Articles

Microbiome-Gut-Brain Axis: AI Insights

Published on: 25th June, 2024

Microbiome-gut-brain axis represents a complex, bidirectional communication network connecting the gastrointestinal tract and its microbial populations with the central nervous system (CNS). This complex system is important for maintaining physiological homeostasis and has significant implications for mental health. The human gut has trillions of microorganisms, collectively termed gut microbiota, which play important roles in digestion, immune function, and production of various metabolites. Some current research shows that these microorganisms strongly influence the brain function and behaviour of individuals, forming the basis of the microbiome-gut-brain axis. The communication between gut microbiota and the brain occurs via multiple pathways: neural pathway (e.g., vagus nerve), endocrine pathway (e.g., hormone production), immune pathway (e.g., inflammation modulation), and metabolic pathway (e.g., production of short-chain fatty acids). Dysbiosis, or imbalance of gut microbiota, has been linked to mental health disorders such as anxiety, depression, multiple sclerosis, autism spectrum disorders, etc, offering new perspectives on their etiology and potential therapeutic interventions. Artificial Intelligence (AI) has emerged as a powerful tool in interpreting the complexities of the microbiome-gut-brain axis. AI techniques, such as machine learning and deep learning, enable the integration and analysis of large, multifaceted datasets, uncovering patterns and correlations that can be avoided by traditional methods. These techniques enable predictive modeling, biomarker discovery, and understanding of underlying biological mechanisms, enhancing research efficiency and covering ways for personalized therapeutic approaches. The application of AI in microbiome research has provided valuable insights into mental health conditions. AI models have identified specific gut bacteria linked to disease, offered predictive models, and discovered distinct microbiome signatures associated with specific diseases. Integrating AI with microbiome research holds promise for revolutionizing mental health care, offering new diagnostic tools and targeted therapies. Challenges remain, but the potential benefits of AI-driven insights into microbiome-gut-brain interactions are immense and offer hope for innovative treatments and preventative measures to improve mental health outcomes.
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Development and Evaluation of a mHealth app - (ReMiT-MS app) for Rehabilitation of Individuals with Relapsing-remitting Multiple Sclerosis - A Mixed Methods, Pragmatic Randomized Controlled Trial - Study Protocol

Published on: 3rd July, 2024

Background: Delaying or slowing functional loss is a valuable goal of Multiple Sclerosis (MS) rehabilitation. The mHealth app-based exercise rehabilitation intervention is expected to overcome barriers related to routine care of MS. Due to the ubiquitous presence of smartphones, they offer an excellent opportunity for remote monitoring, scheduled interaction with experts, and instruction for exercise in a home environment. Challenges in MS routine care include forgotten rehabilitation steps, limited access to local MS experts, and internal barriers such as low health literacy, mobility limitations, and fatigue, alongside external obstacles like service availability and transport costs.Objectives: To develop a mHealth app that is user-centered and context-specific for rehabilitation of MS symptoms, and to evaluate its clinical and cost effectiveness in individuals with RRMS.Methods: The proposed research will be conducted in two phases; the first phase (Phase 1a) will be focused on the development of mHealth app content (ReMiT-MS app trial I). The pilot phase (Phase 1b), where a prototype of the application will be designed, and its usability will be evaluated. Finally, in the second phase (Phase 2), the clinical and cost-effectiveness of the ReMiT-MS app for the rehabilitation of individuals with RRMS will be evaluated (ReMiT-MS app trial II).Conclusion: The findings of this proposed trial may provide a telerehabilitation platform for individuals with RRMS in a resource-limited setting and establish a low-cost healthcare delivery model. In addition, the results of this research work might open a new window in healthcare delivery in India and similar settings.Trial registration:  CTRI/2022/09/045266 [Registered on 06/09/2022]
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3-D Current Density and Magnetic Field of 3-D MR Scanner Gradient Coil

