Medical Biology Research Articles

Methods of Prevention and Mitigation of Autoimmune Diseases - A Review of The Literature

Introduction and purpose: Autoimmune diseases are conditions where the body’s immune system is unable to distinguish between auto- and foreign antigens and mistakenly attacks its cells, tissues, and organs. In recent years it became major public health concern because of the increasing diagnosis rate. Currently, about 5% of the population in Western countries is affected by such diseases, more often in women population. The exact cause of autoimmune diseases is unknown, although most probably it results from a combination of genetic predisposition, environmental risk factors and immune dysregulation. Development of autoantigen-specific lymphocytes and autoantibodies might be decisive in starting the process of autoimmunity. Most common medication used in autoimmune diseases treatment are nonsteroidal anti-inflammatory drugs (NSADs), glucocorticoids, disease-modifying antirheumatic drugs (DMARDs). Additionally, there is biological medication available for many of them. It is known that non-pharmacological interventions, such as specific diets, supplementation or physical exercise is useful to mitigate the disease or even to prevent the body from its onset. Materials and methods: The data for the article was found using the PubMed and Google Scholar websites. The key words used for the search included: ‘diet and autoimmunity’, ‘autoimmunity and estrogens’, ‘microbiota and autoimmunity’. Articles not written in English, conference abstracts only and duplicated papers were excluded. Conclusions: There is still no cure for autoimmune diseases, although various prevention and mitigation strategies can help manage these conditions and improve quality of life for affected individuals. However, for the use of some of them, evidence-based recommendations are not available. This review highlights current non-pharmacological therapeutic options.

Real-World Safety Profile of Biologic Drugs for Severe Uncontrolled Asthma: A Descriptive Analysis from the Spanish Pharmacovigilance Database.

Background: The present investigation provides a thorough analysis of adverse drug reactions (ADRs) reported in the Database of the Spanish Pharmacovigilance System (FEDRA) for biologic medications primarily indicated for severe refractory asthma, including omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, and tezepelumab. Our main objective was to identify ADRs not documented in the drugs' Technical Sheets (summary of product characteristics, SmPC), potentially indicating unrecognized risks meriting pharmacovigilance attention. Methods: Data spanning from each drug's market introduction until 22 January 2024, were analyzed, sourced from direct submissions to the Spanish Pharmacovigilance System, industry communications, and literature reviews. We evaluated notifications impartially to ensure a comprehensive review of all the ADRs associated with these medications. Results: This investigation underlines the critical role of post-marketing surveillance in enhancing patient safety. It emphasizes the necessity for healthcare professionals to report ADRs comprehensively to foster a robust pharmacovigilance system. Furthermore, the study highlights gaps between the reported ADRs and the information provided in SmPCs, signaling potential areas for improvement in drug safety monitoring and regulatory oversight. Conclusions: Finally, these findings may contribute to informed decision making in clinical practice and regulatory policy, ultimately advancing patient care and safety in the management of severe uncontrolled asthma.

