estimated using sex multiple linear regressions. Covariates were tobacco status, diabetes dyslipidaemia, alcohol status, BMI categories, hypertension, mean blood pressure and heart rate.

Results:

Men presented higher ASI levels compared with women (respectively, 9.826 vs. 8.578 m/s, P < 0.001), a higher heavy lifetime cannabis users (4.0 vs. 1.9%, P < 0.001), higher current cannabis users (3.1 vs. 1.7%, P < 0.001), higher current smokers (8.4 vs. 5.8%, P < 0.001) and higher alcohol users (95.6 vs. 93.4%, P < 0.001). After adjustment for all covariates in sex models, heavy lifetime cannabis users were associated with higher ASI levels in men [b = 0.19, 95% confidence interval (0.02; 0.35)] but not in women [b = –0.02 (–0.23; 0.19)]. Current cannabis users were associated with higher ASI levels in men [b = 0.17 (0.01; 0.32)] but not in women [b = –0.01 (–0.20; 0.18)] and among cannabis users, every day frequency was associated with increased ASI levels in men [b = 0.29 (0.07; 0.51)] but not in women [b = 0.10 (–0.17; 0.37)].

Conclusion:

The observed association between cannabis use and ASI could participate in accurate and appropriate cardiovascular risk reduction strategies among cannabis users.
Fungal Keratitis and Corneal Perforation as a Rare Complication of Corneal Collagen Cross-Linking Treatment
Authors: Barut Selver Ozlem , Metin Dilek Yesim , Hilmioglu Polat Suleyha , Dogen Aylin , Palamar Melis
Published: March 2023

Purpose:

The aim of this study was to report a case of fungal keratitis with subsequent corneal perforation after corneal collagen cross-linking (CXL) treatment performed for keratoconus.

Case Report:

A 20-year-old woman presented with redness and discharge in the left eye. She had a history of bilateral CXL procedure performed for keratoconus elsewhere 4 days earlier. The visual acuity was hand motion in the left eye. Slit-lamp examination revealed extended corneal melting with surrounding infiltrates. The patient was hospitalized, and corneal epithelial scraping samples were sent for microbiological assessment. In the meantime, empirical antibiotic therapy (fortified topical antibiotics: vancomycin 50 mg/mL, ceftazidime 50 mg/mL, and fluconazole 2 mg/mL q1 hour) was initiated. In direct microscopy of the corneal scraping, septate hyaline fungal hyphae were detected and topical fluconazole was switched to topical voriconazole (10 mg/mL). Three days after hospitalization, corneal melting progressed to perforation and corneal suturing with 10-0 monofilament was performed to reform the anterior chamber. Complete resolution of keratitis with residual scarring was noticed in 2 weeks. Three months later, penetrating keratoplasty was performed to obtain better visual acuity.

Conclusions:

CXL with riboflavin has become a common procedure to prevent keratoconus progression by strengthening the biomechanical specialties of the cornea. Although the treatment itself has been used in the management of microbial keratitis and related corneal melting, fungal keratitis and corneal perforation after a CXL procedure for keratoconus might also be detected. Clinicians should be aware of this rare but devastating complication of CXL treatment and start prompt treatment when suspected.
Incidence and Risk Factors for Poor Postoperative Visual Outcome After Excision of Orbital Cavernous Venous Malformations
Authors: Vahdani Kaveh , Rose Geoffrey E.
Published: March 2023

Aims:

To determine the incidence and risk factors for poor postoperative visual outcome (PPVO) after removal of orbital cavernous venous malformations (OCVMs).

Methods:

Retrospective case-note and imaging review for patients undergoing excision of OCVMs, with estimation of odds-ratios (ORs) and relative risks (RRs) for visual loss in relation to the position of the mass, surgical approach, and patient factors.