Published on: 28th June, 2024

The topic of this paper is to describe the 3-D current density in the windings of a 3-D coil, which fills the volume between two coaxial cylinders at a precisely defined distance from each other, and which serves to generate a magnetic field gradient in the center of the cylinder axis. The 3-D current density is considered an unknown input quantity, which is calculated from the known gradient magnetic field output. It is an inverse problem in mathematics, where the direct problems are the calculation of unknown output quantities based on known input quantities. Fourier series expansion methods in the context of cylindrical coordinates were used to describe the 3-D current density. In that case, Bessel functions are used as development components. The current densities, at each point in space, were lined up to represent current lines. Each power line is associated with a coil winding through which a current of a certain strength flows. After that, the principle of discretization of coil windings was applied. Each winding is divided into a large number of elementary segments that were considered as current elements, which create, based on Bio-Savar's law, an elementary magnetic field. In this way, the total, continuous magnetic field is broken into many elementary components, which come from different current elements. An important result of this process is that each current element can be controlled independently by a current source. This means that the output magnetic field of the gradient can be controlled by current sources, which are the input sizes, and this is what is at the core of the topic of this paper.
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Lived Experiences of Cervical Cancer Patients Receiving Chemotherapy at Cancer Diseases Hospital in Lusaka, Zambia

Published on: 28th June, 2024

Background: Cervical Cancer poses a significant global health challenge, especially in lowresource settings. It is a significant health problem worldwide, with over half a million new cases diagnosed each year, accounting for approximately 6.6% of all gynecological Cancer cases and over 300,000 deaths each year. In Zambia, it is the leading cause of mortality and morbidity among women. The number of cases has increased by approximately 40%. This study explored the lived experiences of Cervical Cancer patients undergoing chemotherapy at the Cancer Diseases Hospital in Lusaka, Zambia, focusing on their subjective experiences. By examining their journeys through chemotherapy, the study aimed to highlight the subtle complexities in which treatment impacts patients’ lives and well-being.  Methods and procedures: Employing a qualitative descriptive phenomenological study design, in-depth interviews were conducted with 10 participants with diverse demographics. The sample size was determined by data saturation and saturation was reached at 10. Ethical protocols were ensured, and Study approval was obtained from UNZABREC and the National Health Research Authority. Thematic analysis was conducted on audio-recorded interviews with cervical cancer patients, ensuring confidentiality and accuracy while discerning significant patterns and themes in their narratives. Results/findings: Emotional experiences ranged from anxiety to gratitude. Psychological challenges encompassed coping mechanisms, stress management, emotional adjustments, and treatment-related fears. Socially, community support, workplace accommodations, and healthcare provider roles were key. Physical experiences revealed side effects managed through coping strategies. Financial challenges significantly impacted individuals and families.  Conclusions and recommendations: The study revealed that cervical cancer patients undergoing chemotherapy face complex challenges spanning emotional, psychological, social, physical, and financial domains, underscoring the imperative for comprehensive patient-centered care. Recommendations suggest focusing on financial aid for cancer patients and tackling treatment expenses and insurance issues. The Cancer Diseases Hospital should establish multidisciplinary teams for holistic care, and enhance patient education efforts. Nurses should adopt strategies integrating cultural competence and patient-centered care to address diverse challenges during chemotherapy. These aim to enhance the well-being and care quality of Cervical Cancer patients.
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Molecular Mechanisms and Potential Predictive Biomarkers in Advanced Non-small Cell Lung Cancer: A Summary of Current and Future Trends

Published on: 27th June, 2024

Non-small-cell lung cancer (NSCLC) accounts for 85% of lung cancer cases and is associated with different risk factors (smoking habits, gender, and age). In this scenario, many studies have been conducted to pursue improvement of survival, faster and better therapy response, reduced adverse events, and expanded available therapies and treatments against tumor resistance to drugs. These studies have focused on defining the most prevalent NSCLC biomarkers (EGFR, HER2, ALK, MET, ROS1, BRAF, KRAS G12C, HER3, NTRK, and NRG1) and their actionability. It is noteworthy that expressed kinase receptors can have overlapping mechanisms of activation of different pathways (JAK-STAT, MAPK, PI3K-AKT-mTOR, and PLC-c), which can lead to the same outcome of cell proliferation, migration, and survival resulting in increased tumor resistance to treatment. This review provides an overview of the latest findings regarding NSCLC treatment, emphasizing particular biomarkers and potential molecularly altered pathways implicated as targeted therapies. Additionally, it explores the clinical significance of the proposed treatments, their implication on progression-free survival, ongoing clinical trials, and their perspective of evolution so far.
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Germline BRCA1 Mutation inSquamous Cell Carcinoma of Oesophagus: Driver versus Passenger Mutation

