Abigail Gerberick, Charles R Rinaldo, Nicolas Sluis-Cremer
{"title":"Antigen Presenting Cell-Mediated HIV-1 <i>Trans</i> Infection in the Establishment and Maintenance of the Viral Reservoir.","authors":"Abigail Gerberick, Charles R Rinaldo, Nicolas Sluis-Cremer","doi":"10.18103/mra.v11i7.1.4064","DOIUrl":"10.18103/mra.v11i7.1.4064","url":null,"abstract":"<p><p>Despite potent antiretroviral therapy, an HIV-1 reservoir persists that represents a major barrier to a cure. Understanding the mechanisms by which the HIV-1 reservoir is established and maintained is critical for the discovery of effective treatments to significantly reduce or eliminate the viral reservoir. In addition to <i>cis</i> infection, in which HIV-1 directly infects target CD4<sup>+</sup> T cells, cell-to-cell transmission, or <i>trans</i> infection, can also occur. HIV-1 <i>trans</i> infection is significantly more efficient than <i>cis</i> infection, mostly due to the occurrence of multiple infections per cell during transfer. Additionally, <i>trans</i> infection is efficient even in the presence of ART and/or neutralizing antibodies. Cell-to-cell transmission is mediated by CD4<sup>+</sup> T cells and professional antigen presenting cells (APC). Here we focus on APC, i.e., myeloid dendritic cells, B lymphocytes, and monocytes/macrophages, that bind, internalize, and transfer HIV-1 to target CD4<sup>+</sup> T cells via various proposed mechanisms. We assess the potential impact of <i>trans</i> infection on the establishment and maintenance of the HIV-1 reservoir including its role in disease progression. We consider the natural interactions between APC and CD4<sup>+</sup> T cells <i>in vivo</i> that HIV-1 may hijack, allowing for the highly efficient <i>trans</i> infection of CD4<sup>+</sup> T cells, maintaining the viral reservoirs in tissue despite undetectable plasma viral loads in peripheral blood. We propose that these modes of viral pathogenesis need to be addressed in potential cure strategies to ensure eradication of the viral reservoir.</p>","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11616617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83641049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kayla T B Fuselier, Claudia Kruger, J Michael Salbaum, Claudia Kappen
{"title":"Correspondence of Yolk Sac and Embryonic Genotypes in F0 Mouse CRISPants.","authors":"Kayla T B Fuselier, Claudia Kruger, J Michael Salbaum, Claudia Kappen","doi":"10.18103/mra.v11i6.3989","DOIUrl":"10.18103/mra.v11i6.3989","url":null,"abstract":"<p><p>CRISPR-mediated genome editing <i>in vivo</i> can be accompanied by prolonged stability of the Cas9 protein in mouse embryos. Then, genome edited variant alleles will be induced as long as Cas9 protein is active, and unmodified wildtype target loci are available. The corollary is that CRISPR-modified alleles that arise after the first zygotic cell division potentially could be distributed asymmetrically to the cell lineages that are specified early during morula and blastocyst development. This has practical implications for the investigation of F0 generation individuals, as cells in embryonic and extraembryonic tissues, such as the visceral yolk sac, might end up inheriting different genotypes. We here investigated the hypothetically possible scenarios by genotyping individual F0 CRISPants and their associated visceral yolk sacs in parallel. In all cases, we found that embryonic genotype was accurately reflected by yolk sac genotyping, with the two tissues indicating genetic congruence, even when the conceptus was a mosaic of cells with distinct allele configurations. Nevertheless, low abundance of a variant allele may represent a private mutation occurring only in the yolk sac, and in those rare cases, additional genotyping to determine the mutational status of the embryo proper is warranted.