Results:

The 290 patients (179 female; 62%) presented at a mean age of 46.4 years: 243/287 (85%) OCVMs were intraconal, with 213/243 (88%) located freely in the posterior two-thirds of the orbit, and 30/243 (12%) wedged tightly in the apex. PPVO was observed in 6.9% (20/290) patients, solely after removal of intraconal lesions, Univariate analysis showed increased risk with preoperative relative afferent pupillary defect (RAPD) (14/107 [13%]; RR 2.9; P = 0.011), apical lesions (9/30 [30%]; RR 5.8; P < 0.001), situated below optic nerve (15/115 [13%]; RR 3.3; P = 0.007), fibrous masses (14/78 [18%]; RR 6.7; P = 0.005), or intraoperative diastolic blood pressure below 50mmHg (10/64 [16%]; RR 2.8; P = 0.007). Multivariate analysis found apical extension (OR 4.9; P = 0.036) and fibrous lesions (OR 10.0; P = 0.035) as strongest predictors for PPVO. The incidence of complete visual loss (no light perception) was 4.1% (12/290); half of these patients had preoperative acuity of counting fingers or worse, 8 (67%) had RAPD, 7 (58%) wedged apical lesions, and 8 (67%) were below the optic nerve.

Conclusion:

PPVO after excision of OCVMs can occur in up to 5% of “free” retrobulbar intraconal lesions and in approximately one-third of apical lesions.
Positron emission tomography myocardial perfusion imaging (PET MPI) findings predictive of post-liver transplant major adverse cardiac events
Authors: Hughes Dempsey L. , Pan Jason , Answine Adeline R. , Sonnenday Christopher J. , Waits Seth A. , Kumar Sathish S. , Menees Daniel S. , Wanamaker Brett , Bhave Nicole M. , Tincopa Monica A. , Fontana Robert J. , Sharma Pratima
Published: March 2023

Positron emission tomography myocardial perfusion imaging (PET MPI) is a noninvasive diagnostic test capable of detecting coronary artery disease, structural heart disease, and myocardial flow reserve (MFR). We aimed to determine the prognostic utility of PET MPI to predict post-liver transplant (LT) major adverse cardiac events (MACE). Among the 215 LT candidates that completed PET MPI between 2015 and 2020, 84 underwent LT and had 4 biomarker variables of clinical interest on pre-LT PET MPI (summed stress and difference scores, resting left ventricular ejection fraction, global MFR). Post-LT MACE were defined as acute coronary syndrome, heart failure, sustained arrhythmia, or cardiac arrest within the first 12 months post-LT. Cox regression models were constructed to determine associations between PET MPI variable/s and post-LT MACE. The median LT recipient age was 58 years, 71% were male, 49% had NAFLD, 63% reported prior smoking, 51% had hypertension, and 38% had diabetes mellitus. A total of 20 MACE occurred in 16 patients (19%) at a median of 61.5 days post-LT. One-year survival of MACE patients was significantly lower than those without MACE (54% vs. 98%, p=0.001). On multivariate analysis, reduced global MFR ≤1.38 was associated with a higher risk of MACE [HR=3.42 (1.23–9.47), p=0.019], and every % reduction in left ventricular ejection fraction was associated with an 8.6% higher risk of MACE [HR=0.92 (0.86–0.98), p=0.012]. Nearly 20% of LT recipients experienced MACE within the first 12 months of LT. Reduced global MFR and reduced resting left ventricular ejection fraction on PET MPI among LT candidates were associated with increased risk of post-LT MACE. Awareness of these PET-MPI parameters may help improve cardiac risk stratification of LT candidates if confirmed in future studies.
Transfusion medicine approaches for spontaneous intracerebral hemorrhage patients
Authors: Stone Elizabeth F. , Poyraz Fernanda Carvalho , Roh David J.
Published: March 2023

Purpose of review

Spontaneous intracerebral hemorrhage (ICH) is the deadliest stroke subtype. Acute treatments necessitate rapid hemorrhage control to minimize secondary brain injury. Here, we discuss the overlap of transfusion medicine and acute ICH care relating to diagnostic testing and therapies relevant for coagulopathy reversal and secondary brain injury prevention.

Recent findings

Hematoma expansion (HE) is the largest contributor to poor outcomes after ICH. Conventional coagulation assays to diagnose coagulopathy after ICH does not predict HE. Given the testing limitations, empiric pragmatic hemorrhage control therapies have been trialed but have not improved ICH outcomes, with some therapies even causing harm. It is still unknown whether faster administration of these therapies will improve outcomes. Alternative coagulation tests (e.g., viscoelastic hemostatic assays, amongst others) may identify coagulopathies relevant for HE, currently not diagnosed using conventional assays. This provides opportunities for rapid, targeted therapies. In parallel, ongoing work is investigating alternative treatments using transfusion-based or transfusion-sparing pharmacotherapies that can be implemented in hemorrhage control strategies after ICH.