Published on: 2nd July, 2024

We report a rare case of 62-year-old South Asian women who visited the Molecular Pathology and Genomics Department for hereditary germline cancer genetic testing after being diagnosed with oesophageal cancer, reported as invasive keratinizing squamous cell carcinoma metastasized to the lymph nodes. Her personal history revealed that she was diagnosed with triple-negative breast cancer five years before oesophageal cancer. Germline cancer testing showed pathogenic variants in BRCA1 gene c.68_69delAG, which proved it a hereditary breast and ovarian cancer syndrome. She was started on PARP inhibitors but developed some secondary respiratory failure and succumbed to death. Less than 10 cases have been reported in the literature of the association of germline BRCA1 and Squamous cell Carcinoma – the esophagus. The article focuses on the probable pathogenesis of BRCA1 mutation with non-classic malignancies and the response of Poly adenosine diphosphate ribose polymerase inhibitors (PARP) inhibitors in such a scenario. We report an unusual manifestation of the BRCA1 gene with second primary oesophageal squamous cell cancer occurring five years later to triple-negative breast cancer.
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An Interesting Case of COPD Exacerbation Presenting with Mixed Features of Intracranial Hypertension and Hypercapnic Encephalopathy

Published on: 2nd July, 2024

Background: Idiopathic intracranial hypertension (IIH or pseudotumor cerebri) has two major morbidities: papilledema with visual loss and disabling headache. Intracranial Venous Hypertension (IVH) is a fundamental mechanism of IIH. Although traditionally considered limiting to the central nervous system, evidence suggests IIH as a systemic disease associated with cardiorespiratory disorders, which has been far less comprehended. Case Report: A 60-year-old female with Chronic Obstructive Pulmonary Disease (COPD) was admitted for dyspnea and developed a coma with a pH of 7.01 and pCO2 of 158 mmHg. She was intubated and had persistent nuchal rigidity, a brief myoclonus episode with a negative electroencephalogram, and negative CT head studies. A Lumbar Puncture (LP) revealed elevated opening pressure (35 cmH2O) with normal Cerebral Spinal Fluid (CSF) studies. Her nuchal rigidity improved after the removal of 40 mL CSF. The ophthalmology examination the next day after her the large volume LP didn’t show visual loss or papilledema. The patient improved clinically and was extubated two days later. Her echocardiogram showed a dilated right ventricle with pulmonary hypertension. The patient was discharged home.Discussion: IIH is different from hypercapnic encephalopathy and characterized by increased intracranial pressure with papilledema, vision loss, and debilitating headache. Hypercapnia-induced increased intracranial venous flow and pulmonary hypertension-caused elevated central venous pressure with consequent outflow resistance lead to IVH. In hypercapnic encephalopathy, the presentation is mostly cognitive changes. In this case, nuchal rigidity with a negative CT head scan triggered the investigation of IIH. Conclusion: A deep understanding of the relationship between COPD and IIH is vital. There is insufficient evidence to recommend routine eye examinations in COPD patients for papilledema and to conduct a pulmonary function test for a newly diagnosed IIH patient. However, we highly suggest a timely ophthalmology exam prior to performing an LP in COPD patients with suspecting IIH to avoid unnecessary procedures and meanwhile improve clinical outcomes.
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Fifteen year Follow-up of Relapsed/ Refractory Patients with Hodgkin Lymphoma Treated with Autologous Hematopoietic Stem Cell Transplantation

Published on: 2nd July, 2024

We reviewed our outcomes of patients with relapsed/refractory Hodgkin Lymphoma treated with autologous stem cell transplant over a 30-year period, 1992 to 2022 and are reporting 15-year Disease-Free Survival (DFS) and Overall Survival (OS) of the 36 patients treated (19 men, 17 women, median age 41). Over the years there were different preparative regimens employed (carmustine, etoposide, melphalan and BCNU, etoposide, cytarabine, and melphalan) as well as post-transplant consolidation therapy (brentuximab). With a median follow-up of 15 years, the DFS is 52% and OS is 64%. Long-term complications include cardiomyopathy and second malignancies.The use of better salvage regimens and post-transplant consolidation therapy should lead to better outcomes.
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The Use of Thioxopyrimidine Derivatives as New Regulators of Growth and Photosynthesis of Barley

