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Laryngo- Rhino- Otologie Jul 2024Allergies play a pivotal role in the daily practice of ENT specialists. Allergic symptoms induced by inhalant allergens are widespread in the population and can manifest... (Review)
Review
Allergies play a pivotal role in the daily practice of ENT specialists. Allergic symptoms induced by inhalant allergens are widespread in the population and can manifest through a wide range of symptoms, including rhinorrhea, sneezing, conjunctival redness, cough and dyspnea. Inconsistent diagnosis and treatment of allergic conditions can lead to reduced quality of life, decreased work performance, and socioeconomically significant secondary diseases. In addition to the medical history, the skin prick test and serological IgE diagnostics are the most important diagnostic procedure for detecting type-I allergies. To clarify clinical relevance, molecular diagnostics and nasal provocation testing may be employed. The key to effective treatment lies in a comprehensive allergological diagnosis coupled with a detailed patient history. General treatment recommendations such as allergen avoidance and nasal irrigation should complement pharmacological therapy. In the treatment of allergic rhinitis topical steroids are first line treatment options. The primary goal of treatment is symptom control, and if control is insufficient, causal therapy through specific allergen immunotherapy is recommended. Challenges in the ENT clinic involve selecting the necessary diagnostics and appropriate, effective treatments. Hence, using diagnostic and treatment algorithms, as well as standardized patient history questionnaires, can serve as invaluable tools in daily patient interactions, especially considering limited time availability.
Topics: Humans; Immunoglobulin E; Skin Tests; Desensitization, Immunologic; Referral and Consultation; Hypersensitivity
PubMed: 38955155
DOI: 10.1055/a-2073-9474 -
Computers in Biology and Medicine Jul 2024Intervertebral disc disease, a prevalent ailment, frequently leads to intermittent or persistent low back pain, and diagnosing and assessing of this disease rely on...
Intervertebral disc disease, a prevalent ailment, frequently leads to intermittent or persistent low back pain, and diagnosing and assessing of this disease rely on accurate measurement of vertebral bone and intervertebral disc geometries from lumbar MR images. Deep neural network (DNN) models may assist clinicians with more efficient image segmentation of individual instances (discs and vertebrae) of the lumbar spine in an automated way, which is termed as instance image segmentation. In this work, we proposed SymTC, an innovative lumbar spine MR image segmentation model that combines the strengths of Transformer and Convolutional Neural Network (CNN). Specifically, we designed a parallel dual-path architecture to merge CNN layers and Transformer layers, and we integrated a novel position embedding into the self-attention module of Transformer, enhancing the utilization of positional information for more accurate segmentation. To further improve model performance, we introduced a new data synthesis technique to create synthetic yet realistic MR image dataset, named SSMSpine, which is made publicly available. We evaluated our SymTC and the other 16 representative image segmentation models on our private in-house dataset and public SSMSpine dataset, using two metrics, Dice Similarity Coefficient and the 95th percentile Hausdorff Distance. The results indicate that SymTC surpasses the other 16 methods, achieving the highest dice score of 96.169 % for segmenting vertebral bones and intervertebral discs on the SSMSpine dataset. The SymTC code and SSMSpine dataset are publicly available at https://github.com/jiasongchen/SymTC.
PubMed: 38955128
DOI: 10.1016/j.compbiomed.2024.108795 -
Computers in Biology and Medicine Jul 2024Missing data is a common challenge in mass spectrometry-based metabolomics, which can lead to biased and incomplete analyses. The integration of whole-genome sequencing...
BACKGROUND
Missing data is a common challenge in mass spectrometry-based metabolomics, which can lead to biased and incomplete analyses. The integration of whole-genome sequencing (WGS) data with metabolomics data has emerged as a promising approach to enhance the accuracy of data imputation in metabolomics studies.
METHOD
In this study, we propose a novel method that leverages the information from WGS data and reference metabolites to impute unknown metabolites. Our approach utilizes a multi-scale variational autoencoder to jointly model the burden score, polygenetic risk score (PGS), and linkage disequilibrium (LD) pruned single nucleotide polymorphisms (SNPs) for feature extraction and missing metabolomics data imputation. By learning the latent representations of both omics data, our method can effectively impute missing metabolomics values based on genomic information.
RESULTS
We evaluate the performance of our method on empirical metabolomics datasets with missing values and demonstrate its superiority compared to conventional imputation techniques. Using 35 template metabolites derived burden scores, PGS and LD-pruned SNPs, the proposed methods achieved R-scores > 0.01 for 71.55 % of metabolites.
CONCLUSION
The integration of WGS data in metabolomics imputation not only improves data completeness but also enhances downstream analyses, paving the way for more comprehensive and accurate investigations of metabolic pathways and disease associations. Our findings offer valuable insights into the potential benefits of utilizing WGS data for metabolomics data imputation and underscore the importance of leveraging multi-modal data integration in precision medicine research.
