Original Article Research Articles

The NLRP3 inflammasome: a vital player in inflammation and mediating the anti-inflammatory effect of CBD.

The NLRP3 inflammasome is a vital player in the emergence of inflammation. The priming and activation of the NLRP3 inflammasome is a major trigger for inflammation which is a defense response against adverse stimuli. However, the excessive activation of the NLRP3 inflammasome can lead to the development of various inflammatory diseases. Cannabidiol, as the second-most abundant component in cannabis, has a variety of pharmacological properties, particularly anti-inflammation. Unlike tetrahydrocannabinol, cannabidiol has a lower affinity for cannabinoid receptors, which may be the reason why it is not psychoactive. Notably, the mechanism by which cannabidiol exerts its anti-inflammatory effect is still unclear. We have performed a literature review based on published original and review articles encompassing the NLRP3 inflammasome and cannabidiol in inflammation from central databases, including PubMed and Web of Science. In this review, we first summarize the composition and activation process of the NLRP3 inflammasome. Then, we list possible molecular mechanisms of action of cannabidiol. Next, we explain the role of the NLRP3 inflammasome and the anti-inflammatory effect of cannabidiol in inflammatory disorders. Finally, we emphasize the capacity of cannabidiol to suppress inflammation by blocking the NLRP3 signaling pathway, which indicates that cannabidiol is a quite promising anti-inflammatory compound.

Treg in inborn errors of immunity: gaps, knowns and future perspectives.

Regulatory T cells (Treg) are essential for immune balance, preventing overreactive responses and autoimmunity. Although traditionally characterized as CD4+CD25+CD127lowFoxP3hi, recent research has revealed diverse Treg subsets such as Tr1, Tr1-like, and CD8 Treg. Treg dysfunction leads to severe autoimmune diseases and immune-mediated inflammatory disorders. Inborn errors of immunity (IEI) are a group of disorders that affect correct functioning of the immune system. IEI include Tregopathies caused by genetic mutations affecting Treg development or function. In addition, Treg dysfunction is also observed in other IEIs, whose underlying mechanisms are largely unknown, thus requiring further research. This review provides a comprehensive overview and discussion of Treg in IEI focused on: A) advances and controversies in the evaluation of Treg extended subphenotypes and function; B) current knowledge and gaps in Treg disturbances in Tregopathies and other IEI including Treg subpopulation changes, genotype-phenotype correlation, Treg changes with disease activity, and available therapies, and C) the potential of Treg cell-based therapies for IEI with immune dysregulation. The aim is to improve both the diagnostic and the therapeutic approaches to IEI when there is involvement of Treg. We performed a non-systematic targeted literature review with a knowledgeable selection of current, high-quality original and review articles on Treg and IEI available since 2003 (with 58% of the articles within the last 6 years) in the PubMed database.

Older LGBT+ Adults and Physical Activity: A Systematic Review of Qualitative and Quantitative Data

Abstract Introduction The present study represents the first systematic review summarizing existing publications on older sexual and gender minority (LGBT+) people's engagement with physical activity (PA) aged 65 and over. Methods Relevant articles were systematically searched in four scientific databases (i.e., PsychArticles, PsychInfo, Pubmed, and Web of Science) in March 2023. We included original articles published after 1968 with relevant keywords associated with “PA”, “older adults”, and “LGBT+ identity”. Of the 887 records identified, 53 articles were included in the systematic review. Results Studies were critically reviewed according to participants’ subjectivity considered in the publications: (a) sexual minority (LGB+) identities; (b) sexual and gender minority (LGBT+) identities; (c) transgender and gender-diverse identities; (d) gay and bisexual male identities; and (e) lesbian and bisexual female identities. The most frequent research areas, taking together all the five identity categories considered in the present review, were the differences between LGBT+ people and cis-heterosexual people, the discrimination and homophobia/transphobia in sport-related contexts, and the competent interventions and aging well in LGBT+ older adults. Conclusions Findings suggest a lack of information regarding PA in older LGBT+ aged 65 and over. Future research should investigate the barriers and enablers of PA in older LGBT+ people. Policy Implications It is mandatory to promote regular exercise to reduce health disparities between older LGBT+ individuals and their cis-heterosexual counterparts. The policy and environmental implications of the findings for older LGBT+ people are discussed.