Systemic Immunomodulatory Treatments for Atopic Dermatitis

There are multiple approved systemic treatments for atopic dermatitis. Lebrikizumab is a newly licensed biologic medication that has been compared to placebo in clinical trials but not to other systemic treatments. To compare reported measures of efficacy and safety of lebrikizumab to other systemic treatments for atopic dermatitis in a living systematic review and network meta-analysis. The Cochrane Central Register of Controlled Trials, MEDLINE, Embase, the Latin American and Caribbean Health Science Information database, the Global Resource of Eczema Trials database, and trial registries were searched from inception through November 3, 2023. Randomized clinical trials evaluating 8 or more weeks of treatment with systemic immunomodulatory medications for moderate to severe atopic dermatitis. Titles, abstracts, and full texts were screened in duplicate. Data were abstracted in duplicate and random-effects bayesian network meta-analyses were performed. Minimal important differences were used to define important differences between medications. Certainty of evidence was assessed using the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation). The updated analysis was completed from December 13, 2023, to February 20, 2024. Efficacy outcomes were the Eczema Area and Severity Index (EASI), the Patient Oriented Eczema Measure (POEM) Dermatology Life Quality Index (DLQI), and Peak Pruritus Numeric Rating Scales (PP-NRS) and were compared using mean difference (MD) with 95% credible intervals (CrI). Safety outcomes were serious adverse events and withdrawal due to adverse events. Other outcomes included the proportion of participants with 50%, 75%, and 90% improvement in EASI (EASI-50, -75, -90) and the proportion with success on the Investigator Global Assessment compared using odds ratios with 95% CrI. The study sample included 97 eligible trials, with a total of 24 679 patients. Lebrikizumab was associated with no important difference in change in EASI (MD, -2.0; 95% CrI, -4.5 to 0.3; moderate certainty), POEM (MD, -1.1; 95% CrI -2.5 to 0.2; moderate certainty), DLQI (MD, -0.2; 95% CrI -2.1 to 1.6; moderate certainty), or PP-NRS (MD, 0.1; 95% CrI -0.4, 0.6; high certainty) compared to dupilumab among adults with atopic dermatitis who were treated for up to 16 weeks. Dupilumab was associated with higher odds of efficacy in binary outcomes compared with lebrikizumab. The relative efficacy of other approved systemic medications was similar to that found by previous updates of this living study, with high-dose upadacitinib and abrocitinib demonstrating numerically highest relative efficacy. For safety outcomes, low event rates limited useful comparisons. In this living systematic review and network meta-analysis, lebrikizumab was similarly effective to dupilumab for the short-term treatment of atopic dermatitis in adults. Clinicians and patients can use these comparative data to inform treatment decisions.

Modern paradigms in biologic sequencing of inflammatory bowel disease in Aotearoa New Zealand.

The modern treatment of inflammatory bowel disease (IBD) has evolved significantly in recent years. This includes development of new pharmacologic therapies and their implementation in clinical practice. Moderate-to-severe IBD represents a group of patients at risk of poorer outcomes, and mounting evidence suggests biologic and small molecule medications, collectively termed advanced therapies, are the most effective tools clinicians possess. Even with biologic treatment, many patients do not respond or lose response over time. Until recently, most randomised trials demonstrating efficacy and safety of biologics have been placebo-controlled with a lack of head-to-head studies. Therefore, selecting the right medication for the appropriate clinical scenario can be difficult. In addition, there is evidence of differing clinical success when positioning biologic treatments in different sequences. This is important, as one-third of patients treated with biologics will require a switch to a second agent by 12 months, and a further 20% will require a third agent. Over the years, there have been widespread calls in Aotearoa New Zealand for increasing biologic treatment options. Ustekinumab and vedolizumab received public funding for the treatment of moderate-to-severe IBD in 2023, and this has presented long-awaited opportunities for patients, but also new challenges for clinicians in regard to treatment selection. The purpose of this document is to provide guidance to clinicians on biologic selection, sequencing and optimisation for IBD. These recommendations are specific to the domestic prescribing climate, supported by the best available evidence and endorsed by the New Zealand Society of Gastroenterology IBD Working Group.

Blood Sampling and Hormone Measurement for Determining the Stage in the Ovarian Cycle in Marmosets.

Common marmosets are small New World monkeys. Since many of their biological mechanisms are similar to those of humans, marmosets are potentially useful for medical and human biology research across a range of fields, such as neuroscience, regenerative medicine, and development. However, there is a lack of literature describing methods for many basic experiments and procedures. Here, detailed methods for determining the levels of sex hormones (progesterone, estradiol, and chorionic gonadotropin) in marmosets are described. The measurement of these hormones enables the prediction of the stage in the ovarian cycle, which is typically 26-30 days in marmosets; accurate determination is essential for the harvesting of oocytes/zygotes at the correct time point and for the preparation of host females for the generation of genetically modified marmosets. Additionally, the measurement of sex hormone levels is useful for endocrinology, ethology, early development, and reproductive biology studies. This protocol provides a detailed description of the methods for blood sampling from the femoral vein, separation of plasma for hormone measurement, measuring chorionic gonadotropin levels using urine and plasma, resetting the ovarian cycle using injections of a prostaglandin F2α analog to shorten and synchronize the cycle, and promoting follicular growth and ovulation by injecting follicle-stimulating hormone and chorionic gonadotropin. Using these protocols, the stages in the ovarian cycle can be determined for the timely collection of oocytes/zygotes.

