Marjan Assefi

Background: X-linked mutations are highly important in clinical diagnosis, and at least 533 disorders are related to the genes located on the X chromosome. Case Presentation: A 21-year-old Caucasian woman with a 24-year-old Caucasian man as her fiancé referred Clinical genetic lab for premarital genetic counseling (carrier screening). None of them had any abnormal manifestations. Following genetic counseling, Whole Exome Sequencing (WES) test performed to find the possible pathogenic mutations. Also, after drawing the couple's pedigree, candidate mutations were examined in the woman's parents as well as her uncles. Additionally, in silico investigations were performed through SWISS-MODEL, MolProbity, ProSA, Py- Mol, and FATCAT tools. The most important mutation diagnosed in the woman (R1362Q in the 35th exon of CACNA1F), was observed in her mother and her two uncles. The mutation was also screened in both her father and her fiancé, but they had no mutations. After medical examinations of carriers, there was no sign of any eye impairment. Other mutations were TCTN2 (c.1613-2A>G), TARS (p.K319E), SPEG (p.E3020K), CPS1 (p.A1180V), MYO3A (p.I736M), NNT (p.R968Q), MED23 (p.K406T). Bioinformatics analyses indicated no alteration in the mutant structure of CACNA1F (Q1362) compared with the normal structure (R1362). Conclusion: Conclusively, the current study emphasizes the non-pathogenic effect of missense mutation R1362Q in the 35th exon of CACNA1F in association with ocular diseases. This will ensure the reports of this mutation as healthy instead of uncertain in the literature and databanks.

Objectives: Several studies have reported altered cerebrospinal fluid (CSF) concentrations of presynaptic proteins, such as growth-associated protein 43 (GAP-43) in Alzheimer's disease (AD) patients. Given the potential predictive role of CSF GAP-43 for AD, the current study aimed to investigate the relationship between CSF GAP-43 levels and DTI-detected microstructural changes in the white matter (WM).Methods: Data from three groups of participants including 39 control normals (CN), 138 MCI, and 39 AD subjects were obtained from the Alzheimer’s disease Neuroimaging Initiative (ADNI). Linear regression was used to the association of CSF-GAP43 and DTI values (including MD, RD, AxD, and FA) in the brain.Results: We found a significant association between CSF-GAP43 and FA (p-value = 0.011). Also, a negative association was found between CSF-GAP43 concentration and AD, MD, and RD values in MCI (p-value = 0.013, p-value = 0.004, p-value = 0.017). The regression models also revealed a positive association between CSF-GAP43 and FA value in AD subjects (p-value = 0.028). Furthermore, increased CSF-GAP43 level was associated with lower AD, MD, and RD values in brain WM of AD patients (p-value = 0.022, p-value = 0.033, p-value = 0.041).Conclusion: Our study provides a better understanding of the link between CSF GAP-43 and WM changes in patients with MCI and AD. Our findings support the application of CSF GAP-43 as an effective biomarker for monitoring individuals at high risk of AD in the early stages.

Background: Methotrexate (MTX), sulfonamides, hydroxychloroquine, and leflunomide have consistently resulted in remission with relatively mild to moderate adverse effects in patients with rheumatoid arthritis (RA). Modern medications outperform traditional treatments in that they target the pathological processes that underlie the development of RA. Methods: Following PRISMA guidelines, the authors accomplished a systematic review of the clinical efficacy of RA drugs, including the biologics such as Tumor Necrosis Factor-alpha inhibitors (TNF-α i) like Etanercept, Infliximab, Golimumab, and Adalimumab, kinase inhibitors (JAK inhibitors including Baricitinib and Tofacitanib), SyK inhibitors like Fos-tamatinib, MAPK inhibitors such as Talmapimod, T-cell inhibitors (Abatacept), IL6 blockers (Tocilizumab), and B cells depleters (Rituximab). These drugs have been found to increase remission rates when combined with MTX. A bioinformatics-based network was designed applying STRING-MODEL and the DrugBank database for the aforementioned drugs and MTX and, finally, employed for this systematic review. Results: Current research demonstrates that non-TNF-α inhibitor biologicals are particularly helpful in treating patients who did not respond well to conventional medications and TNF-α inhibitors. Despite being effective, these innovative drugs have a higher chance of producing hazardous side effects. The in silico investigations suggested an uncovered molecular interaction in combining MTX with other biological drugs. The STRING-MODEL showed that DHFR, TYMS, and ATIC, as the receptors of MTX, interact with each other but are not connected to the major interacted receptors. Conclusions: New game-changing drugs including Mavrilimumab, Iguratimod, Upadacitinib, Fenebrutinib, and nanoparticles may be crucial in controlling symptoms in poorly managed RA patients. Emerging therapeutic targets like Toll-like 4 receptors, NLRP3 inflammasome complexes, and mesenchymal stem cells can further transform RA therapy.