Use of psychoactive substances among university students from 2019 to 2020: A systematic review

Psychoactive substances act on the central nervous system producing changes in mental processes, such as perception, consciousness, cognition or mood and emotions. The present study aims to identify: (i) the most used psychoactive substances, (ii) how psychoactive substances are acquired, (iii) and possible reasons for the use of psychoactive substances amongst university students. A literature search was carried out without language restrictions and included articles published between 2019 and 2020 in journals indexed in the electronic databases of Pubmed and Scielo. The inclusion criteria considered were: (i) original articles, (ii) studies carried out with university students, (iii) providing data on the use of psychoactive substances. 15 studies were included in this review, of which: 4 studies addressed possible reasons that lead to use of psychoactive substances, 10 studies reported usage profile and demographic data, and 1 study addressed how students acquire psychoactive substances. Reasons that led to the consumption of psychoactive substances include: feelings of loneliness after moving away from family; difficulty making new friends; poor academic performance and susceptible environment to acquisition of these substances. In the selected studies, alcohol was identified as the main drug used. In light of the findings reported in this review, new prevention and harm reduction measures can be formulated, based mainly on the reasons that lead to the use of psychoactive drugs, consumption patterns and how the drugs were acquired by university students.

Corrigendum to “Correspondence imaging through complex scattering media with temporal correction” optics and lasers in engineering, volume 174 (2024) 107957

The authors regret that a typo is in the original text and should be corrected in this corrigendum. This correction does not influence the method, results, descriptions and conclusions of the original article.

Global trends in research of melanoma differentiation-associated gene 5: a bibliometric analysis from 2002 to 2022.

Melanoma differentiation-associated gene 5 (MDA5), as a cytoplasmic sensor for viral double-stranded RNAs, has received increasing attention in recent years. Although considerable headway has been made on the functional role of MDA5 in antiviral immunity and autoimmune disease, the available literature is insufficient to assess the vast field. This study performed a bibliometric analysis to investigate current hotspots in the global scientific output of MDA5 over the past two decades. Related publications and recorded information from 2002 to 2022 in the Web of Science Core Collection (WoSCC) database were retrieved. VOSviewer and CiteSpace were used for quantitative evaluation and visualization. A total of 2267 original articles and reviews were obtained, and the annual number of publications related to MDA5 was increasing rapidly. China has published the most papers, while the USA was the most influential country with the most citations and the highest H-index. The Chinese Academy of Sciences, the United States Department of Health and Human Services, and the Journal of Virology were the most prolific research affiliation, funding source, and journal, respectively. Fujita T (Kyoto University) was the most productive author with the highest H-index and had close cooperation with Kato H and Yoneyama M. The keywords "RIG-I," "MDA5," "innate immunity," "double-stranded-RNA," and "recognition" had the highest frequency, while "dermatomyositis" as well as "autoantibody" seemed to be the emerging hotspots. This study comprehensively demonstrated the research frontiers of MDA5 and will provide a useful resource for scholars to conduct future decisions. We conducted the first in-depth survey of the research frontiers on melanoma differentiation-associated gene 5 (MDA5) over the past two decades via bibliometric analysis. We found that many early breakthroughs have been made in the mechanism of MDA5-mediated antiviral immune responses, and the role of MDA5 in autoimmune and autoinflammatory diseases has raised the recent concern. We identified that the virus infection-associated pathogenesis and effective therapeutic strategy of anti-MDA5 antibody-positive dermatomyositis will remain the hotspots in the future.