Applying Machine Learning Models Derived From Administrative Claims Data to Predict Medication Nonadherence in Patients Self-Administering Biologic Medications for Inflammatory Bowel Disease.

Adherence to self-administered biologic therapies is important to induce remission and prevent adverse clinical outcomes in Inflammatory bowel disease (IBD). This study aimed to use administrative claims data and machine learning methods to predict nonadherence in an academic medical center test population. A model-training dataset of beneficiaries with IBD and the first unique dispense of a self-administered biologic between June 30, 2016 and June 30, 2019 was extracted from the Commercial Claims and Encounters and Medicare Supplemental Administrative Claims Database. Known correlates of medication nonadherence were identified in the dataset. Nonadherence to biologic therapies was defined as a proportion of days covered ratio <80% at 1 year. A similar dataset was obtained from a tertiary academic medical center's electronic medical record data for use in model testing. A total of 48 machine learning models were trained and assessed utilizing the area under the receiver operating characteristic curve as the primary measure of predictive validity. The training dataset included 6998 beneficiaries (n = 2680 nonadherent, 38.3%) while the testing dataset included 285 patients (n = 134 nonadherent, 47.0%). When applied to test data, the highest performing models had an area under the receiver operating characteristic curve of 0.55, indicating poor predictive performance. The majority of models trained had low sensitivity and high specificity. Administrative claims-trained models were unable to predict biologic medication nonadherence in patients with IBD. Future research may benefit from datasets with enriched demographic and clinical data in training predictive models.

Center for Medical and Evacuation Support of State Research Center – Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency: Status and Development Prospects.

Center for Medical and Evacuation Support of State Research Center – Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency: Status and Development Prospects.

Verification of the analytical performance of the anti-cyclic citrullinated peptide assay on ALINITY ci ® experience from the biochemistry laboratory of Mohammed VI University Hospital in Oujda

The aim of our work was to evaluate the analytical performance of the anti-cyclic citrullinated peptide determination by a two-step immunoassay using microparticle chemiluminescence immunoassay (CMIA) technology, in accordance with the Scope A criteria of the guide of the verification/validation of medical biology methods. We evaluated the repeatability and the intermediate precision of the assay. The results obtained are very satisfactory for the two levels (low and high) both for intermediate fidelity, with coefficients of variation (CV) of CV1= 1.9% and CV2=1.8% respectively, and for repeatability, with coefficients of variation of CV1 = 1.7%, CV2= 1.61%. respectively. The results obtained made it possible to verify the method's performance and compare it with the analytical objectives set in order to meet the regulatory and normative requirements set by the supplier and learned societies.

Continuous-Wave Self-Raman Vanadate Lasers Generating Versatile Visible Wavelengths

In this review, the developments of efficient high-power CW orange-lime-green lasers by using intracavity stimulated Raman Scattering (SRS) in Nd-doped vanadate lasers are systematically discussed. The overall properties of the spontaneous Raman spectra in Nd:YVO4 and Nd:GdVO4 crystals are overviewed. The critical phase matchings of using the lithium triborate (LBO) crystals for sum frequency generation (SFG) and second harmonic generation (SHG) are thoroughly reviewed. We make a detailed review for achieving the individual green-lime-orange emissions from the self-Raman Nd:YVO4 and Nd:GdVO4 lasers with LBO crystals. The following is to review the dual-wavelength operations of the lime-green and orange-green lasers. Finally, the procedure for generating the triple-wavelength operation of orange-lime-green simultaneous emissions is completely described. The present review is expected to be useful for developing compact, efficient, high-power CW visible lasers for applications including medical treatment, biology, spectroscopy, and remote sensing.