</p>","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"11 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10601497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54232970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"DISPOSITION OF ADOLESCENTS TOWARD RECEIVING COVID-19 VACCINATIONS IN VILLAVICENCIO: MYTHS AND BELIEFS","authors":"C. Balaguera, M. Osorio, M. Echavarría, M. Garzón","doi":"10.1101/2023.01.10.23284415","DOIUrl":"https://doi.org/10.1101/2023.01.10.23284415","url":null,"abstract":"Global efforts regarding the COVID-19 pandemic have been focused on preventive activities, such as vaccination, since the disease is expected to become endemic. Adolescents were among the last population groups to be included in the vaccination program in Colombia, and adequate coverage has not yet been achieved in this group and in infants. It is important to understand their motivations to improve the willingness of this population to be vaccinated. A cross-sectional study was designed via an online survey in adolescents aged 14-19 years in Villavicencio Meta after validation of the survey and informed consent. The following options were provided for the question on vaccine disposition: willing, undecided, and unwilling. We described the disposition toward receiving COVID-19 vaccine using graphs and absolute and relative frequencies based on age group. A multinomial regression model was used to assess the relationship between our predictor variables and vaccine disposition in adolescents. In this study, 288 adolescents were surveyed. The risk variables for unwillingness to be vaccinated were being male (odds ratio [OR] 2.18, 95% confidence interval [CI] 0.8-5.7, p = 0.62), belonging to low social stratum (OR 2.29, 95% CI 0.9-5.88, p = 0.19), having a monthly family income of less than 1 million Colombian pesos (250 USD) (OR 2.01, 95% CI 0.8-5.16, p = 0.19), and having basic education (OR 2.59, 95% CI 0.33-20.14, p = 0.18). Unproven myths and beliefs exert a profound influence on adolescents, which results in an unwillingness to be vaccinated. Hence, innovative public health strategies should be designed to improve the disposition to be vaccinated in this population group.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78289204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Current Status of Ultrasonography and Fine-Needle Aspiration Citology for the Management of the Axilla in Breast Cancer","authors":"G. de León, Andrés Dell´Acqua, A. Cristiani","doi":"10.18103/mra.v11i5.3851","DOIUrl":"https://doi.org/10.18103/mra.v11i5.3851","url":null,"abstract":"Objetive: to analyze whether ultrasonography with fine-needle aspiration cytology of an axillary suspicious node, in patients with breast cancer, could help to differentiate between patients with low involvement of the axilla (up to 2 nodes with macrometastasis) of those with high involvement of the axilla (more than 2 lymph nodes with macrometastasis). Material and methods: A total of 115 consecutive patients with breast cancer (up to 5 cm in diameter), with clinically negative axilla and pathologically positive axilla. All patients underwent preoperative axillary ultrasound and ultrasound-guided fine-needle aspiration cytology was performed in patients with suspicious nodes. In all patients with positive cytology, lymphadenectomy was performed. In all patients with negative ultrasound and cytology, sentinel lymph node biopsy was performed, and when it was positive, lymphadenectomy was performed. The number of pathological lymph nodes was evaluated after lymphadenectomy. Results: A total of 61 patients had positive axillary ultrasound and cytology. In 42 of them (69%), there were more than 2 pathological lymph nodes. There were 54 patients with negative axillary ultrasound and cytology. In 49 of them (90%), there were only 1 or 2 pathological lymph nodes. Axillary ultrasound and fine-needle aspiration cytology were able to identify 42 of the 47 patients (89%) with more than 2 pathological lymph nodes. Conclusion: ultrasound and ultrasound-guided fine-needle aspiration citology was able to identify, in a preoperative stage, those patients with high axillary involvement (more than 2 lymph nodes with macrometastasis). The latter are the patients who would benefit from lymphadenectomy of the axilla, ignoring the sentinel lymph node biopsy stage.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73659774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
F. Vangroenweghe, Sarah Goethals, Delphine Zele, Anne Bruijn