UPDATED ANALYSIS AND REVIEW OF HALLUX VALGUS, CLINICAL CASE DESCRIPTION, ETIOLOGY, EPIDEMIOLOGY, PATHOPHYSIOLOGY, CLINICAL EVALUATION, CONCOMITANT DISORDERS, RADIOGRAPHIC APPROACH, IMAGING CLASSIFICATION SYSTEMS, TREATMENT, PROGNOSIS AND COMPLICATIONS

Introduction: Hallux valgus (HV) is one of the most constant pathologies in orthopedics, compromising both soft and bony tissues of the first toe, being more common in women. This deformity is generated by a progressive subluxation in valgus of the metatarsophalangeal joint (MTF) of the first toe and a varus deviation of the first metatarsal. Objective: to detail current information related to hallux valgus, case description, etiology, epidemiology, pathophysiology, history, clinical evaluation, imaging approach, classification, treatment, prognosis and complications. Methodology: a total of 50 articles were analyzed in this review, including review and original articles, as well as clinical cases, of which 37 bibliographies were used because the other articles were not relevant for this study. The sources of information were PubMed, Google Scholar and Cochrane; the terms used to search for information in Spanish, Portuguese and English were: hallux valgus, deformity, foot, metatarsal, bunions. Results: Hallux valgus deformity is relatively common, occurring in about 23% of adults aged 18 to 65 years and up to 36% of adults older than 65 years, and particularly in adult women, occurring in up to 30%. Conclusions: Hallux valgus, or bunion, is the valgus deviation of the first orthotic with a varus deviation of the first metatarsal. The establishment of a diagnosis can be made through physical examination, however imaging helps to determine the involvement of the first metatarsophalangeal joint. At the moment there are several surgical techniques developed to restore the deformity. Hallux valgus corrective surgery is effective, presenting high rates of pain relief, deformity correction and patient satisfaction, however it is not free of complications. KEY WORDS: hallux valgus, deformity, foot, metatarsal, bunions.

Visibility of Care Ethics in Adventist Professional Nursing Education from a Philosophical Perspective

Objective: To analyze the scientific evidence on the visibility of care ethics in the professional training of nursing from an Adventist philosophy perspective. Methodology: This study is a literature review. Information was sourced from online databases including Scopus, Web of Science, CINAHL plus, MEDLINE (PubMed), Wiley, Lilacs, and Google Scholar. Selection criteria included original and review articles from 2009 to 2020. Thirty documents related to nursing philosophy and Christian philosophy were analyzed. Of these, 21 met the inclusion criteria, which highlighted the Adventist vision and worldview, the value of human life, care ethics, patient valuation, love for one's neighbor and God, who is the Creator, sustainer, and redeemer. Results: Nursing professionals who incorporate religion into their training adhere to care ethics. Adventist nursing philosophy focuses on the individual and their worldview, encompassing knowledge, logic, epistemology, action, and ethical values. Conclusions: The literature showed that the philosophy of Adventist nurses strengthens and magnifies professional practice. Adventist nursing bears witness to the practice of Christian principles and values throughout its training and professional practice, providing holistic care that covers physical, mental, social, and spiritual aspects.
 
 Received: 5 July 2023 / Accepted: 14 December 2023 / Published: 5 January 2024

Advances in Studies on Psychological Symptoms in Patients Surviving Covid-19: A Bibliometric Analysis