Tuberculosis screening for patients on biologic Medications: A Single-Center experience and Society guideline Review, Monroe County, New York, 2018–2021

RationaleBiologic medications for immune-mediated inflammatory diseases may increase the risk of tuberculosis (TB) reactivation, but data on screening for TB in low TB prevalence areas are limited. ObjectiveTo assess the real-world practice patterns of TB screening among prescribers of biologic medications. MethodsWe conducted a retrospective observational study at a single, university-based healthcare facility in a low TB prevalence area. We enrolled adult patients prescribed a biologic medication between October 2018 and December 2021, and collected data on demographics, biologic medications and TB test results. For patients with positive TB tests, further data including prescriber specialty and response to positive tests were obtained. We reviewed pertinent major society guidelines/ consensus statements regarding TB screening among patients treated with biologic medications. Results4,085 patients were included. 3024 (74.0%) had at least one screening TB test and 42 were positive. Among patients treated with tumor necrosis factor-alpha (TNFα) inhibitors, 1779 of 2129 patients (83.6%) underwent TB testing and 25 (1.4%) were positive. Most with positive TB test results were prescribed biologic medication by gastroenterology (11 patients, 26%), dermatology (12, 29%), or rheumatology (15, 36%) providers. 32 (76%) patients had imaging and roughly half were treated for latent TB infection. Biologic medications were temporarily held for 27 patients (67%). Nine out of 13 society guidelines recommend TB screening for TNFα inhibitors but have differing recommendations for other biologic medications. ConclusionsSignificant practice pattern differences in TB screening for patients receiving biologic medications exist. Multiple society guidelines continue to recommend TB screening even for drugs with no known increased risk of TB reactivation.

Establishment and Application of a Novel Genetic Detection Panel for SNPs in Mongolian Gerbils.

The Mongolian gerbil is a distinctive experimental animal in China, as its genetic qualities possess significant value in the field of medical biology research. Here, we aimed to establish an economical and efficient panel for genetic quality detection in Mongolian gerbils using single-nucleotide polymorphism (SNP) markers. To search for SNPs, we conducted whole-genome sequencing (WGS) in 40 Mongolian gerbils from outbred populations. Reliable screening criteria were established to preliminarily select SNPs with a wide genome distribution and high levels of polymorphism. Subsequently, a multiple-target regional capture detection system based on second-generation sequencing was developed for SNP genotyping. Based on the results of WGS, 219 SNPs were preliminarily selected, and they were established and optimized in a multiple-amplification system that included 206 SNP loci by genotyping three outbred populations. PopGen.32 analysis revealed that the average effective allele number, Shannon index, observed heterozygosity, expected heterozygosity, average heterozygosity, polymorphism information content, and other population genetic parameters of the Capital Medical University (CMU) gerbils were the highest, followed by those of Zhejiang gerbils and Dalian gerbils. Through scientific screening and optimization, we successfully established a novel, robust, and cost-effective genetic detection system for Mongolian gerbils by utilizing SNP markers for the first time.

Patients taking benralizumab, dupilumab, or mepolizumab have lower postvaccination SARS-CoV-2 immunity

Biologic therapies inhibiting the IL-4 or IL-5 pathways are very effective in the treatment of asthma and other related conditions. However, the cytokines IL-4 and IL-5 also play a role in the generation of adaptive immune responses. Although these biologics do not cause overt immunosuppression, their effect in primary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization has not been studied completely. Our aim was to evaluate the antibody and cellular immunity after SARS-CoV-2 mRNA vaccination in patients on biologics (PoBs). Patients with severe asthma or atopic dermatitis who were taking benralizumab, dupilumab, or mepolizumab and had received the initial dose of the 2-dose adult SARS-CoV-2 mRNA vaccine were enrolled in a prospective, observational study. As our control group, we used a cohort of immunologically healthy subjects (with no significant immunosuppression) who were not taking biologics (NBs). We used a multiplexed immunoassay to measure antibody levels, neutralization assays to assess antibody function, and flow cytometry to quantitate Spike-specific lymphocytes. We analyzed blood from 57 patients in the PoB group and 46 control subjects from the NB group. The patients in the PoB group had lower levels of SARS-CoV-2 antibodies, pseudovirus neutralization, live virus neutralization, and frequencies of Spike-specific B and CD8 T cells at 6 months after vaccination. In subgroup analyses, patients with asthma who were taking biologics had significantly lower pseudovirus neutralization than did subjects with asthma who were not taking biologics. The patients in the PoB group had reduced SARS-CoV-2-specific antibody titers, neutralizing activity, and virus-specific B- and CD8 T-cell counts. These results have implications when considering development of a more individualized immunization strategy in patients who receive biologic medications blocking IL-4 or IL-5 pathways.

Update on Non-Interchangeability of Botulinum Neurotoxin Products.