The study of biological processes and functions of the human body under normal circumstances is known as physiology. Cellular physiology is the study of biophysical and biochemistry processes taking place in a cell. Cells age with time. They all have a certain lifespan after which they die common features that can be observed in an aging cell include damaged protein and organelles accumulation even when there is the absence of mutation. Many physiological changes are experienced as cell ages, resulting in the deterioration of normal cell functioning. Examples of such changes include: Cells may enlarge and are unable to multiply or divide, fats and pigments may get deposited in some cells, and some cells may function abnormally, while others may start functioning in the right manner. Any organism that is multicellular and receives energy from the sun can only live for a specific time. As the cellular organism ages, it losses its efficiency and after sometime it might end up dying. Many biologists studying the evolution of organisms deny that aging is genetically caused but rather takes place after natural selection requirements are fulfilled by the organisms. After an organism has had off-springs, it ages with time and eventually dies; however, recent research has shown that genetic components also contribute to aging.

Congenital coronary artery anomalies are relatively rare, occurring in approximately 0.6%-1.3% of cases undergoing coronary angiography. Among these anomalies, a unique cardiac abnormality known as a dual left anterior descending artery (LAD) stands out. A dual LAD is characterized by the presence of 2 LADs in the anterior interventricular sulcus. This structural deviation consists of a shorter LAD that terminates high in the anterior interventricular sulcus and a longer LAD that extends to the distal sulcus, supplying blood to the cardiac apex. Percutaneous procedures on dual LADs are even less frequent. We describe a 53-year-old woman with typical burning chest pain, ST-elevation in leads I and aVL, and positive troponin I enzyme. Coronary angiography revealed a thrombotic lesion with 99% stenosis at the proximal part of the LAD. The main LAD originated properly from the left coronary cusp, and the remainder of its course was supplied by a second branch originating from the right coronary cusp. Computed tomography angiography and echocardiography were performed for the LAD course. The patient was discharged after an uneventful 1-week hospital stay. Our case is particularly noteworthy for several reasons. Firstly, this dual LAD anomaly is uncommon, and patients with dual LADs less frequently have a ramus artery. Secondly, there have been only a few documented cases of percutaneous transluminal coronary angioplasty performed on short LADs. The key takeaway from this scintillating case study is the significance of identifying the artery responsible for blood supply to the cardiac apex.

Background: Previous studies have documented pain as an important concern for quality of life (QoL) and one of the most challenging manifestations for cancer patients. Thus, cancer pain management (CPM) plays a key role in treating pain related to cancer. The aim of this systematic review was to investigate CPM, with an emphasis on personalized medicine, and introduce new pharmacogenomics-based procedures for detecting and treating cancer pain patients. Methods: This study systematically reviewed PubMed from 1990 to 2023 using keywords such as cancer, pain, and personalized medicine. A total of 597 publications were found, and after multiple filtering processes, 75 papers were included. In silico analyses were performed using the GeneCards, STRING-MODEL, miRTargetLink2, and PharmGKB databases. Results: The results reveal that recent reports have mainly focused on personalized medicine strategies for CPM, and pharmacogenomics-based data are rapidly being introduced. The literature review of the 75 highly relevant publications, combined with the bioinformatics results, identified a list of 57 evidence-based genes as the primary gene list for further personalized medicine approaches. The most frequently mentioned genes were CYP2D6, COMT, and OPRM1. Moreover, among the 127 variants identified through both the literature review and data mining in the PharmGKB database, 21 variants remain as potential candidates for whole-exome sequencing (WES) analysis. Interestingly, hsa-miR-34a-5p and hsa-miR-146a-5p were suggested as putative circulating biomarkers for cancer pain prognosis and diagnosis. Conclusions: In conclusion, this study highlights personalized medicine as the most promising strategy in CPM, utilizing pharmacogenomics-based approaches to alleviate cancer pain.