Backgrounds: Currently, more than 700 million people who have acquired the COVID-19 may develop the Post COVID Condition, especially women and people with a history of mental illness, who after the acute phase of the disease will experience physical and psychological symptoms which significantly affect their quality of life. The main objective of this study was to analyze and describe the trends of published research on psychological symptoms in survivors of COVID-19 from 2019 to 2023. Method: A bibliographic search was carried out using the Scopus database, where 370 original articles published up to February 9, 2023, were identified, analyzing characteristics such as the country with the highest production, the institution with the highest number of publications, scientific journals and works with the highest number of citations and impact. Results: The leading country in the number of publications was the United States with 83 articles (22.43%). The institution with the highest production was Rey Juan Carlos University. The journal with the highest number of articles published was the International Journal Of Environmental Research And Public Health from Switzerland, the total number of citations for all publications was 7,525, of which 10 papers had more than 100 citations. Conclusions: An analysis of the scientific production on psychological symptoms in patients surviving COVID-19 was carried out, finding a total of 370 published articles evidencing trends and gaps in scientific production in this field. Limitations: The continuous increase in publications and the change in statistics represent a limitation for the present study because the number of publications continues to increase daily.
 
 Received: 7 September 2023 / Accepted: 24 December 2023 / Published: 5 January 2024

Dynamite plots in surgical research over 10 years: a meta-study using machine-learning analysis.

Bar charts of numerical data, often known as dynamite plots, are unnecessary and misleading. Their tendency to alter the perception of mean's position through the within-the-bar bias and their lack of information on the distribution of the data are two of numerous reasons. The machine learning tool, Barzooka, can be used to rapidly screen for different graph types in journal articles.We aim to determine the proportion of original research articles using dynamite plots to visualize data, and whether there has been a change in their use over time. Original research articles in nine surgical fields of research were sampled based on MeSH terms and then harvested using the Python-based biblio-glutton-harvester tool. After harvesting, they were analysed using Barzooka. Over 40 000 original research articles were included in the final analysis. The results were adjusted based on previous validation data with 95% confidence bounds. Kendall τ coefficient with the Mann-Kendall test for significance was used to determine the trend of dynamite plot use over time. Eight surgical fields of research showed a statistically significant decrease in use of dynamite plots over 10 years. Oral and maxillofacial surgery showed no significant trend in either direction. In 2022, use of dynamite plots, dependent on field and 95% confidence bounds, ranges from ~30% to 70%. Our results show that the use of dynamite plots in surgical research has decreased over time; however, use remains high. More must be done to understand this phenomenon and educate surgical researchers on data visualization practices.

Examining efforts to predict day-of-surgery cancellation (DOSC): a systematic review protocol

Abstract Day-of-surgery cancellation (DOSC) in elective surgery occurs in roughly 18% of elective surgeries worldwide. This impacts patient physical health, psychological wellbeing and social function. Further impacts include reduced health service efficiency and wider economic productivity. There is a range of contributing variables including patient factors, resource constraints and health service pressures which could be integrated into predictive models. This article describes the protocol for a systematic review to evaluate peer-reviewed original research articles and implementation studies of models to predict DOSC. Such statistical models could, if properly integrated into clinical practice, yield benefits to patients and healthcare providers. The systematic review will provide a comprehensive synthesis of evidence in this area to inform future efforts at gold-standard statistical modelling. Predictor-finding studies, subsequent publications of the same model and publications in which the predictive variables have not been disclosed will be excluded. Searches will be conducted in Medline, Embase, Scopus and Web of science. Risk of bias will be assessed using the prediction model risk of bias assessment tool. Data will be collected on included variables, method of prediction, whether prediction was made at the level of the patient or the system, and training and assessment processes. These data will be subject to qualitative synthesis and used to generate a narrative summary and figures. This systematic review will abide by the 2020 PRISMA guidelines. This review is registered on PROSPERO, registration CRD42023478984.

Nanotechnological approaches in the treatment of schistosomiasis: an overview.