{"title":"Application of a β-mannanase enzyme in diets with a reduced net energy content in post-weaning piglets resulted in equal performance and an additional economic benefit","authors":"F. Vangroenweghe, Sarah Goethals, Delphine Zele, Anne Bruijn","doi":"10.18103/mra.v11i6.3954","DOIUrl":"https://doi.org/10.18103/mra.v11i6.3954","url":null,"abstract":"β-Mannans are strongly anti-nutritive polysaccharide fibers found in most vegetable feed ingredients. The estimated content of soluble β-mannans in common swine diets range from 0.15 to 0.40%. In vitro studies have demonstrated that as little as 0.05% soluble β-mannan content in feed can elicit a strong innate immune response. Hemicell HT (Elanco Animal Health) is a β-mannanase enzyme for animal feed that breaks down β-mannans, thereby preventing economic losses from the wasteful immune response to β-mannans. The present study aimed to compare pig performance on a control diet and a reformulated diet with a lower energy content – 45 kcal/kg NE reduction – and the inclusion of a β-mannanase enzyme. A six-week feeding trial was conducted on a commercial post-weaning facility with DanBred x Belgian Piétrain pigs starting at 21 days of age. Standard three-phase control diets were compared to reformulated diets with an energy reduction of 45 kcal NE/kg and inclusion of a β-mannanase enzyme (Hemicell HT; Elanco) at 300 g/tonne. Standard production data were collected. The data were analyzed using JMP 15.0 statistical program. Overall, performance data did not differ significantly between trial groups in both Phase 1 and Phase 2, and overall, during the entire post-weaning period. Mortality was only numerically, but not significantly higher in the Control as compared to the Hemicell HT group. Hemicell HT had an overall benefit of € 1.69 per piglet and € 15.18 per tonne of feed due to the 45 kcal/kg NE reduction. The current trial demonstrated that the inclusion of Hemicell HT in reformulated diets with a lower energy content (45 kcal NE/kg) was able to retain production performance in post-weaned piglets with an economic benefit.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74071905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Infections May Cause Arterial Inflammation, Atherosclerosis, Myocarditis and Cardiovascular Disease","authors":"U. Ravnskov, A. Alabdulgader, K. Mccully","doi":"10.18103/mra.v11i5.3866","DOIUrl":"https://doi.org/10.18103/mra.v11i5.3866","url":null,"abstract":"Effective prevention and treatment of atherosclerosis and cardiovascular disease (CVD), the commonest cause of death in most countries, is still lacking. For many years we have studied the cholesterol hypothesis and found that there are many contradictions to this hypothesis. For instance, no trial has shown exposure response; the lipid values are not associated with degree of atherosclerosis, and people with high LDL-C live just as long or longer than people with low LDL-C. These facts together with the observation that inflammation is a common finding in atherosclerotic arteries have probably contributed to the hypothesis that CVD may be caused by inflammation. However, several trials with anti-inflammatory drugs have shown that such treatment increases the risk of CVD. Therefore, a relevant hypothesis is whether it is infections which cause the inflammation and whether CVD may be caused by infections because many human observations and animal experiments are in accordance with this idea. As cholesterol-lowering treatment is ineffective and may cause serious side effects, we believe that future research should elucidate the importance of infections in the etiology of CVD. A relevant method would be to perform a blood culture on all patients with an acute AMI and if it is positive, to treat the patient with an appropriate antibiotic.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74169690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Guerrero, Joaquín Fernández de la, Concha Castañeda, A. Piñero, F. Javier, G. Md, N. Castellano, J. Ferrer, I. Lozano, Javier Moreno, A. Madrid
{"title":"Avcs-Sonr Pilot Study: N-Terminal Pro-Brain Natriuretic Peptide Inversely Correlates with Sonr Signal in Patients with Dilated Cardiomyopathy and Reduced Left Ventricular Ejection Fraction","authors":"J. Guerrero, Joaquín Fernández de la, Concha Castañeda, A. Piñero, F. Javier, G. Md, N. Castellano, J. Ferrer, I. Lozano, Javier Moreno, A. Madrid","doi":"10.18103/mra.v11i7.2.4169","DOIUrl":"https://doi.org/10.18103/mra.v11i7.2.4169","url":null,"abstract":"Background. Chronic heart failure is a very important public health problem, and brain natriuretic peptide monitoring may help in its management but faces important logistical problems. A readily available surrogate of brain natriuretic peptide would be of value in this field. We hypothesized that SonR measurements might be this brain natriuretic peptide surrogate. Methods. Patients with chronic heart failure, left ventricular ejection fraction ≤ 30% and implanted with a cardiac resynchronization therapy defibrillator able to provide SonR values underwent monthly assessment of brain natriuretic peptide levels for 1 year. The relationship between brain natriuretic peptide levels and paired SonR values was evaluated. Results. An inverse and highly significant relationship between brain natriuretic peptide levels and paired SonR values was obtained. Conclusions. We found an inverse and significant relationship between SonR values and brain natriuretic peptide levels. This finding might lead to the use of SonR values to monitor treatment and preclude hospital admissions in patients with chronic heart failure.