Further work is needed to identify improved laboratory diagnostic approaches and transfusion medicine treatment strategies to prevent HE and optimize hemorrhage control in ICH patients, who appear particularly vulnerable to the impacts of transfusion medicine practices.
Evaluation of the AIX1000 Automated Rapid Plasma Reagin Assay in a High-Prevalence Setting
Authors: Foqué Nikki , Van den Broeck Silke , Verschueren Jacob , Meersman Kathleen , Van Esbroeck Marjan , Van den Bossche Dorien
Published: March 2023

Background

Manually performed nontreponemal assays, such as rapid plasma reagin (RPR), are labor intensive and time consuming. Recently, commercial automated RPR assays gained attention. The aim of this study was to compare the qualitative and quantitative performance of the AIX1000 (RPR-A; Gold Standard Diagnostics) to a manual RPR test (RPR-M; Becton Dickinson Macrovue) within a high-prevalence setting.

Methods

A retrospective panel of 223 samples was selected for comparison between RPR-A and RPR-M, including 24 samples from patients with known syphilis stages and 57 samples from 11 patients in follow-up. In addition, 127 samples obtained during routine syphilis diagnosis with RPR-M were analyzed prospectively with AIX1000.

Results

Overall qualitative concordance (percent agreement) between both assays was 92.0% in the retrospective and 89.0% in the prospective panel. Of 32 discordances, 28 were explained by a treated syphilis infection still positive in one assay and already negative in the other. One sample was false positive with RPR-A, 1 infection remained undetected by RPR-M, and 2 remained undetected by RPR-A. A hook effect was apparent on the AIX1000 at RPR-A titers from 1:32 onward; however, no infections were missed. Accepting a ±1 titer difference, quantitative concordance between both assays reached 73.1% and 98.4% for the retrospective and prospective panels, respectively, with an upper limit of reactivity for RPR-A at 1:256.

Conclusions

The AIX1000 showed a similar performance to Macrovue RPR with the exception of a negative deviation for high-titer samples. Within the reverse algorithm used in our high-prevalence setting, AIX1000's main advantage is automation.
A Prospective Immunogenicity Study of a Quadrivalent Inactivated Influenza Vaccine Among Persons With HIV With Different Levels of CD4 Cell Count
Authors: Satanon Suparerk , Kiertiburanakul Sasisopin , Boonnak Kobporn , Bruminhent Jackrapong
Published: March 2023

Introduction:

Data regarding the immunogenicity of a quadrivalent inactivated influenza vaccine (IIV4) among persons with HIV with different levels of CD4 cell count are limited. Here, we report the immunogenicity of IIV4 in persons with HIV with different CD4 cell count levels by determining seroprotection (SP) and seroconversion rate after vaccination.

Method:

Persons with HIV were prospectively recruited to receive IIV4 (season 2021) between November 2021 and January 2022. Hemagglutination inhibition titers were assessed before and at 28 days after vaccination and classified as SP or seroconversion with comparison of characteristic between CD4 cell count >350 cells/mm3 group and CD4 cell count ≤350 cells/mm3.

Result:

A total of 70 persons with HIV received the IIV4. The mean (SD) age was 48 (9) years, and 64% were men. Most of them (74%) were maintained on a nonnucleoside reverse transcriptase inhibitor–based regimen with an undetectable HIV viral load (100%). There was a significantly greater proportion of persons with HIV who achieved SP against A/Hong Kong/2571/2019-like virus (H3N2) variant in those with CD4 cell count >350 cells/mm3 compared with those with CD4 cell count ≤350 cells/mm3 (98.3% vs. 72.3%), relative risk 1.35 (95% confidence interval: 1.13 to 1.61, P = 0.011). Furthermore, the participants with CD4 cell count >350 cells/mm3 were significantly more likely to achieve SP against B/Phuket/287/2013 strain (98.3% vs. 72.3%, relative risk 1.35; 95% confidence interval: 1.13 to 1.61, P = 0.011).

Conclusion:

Persons with HIV with greater CD4 cell count could achieve a higher chance of SP against B/Phuket/287/2013 and A/Hong Kong/2571/2019-like virus (H3N2) strains after IIV4 vaccination. Therefore, new strategies should be investigated and offered to those with low CD4 cell counts.