Schistosomiasis causes over 200,000 deaths annually. The current treatment option, praziquantel, presents limitations, including low bioavailability and resistance. In this context, nanoparticles have emerged as a promising option for improving schistosomiasis treatment. Several narrative reviews have been published on this topic. Unfortunately, the lack of clear methodologies presented in these reviews leads to the exclusion of many important studies without apparent justification. This integrative review aims to examine works published in this area with a precise and reproducible method. To achieve this, three databases (i.e., Pubmed, Web of Science, and Scopus) were searched from March 31, 2022, to March 31, 2023. The search results included only original research articles that used nanoparticles smaller than 1 µm in the treatment context. Additionally, a search was conducted in the references of the identified articles to retrieve works that could not be found solely using the original search formula. As a result, 65 articles that met the established criteria were identified. Inorganic and polymeric nanoparticles were the most prevalent nanosystems used. Gold was the primary material used to produce inorganic nanoparticles, while poly(lactic-co-glycolic acid) and chitosan were commonly used to produce polymeric nanoparticles. None of these identified works presented results in the clinical phase. Finally, based on our findings, the outlook appears favorable, as there is a significant diversity of new substances with schistosomicidal potential. However, financial efforts are required to advance these nanoformulations.

Application and Efficacy of Management Interventions for the Control of Microplastics in Freshwater Bodies: A Systematic Review

This systematic review represents one of the first attempts to compare the efficacy of the full suite of management interventions developed to control (prevent or remove) microplastics (MPs) in freshwater bodies, both man-made and natural. The review also traces the evolution of research on the topic in relation to the timing of key policy and regulatory events and investigates whether interventions are being applied within regions and freshwater bodies that represent concerns in terms of MP pollution. The review incorporated bibliometric analysis and meta-analysis of 124 original research articles published on the topic between 2012 and April 2023. To supplement the key findings, data were extracted from 129 review articles on the major knowledge gaps and recommendations. The number of articles on the topic increased with each year, coinciding with a range of global policy commitments to sustainability and mitigating plastic pollution. The majority of the studies focused on MPs in general, rather than any particular particle shape or polymer type, and were conducted at wastewater/sludge treatment plants. Upstream interventions accounted for the majority of studies reviewed (91.1%). A smaller proportion (4.8%) of studies involved reduction in production and physical removal at the point of production (1.6%); treatment-related objectives such as removal through filtration and separation and the combination of these with other technologies in hybrid systems were dominant. Of the physical, chemical and biological methods/technologies (and combinations thereof) employed, physical types (particularly membrane filtration) were most common. The majority of the studies within the wastewater/sludge, stormwater and in situ water/sediment categories exhibited removal efficacies >90%. Although new interventions are constantly being developed under laboratory conditions, their scalability and suitability across different settings are uncertain. Downstream interventions lack sustainability without effective upstream interventions. Though in situ methods are technically achievable, they may not be feasible in resource-limited settings.

Vaccination and clozapine use: a systematic review and an analysis of the VAERS database.

In the context of COVID-19 concerns related to the potential interactions between clozapine and vaccination arose. With the ultimate goal of deriving recommendations for clinical practice, we systematically reviewed the current evidence regarding altered vaccine effectiveness in clozapine-treated patients and safety aspects of vaccination, such as haematological changes and the impact of vaccines on clozapine blood levels, in clozapine-treated patients. A systematic PRISMA-conform literature search of four databases (PubMed, PsycINFO, EMBASE and Cochrane Library) complemented by a case-by-case analysis of the Vaccine Adverse Event Reporting System (VAERS) database was performed. We then systematically appraised the joint evidence and tried to derive recommendations for clinical practice. 14 records were included in this analysis. These records consisted of 5 original articles and 9 case reports. Among the original articles, two studies provided data on the association between clozapine use and antibody responses to vaccination, both indicating that clozapine use in schizophrenia may be associated with reduced levels of immunoglobulins. Additionally, three studies examined vaccine safety in clozapine-treated patients, with no clinically significant adverse effects directly attributable to the interplay between vaccinations and clozapine. VAERS Analysis encompassed 137 reports and showed no consistent evidence of an increased risk for clozapine blood level increases or adverse events. We found no evidence indicating that clozapine impairs the effectiveness of vaccines. Moreover, no serious safety concerns seem to apply when patients on clozapine are receiving vaccines. However, it is crucial to acknowledge that data on the interaction between clozapine and vaccines remain limited.