Published on: 2nd July, 2024

New synthetic compounds - thioxopyrimidine derivatives as regulators of vegetative growth and photosynthesis of spring barley (Hordeum vulgare L.) variety Acordine were studied. The growth-regulatory effect of new synthetic compounds, thioxopyrimidine derivatives, used in a concentration of 10-6M, was compared with the growth-regulatory effect of a plant hormone auxin IAA (1H-indol-3-yl)acetic acid) or synthetic plant growth regulators, derivatives of sodium and potassium salts of 6-methyl-2-mercapto-4-hydroxypyrimidine (Methyur, Kamethur), N-oxide-2,6-dimethylpyridine (Ivin), used in a similar concentration of 10-6M. The conducted study showed the similarity of the growth-regulatory effects of synthetic compounds, thioxopyrimidine derivatives, the plant hormone auxin IAA, and synthetic plant growth regulators Methyur, Kamethur, and Ivin. Morphometric parameters (average length of shoots (mm), average length of roots (mm), and average biomass of 10 plants (g)) and biochemical parameters (content of photosynthetic pigments chlorophylls a, b, a+b and carotenoids (µg/ml)) of barley plants treated with the plant hormone auxin IAA or synthetic plant growth regulators Methyur, Kamethur, Ivin or thioxopyrimidine derivatives were increased after 4 weeks compared to control plants. The dependence of the growth-regulatory effect of synthetic compounds, thioxopyrimidine derivatives on their chemical structure was analyzed. The use of the synthetic plant growth regulators, derivatives of sodium salt of 6-methyl-2-mercapto-4-hydroxypyrimidine (Methyur), potassium salt of 6-methyl-2-mercapto-4-hydroxypyrimidine (Kamethur), N-oxide-2,6-dimethylpyridine (Ivin) and selected most active synthetic compounds, thioxopyrimidine derivatives for regulating the growth and photosynthesis of spring barley (Hordeum vulgare L.) variety Acordine is proposed.
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Improving Cardiac Rehabilitation Referral Rates in Patients with Coronary Heart Disease from Diverse Communities Using an Electronic Order System

Published on: 29th June, 2024

Introduction: Despite the benefits of Cardiac Rehabilitation (CR), local and national CR referral and participation rates remain low when compared to established cardiovascular therapies, especially amongst racial/ethnic groups. Objectives: This study investigated the effects of the implementation of a CR program and electronic order set (EOS) in a large health system on CR referral and participation rates among a diverse group of patients with Coronary Heart Disease (CHD). Methods: A total of 360 patients from UCSD Health who presented with ACS were prospectively evaluated during initial hospitalization and 6- and 12-weeks post-discharge. The multivariable logistic regression model assessed referral and participation rates by week 1 and -12 post-discharge, adjusting for gender, age, race, ethnicity, geography, and referring physician subspecialty. Results: UCSD CR program implementation led referral rates to increase at week 1 (Pre- 38.6% and Post-54.9%, p = 0.003) and week-12 (Pre- 54.1% and Post- 59.8%, p = 0.386). Post-CR referrals were more likely at week-1 (OR: 1.93, 95% CI 1.27-2.95) and week-12 (OR: 1.26, 95% CI 0.79-2.00). EOS implementation increased referral rates at week-1 (Pre- 40.3% and Post- 58.7%, p < 0.001) and week-12 (Pre- 54.9% and Post- 60.4%, p = 0.394) with referrals more likely at week-1 (OR: 2.1, 95% CI 1.35-3.29) and week-12 (OR: 1.25, 95% CI 0.795-1.98). Participation in CR following EOS was more likely at both week-1 and week-12. Multivariable analysis revealed disparities in referral based on race, geographic location, and referring physician subspecialty. Conclusion: A CR program and EOS implementation were shown to increase referral rates with long-term potential for increasing referral and participation rates. Condensed abstract: This prospective study investigated the implementation of a Cardiac Rehabilitation (CR) program and Electronic Order Set (EOS) within the same health system on CR referral and participation rates. 360 patients with ACS were evaluated over 12 weeks. UCSD CR program and EOS implementation led referral rates to increase at week-1 and -12. CR participation was more likely to increase at week-1 and -12 following EOS. Multivariable analysis revealed disparities in referrals disproportionally affecting racial and ethnic minority groups and rural communities. CR and EOS implementation may increase CR referral rates for diverse patients with CHD.
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