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"71 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75665630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Potential Impact of Genetic-Code Mutations on Medicine and Health","authors":"T. Wong, Hong Xue","doi":"10.18103/mra.v11i8.4331","DOIUrl":"https://doi.org/10.18103/mra.v11i8.4331","url":null,"abstract":"The genetic code encoding amino acid sequences in ribosomal translation consists of an alphabet of 61 triplet codons for 20 amino acids and three chain termination signals. Basically the same universal code is employed by all organisms from the Last Universal Common Ancestor (LUCA)-proximal Methanobacter kandleri (Mka) to humans. This universal code, which has remained invariant for all living species, enables the transplantation of protein-coding genes between different species without loss of function, and constrains the chemical diversity of the encoded amino acids. Over the initial decades following the discovery of the code, its invariance coupled with the lack of any information regarding its origin have led to the view that the code might represent an inexplicable ‘frozen accident’ in the history of life. However, with the formulation of the coevolution theory of the genetic code and its multifaceted supporting evidence, this view has become untenable. Instead, the encoded amino acids are known to comprise two different classes: ten Class 1 amino acids available on prebiotic Earth were incorporated into the protocells as they evolved into life forms, while the ten Class 2 amino acids were produced by early life through biosynthesis. Thus, the later entry of the Class 2 amino acids identified them as end products of cellular evolution, which suggests the plausibility of continuing alterations of the encoded amino acids after an eons-long pause. Accordingly, attempts were made by our group to replace Trp by 4-fluroTrp (4FTrp) from the proteome of Bacillus subtilis. The targeted replacement obtained proved the inherent mutability of the code, and this has stimulated the development of a wide range of mutated codes through a variety of approaches. Hundreds of genetic code mutants have now been successfully isolated from microbes to animals, transforming the code from an immutable construct to a highly malleable molecular device. The effects of such new codes on medicine and health range from treatments for a variety of diseases to the alleviation of food crisis arising from the degradation of the environment and devastation due to natural disasters.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"61 2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73262792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Minimum Ganglion Cell Layer Thickness is the Best Structural Predictor of Visual Function in Leber Hereditary Optic Neuropathy","authors":"K. Zeng, B. Chou, A. Sadun","doi":"10.18103/mra.v11i7.1.4107","DOIUrl":"https://doi.org/10.18103/mra.v11i7.1.4107","url":null,"abstract":"Background: Patients with Leber hereditary optic neuropathy, a genetic cause of severe optic atrophy and blindness, demonstrate characteristic structural changes measurable through optical coherence tomography, including initial swelling of the retinal nerve fiber layer and progressive thinning of the ganglion cell layer. After symptomatic conversion, patients experience progressive vision loss, often with dense central scotomas. Aims: This study aims to explore the predictive potential of ocular structural measurements to visual function in patients with Leber hereditary optic neuropathy. Methods: Medical records were reviewed retrospectively for patients with Leber hereditary optic neuropathy clinical testing. Structural measurements, including the average thickness of the ganglion cell layer, the retinal nerve fiber layer, and minimum thickness of the ganglion cell layer, measured through optical coherence tomography were obtained