Journal of Asian Medical Students' Association

A Comparative Evaluation of Senolytics and Disease-Modifying Antirheumatic Drugs in Elderly Patients with Autoimmune Diseases

Lijamol Varghese Thoppil — 2024-11-21

Introduction

The study aims to evaluate whether senolytics, targeting senescent cells, are more effective than conventional Disease-modifying antirheumatic Drugs (DMARDs) in managing age-related autoimmune diseases. It highlights the significance of senolytics in these conditions, initially tested in mice with ongoing human trials. Objectives are to review molecular mechanisms and compare the efficacy of senolytics and DMARDs in older individuals.

Methods

The literature review initially found 20 papers, selecting 13 through databases like PubMed, Ovid, and Google Scholar using keywords such as senolytics, elderly, and autoimmune diseases. Inclusion criteria were systematic reviews and meta-analyses that provided empirical data on the molecular mechanisms, clinical effectiveness, or safety profiles of senolytics, specifically in elderly populations with autoimmune diseases. Exclusions included studies on non-senolytic therapies and single case reports, primarily focusing on animal studies. Data on authors, publication years, journals, sample sizes, outcomes, and side effects were compiled into an Excel database to compare senolytics with DMARDs based on predefined objectives.

Results

Senolytics remove senescent cells, reducing inflammation and restoring immune function in age-related autoimmune diseases. By blocking survival pathways like Bcl-2 family proteins, senolytics induce cell death, reduce proinflammatory SASP factors, and improve tissue repair. This approach holds potential for treating autoimmune conditions in the elderly. As Table 1 illustrates, senolytics show potential, yet unlike DMARDs, which are validated through extensive trials, their effectiveness and safety remain unconfirmed.

Conclusion

Senolytics show promise in treating age-related autoimmune diseases by targeting senescent cells. This approach stands in contrast to the well-established DMARDs, which, while effective, are known for theirsignificant side effects. Further research is needed to determine their efficacy and safety.

Creating Attenuated Infectious Bursal Disease Virus from Dual-Promoter Plasmids

Maitry Mensibhai Vala — 2024-11-19

Introduction

Infectious Bursal Disease Virus (IBDV), a virus of the Birnaviridae family, leads to immunosuppression in young chickens by damaging B cells. Due to the increasing number of variant IBDV strains, there is a critical need to develop a method to produce attenuated viruses for vaccine development. Using the approach of reverse genetics, the genome of the virus was manipulated and studied in the lab. To make this process more efficient, researchers developed a method using dual-direction promoters to quickly produce IBDV. This technique makes it easier to weaken strong versions of the IBDV virus, potentially aiding in faster and more efficient vaccine development.

Method

The study used a human kidney cell grown in a nutrient-rich medium along with a chicken cell line. A strain of the IBDV virus was taken from a chicken and adapted to grow in both cell types. Changes were introduced in copies of the virus's genetic material made by RT-PCR to create mutations in these versions that contained either a VP1 or VP3 protein. They later added a version of the VP1 protein with a "FLAG" tag and purified it with anti-FLAG agarose, which was later analyzed using mass spectrometry. They used a system with two plasmids with dual-direction promoters inserted into the human cells. Specific changes in the cells were observed under a microscope to confirm the successful recreation of the IBDV virus.

Result

The results of dual-direction promoters suggested that this new two-plasmid system could improve the efficiency of making the IBDV virus infectious. They also concluded that FLAG-tagged proteins can reduce the activity of proteins in the virus and could help make copies of a part of the virus's genetic material.

Conclusion

In conclusion, the researchers created a dual-promoter plasmid system using two components in which Pol II and Pol I were organized in the same direction to recreate the IBDV virus quickly. This system does not require extra components for the production of two important proteins, VP1 and VP3. Using this system, they created a version of the IBDV virus that expresses VP1-FLAG, which reduces the virus's ability to multiply but does not affect its ability to trigger an immune response. This suggests that this method could be used to create a weakened version of the IBDV virus that could potentially be used as a live vaccine.

Brain Computer-Interface System – The Benefits of it for Patients with Amyotrophic Lateral Sclerosis

Evan Salo Kochumman — 2024-11-21

Purpose

To explore and analyze how the Brain-Computer Interface aids patients with Amyotrophic lateral sclerosis (ALS) afflicted with Locked-In Syndrome (LIS) by enabling them in their movement and communication.

Introduction

Amyotrophic lateral sclerosis is a rare terminal neurodegenerative disorder that affects the motor neurons in the brain and spinal cord, resulting in progressive weakening and atrophy of the muscles. Brain-Computer Interface (BCI) was used as a communication method for a patient with late-stage ALS characterized by aphonia and quadriplegia, with retention of normal cognitive function. The use of the implanted device combined with automated decoding software, enabled independent communication in patients with the use of typing software.

Method

A 58 year-old female with late-stage ALS was able to communicate with her eyes with the help of an eye tracker. She is completely paralyzed and indicates a score of 2 on the ALS functional rating scale on a scale of 0 (high impairment) to 40 (low impairment). A BCI device of subdural electrode strips were implanted through burr holes over the sensorimotor prefrontal cortex by functional MRI and neuro-navigation. The elements of the BCI system also include the transmitter, receiving antenna, receiver and a tablet. After 28 weeks of implantation, the patient was asked to do computer tasks by trying to move the hand on the side opposite the implanted electrodes. The patient was also able to spell words correctly on the screen by selecting each letter.