The growing use of botulinum neurotoxins (BoNTs) for medical and aesthetic purposes has led to the development and marketing of an increasing number of BoNT products. Given that BoNTs are biological medications, their characteristics are heavily influenced by their manufacturing methods, leading to unique products with distinct clinical characteristics. The manufacturing and formulation processes for each BoNT are proprietary, including the potency determination of reference standards and other features of the assays used to measure unit potency. As a result of these differences, units of BoNT products are not interchangeable or convertible using dose ratios. The intrinsic, product-level differences among BoNTs are compounded by differences in the injected tissues, which are innervated by different nerve fiber types (e.g., motor, sensory, and/or autonomic nerves) and require unique dosing and injection sites that are particularly evident when treating complex therapeutic and aesthetic conditions. It is also difficult to compare across studies due to inherent differences in patient populations and trial methods, necessitating attention to study details underlying each outcome reported. Ultimately, each BoNT possesses a unique clinical profile for which unit doses and injection paradigms must be determined individually for each indication. This practice will help minimize unexpected adverse events and maximize efficacy, duration, and patient satisfaction. With this approach, BoNT is poised to continue as a unique tool for achieving individual goals for an increasing number of medical and aesthetic indications.

Artificial Intelligence Learns Protein Prediction.

From AlphaGO over StableDiffusion to ChatGPT, the recent decade of exponential advances in artificial intelligence (AI) has been altering life. In parallel, advances in computational biology are beginning to decode the language of life: AlphaFold2 leaped forward in protein structure prediction, and protein language models (pLMs) replaced expertise and evolutionary information from multiple sequence alignments with information learned from reoccurring patterns in databases of billions of proteins without experimental annotations other than the amino acid sequences. None of those tools could have been developed 10 years ago; all will increase the wealth of experimental data and speed up the cycle from idea to proof. AI is affecting molecular and medical biology at giant steps, and the most important might be the leap toward more powerful protein design.

Ninety years of pulse oximetry: history, current status, and outlook.

This year, 2024, marks the 50th anniversary of the invention of pulse oximetry (PO), which was first presented by Takuo Aoyagi, an engineer from the Nihon Kohden Company, at the 13th Conference of the Japanese Society of Medical Electronics and Biological Engineering in Osaka in 1974. His discovery and the development of PO for the non-invasive measurement of peripheral arterial oxygenation represents one of the most significant chapters in the history of medical technology. It resulted from research and development efforts conducted by biochemists, engineers, physicists, physiologists, and physicians since the 1930s. The objective of this work was to provide a narrative review of the history, current status, and future prospects of PO. A comprehensive review of the literature on oximetry and PO was conducted. Our historical review examines the development of oximetry in general and PO in particular, tracing the key stages of a long and fascinating story that has unfolded from the first half of the twentieth century to the present day-an exciting journey in which serendipity has intersected with the hard work of key pioneers. This work has been made possible by the contributions of numerous key pioneers, including Kurt Kramer, Karl Matthes, Glenn Millikan, Evgenii M. Kreps, Earl H. Wood, Robert F. Show, Scott A. Wilber, William New, and, above all, Takuo Aoyagi. PO has become an integral part of modern medical care and has proven to be an important tool for physiological monitoring. The COVID-19 pandemic not only highlighted the clinical utility of PO but also revealed some of the problems with the technology. Current research in biomedical optics should address these issues to make the technology even more reliable and accurate. We discuss the necessary innovations in PO and present our thoughts on what the next generation of PO might look like.

Abstracts of the 3rd Occitanie Congress of Medical Biology Interns

Abstracts of the 3rd Occitanie Congress of Medical Biology Interns

Influence of Slip Boundary Conditions on Jeffrey Fluid Flow in Tapered Conduit with Hall Current and Soret–Dufour Effects

AbstractThe present work examines the computational analysis and mathematical modeling of peristaltic blood flow in a tapered channel, taking into account slip boundary conditions, Hall current, and Soret–Dufour forces. By neglecting the wave number and employing a long‐wavelength approximation to analyze the fluid model, the investigation was conducted within the framework of a low Reynolds number regime. The study reveals that the values of the Soret number, Dufour number, Prandtl number, and Schmidt number exhibit an upward trend as the fluid temperature rises. In contrast, a rise in the thermal slip parameter causes the fluid temperature to fall. It has been shown that when the mass slip parameter increases, the fluid's concentration rises. The skin friction coefficient rises within the range of x = 0.55 to x = 1 as the velocity, concentration slip parameter, Soret number, and Dufour number increase. Conversely, the skin friction coefficient decreases as the thermal slip parameter increases. The selected characteristics exhibit realism since they find use in many fields such as medical biology, biomechanics, heat exchangers, gas turbines, and several other domains.