Diagnostic Performance of [18F]F-FDG Positron Emission Tomography (PET) in Non-Ophthalmic Malignant Melanoma: A Systematic Review and Meta-Analysis of More Than 10,000 Melanoma Patients.

We described the diagnostic performance of [18F]F-FDG-PET in malignant melanoma by conducting a comprehensive systematic review and meta-analysis of the existing literature. The study was designed following PRISMA-DTA. Original articles with adequate crude data for meta-analytic calculations that evaluated [18F]F-FDG-PET and compared it with a valid reference standard were considered eligible. The pooled measurements were calculated based on the data level (patient/lesion-based). Regarding sub-groups, diagnostic performances were calculated for local, regional and distant involvement. The bivariate model was employed to calculate sensitivity and specificity. The initial search resulted in 6678 studies. Finally, 100 entered the meta-analysis, containing 82 patient-based (10,403 patients) and 32 lesion-based (6188 lesions) datasets. At patient level, overall, [18F]F-FDG-PET had pooled sensitivity and specificity of 81% (95%CI: 73-87%) and 92% (95%CI: 90-94%), respectively. To detect regional lymph node metastasis, the pooled sensitivity and specificity were 56% (95%CI: 40-72%) and 97% (95%CI: 94-99%), respectively. To detect distant metastasis, they were 88% (95%CI: 81-93%) and 94% (95%CI: 91-96%), respectively. At lesion level, [18F]F-FDG-PET had a pooled sensitivity and specificity of 70% (95%CI: 57-80%) and 94% (95%CI: 88-97%), respectively. Thus, [18F]F-FDG-PET is a valuable diagnostic modality for melanoma assessment. It was accurate in various clinical scenarios. However, despite its high specificity, it showed low sensitivity in detecting regional lymph node metastasis and could not replace lymph node biopsy.

Cigarette smoking and urinary bladder cancer: The danger alarm is screaming!

The cancer of urinary bladder is a very common cause of cancer related mortality all over the world and approximately more than half patients suffering from bladder cancer had been smokers. In addition to this, in such patients the cancer is more intense, higher in grade and stage and does not respond well to chemotherapy (Jin et al., 2017). Cigarette smoking is a major risk factor for respiratory and extra respiratory cancers in human body. While the oral and lung cancer result on account of direct contact with the tobacco products, the urinary bladder mucus membrane is exposed to a number of metabolites of tobacco products and if this exposure is sustained for a longer duration, a deadly cancer results (Omare et al., 2022). Over 7000 chemical compounds have been found in tobacco smoke and more than 50 of these have been a labelled as carcinogenic. When tobacco burns, it releases carbon monoxide, benzene, formaldehyde and polycyclic aromatic hydrocarbons (PAH), hydrogen, cyanide, nitrosamine, etc. Recent studies have shown that the bladder cancer patients who have been smoker have been found to have altered metabolanomics of urinary bladder epithelium in variety of ways. Firstly, some metabolites of tobacco create hyper methylation while many types of nitrosamines and nicotine metabolites create genotoxicity resulting in DNA damage, DNA adducts, mutations and ultimately carcinogenesis (Jin et al., 2017; Fuller et al., 2028; Suzuki et al., 2020). Some years ago, an impression was created that if one uses electronic cigarettes, the incidence of urinary bladder cancer can be lowered, but recent studies have refuted that (Fuller et al., 2028). Although tobacco industry is exploring to create less toxic types of tobacco, but the danger of high grade, urinary bladder cancer is still looming large on humanity (Stephen and Hatsukami, 2022) and therefore, one must respond to this alarm. The temptation to adopt smoking is increasing in younger population in developing countries and therefore not only a greater emphasis on laboratory and clinical research is needed but also a wide spread campaign on social media to warn people about the association of cigarette smoking and bladder cancer are the need of hour. Tobacco addiction in various forms is not confined to a particular group, strata, or gender. Every year, ‘World No Tobacco Day” is celebrated on May 31st to draw attention to the adverse effects of tobacco consumption. Despite being labeled as a potent carcinogen and the health risks associated with it, people find it difficult to get out of tobacco addiction. Similarly, there are numerous other toxic substances used daily that are directly linked to health issues like allergies, infertility, birth defects, learning disabilities, different types of cancers, and several more. Across the world, extensive research is being conducted on Environmental Health Toxicology to assess the adverse effects of various chemicals on human health. Journal of Environmental Biology publishes research on different aspects of Environmental Sciences, Biological Sciences and Toxicology, however, to expand our horizon we now provide a forum for Medical and Pharmaceutical researchers to showcase their research pertinent to Toxicants and their impact on human and animal health. ournal of Environmental Biology is of interest to toxicologist, pharmacologist, zoologist, botanist, ecologist, environmental scientist, industry R&D organizations and others engaged in environmental research and consultation. We welcome new submissions (Original Research Articles, Research Reviews & Case Studies) from researchers working in the areas of Environmental Health Toxicology and also encourage scientists to curate Theme-based Special Issues.