PubMed: 38955127
DOI: 10.1016/j.compbiomed.2024.108813 -
Preventive Veterinary Medicine Jun 2024Tick-borne pathogens (TBPs) constitute an emerging threat to public and animal health especially in the African continent, where land-use change, and wildlife loss are... (Review)
Review
INTRODUCTION
Tick-borne pathogens (TBPs) constitute an emerging threat to public and animal health especially in the African continent, where land-use change, and wildlife loss are creating new opportunities for disease transmission. A review of TBPs with a focus on ticks determined the epidemiology of Rhipicephalus ticks in heartwater and the affinity of each Rickettsia species for different tick genera. We conducted a systematic review and meta-analysis to collect, map and estimate the molecular prevalence of Anaplasmataceae, Rickettsiaceae and Coxiellaceae in African wildlife.
MATERIALS AND METHODS
Relevant scientific articles were retrieved from five databases: PubMed, ScienceDirect, Scopus, Ovid and OAIster. Publications were selected according to pre-determined exclusion criteria and evaluated for risk of bias using the appraisal tool for cross-sectional studies (AXIS). We conducted an initial descriptive analysis followed by a meta-analysis to estimate the molecular prevalence of each pathogen. Subgroup analysis and meta-regression models were employed to unravel associations with disease determinants. Finally, the quality of evidence of every estimate was finally assessed.
RESULTS
Out of 577 retrieved papers, a total of 41 papers were included in the qualitative analysis and 27 in the meta-analysis. We retrieved 21 Anaplasmataceae species, six Rickettsiaceae species and Coxiella burnetii. Meta-analysis was performed for a total of 11 target pathogens. Anaplasma marginale, Ehrlichia ruminantium and Anaplasma centrale were the most prevalent in African bovids (13.9 %, CI: 0-52.4 %; 20.9 %, CI: 4.1-46.2 %; 13.9 %, CI: 0-68.7 %, respectively). Estimated TBPs prevalences were further stratified per animal order, family, species and sampling country.
DISCUSSION
We discussed the presence of a sylvatic cycle for A. marginale and E. ruminantium in wild African bovids, the need to investigate A. phagocytophilum in African rodents and non-human primates as well as E. canis in the tissues of wild carnivores, and a lack of data and characterization of Rickettsia species and C. burnetii.
CONCLUSION
Given the lack of epidemiological data on wildlife diseases, the current work can serve as a starting point for future epidemiological and/or experimental studies.
PubMed: 38955115
DOI: 10.1016/j.prevetmed.2024.106257 -
Journal of Plastic, Reconstructive &... Jun 2024Lichen sclerosus et atrophicus is an inflammatory, scarring dermatosis of the female anogenital area and may lead to pain and sexual dysfunction. In select cases which...
INTRODUCTION
Lichen sclerosus et atrophicus is an inflammatory, scarring dermatosis of the female anogenital area and may lead to pain and sexual dysfunction. In select cases which are refractory to conservative therapy, surgery may provide significant symptom improvement. The objective of this study was to expand the range of surgical treatment options for these patients by presenting the operative outcomes of a specialised reconstructive method using the anterior obturator artery perforator (aOAP) flap.
METHODS
A retrospective cohort study was conducted on sexual outcomes following the excision of affected vulvovestibular tissue by skinning vulvectomy and subsequent single-stage reconstruction using the aOAP flap. Additional procedures, such as the Omega-Domed (OD) flap, scar surgery and clitoral re-exposure, were performed when indicated.
RESULTS
Between 2014 and 2022, a total of 61 patients were surgically treated and retrospectively included in this study. Vulvectomy and subsequent reconstruction with bilateral aOAP flaps were performed in 53 (87%) cases. There was a significant reduction in the prevalence of dyspareunia and inability to have sexual intercourse at the 1-year follow-up compared to baseline (p < 0.001). There were several minor, reversible complications that required secondary intervention.
CONCLUSIONS
The outcomes of this study indicate a substantial improvement in sexual function, evidenced by a significant reduction in dyspareunia and an increased ability to engage in sexual intercourse. Altered tissue quality in patients with lichen sclerosus et atrophicus and long-term cortisone application may predispose this patient population to a higher risk of minor post-operative complications.
CLINICAL TRIAL REGISTRATION NUMBER
DRKS00033261.
PubMed: 38955111
DOI: 10.1016/j.bjps.2024.05.046 -
Parkinsonism & Related Disorders Jun 2024Parkinson's disease (PD) presents with a progressive decline in manual dexterity, attributed to dysfunction in the basal ganglia-thalamus-cortex loop, influenced by...