Result

The performance of the patient doing algorithm tests and spelling on the tablet, improved over time showing a correct mean of over 90%. Consistent functional MRI activity was observed in the left sensorimotor hand area when the patient tried to move her hand. The patient was also asked to rate the visual-analogue scores for mood which consistently showed below 30% (lower limit for depression). She was able to use the system at home with minimal assistance and reported high levels of satisfaction with the device.

Conclusion

The patient, with the help of a completely implanted BCI system, was able to control a typing communication software, although at a slow rate. Hence, this system is seen to be effective in the long-term management of ALS patients.

Diagnosis of Rare Duodenal Neuroendocrine Tumor with Carcinoid Syndrome

Aurika Balamurugan — 2024-11-20

Introduction

Duodenal carcinoids are malignant tumors originating from enterochromaffin cells. They develop distant metastases and account for approximately one-third of gastrointestinal neuroendocrine tumors (NETs). They are the primary cause of carcinoid syndrome, a prominent neuroendocrine neoplasm presentation. Primary duodenal carcinoids, accounting for less than 2% of all GI-NETs, are linked to loss of function mutations of the MEN1 gene, and the related NETs show loss of heterozygosity on chromosome 11q13.

Background

Duodenal carcinoids are rare tumors, and the secondary manifestation of carcinoid syndrome makes them a unique occurrence. The incidence is estimated to be approximately 1-2.4 cases per 100,000 population.

Case

A 34-year-old adult male presented with upper abdominal pain, diarrhea, cutaneous flushing, dry cough, exertional dyspnea, and right-sided heart disease due to regurgitant tricuspid valve deposits. Multiple nodules, both <10 mm and ≥10 mm in size, were found in the upper parts of the duodenum, along with long segment wall thickening on contrast-enhanced CT. Duodenal carcinoid elements were confirmed via positive chromogranin A in endoscopy-guided biopsy material and elevated 24-hour urine 5-hydroxyindoleacetic acid (5-HIAA). A 2-dimensional echocardiographic evaluation suggested the diagnosis of carcinoid heart disease.

Discussion

To support clinical decision-making, recent scientific publications from the last 10 years were reviewed using the keyword “duodenal carcinoid” on PubMed. One systematic review and 20 literature reviews were found. Advanced imaging tools for assessing tumor distribution, lesion size, depth of invasion, metastatic conditions, and multifocal disease in the gastrointestinal tract were discussed. The Ki67 proliferative index and depth of invasion were considered in deciding between surgical and endoscopic resection. Approaches to non-resectable metastasized NETs included Peptide Receptor Radionuclide Therapy or 90Y radioembolization as alternative treatments.

Conclusion

The patient, symptomatic with multiple tumors in the duodenum, required radical surgery and regional lymphadenectomy, as tumor size, depth of invasion, and multifocality could not reliably predict lymph nodal metastasis. The benefits of chemotherapy were not proven. The patient was subsequently referred to specialized oncology care. This case report aims to highlight the often-overlooked clinical manifestations of duodenal carcinoids to aid in early recognition and diagnosis, focusing also on the diagnostic methods employed. Large-scale research is required to better understand various aspects of this disease.

Lung Volume Reduction Surgery for Native Lung Hyperinflation Following Single-Lung Transplantation for Emphysema- Which Patient?

Hinaz Jameela Iqbal — 2024-11-21

Abstract

This study aims to assess the eligibility of patients to undergo non-anatomical multiple wedge resection surgery following complications after single lung transplantation to treat emphysema. A number of patients were evaluated using a range of radiological, laboratory, and pulmonary function tests to gauge operative viability. Following assessment, lung volume reduction surgery was carried out successfully indicating its efficacy in treating native lung hyperinflation

Introduction

Double-lung transplantation is a well established treatment method for patients with advanced emphysema and COPD. However, due to unavailability of donors, single-lung transplant is opted for instead. This study evaluates which patients may be eligible for surgical correction of complications following single-lung transplantation.

Method

A retrospective study was done of eight patients that have undergone single lung volume reduction surgery for native lung hyperinflation as a treatment option for COPD. The patients were of equal ratio in gender with the age group ranging from 50 to 69 years. The pre-operative tests indicated included increasing shortness of breath and deterioration in pulmonary function tests. Additional tests also included high-resolution computed tomography (HRCT), V/Q scan for lung function and a detailed history of all eight patients were noted.

Result

There was a post operative success with a thirty day survival being 100% for the patient group under study. It was noted that the patients had different series of short term postoperative complications. The complications included the need of non-invasive respiratory support for two days following surgery, respiratory infections, atrial fibrillation and bleeding. One of the eight patients died due to respiratory failure secondary to pneumonia although the follow up pulmonary function tests showed an improvement in FEV1 in all patients. Alongside, the follow up of the surgery post 6 months demonstrated improved results in the remaining seven patients with improvement in clinical symptoms, exercise tolerance and quality of life.

Conclusion

Single lung transplantation, which was previously considered a high risk treatment, can now be seen in a different light with this and similar studies. Although proven that double lung transplant results in better outcomes in severe cases of COPD comparatively, the unavailability of donors is what leads to the opting of single lung transplantation. But this risk can be significantly reduced with the careful selection of patients and adequate risk assessment.