along with measures of visual function such as visual acuity and mean deviation of visual field testing. Simple and multivariable linear regressions were performed to determine correlations between structural measurements and visual functions. Analyses were conducted for all patients, and subgroup of symptomatic patients. Results: Overall, 92 eyes were included with 78 symptomatic eyes. Across all patients, the minimum ganglion cell layer thickness had the highest correlation coefficient with visual acuity (Beta -0.632, adjusted R2 0.396) and with visual field function (Beta 0.572, adj. R2 0.320) compared to the average thickness of the ganglion cell layer (Beta 0.474, adj. R2 0.216) and retinal nerve fiber layer (Beta 0.481, adj. R2 0.223). In multivariate analysis, the minimum ganglion cell layer thickness was the only significant measurement that correlated with visual acuity across all eyes (Beta -0.527, P<0.001) and symptomatic eyes (Beta -0.479, P<0.001). The minimum ganglion cell layer thickness (Beta 0.440, P<0.001) and retinal nerve fiber layer average thickness (0.258, P=0.023) were significant structural measurements correlating to visual field function. Conclusion: The minimum ganglion cell layer thickness is the best structural measure predictor for visual field and visual acuity compared to other common structural measurements in patients with Leber hereditary optic neuropathy. It is a good predictor even when evaluating only symptomatic eyes. Additional attention toward the minimum ganglion cell layer thickness may offer further insight into a patient’s visual potential and the natural history of this disease.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75387083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Is there a Role for Measuring Direct Oral Anticoagulant Levels in Select Patients?","authors":"L. Baruch, K. Bhatia, P. Lopez, O. Sherman","doi":"10.18103/mra.v11i1.3527","DOIUrl":"https://doi.org/10.18103/mra.v11i1.3527","url":null,"abstract":"Direct oral anticoagulants are recommended as first line therapy for patients with atrial fibrillation and venous thromboembolic disease. Measurement of drug levels or pharmacodynamic effect is not recommended during treatment. Dose adjustments are based on age, weight, kidney function and drug-drug interactions. These adjustments are generally based on an estimate of their effect on drug concentration. DOAC dosing recommendations differ across the world. These differences in prescribing recommendations result in different levels of DOAC exposure in patients with identical clinical characteristics. Additionally, data from clinical trials has shown that drug levels may vary significantly in individual patients with identical clinical characteristics despite taking the same prescribed dose. More concerning is that current prescribing recommendations provide cut points for dose adjustments, as an example age 80 or greater in the case of apixaban in atrial fibrillation, which may result in dramatically higher drug concentrations in patients with significantly higher bleeding risk. Data from outcome trials in both atrial fibrillation and venous thromboembolism have provided mean-median drug concentrations for each of the DOACs. These trial results appear to demonstrate that once a threshold DOAC plasma concentration is reached, higher concentrations fail to provide significant added ischemic stroke reduction while at the same time add an increased risk of bleeding. Bleeding remains a significant problem with DOACs and is associated with an increase in short and long-term mortality, ischemic stroke, myocardial infarction, cost, and drug interruption and discontinuation. Over the past years, our clinic has been assessing DOAC concentration in patients at risk for under or over exposure. Based on our experience, clinical characteristics alone appear to be insufficient, as a significant number of patients with characteristics suggesting high exposure would be under-dosed using a purely clinical approach and an even greater number, who are at elevated risk of bleeding would have had excessive levels, if prescribing were based strictly on the established dose reduction criteria. We propose, and provide our supporting clinical experience, that measuring DOAC levels in select patients will increase the margin of safety of these medications without compromising efficacy.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75531583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}