INTRODUCTION
Parkinson's disease (PD) presents with a progressive decline in manual dexterity, attributed to dysfunction in the basal ganglia-thalamus-cortex loop, influenced by dopaminergic deficits in the striatum. Recent research suggests that the motor cortex may play a pivotal role in mediating the relationship between striatal dopamine depletion and motor function in PD. Understanding this connection is crucial for comprehending the origins of manual dexterity impairments in PD. Therefore, our study aimed to explore how motor cortex activation mediates the association between striatal dopamine depletion and manual dexterity in PD.
MATERIALS AND METHODS
We enrolled 26 mildly affected PD patients in their off-medication phase to undergo [F]FDOPA scans for evaluating striatal dopaminergic function. EEG recordings were conducted during bimanual anti-phase finger tapping tasks to evaluate motor cortex activity, specifically focusing on Event-Related Desynchronization in the beta band. Manual dexterity was assessed using the Purdue Pegboard Test. Regression-based mediation analysis was conducted to examine whether motor cortex activation mediates the association between striatal dopamine depletion and manual dexterity in PD.
RESULTS
Mediation analysis revealed a significant direct effect of putamen dopamine depletion on manual dexterity for the affected hand and assembly tasks (performed with two hands), with motor cortex activity mediating this association. In contrast, while caudate nucleus dopamine depletion showed a significant direct effect on manual dexterity, motor cortex mediation on this association was not observed.
CONCLUSION
Our study confirms the association between striatum dopamine depletion and impaired manual dexterity in PD, with motor cortex activity mediating this relationship.
PubMed: 38955097
DOI: 10.1016/j.parkreldis.2024.107049 -
Biomedicine & Pharmacotherapy =... Jul 2024β2 adrenergic receptor (β2AR) is a G-protein-coupled receptor involved in cardiac protection. In chronic heart failure (CHF), persistent sympathetic nervous system...
β2 adrenergic receptor (β2AR) is a G-protein-coupled receptor involved in cardiac protection. In chronic heart failure (CHF), persistent sympathetic nervous system activation occurs, resulting in prolonged β2AR activation and subsequent receptor desensitization and downregulation. Notoginsenoside R1 (NGR1) has the functions of enhancing myocardial energy metabolism and mitigating myocardial fibrosis. The mechanisms of NGR1 against ischemic heart failure are unclear. A left anterior descending (LAD) artery ligation procedure was performed on C57BL/6 J mice for four weeks. From the 4th week onwards, they were treated with various doses (3, 10, 30 mg/kg/day) of NGR1. Subsequently, the impacts of NGR1 on ischemic heart failure were evaluated by assessing cardiac function, morphological changes in cardiac tissue, and the expression of atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC). H9c2 cells were protected by NGR1 when exposed to OGD/R conditions. H9c2 cells were likewise protected from OGD/R damage by NGR1. Furthermore, NGR1 increased β2AR levels and decreased β2AR ubiquitination. Mechanistic studies revealed that NGR1 enhanced MDM2 protein stability and increased the expression of MDM2 and β-arrestin2 while inhibiting their interaction. Additionally, under conditions produced by OGD/R, the protective benefits of NGR1 on H9c2 cells were attenuated upon administration of the MDM2 inhibitor SP141. According to these findings, NGR1 impedes the interplay between β-arrestin2 and MDM2, thereby preventing the ubiquitination and degradation of β2AR to improve CHF.
PubMed: 38955084
DOI: 10.1016/j.biopha.2024.117004 -
Currents in Pharmacy Teaching & Learning Jul 2024Entrustable Professional Activities (EPAs) are tasks that professionals within a field perform autonomously. EPAs are incorporated in workplace-based assessment tools to...
INTRODUCTION
Entrustable Professional Activities (EPAs) are tasks that professionals within a field perform autonomously. EPAs are incorporated in workplace-based assessment tools to assist training and professional development. Few studies have evaluated medication history-taking EPAs use in pharmacy practice and none have sought stakeholder feedback on their use. This study evaluates the quality of the medication history-taking EPA utilized in South Australian public hospitals and the usability of its assessment tool.
METHODS
A voluntary online questionnaire was conducted from July 15th to September 2nd 2021 to gather the opinions of stakeholders on the use of the medication history-taking EPA. The questionnaire was developed based on tools identified in the literature and utilized 14 open-text and five-point Likert scale questions. The questionnaire was distributed using Survey Monkey® to a purposive sample of staff and students.
RESULTS
82 responses were received from 218 surveys distributed, yielding a response rate of 38%. Respondents believed the EPA promotes learner development (90.6%) and the provision of useful feedback (83%). 94.3% considered the EPA to be easy to use but only 56.6% indicated that using it fits easily within their workday. Time constraints and the presence of context-specific descriptors were commonly perceived as limitations. Some stakeholders indicated a lack of understanding of entrustment decisions.