Evidence on bringing specialised care to the primary level—effects on the Quadruple Aim and cost-effectiveness: a systematic review

BackgroundTo achieve the Quadruple Aim of improving population health, enhancing the patient experience of care, reducing costs and improving professional satisfaction requires reorganisation of health care. One way to accomplish this aim is by integrating healthcare services on different levels. This systematic review aims to determine whether it is cost-effective to bring a hospital specialist into primary care from the perspectives of commissioners, patients and professionals.MethodsThe review follows the PRISMA guidelines. We searched PubMed, Scopus and EBSCO (CINAHL and Academic Search Ultimate) for the period of 1992–2022. In total, 4254 articles were found, and 21 original articles that reported on both quality and costs, were included. The JBI and ROBINS-I tools were used for quality appraisal. In data synthesis, vote counting and effect direction plots were used together with a sign test. The strength of evidence was evaluated with the GRADE.ResultsCost-effectiveness was only measured in two studies, and it remains unclear. Costs and cost drivers for commissioners were lower in the intervention in 52% of the studies; this proportion rose to 67% of the studies when cost for patients was also considered, while health outcomes, patient experience and professional satisfaction mostly improved but at least remained the same. Costs for the patient, where measured, were mainly lower in the intervention group. Professional satisfaction was reported in 48% of the studies; in 80% it was higher in the intervention group. In 24% of the studies, higher monetary costs were reported for commissioners, whereas the clinical outcomes, patient experience and costs for the patient mainly improved.ConclusionsThe cost-effectiveness of the hospital specialist in primary care model remains inconclusive. Only a few studies have comprehensively calculated costs, evaluating cost drivers. However, it seems that when the service is well organised and the population is large enough, the concept can be profitable for the commissioner also. From the patient’s perspective, the model is superior and could even promote equity through improved access. Professional satisfaction is mostly higher compared to the traditional model. The certainty of evidence is very low for cost and low for quality.Trial registrationPROSPERO CRD42022325232, 12.4.2022.

The APE1/REF-1 and the hallmarks of cancer.

APE1/REF-1 (apurinic/apyrimidinic endonuclease 1 / redox factor-1) is a protein with two domains, with endonuclease function and redox activity. Its main activity described is acting in DNA repair by base excision repair (BER) pathway, which restores DNA damage caused by oxidation, alkylation, and single-strand breaks. In contrast, the APE1 redox domain is responsible for regulating transcription factors, such as AP-1 (activating protein-1), NF-κB (Nuclear Factor kappa B), HIF-1α (Hypoxia-inducible factor 1-alpha), and STAT3 (Signal Transducers and Activators of Transcription 3). These factors are involved in physiological cellular processes, such as cell growth, inflammation, and angiogenesis, as well as in cancer. In human malignant tumors, APE1 overexpression is associated with lung, colon, ovaries, prostate, and breast cancer progression, more aggressive tumor phenotypes, and worse prognosis. In this review, we explore APE1 and its domain's role in cancer development processes, highlighting the role of APE1 in the hallmarks of cancer. We reviewed original articles and reviews from Pubmed related to APE1 and cancer and found that both domains of APE1/REF-1, but mainly its redox activity, are essential to cancer cells. This protein is often overexpressed in cancer, and its expression and activity are correlated to processes such as proliferation, invasion, inflammation, angiogenesis, and resistance to cell death. Therefore, APE1 participates in essential processes of cancer development. Then, the activity of APE1/REF-1 in these hallmarks suggests that targeting this protein could be a good therapeutic approach.