Proving clinical superiority of personalized care models in interventional and surgical pain management is challenging. The apparent difficulties may arise from the inability to standardize complex surgical procedures that often involve multiple steps. Ensuring the surgery is performed the same way every time is nearly impossible. Confounding factors, such as the variability of the patient population and selection bias regarding comorbidities and anatomical variations are also difficult to control for. Small sample sizes in study groups comparing iterations of a surgical protocol may amplify bias. It is essentially impossible to conceal the surgical treatment from the surgeon and the operating team. Restrictive inclusion and exclusion criteria may distort the study population to no longer reflect patients seen in daily practice. Hindsight bias is introduced by the inability to effectively blind patient group allocation, which affects clinical result interpretation, particularly if the outcome is already known to the investigators when the outcome analysis is performed (often a long time after the intervention). Randomization is equally problematic, as many patients want to avoid being randomly assigned to a study group, particularly if they perceive their surgeon to be unsure of which treatment will likely render the best clinical outcome for them. Ethical concerns may also exist if the study involves additional and unnecessary risks. Lastly, surgical trials are costly, especially if the tested interventions are complex and require long-term follow-up to assess their benefit. Traditional clinical testing of personalized surgical pain management treatments may be more challenging because individualized solutions tailored to each patient’s pain generator can vary extensively. However, high-grade evidence is needed to prompt a protocol change and break with traditional image-based criteria for treatment. In this article, the authors review issues in surgical trials and offer practical solutions.

Personalized care models are dominating modern medicine. These models are rooted in teaching future physicians the skill set to keep up with innovation. In orthopedic surgery and neurosurgery, education is increasingly influenced by augmented reality, simulation, navigation, robotics, and in some cases, artificial intelligence. The postpandemic learning environment has also changed, emphasizing online learning and skill- and competency-based teaching models incorporating clinical and bench-top research. Attempts to improve work–life balance and minimize physician burnout have led to work-hour restrictions in postgraduate training programs. These restrictions have made it particularly challenging for orthopedic and neurosurgery residents to acquire the knowledge and skill set to meet the requirements for certification. The fast-paced flow of information and the rapid implementation of innovation require higher efficiencies in the modern postgraduate training environment. However, what is taught typically lags several years behind. Examples include minimally invasive tissue-sparing techniques through tubular small-bladed retractor systems, robotic and navigation, endoscopic, patient-specific implants made possible by advances in imaging technology and 3D printing, and regenerative strategies. Currently, the traditional roles of mentee and mentor are being redefined. The future orthopedic surgeons and neurosurgeons involved in personalized surgical pain management will need to be versed in several disciplines ranging from bioengineering, basic research, computer, social and health sciences, clinical study, trial design, public health policy development, and economic accountability. Solutions to the fast-paced innovation cycle in orthopedic surgery and neurosurgery include adaptive learning skills to seize opportunities for innovation with execution and implementation by facilitating translational research and clinical program development across traditional boundaries between clinical and nonclinical specialties. Preparing the future generation of surgeons to have the aptitude to keep up with the rapid technological advances is challenging for postgraduate residency programs and accreditation agencies. However, implementing clinical protocol change when the entrepreneur–investigator surgeon substantiates it with high-grade clinical evidence is at the heart of personalized surgical pain management.

Natural antioxidants are abundant in food and medicinal plants. These natural antioxidants, particularly polyphenols and carotenoids, have numerous biological effects, including anti-inflammatory, anti-aging, anti-atherosclerosis, and anticancer properties. To examine potential cancer prevention agent sources and advance their utilization in useful food varieties, drugs, and food added substances, it is fundamental for separate cell reinforcements from food and restorative plants really and assess them suitably. This paper goes into great detail about the green extraction methods of natural antioxidants, the evaluation of antioxidant activity at the chemical and cellular levels, and their primary sources, which are food and medicinal plants.