CONCLUSION
The EPA and its assessment tool were perceived to have good quality and usability. Reducing the length of the tool, broadening its applicability across contexts, and improving user understanding of entrustment decision-making may support better use of the tool.
PubMed: 38955063
DOI: 10.1016/j.cptl.2024.102134 -
Currents in Pharmacy Teaching & Learning Jul 2024This review article is the first comprehensive evaluation of the available literature surrounding the education of death and dying in pharmacy schools. The purpose of... (Review)
Review
PURPOSE
This review article is the first comprehensive evaluation of the available literature surrounding the education of death and dying in pharmacy schools. The purpose of this review was to describe the available literature and methods utilized regarding the emotional preparation for patient death in pharmacy education.
PROCEDURES
Searches were performed in three pharmacy databases to identify articles that contained descriptions of activities related to death and dying education in pharmacy curriculums.
FINDINGS
Eleven journal articles were reviewed, detailing activities in pharmacy education including simulations, didactic sessions, and an innovative "death over dessert" model. Evaluation methods varied, with surveys being most common, followed by reflection. Didactic courses demonstrated increased empathy and knowledge, while simulations compared to case-based activities improved skills, knowledge, and comfort levels with providing end-of-life care. Simulations often involved interprofessional groups, with third-year pharmacy students most evaluated.
CONCLUSION
Pharmacy students were mainly exposed to death and dying scenarios through didactic courses or simulations, with limited longitudinal exposure. Research suggests that students may lack preparation for handling death-related situations, leading to trauma and dysfunction. While existing studies focus on outward effects like empathy, internal factors such as coping methods receive less attention. Unlike nursing and medicine literature, pharmacy education lacks comprehensive coverage of coping and emotional support strategies for death and dying scenarios. Additional focus should be placed on intentional incorporation of these topics into pharmacy curriculums.
PubMed: 38955062
DOI: 10.1016/j.cptl.2024.102137 -
Phytomedicine : International Journal... Jun 2024Atherosclerosis (AS) is the main pathological basis for the development of cardiovascular diseases. Vascular inflammation is an important factor in the formation of AS,...
BACKGROUND
Atherosclerosis (AS) is the main pathological basis for the development of cardiovascular diseases. Vascular inflammation is an important factor in the formation of AS, and macrophage pyroptosis plays a key role in AS due to its unique inflammatory response. Guizhitongluo Tablet (GZTLT) has shown clinically effective in treating patients with AS, but its mechanism is elusive.
PURPOSE
This study was to determine the effects of GZTLT on atherosclerotic vascular inflammation and pyroptosis and to understand its underlying mechanism.
MATERIALS AND METHODS
The active constituents of GZTLT were analysed by means of UPLC-HRMS. In vivo experiments were performed using ApoE mice fed a high fat diet for 8 weeks, followed by treatment with varying concentrations of GZTLT orally by gavage and GsMTx4 (GS) intraperitoneally and followed for another 8 weeks. Oil red O, Haematoxylin-eosin (HE) and Masson staining were employed to examine the lipid content, plaque size, and collagen fibre content of the mouse aorta. Immunofluorescence staining was utilised to identify macrophage infiltration, as well as the expression of Piezo1 and NLRP3 proteins in aortic plaques. The levels of aortic inflammatory factors were determined using RT-PCR and ELISA. In vitro, foam cell formation in bone marrow-derived macrophages (BMDMs) was observed using Oil Red O staining. Intracellular Ca measurements were performed to detect the calcium influx in BMDMs, and the expression of NLRP3 and its related proteins were detected by Western blot.
RESULTS
The UPLC-HRMS analysis revealed 31 major components of GZTLT. Our data showed that GZTLT inhibited aortic plaque formation in mice and increased plaque collagen fibre content to stabilise plaques. In addition, GZTLT could restrain the expression of serum lipid levels and suppress macrophage foam cell formation. Further studies found that GZTLT inhibited macrophage infiltration in aortic plaques and suppressed the expression of inflammatory factors. It is noteworthy that GZTLT can restrain Piezo1 expression and reduce Ca influx in BMDMs. Additionally, we found that GZTLT could regulate NLRP3 activation and pyroptosis by inhibiting Piezo1.
CONCLUSION
The present study suggests that GZTLT inhibits vascular inflammation and macrophage pyroptosis through the Piezo1/NLRP3 signaling pathway, thereby delaying AS development. Our finding provides a potential target for AS treatment and drug discovery.
PubMed: 38955059
DOI: 10.1016/j.phymed.2024.155827