A quest for universal anti-SARS-CoV-2 T cell assay: systematic review, meta-analysis, and experimental validation

Measuring SARS-CoV-2-specific T cell responses is crucial to understanding an individual’s immunity to COVID-19. However, high inter- and intra-assay variability make it difficult to define T cells as a correlate of protection against COVID-19. To address this, we performed systematic review and meta-analysis of 495 datasets from 94 original articles evaluating SARS-CoV-2-specific T cell responses using three assays – Activation Induced Marker (AIM), Intracellular Cytokine Staining (ICS), and Enzyme-Linked Immunospot (ELISPOT), and defined each assay’s quantitative range. We validated these ranges using samples from 193 SARS-CoV-2-exposed individuals. Although IFNγ ELISPOT was the preferred assay, our experimental validation suggested that it under-represented the SARS-CoV-2-specific T cell repertoire. Our data indicate that a combination of AIM and ICS or FluoroSpot assay would better represent the frequency, polyfunctionality, and compartmentalization of the antigen-specific T cell responses. Taken together, our results contribute to defining the ranges of antigen-specific T cell assays and propose a choice of assay that can be employed to better understand the cellular immune response against viral diseases.

The assessment of paraspinal muscle epimuscular fat in participants with and without low back pain: A case-control study

It remains unclear whether paraspinal muscle fatty infiltration in low back pain (LBP) is i) solely intramuscular, ii) is lying outside the epimysium between the muscle and fascial plane (epimuscular) or iii) or combination of both, as imaging studies often use different segmentation protocols that are not thoroughly described. Epimuscular fat possibly disturbs force generation of paraspinal muscles, but is seldomly explored. This project aimed to 1) compare epimuscular fat in participants with and without chronic LBP, and 2) determine whether epimuscular fat is different across lumbar spinal levels and associated with BMI, age, sex and LBP status, duration or intensity. Fat and water lumbosacral MRIs of 50 chronic LBP participants and 41 healthy controls were used. The presence and extent of epimuscular fat for the paraspinal muscle group (erector spinae and multifidus) was assessed using a qualitative score (0–5 scale; 0 = no epimuscular fat and 5 = epimuscular fat present along the entire muscle) and quantitative manual segmentation method. Chi-squared tests evaluated associations between qualitative epimuscular fat ratings and LBP status at each lumbar level. Bivariate and partial spearman’s rho correlation assessed relationships between quantitative and qualitative epimuscular fat with participants’ characteristics. Epimuscular fat was more frequent at the L4-L5 (X2 = 13.781, p = 0.017) and L5-S1 level (X2 = 27.825, p < 0.001) in participants with LBP compared to controls, which was not found for the higher lumbar levels. The total qualitative score (combined from all levels) showed a significant positive correlation with BMI, age, sex (female) and LBP status (r = 0.23–0.55; p < 0.05). Similarly, the total area of epimuscular fat (quantitative measure) was significantly correlated with BMI, age and LBP status (r = 0.26–0.57; p < 0.05). No correlations were found between epimuscular fat and LBP duration or intensity. Paraspinal muscle epimuscular fat is more common in chronic LBP patients. The functional implications of epimuscular fat should be further explored.