Conception, pregnancy and inflammatory bowel disease-Current concepts for the practising clinician.

The peak incidence of inflammatory bowel disease (IBD) coincides with a woman's prime reproductive years. The management of IBD during pregnancy can be challenging for healthcare professionals, underpinning the need for a multi-disciplinary approach with shared decision-making with the patient. Pre-conception counselling can address patient concerns, improve pregnancy specific IBD patient knowledge and provide a personalized risk assessment, to ensure optimal maternal and fetal outcomes. Most women with IBD have fertility rates comparable with the general population, although voluntary childlessness is common among women with IBD. IBD disease activity at conception and during pregnancy is a key determinant of the course of IBD during pregnancy. Active IBD during pregnancy is associated with adverse pregnancy-related outcomes, including spontaneous abortion, small for gestational age baby and preterm birth, emphasizing the importance of ensuring disease remission prior to conception. Most IBD medications (5-aminosalicylates, thiopurines if already initiated pre-conception, corticosteroids and biologic medications) are considered safe and low risk during pregnancy and breastfeeding, except for methotrexate, JAK-inhibitors, ozanimod and allopurinol and maintaining remission throughout gestation should be the priority. Most women with IBD can have a vaginal delivery, but cesarean section should be considered in active perianal disease and history of ileal pouch surgery. This narrative review outlines the current evidence for themanagement of IBD in pregnancy, as well as considering the pre-conceptual and post-partum period.

Impact of patient support programmes among patients with severe asthma treated with biological therapies: a systematic literature review and indirect treatment comparison

IntroductionEffective treatment of severe asthma requires patient adherence to inhaled and biological medications. Previous work has shown that patient support programmes (PSP) can improve adherence in patients with chronic diseases,...

The relationship of vitamin D to the MHAQ index, activity disease, and inflammation in a sample of Syrian rheumatoid disease patients

Background: Vitamin D has an immunomodulatory and anti-inflammatory role, and its deficiency has been linked with many autoimmune disorders, including rheumatoid arthritis (RA). The correlation ship between the severity of RA and serum levels of vitamin D is a subject of immense interest and therapeutic implications. Patients and Methods: A total of 100 patients previously diagnosed with RA were collected from visitors to the rheumatology clinic at the university hospital and their ages were over 18 years. The serum vitamin D value and the C-reactive protein (CRP) value were measured, and the Disease Activity Score CRP28 (DAS28CRP) and Modified Health Assessment Questionnaire (MHAQ) score were calculated to determine the severity and effectiveness of the disease and its relationship to vitamin D deficiency. Results: The average age of the patients ranged according to the patient’s age (46.03±11.291), we note that individuals whose ages ranged from 26 to 65 accounted for the largest percentage (94%), 83% of women (83) and 17% men (17), and the mean score for sun exposure was 15.80±5.446. Patients were individuals diagnosed with the disease between 5 and 10 years were the highest group, with a percentage of 31%. A total of 72% of the patients were not treated with corticosteroids, and 43% of the patients were treated with vitamin D. We found that the number of patients using biologic medications was 18%, and the number of patients using disease-modifying anti-rheumatic drugs was 88%. The mean of DAS28 was moderate in 63% of patients, and the average of the MHAQ score was 0.80±0.334. We found that there is no statically significant correlation between the serum vitamin D level and DAS28/CRP (P=0.733), and there is also no statically significant correlation between the serum value of vitamin D and the medications used, whether biological or disease-modifying anti-rheumatic drugs (P=0.361). In addition, there is also no significant correlation between the serum vitamin D level and MHAQ score (P=0.100). Conclusion: There was no significant relationship between vitamin D deficiency and the disease activity or severity in a sample of patients with RA.